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  • 235651. Sakurai, Eiichi
    et al.
    Sakurai, Eiko
    Tanaka, Yorihisa
    Watanabe, Takehiko
    Jossan, Sukhwinder Singh
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Oreland, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Effects of histamine H3-receptor ligands on brain monoamine oxidase in various mammalian species2001Inngår i: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 906, nr 1-2, s. 180-183Artikkel i tidsskrift (Fagfellevurdert)
  • 235652. Sakurai, Eiichi
    et al.
    Sakurai, Eiko
    Watanabe, T
    Jossan, S S
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Oreland, L
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Effects of the histamine H3-agonist (R)-a-Methylhistamine and the antagonist Thioperamide in vitro on Monoamine Oxidase Activity in the rat brain1995Inngår i: Meth Find Exp Clin Pharmacol, Vol. 17, s. 46-Artikkel i tidsskrift (Fagfellevurdert)
  • 235653. Sakurai, Eiko
    et al.
    Sakurai, Eiichi
    Oreland, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Farmakologi.
    Nishiyama, S
    Kato, M
    Watanabe, T
    Yanai, K
    Evidence for the presence of histamine uptake into the synaptosomes of rat brain2006Inngår i: Pharmacology, ISSN 0031-7012, E-ISSN 1423-0313, Vol. 78, nr 2, s. 72-80Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Histamine has many physiological roles in the brain and periphery. Neuronal histamine is metabolized almost exclusively by histamine N-methyltransferase. Although several neurotransmitter systems such as dopamine and 5-hydroxytryptamine have their specific reuptake system in their neurons and glial cells, a specific histamine reuptake system into the corresponding nerve terminals or glial cells has not yet been clearly elucidated. We characterized the uptake of histamine into the P2 fractions of rat brain homogenized in 0.32 mol/l sucrose using in vitro uptake techniques. [3H]histamine uptake increased with the increment of added protein amount and elapsed time. [3H]histamine uptake was also temperature-dependent. The uptake of [3H]histamine into the P2 fractions occurs by two saturable processes, a high-affinity and a low-affinity, characterized by K(m) values of 0.16 and 1.2 micromol/l, respectively. Na(+), Cl(-) and HCO(3)(-) ions were essential for the uptake of histamine in P2 fractions. [3H]histamine uptake was inhibited in the presence of several tricyclic antidepressants. In accordance with this, the endogenous release of histamine from brain slices evoked by 100 mmol/l K(+) was augmented in the presence of 20 micromol/l imipramine. These results further support the existence of a specific histamine uptake system in the brain, although the precise molecular entities have not been identified until now.

  • 235654.
    Sakurai, T.
    et al.
    Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo, Japan..
    Isogaya, K.
    Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo, Japan..
    Sakai, S.
    Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo, Japan..
    Morikawa, Masato
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwiginstitutet för cancerforskning. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Morishita, Y.
    Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo, Japan..
    Ehata, S.
    Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo, Japan..
    Miyazono, K.
    Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo, Japan..
    Koinuma, D.
    Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo, Japan..
    RNA-binding motif protein 47 inhibits Nrf2 activity to suppress tumor growth in lung adenocarcinoma2016Inngår i: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 35, nr 38, s. 5000-5009Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    RNA-binding proteins provide a new layer of posttranscriptional regulation of RNA during cancer progression. We identified RNA-binding motif protein 47 (RBM47) as a target gene of transforming growth factor (TGF)-beta in mammary gland epithelial cells (NMuMG cells) that have undergone the epithelial-to-mesenchymal transition. TGF-beta repressed RBM47 expression in NMuMG cells and lung cancer cell lines. Expression of RBM47 correlated with good prognosis in patients with lung, breast and gastric cancer. RBM47 suppressed the expression of cell metabolism-related genes, which were the direct targets of nuclear factor erythroid 2-related factor 2 (Nrf2; also known as NFE2L2). RBM47 bound to KEAP1 and Cullin 3 mRNAs, and knockdown of RBM47 inhibited their protein expression, which led to enhanced binding of Nrf2 to target genomic regions. Knockdown of RBM47 also enhanced the expression of some Nrf2 activators, p21/CDKN1A and MafK induced by TGF-beta. Both mitochondrial respiration rates and the side population cells in lung cancer cells increased in the absence of RBM47. Our findings, together with the enhanced tumor formation and metastasis of xenografted mice by knockdown of the RBM47 expression, suggested tumor-suppressive roles for RBM47 through the inhibition of Nrf2 activity.

    Fulltekst (pdf)
    fulltext
  • 235655.
    Sakwe, Amos M.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    The Role of Protein Kinase C in the Extracellular Ca2+-regulated Secretion of Parathyroid Hormone2004Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Parathyroid hormone (PTH) is the major physiological regulator of the extracellular Ca2+ concentration ([Ca2+]o) in the body. The secretion of this hormone is suppressed at high [Ca2+]o. Previously this was thought to occur by intracellular degradation of the hormone in the secretory pathway of parathyroid (PT) cells but is now believed to result from extracellular Ca2+ stimulus-secretion coupling via the calcium sensing receptor (CaR). In contrast to the stimulation of PTH secretion upon inhibition of mature PTH proteolysis, inhibition of PT proteasomes caused the accumulation of PTH precursors and inhibited secretion of PTH. This suggests that PT proteasomes play a quality control function in the maturation of PTH but they do not directly participate in the [Ca2+]o-regulated secretion of the hormone. Treatment of PT cells with 12-O-tetradecanyolphorbol-13-acetate (TPA) blocks the high [Ca2+]o-induced CaR-mediated suppression of PTH secretion. To delineate the role of DAG-responsive protein kinase C (PKC) isoforms in this process, we complemented pharmacological modulation of PKC activity with physiological activation of the enzyme via the CaR. PKC-α was rapidly activated by high [Ca2+]o and was efficiently down-regulated by prolonged TPA treatment. In CaR-transfected HEK293 cells, TPA and high [Ca2+]o induced the activation of ERK1/2 but the TPA effect was CaR- and Ca2+-independent. The magnitude of neomycin-induced release of Ca2+ from intracellular stores following pharmacological modulation of PKC activity was opposite to that resulting from physiological activation/inhibition of the enzyme via the CaR. Influx of Ca2+ following activation of the receptor occurred by store-operated mechanisms. Over-expression of wt or DN PKC-α or-ε in PT cells using the Tet-On adenovirus gene delivery system revealed that the stimulatory effect of TPA on PTH secretion at high [Ca2+]o was enhanced in cells over-expressing wt PKC-α, but the coupling of the extracellular Ca2+ signal to PTH secretion was not dependent on the physiological activation of this PKC isoform via the CaR.

    Delarbeid
    1. Biosynthesis and secretion of parathyroid hormone are sensitive to proteasome inhibitors in dispersed bovine parathyroid cells
    Åpne denne publikasjonen i ny fane eller vindu >>Biosynthesis and secretion of parathyroid hormone are sensitive to proteasome inhibitors in dispersed bovine parathyroid cells
    2002 (engelsk)Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 277, nr 20, s. 17687-17695Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Preproparathyroid hormone (prepro-PTH) is one of the proteins abundantly synthesized by parathyroid chief cells; yet under normal growth conditions, little or no prepro-PTH can be detected in these cells. Although this may be attributed to effective cotranslational translocation and proteolytic processing, proteasome-mediated degradation of PTH precursors may be important in the regulation of the levels of these precursors and hence PTH secretion. The effects of N-acetyl-Leu-Leu-norleucinal, N-acetyl-Leu-Leu-methional, carbobenzoxy-Leu-Leu-leucinal (MG132), benzyloxycarbonyl-Ile-Glu(t-butyl)-Ala-leucinal (proteasome inhibitor I), and lactacystin on the biosynthesis and secretion of PTH were examined in dispersed bovine parathyroid cells. We demonstrate that treatment of these cells with proteasome inhibitors caused the accumulation of prepro-PTH and pro-PTH. Compared with mock-treated cells, the processing of pro-PTH to PTH was delayed, and the secretion of intact PTH decreased in proteasome inhibitor-treated cells. Relieving the inhibition of the proteasome by chasing MG132-treated cells in medium without the inhibitor led to the rapid disappearance of the accumulated prepro-PTH, and the rate of PTH secretion was restored to levels comparable to those in mock-treated cells. Furthermore, overexpression of the Hsp70 family of molecular chaperones was observed in proteasome inhibitor-treated cells, and we show that PTH/PTH precursors interact with these molecular chaperones. These data suggest the involvement of parathyroid cell proteasomes in the quality control of PTH biosynthesis.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-92300 (URN)10.1074/jbc.M108576200 (DOI)11884387 (PubMedID)
    Eksternt samarbeid:
    Tilgjengelig fra: 2004-11-01 Laget: 2004-11-01 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    2. Involvement of protein kinase C-alpha and -epsilon in extracellular Ca(2+) signalling mediated by the calcium sensing receptor
    Åpne denne publikasjonen i ny fane eller vindu >>Involvement of protein kinase C-alpha and -epsilon in extracellular Ca(2+) signalling mediated by the calcium sensing receptor
    2004 (engelsk)Inngår i: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 297, nr 2, s. 560-573Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The sensing of extracellular Ca(2+) concentration ([Ca(2+)](o)) and modulation of cellular processes associated with acute or sustained changes in [Ca(2+)](o) are cell-type specific and mediated by the calcium sensing receptor (CaR). [Ca(2+)](o) signalling requires protein kinase C (PKC), but the identity and role of PKC isoforms in CaR-mediated responses remain unclear. Here we show that high [Ca(2+)](o) activated PKC-alpha and PKC- in parathyroid cells and in human embryonic kidney (HEK293) cells overexpressing the CaR (HEK-CaR) and that this response correlated with the CaR-dependent activation of mitogen-activated protein kinases ERK1/2. Activation of ERK1/2 by acute high [Ca(2+)](o) required influx of Ca(2+)through Ni(2+)-sensitive Ca(2+)channels and phosphatidylinositol-dependent phospholipase C-beta activity. Inhibition of PKC by co-expression of dominant-negative (DN) mutants of PKC-alpha or - with the CaR attenuated sustained ERK1/2 activation. Overexpression of a PKC phosphorylation site (T888A) mutant CaR in HEK293 cells showed that this site was important for ERK1/2 activation at high [Ca(2+)](o). Activation of ERK1/2 by high [Ca(2+)](o) was not necessary for the [Ca(2+)](o)-regulated secretion of parathyroid hormone (PTH) in dispersed bovine parathyroid cells. These data suggest that the CaR-mediated [Ca(2+)](o) signal leading to regulated PTH secretion that requires diacylglycerol-responsive PKC isoforms is not mediated via the ERK pathway.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-92301 (URN)10.1016/j.yexcr.2004.03.039 (DOI)15212956 (PubMedID)
    Eksternt samarbeid:
    Tilgjengelig fra: 2004-11-01 Laget: 2004-11-01 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    3. Protein kinase C modulates agonist-sensitive release of Ca2+ from internal stores in HEK293 cells over-expressing the calcium sensing receptor
    Åpne denne publikasjonen i ny fane eller vindu >>Protein kinase C modulates agonist-sensitive release of Ca2+ from internal stores in HEK293 cells over-expressing the calcium sensing receptor
    Manuskript (Annet vitenskapelig)
    Identifikatorer
    urn:nbn:se:uu:diva-92302 (URN)
    Tilgjengelig fra: 2004-11-01 Laget: 2004-11-01 Sist oppdatert: 2010-01-13bibliografisk kontrollert
    4. Physiological activation of PKC-alpha via the calcium sensing receptor is not required for the Ca2+-regulated secretion of parathyroid hormone in dispersed bovine parathyroid cells
    Åpne denne publikasjonen i ny fane eller vindu >>Physiological activation of PKC-alpha via the calcium sensing receptor is not required for the Ca2+-regulated secretion of parathyroid hormone in dispersed bovine parathyroid cells
    (engelsk)Manuskript (Annet vitenskapelig)
    Identifikatorer
    urn:nbn:se:uu:diva-92303 (URN)
    Tilgjengelig fra: 2004-11-01 Laget: 2004-11-01 Sist oppdatert: 2011-06-30bibliografisk kontrollert
    Fulltekst (pdf)
    FULLTEXT01
  • 235656.
    Sakwe, Amos M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Akusjärvi, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Rask, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Physiological activation of PKC-alpha via the calcium sensing receptor is not required for the Ca2+-regulated secretion of parathyroid hormone in dispersed bovine parathyroid cellsManuskript (Annet vitenskapelig)
  • 235657.
    Sakwe, Amos M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Engström, Åke
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Larsson, Mårten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Rask, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Biosynthesis and secretion of parathyroid hormone are sensitive to proteasome inhibitors in dispersed bovine parathyroid cells2002Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 277, nr 20, s. 17687-17695Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Preproparathyroid hormone (prepro-PTH) is one of the proteins abundantly synthesized by parathyroid chief cells; yet under normal growth conditions, little or no prepro-PTH can be detected in these cells. Although this may be attributed to effective cotranslational translocation and proteolytic processing, proteasome-mediated degradation of PTH precursors may be important in the regulation of the levels of these precursors and hence PTH secretion. The effects of N-acetyl-Leu-Leu-norleucinal, N-acetyl-Leu-Leu-methional, carbobenzoxy-Leu-Leu-leucinal (MG132), benzyloxycarbonyl-Ile-Glu(t-butyl)-Ala-leucinal (proteasome inhibitor I), and lactacystin on the biosynthesis and secretion of PTH were examined in dispersed bovine parathyroid cells. We demonstrate that treatment of these cells with proteasome inhibitors caused the accumulation of prepro-PTH and pro-PTH. Compared with mock-treated cells, the processing of pro-PTH to PTH was delayed, and the secretion of intact PTH decreased in proteasome inhibitor-treated cells. Relieving the inhibition of the proteasome by chasing MG132-treated cells in medium without the inhibitor led to the rapid disappearance of the accumulated prepro-PTH, and the rate of PTH secretion was restored to levels comparable to those in mock-treated cells. Furthermore, overexpression of the Hsp70 family of molecular chaperones was observed in proteasome inhibitor-treated cells, and we show that PTH/PTH precursors interact with these molecular chaperones. These data suggest the involvement of parathyroid cell proteasomes in the quality control of PTH biosynthesis.

  • 235658.
    Sakwe, Amos M.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Larsson, Mårten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Rask, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Involvement of protein kinase C-alpha and -epsilon in extracellular Ca(2+) signalling mediated by the calcium sensing receptor2004Inngår i: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 297, nr 2, s. 560-573Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The sensing of extracellular Ca(2+) concentration ([Ca(2+)](o)) and modulation of cellular processes associated with acute or sustained changes in [Ca(2+)](o) are cell-type specific and mediated by the calcium sensing receptor (CaR). [Ca(2+)](o) signalling requires protein kinase C (PKC), but the identity and role of PKC isoforms in CaR-mediated responses remain unclear. Here we show that high [Ca(2+)](o) activated PKC-alpha and PKC- in parathyroid cells and in human embryonic kidney (HEK293) cells overexpressing the CaR (HEK-CaR) and that this response correlated with the CaR-dependent activation of mitogen-activated protein kinases ERK1/2. Activation of ERK1/2 by acute high [Ca(2+)](o) required influx of Ca(2+)through Ni(2+)-sensitive Ca(2+)channels and phosphatidylinositol-dependent phospholipase C-beta activity. Inhibition of PKC by co-expression of dominant-negative (DN) mutants of PKC-alpha or - with the CaR attenuated sustained ERK1/2 activation. Overexpression of a PKC phosphorylation site (T888A) mutant CaR in HEK293 cells showed that this site was important for ERK1/2 activation at high [Ca(2+)](o). Activation of ERK1/2 by high [Ca(2+)](o) was not necessary for the [Ca(2+)](o)-regulated secretion of parathyroid hormone (PTH) in dispersed bovine parathyroid cells. These data suggest that the CaR-mediated [Ca(2+)](o) signal leading to regulated PTH secretion that requires diacylglycerol-responsive PKC isoforms is not mediated via the ERK pathway.

  • 235659.
    Sakwe, Amos M.
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Rask, Lars
    Gylfe, Erik
    Protein kinase C modulates agonist-sensitive release of Ca2+ from internal stores in HEK293 cells over-expressing the calcium sensing receptorManuskript (Annet vitenskapelig)
  • 235660.
    Sakwe, Amos M
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Rask, Lars
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Gylfe, Erik
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Protein Kinase C Modulates Agonist-sensitive Release of Ca2+ from Internal Stores in HEK293 Cells Overexpressing the Calcium Sensing Receptor.2005Inngår i: J Biol Chem, ISSN 0021-9258, Vol. 280, nr 6, s. 4436-41Artikkel i tidsskrift (Fagfellevurdert)
  • 235661. Sala, Jonas
    et al.
    Guardia, Elvira
    Marti, Jordi
    Spångberg, Daniel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Strukturkemi.
    Masia, Marco
    Fitting properties from density functional theory based molecular dynamics simulations to parameterize a rigid water force field2012Inngår i: Journal of Chemical Physics, ISSN 0021-9606, E-ISSN 1089-7690, Vol. 136, nr 5, s. 054103-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In the quest towards coarse-grained potentials and new water models, we present an extension of the force matching technique to parameterize an all-atom force field for rigid water. The methodology presented here allows to improve the matching procedure by first optimizing the weighting exponents present in the objective function. A new gauge for unambiguously evaluating the quality of the fit has been introduced; it is based on the root mean square difference of the distributions of target properties between reference data and fitted potentials. Four rigid water models have been parameterized; the matching procedure has been used to assess the role of the ghost atom in TIP4P-like models and of electrostatic damping. In the former case, burying the negative charge inside the molecule allows to fit better the torques. In the latter, since short-range interactions are damped, a better fit of the forces is obtained. Overall, the best performing model is the one with a ghost atom and with electrostatic damping. The approach shown in this paper is of general validity and could be applied to any matching algorithm and to any level of coarse graining, also for non-rigid molecules.

  • 235662.
    Sala, Malin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Verdier, Geraldine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap.
    Prevention av djup ventrombos med graderade kompressionsstrumpor – Effekt, riktlinjer och rekommendationer: En litteraturstudie2012Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    Deep vein thrombosis (DVT) is a serious postoperative complication and nurses should therefore observe symptoms in an early stage and implement preventive provisions, for example use of graduated compression stockings (GCS). The nurse is also responsible for making sure that ordinate GCS tried and used correctly by the patients. The aim of this study was to investigate the latest research regarding the efficacy of GCS in prevention of postoperative DVT and if there are any incorrectness in usage. And assess guidelines and recommendations for the usage of GCS. Method: Literature review. Search was done in database PubMed and Cinahl. Seven scientific articles were analyzed and national guidelines were summarized. The result indicates that GCS has small effect in preventing DVT in postoperative patients, according to some studies. The national guidelines and recommendation comprehends risk assessment of DVT, and daily observation/control of the legs (skin inspection, the correct fitting, well –informed patient and documentation). Conclusion: The result of this review isn´t concurrent but majority of studies shows minor effect in preventing DVT. For correct usage of GCS recommends that national guidelines should be followed. 

    Fulltekst (pdf)
    fulltext
  • 235663.
    Sala, S.
    et al.
    UCL, London, England; Univ Southampton, Southampton, England.
    Daurer, B. J.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Hantke, M. F.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Ekeberg, Tomas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Loh, N. D.
    Natl Univ Singapore, Singapore, Singapore.
    Maia, Filipe R. N. C.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Thibault, P.
    Univ Southampton, Southampton, England.
    Ptychographic imaging for the characterization of X-ray free-electron laser beams2017Inngår i: X-RAY MICROSCOPY CONFERENCE 2016 (XRM 2016) / [ed] Rau, C, 2017, artikkel-id 012032Konferansepaper (Fagfellevurdert)
    Abstract [en]

    We present some preliminary results from a study aimed at the characterization of the wavefront of X-ray free electron laser (XFEL) beams in the same operation conditions as for single particle imaging (or flash X-ray imaging) experiments. The varying illumination produced by wavefront fluctuations between several pulses leads to a partially coherent average beam which can be decomposed into several coherent modes using ptychographic reconstruction algorithms. Such a decomposition can give insight into pulse-to-pulse variations of the wavefront. We discuss data collected at the Linac Coherent Light Source (LCLS) and FERMI.

    Fulltekst (pdf)
    fulltext
  • 235664.
    Sala, Simone
    et al.
    UCL, Dept Phys & Astron, London, England.;Univ Southampton, Dept Phys & Astron, Southampton, Hants, England.;Lund Univ, Max IV Lab, Lund, Sweden..
    Daurer, Benedikt J.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Odstrcil, Michal
    Paul Scherrer Inst, Villigen, Switzerland..
    Capotondi, Flavio
    Elettra Sincrotrone Trieste, Trieste, Italy..
    Pedersoli, Emanuele
    Elettra Sincrotrone Trieste, Trieste, Italy..
    Hantke, Max F.
    Univ Oxford, Dept Chem, Oxford, England..
    Manfredda, Michele
    Elettra Sincrotrone Trieste, Trieste, Italy..
    Loh, N. Duane
    Natl Univ Singapore, Dept Biol Sci, Singapore, Singapore.;Natl Univ Singapore, Dept Phys, Singapore, Singapore..
    Thibault, Pierre
    Univ Southampton, Dept Phys & Astron, Southampton, Hants, England..
    Maia, Filipe R.N.C.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Pulse-to-pulse wavefront sensing at free-electron lasers using ptychography2020Inngår i: Journal of applied crystallography, ISSN 0021-8898, E-ISSN 1600-5767, Vol. 53, s. 949-956Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The pressing need for knowledge of the detailed wavefront properties of ultra-bright and ultra-short pulses produced by free-electron lasers has spurred the development of several complementary characterization approaches. Here a method based on ptychography is presented that can retrieve high-resolution complex-valued wavefunctions of individual pulses without strong constraints on the illumination or sample object used. The technique is demonstrated within experimental conditions suited for diffraction experiments and exploiting Kirkpatrick-Baez focusing optics. This lensless technique, applicable to many other short-pulse instruments, can achieve diffraction-limited resolution.

    Fulltekst (pdf)
    FULLTEXT01
  • 235665. Sala, Xavier
    et al.
    Ertem, Mehmed Z.
    Vigara, Laura
    Todorova, Tanya K.
    Chen, Weizhong
    Rocha, Reginaldo C.
    Aquilante, Francesco
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Kvantkemi.
    Cramer, Christopher J.
    Gagliardi, Laura
    Llobet, Antoni
    The cis-[Ru-II(bpy)(2)(H2O)(2)](2+) Water-Oxidation Catalyst Revisited2010Inngår i: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 49, nr 42, s. 7745-7747Artikkel i tidsskrift (Fagfellevurdert)
  • 235666.
    Saladino, Giovanni Marco
    et al.
    KTH Royal Inst Technol, Dept Appl Phys Biomed & X ray Phys, S-10691 Stockholm, Sweden..
    Kakadiya, Ronak
    KTH Royal Inst Technol, Dept Appl Phys Biomed & X ray Phys, S-10691 Stockholm, Sweden..
    Ansari, Shaquib Rahman
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Teleki, Alexandra
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Toprak, Muhammet Sadaka
    KTH Royal Inst Technol, Dept Appl Phys Biomed & X ray Phys, S-10691 Stockholm, Sweden..
    Magnetoresponsive fluorescent core-shell nanoclusters for biomedical applications2023Inngår i: Nanoscale Advances, E-ISSN 2516-0230, Vol. 5, nr 5, s. 1323-1330Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Nowadays, superparamagnetic iron oxide nanoparticles (SPIONs) have a dominant role in many subfields of biomedicine. Owing to their peculiar properties, they can be employed for magnetic separation, drug delivery, diagnostics, and hyperthermia treatments. However, these magnetic nanoparticles (NPs) suffer from low unit magnetization due to size constraints (up to 20-30 nm) to exhibit superparamagnetic character. In this work, we have designed and synthesized superparamagnetic nanoclusters (SP-NCs) with diameters of up to 400 nm with high unit magnetization for enhanced loading capacity. These were synthesized with conventional or microwave-assisted solvothermal methods, in the presence of either of the two biomolecules (citrate or l-lysine) as the capping agent. Primary particle size, SP-NC size, surface chemistry, and the resultant magnetic properties were observed to be significantly influenced by the choice of synthesis route and capping agent. Selected SP-NCs were then coated with a fluorophore-doped silica shell to provide fluorescence properties, in the near-infrared spectrum region, while silica provided high chemical and colloidal stability. Heating efficiency studies were performed under alternating magnetic field on the synthesized SP-NCs, highlighting their potential in hyperthermia treatment. We envision that their enhanced magnetically-active content, fluorescence, magnetic property, and heating efficiency will pave the way to more effective uses in biomedical applications.

    Fulltekst (pdf)
    fulltext
  • 235667. Salaemae, Wanisa
    et al.
    Junaid, Muhammad
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Angsuthanasombat, Chanan
    Katzenmeier, Gerd
    Structure-guided mutagenesis of active site residues in the dengue virus two-component protease NS2B-NS32010Inngår i: Journal of Biomedical Science, ISSN 1021-7770, E-ISSN 1423-0127, Vol. 17, s. 68-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

     The dengue virus two-component protease NS2B/NS3 mediates processing of the viral polyprotein precursor and is therefore an important determinant of virus replication. The enzyme is not intensively studied with a view to the structure-based development of antiviral inhibitors. Although 3-dimensional structures have now been elucidated for a number of flaviviral proteases, enzyme substrate interactions are characterized only to a limited extend. The high selectivity of the dengue virus protease for the polyprotein precursor offers the distinct advantage of disigning inhibitors with exquisite specificity for the viral enzyme. To identify important determinants of substrate binding and catalysis in the active site of the dengue virus NS3 protease, nine residues, L115, D129, G133, T134, Y150, G151, N152, S163 and I165, located within the S1 and S2 pockets of the enzyme were targeted by alanine substitution mutagenesis and effects on enzyme activity were fluorometrically assayed.

    Methods

     Alanine substitutions were introduced by site directed mutagenesis at residues L115, D129, G133, T134, T150, G151, N152, S163 and I165 and recombinant proteins were purified from overexpressing E. coli. Effects of these substitutions on enzymatic activity of the NS3 protease were assayed by fluorescence release from the synthetic model substrate GRR-amc and kinetic parameters K-m, K-cat and K-cat/K-m were determined.

    Results

     Kinetic data for mutant derivatives in the active site of the dengue virus NS3 protease were essentially in agreement with a functional role of the selected residues for substrate binding and/or catalysis. Only the L115A mutant displayed activity comparable to the wild-type enzyme, whereas mutation of residues Y150 and G151 to alanine completely abrogated enzyme activiey. A G133A mutant had an approximately 10-fold reduced catalytic efficiency thus suggesting a critical role for this residue seemingly as part of the oxyanion binding hole.

    Conclusions

     Kinetic data obtained for mutants in the NS3 protease have confirmed predictions for the conformation of the active site S1 and S2 pockets based on earlier observations. The data presented herein will be useful to further explore structure-activity relationships of the flaviviral proteases important for the structure-guided design of novel antiviral therapeutics.

  • 235668.
    Salah, Heba
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Muscle Wasting in a Rat ICU Model: Underlying Mechanisms and Specific Intervention Strategies2017Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Critical care has undergone several developments in the recent years leading to improved survival. However, acquired muscle weakness in the intensive care unit (ICU) is an important complication that affects severely ill patients and can prolong their ICU stay. Critical illness myopathy (CIM) is the progressive decline in the function and mass of the limb muscles in response to exposure to the ICU condition, while ventilator-induced diaphragm dysfunction (VIDD) is the time dependent decrease in the diaphragm function after the initiation of mechanical ventilation. Since the complete underlying mechanisms for CIM and VIDD are not completely understood, there is a compelling need for research on the mechanisms of CIM and VIDD to develop intervention strategies targeting these mechanisms. The aim of this thesis was to investigate the effects of several intervention strategies and rehabilitation programs on muscle wasting associated with ICU condition. Moreover, muscle specific differences in response to exposure to the ICU condition and different interventions was investigated. Hence, a rodent ICU model was used to address the mechanistic and therapeutic aspects of CIM and VIDD. The effects of heat shock protein 72 co-inducer (HSP72), BGP-15, on diaphragm and soleus for rats exposed to different durations of ICU condition was investigated. We showed that 5 and 10 days treatment with BGP-15 improved diaphragm fiber and myosin function, protected myosin from posttranslational modification, induced HSP72 and improved mitochondrial function. Moreover, BGP-15 treatment for 5 days improved soleus muscle fibers function, improved mitochondrial structure and reduced the levels of some ubiquitin ligases. In addition to BGP-15 treatment, passive mechanical loading of the limb muscles was investigated during exposure to the ICU condition. We showed that mitochondrial dynamics and mitophagy gene expression was affected by Mechanical silencing while mechanical loading counteracted these effects. Our investigation for other pathways that can be involved in muscle wasting associated with ICU condition showed that the Janus kinase 2/ Signal transducer and activator of transcription 3 (JAK2/STAT3) pathway is differentially activated in plantaris, intercostals and diaphragm. However, further studies are required with JAK2/STAT3 inhibitors to fully examine the role of this pathway in the pathogenesis of CIM and VIDD prior to translation to clinical research.

    Delarbeid
    1. The chaperone co-inducer BGP-15 alleviates ventilation-induced diaphragm dysfunction
    Åpne denne publikasjonen i ny fane eller vindu >>The chaperone co-inducer BGP-15 alleviates ventilation-induced diaphragm dysfunction
    Vise andre…
    2016 (engelsk)Inngår i: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 8, nr 350, artikkel-id 350ra103Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Ventilation-induced diaphragm dysfunction (VIDD) is a marked decline in diaphragm function in response to mechanical ventilation, which has negative consequences for individual patients' quality of life and for the health care system, but specific treatment strategies are still lacking. We used an experimental intensive care unit (ICU) model, allowing time-resolved studies of diaphragm structure and function in response to long-term mechanical ventilation and the effects of a pharmacological intervention (the chaperone co-inducer BGP-15). The marked loss of diaphragm muscle fiber function in response to mechanical ventilation was caused by post-translational modifications (PTMs) of myosin. In a rat model, 10 days of BGP-15 treatment greatly improved diaphragm muscle fiber function (by about 100%), although it did not reverse diaphragm atrophy. The treatment also provided protection from myosin PTMs associated with HSP72 induction and PARP-1 inhibition, resulting in improvement of mitochondrial function and content. Thus, BGP-15 may offer an intervention strategy for reducing VIDD in mechanically ventilated ICU patients.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-303060 (URN)10.1126/scitranslmed.aaf7099 (DOI)000380780000005 ()
    Eksternt samarbeid:
    Forskningsfinansiär
    The Swedish Foundation for International Cooperation in Research and Higher Education (STINT)Swedish Research Council, 8651; 4423; 4870; 3074EU, European Research Council, CT-223756; COST CM1001The Karolinska Institutet's Research FoundationStockholm County CouncilNovo Nordisk, 100193
    Tilgjengelig fra: 2016-09-14 Laget: 2016-09-14 Sist oppdatert: 2018-01-10bibliografisk kontrollert
    2. Does chaperone co-inducer BGP-15 mitigate the contractile dysfunction of the soleus muscle in a rat ICU model?
    Åpne denne publikasjonen i ny fane eller vindu >>Does chaperone co-inducer BGP-15 mitigate the contractile dysfunction of the soleus muscle in a rat ICU model?
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-328594 (URN)
    Tilgjengelig fra: 2017-08-28 Laget: 2017-08-28 Sist oppdatert: 2017-08-31
    3. Mechano-signalling pathways in an experimental intensive critical illness myopathy model
    Åpne denne publikasjonen i ny fane eller vindu >>Mechano-signalling pathways in an experimental intensive critical illness myopathy model
    Vise andre…
    2016 (engelsk)Inngår i: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793Artikkel i tidsskrift (Fagfellevurdert) Published
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-322821 (URN)
    Tilgjengelig fra: 2017-08-21 Laget: 2017-08-21 Sist oppdatert: 2022-01-29
    4. Muscle specific differences in activation of the Janus kinase 2/ Signal Transducer and Activator of Transcription 3 following long-term mechanical ventilation and immobilization in rats
    Åpne denne publikasjonen i ny fane eller vindu >>Muscle specific differences in activation of the Janus kinase 2/ Signal Transducer and Activator of Transcription 3 following long-term mechanical ventilation and immobilization in rats
    Vise andre…
    (engelsk)Inngår i: Artikkel i tidsskrift (Fagfellevurdert) Submitted
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-328592 (URN)
    Tilgjengelig fra: 2017-08-28 Laget: 2017-08-28 Sist oppdatert: 2017-08-31
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    preview image
  • 235669.
    Salah, Heba
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi. Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
    Fury, W.
    Regeneron Pharmaceut, Tarrytown, NY USA..
    Gromada, J.
    Regeneron Pharmaceut, Tarrytown, NY USA..
    Bai, Y.
    Regeneron Pharmaceut, Tarrytown, NY USA..
    Tchkonia, T.
    Mayo Clin, Coll Med, Robert & Arlene Kogod Ctr Aging, Rochester, MN USA..
    Kirkland, J. L.
    Mayo Clin, Coll Med, Robert & Arlene Kogod Ctr Aging, Rochester, MN USA..
    Larsson, L.
    Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.;Karolinska Inst, Dept Clin Neurosci, Clin Neurophysiol, Stockholm, Sweden.;Penn State Univ, Dept Biobehav Hlth, State Coll, PA USA..
    Muscle-specific differences in expression and phosphorylation of the Janus kinase 2/Signal Transducer and Activator of Transcription 3 following long-term mechanical ventilation and immobilization in rats2018Inngår i: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 222, nr 3, artikkel-id e12980Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim: Muscle wasting is one of the factors most strongly predicting mortality and morbidity in critically ill intensive care unit (ICU). This muscle wasting affects both limb and respiratory muscles, but the understanding of underlying mechanisms and muscle-specific differences remains incomplete. This study aimed at investigating the temporal expression and phosphorylation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in muscle wasting associated with the ICU condition to characterize the JAK/STAT proteins and the related changes leading or responding to their activation during exposure to the ICU condition.

    Methods: A novel experimental ICU model allowing long-term exposure to the ICU condition, immobilization and mechanical ventilation, was used in this study. Rats were pharmacologically paralysed by post-synaptic neuromuscular blockade and mechanically ventilated for durations varying between 6hours and 14days to study muscle-specific differences in the temporal activation of the JAK/STAT pathway in plantaris, intercostal and diaphragm muscles.

    Results: The JAK2/STAT3 pathway was significantly activated irrespective of muscle, but muscle-specific differences were observed in the temporal activation pattern between plantaris, intercostal and diaphragm muscles.

    Conclusion: The JAK2/STAT3 pathway was differentially activated in plantaris, intercostal and diaphragm muscles in response to the ICU condition. Thus, JAK2/STAT3 inhibitors may provide an attractive pharmacological intervention strategy in immobilized ICU patients, but further experimental studies are required in the study of muscle-specific effects on muscle mass and function in response to both short- and long-term exposure to the ICU condition prior to the translation into clinical research and practice.

  • 235670.
    salah, heba
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi.
    Fury, Wen
    Gromada, Jesper
    Bai, Yu
    Tchkonia, Tamar
    Kirkland, James
    Larsson, Lars
    Muscle specific differences in activation of the Janus kinase 2/ Signal Transducer and Activator of Transcription 3 following long-term mechanical ventilation and immobilization in ratsInngår i: Artikkel i tidsskrift (Fagfellevurdert)
  • 235671.
    Salah, Heba
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Klinisk neurofysiologi. Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden..
    Li, Meishan
    Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden..
    Cacciani, Nicola
    Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden..
    Gastaldello, Stefano
    Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden..
    Ogilvie, Hannah
    Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden..
    Akkad, Hazem
    Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden..
    Namuduri, Arvind Venkat
    Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden..
    Morbidoni, Valeria
    Univ Padua, Dept Womens & Childrens Hlth, Clin Genet Unit, I-35128 Padua, Italy..
    Artemenko, Konstantin A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Balogh, Gabor
    Hungarian Acad Sci, Biol Res Ctr, Inst Biochem, H-6726 Szeged, Hungary..
    Martinez-Redondo, Vicente
    Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden..
    Jannig, Paulo
    Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden..
    Hedström, Yvette
    Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden..
    Dworkin, Barry
    Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden.;Penn State Univ, Dept Neurosci, Hershey, PA 17033 USA..
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT 84112 USA.;Binzhou Med Univ, Precis Med, Yantai 264003, Shandong, Peoples R China..
    Ruas, Jorge
    Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden..
    Vigh, Laszlo
    Hungarian Acad Sci, Biol Res Ctr, Inst Biochem, H-6726 Szeged, Hungary..
    Salviati, Leonardo
    Univ Padua, Dept Womens & Childrens Hlth, Clin Genet Unit, I-35128 Padua, Italy..
    Larsson, Lars
    Karolinska Inst, Dept Physiol & Pharmacol, SE-17777 Stockholm, Sweden.;Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA.;Karolinska Inst, Clin Neurophysiol, Dept Clin Neurosci, SE-17777 Stockholm, Sweden..
    The chaperone co-inducer BGP-15 alleviates ventilation-induced diaphragm dysfunction2016Inngår i: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 8, nr 350, artikkel-id 350ra103Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Ventilation-induced diaphragm dysfunction (VIDD) is a marked decline in diaphragm function in response to mechanical ventilation, which has negative consequences for individual patients' quality of life and for the health care system, but specific treatment strategies are still lacking. We used an experimental intensive care unit (ICU) model, allowing time-resolved studies of diaphragm structure and function in response to long-term mechanical ventilation and the effects of a pharmacological intervention (the chaperone co-inducer BGP-15). The marked loss of diaphragm muscle fiber function in response to mechanical ventilation was caused by post-translational modifications (PTMs) of myosin. In a rat model, 10 days of BGP-15 treatment greatly improved diaphragm muscle fiber function (by about 100%), although it did not reverse diaphragm atrophy. The treatment also provided protection from myosin PTMs associated with HSP72 induction and PARP-1 inhibition, resulting in improvement of mitochondrial function and content. Thus, BGP-15 may offer an intervention strategy for reducing VIDD in mechanically ventilated ICU patients.

  • 235672.
    Salah, Omar-Alfred
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för informatik och media.
    Understanding Reasons Behind the Lack of Adoption of Units of Measure (UoM) Libraries2019Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Abstract [en]

    The concepts of units and units of measurement (UoM) are used in scientific and mathematicalapplications to encode variables and their types with units. There are many UoMlibraries, as identified by previous research, that exist that can handle and prevent unit errorsand failures that can arise if units are not handled properly, otherwise, the consequences ofnot using UoM libraries may have possibly disastrous implications. Previous research hascategorised thousands of UoM libraries, an indication that the ’wheel is being reinvented’time and time again instead of building on what was already done, indicating that thereexists a lack of adoption of these UoM libraries. It is therefore important to understand thescale of the lack of adoption and why that is the case. An exploratory-DSR style researchwas employed and developers and scientists were surveyed and interviewed to inquire whythis is the case, with results ranging from unawareness of these UoM libraries, to specificperformance concerns and even tradition and sticking to what already works. Towards theend, the thesis suggests possible solutions to relieving the lack of adoption of these UoMlibraries as recommendation for further UoM solutions, with recommendations rangingfrom including UoM libraries in standard libraries of programming languages to reducingthe complexity and verbosity of UoM solutions.

    Fulltekst (pdf)
    fulltext
  • 235673.
    Salah, Omar-Alfred
    et al.
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för informatik och media.
    McKeever, Steve
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för informatik och media, Informationssystem.
    Lack of Adoption of Units of Measurement Libraries: Survey and Anecdotes2020Inngår i: 2020 IEEE/ACM 42nd International Conference On Software Engineering: Software Engineering In Practice (ICSE-SEIP), New York: Association for Computing Machinery ACM , 2020, s. 81-89Konferansepaper (Fagfellevurdert)
    Abstract [en]

    Units of measurement (UoM) libraries are mostly used to appropriately encode unit variables and convert between them in a type-safe manner. Approximately 3700 functioning unit measurement libraries exist on the web, indicating that the wheel is being reinvented time and time again. Previous research has postulated that too much diversity, lack of code sharing and duplicated efforts are discouraging adoption, yet more remains to be known. Three developers and a scientist were interviewed and 91 practitioners of varying experiences from online forums were surveyed to explain their dissatisfaction with UoM libraries and possible reasons behind the lack of adoption. Our findings range from insufficient awareness of these UoM's, to development processes that exclude unit information through to specific performance concerns. We conclude with recommendations to UoM library creators stemming from these points that could help alleviate the problem and lead to an increased adoption rate of methodologies that support unit annotation and checking.

  • 235674. Salahshor, S
    et al.
    Kressner, U
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Fischer, H
    Lindmark, G
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Glimelius, B
    Institutionen för onkologi, radiologi och klinisk immunologi.
    Pahlman, L
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Lindblom, A
    Microsatellite instability in sporadic colorectal cancer is not an independent prognostic factor.1999Inngår i: Br J Cancer, Vol. 81, s. 190-Artikkel i tidsskrift (Fagfellevurdert)
  • 235675. Salahshor, S
    et al.
    Kressner, Ulf
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Pahlman, Lars
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Glimelius, Bengt
    Institutionen för onkologi, radiologi och klinisk immunologi.
    Lindmark, Gudrun
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Lindblom, A
    Colorectal cancer with and without microsatellite instability involves different genes.1999Inngår i: Genes Chrom Cancer, Vol. 26, s. 247-Artikkel i tidsskrift (Fagfellevurdert)
  • 235676.
    Salahshour Torshizi, Sara
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Statistiska institutionen. RISE-Research Institue of Sweden.
    Software Performance Anomaly Detection Through Analysis Of Test Data By Multivariate Techniques2022Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Abstract [en]

    This thesis aims to uncover anomalies in the data describing the performance behavior of a "robot controller" as measured by software metrics. The purpose of analyzing data is mainly to identify the changes that have resulted in different performance behaviors which we refer to as performance anomalies. To address this issue, two separate pre-processing approaches have been developed: one that adds the principal component to the data after cleaning steps and another that does not regard the principal component. Next, Isolation Forest is employed, which uses an ensemble of isolation trees for data points to segregate anomalies and generate scores that can be used to discover anomalies. Further, in order to detect anomalies, the highest distances matching cluster centroids are employed in the clustering procedure. These two data preparation methods, along with two anomaly detection algorithms, identified software builds that are very likely to be anomalies. According to an industrial evaluation conducted based on engineers’ domain knowledge, around 70% of the detected software builds as anomalous builds were successfully identified, indicating system variable deviations or software bugs.

    Fulltekst (pdf)
    fulltext
  • 235677.
    Salahuddin, Tyaba S.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten.
    Consequences of opening the blood-brain barrier by carotid infusion of hyperosmolar solutions: an experimental study in the rat1991Doktoravhandling, med artikler (Annet vitenskapelig)
  • 235678.
    Salajan, Andreea-Lorena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Internationell mödra- och barnhälsovård (IMCH).
    Exploring pandemic preparedness in Austria and Switzerland: A comparative analysis of national pandemic influenza preparedness plans2017Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Abstract [en]

    Background: Influenza pandemics are unpredictable but recurring global health threats which require planning and preparedness. In the past, European pandemic influenza preparedness plans lacked coherence and interoperability. Recent avian influenza outbreaks in Switzerland and Austria highlight the potential risks of emerging influenza viruses at the animal-human- ecosystem interface. Collaboration between public health, veterinary and environmental sectors could improve risk management of emerging pandemic threats. Whether pandemic preparedness plans in Switzerland and Austria are coherent and consider the concept of One Health is currently unknown.

    Methods: A qualitative approach was used for this comparative study. National pandemic influenza preparedness plans of Austria and Switzerland were analyzed and compared during inductive content analysis.

    Results: Four key elements of pandemic preparedness were identified in both documents: planning and coordination, monitoring and surveillance, risk management and communication and information. The plans are coherent regarding their underlying principles and priorities but demonstrate differences in the interpretation and operationalization of all four elements. Core components of One Health were partially integrated in both plans through collaboration with the veterinary sector.

    Conclusion: Common conceptualizations of pandemic influenza preparedness and shared priorities do not guarantee coherence and interoperability. The identified differences could challenge future pandemic preparedness and response in Europe. The prioritization of public health preparedness in Switzerland and Austria leaves little room for integrative One Health approaches. The further improvement of pandemic influenza preparedness in Europe will require strong governance and leadership and more active approaches to promote intercountry and cross-sectoral coordination and collaboration. 

  • 235679.
    Sala-Jarque, Julia
    et al.
    Univ Barcelona, Sch Med, Inst Invest Biomed August Pi & Sunyer, Dept Biomed Sci,Biochem & Mol Biol Unit, Barcelona, Catalonia, Spain..
    Garcia-Lara, Elisa
    Univ Barcelona, Sch Med, Inst Invest Biomed August Pi & Sunyer, Dept Biomed Sci,Biochem & Mol Biol Unit, Barcelona, Catalonia, Spain..
    Carreras-Dominguez, Paula
    Univ Barcelona, Sch Med, Inst Invest Biomed August Pi & Sunyer, Dept Biomed Sci,Biochem & Mol Biol Unit, Barcelona, Catalonia, Spain..
    Zhou, Chunfang
    Nanologica AB, Södertälje, Sweden..
    Rabaneda-Lombarte, Neus
    Univ Barcelona, Sch Med, Inst Invest Biomed August Pi & Sunyer, Dept Biomed Sci,Biochem & Mol Biol Unit, Barcelona, Catalonia, Spain.;Inst Invest Biomed August Pi & Sunyer, Inst Invest Biomed Barcelona, Dept Cerebral Ischemia & Neurodegenerat, CSIC, Barcelona, Catalonia, Spain..
    Sola, Carme
    Inst Invest Biomed August Pi & Sunyer, Inst Invest Biomed Barcelona, Dept Cerebral Ischemia & Neurodegenerat, CSIC, Barcelona, Catalonia, Spain..
    Vidal-Taboada, Jose M.
    Univ Barcelona, Sch Med, Inst Invest Biomed August Pi & Sunyer, Dept Biomed Sci,Biochem & Mol Biol Unit, Barcelona, Catalonia, Spain.;Vall dHebron Hosp Univ, Vall dHebron Inst Recerca, Peripheral Nervous Syst, Barcelona, Catalonia, Spain..
    Feiler, Adam
    Nanologica AB, Södertälje, Sweden.;KTH Royal Inst Technol, Stockholm, Sweden..
    Abrahamsson, Ninnie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Kozlova, Elena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Genomik och neurobiologi.
    Saura, Josep
    Univ Barcelona, Sch Med, Inst Invest Biomed August Pi & Sunyer, Dept Biomed Sci,Biochem & Mol Biol Unit, Barcelona, Catalonia, Spain.;Univ Barcelona, Inst Neurosci, Barcelona, Catalonia, Spain..
    Mesoporous silica particles are phagocytosed by microglia and induce a mild inflammatory response in vitro2022Inngår i: Nanomedicine, ISSN 1743-5889, E-ISSN 1748-6963, Vol. 17, nr 15, s. 1077-1094Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Plain language summary Mesoporous silica particles (MSPs) are broadly used drug delivery carriers. In this study, the authors analyzed the responses of two types of brain cells, astrocytes and microglia, to MSPs. Mouse astrocytes and microglia were kept alive in cultures and were treated with MSPs that were labeled with a red fluorescent agent to facilitate visualization under the microscope. MSPs are avidly internalized by microglial cells and remain inside the cells for at least 14 days. Despite this, MSPs do not affect glial cell viability or morphology, basal metabolic activity or oxidative stress. When given alone, MSPs do not affect mRNA levels of key proinflammatory genes. However, MSPs given in combination with lipopolysaccharide, a strong proinflammatory agent, significantly increase extracellular levels of IL-1 beta, one of the proinflammatory mediators studied. These results suggest that MSPs could be novel tools for specific drug delivery to microglial cells. Aim: Mesoporous silica particles (MSPs) are broadly used drug delivery carriers. In this study, the authors analyzed the responses to MSPs of astrocytes and microglia, the two main cellular players in neuroinflammation. Materials & methods: Primary murine cortical mixed glial cultures were treated with rhodamine B-labeled MSPs. Results: MSPs are avidly internalized by microglial cells and remain inside the cells for at least 14 days. Despite this, MSPs do not affect glial cell viability or morphology, basal metabolic activity or oxidative stress. MSPs also do not affect mRNA levels of key proinflammatory genes; however, in combination with lipopolysaccharide, they significantly increase extracellular IL-1 beta levels. Conclusion: These results suggest that MSPs could be novel tools for specific drug delivery to microglial cells.

  • 235680.
    Salakka, Seela
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Geovetenskapliga sektionen, Institutionen för geovetenskaper, Paleobiologi.
    Tooth Replacement of Euhelopus zdanskyi (Dinosauria: Sauropoda) and the Evolution of Titanosaurian Tooth Morphology2014Independent thesis Advanced level (degree of Master (Two Years)), 80 poäng / 120 hpOppgave
    Abstract [en]

    Sauropod tooth morphologies and tooth replacement patterns bear important information on feeding habits and sauropod evolution. Euhelopus zdanskyi is an Early Cretaceous neosauropod, and belongs to the group Euhelopodidae, which is the sister group of Titanosauria. Euhelopus is a key taxon in the evolution of sauropod teeth, because it displays a very conservative tooth morphology compared to that seen in Titanosauria, despite being a close relative. The teeth of Euhelopus resemble those of Camarasaurus, as well as many basal sauropods that are not closely related to Euhelopus. The teeth of Euhelopus are spoon-shaped, and they have approximately two replacement teeth for each functional tooth. Their robust morphology and low number of replacement teeth suggest that they were worn down a lot more slowly than the pencil-shaped teeth of Titanosauria and Diplodocoidea. Diplodocoids, whose teeth have been studied widely, especially show very rapid tooth replacement rates, and the tooth morphology of titanosaurs suggests that they might have had similar replacement rates. On the contrary, Euhelopus was likely to have replacement rates similar to the relatively low rates of Camarasaurus, whose tooth battery is much like that of Euhelopus. Furthermore, some euhelopodids are known to have had pencil-shaped teeth, which indicates that there was a strong evolutionary pressure towards the development of narrow teeth during the Late Cretaceous. This pressure may have been caused by a change in vegetation or may merely represent somphospondylans occupying the niches vacated by the diplodocoids, which appear to have gone extinct before the end of the Cretaceous. This study uses 3D modelling for inspecting tooth replacement of Euhelopus and evolution of sauropod teeth.

    Fulltekst (pdf)
    fulltext
  • 235681.
    Salam, Abdul
    et al.
    Univ New South Wales, George Inst Global Hlth, Hyderabad, India.
    Atkins, Emily
    Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia.
    Sundström, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Kardiologi.
    Hirakawa, Yoichiro
    Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia.
    Ettehad, Dena
    Univ Oxford, George Inst Global Hlth, 1st Floor,Hayes House,George St, Oxford OX1 2BQ, England.
    Emdin, Connor
    Univ Oxford, George Inst Global Hlth, 1st Floor,Hayes House,George St, Oxford OX1 2BQ, England.
    Neal, Bruce
    Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia.
    Woodward, Mark
    Univ Sydney, Sydney, NSW, Australia.
    Chalmers, John
    Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia.
    Berge, Eivind
    Oslo Univ Hosp, Oslo, Norway.
    Yusuf, Salim
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Rahimi, Kazem
    Univ Oxford, George Inst Global Hlth, 1st Floor,Hayes House,George St, Oxford OX1 2BQ, England.
    Rodgers, Anthony
    Univ New South Wales, George Inst Global Hlth, Sydney, NSW, Australia.
    Effects of blood pressure lowering on cardiovascular events, in the context of regression to the mean: a systematic review of randomized trials2019Inngår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 37, nr 1, s. 16-23Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Objective: To assess the clinical relevance of regression to the mean for clinical trials and clinical practice. Methods: MEDLINE was searched until February 2018 for randomized trials of BP lowering with over 1000 patient-years follow-up per group. We estimated baseline mean BP, follow-up mean (usual) BP amongst patients grouped by 10 mmHg strata of baseline BP, and assessed effects of BP lowering on coronary heart disease (CHD) and stroke according to these BP levels. Results: Eighty-six trials (349 488 participants), with mean follow-up of 3.7 years, were included. Most mean BP change was because of regression to the mean rather than treatment. At high baseline BP levels, even after rigorous hypertension diagnosis, downwards regression to the mean caused much of the fall in BP. At low baseline BP levels, upwards regression to the mean increased BP levels, even in treatment groups. Overall, a BP reduction of 6/3 mmHg lowered CHD by 14% (95% CI 11-17%) and stroke by 18% (15-22%), and these treatment effects occurred at follow-up BP levels much closer to the mean than baseline BP levels. In particular, more evidence was available in the SBP 130-139 mmHg range than any other range. Benefits were apparent in numerous high-risk patient groups with baseline mean SBP less than 140 mmHg. Conclusion: Clinical practice should focus less on pretreatment BP levels, which rarely predict future untreated BP levels or rule out capacity to benefit from BP lowering in high cardiovascular risk patients. Instead, focus should be on prompt, empirical treatment to maintain lower BP for those with high BP and/or high risk.

  • 235682.
    Salam Ridha Shareef, Sarah
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Kemisk biologi för biomarkörer. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Effekter av oxysteroler på cellmigration: en roll i cancerutveckling?2023Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Abstrakt

     

    Nyckelord: Oxysteroler, 27-OH, CYP27A1, 27-hydroxykolesterol, bröstcancer, tumörspridning, metastas, migrering.

     

    Bakgrund Cancer är den näst vanligaste dödsorsaken i västvärlden, med en komplex genetisk orsak som involverar flera mutationer. Cancerceller karaktäriseras som överaktiva och har accelererad cellcykel samt ökad rörlighet. Tumörer, särskilt benigna, kan behandlas om de upptäcks tidigt, medan metastasering, där tumören sprider sig till andra vävnader, är den största orsaken till hög mortalitet. Oxysteroler, som är metaboliter av kolesterol, har funktioner i kroppens homeostas och har under senare tid upptäckts underlätta migrationen av tumörceller. Särskilt fokuseras det på 27-hydroxykolesterol (27-OH) och dess roll i cancer. Det framhålls att 27-OH är involverad i reglering av cellcykeln och att den kan kopplas till bröstcancer genom dess effekt på östrogenreceptorer och lever X-receptorer (LXR). Denna studie betonar behovet av att förstå oxysterolernas roll i cancermetastasering och hur de kan vara kopplade till bröstcancerspridning. Syfte Syftet med detta projekt är att undersöka kopplingen mellan oxysterolers roll i kroppen och cancercellers migration vid metastasering av bröstcancer. Metod Studien utfördes som en systematisk litteraturöversikt. Insamlade artiklar kom från PubMed och genomgick två steg av urval. Stegen involverade grovsållning av artiklar baserat på titlar respektive abstrakt, där relevanta studier om mekanismer relaterade till oxysteroler och bröstcancermetastasering identifierades. Inklusionskriterierna var studier om oxysterolers åverkan på cellbiologi och att de var skrivna på engelska. Studien fokuserade på cellmekanismer och därför uteslöts studier som involverade människor. Resultat och diskussion Oxysterolen 27-OH är involverad i flera mekanismer som kan underlätta migrationen av bröstcancer. Studierna har observerat att 27-OH binder in till intracellulära receptorer i cellkärnan och därmed inducerar uttryck av proteiner. Dessa transkriptionsfaktorer kan underlätta övergången från en epitelial cell till en cell som kan förflytta sig enklare (mesenkymal cell). I denna mekanism är proteiner som STAT-3, MMP9, interleukiner och TGF involverade, vilka är viktiga molekyler inom immunförsvaret och cancerutveckling. Slutsats Denna systematiska litteraturöversikt har presenterat komplexa samband mellan 27-OH och förändringen av uttrycket av gener i metastaserade bröstcancerceller. En av de mest betydelsefulla observationerna är den 27-OHs effekt på epitel-mesenkymal övergång.

  • 235683.
    Salam Shareef, sarah
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Effekter av oxysteroler på cellmigration: en roll i cancerutveckling?2023Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [sv]

    Bakgrund Cancer är den näst vanligaste dödsorsaken i västvärlden, med en komplex genetisk orsak som involverar flera mutationer. Cancerceller karaktäriseras som överaktiva och har accelererad cellcykel samt ökad rörlighet. Tumörer, särskilt benigna, kan behandlas om de upptäcks tidigt, medan metastasering, där tumören sprider sig till andra vävnader, är den största orsaken till hög mortalitet. Oxysteroler, som är metaboliter av kolesterol, har funktioner i kroppens homeostas och har under senare tid upptäckts underlätta migrationen av tumörceller. Särskilt fokuseras det på 27-hydroxykolesterol (27-OH) och dess roll i cancer. Det framhålls att 27-OH är involverad i reglering av cellcykeln och att den kan kopplas till bröstcancer genom dess effekt på östrogenreceptorer och lever X-receptorer (LXR). Denna studie betonar behovet av att förstå oxysterolernas roll i cancermetastasering och hur de kan vara kopplade till bröstcancerspridning. Syfte Syftet med detta projekt är att undersöka kopplingen mellan oxysterolers roll i kroppen och cancercellers migration vid metastasering av bröstcancer. Metod Studien utfördes som en systematisk litteraturöversikt. Insamlade artiklar kom från PubMed och genomgick två steg av urval. Stegen involverade grovsållning av artiklar baserat på titlar respektive abstrakt, där relevanta studier om mekanismer relaterade till oxysteroler och bröstcancermetastasering identifierades. Inklusionskriterierna var studier om oxysterolers åverkan på cellbiologi och att de var skrivna på engelska. Studien fokuserade på cellmekanismer och därför uteslöts studier som involverade människor. Resultat och diskussion Oxysterolen 27-OH är involverad i flera mekanismer som kan underlätta migrationen av bröstcancer. Studierna har observerat att 27-OH binder in till intracellulära receptorer i cellkärnan och därmed inducerar uttryck av proteiner. Dessa transkriptionsfaktorer kan underlätta övergången från en epitelial cell till en cell som kan förflytta sig enklare (mesenkymal cell). I denna mekanism är proteiner som STAT-3, MMP9, interleukiner och TGF involverade, vilka är viktiga molekyler inom immunförsvaret och cancerutveckling. Slutsats Denna systematiska litteraturöversikt har presenterat komplexa samband mellan 27-OH och förändringen av uttrycket av gener i metastaserade bröstcancerceller. En av de mest betydelsefulla observationerna är den 27-OHs effekt på epitel-mesenkymal övergång.

  • 235684.
    Salama, Suzy M.
    et al.
    Univ Malaya, Dept Biomed Sci, Fac Med, Kuala Lumpur 50603, Malaysia..
    Gwaram, Nura Suleiman
    Univ Malaya, Dept Chem, Fac Sci, Kuala Lumpur 50603, Malaysia..
    AlRashdi, Ahmed S.
    Univ Malaya, Dept Biomed Sci, Fac Med, Kuala Lumpur 50603, Malaysia..
    Khalifa, Shaden A. M.
    Karolinska Univ Hosp, Dept Expt Hematol, SE-14186 Stockholm, Sweden.;Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, S-10691 Stockholm, Sweden.;Kumamoto Univ, Dept Otolaryngol Head & Neck Surg, 1-1-1 Honjo, Kumamoto, Japan..
    Abdulla, Mahmood A.
    Univ Malaya, Dept Biomed Sci, Fac Med, Kuala Lumpur 50603, Malaysia..
    Ali, Hapipah M.
    Univ Malaya, Dept Chem, Fac Sci, Kuala Lumpur 50603, Malaysia..
    El-Seedi, Hesham R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Univ Malaya, Dept Chem, Fac Sci, Kuala Lumpur 50603, Malaysia.;Karolinska Univ Hosp, Dept Expt Hematol, SE-14186 Stockholm, Sweden..
    A Zinc Morpholine Complex Prevents HCl/Ethanol-Induced Gastric Ulcers in a Rat Model2016Inngår i: Scientific Reports, E-ISSN 2045-2322, Vol. 6, artikkel-id 29646Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Zinc is a naturally occurring element with roles in wound healing and rescuing tissue integrity, particularly in the gastrointestinal system, where it can be detected in the mucosal and submucosal layers. Zinc chelates are known to have beneficial effects on the gastrointestinal mucosa and in cases of gastric ulcer. We synthesized complexes of zinc featuring a heterocyclic amine binding amino acids then investigated their ability to enhance the gastric self-repair. Zinc-morpholine complex, Zn(L)SCN, namely showed strong free-radical scavenging, promotion of the DNA and RNA polymerases reconstruction and suppression of cell damage. The complex's mode of action is proposed to involve hydrogen bond formation via its bis(thiocyanato-k) zinc moiety. Zn(L) SCN complex had potent effects on gastric enzymatic activity both in vitro and in vivo. The complex disrupted the ulcerative process as demonstrated by changes in the intermediate metabolites of the oxidative pathway - specifically, reduction in the MDA levels and elevation of reduced glutathione together with an attenuation of oxidative DNA damage. Additionally, Zn(L) SCN restored the gastric mucosa, inhibited the production of pro-inflammatory cytokines (IL-6, TNF and the caspases), and preserved the gastric mucous balance. Zn(L) SCN thus exhibited anti-oxidative, anti-inflammatory and anti-apoptotic activities, all of which have cytoprotective effects on the gastric lining.

    Fulltekst (pdf)
    fulltext
  • 235685.
    Salama, Suzy
    et al.
    Ghibaish Coll Sci & Technol, Indigenous Knowledge & Heritage Ctr, Ghibaish 51111, Sudan..
    Shou, Qiyang
    Zhejiang Chinese Med Univ, Clin Med Coll 2, Hangzhou 310053, Peoples R China..
    Abd El-Wahed, Aida A.
    Agr Res Ctr, Plant Protect Res Inst, Dept Bee Res, Giza 12627, Egypt..
    Elias, Nizar
    Univ Kalamoon, Fac Med, POB 222, Dayr Atiyah, Syria..
    Xiao, Jianbo
    Univ Vigo, Fac Sci, Dept Analyt & Food Chem, Nutr & Bromatol Grp, Orense 32004, Spain..
    Swillam, Ahmed
    Menoufia Univ, Fac Pharm, Shibin Al Kawm 32512, Egypt..
    Umair, Muhammad
    Shenzhen Univ, Coll Chem & Engn, Dept Food Sci & Technol, Shenzhen 518060, Peoples R China..
    Guo, Zhiming
    Jiangsu Univ, Sch Food & Biol Engn, Zhenjiang 212013, Jiangsu, Peoples R China..
    Daglia, Maria
    Univ Napoli Federico II, Dept Pharm, Via D Montesano 49, I-80131 Naples, Italy.;Jiangsu Univ, Int Res Ctr Food Nutr & Safety, Zhenjiang 212013, Jiangsu, Peoples R China..
    Wang, Kai
    Chinese Acad Agr Sci, Inst Apicultural Res, Beijing 100093, Peoples R China..
    Khalifa, Shaden A. M.
    Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, S-10691 Stockholm, Sweden..
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap. Jiangsu Univ, Int Res Ctr Food Nutr & Safety, Zhenjiang 212013, Jiangsu, Peoples R China.;Menoufia Univ, Fac Sci, Dept Chem, Shibin Al Kawm 32512, Egypt.;Jiangsu Univ, Jiangsu Educ Dept, Int Joint Res Lab Intelligent Agr & Agriprod Proc, Nanjing 210024, Peoples R China..
    Royal Jelly: Beneficial Properties and Synergistic Effects with Chemotherapeutic Drugs with Particular Emphasis in Anticancer Strategies2022Inngår i: Nutrients, E-ISSN 2072-6643, Vol. 14, nr 19, artikkel-id 4166Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Cancer is one of the major causes of death globally. Currently, various methods are used to treat cancer, including radiotherapy, surgery, and chemotherapy, all of which have serious adverse effects. A healthy lifestyle, especially a nutritional diet, plays a critical role in the treatment and prevention of many disorders, including cancer. The above notion, plus the trend in going back to nature, encourages consumers and the food industry to invest more in food products and to find potential candidates that can maintain human health. One of these agents, and a very notable food agent, is royal jelly (RJ), known to be produced by the hypopharyngeal and mandibular salivary glands of young nurse honeybees. RJ contains bioactive substances, such as carbohydrates, protein, lipids, peptides, mineral salts and polyphenols which contribute to the appreciated biological and pharmacological activities. Antioxidant, anticancer, anti-inflammatory, antidiabetic, and antibacterial impacts are among the well-recognized benefits. The combination of RJ or its constituents with anticancer drugs has synergistic effects on cancer disorders, enhancing the drug's effectiveness or reducing its side effects. The purpose of the present review is to emphasize the possible interactions between chemotherapy and RJ, or its components, in treating cancer illnesses.

    Fulltekst (pdf)
    FULLTEXT01
  • 235686.
    Salamanova, Evdokiya
    et al.
    Karolinska Inst, Dept Biosci & Nutr, Neo, TTI, SE-14183 Huddinge, Sweden;Bulgarian Acad Sci, Inst Mol Biol, 21 G Bontchev Str, BU-1113 Sofia, Bulgaria.
    Costeira-Paulo, Joana
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Biokemi. Karolinska Inst, Dept Biosci & Nutr, Neo, TTI, SE-14183 Huddinge, Sweden.
    Han, Kyou-Hoon
    Korea Res Inst Biosci & Biotechnol, Genome Editing Res Ctr, Future Biotechnol Res Div, 125 Gwahak Ro, Daejeon 305806, South Korea;Univ Sci & Technol, Dept Nano & Bioinformat, 113 Gwahak Ro, Daejeon 305333, South Korea.
    Kim, Do-Hyoung
    Korea Res Inst Biosci & Biotechnol, Genome Editing Res Ctr, Future Biotechnol Res Div, 125 Gwahak Ro, Daejeon 305806, South Korea.
    Nilsson, Lennart
    Karolinska Inst, Dept Biosci & Nutr, Neo, TTI, SE-14183 Huddinge, Sweden.
    Wright, Anthony P. H.
    Novum, Karolinska Inst, Dept Lab Med, Clin Res Ctr, Level 5,Halsovagen 7, SE-14157 Huddinge, Sweden.
    A subset of functional adaptation mutations alter propensity for alpha-helical conformation in the intrinsically disordered glucocorticoid receptor taulcore activation domain2018Inngår i: Biochimica et Biophysica Acta - General Subjects, ISSN 0304-4165, E-ISSN 1872-8006, Vol. 1862, nr 6, s. 1452-1461Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Adaptive mutations that alter protein functionality are enriched within intrinsically disordered protein regions (IDRs), thus conformational flexibility correlates with evolvability. Pre-structured motifs (PreSMos) with transient propensity for secondary structure conformation are believed to be important for IDR function. The glucocorticoid receptor taulcore transcriptional activation domain (GR taulcore) domain contains three a-helical PreSMos in physiological buffer conditions.

    Methods: Sixty change-of-function mutants affecting the intrinsically disordered 58-residue GR taulcore were studied using disorder prediction and molecular dynamics simulations.

    Results: Change-of-function mutations were partitioned into seven clusters based on their effect on IDR predictions and gene activation activity. Some mutations selected from clusters characterized by mutations altering the IDR prediction score, altered the apparent stability of the a-helical form of one of the PreSMos in molecular dynamics simulations, suggesting PreSMo stabilization or destabilization as strategies for functional adaptation. Indeed all tested gain-of-function mutations affecting this PreSMo were associated with increased stability of the a-helical PreSMo conformation, suggesting that PreSMo stabilization may be the main mechanism by which adaptive mutations can increase the activity of this IDR type. Some mutations did not appear to affect PreSMo stability.

    Conclusions: Changes in PreSMo stability account for the effects of a subset of change-of-function mutants affecting the GR taulcore IDR. General significance: Long IDRs occur in about 50% of human proteins. They are poorly characterized despite much recent attention. Our results suggest the importance of a subtle balance between PreSMo stability and IDR activity, which may provide a novel target for future pharmaceutical intervention.

  • 235687.
    Salameh, Ramy
    et al.
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Företagsekonomiska institutionen.
    Crona, Samuel
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Företagsekonomiska institutionen.
    Belöningars inverkan på motivation: En fallstudie på låg organisatorisk nivå inom telefonförsäljningsbranschen2010Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Fulltekst (pdf)
    FULLTEXT01
  • 235688.
    Salameh, Rania
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för freds- och konfliktforskning.
    WOMEN IN PEACE NEGOTIATIONS   A study of women´s inclusion in peace negotiations and its effect on the content of the peace agreement2018Independent thesis Advanced level (degree of Master (Two Years)), 20 poäng / 30 hpOppgave
    Abstract [en]

    Women´s substantial inclusion in peace processes has since the adoption of UN SCR 1325 been much emphasized, but little studied. Furthermore, the research conducted has largely abstained from using clear definitions of what women´s inclusion entails, which difficult the intent to understand if and how the inclusion may have affected the content of the peace agreement. This study seeks to address this gap and contribute to the field by looking specifically at women´s substantial inclusion during the peace negotiations. The study argues that when women are substantially included in the peace negotiations, the content of the peace agreement will be widened to include social equality provisions. By employing a comparative case study, the hypothesis is tested on the peace negotiations that took place between the Colombian government and the M-19 and the FARC-EP. The findings suggests support for the proposed hypothesis. However, the findings also indicate that the support of international gender experts during the peace negotiations seems to have exerted some influence on the content of the provisions the women in the peace negotiations were to raise, thus calling for the need of more research to be conducted in the field.

  • 235689.
    Salami, Falastin
    et al.
    Lund Univ, Clin Res Ctr, Skåne Univ Hosp, Dept Clin Sci, Malmö, Sweden.
    Lee, Hye-Seung
    Univ S Florida, Hlth Informat Inst, Dept Pediat, Tampa, FL USA.
    Freyhult, Eva
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Larsson, Helena Elding
    Lund Univ, Clin Res Ctr, Skåne Univ Hosp, Dept Clin Sci, Malmö, Sweden.
    Lernmark, Åke
    Lund Univ, Clin Res Ctr, Skåne Univ Hosp, Dept Clin Sci, Malmö, Sweden.
    Törn, Carina
    Lund Univ, Clin Res Ctr, Skåne Univ Hosp, Dept Clin Sci, Malmö, Sweden.
    Reduction in White Blood Cell, Neutrophil and Red Blood Cell counts Related to Gender, HLA and Islet Autoantibodies in Swedish TEDDY Children at Increased Risk for Type 1 Diabetes2018Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 67, nr 11, s. 2329--2336, artikkel-id db180355Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Islet autoantibodies (IAs) precede the clinical onset of type 1 diabetes (T1D); however, the knowledge is limited about whether the prodrome affects complete blood counts (CBCs) in 4- to 12-year-old children with increased genetic risk for T1D. This study tested whether CBCs were altered in 4- to 12-year-old children without (n = 376) or with one or several IAs against insulin, GAD65, or IA-2 (n = 72). CBC was analyzed during longitudinal follow-up in 448 Swedish children enrolled in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A linear mixed-effects model was used to assess potential association between IA and CBC measurements over time. The white blood cell and neutrophil counts were reduced in children with IAs, primarily in boys. In contrast, girls had lower levels of hemoglobin and hematocrit. Positivity for multiple IAs showed the lowest counts in white blood cells and neutrophils in boys and red blood cells, hemoglobin, and hematocrit in girls. These associations were primarily observed in children with the HLA-DR3-DQ2/DR4-DQ8 genotype. We conclude that the reduction in neutrophils and red blood cells in children with multiple IAs and HLA-DR3-DQ2/DR4-DQ8 genotype may signal a sex-dependent islet autoimmunity detected in longitudinal CBCs.

  • 235690.
    Salamon, John
    et al.
    South Australian Hlth & Med Res Inst, EMBL Australia Grp, Infect & Immun Theme, North Terrace, Adelaide, SA 5000, Australia;Flinders Univ S Australia, Sch Med, Bedford Pk, SA 5042, Australia.
    Qian, Xiaoyan
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi. Stockholm Univ, Dept Biophys & Biochem, Sci Life Lab, Box 1031, S-17121 Solna, Sweden.
    Nilsson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Molekylära verktyg. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Stockholm Univ, Dept Biophys & Biochem, Sci Life Lab, Box 1031, S-17121 Solna, Sweden.
    Lynn, David John
    South Australian Hlth & Med Res Inst, EMBL Australia Grp, Infect & Immun Theme, North Terrace, Adelaide, SA 5000, Australia;Flinders Univ S Australia, Sch Med, Bedford Pk, SA 5042, Australia.
    Network Visualization and Analysis of Spatially Aware Gene Expression Data with InsituNet2018Inngår i: Cell Systems, ISSN 2405-4712, Vol. 6, nr 5, s. 626-630.E3Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In situ sequencing methods generate spatially resolved RNA localization and expression data at an almost single-cell resolution. Few methods, however, currently exist to analyze and visualize the complex data that is produced, which can encode the localization and expression of a million or more individual transcripts in a tissue section. Here, we present InsituNet, an application that converts in situ sequencing data into interactive network-based visualizations, where each unique transcript is a node in the network and edges represent the spatial co-expression relationships between transcripts. InsituNet is available as an app for the Cytoscape platform at http://apps.cytoscape.org/apps/insitunet. InsituNet enables the analysis of the relationships that exist between these transcripts and can uncover how spatial co-expression profiles change in different regions of the tissue or across different tissue sections.

  • 235691. Salamone, Dominic
    et al.
    Annuzzi, Giovanni
    Univ Naples Federico II, Dept Clin Med & Surg, Med Sch, Via Pansini 5, I-80131 Naples, Italy. Univ Naples Federico II, Task Force Microbiome Studies, Naples, Italy. Uppsala Univ, Dept Publ Hlth & Caring Sci, Clin Nutr & Metab, Uppsala, Sweden. Aarhus Univ, Dept Clin Med, Aarhus, Denmark. Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland. Univ Wollongong, Sch Med Indigenous & Hlth Sci, Wollongong, Australia. Univ Wollongong, Illawarra Hlth & Med Res Inst, Wollongong, Australia. Univ Wollongong, Mol Horizons, Wollongong, Australia..
    Vessby, Bengt
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
    Rivellese, Angela A.
    Bozzetto, Lutgarda
    Costabile, Giuseppina
    Hermansen, Kjeld
    Uusitupa, Matti
    Meyer, Barbara J.
    Riccardi, Gabriele
    Fatty acid composition of cholesterol esters reflects dietary fat intake after dietary interventions in a multinational population2023Inngår i: Journal of Clinical Lipidology, ISSN 1933-2874, E-ISSN 1876-4789, Vol. 17, nr 4, s. 466-474Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    The effects of different dietary fatty acids (FA) on cardiovascular risk still needs clarification. Plasma lipids composition may be a biomarker of FA dietary intake.

    Purpose

    To evaluate in a composite population the relationships between changes in dietary fat intake and changes in FA levels in serum cholesterol esters.

    Methods

    In a multinational, parallel-design, dietary intervention (KANWU study), dietary intakes (3-day food record) and FA composition of serum cholesterol esters (gas-liquid chromatography) were evaluated at baseline and after 3 months in 162 healthy individuals, randomly assigned to a diet containing a high proportion of saturated (SFA) or monounsaturated (MUFA) fat, with a second random assignment to fish oil or placebo supplements.

    Results

    Main differences in serum lipid composition after the two diets included saturated (especially myristic, C14:0, and pentadecanoic, C15:0) and monounsaturated (oleic acid, C18:1 n-9) FA. C14:0 and C15:0 were related to SFA intake, while C18:1 n-9 was associated with MUFA intake. Fish oil supplementation induced a marked increase in eicosapentaenoic (C20:5 n-3) and docosahexaenoic (C22:6 n-3) acids. After the 3-month intervention, Δ-9 desaturase activity, calculated as palmitoleic acid/palmitic acid (C16:1/C16:0) ratio, was more reduced after the MUFA (0.31±0.10 vs 0.25±0.09, p<0.0001) than SFA diet (0.31±0.09 vs 0.29±0.08, p=0.006), with a statistically significant difference between the two groups (p<0.0001).

    Conclusions

    This study shows that serum cholesterol ester FA composition can be used during randomized controlled trials as an objective indicator of adherence to experimental diets based on saturated and monounsaturated fat modifications, as well as fish oil supplementation.

  • 235692. Salander, Par
    et al.
    Isaksson, Joakim
    Granstrom, Brith
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar.
    How Patients Make use of a Specialist Nurse Function in Head and Neck Cancer: An Empirical Study2014Inngår i: Psycho-Oncology, ISSN 1057-9249, E-ISSN 1099-1611, Vol. 23, nr 3, s. 159-159Artikkel i tidsskrift (Annet vitenskapelig)
  • 235693.
    Salander, Pär
    et al.
    Umea Univ, Dept Social Work, S-90187 Umea, Sweden..
    Isaksson, Joakim
    Umea Univ, Dept Social Work, S-90187 Umea, Sweden..
    Granström, Brith
    Umea Univ, Dept Clin Sci Otorhinolaryngol, Umea, Sweden..
    Laurell, Göran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Öron-, näs- och halssjukdomar. Uppsala Univ, Dept Surg Sci Otolaryngol & Head & Neck Surg, Uppsala, Sweden..
    Motives that head and neck cancer patients have for contacting a specialist nurse - an empirical study2016Inngår i: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 25, nr 21-22, s. 3160-3166Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aims and objectives. The purpose of this study is to systematically explore the motives for patients with head and neck cancer to contact a specialist nurse during two years postdiagnosis. Background. Research focusing on the role of specialist nurses in cancer care almost exclusively concern cancers other than head and neck cancer. Design. Qualitative, descriptive study based on the contacts between patients with head and neck cancer and a specialist nurse. Methods. Patients were invited to contact a specialist nurse by telephone. The specialist nurse took systematic field notes, that is, she registered who contacted her, the nature of the call and the outcome. Sixty patients were included. Results. In descending order, the motives for contact were questions about practical and uncomplicated matters, consultations about medical troubles/worries, presenting a report of the patient's situation, requests for additional information about the treatment plan and requests for medical information. The pattern of the patients' motivations for calling was not related to medical or social factors, suggesting that the initiative to make contact is very much a question of the complexity of individual life circumstances. Very few referrals were sent from the specialist nurse to other professionals. Conclusions. The specialist nurse turned out to be more than just a coordinator of health-care resources. The findings bring up questions about the potential of the nurse's function as a coordinator, but also as a potential attachment figure, and questions about the nurse's relationships to other professionals. Relevance to clinical practice. When implementing a specialist nurse function, it is important to decide whether the function should be inspired by a broader relational perspective. In addition to the indispensible competence and experience in the clinical field of head and neck cancer, training in counselling and acquaintance with object-relational psychology will then be desirable.

  • 235694.
    Salaneck, E
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Molecular evolution of neuropeptide Y receptors in vertebrates2001Bok (Annet vitenskapelig)
  • 235695.
    Salaneck, E
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Ardell, EW
    Larson, ET
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Larhammar, D
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Three neuropeptide Y receptors in the spiny dogfish, Squalus acanthias, support chromosome doublings in early vertebrate evolution2003Inngår i: Mol Biol Evol, Vol. 20, s. 1271-Artikkel i tidsskrift (Fagfellevurdert)
  • 235696.
    Salaneck, E
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Holmberg, SKS
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Berglund, M
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Boswell, T
    Larhammar, D
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Chicken neuropeptide Y receptor Y2: Structural and pharmacological differnces to mammalian Y2.2000Inngår i: FEBS Lett, Vol. 484, s. 229-Artikkel i tidsskrift (Fagfellevurdert)
  • 235697.
    Salaneck, E
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. Farmakologi 2.
    Larson, ET
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. Farmakologi 2.
    Larsson, TA
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. Farmakologi 2.
    Larhammar, D
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap. Farmakologi 2.
    Effects of a teleost tetraploidization on neuropeptide Y receptor gene repertoire in ray-finned fishes2005Inngår i: Ann. N. Y. Acad. Sci., Vol. 1040, s. 457-459Artikkel i tidsskrift (Fagfellevurdert)
  • 235698.
    Salaneck, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Fästingburen viral hemorragisk feber via flyttfåglar2012Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, nr 51, s. 2343-Artikkel i tidsskrift (Annet vitenskapelig)
  • 235699.
    Salaneck, Erik
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Molecular Evolution of Neuropeptide Y Receptors in Vertebrates2001Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The three evolutionarily related peptides neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) are ligands to at least five G-protein coupled receptors in mammals, which are denoted by numbers. NPY has many physiological effects including stimulation of appetite and regulation of circadian rhythm and blood pressure. This work describes the ancient origin of the NPY receptor genes as deduced from molecular cloning of six receptors in four distantly related vertebrate species. Three of the receptors have been functionally expressed in vitro to determine ligand binding properties.

    The first Y2 receptor from any non-mammalian species was cloned from the chicken. The receptor was found to exhibit substantial structural and pharmacological differences to mammalian Y2, but showed similar anatomical distribution.

    A receptor was cloned in a primitive vertebrate, an agnathan fish, the river lamprey Lampetra fluviatilis. Phylogenetic analyses indicated that it represents an orthologue to the ancestor of Y4 and the teleost subtypes Yb and Yc.

    Three NPY receptors were cloned from a shark, the spiny dogfish Squalus acanthias. These were found to correspond to the three mammalian subtypes Y1, Y4 and y6, and was thereby the first complete Y1 subfamily in any species outside the mammalian lineage. This suggests that all three receptor subtypes arose in the common ancestor of sharks and mammals 420-450 million years ago.

    The sixth described receptor was cloned from the zebrafish, Danio rerio, and was shown to have equal identity to all three mammalian Y1 subfamily receptors. Phylogenetic analyses including the shark and lamprey sequences suggested that Yb may represent a fourth Y1 subfamily gene.

    It has previously been found that the genes for Y1, Y4 and y6 are located on separate chromosomes. Taken together, these results show that the NPY receptor family expanded by chromosomal duplications early in vertebrate evolution, prior to the origin of gnathostomes. This work will be important for the determination of the time points for the origin of the many functions of NPY as well as for the understanding of the processes that shaped the vertebrate genome.

    Fulltekst (pdf)
    FULLTEXT01
  • 235700.
    Salaneck, Erik
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Fredriksson, Robert
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Larson, Earl T
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    Conlon, Michael
    Larhammar, Dan
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap.
    A neuropeptide Y receptor Y1-subfamily gene from agnathan, the European river lamprey. A potental ancestral gene2001Inngår i: Eur J Biochem, Vol. 268, s. 6146-Artikkel i tidsskrift (Fagfellevurdert)
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