Biology subjects

Martin, P.

Publications and source records attributed to Martin, P..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Development of intimin-enriched outer membrane vesicles (OMVs) as a vaccine to control intestinal carriage of Enterohemorrhagic Escherichia coli

Enterohemorrhagic Escherichia coli (EHEC) are foodborne pathogens causing severe human infections including hemorrhagic colitis and hemolytic uremic syndrome (HUS), particularly in children. Ruminants are the main reservoir of EHEC which colonize their intestinal tract through a mechanism involving the bacterial outer membrane adhesin intimin. Vaccination of cattle has shown efficacy in reducing EHEC O157:H7 shedding in feces. However, most of these vaccines are based on purified proteins and/or require the addition of adjuvants, resulting in expensive vaccines that are not used by breeders. This study introduces the development of a new type of vaccine based on Outer Membrane Vesicles (OMVs) carrying the C-terminal domain of intimin (Int280). A vaccine which combines OMVs carrying luminal Int280 and OMVs displaying surface-exposed Int280 was produced using two addressing systems based on PelB peptide signal and Lpp-OmpA hybrid protein, respectively. This mixed vaccine was tested in a mouse model as a proof of concept using the murine host-specific intestinal pathogen Citrobacter rodentium which shares a similar intimin-based adhesion mechanism with EHEC. Vaccination of mice with OMV-Int280 elicited a strong anti-intimin IgG response. Interestingly, we observed a shortened C. rodentium fecal shedding duration in immunized mice compared to the control group. This OMVs-intimin vaccine therefore represents a promising candidate for the control of EHEC intestinal carriage and fecal shedding in ruminants. IMPORTANCEEnterohemorrhagic Escherichia coli (EHEC) are foodborne pathogenic bacteria causing intestinal infection that may lead to hemorrhagic colitis and hemolytic uremic syndrome (HUS) particularly in young children. There is no effective treatment, and antibiotics are contraindicated because they promote the development of HUS. Vaccination of ruminants, the main reservoir of EHEC, has been proposed as an important strategy to reduce the fecal shedding of EHEC to reduce transmission to humans. Outer Membrane Vesicles (OMVs) derived from E. coli are a highly attractive vaccine platform. Here, we produced OMVs enriched with the C-terminal part of the intimin (Int280). As a proof of concept, we used a mice model of Citrobacter rodentium colonization as a surrogate for EHEC intestinal colonization. Vaccination elicited antibodies against intimin and decreased the duration of fecal shedding of C. rodentium. Therefore, this OMV-Int280 vaccine is a promising candidate to control EHEC intestinal carriage and fecal shedding in ruminants.

microbiology↗

bioRxiv2024

Mechanical coupling between dorsal and ventral surfaces shapes the Drosophila haltere

The extracellular matrix is an essential determinant of animal form, enabling organization of cells and tissues into organs with complex 3D shapes. In contrast with the dorso-ventrally flat Drosophila wing, its serial homolog the haltere adopts a globular shape thought to arise from a lack of matrix-mediated adhesion between its dorsal and ventral surfaces. Contradicting this model, however, matrix manipulations are known to deform halteres. To understand haltere morphogenesis, we characterized matrix behavior and monitored metamorphic development of the haltere. We found that, similar to the wing, correct haltere morphogenesis requires Collagen IV degradation, which we show is mediated by ecdysone-controlled expression of Matrix metalloprotease 2 in both wing and haltere. After Collagen IV is degraded, similar again to the wing, dorsal and ventral haltere surfaces establish Laminin-mediated contact through long cytoskeletal projections. Furthermore, time-lapse analysis of shape changes in wild type and mutant halteres indicates that these projections couple the two surfaces through a central tensor, ensuring load distribution across the whole organ to create a globular shape against tissue-wide deforming forces. Our findings reveal an unexpected role for matrix-mediated adhesion in haltere morphogenesis and describe a novel type of matrix-based tensor structure building 3D shape from 2D epithelia.

developmental biology↗

bioRxiv2024

Ambivalent partnership of the Drosophila posterior class Hox protein Abdominal-B with the Extradenticle and Homothorax cofactors

Hox proteins, a sub-group of the homeodomain (HD) transcription factor family, provide positional information for axial patterning in development and evolution. Hox protein functional specificity is reached, at least in part, through Pbc (Extradenticle (Exd) in Drosophila) and Meis/Prep (Homothorax (Hth) in Drosophila) cofactor interactions. Most of our current knowledge of Hox protein specificity stems from the study of anterior and central Hox proteins, identifying the molecular and structural bases for Hox/Pbc/Meis-Prep cooperative action. Posterior Hox class proteins, Abd-B in Drosophila and Hox9-13 in vertebrates, have been comparatively less studied. They strongly diverge from anterior and central class Hox proteins, with a low degree of HD sequence conservation and the absence of a core canonical Pbc interaction motif. Here we explore how Abd-B function interface with that of Exd/Hth using several developmental contexts, studying mutual expression control, functional dependency and intrinsic protein requirements. Results identify cross regulatory interactions setting relative expression and activity levels required for proper development. They also reveal organ-specific requirement and a binary functional interplay with Exd and Hth, either synergistic or antagonistic. This highlights context specific use of Exd/Hth cofactors, and a similar context specific use of Abd-B protein intrinsic protein requirements.

developmental biology↗

bioRxiv2024

UltraCortex: Submillimeter Ultra-High Field 9.4 T Brain MR Image Collection and Manual Cortical Segmentations

The UltraCortex repository (https://www.ultracortex.org) houses magnetic resonance imaging data of the human brain obtained at an ultra-high field strength of 9.4 T. It contains 86 structural MR images with spatial resolutions ranging from 0.6 to 0.8 mm. Additionally, the repository includes segmentations of 12 brains into gray and white matter compartments. These segmentations have been independently validated by two expert neuroradiologists, thus establishing them as a reliable gold standard. This resource provides researchers with access to high-quality brain imaging data and validated segmentations, facilitating neuroimaging studies and advancing our understanding of brain structure and function. Existing repositories do not accommodate field strengths beyond 7 T, nor do they offer validated segmentations, underscoring the significance of this new resource.

neuroscience↗

bioRxiv2024

TSC2 loss in neural progenitor cells suppresses translation of ASD/NDD-associated transcripts in an mTORC1- and MNK1/2-reversible fashion

Tuberous sclerosis complex (TSC) is an inherited neurodevelopmental disorder (NDD) with frequent manifestations of epilepsy and autism spectrum disorder (ASD). TSC is caused by inactivating mutations in TSC1 or TSC2 tumor suppressor genes, with encoded proteins hamartin (TSC1) and tuberin (TSC2) forming a functional complex inhibiting mechanistic target of rapamycin complex 1 (mTORC1) signaling. This has led to treatment with allosteric mTORC1 inhibitor rapamycin analogs ("rapalogs") for TSC tumors; however, rapalogs are ineffective for treating neurodevelopmental manifestations. mTORC1 signaling controls protein synthesis by regulating formation of the eIF4F complex, with further modulation by MNK1/2 kinases via phosphorylation of the eIF4F subunit eIF4E. While both these pathways modulate translation, comparing their impact on transcriptome-wide mRNA translation, as well as effects of inhibiting these pathways in TSC has not been explored. Here, employing CRISPR-modified, isogenic TSC2 patient-derived neural progenitor cells (NPCs), we have examined transcriptome-wide changes in mRNA translation upon TSC2 loss. Our results reveal dysregulated translation in TSC2-Null NPCs, which significantly overlaps with the translatome from TSC1-Null NPCs. Interestingly, numerous non-monogenic ASD-, NDD-and epilepsy-associated genes identified in patients harboring putative loss-of-function mutations, were translationally suppressed in TSC2-Null NPCs. Importantly, translation of these ASD- and NDD-associated genes was reversed upon inhibition of either mTORC1 or MNK1/2 signaling using RMC-6272 or eFT-508, respectively. This study establishes the importance of mTORC1-eIF4F- and MNK-eIF4E-sensitive mRNA translation in TSC, ASD and other neurodevelopmental disorders laying the groundwork for evaluating drugs in clinical development that target these pathways as a treatment strategy for these disorders.

molecular biology↗

bioRxiv2024

AI reveals a damage signalling hierarchy that coordinates different cell behaviours driving wound re-epithelialisation

One of the key tissue movements driving closure of a wound is re-epithelialisation. Earlier wound healing studies have described the dynamic cell behaviours that contribute to wound re-epithelialisation, including cell division, cell shape changes and cell migration, as well as the signals that might regulate these cell behaviours. Here, we use a series of deep learning tools to quantify the contributions of each of these cell behaviours from movies of repairing wounds in the Drosophila pupal wing epithelium. We test how each is altered following knockdown of the conserved wound repair signals, Ca2+ and JNK, as well as ablation of macrophages which supply growth factor signals believed to orchestrate aspects of the repair process. Our genetic perturbation experiments provide quantifiable insights regarding how these wound signals impact cell behaviours. We find that Ca signalling is a master regulator required for all contributing cell behaviours; JNK signalling primarily drives cell shape changes and divisions, whereas signals from macrophages regulate largely cell migration and proliferation. Our studies show AI to be a valuable tool for unravelling complex signalling hierarchies underlying tissue repair.

developmental biology↗

bioRxiv2024

A worldwide ENIGMA study on epilepsy-related gray and white matter compromise across the adult lifespan

ObjectivesTemporal lobe epilepsy (TLE) is commonly associated with mesiotemporal pathology and widespread alterations of grey and white matter structures. Evidence supports a progressive condition although the temporal evolution of TLE is poorly defined. This ENIGMA-Epilepsy study utilized multimodal magnetic resonance imaging (MRI) data to investigate structural alterations in TLE patients across the adult lifespan. We charted both grey and white matter changes and explored the covariance of age-related alterations in both compartments. MethodsWe studied 769 TLE patients and 885 healthy controls across an age range of 17-73 years, from multiple international sites. To assess potentially non-linear lifespan changes in TLE, we harmonized data and combined median split assessments with cross-sectional sliding window analyses of grey and white matter age-related changes. Covariance analyses examined the coupling of grey and white matter lifespan curves. ResultsIn TLE, age was associated with a robust grey matter thickness/volume decline across a broad cortico-subcortical territory, extending beyond the mesiotemporal disease epicentre. White matter changes were also widespread across multiple tracts with peak effects in temporo-limbic fibers. While changes spanned the adult time window, changes accelerated in cortical thickness, subcortical volume, and fractional anisotropy (all decreased), and mean diffusivity (increased) after age 55 years. Covariance analyses revealed strong limbic associations between white matter tracts and subcortical structures with cortical regions. ConclusionsThis study highlights the profound impact of TLE on lifespan changes in grey and white matter structures, with an acceleration of aging-related processes in later decades of life. Our findings motivate future longitudinal studies across the lifespan and emphasize the importance of prompt diagnosis as well as intervention in patients.

neuroscience↗

bioRxiv2024

Network studies unveil new groups of highly divergent proteins in families as old as cellular life with important biological functions in the ocean

BackgroundMetagenomics has considerably broadened our knowledge of microbial diversity, unravelling fascinating adaptations and characterising multiple novel major taxonomic groups, e.g. CPR bacteria, DPANN and Asgard archaea, and novel viruses. Such findings profoundly reshaped the structure of the known tree of life and emphasised the central role of investigating uncultured organisms. However, despite significant progresses, a large portion of proteins predicted from metagenomes remain today unannotated, both taxonomically and functionally, across many biomes and in particular in oceanic waters, including at relatively lenient clustering thresholds. ResultsHere, we used an iterative, network-based approach for remote homology detection, to probe a dataset of 40 million ORFs predicted in marine environments. We assessed the environmental diversity of 53 gene families as old as cellular life, broadly distributed across the Tree of Life. About half of them harboured clusters of environmental homologues that diverged significantly from the known diversity of published complete genomes, with representatives distributed across all the oceans. In particular, we report the detection of environmental clades with new structural variants of essential genes (SMC), divergent polymerase subunits forming deep-branching clades in the polymerase tree, and variant DNA recombinases of unknown origin in the ultra-small size fraction. ConclusionsThese results indicate that significant environmental diversity may yet be unravelled even in strongly conserved gene families. Protein sequence similarity network approaches, in particular, appear well-suited to highlight potential sources of biological novelty and make better sense of microbial dark matter across taxonomical scales.

evolutionary biology↗

bioRxiv2023

Patterns of subregional cerebellar atrophy across epilepsy syndromes: An ENIGMA-Epilepsy study

ObjectiveThe intricate neuroanatomical structure of the cerebellum is of longstanding interest in epilepsy, but has been poorly characterized within the current cortico-centric models of this disease. We quantified cross-sectional regional cerebellar lobule volumes using structural MRI in 1,602 adults with epilepsy and 1,022 healthy controls across twenty-two sites from the global ENIGMA-Epilepsy working group. MethodsA state-of-the-art deep learning-based approach was employed that parcellates the cerebellum into 28 neuroanatomical subregions. Linear mixed models compared total and regional cerebellar volume in i) all epilepsies; ii) temporal lobe epilepsy with hippocampal sclerosis (TLE-HS); iii) non-lesional temporal lobe epilepsy (TLE-NL); iv) genetic generalised epilepsy; and (v) extra-temporal focal epilepsy (ETLE). Relationships were examined for cerebellar volume versus age at seizure onset, duration of epilepsy, phenytoin treatment, and cerebral cortical thickness. ResultsAcross all epilepsies, reduced total cerebellar volume was observed (d=0.42). Maximum volume loss was observed in the corpus medullare (dmax=0.49) and posterior lobe grey matter regions, including bilateral lobules VIIB (dmax= 0.47), Crus I/II (dmax= 0.39), VIIIA (dmax=0.45) and VIIIB (dmax=0.40). Earlier age at seizure onset ({eta}{rho}2max=0.05) and longer epilepsy duration ({eta}{rho}2max=0.06) correlated with reduced volume in these regions. Findings were most pronounced in TLE-HS and ETLE with distinct neuroanatomical profiles observed in the posterior lobe. Phenytoin treatment was associated with reduced posterior lobe volume. Cerebellum volume correlated with cerebral cortical thinning more strongly in the epilepsy cohort than in controls. SignificanceWe provide robust evidence of deep cerebellar and posterior lobe subregional grey matter volume loss in patients with chronic epilepsy. Volume loss was maximal for posterior subregions implicated in non-motor functions, relative to motor regions of both the anterior and posterior lobe. Associations between cerebral and cerebellar changes, and variability of neuroanatomical profiles across epilepsy syndromes argue for more precise incorporation of cerebellum subregions into neurobiological models of epilepsy. Key pointsO_LICerebellar involvement in epilepsy is poorly understood within current cortico-centric models of this disease C_LIO_LIWe used a novel, deep learning segmentation tool to parcellate the cerebellum into 28 anatomical subunits using an international MRI dataset of 1,602 individuals with epilepsy (aged between 18 and 65 years old) including temporal lobe epilepsy with hippocampal sclerosis (TLE-HS, n=562), TLE non-lesional (TLE-NL, n=284), generalised genetic epilepsy (GGE, n=186) and extra temporal focal epilepsy (ETLE, n=251) and 1,022 controls. C_LIO_LIAcross all epilepsies (vs. controls) robust changes in the corpus medullare and posterior lobe "non-motor" regions were observed, with maximal differences in bilateral VIIB and Crus II lobules. Lower volume of these regions correlated with longer disease duration. Anterior "motor lobe" regions were relatively spared. C_LIO_LIFindings were most pronounced in TLE-HS and ETLE groups, with distinct neuroanatomical profiles observed. C_LIO_LICortical thinning was associated with pronounced cerebellar volume loss in TLE-HS epilepsy, relative to controls. C_LI ETHICAL PUBLICATION STATEMENTWe confirm that we have read the Journals position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

neuroscience↗

bioRxiv2023

Lack of p38 activation in T cells increases IL-35 production and protects against obesity by promoting thermogenesis

Obesity is characterized with low grade inflammation, energy imbalance and impaired thermogenesis. The role of regulatory T cells (Treg) in inflammation-mediated maladaptive thermogenesis has not been well established. We discovered that p38 pathway is a key regulator of T cell-mediated adipose tissue (AT) inflammation and browning. Mice with T cells specific deletion of the p38 activators, MKK3/6, were protected against diet-induced obesity and AT inflammation improving their metabolic profile, higher browning and thermogenesis. We identified IL-35 as a driver of adipocyte thermogenic program through ATF2/UCP1/FGF21 pathway. IL-35 limits CD8+ T cell infiltration and inflammation in AT. Interestingly, we found that IL35 was reduced in visceral fat from obese patients. Mechanistically we showed that p38 controls the expression of IL-35 in human and mouse Treg cells through mTOR pathway activation. Our findings highlight p38 signaling as a molecular orchestrator of AT T cell accumulation and function and identify p38 and IL-35 as promising targets for metabolic diseases.

immunology↗

bioRxiv2023

Allergic inflammation triggers dyslipidemia via IgG signalling

BackgroundAllergic diseases begin early in life and are often chronic, thus creating an inflammatory environment that may precede or exacerbate other pathologies. In this regard, allergy has been associated to metabolic disorders and with a higher risk of cardiovascular disease, but the underlying mechanisms remain incompletely understood. MethodsWe used a murine model of allergy and atherosclerosis, different diets and sensitization methods, and cell-depleting strategies to ascertain the contribution of acute and late phase inflammation to dyslipidemia. Untargeted lipidomic analyses were applied to define the lipid fingerprint of allergic inflammation at different phases of allergic pathology. Expression of genes related to lipid metabolism was assessed in liver and adipose tissue at different times post-allergen challenge. Also, changes in serum triglycerides (TG) were evaluated in a group of 59 patients [≥]14 days after the onset of an allergic reaction. ResultsWe found that allergic inflammation induces a unique lipid signature that is characterized by increased serum TG and changes in the expression of genes related to lipid metabolism in liver and adipose tissue. Alterations in blood TGs following an allergic reaction are independent of T-cell-driven late phase inflammation. On the contrary, the IgG-mediated alternative pathway of anaphylaxis is sufficient to induce a TG increase and a unique lipid profile. Lastly, we demonstrated an increase in serum TG in 59 patients after undergoing an allergic reaction. ConclusionOverall, this study reveals that IgG-mediated allergic inflammation regulates lipid metabolism.

immunology↗

bioRxiv2023

Locus specific human endogenous retroviruses reveal new lymphoma subtypes

The heterogeneity of cancers are driven by diverse mechanisms underlying oncogenesis such as differential cell-of-origin (COO) progenitors, mutagenesis, and viral infections. Classification of B-cell lymphomas have been defined by considering these characteristics. However, the expression and contribution of transposable elements (TEs) to B cell lymphoma oncogenesis or classification have been overlooked. We hypothesized that incorporating TE signatures would increase the resolution of B-cell identity during healthy and malignant conditions. Here, we present the first comprehensive, locus-specific characterization of TE expression in benign germinal center (GC) B-cells, diffuse large B-cell lymphoma (DLBCL), Epstein-Barr virus (EBV)-positive and EBV-negative Burkitt lymphoma (BL), and follicular lymphoma (FL). Our findings demonstrate unique human endogenous retrovirus (HERV) signatures in the GC and lymphoma subtypes whose activity can be used in combination with gene expression to define B-cell lineage in lymphoid malignancies, highlighting the potential of retrotranscriptomic analyses as a tool in lymphoma classification, diagnosis, and the identification of novel treatment groups.

cancer biology↗

bioRxiv2023

Deep learning for rapid analysis of cell divisions in vivo during epithelial morphogenesis and repair

Cell division is fundamental to all healthy tissue growth, as well as being rate-limiting in the tissue repair response to wounding and during cancer progression. However, the role that cell divisions play in tissue growth is a collective one, requiring the integration of many individual cell division events. It is particularly difficult to accurately detect and quantify multiple features of large numbers of cell divisions (including their spatio-temporal synchronicity and orientation) over extended periods of time. It would thus be advantageous to perform such analyses in an automated fashion, which can naturally be enabled using Deep Learning. Hence, we develop a pipeline of Deep Learning Models that accurately identify dividing cells in time-lapse movies of epithelial tissues in vivo. Our pipeline also determines their axis of division orientation, as well as their shape changes before and after division. This strategy enables us to analyse the dynamic profile of cell divisions within the Drosophila pupal wing epithelium, both as it undergoes developmental morphogenesis and as it repairs following laser wounding. We show that the division axis is biased according to lines of tissue tension and that wounding triggers a synchronised (but not oriented) burst of cell divisions back from the leading edge. Highlights{square} Accurate and efficient detection of epithelial cell divisions can be automated by deep learning of dynamic time-lapse imaging data {square}Optimal division detection is achieved using multiple timepoints and dual channels for visualisation of nuclei and cell boundaries {square}Epithelial cell divisions are orientated according to lines of global tissue tension after post-division shuffling {square}Spatio-temporal cell division analyses following wounding reveal spatial synchronicity that scales with wound size {square}Additional deep learning tools enable rapid analysis of cell division orientation

bioinformatics↗

bioRxiv2022

Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA.5 Omicron variant

The emergence of SARS-CoV-2 variants in the Omicron lineage with large numbers of substitutions in the spike protein that can evade antibody neutralization has resulted in diminished vaccine efficacy and persistent transmission. One strategy to broaden vaccine-induced immunity is to administer bivalent vaccines that encode for spike proteins from both historical and newly-emerged variant strains. Here, we evaluated the immunogenicity and protective efficacy of two bivalent vaccines that recently were authorized for use in Europe and the United States and contain two mRNAs encoding Wuhan-1 and either BA.1 (mRNA-1273.214) or BA.4/5 (mRNA-1273.222) spike proteins. As a primary immunization series in BALB/c mice, both bivalent vaccines induced broader neutralizing antibody responses than the constituent monovalent vaccines (mRNA-1273 [Wuhan-1], mRNA-1273.529 [BA.1], and mRNA-1273-045 [BA.4/5]). When administered to K18-hACE2 transgenic mice as a booster at 7 months after the primary vaccination series with mRNA-1273, the bivalent vaccines induced greater breadth and magnitude of neutralizing antibodies compared to an mRNA-1273 booster. Moreover, the response in bivalent vaccine-boosted mice was associated with increased protection against BA.5 infection and inflammation in the lung. Thus, boosting with bivalent Omicron-based mRNA-1273.214 or mRNA-1273.222 vaccines enhances immunogenicity and protection against currently circulating SARS-CoV-2 strains.

microbiology↗

bioRxiv2022

High-Field Asymmetric Waveform Ion Mobility Spectrometry and Parallel Reaction Monitoring Increases Sensitivity for Clinical Biomarker Quantitation from Formalin-Fixed, Paraffin-Embedded Tumor Biopsies

Mass spectrometry-based targeted proteomics allows objective protein quantitation of clinical biomarkers from a single section of formalin-fixed, paraffin-embedded (FFPE) tumor tissue biopsies. We combined high-field asymmetric waveform ion mobility spectrometry (FAIMS) and parallel reaction monitoring (PRM) to increase assay sensitivity. The modular nature of the FAIMS source allowed direct comparison of the performance of FAIMS-PRM to PRM. Limits of quantitation were determined by spiking synthetic peptides into a human spleen matrix. In addition, 20 clinical samples were analyzed using FAIMS-PRM and the quantitation of HER2 was compared with that obtained with the Ventana immunohistochemistry assay. FAIMS-PRM improved the overall signal-to-noise ratio over that from PRM and increased assay sensitivity in FFPE tissue analysis for four (HER2, EGFR, cMET, and KRAS) of five proteins of clinical interest. FAIMS-PRM enabled sensitive quantitation of basal HER2 expression in breast cancer samples classified as HER2 negative by immunohistochemistry. Furthermore, we determined the degree of FAIMS-dependent background reduction and showed that this correlated with an improved lower limit of quantitation with FAIMS. FAIMS-PRM is anticipated to benefit clinical trials in which multiple biomarker questions must be addressed and the availability of tumor biopsy samples is limited.

cancer biology↗

bioRxiv2021

Structural network alterations in focal and generalized epilepsy follow axes of epilepsy risk gene expression: An ENIGMA study

Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem co-expression patterns of epilepsy risk genes. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1,328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-genetic signatures could guide diagnosis, and ultimately, tailor therapeutic approaches to specific epilepsy syndromes.

neuroscience↗

bioRxiv2021

Tapping into non-English-language science for the conservation of global biodiversity

The widely held assumption that any important scientific information would be available in English underlies the underuse of non-English-language science across disciplines. However, non-English-language science is expected to bring unique and valuable scientific information, especially in disciplines where the evidence is patchy, and for emergent issues where synthesising available evidence is an urgent challenge. Yet such contribution of non-English-language science to scientific communities and the application of science is rarely quantified. Here we show that non-English-language studies provide crucial evidence for informing global biodiversity conservation. By screening 419,680 peer-reviewed papers in 16 languages, we identified 1,234 non-English-language studies providing evidence on the effectiveness of biodiversity conservation interventions, compared to 4,412 English-language studies identified with the same criteria. Relevant non-English-language studies are being published at an increasing rate, and can expand the geographical (by 12-25%) and taxonomic (by 5-32%) coverage of English-language evidence, especially in biodiverse regions, albeit often based on less robust study designs. Our results show that synthesising non-English-language studies is key to overcoming the widespread lack of local, context-dependent evidence and facilitating evidence-based conservation globally. We urge wider disciplines to rigorously reassess the untapped potential of non-English-language science in informing decisions to address other global challenges.

scientific communication and education↗

bioRxiv2021

Early cross-coronavirus reactive signatures of protective humoral immunity against COVID-19

The introduction of vaccines has inspired new hope in the battle against SARS-CoV-2. However, the emergence of viral variants, in the absence of potent antivirals, has left the world struggling with the uncertain nature of this disease. Antibodies currently represent the strongest correlate of immunity against COVID-19, thus we profiled the earliest humoral signatures in a large cohort of severe and asymptomatic COVID-19 individuals. While a SARS-CoV-2-specific immune response evolved rapidly in survivors of COVID-19, non-survivors exhibited blunted and delayed humoral immune evolution, particularly with respect to S2-specific antibody evolution. Given the conservation of S2 across {beta}-coronaviruses, we found the early development of SARS-CoV-2-specific immunity occurred in tandem with pre-existing common {beta}-coronavirus OC43 humoral immunity in survivors, which was selectively also expanded in individuals that develop paucisymptomatic infection. These data point to the importance of cross-coronavirus immunity as a correlate of protection against COVID-19.

immunology↗