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  • 1.
    Aarnio, Riina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Isacson, Isabella
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Sanner, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Gustavsson, Inger M.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Gyllensten, Ulf B.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Comparison of vaginal self-sampling and cervical sampling by medical professionals for the detection of HPV and CIN2+: a randomized studyManuscript (preprint) (Other academic)
    Abstract [en]

    Primary screening with human papillomavirus (HPV) test is more effective in reducing cervical cancer incidence than cytology and it also offers the opportunity to self-sample. We conducted a randomized study to compare vaginal self-sampling with cervical sampling by medical professionals for HPV testing concerning prevalence of HPV and detection of cervical intraepithelial neoplasia (CIN) of grade 2 or worse (CIN2+)  or grade 3 or worse (CIN3+) in primary screening. In total, 11 951 women aged 30–60 years were randomized into two groups, 5961 for self-sampling (SS arm) and 5990 for sampling by medical professionals (SMP arm). Sampling was performed with a Rovers®Viba-brush in the SS arm and a cytobrush in the SMP arm. All samples were applied to an indicating FTA elute card and analyzed for HPV using a clinically validated real-time PCR test (hpVIR). All HPV-positive women performed repeated sampling about six months later using the same procedure as used initially. All HPV-positive women in the second sampling were referred to colposcopy. HPV prevalence in the first test did not differ between the SS arm (6.8%, 167/2466) and the SMP arm (7.8%, 118/1519) (p=0.255). The prevalence of CIN2+ per 1000 screened women was 17 (43/2466 × 1000) (95%CI 13–24) in the SS arm and 21 (32/1519 × 1000) (95%CI 15–30) in the SMP arm. For CIN3+, the prevalence per 1000 screened women was 14 (35/2466 × 1000) (95%CI 10–20) in the SS arm and 15 (23/1519 × 1000) (95%CI 10–23) in the SMP arm.  In conclusion, self-sampling and sampling by medical professionals showed the same prevalence of HPV and detection rate of CIN2+ and CIN3+ in histology.

    Novelty and Impact

    Offering self-sampling in primary cervical screening results in similar rates of HPV prevalence and detection of CIN2+ and CIN3+ compared with sampling by medical professionals when using an FTA card as storage medium and PCR-based HPV test (hpVIR). Considering health-economic aspects, resources should be directed towards self-sampling as a first choice for primary cervical screening, with careful follow-up of this strategy.

  • 2.
    Aarnio, Riina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Wikström, Ingrid
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Gustavsson, Inger M.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Gyllensten, Ulf B.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Diagnostic excision of the cervix in women over 40 years with human papilloma virus persistency and normal cytology2019In: European journal of obstetrics & gynecology and reproductive biology: X, ISSN 2590-1613, Vol. 3, article id 100042Article in journal (Refereed)
    Abstract [en]

    Objective: Persistent infection with human papillomavirus (HPV) is recognized as the main risk factor of cervical cancer. Investigation via cytology and colposcopy have lower sensitivity than HPV testing in the diagnosis of high-grade cervical intraepithelial neoplasia (CIN2+). Despite normal cytology and colposcopy findings women with persistent HPV infection have an increased risk of CIN2+. The aim of the study was to evaluate the proportion of histologically confirmed CIN2+ in women with persistent HPV infection and normal Pap smears.

    Study design: From April 2013 until March 2016 we prospectively recruited 91 women over 40 years with persistent HPV infection without any abnormalities in cytology. Of these, 40 women attended a gynecological examination including an HPV test, Pap smear, endocervical cytology, colposcopy with biopsies and diagnostic loop electrosurgical excision procedure (LEEP). Biopsy and LEEP samples were subjected to histological examination.

    Results: CIN2+ was verified by histological examination of the LEEP sample in 6/40 (15%) of the women. All the cytological samples were normal and none of the biopsies confirmed CIN2+. Only 19/40 women still had a persistent HPV infection at the study visit. None of the 21/40 women who had cleared their HPV infection at the study visit had CIN2+ in histology of the LEEP sample.

    Conclusions: A persistent HPV infection needs to be monitored despite normal Pap smears, since 6/40 (15%) women older than 40 years, was revealed to have an undiagnosed CIN2+ when LEEP was performed. Counseling women regarding the risk of cervical cancer and the expected effect of an eventual LEEP can help them to make an optimal informed choice.

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    fulltext
  • 3.
    Aarnio, Riina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Östensson, Ellinor
    Karolinska Institutet.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Reproductive biology.
    Gustavsson, Inger M.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Gyllensten, Ulf B.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Cost-effectiveness analysis of repeated self-sampling for HPV testing in primary cervical screening: a randomized studyManuscript (preprint) (Other academic)
    Abstract [en]

    Background

    Human papillomavirus (HPV) testing is recommended in primary cervical screening to improve cancer prevention. An advantage of HPV testing is that it can be performed on self-samples, which could increase population coverage and result in a more efficient strategy to identify women at risk of developing cervical cancer. Our objective was to assess whether repeated self-sampling for HPV testing is cost-effective in comparison with Pap smear cytology for detection of cervical intraepithelial neoplasia grade 2 or more (CIN2+) in increasing participation rate in primary cervical screening.

    Methods

    A cost-effectiveness analysis (CEA) was performed on data from a previously published randomized clinical study including 36 390 women aged 30–49 years. Participants were randomized either to perform repeated self-sampling of vaginal fluid for HPV testing (n = 17 997, HPV self-sampling arm) or to midwife-collected Pap smears for cytological analysis (n = 18 393, Pap smear arm).

    Results

    Self-sampling for HPV testing led to 1633 more screened women and 107 more histologically diagnosed CIN2+ at a lower cost vs. midwife-collected Pap smears (€ 228 642 vs. € 781 139). 

    Conclusions

    This study projected that repeated self-sampling for HPV testing increased participation and detection of CIN2+ at a lower cost than midwife-collected Pap smears in primary cervical screening. Offering women a home-based self-sampling may therefore be a more cost-effective alternative than clinic-based screening.

     

  • 4.
    Aasebo, Kristine
    et al.
    Univ Bergen, Dept Clin Sci, Bergen, Norway.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Department of Pathology, Uppsala University Hospital, Uppsala, Sweden.
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Department of Pathology, Uppsala University Hospital, Uppsala, Sweden.
    Mezheyeuski, Artur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Edqvist, Per-Henrik D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Eide, Geir Egil
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Lifestyle Epidemiol Grp, Bergen, Norway;Haukeland Hosp, Clin Res Ctr, Bergen, Norway.
    Pontén, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pfeiffer, Per
    Odense Univ Hosp, Dept Oncol, Odense, Denmark.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sorbye, Halfdan
    Univ Bergen, Dept Clin Sci, Bergen, Norway;Haukeland Hosp, Dept Oncol, Bergen, Norway.
    CDX2: A Prognostic Marker in Metastatic Colorectal Cancer Defining a Better BRAF Mutated and a Worse KRAS Mutated Subgroup2020In: Frontiers in Oncology, ISSN 2234-943X, E-ISSN 2234-943X, Vol. 10, article id 8Article in journal (Refereed)
    Abstract [en]

    Background: Survival of metastatic colorectal cancer (mCRC) patients has improved, but mainly for trial patients. New predictive and prognostic biomarkers validated in the general mCRC population are needed. Caudal-type homeobox 2 (CDX2) is an intestine-specific transcription factor with potential prognostic and predictive effect, but the importance in mCRC has not been fully investigated. Methods: Immunohistochemistry analysis of CDX2 was performed in a Scandinavian population-based cohort of mCRC (n = 796). Frequency, clinical and tumor characteristics, response rate, progression-free survival, and overall survival (OS) were estimated. Results: Loss of CDX2 expression was found in 87 (19%) of 452 stained cases, in 53% if BRAF mutated (BRAFmut) and in 9% if KRAS mutated (KRASmut). CDX2 loss was associated with microsatellite instability, BRAFmut, and poor differentiation and inversely associated with KRASmut. Patients with CDX2 loss received less first-line (53 vs. 64%, p = 0.050) and second-line (23 vs. 39%, p = 0.006) chemotherapy and secondary surgery (1 vs. 9%, p = 0.019). Median progression-free survival and OS for patients given first-line combination chemotherapy was 4 and 10 months if CDX2 loss vs. 9 and 24 months if CDX2 expressed (p = 0.001, p < 0.001). Immediate progression on first-line combination chemotherapy was seen in 35% of patients with CDX2 loss vs. 10% if CDX2 expressed (p = 0.003). Median OS in patients with BRAFmut or KRASmut and CDX2 expressed in tumor (both 21 months) was comparable to wild-type patients (27 months). However, if CDX2 loss, median OS was only 8 and 11 months in BRAFmut and KRASmut cases, respectively, and 10 months in double wild-type patients. In multivariate analysis, CDX2 loss (hazard ratio: 1.50, p = 0.027) and BRAFmut (hazard ratio: 1.62, p = 0.012) were independent poor prognostic markers for OS. Conclusion: In a population-based cohort of mCRC patients, CDX2 loss is an independent poor prognostic marker. Expression of CDX2 defines a new subgroup of BRAFmut cases with a much better prognosis. Loss of CDX2 defines a small group of KRASmut cases with a worse prognosis. Patients with CDX2 loss receive less palliative chemotherapy with less benefit and rarely reach secondary surgery.

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  • 5.
    Aasebö, Kristine Ö.
    et al.
    Univ Bergen, Dept Clin Sci, Bergen, Norway.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Sundström, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Mezheyeuski, Artur
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Edqvist, Per-Henrik D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Eide, Geir Egil
    Univ Bergen, Dept Global Publ Hlth & Primary Care, Lifestyle Epidemiol Grp, Bergen, Norway;Haukeland Hosp, Ctr Clin Res, Bergen, Norway.
    Pontén, Fredrik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Pfeiffer, Per
    Odense Univ Hosp, Dept Oncol, Odense, Denmark.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Sorbye, Halfdan
    Univ Bergen, Dept Clin Sci, Bergen, Norway;Haukeland Hosp, Dept Oncol, Bergen, Norway.
    Consequences of a high incidence of microsatellite instability and BRAF-mutated tumors: A population-based cohort of metastatic colorectal cancer patients2019In: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 8, no 7, p. 3623-3635Article in journal (Refereed)
    Abstract [en]

    Background: Immunotherapy for patients with microsatellite-instable (MSI-H) tumors or BRAF-inhibitors combination treatment for BRAF-mutated (mutBRAF) tumors in metastatic colorectal cancer (mCRC) is promising, but the frequency of these molecular changes in trial patients are low. Unselected population-based studies of these molecular changes are warranted.

    Methods: A population-based cohort of 798 mCRC patients in Scandinavia was studied. Patient and molecular tumor characteristics, overall survival (OS) and progression-free survival (PFS) were estimated.

    Results: Here, 40/583 (7%) tumor samples were MSI-H and 120/591 (20%) were mutBRAF; 87% of MSI-H tumors were mutBRAF (non-Lynch). Elderly (>75 years) had more often MSI-H (10% vs 6%) and MSI-H/mutBRAF (9% vs 4%) tumors. Response rate (5% vs 44%), PFS (4 vs 8 months), and OS (9 vs 18 months) after first-line chemotherapy was all significantly lower in patients with MSI-H compared to patients with microsatellite stable tumors. MSI-H and mutBRAF were both independent poor prognostic predictors for OS (P = 0.049, P < 0.001) and PFS (P = 0.045, P = 0.005) after first-line chemotherapy. Patients with MSI-H tumors received less second-line chemotherapy (15% vs 37%, P = 0.005).

    Conclusions: In unselected mCRC patients, MSI-H and mutBRAF cases were more common than previously reported. Patients with MSI-H tumors had worse survival, less benefit from chemotherapy, and they differed considerably from recent third-line immunotherapy trial patients as they were older and most had mutBRAF tumor (non-Lynch).

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  • 6.
    Abadpour, Shadab
    et al.
    Oslo Univ Hosp, Sect Transplant Surg, Oslo, Norway.;Oslo Univ Hosp, Inst Surg Res, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Göpel, Sven O.
    AstraZeneca R&D Gothenburg, Dept CVMD Biosci, Gothenburg, Sweden..
    Schive, Simen W.
    Oslo Univ Hosp, Sect Transplant Surg, Oslo, Norway.;Oslo Univ Hosp, Inst Surg Res, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Foss, Aksel
    Oslo Univ Hosp, Sect Transplant Surg, Oslo, Norway.;Oslo Univ Hosp, Inst Surg Res, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Scholz, Hanne
    Oslo Univ Hosp, Sect Transplant Surg, Oslo, Norway.;Oslo Univ Hosp, Inst Surg Res, Oslo, Norway.;Univ Oslo, Inst Clin Med, Oslo, Norway..
    Glial cell-line derived neurotrophic factor protects human islets from nutrient deprivation and endoplasmic reticulum stress induced apoptosis2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 1575Article in journal (Refereed)
    Abstract [en]

    One of the key limitations to successful human islet transplantation is loss of islets due to stress responses pre- and post-transplantation. Nutrient deprivation and ER stress have been identified as important mechanisms leading to apoptosis. Glial Cell-line Derived Neurotrophic Factor (GDNF) has recently been found to promote islet survival after isolation. However, whether GDNF could rescue human islets from nutrient deprivation and ER stress-mediated apoptosis is unknown. Herein, by mimicking those conditions in vitro, we have shown that GDNF significantly improved glucose stimulated insulin secretion, reduced apoptosis and proinsulin: insulin ratio in nutrient deprived human islets. Furthermore, GDNF alleviated thapsigargin-induced ER stress evidenced by reduced expressions of IRE1 alpha and BiP and consequently apoptosis. Importantly, this was associated with an increase in phosphorylation of PI3K/AKT and GSK3B signaling pathway. Transplantation of ER stressed human islets pre- treated with GDNF under kidney capsule of diabetic mice resulted in reduced expressions of IRE1 alpha and BiP in human islet grafts with improved grafts function shown by higher levels of human C-peptide post-transplantation. We suggest that GDNF has protective and anti-apoptotic effects on nutrient deprived and ER stress activated human islets and could play a significant role in rescuing human islets from stress responses.

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  • 7.
    Abalo, Xesus
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Boije: Zebrafish Neuronal Networks. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Lagman, David
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Univ Bergen, Sars Int Ctr Marine Mol Biol, Bergen, Norway.
    Heras, Gabriel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    del Pozo, Ana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Boije: Zebrafish Neuronal Networks. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eggert, Joel
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience. Emory Univ, Dept Med, Atlanta, GA 30322 USA.
    Larhammar, Dan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Larhammar: Pharmacology.
    Circadian regulation of phosphodiesterase 6 genes in zebrafish differs between cones and rods: Implications for photopic and scotopic vision2020In: Vision Research, ISSN 0042-6989, E-ISSN 1878-5646, Vol. 166, p. 43-51Article in journal (Refereed)
    Abstract [en]

    A correlation is known to exist between visual sensitivity and oscillations in red opsin and rhodopsin gene expression in zebrafish, both regulated by the clock gene. This indicates that an endogenous circadian clock regulates behavioural visual sensitivity, apart from the regulation exerted by the pineal organ. However, the specific mechanisms for cones (photopic vision) and rods (scotopic vision) are poorly understood. In this work, we performed gene expression, cosinor and immunohistochemical analyses to investigate other key genes involved in light perception, encoding the different subunits of phosphodiesterase pde6 and transducin G alpha(T), in constant lighting conditions and compared to normal light-dark conditions. We found that cones display prominent circadian oscillations in mRNA levels for the inhibitory subunit gene pde6ha that could contribute to the regulation of photopic sensitivity by preventing overstimulation in photopic conditions. In rods, the mRNA levels of the inhibitory subunit gene pde6ga oscillate under normal conditions and dampen down in constant light but continue oscillating in constant darkness. There is an increase in total relative expression for pde6gb in constant conditions. These observations, together with previous data, suggest a complex regulation of the scotopic sensitivity involving endogenous and non-endogenous components, possibly present also in other teleost species. The G alpha(T) genes do not display mRNA oscillations and therefore may not be essential for the circadian regulation of photosensitivity. In summary, our results support different regulation for the zebrafish photopic and scotopic sensitivities and suggest circadian regulation of pde6ha as a key factor regulating photopic sensitivity, while the regulatory mechanisms in rods appear to be more complex.

  • 8.
    Abouzayed, Ayman
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics.
    Yim, Cheng-Bin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics.
    Mitran, Bogdan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics.
    Rinne, Sara S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Larhed, Mats
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics.
    Rosenström, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Orlova, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Synthesis and Preclinical Evaluation of Radio-Iodinated GRPR/PSMA Bispecific Heterodimers for the Theranostics Application in Prostate Cancer2019In: Pharmaceutics, ISSN 1999-4923, E-ISSN 1999-4923, Vol. 11, no 7, article id 358Article in journal (Refereed)
    Abstract [en]

    Gastrin-releasing peptide receptor (GRPR) and prostate-specific membrane antigen (PSMA) are overexpressed in most prostate cancers. GRPR expression is higher in early stages while PSMA expression increases with progression. The possibility of targeting both markers with a single theranostics radiotracer could improve patient management. Three GRPR/PSMA-targeting bispecific heterodimers (urea derivative PSMA-617 and bombesin-based antagonist RM26 linked via X-triazolyl-Tyr-PEG2, X = PEG2 (BO530), (CH2)(8) (BO535), none (BO536)) were synthesized by solid-phase peptide synthesis. Peptides were radio-iodinated and evaluated in vitro for binding specificity, cellular retention, and affinity. In vivo specificity for all heterodimers was studied in PC-3 (GRPR-positive) and LNCaP (PSMA-positive) xenografts. [I-125]I-BO530 was evaluated in PC-3pip (GRPR/PSMA-positive) xenografts. Micro single-photon emission computed tomography/computed tomography (microSPECT/CT) scans were acquired. The heterodimers were radiolabeled with high radiochemical yields, bound specifically to both targets, and demonstrated high degree of activity retention in PC-3pip cells. Only [I-125]I-BO530 demonstrated in vivo specificity to both targets. A biodistribution study of [I-125]I-BO530 in PC-3pip xenografted mice showed high tumor activity uptake (30%-35%ID/g at 3 h post injection (pi)). Activity uptake in tumors was stable and exceeded all other organs 24 h pi. Activity uptake decreased only two-fold 72 h pi. The GRPR/PSMA-targeting heterodimer [I-125]I-BO530 is a promising agent for theranostics application in prostate cancer.

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  • 9.
    Abramov, Sergei
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Kazan Fed Univ, Inst Fundamental Med & Biol, Kazan, Russia.
    Kozyrev, Sergey V.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Farias, Fabiana H. G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Washington Univ, Genome Inst, Sch Med, St Louis, MO USA.
    Dahlqvist, Johanna
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Leonard, Dag
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wilbe, Maria
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Swedish Univ Agr Sci SLU, Dept Anim Breeding & Genet, Uppsala, Sweden.
    Alexsson, Andrei
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pielberg, Gerli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hansson-Hamlin, H.
    Swedish Univ Agr Sci SLU, Dept Clin Sci, Uppsala, Sweden.
    Andersson, G.
    Swedish Univ Agr Sci SLU, Dept Anim Breeding & Genet, Uppsala, Sweden.
    Tandre, Karolina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eloranta, Maija-Leena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ronnblom, L.
    Swedish Univ Agr Sci SLU, Dept Clin Sci, Uppsala, Sweden.
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    The risk allele A of rs200395694 associated with SLE in Swedish patients affects on MEF2D gene regulation and alternative splicing2018In: Human Gene Therapy, ISSN 1043-0342, E-ISSN 1557-7422, Vol. 29, no 12, p. A44-A44Article in journal (Other academic)
  • 10.
    Acharya, Shikha
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Odontol, Dept Oral Microbiol & Immunol, PO 450, S-40530 Gothenburg, Sweden.
    Jin, Chunsheng
    Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Med Biochem & Cell Biol, Gothenburg, Sweden.
    Bylund, Johan
    Univ Gothenburg, Sahlgrenska Acad, Inst Odontol, Dept Oral Microbiol & Immunol, PO 450, S-40530 Gothenburg, Sweden.
    Shen, Qiujin
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jontell, Mats
    Univ Gothenburg, Sahlgrenska Acad, Inst Odontol, Dept Oral Med & Pathol, Gothenburg, Sweden.
    Carlen, Anette
    Univ Gothenburg, Sahlgrenska Acad, Inst Odontol, Dept Oral Microbiol & Immunol, PO 450, S-40530 Gothenburg, Sweden.
    Karlsson, Niclas G.
    Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Med Biochem & Cell Biol, Gothenburg, Sweden.
    Reduced sialyl-Lewis(x) on salivary MUC7 from patients with burning mouth syndrome2019In: MOLECULAR OMICS, ISSN 2515-4184, Vol. 15, no 5, p. 331-339Article in journal (Refereed)
    Abstract [en]

    We analysed and compared MUC7 O-glycosylation and inflammatory biomarkers in saliva from female patients with burning mouth syndrome (BMS) and gender/age-matched controls. Oligosaccharides from salivary MUC7 from BMS and controls were released. Inflammatory mediators were measured by multiplex proximity extension assay. Presence of sialyl-Lewis(x) (Si-Le(x)) epitope on MUC7 was confirmed using Western blot. MUC7 O-glycans and measured inflammatory biomarkers were found to be similar between BMS and controls. However, oligosaccharides sialyl-Lewis(x) (Si-Le(x)) was found to be reduced in samples from BMS patients. Positive correlation (combined patients and controls) was found between levels of C-C motif chemokine 19 (CCL-19) and the amount of core-2 oligosaccharides on MUC7 as well as fractalkine (CX3CL1) and level of sialylation. Patients with BMS were shown to represent a heterogeneous group in terms of inflammatory biomarkers. This indicates that BMS patients could be further stratified on the basis of low-level inflammation. The results furthermore indicate that reduced sialylation of MUC7, particularly Si-Le(x), may be an important feature in patients with BMS. However, the functional aspects and potential involvement in immune regulation of Si-Le(x) remains unclear. Our data suggests a chemokine driven alteration of MUC7 glycosylation.

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  • 11.
    Adams, Hieab H. H.
    et al.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Radiol & Nucl Med, Rotterdam, Netherlands..
    Hibar, Derrek P.
    Univ Southern Calif, Keck Sch Med, USC Mark & Mary Stevens Neuroimaging & Informat I, Imaging Genet Ctr, Los Angeles, CA USA..
    Chouraki, Vincent
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.;Univ Lille, RID AGE Risk Factors & Mol Determinants Aging Rel, CHU Lille, Inserm,Inst Pasteur Lille, Lille, France.;Framingham Heart Dis Epidemiol Study, Framingham, MA USA..
    Stein, Jason L.
    Univ Southern Calif, Keck Sch Med, USC Mark & Mary Stevens Neuroimaging & Informat I, Imaging Genet Ctr, Los Angeles, CA USA.;Univ N Carolina, Dept Genet, Chapel Hill, NC USA.;Univ N Carolina, UNC Neurosci Ctr, Chapel Hill, NC USA..
    Nyquist, Paul A.
    Johns Hopkins Univ, Dept Neurol, Dept Anesthesia Crit Care Med, Dept Neurosurg, Baltimore, MD 21218 USA..
    Renteria, Miguel E.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    Trompet, Stella
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands..
    Arias-Vasquez, Alejandro
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands..
    Seshadri, Sudha
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.;Framingham Heart Dis Epidemiol Study, Framingham, MA USA..
    Desrivieres, Sylvane
    Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, London, England..
    Beecham, Ashley H.
    Univ Miami, Miller Sch Med, Dept Human Genet, Dr John T Macdonald Fdn, Miami, FL 33136 USA.;Univ Miami, Miller Sch Med, John P Hussman Inst Human Gen, Miami, FL 33136 USA..
    Jahanshad, Neda
    Univ Southern Calif, Keck Sch Med, USC Mark & Mary Stevens Neuroimaging & Informat I, Imaging Genet Ctr, Los Angeles, CA USA..
    Wittfeld, Katharine
    German Ctr Neurodegenerat Dis DZNE Rostock Greifs, Greifswald, Germany.;Univ Med Greifswald, Dept Psychiat, Greifswald, Germany..
    Van der Lee, Sven J.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Abramovic, Lucija
    UMC Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Alhusaini, Saud
    McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Montreal, PQ, Canada.;Royal Coll Surgeons Ireland, Dublin 2, Ireland..
    Amin, Najaf
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Andersson, Micael
    Umea Univ, Dept Integrat Med Biol, Umea, Sweden.;Umea Univ, Umea Ctr Funct Brain Imaging, Umea, Sweden..
    Arfanakis, Konstantinos
    IIT, Dept Biomed Engn, Chicago, IL 60616 USA.;Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.;Rush Univ, Med Ctr, Dept Diagnost Radiol & Nucl Med, Chicago, IL 60612 USA..
    Aribisala, Benjamin S.
    Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh, Midlothian, Scotland.;Lagos State Univ, Dept Comp Sci, Lagos, Nigeria.;Univ Edinburgh, Dept Neuroimaging Sci, Scottish Imaging Network, Edinburgh, Midlothian, Scotland..
    Armstrong, Nicola J.
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia.;Murdoch Univ, Math & Stat, Perth, WA, Australia..
    Athanasiu, Lavinia
    Univ Oslo, Inst Clin Med, NORMENT KG Jebsen Ctr, Oslo, Norway.;Oslo Univ Hosp, Div Mental Hlth & Addict, NORMENT KG Jebsen Ctr, Oslo, Norway..
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Beiser, Alexa
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.;Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Bernard, Manon
    Univ Toronto, Hosp Sick Children, Toronto, ON, Canada..
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA..
    Blanken, Laura M. E.
    Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands.;Erasmus MC Sophia Childrens Hosp, Dept Child & Adolescent Psychiat Psychol, Rotterdam, Netherlands..
    Blanton, Susan H.
    Univ Miami, Miller Sch Med, Dept Human Genet, Dr John T Macdonald Fdn, Miami, FL 33136 USA.;Univ Miami, Miller Sch Med, John P Hussman Inst Human Gen, Miami, FL 33136 USA..
    Bohlken, Marc M.
    UMC Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Boks, Marco P.
    UMC Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Bralten, Janita
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands..
    Brickman, Adam M.
    Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA.;Columbia Univ, GH Sergievsky Ctr, Med Ctr, New York, NY USA.;Columbia Univ, Dept Neurol, Med Ctr, New York, NY USA..
    Carmichael, Owen
    Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA..
    Chakravarty, M. Mallar
    Douglas Mental Hlth Univ Inst, Cerebral Imaging Ctr, Montreal, PQ, Canada.;McGill Univ, Dept Psychiat & Biomed Engn, Montreal, PQ, Canada..
    Chauhan, Ganesh
    Univ Bordeaux, INSERM Unit U1219, Bordeaux, France..
    Chen, Qiang
    Lieber Inst Brain Dev, Baltimore, MD USA..
    Ching, Christopher R. K.
    Univ Southern Calif, Keck Sch Med, USC Mark & Mary Stevens Neuroimaging & Informat I, Imaging Genet Ctr, Los Angeles, CA USA.;Univ Calif Los Angeles, Sch Med, Interdept Neurosci Grad Program, Los Angeles, CA USA..
    Cuellar-Partida, Gabriel
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    Den Braber, Anouk
    Vrije Univ Amsterdam, Biol Psychol, Neurosci Campus Amsterdam, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Doan, Nhat Trung
    Univ Oslo, Inst Clin Med, NORMENT KG Jebsen Ctr, Oslo, Norway..
    Ehrlich, Stefan
    Tech Univ Dresden, Fac Med, Div Psychol & Social Med & Dev Neurosci, Dresden, Germany.;Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA..
    Filippi, Irina
    Univ Paris Sud, Univ Paris Descartes, NSERM Unit Neuroimaging & Psychiat 1000, Paris, France.;Hosp Cochin, AP HP, Maison Solenn Adolescent Psychopathol & Med Dept, Paris, France..
    Ge, Tian
    Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.;Harvard Med Sch, Boston, MA USA.;Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Boston, MA USA..
    Giddaluru, Sudheer
    Univ Bergen, Dept Clin Sci, NORMENT KG Jebsen Ctr Psychosis Res, N-5020 Bergen, Norway.;Haukeland Hosp, Ctr Med Genet & Mol Med, Dr Einar Martens Res Grp Biol Psychiat, Bergen, Norway..
    Goldman, Aaron L.
    Lieber Inst Brain Dev, Baltimore, MD USA..
    Gottesman, Rebecca F.
    Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA..
    Greven, Corina U.
    Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Nijmegen, Netherlands.;Karakter Child & Adolescent Psychiat Univ Ctr, Nijmegen, Netherlands.;Kings Coll London, Med Res Council Social, Genet & Dev Psychiat Ctr, Inst Psychol Psychiat & Neurosci, London, England..
    Grimm, Oliver
    Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Mannheim, Germany..
    Griswold, Michael E.
    Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA..
    Guadalupe, Tulio
    Max Planck Inst Psycholinguist, Language & Genet Dept, Nijmegen, Netherlands.;Int Max Planck Res Sch Language Sci, Nijmegen, Netherlands..
    Hass, Johanna
    Tech Univ Dresden, Fac Med, Dept Child & Adolescent Psychiat, Dresden, Germany..
    Haukvik, Unn K.
    Univ Oslo, Inst Clin Med, NORMENT KG Jebsen Ctr, Oslo, Norway.;Diakonhjemmet Hosp, Dept Res & Dev, Oslo, Norway..
    Hilal, Saima
    Natl Univ Singapore, Dept Pharmacol, Singapore, Singapore.;Natl Univ Hlth Syst, Mem Aging & Cognit Ctr, Singapore, Singapore..
    Hofer, Edith
    Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, Graz, Austria.;Med Univ Graz, Inst Med Informat Stat & Documentat, Graz, Austria..
    Hoehn, David
    Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany..
    Holmes, Avram J.
    Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.;Yale Univ, Dept Psychol, New Haven, CT USA..
    Hoogman, Martine
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands..
    Janowitz, Deborah
    Univ Med Greifswald, Dept Psychiat, Greifswald, Germany..
    Jia, Tianye
    Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, London, England..
    Kasperaviciute, Dalia
    UCL, Inst Neurol, London, England.;Epilepsy Soc, Gerrards Cross, Bucks, England.;Imperial Coll London, Dept Med, London, England..
    Kim, Sungeun
    Indiana Univ, Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN USA.;Indiana Univ, Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN USA..
    Klein, Marieke
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands..
    Kraemer, Bernd
    Heidelberg Univ, Dept Gen Psychiat, Sect Expt Psychopathol & Neuroimaging, Heidelberg, Germany..
    Lee, Phil H.
    Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.;Harvard Med Sch, Boston, MA USA.;Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Boston, MA USA.;Harvard Med Sch, Massachusetts Gen Hosp, Lurie Ctr Autism, Lexington, MA USA..
    Liao, Jiemin
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore..
    Liewald, David C. M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol, Edinburgh, Midlothian, Scotland..
    Lopez, Lorna M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol, Edinburgh, Midlothian, Scotland..
    Luciano, Michelle
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol, Edinburgh, Midlothian, Scotland..
    Macare, Christine
    Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, London, England..
    Marquand, Andre
    Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Ctr Cognit Neuroimaging, Nijmegen, Netherlands..
    Matarin, Mar
    UCL, Inst Neurol, London, England.;Epilepsy Soc, Gerrards Cross, Bucks, England.;UCL Inst Neurol, Reta Lila Weston Inst, London, England.;UCL Inst Neurol, Dept Mol Neurosci, London, England..
    Mather, Karen A.
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia..
    Mattheisen, Manuel
    Aarhus Univ, Dept Biomed, Aarhus, Denmark.;iPSYCH, Lundbeck Fdn Initiat Integrat Psychiat Res, Aarhus, Denmark.;iPSYCH, Lundbeck Fdn Initiat Integrat Psychiat Res, Copenhagen, Denmark.;Aarhus Univ, iSEQ, Ctr Integrated Sequencing, Aarhus, Denmark..
    Mazoyer, Bernard
    UMR5296 Univ Bordeaux, CNRS, CEA, Bordeaux, France..
    Mckay, David R.
    Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.;Olin Neuropsychiat Res Ctr, Hartford, CT USA..
    McWhirter, Rebekah
    Univ Tasmania, Menzies Inst Med Res, Hobart, Tas, Australia..
    Milaneschi, Yuri
    VU Univ Med Ctr GGZ Geest, EMGO Inst Hlth & Care Res, Dept Psychiat, Amsterdam, Netherlands.;VU Univ Med Ctr GGZ Geest, Neurosci Campus Amsterdam, Amsterdam, Netherlands..
    Mirza-Schreiber, Nazanin
    Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany..
    Muetzel, Ryan L.
    Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands.;Erasmus MC Sophia Childrens Hosp, Dept Child & Adolescent Psychiat Psychol, Rotterdam, Netherlands..
    Maniega, Susana Munoz
    Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Neuroimaging Sci, Scottish Imaging Network, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol, Edinburgh, Midlothian, Scotland..
    Nho, Kwangsik
    Indiana Univ, Sch Med, Ctr Neuroimaging Radiol & Imaging Sci, Indianapolis, IN USA.;Indiana Univ, Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN USA.;Indiana Univ, Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN USA..
    Nugent, Allison C.
    NIMH, Exp Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA..
    Loohuis, Loes M. Olde
    Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA..
    Oosterlaan, Jaap
    Vrije Univ Amsterdam, Dept Clin Neuropsychol, Amsterdam, Netherlands..
    Papmeyer, Martina
    Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland.;Univ Bern, Univ Hosp Psychiat, Translat Res Ctr, Div Syst Neurosci Psychopathol, CH-3012 Bern, Switzerland..
    Pappa, Irene
    Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands.;Erasmus Univ, Sch Pedag & Educ Sci, Rotterdam, Netherlands..
    Pirpamer, Lukas
    Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, Graz, Austria..
    Pudas, Sara
    Umea Univ, Dept Integrat Med Biol, Umea, Sweden.;Umea Univ, Umea Ctr Funct Brain Imaging, Umea, Sweden..
    Puetz, Benno
    Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany..
    Rajan, Kumar B.
    Rush Univ, Med Ctr, Rush Inst Healthy Aging, Chicago, IL 60612 USA..
    Ramasamy, Adaikalavan
    UCL Inst Neurol, Reta Lila Weston Inst, London, England.;UCL Inst Neurol, Dept Mol Neurosci, London, England.;Kings Coll London, Dept Med & Mol Genet, London, England.;Univ Oxford, Jenner Inst Labs, Oxford, England..
    Richards, Jennifer S.
    Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Karakter Child & Adolescent Psychiat Univ Ctr, Nijmegen, Netherlands..
    Risacher, Shannon L.
    Indiana Univ, Sch Med, Ctr Neuroimaging Radiol & Imaging Sci, Indianapolis, IN USA.;Indiana Univ, Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN USA..
    Roiz-Santianez, Roberto
    Univ Cantabria IDIVAL, Sch Med, Dept Med & Psychiat, Univ Hosp Marques de Valdecilla, Santander, Spain.;CIBERSAM Ctr Invest Biomed Red Salud Med, Santander, Spain..
    Rommelse, Nanda
    Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Karakter Child & Adolescent Psychiat Univ Ctr, Nijmegen, Netherlands..
    Rose, Emma J.
    Trinity Coll Dublin, Psychosis Res Grp, Dept Psychiat, Dublin, Ireland.;Trinity Coll Dublin, Trinity Translat Med Inst, Dublin, Ireland..
    Royle, Natalie A.
    Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Neuroimaging Sci, Scottish Imaging Network, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland..
    Rundek, Tatjana
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.;Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth Sci, Miami, FL 33136 USA..
    Saemann, Philipp G.
    Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany..
    Satizabal, Claudia L.
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.;Framingham Heart Dis Epidemiol Study, Framingham, MA USA..
    Schmaal, Lianne
    Orygen, Melbourne, Vic, Australia.;Univ Melbourne, Ctr Youth Mental Hlth, Melbourne, Vic, Australia.;Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Neurosci Campus Amsterdam, Amsterdam, Netherlands..
    Schork, Andrew J.
    Univ Calif San Diego, Dept Neurosci, Multimodal Imaging Lab, San Diego, CA 92103 USA.;Univ Calif San Diego, Dept Cognit Sci, San Diego, CA 92103 USA..
    Shen, Li
    Indiana Univ, Sch Med, Ctr Neuroimaging Radiol & Imaging Sci, Indianapolis, IN USA.;Indiana Univ, Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN USA.;Indiana Univ, Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN USA..
    Shin, Jean
    Univ Toronto, Hosp Sick Children, Toronto, ON, Canada..
    Shumskaya, Elena
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Ctr Cognit Neuroimaging, Nijmegen, Netherlands..
    Smith, Albert V.
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Sprooten, Emma
    Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.;Olin Neuropsychiat Res Ctr, Hartford, CT USA.;Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland.;Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA..
    Strike, Lachlan T.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.;Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia..
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany..
    Thomson, Russell
    Tordesillas-Gutierrez, Diana
    CIBERSAM Ctr Invest Biomed Red Salud Med, Santander, Spain.;Valdecilla Biomed Res Inst IDIVAL, Neuroimaging Unit, Technol Facil, Santander, Cantabria, Spain..
    Toro, Roberto
    Inst Pasteur, Paris, France..
    Trabzuni, Daniah
    UCL Inst Neurol, Reta Lila Weston Inst, London, England.;UCL Inst Neurol, Dept Mol Neurosci, London, England.;King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh, Saudi Arabia..
    Vaidya, Dhananjay
    Johns Hopkins Univ, Sch Med, Dept Med, GeneSTAR Res Ctr, Baltimore, MD 21205 USA..
    Van der Grond, Jeroen
    Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands..
    van der Meer, Dennis
    Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands..
    Van Donkelaar, Marjolein M. J.
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands..
    Van Eijk, Kristel R.
    UMC Utrecht, Human Neurogenet Unit, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Van Erp, Theo G. M.
    Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA..
    Van Rooij, Daan
    Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands..
    Walton, Esther
    Tech Univ Dresden, Fac Med, Dept Child & Adolescent Psychiat, Dresden, Germany..
    Westlye, Lars T.
    Oslo Univ Hosp, Div Mental Hlth & Addict, NORMENT KG Jebsen Ctr, Oslo, Norway.;Univ Oslo, Dept Psychol, NORMENT KG Jebsen Ctr, Oslo, Norway..
    Whelan, Christopher D.
    Univ Southern Calif, Keck Sch Med, USC Mark & Mary Stevens Neuroimaging & Informat I, Imaging Genet Ctr, Los Angeles, CA USA.;Royal Coll Surgeons Ireland, Dublin 2, Ireland..
    Windham, Beverly G.
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA..
    Winkler, Anderson M.
    Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.;Univ Oxford, FMRIB Ctr, Oxford, England..
    Woldehawariat, Girma
    NIMH, Exp Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA..
    Wolf, Christiane
    Univ Wurzburg, Dept Psychiat Psychosomat & Psychotherapy, Wurzburg, Germany..
    Wolfers, Thomas
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands..
    Xu, Bing
    Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, London, England..
    Yanek, Lisa R.
    Johns Hopkins Univ, Sch Med, Dept Med, GeneSTAR Res Ctr, Baltimore, MD 21205 USA..
    Yang, Jingyun
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.;Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA..
    Zijdenbos, Alex
    Biospect Inc, Montreal, PQ, Canada..
    Zwiers, Marcel P.
    Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Ctr Cognit Neuroimaging, Nijmegen, Netherlands..
    Agartz, Ingrid
    Univ Oslo, Inst Clin Med, NORMENT KG Jebsen Ctr, Oslo, Norway.;Diakonhjemmet Hosp, Dept Res & Dev, Oslo, Norway.;Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden..
    Aggarwal, Neelum T.
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.;Rush Univ, Med Ctr, Rush Inst Healthy Aging, Chicago, IL 60612 USA.;Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA..
    Almasy, Laura
    Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, San Antonio, TX USA.;Univ Penn, Dept Genet, Perelman Sch Med, Philadelphia, PA 19104 USA.;Childrens Hosp Philadelphia, Dept Biomed & Hlth Informat, Philadelphia, PA 19104 USA..
    Ames, David
    Royal Melbourne Hosp, Natl Ageing Res Inst, Melbourne, Vic, Australia.;Univ Melbourne, Acad Unit Psychiat Old Age, Melbourne, Vic, Australia..
    Amouyel, Philippe
    Univ Lille, RID AGE Risk Factors & Mol Determinants Aging Rel, CHU Lille, Inserm,Inst Pasteur Lille, Lille, France..
    Andreassen, Ole A.
    Univ Oslo, Inst Clin Med, NORMENT KG Jebsen Ctr, Oslo, Norway.;Oslo Univ Hosp, Div Mental Hlth & Addict, NORMENT KG Jebsen Ctr, Oslo, Norway..
    Arepalli, Sampath
    NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA..
    Assareh, Amelia A.
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia..
    Barral, Sandra
    Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA..
    Bastin, Mark E.
    Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Neuroimaging Sci, Scottish Imaging Network, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland..
    Becker, Diane M.
    Johns Hopkins Univ, Sch Med, Dept Med, GeneSTAR Res Ctr, Baltimore, MD 21205 USA..
    Becker, James T.
    Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.;Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA.;Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA..
    Bennett, David A.
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.;Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA..
    Blangero, John
    Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, San Antonio, TX USA..
    van Bokhoven, Hans
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands..
    Boomsma, Dorret I.
    Vrije Univ Amsterdam, Biol Psychol, Neurosci Campus Amsterdam, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Brodaty, Henry
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia.;UNSW, Dementia Collaborat Res Ctr Assessment & Better, Sydney, NSW, Australia..
    Brouwer, Rachel M.
    UMC Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Brunner, Han G.
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Maastricht Univ, Med Ctr, Dept Clin Genet, Maastricht, Netherlands..
    Buckner, Randy L.
    Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.;Harvard Univ, Dept Psychol, Ctr Brain Sci, 33 Kirkland St, Cambridge, MA 02138 USA..
    Buitelaar, Jan K.
    Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Karakter Child & Adolescent Psychiat Univ Ctr, Nijmegen, Netherlands..
    Bulayeva, Kazima B.
    Dagestan State Univ, Dept Evolut & Genet, Makhachkala, Dagestan, Russia..
    Cahn, Wiepke
    UMC Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Calhoun, Vince D.
    Mind Res Network, Albuquerque, NM USA.;LBERI, Albuquerque, NM USA.;Univ New Mexico, Dept ECE, Albuquerque, NM 87131 USA..
    Cannon, Dara M.
    NIMH, Exp Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.;Natl Univ Ireland Galway, Ctr Neuroimaging & Cognit Genom NICOG, NCBES Galway Neurosci Ctr, Coll Med Nursing & Hlth Sci,Clin Neuroimaging Lab, Galway, Ireland..
    Cavalleri, Gianpiero L.
    Royal Coll Surgeons Ireland, Dublin 2, Ireland..
    Chen, Christopher
    Natl Univ Singapore, Dept Pharmacol, Singapore, Singapore.;Natl Univ Hlth Syst, Mem Aging & Cognit Ctr, Singapore, Singapore..
    Cheng, Ching -Yu
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Duke NUS Grad Med Sch, Acad Med Res Inst, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore..
    Cichon, Sven
    Univ Basel, Dept Biomed, Div Med Genet, Basel, Switzerland.;Univ Bonn, Inst Human Genet, Bonn, Germany.;Res Ctr Julich, Inst Neurosci & Med INM1, Julich, Germany..
    Cookson, Mark R.
    NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA..
    Corvin, Aiden
    Trinity Coll Dublin, Psychosis Res Grp, Dept Psychiat, Dublin, Ireland.;Trinity Coll Dublin, Trinity Translat Med Inst, Dublin, Ireland..
    Crespo-Facorro, Benedicto
    Univ Cantabria IDIVAL, Sch Med, Dept Med & Psychiat, Univ Hosp Marques de Valdecilla, Santander, Spain.;CIBERSAM Ctr Invest Biomed Red Salud Med, Santander, Spain..
    Curran, Joanne E.
    Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, San Antonio, TX USA..
    Czisch, Michael
    Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany..
    Dale, Anders M.
    Univ Calif San Diego, Ctr Multimodal Imaging & Genet, San Diego, CA 92103 USA.;Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA.;Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA.;Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.;Univ Calif San Diego, Dept Cognit Sci, San Diego, CA 92103 USA..
    Davies, Gareth E.
    Avera Inst Human Genet, Sioux Falls, SD USA.;Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiat Gen, 75 Francis St, Boston, MA 02115 USA.;Brigham & Womens Hosp, Dept Psychiat, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    De Geus, Eco J. C.
    Vrije Univ Amsterdam, Biol Psychol, Neurosci Campus Amsterdam, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    De Jager, Philip L.
    Harvard Med Sch, Boston, MA USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Broad Inst, Cambridge, MA USA..
    de Zubicaray, Greig I.
    Queensland Univ Technol, Fac Hlth, Brisbane, Qld, Australia.;Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld, Australia..
    Delanty, Norman
    Royal Coll Surgeons Ireland, Dublin 2, Ireland.;Beaumont Hosp, Div Neurol, Dublin 9, Ireland..
    Depondt, Chantal
    Univ Libre Bruxelles, Hop Erasme, Dept Neurol, Brussels, Belgium..
    DeStefano, Anita L.
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA.;Haukeland Hosp, Ctr Med Genet & Mol Med, Dr Einar Martens Res Grp Biol Psychiat, Bergen, Norway..
    Dillman, Allissa
    NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA..
    Djurovic, Srdjan
    Univ Bergen, Dept Clin Sci, NORMENT KG Jebsen Ctr Psychosis Res, N-5020 Bergen, Norway.;Oslo Univ Hosp, Dept Med Genet, Oslo, Norway..
    Donohoe, Gary
    Natl Univ Ireland Galway, Cognit Genet & Cognit Therapy Grp, Neuroimaging Cognit & Genom Ctr NICOG, Galway, Ireland.;Natl Univ Ireland Galway, NCBES Galway Neurosci Ctr, Sch Psychol, Galway, Ireland.;Natl Univ Ireland Galway, Discipline Biochem, Galway, Ireland.;Trinity Coll Dublin, Dept Psychiat, Neuropsychiat Genet Res Grp, Dublin 8, Ireland.;Trinity Coll Dublin, Inst Psychiat, Dublin 8, Ireland..
    Drevets, Wayne C.
    NIMH, Exp Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.;Janssen Res & Dev LLC, Titusville, NJ USA..
    Duggirala, Ravi
    Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, San Antonio, TX USA..
    Dyer, Thomas D.
    Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, San Antonio, TX USA..
    Erk, Susanne
    Charite, CCM, Dept Psychiat & Psychotherapy, Berlin, Germany..
    Espeseth, Thomas
    Oslo Univ Hosp, Div Mental Hlth & Addict, NORMENT KG Jebsen Ctr, Oslo, Norway.;Univ Oslo, Dept Psychol, NORMENT KG Jebsen Ctr, Oslo, Norway..
    Evans, Denis A.
    Rush Univ, Med Ctr, Rush Inst Healthy Aging, Chicago, IL 60612 USA..
    Fedko, Iryna
    Vrije Univ Amsterdam, Biol Psychol, Neurosci Campus Amsterdam, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Fernandez, Guillen
    Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands..
    Ferrucci, Luigi
    NIA, Intramural Res Program, Baltimore, MD 21224 USA..
    Fisher, Simon E.
    Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Max Planck Inst Psycholinguist, Language & Genet Dept, Nijmegen, Netherlands..
    Fleischman, Debra A.
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.;Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.;Rush Univ, Med Ctr, Dept Behav Sci, Chicago, IL 60612 USA..
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland..
    Foroud, Tatiana M.
    Indiana Univ, Sch Med, Ctr Computat Biol & Bioinformat, Indianapolis, IN USA.;Indiana Univ, Sch Med, Med & Mol Genet, Indianapolis, IN USA..
    Fox, Peter T.
    Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA..
    Francks, Clyde
    Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands.;Max Planck Inst Psycholinguist, Language & Genet Dept, Nijmegen, Netherlands..
    Fukunaga, Masaki
    Natl Inst Physiol Sci, Div Cerebral Integrat, Aichi, Japan..
    Gibbs, J. Raphael
    UCL Inst Neurol, Reta Lila Weston Inst, London, England.;UCL Inst Neurol, Dept Mol Neurosci, London, England.;NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA..
    Glahn, David C.
    Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.;Olin Neuropsychiat Res Ctr, Hartford, CT USA..
    Gollub, Randy L.
    Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA.;Harvard Med Sch, Boston, MA USA..
    Goring, Harald H. H.
    Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Edinburg, TX USA.;Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, San Antonio, TX USA..
    Grabe, Hans J.
    Univ Med Greifswald, Dept Psychiat, Greifswald, Germany..
    Green, Robert C.
    Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA..
    Gruber, Oliver
    Heidelberg Univ, Dept Gen Psychiat, Sect Expt Psychopathol & Neuroimaging, Heidelberg, Germany..
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Guelfi, Sebastian
    UCL Inst Neurol, Reta Lila Weston Inst, London, England.;UCL Inst Neurol, Dept Mol Neurosci, London, England..
    Hansell, Narelle K.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.;Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia..
    Hardy, John
    UCL Inst Neurol, Reta Lila Weston Inst, London, England.;UCL Inst Neurol, Dept Mol Neurosci, London, England..
    Hartman, Catharina A.
    Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands..
    Hashimoto, Ryota
    Osaka Univ, Grad Sch Med, Dept Psychiat, Osaka, Japan.;Osaka Univ, United Grad Sch Child Dev, Mol Res Ctr Childrens Mental Dev, Osaka, Japan..
    Hegenscheid, Katrin
    Univ Med Greifswald, Inst Diagnost Radiol & Neuroradiol, Greifswald, Germany..
    Heinz, Andreas
    Charite, CCM, Dept Psychiat & Psychotherapy, Berlin, Germany..
    Le Hellard, Stephanie
    Univ Bergen, Dept Clin Sci, NORMENT KG Jebsen Ctr Psychosis Res, N-5020 Bergen, Norway.;Haukeland Hosp, Ctr Med Genet & Mol Med, Dr Einar Martens Res Grp Biol Psychiat, Bergen, Norway..
    Hernandez, Dena G.
    UCL Inst Neurol, Reta Lila Weston Inst, London, England.;UCL Inst Neurol, Dept Mol Neurosci, London, England.;NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.;German Ctr Neurodegenerat Dis DZNE, Tubingen, Germany..
    Heslenfeld, Dirk J.
    Vrije Univ Amsterdam, Dept Psychol, Amsterdam, Netherlands..
    Ho, Beng-Choon
    Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA..
    Hoekstra, Pieter J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands..
    Hoffmann, Wolfgang
    German Ctr Neurodegenerat Dis DZNE Rostock Greifs, Greifswald, Germany.;Univ Med Greifswald, Inst Community Med, Greifswald, Germany..
    Hofman, Albert
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Holsboer, Florian
    Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany.;HMNC Brain Hlth, Munich, Germany..
    Homuth, Georg
    Univ Med Greifswald, Interfac Inst Genet & Funct Gen, Greifswald, Germany..
    Hosten, Norbert
    Univ Med Greifswald, Inst Diagnost Radiol & Neuroradiol, Greifswald, Germany..
    Hottenga, Jouke-Jan
    Vrije Univ Amsterdam, Biol Psychol, Neurosci Campus Amsterdam, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Pol, Hilleke E. Hulshoff
    UMC Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Ikeda, Masashi
    Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi, Japan..
    Ikram, M. Kamran
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Natl Univ Singapore, Dept Pharmacol, Singapore, Singapore.;Natl Univ Hlth Syst, Mem Aging & Cognit Ctr, Singapore, Singapore.;Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Duke NUS Grad Med Sch, Acad Med Res Inst, Singapore, Singapore..
    Jack, Clifford R., Jr.
    Mayo Clin, Dept Radiol, Rochester, MN USA..
    Jenldnson, Mark
    Univ Oxford, FMRIB Ctr, Oxford, England..
    Johnson, Robert
    Univ Maryland, Sch Med, NICHD Brain & Tissue Bank Dev Disorders, Baltimore, MD 21201 USA..
    Jonsson, Erik G.
    Univ Oslo, Inst Clin Med, NORMENT KG Jebsen Ctr, Oslo, Norway.;Univ Oxford, FMRIB Ctr, Oxford, England..
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands..
    Kahn, Rene S.
    UMC Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Kanai, Ryota
    Univ Sussex, Sch Psychol, Brighton, E Sussex, England.;UCL, Inst Cognit Neurosci, London, England.;Araya Brain Imaging, Dept Neuroinformat, Tokyo, Japan..
    Kloszewska, Iwona
    Med Univ Lodz, Lodz, Poland..
    Knopman, David S.
    Mayo Clin, Dept Neurol, Rochester, MN USA..
    Kochunov, Peter
    Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21201 USA..
    Kwok, John B.
    Neurosci Res Australia, Sydney, NSW, Australia.;UNSW, Sch Med Sci, Sydney, NSW, Australia..
    Lawrie, Stephen M.
    Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland..
    Lemaitre, Herve
    Univ Paris Sud, Univ Paris Descartes, NSERM Unit Neuroimaging & Psychiat 1000, Paris, France.;Hosp Cochin, AP HP, Maison Solenn Adolescent Psychopathol & Med Dept, Paris, France..
    Liu, Xinmin
    NIMH, Exp Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.;Columbia Univ, Med Ctr, New York, NY USA..
    Longo, Dan L.
    NIA, Genet Lab, NIH, Baltimore, MD 21224 USA..
    Longstreth, W. T., Jr.
    Univ Washington, Dept Neurol, Seattle, WA 98195 USA.;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA..
    Lopez, Oscar L.
    Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA.;Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA..
    Lovestone, Simon
    Univ Oxford, Dept Psychiat, Oxford, England.;Kings Coll London, NIHR Dementia Biomed Res Unit, London, England..
    Martinez, Oliver
    Univ Calif Davis, Dept Neurol, Imaging Dementia & Aging IDeA Lab, Sacramento, CA 95817 USA.;Univ Calif Davis, Ctr Neurosci, Sacramento, CA 95817 USA..
    Martinot, Jean-Luc
    Univ Paris Sud, Univ Paris Descartes, NSERM Unit Neuroimaging & Psychiat 1000, Paris, France.;Hosp Cochin, AP HP, Maison Solenn Adolescent Psychopathol & Med Dept, Paris, France..
    Mattay, Venkata S.
    Lieber Inst Brain Dev, Baltimore, MD USA.;Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.;Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA..
    McDonald, Colm
    Natl Univ Ireland Galway, Ctr Neuroimaging & Cognit Genom NICOG, NCBES Galway Neurosci Ctr, Coll Med Nursing & Hlth Sci,Clin Neuroimaging Lab, Galway, Ireland..
    McIntosh, Andrew M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland..
    McMahon, Katie L.
    Univ Queensland, Ctr Adv Imaging, Brisbane, Qld, Australia..
    McMahon, Francis J.
    NIMH, Exp Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA..
    Mecocci, Patrizia
    Univ Perugia, Dept Med, Sect Gerontol & Geriatr, Perugia, Italy..
    Melle, Ingrid
    Univ Oslo, Inst Clin Med, NORMENT KG Jebsen Ctr, Oslo, Norway.;Oslo Univ Hosp, Div Mental Hlth & Addict, NORMENT KG Jebsen Ctr, Oslo, Norway..
    Meyer-Lindenberg, Andreas
    Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Mannheim, Germany..
    Mohnke, Sebastian
    Charite, CCM, Dept Psychiat & Psychotherapy, Berlin, Germany..
    Montgomery, Grant W.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    Morris, Derek W.
    Natl Univ Ireland Galway, Cognit Genet & Cognit Therapy Grp, Neuroimaging Cognit & Genom Ctr NICOG, Galway, Ireland.;Natl Univ Ireland Galway, NCBES Galway Neurosci Ctr, Sch Psychol, Galway, Ireland.;Natl Univ Ireland Galway, Discipline Biochem, Galway, Ireland.;Trinity Coll Dublin, Dept Psychiat, Neuropsychiat Genet Res Grp, Dublin 8, Ireland.;Trinity Coll Dublin, Inst Psychiat, Dublin 8, Ireland..
    Mosley, Thomas H.
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA..
    Muhleisen, Thomas W.
    Natl Univ Ireland Galway, Ctr Neuroimaging & Cognit Genom NICOG, NCBES Galway Neurosci Ctr, Coll Med Nursing & Hlth Sci,Clin Neuroimaging Lab, Galway, Ireland.;Res Ctr Julich, Inst Neurosci & Med INM1, Julich, Germany..
    Mueller-Myhsok, Bertram
    Max Planck Inst Psychiat, Dept Translat Res Psychiat, Munich, Germany.;Munich Cluster Syst Neurol SyNergy, Munich, Germany.;Univ Liverpool, Inst Translat Med, Liverpool, Merseyside, England..
    Nalls, Michael A.
    NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA..
    Nauck, Matthias
    Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany.;German Ctr Cardiovasc Res DZHK eV, Partner Site Greifswald, Berlin, Germany..
    Nichols, Thomas E.
    Univ Oxford, FMRIB Ctr, Oxford, England.;Univ Warwick, Dept Stat, Coventry, W Midlands, England.;Univ Warwick, Warwick Mfg Grp, Coventry, W Midlands, England..
    Niessen, Wiro J.
    Erasmus MC, Dept Radiol & Nucl Med, Rotterdam, Netherlands.;Erasmus MC, Dept Med Informat, Rotterdam, Netherlands.;Delft Univ Technol, Fac Sci Appl, Delft, Netherlands..
    Noethen, Markus M.
    Univ Bonn, Inst Human Genet, Bonn, Germany.;Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany..
    Nyberg, Lars
    Umea Univ, Dept Integrat Med Biol, Umea, Sweden.;Umea Univ, Umea Ctr Funct Brain Imaging, Umea, Sweden..
    Ohi, Kazutaka
    Osaka Univ, Grad Sch Med, Dept Psychiat, Osaka, Japan..
    Olvera, Rene L.
    Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA..
    Ophoff, Roel A.
    UMC Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands.;Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA..
    Pandolfo, Massimo
    Univ Libre Bruxelles, Hop Erasme, Dept Neurol, Brussels, Belgium..
    Paus, Tomas
    Univ Toronto, Rotman Res Inst, Toronto, ON, Canada.;Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada.;Univ Toronto, Dept Psychiat, Toronto, ON M5S 1A1, Canada.;Child Mind Inst, New York, NY USA..
    Pausova, Zdenka
    Univ Toronto, Hosp Sick Children, Toronto, ON, Canada.;Univ Toronto, Dept Phys, Toronto, ON, Canada.;Univ Toronto, Dept Nutr Sci, Toronto, ON, Canada..
    Penninx, Brenda W. J. H.
    Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Neurosci Campus Amsterdam, Amsterdam, Netherlands..
    Pike, G. Bruce
    Univ Calgary, Dept Radiol, Calgary, AB, Canada.;Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada..
    Potkin, Steven G.
    Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA..
    Psaty, Bruce M.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Univ Washington, Dept Med, Seattle, WA USA.;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.;Grp Hlth Res Inst, Grp Hlth, Seattle, WA USA..
    Reppermund, Simone
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia.;UNSW Med, Sch Psychiat, Dept Dev Disabil Neuropsychiat, Kensington, NSW, Australia..
    Rietschel, Marcella
    Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Mannheim, Germany..
    Roffman, Joshua L.
    Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA..
    Romanczuk-Seiferth, Nina
    Charite, CCM, Dept Psychiat & Psychotherapy, Berlin, Germany..
    Rotter, Jerome I.
    Univ Calif Los Angeles, Med Ctr, Ilnst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst & Pediat Harbor, Torrance, CA 90509 USA..
    Ryten, Mina
    UCL Inst Neurol, Reta Lila Weston Inst, London, England.;UCL Inst Neurol, Dept Mol Neurosci, London, England.;Kings Coll London, Dept Med & Mol Genet, London, England..
    Sacco, Ralph L.
    Univ Miami, Miller Sch Med, John P Hussman Inst Human Gen, Miami, FL 33136 USA.;Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.;Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth Sci, Miami, FL 33136 USA.;Univ Miami, Miller Sch Med, Evelyn F McKnight Brain Inst, Miami, FL 33136 USA..
    Sachdev, Perminder S.
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia.;Prince Wales Hosp, Neuropsychiat Inst, Sydney, NSW, Australia..
    Saykin, Andrew J.
    Indiana Univ, Sch Med, Ctr Neuroimaging Radiol & Imaging Sci, Indianapolis, IN USA.;Indiana Univ, Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN USA.;Indiana Univ, Sch Med, Med & Mol Genet, Indianapolis, IN USA..
    Schmidt, Reinhold
    Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, Graz, Austria..
    Schofield, Peter R.
    Neurosci Res Australia, Sydney, NSW, Australia.;UNSW, Sch Med Sci, Sydney, NSW, Australia..
    Sigurdsson, Sigurdur
    Iceland Heart Assoc, Kopavogur, Iceland..
    Simmons, Andy
    Kings Coll London, Inst Psychiat, Dept Neuroimaging, London, England.;Kings Coll London, Biomed Res Ctr Mental Hlth, London, England.;Kings Coll London, Biomed Res Unit Dementia, London, England..
    Singleton, Andrew
    NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA..
    Sisodiya, Sanjay M.
    UCL, Inst Neurol, London, England.;Epilepsy Soc, Gerrards Cross, Bucks, England..
    Smith, Colin
    Univ Edinburgh, Acad Dept Neuropathol, Ctr Clin Brain Sci, MRC Edinburgh Brain Bank, Edinburgh, Midlothian, Scotland..
    Smoller, Jordan W.
    Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.;Harvard Med Sch, Boston, MA USA.;Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Boston, MA USA..
    Soininen, Hindu.
    Univ Eastern Finland, Inst Clin Med Neurol, Kuopio, Finland.;Kuopio Univ Hosp, Neuroctr Neurol, Kuopio, Finland..
    Srikanth, Velandai
    Peninsula Hlth & Monash Univ, Dept Med, Melbourne, Vic, Australia..
    Steen, Vidar M.
    Univ Bergen, Dept Clin Sci, NORMENT KG Jebsen Ctr Psychosis Res, N-5020 Bergen, Norway.;Haukeland Hosp, Ctr Med Genet & Mol Med, Dr Einar Martens Res Grp Biol Psychiat, Bergen, Norway..
    Stott, David J.
    Univ Glasgow, Fac Med, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Sussmann, Jessika E.
    Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland..
    Thalamuthu, Anbupalam
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia..
    Tiemeier, Henning
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC Sophia Childrens Hosp, Dept Child & Adolescent Psychiat Psychol, Rotterdam, Netherlands..
    Toga, Arthur W.
    Univ Southern Calif, Keck Sch Med, Inst Neuroimaging & Informat, Lab Neuro Imaging, Los Angeles, CA USA..
    Traynor, Bryan J.
    NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA..
    Troncoso, Juan
    Johns Hopkins Univ, Brain Resource Ctr, Baltimore, MD USA..
    Turner, Jessica A.
    Georgia State Univ, Atlanta, GA 30303 USA..
    Tzourio, Christophe
    Univ Bordeaux, Institute Neurodegenerat Disorders, CEA, CNRS,UMR 5293, Bordeaux, France..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Hernandez, Maria C. Valdes
    Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Neuroimaging Sci, Scottish Imaging Network, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland..
    Van der Brug, Marcel
    Genentech Inc, San Francisco, CA 94080 USA..
    Van der Lugt, Aad
    Erasmus MC, Dept Radiol & Nucl Med, Rotterdam, Netherlands..
    Van der Wee, Nic J. A.
    Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands.;Leiden Univ, Med Ctr, Leiden Inst Brain & Cognit, Leiden, Netherlands..
    Van Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Van Haren, Neeltje E. M.
    UMC Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Van't Ent, Dennis
    Vrije Univ Amsterdam, Biol Psychol, Neurosci Campus Amsterdam, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Van Tol, Marie Jose
    Univ Groningen, Univ Med Ctr Groningen, Neuroimaging Ctr, Groningen, Netherlands..
    Vardarajan, Badri N.
    Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA..
    Veltman, Dick J.
    Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Neurosci Campus Amsterdam, Amsterdam, Netherlands..
    Vernooij, Meike W.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Radiol & Nucl Med, Rotterdam, Netherlands..
    Voelzke, Henry
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany..
    Walter, Henrik
    Charite, CCM, Dept Psychiat & Psychotherapy, Berlin, Germany..
    Wardlaw, Joanna M.
    Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Neuroimaging Sci, Scottish Imaging Network, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland..
    Wassink, Thomas H.
    Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA..
    Weale, Michael E.
    Kings Coll London, Dept Med & Mol Genet, London, England..
    Weinberger, Daniel R.
    Lieber Inst Brain Dev, Baltimore, MD USA.;Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA.;Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.;Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.;Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA..
    Weiner, Michael W.
    Univ Calif San Francisco, San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94143 USA..
    Wen, Wei
    Univ New South Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia..
    Westman, Eric
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden..
    White, Tonya
    Erasmus MC, Dept Radiol & Nucl Med, Rotterdam, Netherlands.;Erasmus MC Sophia Childrens Hosp, Dept Child & Adolescent Psychiat Psychol, Rotterdam, Netherlands..
    Wong, Tien Y.
    Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore.;Dagestan State Univ, Dept Evolut & Genet, Makhachkala, Dagestan, Russia.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore..
    Wright, Clinton B.
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.;Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth Sci, Miami, FL 33136 USA.;Univ Miami, Miller Sch Med, Evelyn F McKnight Brain Inst, Miami, FL 33136 USA..
    Zielke, H. Ronald
    Univ Maryland, Sch Med, NICHD Brain & Tissue Bank Dev Disorders, Baltimore, MD 21201 USA..
    Zonderman, Alan B.
    NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA..
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol Psychol, Edinburgh, Midlothian, Scotland..
    DeCarli, Charles
    Univ Calif Davis, Dept Neurol, Imaging Dementia & Aging IDeA Lab, Sacramento, CA 95817 USA.;Univ Calif Davis, Ctr Neurosci, Sacramento, CA 95817 USA..
    Schmidt, Helena
    Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria..
    Martin, Nicholas G.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    De Craen, Anton J. M.
    Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands..
    Wright, Margaret J.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Ctr Adv Imaging, Brisbane, Qld, Australia..
    Launer, Lenore J.
    NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA..
    Schumann, Gunter
    Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC SGDP Ctr, London, England..
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Inst Mol Med & Human Genet Ctr, Houston, TX 77030 USA..
    Franke, Barbara
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Dept Psychiat, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands..
    Debette, Stephanie
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.;Lieber Inst Brain Dev, Baltimore, MD USA.;Bordeaux Univ Hosp, Dept Neurol, Bordeaux, France..
    Medland, Sarah E.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    Ikram, M. Arfan
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Radiol & Nucl Med, Rotterdam, Netherlands.;Erasmus MC, Dept Neurol, Rotterdam, Netherlands..
    Thompson, Paul M.
    Univ Southern Calif, Keck Sch Med, USC Mark & Mary Stevens Neuroimaging & Informat I, Imaging Genet Ctr, Los Angeles, CA USA.;Univ Western Sydney, Sch Comp Engn & Math, Parramatta, NSW, Australia..
    Novel genetic loci underlying human intracranial volume identified through genome-wide association2016In: Nature Neuroscience, ISSN 1097-6256, E-ISSN 1546-1726, Vol. 19, no 12, p. 1569-1582Article in journal (Refereed)
    Abstract [en]

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rho(genetic) = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N-combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

  • 12.
    Adeyemi, Ahmed
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
    Bergman, Joakim
    AstraZeneca, Dept Med Chem Cardiovasc & Metab Dis, Innovat Med & Early Dev Biotech Unit, Pepparedsleden 1, S-43183 Molndal, Sweden..
    Branalt, Jonas
    AstraZeneca, Dept Med Chem Cardiovasc & Metab Dis, Innovat Med & Early Dev Biotech Unit, Pepparedsleden 1, S-43183 Molndal, Sweden..
    Sävmarker, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Larhed, Mats
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Continuous Flow Synthesis under High-Temperature/High-Pressure Conditions Using a Resistively Heated Flow Reactor2017In: Organic Process Research & Development, ISSN 1083-6160, E-ISSN 1520-586X, Vol. 21, no 7, p. 947-955Article in journal (Refereed)
    Abstract [en]

    A cheap, easy-to-build, and effective resistively heated reactor for continuous flow synthesis at high temperature and pressure is herein presented. The reactor is rapidly heated directly using, an electric current and is capable of rapidly delivering temperatures and pressures up to 400 degrees C and 200 bar, respectively. High-temperature and high-pressure applications of this reactor were safely performed and demonstrated by selected transformations such as esterifications, transesterifications, and direct carboxylic acid to nitrile reactions using supercritical ethanol, methanol, and acetonitrile. Reaction temperatures were between 300 and 400 degrees C with excellent conversions and good to excellent isolated product yields. Examples of Diels-Alder reactions were also carried out at temperatures up to 300 degrees C in high yield. No additives or catalysts were used in the reactions.

  • 13.
    Adeyemi, Ahmed
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Wetzel, Alexander
    AstraZeneca, Dept Med Chem, Cardiovasc Renal & Metab IMED Biotech Unit, Pepparedsleden 1, S-43183 Molndal, Sweden.
    Bergman, Joakim
    AstraZeneca, Dept Med Chem, Cardiovasc Renal & Metab IMED Biotech Unit, Pepparedsleden 1, S-43183 Molndal, Sweden.
    Brånalt, Jonas
    AstraZeneca, Dept Med Chem, Cardiovasc Renal & Metab IMED Biotech Unit, Pepparedsleden 1, S-43183 Molndal, Sweden.
    Larhed, Mats
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preparative Medicinal Chemistry.
    Regio- and Stereoselective Synthesis of Spirooxindoles via Mizoroki-Heck Coupling of Aryl Iodides2019In: Synlett: Accounts and Rapid Communications in Synthetic Organic Chemistry, ISSN 0936-5214, E-ISSN 1437-2096, Vol. 30, no 1, p. 82-88Article in journal (Refereed)
    Abstract [en]

    A method for highly regio- and stereoselective intramolecular Mizoroki-Heck 5- exo cyclization of aryl iodides to the corresponding spirooxindoles has been developed. Electron-rich and electron-deficient aryl iodide precursors were selectively ring-closed with high stereoselectivity and good yields. The double-bond position in the cyclopentene ring was controlled by careful choice of reaction conditions. These rare spiro compounds were further functionalized to rigidified unnatural amino acid derivatives by a subsequent gas-free Pd(0)-catalyzed alkoxycarbonylation, followed by selective O - and N -deprotections.

  • 14.
    Adl, Sina M.
    et al.
    Univ Saskatchewan, Dept Soil Sci, Coll Agr & Bioresources, 51 Campus Dr, Saskatoon, SK S7N 5A8, Canada.
    Bass, David
    Nat Hist Museum, Dept Life Sci, Cromwell Rd, London SW7 5BD, England;CEFAS, Barrack Rd, Weymouth DT4 8UB, Dorset, England.
    Lane, Christopher E.
    Univ Rhode Isl, Dept Biol Sci, Kingston, RI 02881 USA.
    Lukes, Julius
    Czech Acad Sci, Biol Ctr, Inst Parasitol, Ceske Budejovice 37005, Czech Republic;Univ South Bohemia, Fac Sci, Ceske Budejovice 37005, Czech Republic.
    Schoch, Conrad L.
    Natl Inst Biotechnol Informat, Natl Lib Med, NIH, Bethesda, MD 20892 USA.
    Smirnov, Alexey
    St Petersburg State Univ, Fac Biol, Dept Invertebrate Zool, St Petersburg 199034, Russia.
    Agatha, Sabine
    Univ Salzburg, Dept Biosci, Hellbrunnerstr 34, A-5020 Salzburg, Austria.
    Berney, Cedric
    CNRS, UMR 7144 AD2M, Grp Evolut Protistes & Ecosyst Pelag, Stn Biol Roscoff, Pl Georges Teissier, F-29680 Roscoff, France.
    Brown, Matthew W.
    Mississippi State Univ, Dept Biol Sci, Starkville, MS 39762 USA;Mississippi State Univ, Inst Genom Biocomp & Biotechnol, Starkville, MS 39762 USA.
    Burki, Fabien
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Cárdenas, Paco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Farmakognosi.
    Cepicka, Ivan
    Charles Univ Prague, Dept Zool, Fac Sci, Vinicna 7, CR-12844 Prague, Czech Republic.
    Chistyakova, Lyudmila
    St Petersburg State Univ, Core Facil Ctr Culture Collect Microorganisms, St Petersburg 198504, Russia.
    del Campo, Javier
    CSIC, Inst Ciencies Mar, Passeig Maritim Barceloneta 37-49, E-08003 Barcelona, Catalonia, Spain.
    Dunthorn, Micah
    Univ Kaiserslautern, Dept Ecol, Erwin Schroedinger St, D-67663 Kaiserslautern, Germany;Univ Duisburg Essen, Dept Eukaryot Microbiol, Univ Str 5, D-45141 Essen, Germany.
    Edvardsen, Bente
    Univ Oslo, Dept Biosci, POB 1066 Blindern, N-0316 Oslo, Norway.
    Eglit, Yana
    Dalhousie Univ, Dept Biol, Halifax B3H 4R2, NS, Canada.
    Guillou, Laure
    Univ Paris 06, Sorbonne Univ, Paris 6, CNRS,UMR 7144 AD2M,Stn Biol Roscoff, Pl Georges Teissier,,CS90074, F-29688 Roscoff, France.
    Hampl, Vladimir
    Charles Univ Prague, Dept Parasitol, Fac Sci, BIOCEV, Prumyslov 595, Vestec 25242, Czech Republic.
    Heiss, Aaron A.
    Amer Museum Nat Hist, Dept Invertebrate Zool, New York, NY 10024 USA.
    Hoppenrath, Mona
    DZMB German Ctr Marine Biodivers Res, D-26382 Wilhelmshaven, Germany.
    James, Timothy Y.
    Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
    Karnkowska, Anna
    Univ Warsaw, Dept Mol Phylogenet & Evolut, PL-02089 Warsaw, Poland.
    Karpov, Sergey
    St Petersburg State Univ, Fac Biol, Dept Invertebrate Zool, St Petersburg 199034, Russia;RAS, Lab Parasit Worms & Protistol, Zool Inst, St Petersburg 199034, Russia.
    Kim, Eunsoo
    Amer Museum Nat Hist, Dept Invertebrate Zool, New York, NY 10024 USA.
    Kolisko, Martin
    Czech Acad Sci, Biol Ctr, Inst Parasitol, Ceske Budejovice 37005, Czech Republic.
    Kudryavtsev, Alexander
    St Petersburg State Univ, Fac Biol, Dept Invertebrate Zool, St Petersburg 199034, Russia;RAS, Lab Parasit Worms & Protistol, Zool Inst, St Petersburg 199034, Russia.
    Lahr, Daniel J. G.
    Univ Sao Paulo, Dept Zool, Inst Biosci, Matao Travessa 14 Cidade Univ, BR-05508090 Sao Paulo, SP, Brazil.
    Lara, Enrique
    Univ Neuchatel, Lab Soil Biodivers, Rue Emile Argand 11, CH-2000 Neuchatel, Switzerland;CSIC, Real Jardim Bot,Plaza Murillo 2, E-28014 Madrid, Spain.
    Le Gall, Line
    Sorbonne Univ, Museum Natl Hist Nat, Inst Systemat Evolut Biodiversit, 57 Rue Cuvier,CP 39, F-75005 Paris, France.
    Lynn, Denis H.
    Univ Guelph, Dept Integrat Biol, Summerlee Sci Complex, Guelph, ON N1G 2W1, Canada;Univ British Columbia, Dept Zool, 4200-6270 Univ Blvd, Vancouver, BC V6T 1Z4, Canada.
    Mann, David G.
    Royal Bot Garden, Edinburgh EH3 5LR, Midlothian, Scotland;Inst Agrifood Res & Technol, C Poble Nou Km 5-5, E-43540 San Carlos de la Rapita, Spain.
    Massana, Ramon
    CSIC, Inst Ciencies Mar, Passeig Maritim Barceloneta 37-49, E-08003 Barcelona, Catalonia, Spain.
    Mitchell, Edward A. D.
    Univ Neuchatel, Lab Soil Biodivers, Rue Emile Argand 11, CH-2000 Neuchatel, Switzerland;Jardin Bot Neuchatel,Chemin Perthuis du Salut 58, CH-2000 Neuchatel, Switzerland.
    Morrow, Christine
    Natl Museums Northern Ireland, Dept Nat Sci, 153 Bangor Rd, Holywood BT18 0EU, England.
    Park, Jong Soo
    Kyungpook Natl Univ, Sch Earth Syst Sci, Dept Oceanog, Daegu, South Korea;Kyungpook Natl Univ, Sch Earth Syst Sci, Kyungpook Inst Oceanog, Daegu, South Korea.
    Pawlowski, Jan W.
    Univ Geneva, Dept Genet & Evolut, CH-1211 Geneva 4, Switzerland.
    Powell, Martha J.
    Univ Alabama, Dept Biol Sci, Tuscaloosa, AL 35487 USA.
    Richter, Daniel J.
    Univ Pompeu Fabra, CSIC, Inst Biol Evolut, Passeig Maritim Barceloneta 37-49, Barcelona 08003, Spain.
    Rueckert, Sonja
    Edinburgh Napier Univ, Sch Appl Sci, Edinburgh EH11 4BN, Midlothian, Scotland.
    Shadwick, Lora
    Univ Arkansas, Dept Biol Sci, Fayetteville, AR 72701 USA.
    Shimano, Satoshi
    Hosei Univ, Sci Res Ctr, Chiyoda Ku, 2-17-1 Fujimi, Tokyo, Japan.
    Spiegel, Frederick W.
    Univ Arkansas, Dept Biol Sci, Fayetteville, AR 72701 USA.
    Torruella, Guifre
    Univ Paris XI, Lab Evolut & Systemat, F-91405 Orsay, France.
    Youssef, Noha
    Oklahoma State Univ, Dept Microbiol & Mol Genet, Stillwater, OK 74074 USA.
    Zlatogursky, Vasily V.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology. St Petersburg State Univ, Fac Biol, Dept Invertebrate Zool, St Petersburg 199034, Russia.
    Zhang, Qianqian
    Chinese Acad Sci, Yantai Inst Coastal Zone Res, Yantai 264003, Peoples R China.
    Revisions to the Classification, Nomenclature, and Diversity of Eukaryotes2019In: Journal of Eukaryotic Microbiology, ISSN 1066-5234, E-ISSN 1550-7408, Vol. 66, no 1, p. 4-119Article in journal (Refereed)
    Abstract [en]

    This revision of the classification of eukaryotes follows that of Adl et al., 2012 [J. Euk. Microbiol. 59(5)] and retains an emphasis on protists. Changes since have improved the resolution of many nodes in phylogenetic analyses. For some clades even families are being clearly resolved. As we had predicted, environmental sampling in the intervening years has massively increased the genetic information at hand. Consequently, we have discovered novel clades, exciting new genera and uncovered a massive species level diversity beyond the morphological species descriptions. Several clades known from environmental samples only have now found their home. Sampling soils, deeper marine waters and the deep sea will continue to fill us with surprises. The main changes in this revision are the confirmation that eukaryotes form at least two domains, the loss of monophyly in the Excavata, robust support for the Haptista and Cryptista. We provide suggested primer sets for DNA sequences from environmental samples that are effective for each clade. We have provided a guide to trophic functional guilds in an appendix, to facilitate the interpretation of environmental samples, and a standardized taxonomic guide for East Asian users.

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  • 15.
    Adler, Jeremy
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Parmryd, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Quantifying colocalization: thresholding, void voxels and the H-coef2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 11, p. e111983-Article in journal (Refereed)
    Abstract [en]

    A critical step in the analysis of images is identifying the area of interest e.g. nuclei. When the nuclei are brighter than the remainder of the image an intensity can be chosen to identify the nuclei. Intensity thresholding is complicated by variations in the intensity of individual nuclei and their intensity relative to their surroundings. To compensate thresholds can be based on local rather than global intensities. By testing local thresholding methods we found that the local mean performed poorly while the Phansalkar method and a new method based on identifying the local background were superior. A new colocalization coefficient, the Hcoef, highlights a number of controversial issues. (i) Are molecular interactions measurable (ii) whether to include voxels without fluorophores in calculations, and (iii) the meaning of negative correlations. Negative correlations can arise biologically (a) because the two fluorophores are in different places or (b) when high intensities of one fluorophore coincide with low intensities of a second. The cases are distinct and we argue that it is only relevant to measure correlation using pixels that contain both fluorophores and, when the fluorophores are in different places, to just report the lack of co-occurrence and omit these uninformative negative correlation. The Hcoef could report molecular interactions in a homogenous medium. But biology is not homogenous and distributions also reflect physico-chemical properties, targeted delivery and retention. The Hcoef actually measures a mix of correlation and co-occurrence, which makes its interpretation problematic and in the absence of a convincing demonstration we advise caution, favouring separate measurements of correlation and of co-occurrence.

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  • 16.
    Adler, Jeremy
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sintorn, Ida-Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Parmryd, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Conventional analysis of movement on non-flat surfaces like the plasma membrane makes Brownian motion appear anomalous2019In: Communications Biology, ISSN 2399-3642, Vol. 2, article id 12Article in journal (Refereed)
  • 17. Adoue, Veronique
    et al.
    Schiavi, Alicia
    Light, Nicholas
    Carlsson Almlöf, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lundmark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ge, Bing
    Kwan, Tony
    Caron, Maxime
    Rönnblom, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology.
    Wang, Chuan
    Chen, Shu-Huang
    Goodall, Alison H
    Cambien, Francois
    Deloukas, Panos
    Ouwehand, Willem H
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pastinen, Tomi
    Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs2014In: Molecular Systems Biology, ISSN 1744-4292, E-ISSN 1744-4292, Vol. 10, no 10, p. 754-Article in journal (Refereed)
    Abstract [en]

    Most complex disease-associated genetic variants are located in non-coding regions and are therefore thought to be regulatory in nature. Association mapping of differential allelic expression (AE) is a powerful method to identify SNPs with direct cis-regulatory impact (cis-rSNPs). We used AE mapping to identify cis-rSNPs regulating gene expression in 55 and 63 HapMap lymphoblastoid cell lines from a Caucasian and an African population, respectively, 70 fibroblast cell lines, and 188 purified monocyte samples and found 40-60% of these cis-rSNPs to be shared across cell types. We uncover a new class of cis-rSNPs, which disrupt footprint-derived de novo motifs that are predominantly bound by repressive factors and are implicated in disease susceptibility through overlaps with GWAS SNPs. Finally, we provide the proof-of-principle for a new approach for genome-wide functional validation of transcription factor-SNP interactions. By perturbing NFκB action in lymphoblasts, we identified 489 cis-regulated transcripts with altered AE after NFκB perturbation. Altogether, we perform a comprehensive analysis of cis-variation in four cell populations and provide new tools for the identification of functional variants associated to complex diseases.

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  • 18.
    Agarwal, Prasoon
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Collier, Paul
    Fritz, Markus Hsi-Yang
    Benes, Vladimir
    Wiklund, Helena Jernberg
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Westermark, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Singh, Umashankar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    CGGBP1 mitigates cytosine methylation at repetitive DNA sequences2015In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 16, article id 390Article in journal (Refereed)
    Abstract [en]

    Background: CGGBP1 is a repetitive DNA-binding transcription regulator with target sites at CpG-rich sequences such as CGG repeats and Alu-SINEs and L1-LINEs. The role of CGGBP1 as a possible mediator of CpG methylation however remains unknown. At CpG-rich sequences cytosine methylation is a major mechanism of transcriptional repression. Concordantly, gene-rich regions typically carry lower levels of CpG methylation than the repetitive elements. It is well known that at interspersed repeats Alu-SINEs and L1-LINEs high levels of CpG methylation constitute a transcriptional silencing and retrotransposon inactivating mechanism. Results: Here, we have studied genome-wide CpG methylation with or without CGGBP1-depletion. By high throughput sequencing of bisulfite-treated genomic DNA we have identified CGGBP1 to be a negative regulator of CpG methylation at repetitive DNA sequences. In addition, we have studied CpG methylation alterations on Alu and L1 retrotransposons in CGGBP1-depleted cells using a novel bisulfite-treatment and high throughput sequencing approach. Conclusions: The results clearly show that CGGBP1 is a possible bidirectional regulator of CpG methylation at Alus, and acts as a repressor of methylation at L1 retrotransposons.

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  • 19.
    Agathangelidis, Andreas
    et al.
    Univ Vita Salute San Raffaele, Strateg Res Program CLL, Milan, Italy;Univ Vita Salute San Raffaele, Div Expt Oncol, B Cell Neoplasia Unit, Milan, Italy;IRCCS Ist Sci San Raffaele, Milan, Italy.
    Ljungström, Viktor
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
    Scarfo, Lydia
    Univ Vita Salute San Raffaele, Strateg Res Program CLL, Milan, Italy;Univ Vita Salute San Raffaele, Div Expt Oncol, B Cell Neoplasia Unit, Milan, Italy;IRCCS Ist Sci San Raffaele, Milan, Italy.
    Fazi, Claudia
    Univ Vita Salute San Raffaele, Strateg Res Program CLL, Milan, Italy;Univ Vita Salute San Raffaele, Div Expt Oncol, B Cell Neoplasia Unit, Milan, Italy;IRCCS Ist Sci San Raffaele, Milan, Italy.
    Gounari, Maria
    Univ Vita Salute San Raffaele, Strateg Res Program CLL, Milan, Italy;Univ Vita Salute San Raffaele, Div Expt Oncol, B Cell Neoplasia Unit, Milan, Italy;IRCCS Ist Sci San Raffaele, Milan, Italy;Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    Pandzic, Tatjana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sutton, Lesley-Ann
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Stamatopoulos, Kostas
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    Tonon, Giovanni
    IRCCS Ist Sci San Raffaele, Funct Genom Canc Unit, Div Expt Oncol, Milan, Italy.
    Rosenquist, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ghia, Paolo
    Univ Vita Salute San Raffaele, Strateg Res Program CLL, Milan, Italy;Univ Vita Salute San Raffaele, Div Expt Oncol, B Cell Neoplasia Unit, Milan, Italy;IRCCS Ist Sci San Raffaele, Milan, Italy.
    Highly similar genomic landscapes in monoclonal B-cell lymphocytosis and ultra-stable chronic lymphocytic leukemia with low frequency of driver mutations2018In: Haematologica, ISSN 0390-6078, E-ISSN 1592-8721, Vol. 103, no 5, p. 865-873Article in journal (Refereed)
    Abstract [en]

    Despite the recent discovery of recurrent driver mutations in chronic lymphocytic leukemia, the genetic factors involved in disease onset remain largely unknown. To address this issue, we per-formed whole-genome sequencing in 11 individuals with monoclonal B-cell lymphocytosis, both of the low-count and high-count subtypes, and 5 patients with ultra-stable chronic lymphocytic leukemia (>10 years without progression from initial diagnosis). All three entities were indistinguishable at the genomic level exhibiting low genomic complexity and similar types of somatic mutations. Exonic mutations were not frequently identified in putative chronic lymphocytic leukemia driver genes in all settings, including low-count monoclonal B-cell lymphocytosis. To corroborate these findings, we also performed deep sequencing in 11 known frequently mutated genes in an extended cohort of 28 monoclonal B-cell lym phocytosis/chronic lymphocytic leukemia cases. Interestingly, shared mutations were detected between clonal B cells and paired polymorphonuclear cells, strengthening the notion that at least a fraction of somatic mutations may occur before disease onset, likely at the hematopoietic stem cell level. Finally, we identified previously unreported non-coding variants targeting pathways relevant to B-cell and chronic lymphocytic leukemia development, likely associated with the acquisition of the characteristic neoplastic phenotype typical of both monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia.

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  • 20.
    Agathangelidis, Andreas
    et al.
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    Sutton, Lesley Ann
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Hadzidimitriou, Anastasia
    Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    Tresoldi, Cristina
    IRCCS San Raffaele Sci Inst, Div Immunol Transplantat & Infect, Milan, Italy.
    Langerak, Anton W.
    Erasmus Univ, Med Ctr, Lab Med Immunol, Dept Immunol, Rotterdam, Netherlands.
    Belessi, Chrysoula
    Nikea Gen Hosp, Hematol Dept, Piraeus, Greece.
    Davi, Frederic
    Hop La Pitie Salpetriere, AP HP, Dept Hematol, Paris, France;UPMC Univ Paris 06, UMRS 1138, Paris, France.
    Rosenquist, Richard
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Stamatopoulos, Kostas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
    Ghia, Paolo
    IRCCS Ist Scientifico San Raffaele, Div Expt Oncol, Milan, Italy;Univ Vita Salute San Raffaele, Milan, Italy.
    Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation2018In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, no 141, article id e57787Article in journal (Refereed)
    Abstract [en]

    During B cell maturation, the complex process of immunoglobulin (IG) gene V(D)J recombination coupled with somatic hypermutation (SHM) gives rise to a unique DNA sequence within each individual B cell. Since B cell malignancies result from the clonal expansion of a single cell, IG genes represent a unique molecular signature common to all the malignant cells within an individual patient; thus, IG gene rearrangements can be used as clonal markers. In addition to serving as an important clonal identifier, the IG gene sequence can act as a 'molecular timeline' since it is associated with specific developmental stages and hence reflects the history of the B cell involved in the neoplastic transformation. Moreover, for certain malignancies, in particular chronic lymphocytic leukemia (CLL), the IG gene sequence holds prognostic and potentially predictive capabilities. That said, extrapolating meaningful conclusions from IG gene sequence analysis would be impossible if robust methods and tools were not available to aid in their analysis. This article, drawing on the vast experience of the European Research Initiative on CLL (ERIC), details the technical aspects and essential requirements necessary to ensure reliable and reproducible IG gene sequence analysis in CLL, a test that is now recommended for all CLL patients prior to treatment. More specifically, the various analytical stages are described ranging from the identification of the clonotypic IG gene rearrangement and the determination of the nucleotide sequence to the accurate clinical interpretation of the IG gene sequence data.

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  • 21.
    Ahlgren, Kerstin M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Landegren, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Grimelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    von Euler, Henrik
    Sundberg, Katarina
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lobell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hedhammar, Åke
    Andersson, Göran
    Hansson-Hamlin, Helene
    Lernmark, Åke
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lack of evidence for a role of islet autoimmunity in the aetiology of canine diabetes mellitus2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 8, p. e105473-Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS:

    Diabetes mellitus is one of the most common endocrine disorders in dogs and is commonly proposed to be of autoimmune origin. Although the clinical presentation of human type 1 diabetes (T1D) and canine diabetes are similar, the aetiologies may differ. The aim of this study was to investigate if autoimmune aetiology resembling human T1D is as prevalent in dogs as previously reported.

    METHODS:

    Sera from 121 diabetic dogs representing 40 different breeds were tested for islet cell antibodies (ICA) and GAD65 autoantibodies (GADA) and compared with sera from 133 healthy dogs. ICA was detected by indirect immunofluorescence using both canine and human frozen sections. GADA was detected by in vitro transcription and translation (ITT) of human and canine GAD65, followed by immune precipitation. Sections of pancreata from five diabetic dogs and two control dogs were examined histopathologically including immunostaining for insulin, glucagon, somatostatin and pancreas polypeptide.

    RESULTS:

    None of the canine sera analysed tested positive for ICA on sections of frozen canine or human ICA pancreas. However, serum from one diabetic dog was weakly positive in the canine GADA assay and serum from one healthy dog was weakly positive in the human GADA assay. Histopathology showed marked degenerative changes in endocrine islets, including vacuolisation and variable loss of immune-staining for insulin. No sign of inflammation was noted.

    CONCLUSIONS/INTERPRETATIONS:

    Contrary to previous observations, based on results from tests for humoral autoreactivity towards islet proteins using four different assays, and histopathological examinations, we do not find any support for an islet autoimmune aetiology in canine diabetes mellitus.

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  • 22. Ahmad, Shafqat
    et al.
    Rukh, Gull
    Varga, Tibor V.
    Ali, Ashfaq
    Kurbasic, Azra
    Shungin, Dmitry
    Ericson, Ulrika
    Koivula, Robert W.
    Chu, Audrey Y.
    Rose, Lynda M.
    Ganna, Andrea
    Qi, Qibin
    Stancakova, Alena
    Sandholt, Camilla H.
    Elks, Cathy E.
    Curhan, Gary
    Jensen, Majken K.
    Tamimi, Rulla M.
    Allin, Kristine H.
    Jorgensen, Torben
    Brage, Soren
    Langenberg, Claudia
    Aadahl, Mette
    Grarup, Niels
    Linneberg, Allan
    Pare, Guillaume
    Magnusson, Patrik K. E.
    Pedersen, Nancy L.
    Boehnke, Michael
    Hamsten, Anders
    Mohlke, Karen L.
    Pasquale, Louis T.
    Pedersen, Oluf
    Scott, Robert A.
    Ridker, Paul M.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Laakso, Markku
    Hansen, Torben
    Qi, Lu
    Wareham, Nicholas J.
    Chasman, Daniel I.
    Hallmans, Goran
    Hu, Frank B.
    Renstrom, Frida
    Orho-Melander, Marju
    Franks, Paul W.
    Gene x Physical Activity Interactions in Obesity: Combined Analysis of 111,421 Individuals of European Ancestry2013In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 9, no 7, p. e1003607-Article in journal (Refereed)
    Abstract [en]

    Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS x physical activity interaction effect estimate (P-interaction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, P-interaction = 0.014 vs. n = 71,611, P-interaction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (P-interaction = 0.003) and the SEC16B rs10913469 (P-interaction = 0.025) variants showed evidence of SNP x physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.

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  • 23.
    Ahmed Osman, Omneya
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Beier, Sara
    Leibniz Inst Balt Sea Res, Warnemunde, Germany..
    Grabherr, Manfred
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bertilsson, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Interactions of Freshwater Cyanobacteria with Bacterial Antagonists2017In: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 83, no 7, article id UNSP e02634Article in journal (Refereed)
    Abstract [en]

    Cyanobacterial and algal mass development, or blooms, have severe effects on freshwater and marine systems around the world. Many of these phototrophs produce a variety of potent toxins, contribute to oxygen depletion, and affect water quality in several ways. Coexisting antagonists, such as cyanolytic bacteria, hold the potential to suppress, or even terminate, such blooms, yet the nature of this interaction is not well studied. We isolated 31 cyanolytic bacteria affiliated with the genera Pseudomonas, Stenotrophomonas, Acinetobacter, and Delftia from three eutrophic freshwater lakes in Sweden and selected four phylogenetically diverse bacterial strains with strong-to-moderate lytic activity. To characterize their functional responses to the presence of cyanobacteria, we performed RNA sequencing (RNA-Seq) experiments on coculture incubations, with an initial predator-prey ratio of 1: 1. Genes involved in central cellular pathways, stress-related heat or cold shock proteins, and antitoxin genes were highly expressed in both heterotrophs and cyanobacteria. Heterotrophs in coculture expressed genes involved in cell motility, signal transduction, and putative lytic activity. L, D-Transpeptidase was the only significantly upregulated lytic gene in Stenotrophomonas rhizophila EK20. Heterotrophs also shifted their central metabolism from the tricarboxylic acid cycle to the glyoxylate shunt. Concurrently, cyanobacteria clearly show contrasting antagonistic interactions with the four tested heterotrophic strains, which is also reflected in the physical attachment to their cells. In conclusion, antagonistic interactions with cyanobacteria were initiated within 24 h, and expression profiles suggest varied responses for the different cyanobacteria and studied cyanolytes. IMPORTANCE Here, we present how gene expression profiles can be used to reveal interactions between bloom-forming freshwater cyanobacteria and antagonistic heterotrophic bacteria. Species-specific responses in both heterotrophs and cyanobacteria were identified. The study contributes to a better understanding of the interspecies cellular interactions underpinning the persistence and collapse of cyanobacterial blooms.

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  • 24.
    Ahsan, Muhammad
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Ek, Weronica E
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Rask-Andersen, Mathias
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Karlsson, Torgny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind-Thomsen, Allan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Enroth, Stefan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Gyllensten, Ulf B.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Johansson, Åsa
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    The relative contribution of DNA methylation and genetic variants on protein biomarkers for human diseases.2017In: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, no 9, article id e1007005Article in journal (Refereed)
    Abstract [en]

    Associations between epigenetic alterations and disease status have been identified for many diseases. However, there is no strong evidence that epigenetic alterations are directly causal for disease pathogenesis. In this study, we combined SNP and DNA methylation data with measurements of protein biomarkers for cancer, inflammation or cardiovascular disease, to investigate the relative contribution of genetic and epigenetic variation on biomarker levels. A total of 121 protein biomarkers were measured and analyzed in relation to DNA methylation at 470,000 genomic positions and to over 10 million SNPs. We performed epigenome-wide association study (EWAS) and genome-wide association study (GWAS) analyses, and integrated biomarker, DNA methylation and SNP data using between 698 and 1033 samples depending on data availability for the different analyses. We identified 124 and 45 loci (Bonferroni adjusted P < 0.05) with effect sizes up to 0.22 standard units' change per 1% change in DNA methylation levels and up to four standard units' change per copy of the effective allele in the EWAS and GWAS respectively. Most GWAS loci were cis-regulatory whereas most EWAS loci were located in trans. Eleven EWAS loci were associated with multiple biomarkers, including one in NLRC5 associated with CXCL11, CXCL9, IL-12, and IL-18 levels. All EWAS signals that overlapped with a GWAS locus were driven by underlying genetic variants and three EWAS signals were confounded by smoking. While some cis-regulatory SNPs for biomarkers appeared to have an effect also on DNA methylation levels, cis-regulatory SNPs for DNA methylation were not observed to affect biomarker levels. We present associations between protein biomarker and DNA methylation levels at numerous loci in the genome. The associations are likely to reflect the underlying pattern of genetic variants, specific environmental exposures, or represent secondary effects to the pathogenesis of disease.

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  • 25.
    Ajalloueian, Fatemeh
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Fransson, Moa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Tavanai, Hossein
    Massuni, Mohammad
    Hilborn, Jöns
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    LeBlanc, Katarina
    Arpanaei, Ayyoob
    Magnusson, Peetra
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Investigation of Human Mesenchymal Stromal Cells Cultured on PLGA orPLGA/Chitosan Electrospun Nanofibers2015In: Journal of Bioprocessing & Biotechniques, ISSN 2155-9821, Vol. 5, no 6, article id 230Article in journal (Refereed)
    Abstract [en]

    We compared the viability, proliferation, and differentiation of human Mesenchymal Stromal Cells (MSC)after culture on poly(lactic-co-glycolic acid) (PLGA) and PLGA/chitosan (PLGA/CH) hybrid scaffolds. We appliedconventional and emulsion electrospinning techniques, respectively, for the fabrication of the PLGA and PLGA/CH scaffolds. Electrospinning under optimum conditions resulted in an average fiber diameter of 166 ± 33 nmfor the PLGA/CH and 680 ± 175 nm for the PLGA scaffold. The difference between the tensile strength of thePLGA and PLGA/CH nanofibers was not significant, but PLGA/CH showed a significantly lower tensile modulusand elongation at break. However, it should be noted that the extensibility of the PLGA/CH was higher than thatof the nanofibrous scaffolds of pure chitosan. As expected, a higher degree of hydrophilicity was seen with PLGA/CH, as compared to PLGA alone. The biocompatibility of the PLGA and PLGA/CH scaffolds was compared usingMTS assay as well as analysis by scanning electron microscopy and confocal microscopy. The results showed thatboth scaffold types supported the viability and proliferation of human MSC, with significantly higher rates on PLGA/CH nanofibers. Nonetheless, an analysis of gene expression of MSC grown on either PLGA or PLGA/CH showed asimilar differentiation pattern towards bone, nerve and adipose tissues.

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  • 26.
    Ajalloueian, Fatemeh
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Zeiai, Said
    Fossum, Magdalena
    Hilborn, Jöns G.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Polymer Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Constructs of electrospun PLGA, compressed collagen and minced urothelium for minimally manipulated autologous bladder tissue expansion2014In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 35, no 22, p. 5741-5748Article in journal (Refereed)
    Abstract [en]