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Preparation of cryoelectron microscopy (cryo-EM) grids for imaging of amyloid fibrils is notoriously challenging. The human islet amyloid polypeptide (hIAPP) serves as a notable example, as the majority of reported structures have relied on the use of nonphysiological pH buffers, N -terminal tags, and seeding. This highlights the need for more efficient, reproducible methodologies that can elucidate amyloid fibril structures formed under diverse conditions. In this work, we demonstrate that the distribution of fibrils on cryo-EM grids is predominantly determined by the solution composition, which is critical for the stability of thin vitreous ice films. We discover that, among physiological pH buffers, HEPES uniquely enhances the distribution of fibrils on cryo-EM grids and improves the stability of ice layers. This improvement is attributed to direct interactions between HEPES molecules and hIAPP, effectively minimizing the tendency of hIAPP to form dense clusters in solutions and preventing ice nucleation. Furthermore, we provide additional support for the idea that denatured protein monolayers forming at the interface are also capable of eliciting a surfactant -like effect, leading to improved particle coverage. This phenomenon is illustrated by the addition of nonamyloidogenic rat IAPP (rIAPP) to a solution of preaggregated hIAPP just before the freezing process. The resultant grids, supplemented with this "spectator protein", exhibit notably enhanced coverage and improved ice quality. Unlike conventional surfactants, rIAPP is additionally capable of disentangling the dense clusters formed by hIAPP. By applying the proposed strategies, we have resolved the structure of the dominant hIAPP polymorph, formed in vitro at pH 7.4, to a final resolution of 4 A & ring; . The advances in grid preparation presented in this work hold significant promise for enabling structural determination of amyloid proteins which are particularly resistant to conventional grid preparation techniques.

Inhibitors targeting amyloids formed by the human Islet Amyloid Polypeptide (hIAPP) are promising therapeutic candidates for type 2 diabetes. Peptide formulations derived from the nonamyloidogenic rat IAPP (rIAPP) sequence are currently used as hIAPP mimetics to support insulin therapy. rIAPP itself acts as a peptide inhibitor; yet, the structural-level consequences of such inhibition, particularly its impact on amyloid polymorphism, have not been studied in detail. Here, we conduct coaggregation experiments with varying rIAPP-to-hIAPP concentration ratios and employ high-resolution cryo-electron microscopy (Cryo-EM) to elucidate the polymorphism of the resulting fibril structures. Our results demonstrate that the polymorphism of hIAPP amyloids is highly sensitive to the electrostatic environment, which can be modulated by buffer composition, the concentration of the inhibitor, and cosolvents such as hexafluoroisopropanol (HFIP). Under native conditions, rIAPP associates with hIAPP but does not cross-aggregate, resulting in fibrils primarily composed of hIAPP. Significant inhibition is observed at relatively high concentrations of rIAPP. However, trace amounts of HFIP disrupt this inhibition, leading to increased fibril concentrations due to the formation of cross-seeded products composed of both hIAPP and rIAPP, as evidenced by mass spectrometry and two-dimensional infrared (2D IR) spectroscopy. These findings highlight the critical role of experimental conditions, particularly the electrostatic environment, in modulating amyloid polymorphism, cross-seeding, and inhibition. By providing structural insights into these processes, this study advances our understanding of peptide aggregation and offers valuable guidance for the rational design of more effective therapeutic inhibitors targeting hIAPP-related amyloidosis.

In the pursuit of potential therapeutic agents for type 2 diabetes, non-amyloidogenic forms of the human Islet Amyloid Polypeptide (hIAPP) containing site-specific mutations are of significant interest. In the present study, we dissect the three proline mutations present in the core region of the non-amyloidogenic rat IAPP into single-point mutations at A25P, S28P, and S29P sites. We apply high-resolution cryo-electron microscopy and solve the structures of 6 polymorphs formed by these mutants, revealing the peptide's self-assembly patterns and identifying critical interactions that reinforce these structures in the presence of the b-sheet breaker. A unique trimeric aggregate with C3 symmetry was identified in the A25P mutant, which we resolved with a 3.05 A resolution, while asymmetric trimeric assemblies were observed in the other mutants. Guided by the high-resolution structural models of A25P and S28P fibrils obtained in our study, we successfully designed novel non-amyloidogenic mutants of IAPP with potential therapeutic value. Our findings demonstrate the immense potential of structure-based approaches in developing effective therapeutics against amyloid diseases. 

The human islet amyloid polypeptide (hIAPP) aggregates into amyloid fibrils that contribute to β-cell failure in type 2 diabetes. hIAPP is produced from a 67-residue precursor, proIAPP, but incomplete cleavage by prohormone convertase 2 (PC2) produces the 48-residue intermediate proIAPP(1–48), which accelerates amyloid formation in vivo. Here we show that proIAPP(1–48) assembles almost exclusively into a single fibril polymorph. Using cryo-electron microscopy we solved its structure at 3.5 Å resolution and uncovered a P-shaped, C2-symmetric dimer whose backbone and side-chain packing are nearly identical to the disease-associated TW2 polymorph propagated from pancreatic tissue, although with different helical symmetry. All eleven extra N-terminal residues remain disordered but create a weak density around His29. Based on time-averaged density derived from molecular dynamics (MD) simulations, we identified multiple hydrogen(H)-bonding interactions, which may contribute to stabilising the TW2-like fold and explain the peripheral cryo-EM density. These data establish a structural link between defective proIAPP processing and the polymorphic spectrum of islet amyloid and suggest a seeding pathway by which proIAPP(1–48) templates pathogenic architectures that fully processed hIAPP rarely adopts in vitro.

Given a tree T and a subtree S of T, one can define the local mean at S, μ_T(S),to be the average order of the subtrees of T containing S. In 1983, Jamison showed that μ_T(S)< μ_T(S′) if S ⊂ S′ as subtrees of T. Therefore, it is natural to ask the following question. Among all the k-subtrees (subtrees of order k), which one achieves the maximal/minimal local mean and what properties does it have? We call such k-subtrees k-maximal/k-minimal. Wagner and H. Wang showed in 2016t hat a 1-maximal subtree has degree 1 or 2. In this paper, we show that if T is not a path, a 1-minimal subtree of T has degree at least 3. For  k≥2, we show that a  k-maximal subtree has at most one leaf whose degree in T is greater than 2, and that such a leaf can only occur when all other leaves in S are also leaves in T. Parallel results hold for k-minimal subtrees. Roughly speaking, the leaves of a k-maximal subtree tend to have degree 1 or 2 in T, while the leaves of a k-minimal subtree tend to have degree at least 3 in T. In the second part, this paper introduces the local density as a normalization oflocal means, for the sake of comparing subtrees of different orders. We show that the local density at subtree S is lower-bounded by 1/2 with equality if and only if S contains all the vertices of degree at least 3 in T. On the other hand, local density can be arbitrarily close to 1.

Given a tree T of order n , one can contract any edge and obtain a new tree T & lowast; of order n - 1. In 1983, Jamison made a conjecture that the mean subtree order, i.e., the average order of all subtrees, decreases at least 31 in contracting an edge of a tree. In 2023, Luo, Xu, Wagner and Wang proved the case when the edge to be contracted is a pendant edge. In this article, we prove that the conjecture is true in general. (c) 2024 The Author. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Submersed aquatic vegetation (SAV) provides essential habitat and food to numerous coastal invertebrate species. In the eutrophic Baltic Sea, fast-growing drifting algae form extensive mats that can negatively impact SAV. However, these mats also offer additional habitat and food to epifauna. The aim of this study was to assess the effects of SAV and filamentous mats on epifaunal communities in shallow soft-bottom habitats around Gotland, Sweden, in the central Baltic Sea. We used generalised linear models (GLMs) to evaluate the influence of SAV vertical structure, biomass and macrophyte species richness (including macroalgae) and filamentous mat biomass on epifaunal community properties as well as on those of key grazer species. Diversity, vertical structure and biomass of SAV were positively associated with higher total epifaunal abundance and greater abundance gastropod grazers. In contrast, filamentous mats only increased gastropod abundance and biomass. In addition to introducing a rapid tool for quantifying vegetation structural complexity, this study highlights the selective effects of different habitat types on invertebrate communities in a relatively understudied region of the Baltic Sea. As warming temperatures and eutrophication promote filamentous mat growth, reducing nutrient pollution and protecting SAV will be crucial for sustaining abundant and diverse epifaunal communities.

Three-spined sticklebacks (Gasterosteus aculeatus) have become dominant in many Baltic Sea coastal fish assemblages, yet life-stage-specific habitat use remains poorly understood. We surveyed shallow water habitats along the coast of Gotland, Sweden, to examine how juvenile and adult stickleback abundances relate to variables such as submersed aquatic vegetation (SAV) biomass and vertical structure, macrophyte species richness, biomass of drift filamentous algae and potential invertebrate prey abundance. Juvenile stickleback abundance increased with SAV variables, macrophyte species richness, and drift filamentous algae, whereas, in contrast, adult abundance was only significantly associated with potential prey (invertebrate abundance). Our findings reveal life-stage-specific habitat associations of three-spined sticklebacks and highlights the importance of both long-living vegetation and ephemeral drift algae in supporting juvenile sticklebacks. This study contributes to a better understanding of sticklebacks' coastal ecology in the central Baltic Sea.

Background: Plasma hyaluronan concentrations are increased during sepsis but underlying mechanisms leading to high plasma hyaluronan concentration are poorly understood. In this study we evaluate the roles of plasma hyaluronan, effective plasma hyaluronidase (HYAL) activity and its endogenous plasma inhibition in clinical and experimental sepsis. We specifically hypothesized that plasma HYAL acts as endothelial glycocalyx shedding enzyme, sheddase. Methods: Plasma hyaluronan, effective HYAL activity and HYAL inhibition were measured in healthy volunteers (n = 20), in patients with septic shock (n = 17, day 1 and day 4), in patients with acute pancreatitis (n = 7, day 1 and day 4) and in anesthetized and mechanically ventilated pigs (n = 16). Sixteen pigs were allocated (unblinded, open label) into three groups: Sepsis-1 with infusion of live Escherichia coli (E. coli) 1 x 10(8) CFU/h of 12 h (n = 5), Sepsis-2 with infusion of E. coli 1 x 10(8) CFU/h of 6 h followed by 1 x 10(9) CFU/h of the remaining 6 h (n = 5) or Control with no E. coli infusion (n = 6). Results: In experimental E. coli porcine sepsis and in time controls, plasma hyaluronan increases with concomitant decrease in effective plasma HYAL activity and increase of endogenous HYAL inhibition. Plasma hyaluronan increased in patients with septic shock but not in acute pancreatitis. Effective plasma HYAL was lower in septic shock and acute pancreatitis as compared to healthy volunteers, while plasma HYAL inhibition was only increased in septic shock. Conclusion: Elevated plasma hyaluronan levels coincided with a concomitant decrease in effective plasma HYAL activity and increase of endogenous plasma HYAL inhibition both in experimental and clinical sepsis. In acute pancreatitis, effective plasma HYAL activity was decreased which was not associated with increased plasma hyaluronan concentrations or endogenous HYAL inhibition. The results suggest that plasma HYAL does not act as sheddase in sepsis or pancreatitis.

While fluid resuscitation is fundamental in the treatment of sepsis-induced tissue hypo-perfusion, a sustained positive fluid balance is associated with excess mortality. Hyaluronan, an endogenous glycosaminoglycan with high affinity to water, has not been tested previously as adjuvant to fluid resuscitation in sepsis.

In a prospective, parallel-grouped, blinded model of porcine peritonitis-sepsis, we randomized animals to intervention with adjuvant hyaluronan (add-on to standard therapy) (n=8) or 0.9% saline (n=8). After the onset of hemodynamic instability the animals received an initial bolus of 0.1 % hyaluronan 1 mg/kg/10 min or placebo (0.9% saline) followed by a continuous infusion of 0.1% hyaluronan (1 mg/kg/h) or saline during the experiment. We hypothesized that the administration of hyaluronan would reduce the volume of fluid administered (aiming at stroke volume variation <13%) and/or attenuate the inflammatory reaction.

Total volumes of intravenous fluids infused were 17.5 ± 11 ml/kg/h vs. 19.0 ± 7 ml/kg/h in intervention and control groups, respectively (p = 0.442). Plasma IL-6 increased to 2450 (1420 – 6890) pg/ml and 3690 (1410 – 11960) pg/ml (18 hours of resuscitation) in the intervention and control groups (NS). The intervention counteracted the increase in proportion of fragmented hyaluronan associated with peritonitis-sepsis alone (mean peak elution fraction (18 hours of resuscitation) control group: 17.9 ± 0.6 vs. intervention group: 16.8 ± 0.9 (p = 0.031).

In conclusion, hyaluronan did not reduce the volume needed for fluid resuscitation or decrease the inflammatory reaction, even though it counterbalanced the peritonitis induced shift towards increased proportion of fragmented hyaluronan.

Sepsis is a condition with high morbidity and mortality. Prompt recognition and initiation of treatment is essential. Despite forming an integral part of sepsis management, fluid resuscitation may also lead to volume overload, which in turn is associated with increased mortality. The optimal fluid strategy in sepsis resuscitation is yet to be defined. Hyaluronan, an endogenous glycosaminoglycan with high affinity to water is an important constituent of the endothelial glycocalyx. We hypothesized that exogenously administered hyaluronan would counteract intravascular volume depletion and contribute to endothelial glycocalyx integrity in a fluid restrictive model of peritonitis. In a prospective, blinded model of porcine peritonitis sepsis, we randomized animals to intervention with hyaluronan (n = 8) or 0.9% saline (n = 8). The animals received an infusion of 0.1% hyaluronan 6 ml/kg/h, or the same volume of saline, during the first 2 h of peritonitis. Stroke volume variation and hemoconcentration were comparable in the two groups throughout the experiment. Cardiac output was higher in the intervention group during the infusion of hyaluronan (3.2 ± 0.5 l/min in intervention group vs 2.7 ± 0.2 l/min in the control group) (p = 0.039). The increase in lactate was more pronounced in the intervention group (3.2 ± 1.0 mmol/l in the intervention group and 1.7 ± 0.7 mmol/l in the control group) at the end of the experiment (p < 0.001). Concentrations of surrogate markers of glycocalyx damage; syndecan 1 (0.6 ± 0.2 ng/ml vs 0.5 ± 0.2 ng/ml, p = 0.292), heparan sulphate (1.23 ± 0.2 vs 1.4 ± 0.3 ng/ml, p = 0.211) and vascular adhesion protein 1 (7.0 ± 4.1 vs 8.2 ± 2.3 ng/ml, p = 0.492) were comparable in the two groups at the end of the experiment. In conclusion, hyaluronan did not counteract intravascular volume depletion in early peritonitis sepsis. However, this finding is hampered by the short observation period and a beneficial effect of HMW-HA in peritonitis sepsis cannot be discarded based on the results of the present study.

Background: Sepsis is a critical condition characterized by a dysregulated immune response to infection. As sepsis develops to septic shock, its most severe form, morbidity and mortality increases. Hyaluronan is a key component of the extracellular matrix and the endothelial glycocalyx. In sepsis, plasma hyaluronan concentrations are increased and correlate with disease severity. In this study we aimed to explore and compare the proteomic profiles of hyaluronan-associated proteins in patients with the dysregulated immune response of septic shock and the sterile inflammation of acute alcohol-related pancreatitis.

Methods: The present study involved proteomic analysis of patients with septic shock (n = 13), pancreatitis (n = 8), and healthy controls (n = 8). LC-MS/MS was conducted for peptide analysis. Hyaluronan-associated proteins were identified using the UniProt REST API, followed by functional and pathway enrichment analyses with GOATOOLS and GSEApy. Statistical analyses, including ANOVA and post hoc tests, were performed using Python and SPSS, with significance set at p < 0.05.

Results: From a total sum of 663 detected unique plasma proteins, 15 were identified as hyaluronan-related proteins. Plasma levels of 11/15 proteins separated septic shock from pancreatitis in a statistically significant manner. Between the groups differences were apparent on day 1 (8 proteins in septic shock versus 3 in pancreatitis) and day 4 (6 proteins in septic shock versus 3 in pancreatitis) relative to controls. Functional enrichment analysis revealed associations with extracellular matrix organization, proteolytic enzyme regulation, and hyaluronan metabolism. Notably, members of the inter-alpha-inhibitor family demonstrated distinct patterns, with ITIH3 levels increasing and ITIH1, ITIH2, and ITIH4 levels decreasing in septic shock compared to controls. Additionally, plasma hyaluronidase inhibition correlated positively with ITIH3 levels.

Conclusion: The present study explored the role of hyaluronan-related proteins in septic shock pathophysiology, revealing potential dysregulation associated with sepsis severity. The decrease in ITIH1, ITIH2 and ITIH4, as compared to the increase in ITIH3, suggest a complex alteration in the protein balance of the I alpha I-family in sepsis. Overall, the altered proteomic profile of hyaluronan-related proteins as reflected by the GO terms indicates a complex dysregulation not only in hyaluronan metabolism and extracellular matrix, but also in the regulation of several proteolytic enzymes. Future studies on this area are warranted.

The study delves into the perspectives of pre-service science teachers in Sweden regarding science education and how these perspectives influence their learning process to teach science. By utilizing visions of scientific literacy and curriculum emphases as an analytical framework, interviews were conducted to gain insights into how pre-service teachers reflect on what is essential to teach in science and how they approach it. Thereby, the present study contributes to the knowledge of science teacher education regarding how pre-service science teachers` perspectives on science education guide their future teaching. The study found that the pre-service teachers described science education primarily in terms of learning scientific facts and concepts. Being able to make use of scientific facts for everyday issues was also part of their goal of teaching. Scientific engagement in relation to society and taking action were absent in their talk about scientific literacy and future teaching plans. The findings are discussed in terms of implications for research and teacher education and underscore that teacher education is central to the students’ perspectives. Those perspectives are important to foster scientific literacy of the pupils who are engaged in society.

This study has two related aims; to investigate the perspectives of pre-service science teachers from Türkiye and Sweden on scientific literacy including what content is relevant and important and how these perspectives might be related to their future teaching practices. Utilizing the framework of Visions of Scientific Literacy and Curriculum Emphases by Roberts (1998, 2007), the research conducts a comparative analysis to give an overview of how pre-service teachers privilege specific contents that they attributed to science education in terms of “why to teach science” according to their perspectives. The findings reveal that participants from both countries referred to the curriculum emphases, Everyday Coping (EC) and Correct Explanation (CE), as the most important reasons to teach science, whereas Scientific Skills Development (SSD) and Science, Technology, and Decision (STD) were notably underemphasized in both contexts. However, the study also revealed differences in the perspectives of pre-service science teachers. For the pre-service teachers from Türkiye, teaching science was important to deal with daily life issues, whereas the ones from Sweden privileged more scientific facts and processes. Furthermore, participants from both countries problematized science teacher education but in different ways, including teaching evolution, having too few or too many subject courses in the teacher education. This cross-cultural comparison provides insights into how scientific literacy is promoted within diverse educational environments; the results help to reflect on what may be included and excluded in science teacher education and inform possible future improvements within science teacher education.

Scientific literacy (SL) is a widely recognized goal of science education, yet its meaning and purpose are interpreted differently across contexts. This study compares how SL is conceptualized and related to future teaching in elementary science teacher education curricula in Türkiye and Sweden. A pragmatic discourse analysis was conducted on national guidelines and university curriculum documents. The analysis reveals two distinct discourses: the Disciplinary discourse, dominant in the Turkish documents, and the Integrative discourse, foregrounded in the Swedish documents. The Disciplinary discourse presents SL as an explicit and separate body of knowledge, emphasizing subject mastery and preparing pre-service teachers to teach this knowledge. In contrast, the Integrative discourse frames SL as embedded in teaching practices that connect science with sustainability, democracy, and critical engagement with socioscientific issues. The comparison underscores how curriculum and teaching traditions and policy frameworks guide teacher education.

Objective

Tumor deposits (TDs) are a negative prognostic factor in colorectal cancer, independent of lymph node metastasis (LNM). This study aimed to investigate the ability of pre-operative MRI to identify TDs and differentiate them from LNM in rectal cancer.

Materials and methods

Patients with histopathological N1-N2 rectal cancer with and without TDs who underwent curative-intent primary surgery between 2013 and 2023 were retrospectively included. Three radiologists independently reviewed pre-operative MR images for the presence of TDs and LNM. Histopathology served as the reference standard from which interobserver agreement by Cohen’s kappa (κ) was calculated. Unblinded node-to-node comparison of MRI and histopathological images was used to identify sources of discrepancies between the modalities. Post hoc analysis stratified on nodal size (> or ≤ 5 mm) was performed.

Results

Eighty-eight patients (50% with TDs on histopathology, 74% male, median age 70 [20–89] years) were included, of whom 27 were excluded due to poor image quality. Agreement between MRI and histopathology (p), both for TD-presence (κ = −0.04) and LNM-presence (κ = 0.16), was low. In the node-by-node comparison, 43 out of 50 pTDs (86%) measured ≤ 5 mm, and 131 of 167 pLNM (78%) measured ≤ 5 mm. In post hoc analysis of smaller (≤ 5 mm) nodules, no pTDs and 3% of pLNM were diagnosed using MRI.

Conclusion

MRI demonstrated limited ability in detecting and differentiating TDs and LNM in pre-operative low-risk patients. Diagnostic performance was particularly poor for nodules ≤ 5 mm, which constituted 174 out of 217 (80%) pathological nodular structures.

Purpose The aim of this study was to evaluate the possible risk factors for developing a parastomal hernia (PSH) in a cohort of rectal cancer patients with and without the application of a retro-muscular prophylactic mesh. The evaluated risk factors included the position of the stoma in the rectus abdominis muscle (RAM), RAM atrophy and shift of abdominal wall midline structures. Methods Rectal cancer patients treated with an abdominoperineal excision or Hartmann's procedure between 2002 and 2015 at Vastmanland Hospital, Sweden was included. Postoperative CT examinations were retrospectively reviewed regarding the presence of PSH and RAM atrophy and for measurements such as position of the stoma in the RAM. Results 116 patients were included, with a median age of 71 years. 70 patients received a prophylactic stoma mesh. 55 patients (47%) had a parastomal hernia at three-year follow-up. Rectus abdominis muscle atrophy was significantly higher in the mesh group compared with the non-mesh group (37% vs 2%; P = 0.04). RAM atrophy was a significant independent protective factor for developing a PSH (P = 0.007; OR 0.15; 95% CI 0.03-0.55). Conclusion Placement of a prophylactic retro-muscular stoma mesh resulted in a high frequency of RAM atrophy distal to the stomal aperture and patients with such atrophy had a lower risk of developing a PSH.

Purpose

The primary aim of this study was to investigate whether rectus abdominis muscle atrophy is associated with a lower risk of developing parastomal hernia. Secondary objectives were to assess whether the use of prophylactic mesh is a risk factor for rectus abdominis muscle atrophy and whether the position of the stoma within the rectus abdominis muscle affects the risk of parastomal hernia.

Methods

This retrospective study analysed patients from a prospective, randomised, multicentre trial in which rectal cancer patients were randomised to stoma creation with or without prophylactic mesh. Computed tomography at 12 months was evaluated to identify parastomal hernia, rectus abdominis muscle atrophy and position of stoma in the rectus abdominis muscle.

Results

Out of 149 patients, rectus abdominis muscle atrophy was observed in 9% and parastomal hernia in 42% of patients. There was no association between rectus abdominis muscle atrophy and parastomal hernia (p = 0.80; RR 1.07; CI 0.62–1.86), nor between prophylactic mesh and rectus abdominis muscle atrophy (p = 0.19; RR 2.00; CI 0.7–5.73). Stoma placement within the rectus abdominis muscle also showed no association with parastomal hernia development (p = 0.69; RR 0.97; CI 0.81–1.15).

Conclusion

This study found no statistically significant association between rectus abdominis muscle atrophy and parastomal hernia. The use of prophylactic mesh was not a risk factor for rectus abdominis muscle atrophy, and stoma placement within the rectus abdominis muscle was not associated with parastomal hernia. The previously reported association between prophylactic mesh, rectus abdominis muscle atrophy, and parastomal hernia was not confirmed in this cohort.

Flexibility is the defining promise of the gig economy, yet also its central contradiction. Often framed as a benefit, flexibility operates dialectically, as both a mechanism of control and a potential site of agency. Workers’ ability to navigate or resist precarity is shaped by their position within segmented labour markets, their subjectivities, and broader socio-economic structures. The gig economy is not a single labour market, then, but a stratified one in which conditions vary drastically across sectors and worker groups. This paper examines two differently situated workers in distinct segments of gig work to explore the determinants of precarity. It identifies three key dialectical tensions: (1) flexibility as both freedom and control; (2) gig work as promizing autonomy but delivering insecurity; and (3) the gig economy as simultaneously embedded in and excluded from Sweden’s labour market model, undermining protections whilst reproducing exclusion. Through digital mediation, task atomization, and misclassification, gig work entrenches inequality in new ways. In Sweden, Europe’s most segregated labour market, the gig economy exacerbates existing divisions. Whilst some workers benefit, others, particularly racialized migrants, face deepened precarity and algorithmic discipline. Rather than disrupting hierarchies, Sweden’s gig economy reinforces them through new forms of segmentation and spatio-temporal discipline.

This paper concerns migrants in Sweden working in various types of on and offline gig work. It explores how the temporal and spatial flexibility afforded to gig customers is predicated on temporal and spatial inflexibility for workers. The argument moves discussions beyond relational space by promoting a more fully dialectical view of space that understands it as simultaneously relational, relative, and absolute. Without such a view of space-which understands that space is not always open and fluid but just as often closed and fixed-it is impossible to understand the specific relations of labour that structure gig work, particularly offline gig work in such ways as to provide maximal flexibility for customers. This paper shows that the Marxian adage concerning how, in capitalism, space is annihilated by time, does not always hold. For workers doing cleaning and delivery gig work, the converse is oftentimes truer: time is annihilated by space. Gig workers-and even more so migrant gig workers crowded in the above-mentioned industries-experience the annihilation of time by space through the dual mandate that they must be available "just-in-time" and "just-in-place" to produce the spatiotemporal flexibility upon which the gig companies base their model and their success.

This paper examines labour agency in Sweden’s gig economy through a spatio-temporal reading of resilience, reworking, and resistance. Drawing on qualitative interviews with platform workers and union representatives, alongside policy, media, and observational material, it argues that worker agency is not absent under platform capitalism, but fragmented and unevenly organised through the spatial and temporal logics of platform work. Building on Katz’s framework of the 3Rs, the paper shows how resilience emerges under conditions of temporal compression and spatial isolation; how reworking becomes possible through partial decompressions of these pressures; and how resistance depends on fragile moments of synchronisation, when dispersed workers are able to recognise shared grievances and act collectively. Focusing on platform labour in Sweden, the paper demonstrates that these forms of agency are unevenly distributed across lines of migration status, race, gender, sector, and access to institutional support. In doing so, it contributes to labour geography and platform labour studies by developing a spatio-temporal account of disaggregated agency, while also showing how platform labour exposes the limits of collective representation within the Swedish model.

This paper develops the concept of spectral infrastructures to examine how platform capitalism reorganises visibility, labour, and value in the contemporary city. Drawing on debates across urban theory, labour geography, logistical urbanism, and the infrastructural turn, it argues that the fulfilment city is sustained by infrastructures that are simultaneously ubiquitous and elusive: dark stores, ghost kitchens, platform interfaces, automated delivery systems, and the workers whose movement keeps these circuits in motion. Through empirical exemplification from Stockholm, the paper shows how these infrastructures appear unevenly across urban space, from branded façades and containerised ghost kitchens to vacant shopfronts, digital traces, dark stores, and delivery robots. Drawing on Walter Benjamin’s analysis of the phantasmagoria of commodity culture, the paper conceptualises spectrality not as absence, but as a regime of selective appearance in which labour is made visible as movement, service, or spectacle whilst remaining socially and politically obscured. By tracing how logistical rationality mediates visibility, value, and everyday urban experience, the paper contributes to debates on urban infrastructural politics and the changing geographies of work. In doing so, it re-embeds labour within analyses of infrastructure and urban form, showing how the apparent smoothness of platform urbanism depends on the uneven organisation of work, visibility, and friction.

New research indicates that genetic variants related to educational attainment influence individuals’ political participation. This suggests that political inequality of opportunity is partially rooted in an inequality in genetic resources. However, the possibility that these genetic influences are contingent on individuals’ environments, such that they are amplified or reduced by certain environmental characteristics, remains unexplored. Using longitudinal and geo-coded register data for a large sample of genotyped twins in the Swedish Twin Registry, this paper explores whether early-life proximal environments that are conducive to participation modifies the effects of individuals’ education-related genetic resources on voting, as measured by a polygenic index for educational attainment. The results suggest that the level of political engagement, and of SES, both within the family and within the neighbourhood, can reduce the effects of genetic resources on voting. This has implications for how we can direct policy to ameliorate genetic inequalities in political participation.

For half a century, scholars have debated the societal implications of research that suggests genetic explanations for socioeconomic disparities. However, studies of whether and how such genetic explanations affect the attitudes of citizensare surprisingly limited. Using two identical, pre-registered survey experiments fielded in the United States (N=2003) and Sweden (N=2005), this study tests whether a short, twin study-based genetic explanation for income and education differencesleads to citizens adopting a lower perceived possibility, as well as a lower perceived fairness, of the government reducing socioeconomic differences. The results do not provide systematic evidence to this effect. Rather, there are indications that citizens increase their belief in the effectiveness, as well as in the fairness of government intervention. Most clearly, the treatment increased citizens’ support for a set of redistributive policy proposals, particularly in Sweden. Overall, however, the treatment effects appear to have been limited. This is likely attributable to the experimental manipulationbeing inadequate in magnitude. This study suggests that genetic explanations for socioeconomic differences do not necessarily have to cause a naturalization of inequality among citizens, but further research on this important topic is needed.

Interest in the role of genetics in influencing key life outcomes such as educational attainment has grown quickly. However, the question of whether genetic influences on educational attainment, on average as well as in conjunction with socioeconomic circumstances, are moderated by macro-level factors has not yet received sufficient attention. This study combines polygenic indices for educational attainment (EA PGI) with high-quality register data in a large sample of Swedish twins of European ancestry born 1920–1999. Employing both conventional between-family and within-family models, the analyses suggest that the influences of education-related genetic propensities on educational attainment have increased in Sweden during the twentieth century, a period featuring major expansions of the Swedish educational system, and decreasing economic inequality. The analyses also suggest that the degree to which socioeconomic background enhances genetic influences on education has decreased across cohorts. Genetic influences on education do not appear to have translated into increased genetic influences on income. Additionally, there is some evidence of floor and ceiling effects in the analyses of dichotomous educational outcomes.

Pathogenic multidrug-resistant bacteria with hybrid chromosomes have emerged as a significant global healthcare threat. These include the pandemic Escherichia coli ST1193, the product of homologous recombination events involving two phylogenetically distant strains of E. coli, in which mutant alleles of the widely separated genes, gyrA and parC, generating high-level fluoroquinolone resistance were acquired. The mechanisms and frequency of hybrid formation are poorly understood. We developed a robust hybrid selection procedure and applied it to 118 clinical UTI isolates of E. coli mixed with suitable recipient strains. Hybrids were selected from 39% of isolates. All hybrids were recombinants of donor and recipient chromosomal DNA (median length of donor DNA 367 kb), with 90% also acquiring conjugative mobile genetic elements (MGE) from the donor. We showed that individual conjugative plasmids, and integrative conjugative elements (ICE), from donors were sufficient to drive hybrid formation. These observations strongly support conjugative chromosomal DNA transfer as the major mechanism underlying hybrid formation. ICE are genome-integrated and passively propagated but when transferring to recipients they normally do so by excising and producing their own conjugation machinery. We found that ICE were responsible for the highest frequencies of hybrid chromosome formation. They could mobilize DNA around the full length of the chromosome, including the simultaneous acquisition of mutant variants of gyrA and parC, separated by ∼826 kb, generating highly fluoroquinolone-resistant bacteria in a single event. Bacterial hybrid chromosome formation driven by conjugative MGE may be an important and widespread mechanism in the emergence and evolution of high-risk bacterial pathogens.

Horizontal gene transfer (HGT) between bacterial species is an important contributor to the development of multidrug-resistant (MDR) clinical pathogens. One example is the transfer of MDR conjugative plasmids from Klebsiella pneumoniae into Escherichia coli occurring within co-infected human hosts. Here, we asked whether, in mixed-species bacterial populations, we could also detect the transfer of chromosomal DNA. To address this, we screened 50 K. pneumoniae clinical isolates for their ability to generate chromosomal hybrids with E. coli as recipient. We found that 7/50 (14%) generated chromosomal hybrids at frequencies above our limit of detection (~10-11) up to a frequency of 5x10-10. Genome sequence analysis of 28 hybrids revealed multiple underlying mechanisms of DNA transfer and recombination. These included two different mechanisms by which a region of the E. coli chromosome was replaced with K. pneumoniae chromosomal DNA (Hfr-like mechanisms, with up to 586 kb of K. pneumoniae DNA acquired), and three different mechanisms by which F’-like plasmids carrying K. pneumoniae chromosomal DNA were created and transferred into E. coli. Accordingly, clinical isolates of K. pneumoniae have the ability to transfer, not just plasmids, but also intrinsically non-mobile chromosomal DNA into E. coli to create novel hybrid strains. Several of the isolated hybrids acquired genes related to virulence or antibiotic resistance. Chromosomal hybrids were stable after evolution in rich media and had a 70-95% fitness compared to MG1655. The results provide insights into the mechanisms involved in creating bacteria with novel hybrid chromosomes, which may have important implications for bacterial evolution, and the spread of antibiotic resistance and virulence genes.

Integrated conjugative elements can drive the transfer of chromosomal DNA from one Escherichia coli strain into another, generating strains with hybrid chromosomes. Several pandemic virulent multidrug-resistant strains of E. coli are chromosomal hybrids. Here we show that the frequency of hybrid formation can differ by orders of magnitude depending on the parental combination. However, the donor-recipient characteristics affecting hybridization efficiency are poorly understood. The laboratory workhorse strain E. coli MG1655 is significantly more proficient as a recipient in hybrid generation than E. coli ATCC25922, the strain used for quality control in antibiotic susceptibility testing. Focusing on these two strains we tested several hypotheses to identify barriers to hybrid formation. Among these, we found that relative conjugation efficiency correlated with hybrid formation frequency. To explore this, we used transposon mutagenesis to identify genes in ATCC25922 whose inactivation relieves a conjugation barrier. Among the first 1500 mutants tested we isolated and identified one that was 500-fold more conjugation-permissive than the parental strain. Whole genome sequencing identified this candidate ‘barrier’ gene as a protein-coding sequence on plasmid 3. Understanding the barrier mechanism will require further study. We are currently testing whether inactivation of this gene also increases chromosomal hybrid formation. The importance of this work is that it could significantly deepen our understanding of preferred pathways of HGT, something that will have broad application in both clinical and evolutionary biology.

Escherichia coli is a prototroph and can synthesize all twenty proteinogenic amino acids when required to grow in minimal medium. There are approximately sixty protein-coding genes individually essential for amino acid synthesis. This is a large mutational target for the accumulation of detrimental mutations. E. coli can rewire biosynthetic pathways in response to mutational damage but the limits of this capacity are poorly understood. Here, to address evolutionary robustness, we asked whether and how the phenotypes of irreversible mutations causing auxotrophy could be suppressed or bypassed in the absence of horizontal gene transfer (HGT). Spontaneous suppressors could be selected for only ten of fifty-nine mutants tested (detection limit ~7x10^-11). Mechanisms of suppression included: regional amplifications; mutations increasing gene or operon expression; mutations relaxing enzyme specificity; and mutations causing biochemical pathway diversions. Overall, the data show that spontaneous suppression of auxotrophy caused by an irreversible mutation is an evolutionary survival mechanism relevant only to a minority of the genes essential for amino acid synthesis. As a consequence, the essential genetic foundations for amino acid prototrophy are expected to be degraded over time by mutations (Muller’s ratchet) and metabolic rewiring alone will be insufficient to counteract this effect. This implies that maintaining phenotypes, including prototrophy in E. coli, and potentially other bacterial species, is likely to be reliant on HGT of housekeeping genes to counteract the effects of inevitable mutational inactivation. Accordingly, chromosomal HGT in bacteria may be critical for survival across diverse environmental niches.