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In situ molecular organization and heterogeneity of the Legionella Dot/Icm T4SS
No full textThe Dot/Icm type IV secretion system (T4SS) is essential for Legionella pneumophila infection, but its in situ architecture and mechanism remain incompletely understood. Using cryoโelectron tomography, we performed subtomogram averaging and 3D classification to resolve structural heterogeneity within the complex. We identified multiple assembly states of the inner membrane complex, including a fully assembled form with a hexamerโofโdimers DotO ATPase and symmetry mismatches between subcomplexes. A composite in situ model revealed a central channel above the inner membrane, likely used for substrate secretion. Imaging of infected macrophages showed T4SSs tethered to host vacuoles and extracellular vesicle release, suggesting additional effector delivery routes. These findings provide insight into Dot/Icm T4SS structure and infectionโrelated dynamics
Microplastic exposure and body condition in White-throated dipper (Cinclus cinclus) nestlings across anthropogenic landscapes in Scotland and the Basque Country (Spain)
No full textMicroplastics (MPs) are widely distributed throughout freshwater ecosystems and are easily ingested by aquatic organisms. However, the uptake of MPs by freshwater birds and their potentially detrimental impacts on fitness and health remain poorly understood. We collected faecal samples from White-throated dipper (Cinclus cinclus) nestlings across Scotland and the Basque Country (Spain), encompassing territories with varying degrees of anthropogenic land use. We analysed MP concentrations in the faeces alongside body condition, a proxy for growth conditions and health during early development. MPs, mostly fibres, were detected in 62.5% of broods, with concentrations positively correlated with urban and agricultural land cover. Despite this, MP load exhibited only a weak association with nestling body condition, likely reflecting underlying variation in diet quantity or quality. Overall, our findings highlight the widespread presence of MPs in freshwater birds inhabiting anthropogenic landscapes but indicate no short-term effects on nestling growth. Further research is needed to understand the long-term health implications of MPs and to determine optimal proxies for assessing their effects on freshwater bird health
Generation Moulinex: Work, Consumption and Gender in France, 1950s-2010s
No full textNo abstract available
Pre-assembly of biomolecular condensate seeds drives RSV replication
Full text linkDuring infection, many RNA viruses, including respiratory syncytial virus (RSV), form specialized biomolecular condensates, viral factories (VFs), where viral transcription and replication occur1,2. Paradoxically, high protein concentrations are typically required for condensate nucleation3, yet attaining sufficient protein levels in infection is thought to require VFs for viral transcription and replication. Here, to uncover how viruses solve this paradox to establish VFs, we visualized early infection of RSV in real time with single genomic viral ribonucleoprotein (vRNP) resolution. Our results reveal that VFs are nucleated from infecting vRNPs rather than de novo in the cytoplasm. VF nucleation further requires in-virion pre-assembly of viral proteinโprotein interaction networks on vRNPs to form โpre-replication centresโ (PRCs). PRCs are potent condensate nucleation seeds due to their efficient recruitment and retention of viral proteins. The high affinity of PRCs also results in increased association of the viral polymerase and its co-factors, allowing efficient viral transcription even in the absence of VFs. Together, these activities create a feed-forward loop that drives rapid VF formation. PRC assembly depends on in-virion viral protein levels and is highly heterogeneous among virions, explaining cell-to-cell heterogeneity in infection progression, and identifying heterogeneous virions as an important origin of infection heterogeneity. Together, our results show that in-virion pre-assembly of PRCs kick-starts viral condensate nucleation upon host-cell entry and explains cell-to-cell heterogeneity in RSV infection
Simulated catch and release angling of Atlantic salmon before spawning alters activity, exploratory behaviour and aggression of offspring
Full text link1. Recreational catch and release (C and R) is increasingly adopted as a conservation measure during the spawning migration of wild salmon, yet its impacts on their reproduction are little known.
2. This study examines how stressors related to C and R experienced by wild Atlantic salmon shortly before spawning affected the behaviour of their offspring. Adults collected during their migration were randomly allocated to one of four simulated disturbance treatments that comprised exercise and air exposure of different durations. Treated adults were mated (using IVF) with an unstressed mate, and behavioural traits of offspring were tested when these were 3โ4โmonths old.
3. Results revealed that activity and exploration of a novel environment was reduced in offspring whose experimental parent (of either sex) was exercised and air exposed for an extended period. Offspring from the exercise or exerciseโ+โextended air group also displayed higher aggression levels compared to control individuals.
4. Adult Atlantic salmon experiencing stress close to spawning can therefore potentially induce an adverse effect on their offspring's behaviour during critical early life stages, when young fish are dispersing and competing for feeding territories.
5. Practical implications: C and R angling, of either parental sex, may result in intergenerational effects, with affected salmon producing offspring with altered behaviour. Best practice should aim to minimise fish air exposure, while C and R should be avoided close to the expected spawning time
Plasma inflammatory biomarker profiles across the Alzheimer's disease spectrum in the Bio-Hermes cohort
Full text linkIntroduction:
Inflammation contributes to Alzheimer's disease (AD), but its stage-specific and amyloid-dependent patterns remain unclear.
Methods:
We analyzed 964 participants from the Bio-Hermes cohort (cognitively normal [CN] = 404, mild cognitive impairment [MCI] = 302, mild AD = 258). Plasma levels of 32 cytokines, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were quantified alongside core AD biomarkers. Associations with cognition, amyloid, apolipoprotein E (APOE) ฮต4, and clinical outcomes were assessed using analysis of covariance, partial correlations, and regression models.
Results:
Twenty-four cytokines, NfL, and GFAP differed across cognitive groups. Amyloid stratification revealed a core amyloid-independent profile (14 cytokines + NfL) and a broader amyloid-specific profile including GFAP, interleukin (IL)-1ฮฒ, and IL-18, implicating microglial inflammasome and astrocytic activation. Stage-dependent patterns suggested inflammation may act as early driver, concurrent process, or late amplifier. Paradoxical associations (e.g., eotaxin-2, IL-2R with better memory) and APOE ฮต4-linked immune differences indicated context-dependent roles.
Discussion:
This exploratory study reveals biologically plausible, inflammatory heterogeneity in AD and highlights plasma cytokine profiles as candidate biomarkers and therapeutic targets, warranting investigation
Epcoritamab, lenalidomide, and rituximab versus lenalidomide and rituximab for relapsed or refractory follicular lymphoma (EPCORE FL-1): a global, open-label, randomised, phase 3 trial
Full text linkBackground:
An unmet need persists for chemotherapy-free regimens that induce durable responses for relapsed or refractory follicular lymphoma. Lenalidomide and rituximab (Rยฒ) is an accepted standard of care in this population. The EPCORE FL-1 trial aimed to evaluate the efficacy and safety of epcoritamab plus Rยฒ versus Rยฒ in participants with relapsed or refractory follicular lymphoma after at least one previous line of chemoimmunotherapy.
Methods:
In this multicountry, open-label, phase 3 trial, participants were randomly allocated (1:1) to fixed-duration epcoritamab plus Rยฒ or Rยฒ for up to 12 cycles. Epcoritamab was administered weekly in cycles 1โ3 and every 4 weeks in cycles 4โ12, lenalidomide once daily during cycles 1โ12 (days 1โ21), and rituximab weekly during cycle 1 and monthly in cycles 2โ5. The dual primary endpoints were overall response rate and progression-free survival by independent review committee. The data reported here are from a planned interim analysis carried out after 78% of progression-free survival events had occurred. This study is registered with ClinicalTrials.gov, NCT05409066, and EudraCT, 2021โ000169โ34, and is ongoing (closed to recruitment).
Findings:
Out of 668 participants screened for eligibility across 189 academic and non-academic centres in 30 countries across Africa, Asia, Australia, Europe, North America, and South America, a total of 488 participants were randomly allocated, 243 to epcoritamab plus Rยฒ and 245 to Rยฒ. The trial met its dual primary endpoints, showing superiority of epcoritamab plus Rยฒ over Rยฒ in overall response rate and progression-free survival. With a median follow-up of 14ยท8 months (IQR 11ยท4โ19ยท0), overall response rate was 95% (95% CI 92โ97) with epcoritamab plus Rยฒ versus 79% (74โ84; p<0ยท0001) with Rยฒ. Progression-free survival was longer with epcoritamab plus Rยฒ versus Rยฒ (hazard ratio 0ยท21 [95% CI 0ยท14โ0ยท31], p<0ยท0001); estimated 16-month progression-free survival favoured epcoritamab plus Rยฒ (85ยท5% vs 40ยท2%). Grade 3 or higher adverse events were more frequent with epcoritamab plus Rยฒ (219 [90%] of 243 participants) versus Rยฒ (161 [68%] of 238 participants). Cytokine release syndrome was low grade with epcoritamab plus Rยฒ (grade 1 in 28 [21%] participants and grade 2 in seven [5%] participants) and manageable, and all events were resolved.
Interpretation:
Epcoritamab plus Rยฒ resulted in significantly higher response rate and longer progression-free survival versus Rยฒ among participants with follicular lymphoma who had received at least one line of therapy. Epcoritamab plus Rยฒ had more grade 3 or higher adverse events versus Rยฒ. Adverse events were manageable and consistent with the established safety profiles of the individual components, with no new safety findings identified. These findings position epcoritamab plus Rยฒ as a new standard of care for second-line or subsequent treatment of follicular lymphoma
Law as a technology of exclusion: the legal construction of racialized and gendered work relations through the case study of international labour law in the first half of the twentieth century
No full textThis article explores the role of labour law in processes of racialization and gendering of work. It argues that labour law not only protects certain forms of work (law as a protective mechanism), but also systematically excludes other forms of work, especially those performed by racialized and gendered individuals (law as a technology of exclusion). The article traces the oscillation between protection and exclusion in international labour law (ILL) from the interwar period to the post-Second World War era. During the interwar period, the International Labour Organization (ILO) codified the โstandard employment relationshipโ (SER) as a universal model, while simultaneously codifying racialized and gendered work as less valued by relying on biological justifications. After the Second World War, the ILO shifted from a model grounded in biological determinism to a paradigm based on human rights and anti-discrimination law. However, this shift did not eradicate law's function as a technology of exclusion but rather reconfigured it through two mechanisms: externalization and individualization. The article sheds light on both mechanisms and argues that, ultimately, they obscure law's active role in perpetuating dynamics of racialization and gendering of work
The emergency will last a long time: hyperabjection, slow violence, and the enduring politics of waste in Indonesia
No full textThis article explores the dimensions of hyperabjection and slow violence in the context of the โgarbage emergencyโ in Yogyakarta, Indonesia, particularly in relation to the closure of the provinceโs largest landfill in Piyungan. Urban centres in Indonesia often externalize their waste problem to suburban โsacrifice zonesโ wherein informal workers with minimal protection manage massive volumes of untreated waste. We argue that this reflects a deeper systemic condition marked by socio-spatial inequality and environmental injustice that is left obscured by ontological and ideological framings that typically inform local government, media, and other social actors, particularly affecting peripheral communities as a result. Drawing on the concept of hyperobject proposed by Timothy Morton and the political rearticulation of that concept in terms of the hyperabject by Mikkel Krause Frantze and Jens Bjering, we show how the โgarbage emergencyโ framing in the case of Yogyakartaโs waste problem both results from and helps to perpetuate structural conditions shaped by neglect and disavowal โ an outcome we characterize using Rob Nixonโs notion of โslow violenceโ. Ultimately, this article suggests waste be rethought, not as a discrete problem of disposal, but as a socio-ecological crisis that demands more than techno-bureaucratic solutions
Benchmarking radar preprocessing techniques and transfer learning models for FMCW-based human activity recognition
Full text linkHuman Activity Recognition (HAR) using radar signals has gained significant attention due to its non-intrusive nature and robustness in various environments. However, the impact of radar signal preprocessing techniques on the performance of deep learning (DL) models remains an active area of research. This study investigates how different radar domain representations affect HAR accuracy by evaluating four preprocessing methods: Time-Range (TR) maps generated via Range-Fast Fourier Transform (FFT), Range-Doppler (RD) maps obtained through sequential FFTs, and Time-Doppler (TD) features extracted using Short Time Fourier Transform (STFT) and Smoothed Pseudo Wigner Ville Distribution (SPWVD). We employ a baseline Convolutional Neural Network (CNN) and state-of-the-art Transfer Learning (TL) models to assess whether advanced preprocessing or increased model complexity yields greater performance gains. The results reveal that high-resolution TD analysis using SPWVD does not significantly enhance classification performance and incurs substantial computational overhead, limiting its real-time applicability. Conversely, the TR representation offers computational efficiency but struggles to classify complex activities with the baseline CNN accurately. RD and STFT methods provide a favorable balance between classification accuracy and computational efficiency. Notably, transitioning from the baseline CNN to TL models leads to substantial improvements in recognition accuracy: up to 29.36% for TR, 21.42% for RD, 16.66% for STFT, and 11.11% for SPWVD representations. Overall, our findings demonstrate that TL models, when combined with computationally efficient radar preprocessing techniques like RD or STFT, significantly improve recognition accuracy and generalize well across datasets, as confirmed by evaluation on two publicly available radar-based HAR datasets. Among these, the RD representation combined with VGG-19 yielded the best trade-off between accuracy and latency, achieving a total processing time of 0.91 s per sample for a 10 s activity duration, making it highly suitable for latency-sensitive HAR applications
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