bluuebunny/crossref_metadata_2025 huggingface dataset:
How biotic interactions structure species’ responses to perturbations
Authors: Lajaaiti Ismaël , Kéfi Sonia , Arnoldi Jean-François
Published: October 2024

Predicting how ecological communities will respond to disturbances is notoriously challenging, especially given the variability in species’ responses within the same community. Focusing solely on aggregate responses may obscure extinction risks for certain species owing to compensatory effects, emphasizing the need to understand the drivers of the response variability at the species level. Yet, these drivers remain poorly understood. Here, we reveal that despite the typical complexity of biotic interaction networks, species’ responses follow a discernible pattern. Specifically, we demonstrate that the species whose population abundances are most reduced by biotic interactions—which are not always the rarest species—are those that exhibit the strongest responses to disturbances. This insight enables us to pinpoint sensitive species within communities without requiring precise information about biotic interactions. Our novel approach introduces avenues for future research aimed at identifying sensitive species and elucidating their impacts on entire communities.
Behavioural responses to mammalian grazing expose insect herbivores to elevated risk of avian predation
Authors: Zhu Yu , Li Xiaofei , Tu Xiongbing , Risch Anita C. , Wang Zhaojun , Ma Quanhui , Jiang Ming , Zou Yuanchun , Wang Deli , Inbar Moshe , Hawlena Dror , Zhong Zhiwei
Published: October 2024

Large mammalian herbivores (LMH) are important functional components and drivers of biodiversity and ecosystem functioning in grasslands. Yet their role in regulating food-web dynamics and trophic cascades remains poorly understood. In the temperate grasslands of northern China, we explored whether and how grazing domestic cattle (
Bos taurus
) alter the predator–prey interactions between a dominant grasshopper (
Euchorthippus unicolor
) and its avian predator the barn swallow (
Hirundo rustica
). Using two large manipulative field experiments, we found that in the presence of cattle, grasshoppers increased their jumping frequency threefold, swallows increased foraging visits to these fields sixfold, and grasshopper density was reduced by about 50%. By manipulatively controlling the grasshoppers’ ability to jump, we showed that jumping enables grasshoppers to avoid being incidentally consumed or trampled by cattle. However, jumping behaviour increased their consumption rates by swallows 37-fold compared with grasshoppers that were unable to jump. Our findings illustrate how LMH can indirectly alter predator–prey interactions by affecting behaviour of avian predators and herbivorous insects. These non-plant-mediated effects of LMH may influence trophic interactions in other grazing ecosystems and shape community structure and dynamics. We highlight that convoluted multispecies interactions may better explain how LMH control food-web dynamics in grasslands.
Archaeogenomic analysis of Chesapeake Atlantic sturgeon illustrates shaping of its populations in recovery from severe overexploitation
Authors: Przelomska Natalia A. S. , Balazik Matthew T. , Lin Audrey T. , Reeder-Myers Leslie A. , Rick Torben C. , Kistler Logan
Published: October 2024

Atlantic sturgeon (Acipenser oxyrinchusssp.oxyrinchus) has been a food resource in North America for millennia. However, industrial-scale fishing activities following the establishment of European colonies led to multiple collapses of sturgeon stocks, driving populations such as those in the Chesapeake area close to extinction. While recent conservation efforts have been successful in restoring census numbers, little is known regarding genomic consequences of the population bottleneck. Here, we characterize its effect on present-day population structuring and genomic diversity in James River populations. To establish a pre-collapse baseline, we collected genomic data from archaeological remains from Middle Woodland Maycock’s Point (c. 200–900 CE), as well as Jamestown and Williamsburg colonial sites. Demographic analysis of recovered mitogenomes reveals a historical collapse in effective population size, also reflected in diminished present-day mitogenomic diversity and structure. We infer that James River fall- and spring-spawning populations likely took shape in recent years of population recovery, where genetic drift enhanced the degree of population structure. The mismatch of mitogenomic lineages to geographical–seasonal groupings implies that despite their homing instinct and differential adaptation manifested as season-specific behaviour, colonization of new rivers has been a key ecological strategy for Atlantic sturgeon over evolutionary timescales.
Interaction between three key species in the sea ice-reduced Arctic Barents Sea system
Authors: Durant Joël M. , Dupont Nicolas , Ono Kotaro , Langangen Øystein
Published: October 2024

Population dynamics depend on trophic interactions that are affected by climate change. The rise in sea temperature is associated with the disappearance of sea ice in the Arctic. In the Arctic part of the Barents Sea, Atlantic cod, capelin and polar cod are three fish populations that interact and are confronted with climate-induced sea ice reductions. The first is a major predator in the system, while the last two are key species in Arctic and sub-Arctic ecosystems, respectively. There are still many unknowns regarding how predicted environmental change may influence the joint dynamics of these populations. Using time series from a 32 year long survey, we developed a state-space model that jointly modelled the dynamics of cod, capelin and polar cod. Using a hindcast scenario approach, we projected the effect of reduced sea ice on these populations. We show that the impact of sea ice reduction and concomitant sea temperature increase may lead to a decrease of polar cod abundance at the benefit of capelin but not of cod which may decrease, resulting in strong changes in the food web. Our analyses show that climate change in the Arcto-boreal system can generate different species assemblages and new trophic interactions, which is the knowledge needed for effective management measures.
A rare case of Aerococcus urinae native valve endocarditis
Authors: Goes Sofie Eva , Callebaut Kim , Pierard Denis , Wybo Ingrid , De Geyter Deborah , Muyldermans Astrid , Geers Jolien , Kerselaers Laura , Demuyser Thomas
Published: October 2024

Background

Aerococcus urinae, was initially considered a commensal of the urinary tract, but there is now increasing evidence for its involvement in urinary tract and systemic infections. A. urinae endocarditis has a high mortality rate and occurs mainly in patients with underlying conditions or presence of extraneous material.

Case presentation

This report handles the case of a 65 year old male with cardiac antecedents, who was admitted to the cardiology department after a syncope of unknown origin and diagnosed with severe mixed aortic valve disease and mitral valve sclerosis through the means of a transesophageal echocardiography (TEE). During hospitalisation, the patient progressively deteriorated with the development of shortness of breath and an inflammatory syndrome. Urinary laboratory analysis showed an A. urinae infection and blood cultures depicted A. urinae growth. Treatment with piperacillin/tazobactam was started empirically. Repeated TEE showed evidence for endocarditis with vegetation and perforation of the mitral valve that required an emergency surgery with mitral valve repair. After surgery, gentamicin and penicillin G were administered for 48 hours, followed by combined ceftriaxone/penicillin G treatment for 6 weeks. At first, flucloxacillin was also associated as the culture of the valve was negative. Finally, 16S rRNA polymerase chain reaction (PCR) on the valve tissue, confirmed the A. urinae endocarditis.

Conclusion

A. urinae is an underestimated cause of serious infections such as endocarditis. Urinary tract infections mainly in older men can be an entry point for this type of invasive infection.
Robust prediction of colorectal cancer via gut microbiome 16S rRNA sequencing data
Authors: Porreca Annamaria , Ibrahimi Eliana , Maturo Fabrizio , Marcos Zambrano Laura Judith , Meto Melisa , Lopes Marta B.
Published: October 2024

Introduction. The study addresses the challenge of utilizing human gut microbiome data for the early detection of colorectal cancer (CRC). The research emphasizes the potential of using machine learning techniques to analyze complex microbiome datasets, providing a non-invasive approach to identifying CRC-related microbial markers.

Hypothesis/Gap Statement. The primary hypothesis is that a robust machine learning-based analysis of 16S rRNA microbiome data can identify specific microbial features that serve as effective biomarkers for CRC detection, overcoming the limitations of classical statistical models in high-dimensional settings.

Aim. The primary objective of this study is to explore and validate the potential of the human microbiome, specifically in the colon, as a valuable source of biomarkers for colorectal cancer (CRC) detection and progression. The focus is on developing a classifier that effectively predicts the presence of CRC and normal samples based on the analysis of three previously published faecal 16S rRNA sequencing datasets.

Methodology. To achieve the aim, various machine learning techniques are employed, including random forest (RF), recursive feature elimination (RFE) and a robust correlation-based technique known as the fuzzy forest (FF). The study utilizes these methods to analyse the three datasets, comparing their performance in predicting CRC and normal samples. The emphasis is on identifying the most relevant microbial features (taxa) associated with CRC development via partial dependence plots, i.e. a machine learning tool focused on explainability, visualizing how a feature influences the predicted outcome.

Results. The analysis of the three faecal 16S rRNA sequencing datasets reveals the consistent and superior predictive performance of the FF compared to the RF and RFE. Notably, FF proves effective in addressing the correlation problem when assessing the importance of microbial taxa in explaining the development of CRC. The results highlight the potential of the human microbiome as a non-invasive means to detect CRC and underscore the significance of employing FF for improved predictive accuracy.

Conclusion. In conclusion, this study underscores the limitations of classical statistical techniques in handling high-dimensional information such as human microbiome data. The research demonstrates the potential of the human microbiome, specifically in the colon, as a valuable source of biomarkers for CRC detection. Applying machine learning techniques, particularly the FF, is a promising approach for building a classifier to predict CRC and normal samples. The findings advocate for integrating FF to overcome the challenges associated with correlation when identifying crucial microbial features linked to CRC development.
Spatiotemporal control of a multilayered co-axial flow in a 3D printed microchannel with cascaded nozzles
Authors: Werner Helen , TaiediNejad Ebrahim , Sahin Mehmet Akif , Leuthner Moritz , Erfle Peer , Hayden Oliver , Dietzel Andreas , Destgeer Ghulam
Published: October 2024

Sculpting and stopping multilayered co-flowing streams is challenging due to inhomogeneous pressure distribution within a fluidic circuit composed of multiple interconnected microchannels having variable flow resistances. Here, we have investigated three different flow control methods to effectively stop a multilayered flow inside a 3D-printed microfluidic channel by bringing the average flow velocity from >100 mm s-1to below a critical velocity of 200 µm s-1within a certain delay timetDof ∼2s. Firstly, we 3D printed a sequence of three concentric nozzles (∼75 µm) embedded serially inside the microchannel (∼200 µm) using a two-photon polymerization (2PP) method. Secondly, we used the 2PP-based 3D printed device to produce a structured coaxial flow of four streams with individual layer thicknesses ofO(10 µm) within the outlet section of the microchannel. Thirdly, we removed the pressure gradient across the fluidic circuit, from > 2 bar to ∼0 bar, to stop the multilayered flow and measuredtDto assess the performance of the three stop flow methods. During the stop-flow phase, an inhomogeneous pressure gradient across different inlets resulted in a backflow to inlet channels with lower pressures. In the three stop-flow methods investigated, we systemically managed the fluidic capacitance to minimize a dimensionless backflow index (BFI) value from ∼0.3 (worst case) to ∼0.03 (best case) for a total flow rate ranging from 16.8 µl min-1to 168 µl min-1. Finally, we have recommended the best stop-flow conditions, which resulted in a minimal delay time oftD∼ 2s and a BFI < 0.05.
Spike mRNA Vaccine Encapsulated in a Lipid Nanoparticle Composed of Phospholipid 1,2-Dioleoyl-sn-Glycero-3-Phosphoethanolamine Induced Potent B- and T-cell Responses Associated with Protection against COVID-19 in Hamsters
Authors: Quadiri Afshana , Prakash Swayam , Zayou Latifa , Dhanushkodi Nisha Rajeswari , Chilukuri Amruth , Ryan Gemma , Wang Kelly , Vahed Hawa , BenMohamed Lbachir
Published: October 2024

Lipid nanoparticles (LNPs) have recently emerged as one of the most advanced vehicle platforms for efficient in vivo delivery of nucleoside-modified mRNA vaccine, particularly for COVID-19. LNPs comprise four different lipids: ionizable lipids, helper or neutral lipids, cholesterol, and lipids attached to polyethylene glycol (PEG). Studies on using the mRNA-LNP platform for vaccines have largely focused on the nucleic acid cargo with less attention to the LNP vehicle. While the LNPs protect mRNA from degradation and efficiently deliver the mRNA to antigen-presenting cells the effect of lipid composition and biophysical properties on the immunogenic and protective mRNA vaccine remain to be fully elucidated. In the present study, we used SARS-CoV-2 Spike-mRNA as a prototype vaccine, to study the effect of 4 different of LNPs with various lipid compositions. We demonstrate that when the same Spike-mRNA was delivered in the LNP4 formulation based on phospholipid 1,2-dioleoyl-sn-glycero-3- Phosphoethanolamine it outperformed the immunogenicity and protective efficacy of three LNPs (LNP1, LNP2, and LNP3) that are based on different lipids. Compared to other three LNPs, the LNP4: (i) enhanced phenotypic and functional maturation of dendritic cells; (ii) induced strong T-cell responses, (iii) increased secretion of proinflammatory, pro-follicular T helper (Tfh) cell cytokines; (iv) induced higher neutralization IgG titers; and (v) and provided better protection against SARS-CoV-2 infection and COVID-19 in the hamster model. We discussed the potential mechanisms by which LNP which include the phospholipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine may activate protective B- and T-cell responses.
Similarity-weighted entropy for quantifying genetic diversity in viral quasispecies
Authors: Wu Jian
Published: October 2024

Viral quasispecies are dynamic populations of genetically diverse viruses, often exhibiting high mutation rates. Understanding the genetic diversity within these quasispecies is critical for analyzing viral evolution, adaptation, and treatment resistance. Entropy and normalized Shannon entropy are widely used metrics to quantify this diversity. However, these metrics ignore genetic similarities between sequences, potentially underestimating the true diversity. In this paper, we introduce two methods for similarity-weighted normalized entropy that account for sequence similarities and provide more accurate measures of genetic diversity. By applying these methods to two hypothetical viral quasispecies populations, we compare the traditional entropy, normalized entropy, and the proposed similarity-weighted measures. Our results demonstrate that the similarity-weighted entropies better capture the true genetic diversity in highly related viral populations, while retaining the simplicity of the original entropy calculations. We discuss the advantages and limitations of both similarity-weighted measures and propose their application in viral quasispecies studies.
Exploring associations between psychotic experiences and structural brain age: a population-based study in late adolescence
Authors: Constantinides Constantinos , Caramaschi Doretta , Zammit Stanley , Freeman Tom P , Walton Esther
Published: October 2024

Neuroimaging studies show advanced structural “brain age” in schizophrenia and related psychotic disorders, potentially reflecting aberrant brain ageing or maturation. The extent to which altered brain age is associated with subthreshold psychotic experiences (PE) in youth remains unclear.

We investigated the association between PE and brain-predicted age difference (brain-PAD) in late adolescence using a population-based sample of 117 participants with PE and 115 without PE (aged 19-21 years) from the Avon Longitudinal Study of Parents and Children. Brain-PAD was estimated using a publicly available machine learning model previously trained on a combination of region-wise T1-weighted grey-matter measures.

We found little evidence for an association between PEs and brain-PAD after adjusting for age and sex (Cohen’s d = -0.21 [95% CI -0.47, 0.05], p = 0.11). While there was some evidence for lower brain-PAD in those with PEs relative to those without PEs after additionally adjusting for parental social class (Cohen’sd= -0.31 [95% CI -0.58, -0.03], p = 0.031) or birth weight (Cohen’sd= -0.29 [95% CI -0.55, -0.03], p = 0.038), adjusting for maternal education or childhood IQ did not alter the primary results.

These findings do not support the notion of advanced brain age in older adolescents with PEs. However, they weakly suggest there might be a younger-looking brain in those individuals, indicative of subtle delays in structural brain maturation. Future studies with larger samples covering a wider age range and multimodal measures could further investigate brain age as a marker of psychotic experiences in youth.
Plasma proteome-wide analysis of cerebral small vessel disease identifies novel biomarkers and disease pathways
Authors: Gomez Gabriela T. , Shi Liu , Fohner Alison E. , Chen Jingsha , Yang Yunju , Fornage Myriam , Duggan Michael R. , Peng Zhongsheng , Daya Gulzar N. , Tin Adrienne , Schlosser Pascal , Longstreth W.T. , Kalani Rizwan , Sharma Malveeka , Psaty Bruce M. , Nevado-Holgado Alejo J. , Buckley Noel J. , Gottesman Rebecca F. , Lutsey Pamela L. , Jack Clifford R. , Sullivan Kevin J. , Mosley Thomas , Hughes Timothy M. , Coresh Josef , Walker Keenan A.
Published: October 2024

Cerebral small vessel disease (SVD), as defined by neuroimaging characteristics such as white matter hyperintensities (WMHs), cerebral microhemorrhages (CMHs), and lacunar infarcts, is highly prevalent and has been associated with dementia risk and other clinical sequelae. Although conditions such as hypertension are known to contribute to SVD, little is known about the diverse set of subclinical biological processes and molecular mediators that may also influence the development and progression of SVD. To better understand the mechanisms underlying SVD and to identify novel SVD biomarkers, we used a large-scale proteomic platform to relate 4,877 plasma proteins to MRI-defined SVD characteristics within 1,508 participants of the Atherosclerosis Risk in Communities (ARIC) Study cohort. Our proteome-wide analysis of older adults (mean age: 76) identified 13 WMH-associated plasma proteins involved in synaptic function, endothelial integrity, and angiogenesis, two of which remained associated with late-life WMH volume when measured nearly 20 years earlier, during midlife. We replicated the relationship between 9 candidate proteins and WMH volume in one or more external cohorts; we found that 11 of the 13 proteins were associated with risk for future dementia; and we leveraged publicly available proteomic data from brain tissue to demonstrate that a subset of WMH-associated proteins was differentially expressed in the context of cerebral atherosclerosis, pathologically-defined Alzheimer’s disease, and cognitive decline. Bidirectional two-sample Mendelian randomization analyses examined the causal relationships between candidate proteins and WMH volume, while pathway and network analyses identified discrete biological processes (lipid/cholesterol metabolism, NF-kB signaling, hemostasis) associated with distinct forms of SVD. Finally, we synthesized these findings to identify two plasma proteins, oligodendrocyte myelin glycoprotein (OMG) and neuronal pentraxin receptor (NPTXR), as top candidate biomarkers for elevated WMH volume and its clinical manifestations.
Low prevalence of soil transmitted helminth infection in Ugandan children hospitalized with severe malaria
Authors: Capone Drew , Jahan Nuzrath , Namazzi Ruth , Opoka Robert O. , John Chandy C.
Published: October 2024

Co-infection by intestinal helminths andPlasmodiumspp. may be common in endemic communities. Several studies have identified a relationship between helminth infection,Plasmodiumspp. infection and malaria severity. However, the relationship is not well defined, and results are inconclusive. We analyzed 202 stool samples from a cohort of children with severe malaria enrolled in two hospitals in Uganda from 2014-2017 and asymptomatic community children from the same household or neighborhood and enrolled at the same time, all 6 months to 48 months of age. We investigated if intestinal helminth infection modified risk of severe malaria. We extracted nucleic acids from stool and tested them for six helminth species (Anyclostoma duodenale, Ascaris lumbricoides, Necator americanus, Strongyloides stercolaris, Trichuris trichiura, Shistosoma mansoni) using highly sensitive quantitative PCR. We found a low prevalence of infection by ≥1 intestinal helminth species in children with severe malaria (5.1%, n=9/177) and community control children (4.0%, n=1/25). Infection by ≥1 of the helminths assessed was not associated with severe malaria (aRR = 1.0, 95% Confidence Interval = 0.82, 1.3, p = 0.78). In 2003 Uganda instituted a national deworming program, with anti-helminth medication provided twice annually to children 6 months to 5 years of age. In these areas of Uganda, the national deworming campaign has been highly successful, as stool-based helminth infection was rare even when using highly sensitive methods of detection and was not a major contributor to risk of severe malaria.
Multi-source coherence analysis of the first European multi-centre cohort study for cancer prevention in people experiencing homelessness: a data quality study
Authors: Blasco-Calafat Antonio , Blanes-Selva Vicent , Fragner Tobias , Doñate-Martínez Ascensión , Alhambra-Borrás Tamara , García-Gómez Juan M. , Grabovac Igor , Saez Carlos
Published: October 2024

Background and objective

People experiencing homelessness (PEH) face significant health challenges and disparities in healthcare access due to barriers such as unstable housing, limited resources, and social stigma. In response, the European Union has initiated efforts to address these disparities. The CANCERLESS project, part of this initiative, has created the first European multi-centre dataset for cancer prevention in PEH. This work aims to evaluate and describe the heterogeneity of PEH across pilot sites and to provide data quality metrics for reliable future research.

Methods

The dataset comprises 652 cases: 142 from Vienna, 158 from Athens and Thessaloniki, 197 from Madrid, and 155 from the United Kingdom. All participants fit classifications from the European Typology of Homelessness and Housing Exclusion. This longitudinal study collected questionnaires at baseline, four weeks, and at the end of the intervention. The 180-question survey covered socio-demographic data, overall health, mental health, empowerment, and interpersonal communication. Data variability was assessed using information theory and geometric methods to analyse discrepancies in distributions and completeness across the dataset.

Results

Significant variability was found among the four pilot countries, both overall and within specific sections, except for the health section. Madrid showed the largest discrepancies, with a high number of missing values related to interpersonal communication and healthcare service use.

Conclusion

Health data may be comparable across the four countries, but further analysis should account for location-specific differences. This study underscores the heterogeneity among PEH and the critical need for data quality assessments to inform future research and policymaking in this field.
Evaluating the World Health Organization’s HEARTS Model for Hypertension and Diabetes Management: A Pilot Implementation Study in Guatemala
Authors: Wellmann Irmgardt Alicia , Ayala Luis Fernando , Valley Taryn M. , Irazola Vilma , Huffman Mark D. , Heisler Michele , Rohloff Peter , Donis Rocío , Palacios Eduardo , Ramírez-Zea Manuel , Flood David
Published: October 2024

Background

The World Health Organization HEARTS Technical Package is a widely implemented global initiative to improve the primary care management of cardiovascular disease risk factors. The study’s objective is to report outcomes from a pilot implementation trial of integrated hypertension and diabetes management based on the HEARTS model in Guatemala.

Methods

We conducted a single-arm pilot implementation trial over 6 months from October 2023 to May 2024 in 11 Guatemalan Ministry of Health primary care facilities in two districts. The pilot evaluated a package of five HEARTS-aligned implementation strategies to improve the pharmacological treatment of hypertension and diabetes. The primary outcomes were feasibility and acceptability, measured through 20 structured interviews with Ministry of Health employees and by examining enrollment and retention. Secondary outcomes included a suite of implementation and clinical outcomes, including treatment rate.

Results

The study enrolled 964 patients, of whom 58.8% had hypertension only, 30.4% had diabetes only, and 10.8% had both conditions. Surveys on feasibility and acceptability among Ministry of Health staff had a median score of 5.0 (IQR: 5.0 to 5.0) and 5.0 (IQR range: 4.8 to 5.0), respectively, exceeding the prespecified benchmark of ≥3.5. Both districts achieved the prespecified benchmark of enrolling ≥25 hypertension patients and ≥25 diabetes patients. Only 36% of patients attended a follow-up visit within three months, lower than the prespecified benchmark of ≥75%. M treatment rates during the pilot increased by 22.3 (95% CI: 16.2 to 28.4; P<0.001) and 3.5 (95% CI: -1.6 to 8.7; P=0.17) patients per month for hypertension and diabetes, respectively.

Conclusions

Implementation of an integrated hypertension and diabetes model based on HEARTS was generally feasible and acceptable in the Ministry of Health in Guatemala. Findings can refine national scale-up in Guatemala and inform HEARTS implementation projects in other settings.
Enhancing Leptospirosis Diagnosis through an integration of Machine Learning with Classification of Microscopic Agglutination Images
Authors: Mohammad Norhasmira , Hassan Murnihayati , Zawani Rosli Siti Nur , Tahir Natasya Amirah , Mohamed Nurul Azmawati , Sukri Khairunnisa Mohd , Azmi Liyana
Published: October 2024

Leptospirosis, a widespread zoonotic disease, poses substantial challenges to global public health. In Malaysia, leptospirosis is an endemic disease, with annual cases peaking during the monsoon season. The microscopic agglutination test (MAT) is the gold-standard serological method for confirmation of leptospirosis. However, it is labour-intensive and time-consuming, as it relies on the subjective interpretation of medical lab technicians. This study investigates and describes the development of a semi-automated workflow for leptospira screening by integrating a TensorFlow and custom-designed Keras-based Deep Convolutional Neural Network (DCNN) with conventional MAT. We used a dataset of 442 positive and 442 negative MAT images, which consisted of a mixture of leptospira serovars to train the model. We then subjected our model to hyperparameter tuning, where we adjusted various settings to optimise the model’s performance. These settings included the number of convolutional layers, filters, kernel sizes, units in dense layers, activation functions, and the learning rate. We then tailored several convolutional layers to find the optimal balance between model complexity and performance. Verification of our tested model compared to the control samples (verified patient MAT results) achieved the following metrics: a Precision score of 0.8125, a Recall of 0.9286, and an F1-Score of 0.8667. Combining our model with the current Malaysia leptospira workflow can significantly speed up, reduce inaccuracies and improve the management of leptospirosis. Furthermore, the application of this model is practical and adaptable, making it suitable for other labs that observe MAT as their leptospira diagnosis. To our knowledge, this approach is Malaysia’s first hybrid diagnostic approach for leptospira diagnosis. Scaling up the dataset would enhance the model’s accuracy, making it adaptable in other regions where leptospirosis is endemic.
Geometry-Induced Competitive Release in a Meta-Population Model of Range Expansions in Disordered Environments
Authors: Nuñez Jimmy Gonzalez , Beller Daniel A.
Published: October 2024

Abstract

Rare evolutionary events, such as the rise to prominence of deleterious mutations, can have drastic impacts on the evolution of growing populations. Heterogeneous environments may reduce the influence of selection on evolutionary outcomes through various mechanisms, including pinning of genetic lineages and of the population fronts. These effects play significant roles in enabling competitive release of otherwise trapped mutations. In this work we show that environments containing random arrangements of “hotspot” patches, where locally abundant resources enhance growth rates equally for all sub-populations, give rise to massively enriched deleterious mutant clones. We derive a geometrical optics description of mutant bubbles, which result from interactions with hotspots, that successfully predicts the observed increase in mutant survival. This prediction requires no fitting parameters and holds well in scenarios of rare mutations and of adaptation from standing variation. In addition, we find that the influence of environmental noise in shaping the fate of rare mutations is maximal near a percolation transition of overlapping discs, beyond which mutant survival decreases.
The biogeography of evolutionary radiations on oceanic archipelagos
Authors: Bree Baptiste , Matthews Thomas J. , Fernandez-Palacios Jose Maria , Paroissin Christian , Triantis Kostas A. , Whittaker Robert J. , Rigal Francois
Published: October 2024

Evolutionary radiations on oceanic archipelagos (ROAs) have long served as models for understanding evolutionary and ecological processes underlying species diversification. Yet, diversity patterns emerging from ROAs have received relatively little attention from biogeographers, even though characterizing the effect of key geo-environmental factors on island clades species distribution could be important for unraveling diversification dynamics. In this study, we conducted a comparative analysis using island-specific species richness values for approximately one hundred ROAs across major oceanic archipelagos (mostly Hawaii, Canary Islands, Galapagos and Fiji) and taxa (vascular plants, invertebrates and vertebrates). Our aim was to determine whether (1) ROA species richness patterns scale as a function of key geo-environmental factors including island area, geological age, environmental heterogeneity (elevation and topographic complexity) and inter-island isolation, and (2) whether the magnitude of the effects of these factors varies across archipelagos and taxa. Our results identified elevation as a key driver of ROA species richness patterns on islands, supporting existing theoretical and empirical work that highlighted the central role of environmental heterogeneity in driving diversification on oceanic islands. As importantly, we found that the influence of geo-environmental factors varies across archipelagos and taxa, suggesting that unique archipelagic dynamics and biological traits together shape diversification differently. Our findings emphasize the value of applying biogeographical modeling at resolution of individual radiations to improve our understanding of evolutionary processes on oceanic archipelagos.
Pulmonary Mitochondrial DNA Release and Activation of the cGAS-STING Pathway in LethalStx12Knockout Mice
Authors: Liu Dan-Hua , Li Fang , Yang Run-Zhou , Wu Zhuanbin , Meng Xiao-Yan , Li Sen-Miao , Li Wen-Xiu , Li Jia-Kang , Wang Dian-Dian , Wang Rui-Yu , Li Shu-Ang , Liu Pei-Pei , Kang Jian-Sheng
Published: October 2024

STX12 (syntaxin12 or syntaxin13), a member of the SNARE protein family, plays a crucial role in intracellular vesicle transport and membrane fusion. Our previous research has demonstrated thatStx12knockout mice exhibit perinatal lethality with iron deficiency anemia. Despite its importance, the comprehensive physiological and pathological mechanism of STX12 remain largely unknown. Here, we uncover that STX12 deficiency causes the depolarization of mitochondrial membrane potential in zebrafish embryos and mouse embryonic fibroblasts. Additionally, the loss of STX12 decreases levels of mitochondrial complex subunits, accompanying mitochondrial DNA (mtDNA) release and activating cGAS-STING pathway and Type I interferon pathway in the lung tissue ofStx12−/−mice. Additionally, we have observed a substantial increase in cytokines and neutrophil infiltration within the lung tissues ofStx12knockout mice, indicating a severe inflammation, which could be a contributing factor forStx12−/−mortality. Various interventions have failed to rescue the lethal phenotype, suggesting that systemic effects may contribute to lethality. Further research is warranted to elucidate potential intervention strategies. Overall, our findings uncover the critical role of STX12 in maintaining mitochondrial function and mtDNA stability in pulmonary cells, and reveal that STX12 depletion results in pulmonary mtDNA release and activates mtDNA-dependent innate immunity.
LRRK2-mutant microglia trigger dopaminergic neurodegeneration when activated by neuromelanin
Authors: Blasco-Agell Lucas , Pons-Espinal Meritxell , Testa Veronica , Roch Gerard , Montero-Muñoz Jara , Fernandez-Carasa Irene , Baruffi Valentina , Gonzalez-Sepulveda Marta , Richaud-Patin Yvonne , Jimenez Senda , Cuadros Thais , Cladera-Sastre Joana M. , Compte Joan , Juan-Otero Manel , Tolosa Eduardo , Raya Angel , Vila Miquel , Consiglio A.
Published: October 2024

Parkinson’s disease (PD) is a progressive and yet incurable neurodegenerative condition characterized by loss of neuromelanin-containing dopamine neurons in thesubstantia nigraof the midbrain. The contribution of non-neuronal cells to neuron degeneration in PD is receiving increasing attention. Here, we generated functional microglia-like cells from induced pluripotent stem cells (iPSC) from patients with PD associated toLRRK2mutations, the most common cause of genetic PD, along with their gene-corrected isogenic controls and with iPSC from healthy donors. Microglia-like cells of either genotype did not induce neurodegeneration of healthy dopamine neurons in co-culture experiments. However, LRRK2-mutant microglia became hyperreactive upon LPS stimulation when compared with controls, as judged by cytokine expression profile, production of reactive oxygen species. We then tested α-synuclein and neuromelanin as potential endogenous stimuli for activating mutant microglia. Upon exposure to neuromelanin-containing particles, but not to preformed α-synuclein fibrils, LRRK2-mutant microglia induced the degeneration of healthy dopamine neurons, in a process that could be prevented by pre-treatment with the immunomodulatory drug ivermectin. Finally, the analysis of post-mortem midbrain tissue of LRRK2-PD patients found increased numbers of activated microglia cells in close contact with neuromelanin-containing neurons. Taken together, our findings uncover a potential critical role of neuromelanin-activated microglia in the context of PD progression, and provide an experimental model of PD to test new therapeutic targets.
FungAMR: A comprehensive portrait of antimicrobial resistance mutations in fungi
Authors: Bédard Camille , Pageau Alicia , Fijarczyk Anna , Mendoza-Salido David , Alcañiz Alejandro J , Després Philippe C. , Durand Romain , Plante Samuel , Alexander Emilie M. M. , Rouleau François D. , Giguère Mathieu , Bernier Mégane , Sharma Jehoshua , Maroc Laetitia , Gervais Nicholas C. , Menon Anagha C.T. , Gagnon-Arsenault Isabelle , Bakker Sibbe , Rhodes Johanna , Dufresne Philippe J. , Bharat Amrita , Sellam Adnane , De Luca Domenica G. , Gerstein Aleeza , Shapiro Rebecca S. , Quijada Narciso M. , Landry Christian R.
Published: October 2024

Antimicrobial resistance (AMR) is a global threat. To optimize the use of our antifungal arsenal, we need rapid detection and monitoring tools that rely on high-quality AMR mutation data. Here, we performed a thorough manual curation of published AMR mutations in fungal pathogens to produce the FungAMR reference dataset. A total of 462 papers were curated, leading to 54,666 mutation entries all classified with the degree of evidence that supports their role in resistance. FungAMR covers 92 species, 202 genes and 184 drugs. We combined variant effect predictors with FungAMR resistance mutations and showed that these tools could be used to help predict the potential impact of mutations on AMR. Additionally, a comparative analysis among species revealed a high level of convergence in the molecular basis of resistance, revealing some potentially universal resistance mutations. The analysis also showed that a significant number of resistance mutations lead to cross-resistance within antifungals of a class, as well as between classes for certain mutated genes. The acquisition of fungal resistance in the clinic and the field is an urging concern. Finally, we provide a computational tool, ChroQueTas, that leverages FungAMR to screen fungal genomes for AMR mutations. These resources are anticipated to have great utility for researchers in the fight against antifungal resistance.
Oxytocin Gαisignaling-induced amygdala astrocytes processes retraction shapes behavioral stress response
Authors: Baudon Angel , Grelot Valentin , Althammer Ferdinand , Wang Kai-Yi , Denis Clémence , Ali Syed Azmal , Yan Yudong , Castillo-Diaz Fernando , Piacentini Francesca , Creusot Etienne Clauss , Hovhannisyan Volodya , Schubert Tim , Kleinwaechter Annabel C. , Helen Jemima , Lakomy Tom , Krabichler Quirin , Breton Rachel , Derrien Pierre-Alexis , Andry Virginie , Sauvage Maria-Angeles Carrillo-de , Demais Valérie , Ces Aurélia , Kremer Mélanie , Di-Benedetto Barbara , Goumon Yannick , Schaaf Christian P. , Grinevich Valery , Rouach Nathalie , Darbon Pascal , Neumann Inga D. , Adamantidis Antoine , Busnelli Marta , Benhaim Lucile , Krijgsveld Jeroen , Pfrieger Frank W. , Charlet Alexandre
Published: October 2024

Anticipated reactions to stressful situations are vital for the survival and well-being of organisms, and abnormal reactions are involved in stress-related disorders. The neuropeptide oxytocin is a key modulator ensuring well-adapted stress responses. Oxytocin acts on both neurons and astrocytes, but the molecular and cellular mechanisms mediating stress response remain poorly understood. Here, we focus on the amygdala, a crucial hub that integrates and processes sensory information through oxytocin- dependent mechanisms. Using an acute stress paradigm in mice, genetic and pharmacological manipulations combined with proteomic, morphological, electrophysiological and behavioral approaches, we reveal that oxytocinergic modulation of the freezing response to stress is mediated by transient Gαi-dependent retraction of astrocytic processes, followed by enhanced neuronal sensitivity to extracellular potassium in the amygdala. Our findings elucidate a pivotal role for astrocytes morphology- dependent modulation of brain circuits that is required for proper anticipated behavioral response to stressful situations.
Characterization of thePlasmodium falciparumhomologue of Vps16, a member of the Vps-C tethering complex
Authors: Galaup Thomas , Lauruol Florian , Sergerie Audrey , Richard Dave
Published: October 2024

The organelles of the apical complex (rhoptries, micronemes and dense granules) are critical for erythrocyte invasion by the malaria parasitePlasmodium falciparum. Though they have essential roles in the parasite lifecycle, the mechanisms behind their biogenesis are still poorly defined. The Class C Vps proteins Vps11, 16, 18 and 33 constitute the core of the CORVET and HOPS complexes implicated in vesicle tethering and fusion in the eukaryotic endolysosomal system. Work in the model apicomplexanToxoplasma gondiihas revealed that TgVps11 is essential for the generation of the apical complex.P. falciparumpossesses all the four subunits of the Vps-C complex but their function is currently unknown. We here present an initial characterization of theP. falciparumorthologue of Vps16, a member of the Vps-C complex. Our structural predictions suggest that the structure of PfVps16 is similar to its other eukaryotic counterparts and that the binding region responsible for its interaction with PfVps33 is conserved. We next show that PfVps16 is expressed throughout the asexual erythrocytic cycle and that it is potentially associated with the rhoptries in schizont stage parasites. Finally, we present our unsuccessful attempts at studying its function using knock sideways.
DNA topoisomerase I acts as supercoiling sensor for transcription elongation inE. coli
Authors: Vidmar Vita , Borde Céline , Bruno Lisa , Takacs Maria , Batisse Claire , Saint-André Charlotte , Zhu Chengjin , Espéli Olivier , Lamour Valérie , Weixlbaumer Albert
Published: October 2024

When DNA is transcribed to RNA, the DNA double helix is constantly unwound and rewound to provide access for RNA polymerase (RNAP). This induces DNA supercoiling as a function of transcript length due to over- and under-twisting of the DNA downstream and upstream of RNAP, respectively. Using single-particle cryo-EM andin vivoassays we investigated the relationship between bacterial RNAP and DNA Topoisomerase I (TopoI), which removes negative supercoils accumulating upstream of RNAP. TopoI binds to relaxed DNA upstream of RNAP in a manner suggesting a sensory role awaiting the formation of negative supercoils and involving a conformational switch in the functional domains of TopoI. On DNA substrates mimicking negatively supercoiled DNA, TopoI threads one strand into the active site for cleavage while binding the complementary strand with an auxiliary domain. We propose a comprehensive model for DNA relaxation in the context of a transcribing RNAP.
Impact of soil moisture on microbial diversity and their enzyme activity on agricultural soil
Authors: Bogati Kalisa , Sewerniak Piotr , Walczak Maciej
Published: October 2024

In this study, the impact of a two-month of drought stress on the microbial abundance, their enzymes and functional diversity in four agricultural soil (Gniewkowo (G), Lulkowo (L), Nieszawa (N), and Suchatówka (S) sites from Poland) was investigated during summer season. The physicochemical parameters (pH, organic carbon (C), calcium carbonate (CaCO3), total nitrogen (N), nitrate (NO3-), ammonium (NH4+), total phosphorus (P), available phosphate (P2O5)), and specific biological parameters (microbial abundance, CLPP, and soil enzymes (phosphatases (acid; ACP and alkaline; AKP), dehydrogenase (DH), and urease (UR)) were conducted on the soil samples in this study. The physicochemical and biological data were compared between zero-week (T0) and 8thweek (T8) time intervals. The microbial enumeration showed higher bacterial populations (496.63 x 104CFU g-1dry soil) compared to actinomycetes (13.43 x 104CFU g−1dry soil), and lowest were the fungal population (67.68 x 102CFU g-1dry soil) at T8. The functional diversity showed strong positive significance in the G, N and S sites at T8. On the contrary, most of the L sites showed negative significance with the utilization of amines only, by the end of the experiment. Overall, the microbial population, their enzymes and functional diversity showed positive correlation with soil moisture content in all four investigated sites. The findings of our study indicate that soil biological activities in agricultural regions can be modified by a mere two months of drought.
Structural extension of the human exocyst is enabled by a minimal interface
Authors: Xu Haonan D. , Badonyi Mihaly , Sopipong Watanyoo , MacGowan Stuart A. , Marsh Joseph A. , Murray David H.
Published: October 2024

In multicellular organisms, the machinery responsible for polarized trafficking directs constitutive cargo secretion at distinct sites of the plasma membrane, cilia, and junctional structures. Central to this machinery is the exocyst complex, which tethers cargo vesicles to their destination membrane, alongside other intracellular membrane tethering roles. Precisely how the exocyst spatially integrates membranes and membrane resident binding partners is unclear. Here, we address the structural morphology and formation of the human exocyst complex. Through structural approaches coupled to predictive models, we determined that the exocyst and its subcomplexes have extended ‘arm-like’ structures that help maximize its reach. Moreover, we demonstrate minimal intersubunit interaction, in contrast to prior models. Nucleation of the holocomplex occurs through a single site, explaining its spatial extension. Our results provide the biochemical basis for exocyst complex assembly, suggesting an ornate extended architecture.

Significance

Cargo transport to the eukaryotic cell plasma membrane predominantly relies on the exocyst as a central, signal-integrating polarized trafficking complex. How this single cargo vesicle tethering complex can target diverse vesicles to destination membrane is poorly understood, partly due to inconsistent structural models. Here, we show an extended architecture of the human exocyst complex, revealing a minimal nucleation interface between its two subcomplexes. The distinct morphology of human exocyst, compared to yeast models, suggests a novel mechanism that supports its versatile role in membrane trafficking.
Tapering-enhanced high-efficiency THz waveguide oscillator
Authors: Yang Y. N. , Fisher A. , Musumeci P. , Li R. K. , Kravchenko M. , Agustsson R. , Chen Y. , Murokh A.
Published: October 2024

Using a waveguide in a THz FEL has been shown to maximize the coupling and enable efficient extraction of relativistic electron beam energy from a single passage through a tapered helical undulator. An oscillator configuration can further boost energy extraction above the single-pass limits and open the door toward very high average power THz sources. Embedding the undulator in an oscillator cavity is particularly useful in combination with high repetition rate electron sources, even if at reduced peak brightness, since recycling a fraction of the radiation as an intense seed can compensate for lower single-pass gain. In this paper, we investigate the efficiency scaling of a tapering-enhanced waveguide oscillator, showcasing its capability for frequency-tuning operation and high-efficiency operation at different wavelengths. Using a thermionic-driven beamline equipped with compression elements, numerical start-to-end simulation results indicate a 16% efficiency at 200 GHz and a 2.1% efficiency at 1.5 THz, resulting in kW-level average power out-coupled in radiation pulses with few hundred μJ energy and tens of MW peak power.

Published by the American Physical Society
2024