bluuebunny/crossref_metadata_2025 huggingface dataset:
Reappraisal of the Dilution and Amplification Effect Framework: A Case Study in Lyme Disease
Authors: Chen Shirley , McFarlane S. Eryn
Published: January 2025

The role of biodiversity in regulating zoonotic disease in ecological communities has been broadly referred to as the biodiversity-disease relationship in disease ecology. Whether biodiversity decreases or increases disease risk, known as a dilution or amplification effect respectively, remains unclear. The literature has focused on the strength, generality, nature, and context dependencies that could explain contradictory evidence. We suggest that a continued focus on this approach to resolving the biodiversity-disease debate detracts from a more foundational problem with testing these dilution and amplification hypotheses, in that these hypotheses are not falsifiable as proposed. When tested and interpreted as net effects in a system, these hypotheses do not possess a true null outcome and they are vulnerable toad hocexplanations. To remedy this problem, we propose that biodiversity and disease risk can be modelled as latent variables in multivariate causal models to test specific mechanistic pathways. We present a case study on Lyme disease through a systematic review and meta-analysis, concluding that there is little evidence for a net dilution or amplification effect. We demonstrate how testing these net effect hypotheses falls short of providing robust evidence for its underlying mechanisms. While these hypotheses have previously been helpful in conceptualizing this idea of biodiversity as a potentially protective factor for human health, they need further specificity and clarity to move forwards with greater unity.
Community, Belonging, and Peer-Engagement: Participant Experiences Reflect Consistency of Facilitation Practices in Inclusive STEM Teaching Learning Communities
Authors: Codding Diane , Yen Alexandria H. , Lewis Haley , Johnson-Ojeda Vanessa , Hokanson Sarah Chobot , Goldberg Bennett B.
Published: January 2025

A primary reason for the persistent underrepresentation of minoritized people in STEM careers are their marginalizing experiences in STEM courses, which has spurred efforts to prepare STEM faculty to implement inclusive teaching practices. The Inclusive STEM Teaching Project (ISTP) addresses this nationwide challenge by providing STEM faculty a free, online course and associated learning communities (LCs) led by project-trained facilitators. ISTP centers identity, power, privilege and positionality and has successfully shifted educators’ mindsets and abilities. A central question is whether local LCs across contexts maintain equity-minded core practices and achieve inclusive, reflective practitioner outcomes. Our mixed methods analysis of LC participant (n= 165) and facilitator (n= 83) matching survey data spanning five course offerings over two years directly explores the relationship between the learning environments created by facilitators and their participant experiences. Findings demonstrate high fidelity of implementation to training by facilitators that resulted in consistent LC experiences of participants, especially around building a community, sense of belonging and positive peer engagement. Participants overall speak to the importance of facilitated LCs as an inclusive space where they can critically engage with one another as they reflect on, discuss, and ultimately improve their inclusive teaching practices.
Combinatorial phenotypic landscape enables bacterial resistance to phage infection
Authors: Gupta Anika , Morella Norma , Sutormin Dmitry , Li Naisi , Gaisser Karl , Robertson Alexander , Ispolatov Yaroslav , Seelig Georg , Dey Neelendu , Kuchina Anna
Published: January 2025

Abstract

Success of phage therapies is limited by bacterial defenses against phages. While a large variety of anti- phage defense mechanisms has been characterized, how expression of these systems is distributed across individual cells and how their combined activities translate into protection from phages has not been studied. Using bacterial single-cell RNA sequencing, we profiled the transcriptomes of ∼50,000 cells from cultures of a human pathobiont,Bacteroides fragilis,infected with a lytic bacteriophage. We quantified the asynchronous progression of phage infection in single bacterial cells and reconstructed the infection timeline, characterizing both host and phage transcriptomic changes as infection unfolded. We discovered a subpopulation of bacteria that remained uninfected and determined the heterogeneously expressed host factors associated with protection. Each cell’s vulnerability to phage infection was defined by combinatorial phase-variable expression of multiple genetic loci, including capsular polysaccharide (CPS) biosynthesis pathways, restriction-modification systems (RM), and a previously uncharacterized operon likely encoding fimbrial genes. By acting together, these heterogeneously expressed phase-variable systems and anti-phage defense mechanisms create a phenotypic landscape where distinct protective combinations enable the survival and re-growth of bacteria expressing these phenotypes without acquiring additional mutations. The emerging model of complementary action of multiple protective mechanisms heterogeneously expressed across an isogenic bacterial population showcases the potent role of phase variation and stochasticity in bacterial anti-phage defenses.

One Sentence Summary

Combinatorial phenotypic states with differential vulnerability to phage infection across aBacteroides fragilispopulation enable a small number of super-resistant bacterial cells to evade the phage without the need for acquiring mutations.
Exploring FDA-Approved Antiviral Drugs for Human Metapneumovirus Treatment: Integrative Computational Insights
Authors: Dubey Amit , Kumar Manish , Tufail Aisha , Dwivedi Vivek Dhar
Published: January 2025

This study leverages advanced computational methodologies to identify potential antiviral therapies targeting human metapneumovirus (HMPV), focusing on FDA-approved antiviral drugs and control compounds. A comprehensive computational framework, encompassing virtual screening, molecular docking, molecular dynamics (MD) simulations, density functional theory (DFT) analysis, and ADMET profiling, was employed. Key findings highlight Remdesivir and Peramivir as the most promising candidates, with superior binding energies (−9.5 kcal/mol and - 9.2 kcal/mol, respectively), stable interaction profiles, and robust pharmacological properties. Molecular dynamics revealed exceptional stability for Remdesivir, with the lowest RMSD (0.20 nm), and pharmacophore analysis emphasized its strong hydrogen bonding and hydrophobic interactions. ADMET profiling confirmed their high bioavailability (85% ± 3 for Remdesivir) and low toxicity, positioning these drugs for repurposing against HMPV. This integrative study underscores the potential of computational tools in streamlining drug discovery and advancing therapeutic interventions.
Impact of Hormonal Contraceptives on HPV Dynamics in Adolescent Girls and Young Women: Insights from a Randomized Controlled Sub-Study in South Africa
Authors: Tanko Ramla F. , Taku Ongeziwe , Mbulawa Zizipho Z. A. , Phohlo Keletso , Konstantinus Iyaloo , Balle Christina , Pidwell Tanya , Happel Anna-Ursula , Gill Katherine , Bekker Linda-Gail , Jaspan Heather B. , Williamson Anna-Lise , Passmore Jo-Ann S.
Published: January 2025

Objectives

Human papillomavirus (HPV) is the leading cause of cervical cancer, with adolescent girls and young women (AGYW) in sub-Saharan Africa carrying a disproportionately high burden of infection. Hormonal contraceptives may influence HPV acquisition, persistence, and clearance, but evidence remains inconclusive. This sub-study aimed to evaluate the impact of different hormonal contraceptives on HPV prevalence and genotype distribution in AGYW.

Methods

Ninety-eight HIV-seronegative AGYW aged 15–19 years from South Africa were randomized to receive one of three hormonal contraceptive methods: norethisterone enanthate (Net-EN) injectable, combined oral contraceptive pills (COCPs), or the etonorgesterol/ethinyl estradiol combined contraceptive vaginal ring (CCVR). Cervical DNA samples were collected at baseline and after 16 weeks for HPV genotyping using the HPV Direct Flow Chip test. HPV prevalence, persistence, clearance, and acquisition were analyzed across contraceptive methods.

Results

At baseline, HPV prevalence was high (94.9%), with no differences among contraceptive arms. After 16 weeks, HPV prevalence remained high (89.5%) across groups. No significant differences were observed in overall HPV prevalence or genotype distribution by contraceptive method. Longitudinal analysis revealed that AGYW using Net-EN tended to have a higher cumulative number of high-risk HPV (HR-HPV) genotypes that cleared whereas those using CCVR acquired more HR-HPV types and had greater HR-HPV persistence compared to other groups.

Conclusions

This study highlights the high burden of HPV among South African AGYW. However, different hormonal contraceptive methods did not significantly influence HR-HPV dynamics.
Level of Adherence to Recommended Lifestyle Modifications and Associated Factors Among Adult Hypertensive Patients Attending Chronic Follow-Up Units at Hypertension Sentinel Site Health Facilities - Bahir Dar City, Northwest Ethiopia, 2024
Authors: Abebe Melaku , Muchie Kindie Fentahun , Taddege Tesfahun , Mulat Kebadnew
Published: January 2025

Background

Hypertension is one of the leading risk factors for mortality and morbidity worldwide. It is a chronic medical condition characterized by blood pressure (BP) consistently elevated above normal. Even though it is a global public health issue, it disproportionately affects populations in low- and middle-income countries that account for nearly 80% of deaths where health systems are weak. Adherence to medication therapy and lifestyle change is an aspect of patients’ care that is often overlooked and should be evaluated as a crucial part of cardiovascular management.

Objective

To assess the adherence to recommended lifestyle modifications and associated factors among adult hypertensive patients attending chronic follow-up units at hypertension sentinel site health facilities in Bahir Dar City, northwest Ethiopia in 2024.

Methods

A facility-based cross-sectional study was conducted in hypertension sentinel site health facilities in Bahir Dar city from April 24 to May 23, 2024. A total of 421 hypertensive patients were included in the study using a systematic random sampling technique. Data were collected through Computer-Assisted Personal Interviews (CAPI) and patient reviews using the KoboCollect. Data were analyzed using SPSS. Logistic regression analysis was used to identify factors associated with adherence to lifestyle modifications.

Results

The study found that 271 (64.4%) of the respondents were adherent to all studied lifestyle practices. Participants with good knowledge about lifestyle modification (AOR = 4.48 (2.30-8.75), good self-efficacy (AOR = 2.84 (1.61-5.01), good adherence to antihypertensive medication (AOR = 4.64 (2.54-8.45), primary education (AOR = 0.40 (0.18-0.89), underweight (AOR = 0.26(0.08-0.87), and overweight/ obese (AOR = 0.07 (0.04 -0.14) were factors associated with adherence to lifestyle modification.

Conclusions

The study revealed moderate level of adherence to lifestyle modifications among hypertensive patients. Good knowledge about lifestyle modification, good self-efficacy, and good adherence to antihypertensive medication were the factors positively associated with adherence to lifestyle modification, whereas, Patients with Primary education, underweight, and overweight/ obese were the factors negatively associated. Interventions targeting primary education, and underweight and overweight to raise knowledge status, medication adherence, and good self-efficacy will result in increased adherence.
Lower Cancer Incidence Three Years After COVID-19 Infection in a Large Veteran Population
Authors: Bradley Jerry , Tang Fei , Resendes Natasha , Tosi Dominique , Hammel Iriana
Published: January 2025

Background

The role of COVID-19 infection in cancer incidence risk is not known. COVID-19 infection could lead to increased cancer risk, as seen with other viruses, or it could lead to decreased risk due to the activation of the immune response during acute infection. This study aimed to determine the association between cancer incidence in US Veterans after COVID-19 infection.

Methods

We conducted a retrospective cohort study of US Veterans comparing those who tested positive for COVID-19 during the first wave of COVID-19 between March 15, 2020, and Nov 30, 2020, to those who tested negative. We used data from the COVID-19 Shared Data Resource and used Cox proportional hazard regression models to determine the hazard ratio of a new cancer diagnosis within a three-year follow-up period for the COVID-19 positive patients compared to those who were negative. Covariates included age, race, ethnicity, sex, BMI, smoking, being an active patient in the VHA system in the past 12 months of the COVID-19 test, and other factors.

Results

516156 patients were included in this study, with 88590 (17.2%) COVID-19 positive, 427566 (82.8%) COVID-19 negative. The ages of the COVID-19 positive and negative patients were 57.8±16.4 and 59.4±15.8, respectively. For those who survived for at least 30 days after COVID-19 testing, COVID-19 infection was associated with a 32% reduction in the hazard of cancer. The reduction of the hazard was similar across sexes and races, except in Asians. Above 45 years of age, the hazard of cancer incidence further decreases with advancing age.

Conclusions

Patients who were diagnosed with COVID-19 in the first wave of the pandemic had a decreased risk of cancer incidence in a 3-year follow-up across gender and race. Further multicenter prospective cohort studies are needed to evaluate the mechanism of this interaction.
Associations between social capital and other living conditions among young Angolan women: A cross-sectional study in three provinces
Authors: Priebe Gunilla Elise , Macama Arciolanda , Kessel Barbora , dos Reis Francisca Van Dúnem , Van Dúnem João E , Katito José , Ng Nawi , Engström Karin
Published: January 2025

Social support systems play a crucial role in promoting young women’s well-being and their human rights fulfilment, not least in contexts where institutions are weak and socioeconomic and gender inequalities prevail. However, research on young women’s social networks and trust in their benevolent function is scarce. This study attempts to reduce this knowledge gap by exploring young Angolan women’s access to social capital and how it clustered and was associated with other living conditions. The data were derived from a cross-sectional study of 2,071 women, aged 18-24 years, from rural and urban areas in Huambo, Luanda and Lunda Sul provinces. The results included a univariate description of the participants socioeconomic and social capital characteristics stratified by province and residential area, an exploratory factor analysis of 17 social capital variables, and tests for associations between social capital factors and socioeconomic variables (literacy, household wealth, work and pregnancy), the latter measured by means of logistic regressions. The study revealed that the women in Luanda had generally better living conditions, those from Lunda Sul were worse off, and those from Huambo were often in between. The factor analysis’ identification of structural, cognitive, and applied factors aligned well with established research. Literate and wealthier participants often had higher structural but less cognitive social capital. Social capital measures showed less variability compared to literacy and household wealth. The social capital factors were distributed and associated differently with the socioeconomic attributes based on location. The study highlights the intricate relationship between social capital and other living conditions, conditional on where women live. It draws attention to the need for further investigations into which social spheres young women perceive as supportive. The study emphasises the importance of analysing social capital domains separately, appreciating links to other resources and local uniqueness in social capital-enhancing interventions.
SPIRIT-CONSORT-TM: a corpus for assessing transparency of clinical trial protocol and results publications
Authors: Jiang Lan , Vorland Colby J , Ying Xiangji , Brown Andrew W , Menke Joe D , Hong Gibong , Lan Mengfei , Mayo-Wilson Evan , Kilicoglu Halil
Published: January 2025

Randomized controlled trials (RCTs) can produce valid estimates of the benefits and harms of therapeutic interventions. However, incomplete reporting can undermine the validity of their conclusions. Reporting guidelines, such as SPIRIT for protocols and CONSORT for results, have been developed to improve transparency in RCT publications. In this study, we report a corpus of 200 RCT publications, named SPIRIT-CONSORT-TM, annotated for transparency. We used a comprehensive data model that includes 83 items from SPIRIT and CONSORT checklists for annotation. Inter-annotator agreement was calculated for 30 pairs. The dataset includes 26,613 sentences annotated with checklist items and 4,231 terms. We also trained natural language processing (NLP) models that automatically identify these items in publications. The sentence classification model achieved 0.742 micro-F1 score (0.865 at the article level). The term extraction model yielded 0.545 and 0.663 micro-F1 score in strict and lenient evaluation, respectively. The corpus serves as a benchmark to train models that assist stakeholders of clinical research in maintaining high reporting standards and synthesizing information on study rigor and conduct.
Self-Organizing Assembloids Reveal Enteric Nervous System Dynamics in Gut Homeostasis and Regeneration
Authors: Sari Ilke , Uzun Beliz , Oguz Melda O. , Gursoy Eren , Satlykov Nurmuhammet , Gemalmayan Dila A. , Gonullu Nagihan , Valenta Tomas , Kaya Fatima Aerts , Gizer Merve , Korkusuz Petek , Degirmenci Bahar
Published: January 2025

The enteric nervous system (ENS) is essential for intestinal health, exhibiting adaptability to environmental and physiological challenges. However, the mechanisms underlying ENS plasticity and resilience remain poorly understood. Organoid technology has revolutionized in vitro modeling by accurately replicating epithelial structures and enabling significant advancements in understanding gastrointestinal biology. However, traditional organoids are limited in their ability to study the ENS, as they lack the multicellular composition and functional architecture necessary to model complex interactions between neurons, glia, mesenchymal, smooth muscle, and epithelial cells. To address these limitations, we developed murine ENS-Rich Assembloids (ERAs) that self-organize to replicate the cellular diversity, including the epithelial structure, and functional architecture of native colonic tissue. These assembloids recreate neuron-glia interactions, reflect regenerative processes, and provide a novel platform for studying ENS dynamics under controlled conditions. Integrating findings from assembloids and an in vivo murine model, we demonstrate that inflammation induces coordinated reorganization of S100b+ glial cells, TUJ1+ neurons, PDGFRA+ mesenchymal cells, and epithelial cells, revealing conserved mechanisms of ENS plasticity. We identify pleiotrophin (PTN) signaling via Protein Tyrosine Phosphatase Receptor Type Z1 (PTPRZ1) as a key pathway facilitating neural elongation and enhancing neuron-glia interactions. Moreover, we show that activated neurons transfer lipids to glial cells, revealing a novel support mechanism during inflammation. These findings position enteric glia as protective hubs for neurons, fostering ENS adaptability and tissue regeneration. By building on the foundational success of organoid technology and addressing its limitations for studying the ENS, ENS-rich assembloids establish a transformative tool for investigating ENS responses in health, disease, and tissue repair.
Resolution of a human super-enhancer by targeted genome randomisation
Authors: Koeppel Jonas , Murat Pierre , Girling Gareth , Peets Elin Madli , Gouley Mélanie , Rebernig Valentin , Maheshwari Anant , Hepkema Jacob , Weller Juliane , Johnkingsly Jebaraj Jenie Hannah , Crawford Ronnie , Liberante Fabio Giuseppe , Parts Leopold
Published: January 2025

Human gene expression is controlled from distance via enhancers, which can form longer ‘super-enhancer’-regions of intense regulatory activity. Whether super-enhancers constitute a separate regulatory paradigm remains unclear, largely due to the difficulty of dissecting the contributions and interactions of individual elements within their natural chromosomal context. To address this challenge, we developed enhancer scrambling, a high-throughput strategy to generate stochastic inversions and deletions of targeted enhancer regions by combining CRISPR prime editing insertion of symmetrical loxP sites with Cre recombinase-induced rearrangements. We applied our approach to dissect a distal super-enhancer of theOTX2gene, generating up to 134 alternative regulatory configurations in a single experiment, and establishing how they drive gene expression and chromatin accessibility, as well as the individual contributions of its elements to this activity. Surprisingly, the presence of the sequence containing a single DNase I hypersensitive site predominantly controlsOTX2expression. Our findings highlight that enhancer-driven regulation of some highly expressed, cell-type-specific genes can rely on an individual element within a cluster of non-interacting, dispensable components, and suggest a simple functional core to a subset of super-enhancers. The targeted randomisation method to scramble enhancers can scale to resolve many super-enhancers and human gene regulatory landscapes.
Spatiotemporal Complexity in the Psychotic Brain
Authors: Li Qiang , Liu Jingyu , Pearlson Godfrey D. , Chen Jiayu , Wang Yu-Ping , Turner Jessica A. , Calhoun Vince D.
Published: January 2025

Psychotic disorders, such as schizophrenia and bipolar disorder, pose significant diagnostic challenges with major implications on mental health. The measures of resting-state fMRI spatiotemporal complexity offer a powerful tool for identifying irregularities in brain activity. To capture global brain connectivity, we employed information-theoretic metrics, overcoming the limitations of pairwise correlation analysis approaches. This enables a more comprehensive exploration of higher-order interactions and multiscale intrinsic connectivity networks (ICNs) in the psychotic brain. In this study, we provide converging evidence suggesting that the psychotic brain exhibits states of randomness across both spatial and temporal dimensions. To further investigate these disruptions, we estimated brain network connectivity using redundancy and synergy measures, aiming to assess the integration and segregation of topological information in the psychotic brain. Our findings reveal a disruption in the balance between redundant and synergistic information, a phenomenon we termbrainquakein this study, which highlights the instability and disorganization of brain networks in psychosis. Moreover, our exploration of higher-order topological functional connectivity reveals profound disruptions in brain information integration. Aberrant information interactions were observed across both cortical and subcortical ICNs. We specifically identified the most easily affected irregularities in the sensorimotor, visual, temporal, default mode, and fronto-parietal networks, as well as in the hippocampal and amygdalar regions, all of which showed disruptions. These findings underscore the severe impact of psychotic states on multiscale critical brain networks, suggesting a profound alteration in the brain’s complexity and organizational states.
Phage susceptibility to a minimal, modular synthetic CRISPR-Cas system inPseudomonas aeruginosais nutrient dependent
Authors: Elliott Josie F K , Watson Bridget N J , Cozens Keira , Westra Edze R , Taylor Tiffany B
Published: January 2025

CRISPR-Cas systems can provide adaptive, heritable immunity to their prokaryotic hosts against invading genetic material such as phages. It is clear that the importance of acquiring CRISPR-Cas immunity to anti-phage defence varies across environments, but it is less clear if and how this varies across different phages. To explore this, we created a synthetic, modular version of the type I-F CRISPR-Cas system ofPseudomonas aeruginosa. We used this synthetic system to test CRISPR-Cas interference against a panel of 13 diverse phages using engineered phage-targeting spacers. We observed complete protection against eight of these phages, both lytic and lysogenic and with a range of infectivity profiles. However, for two phages CRISPR-Cas interference was only partially protective in high nutrient conditions, yet completely protective in low nutrient conditions. This work demonstrates that nutrient conditions modulate the strength of CRISPR-Cas immunity and highlights the importance of environmental conditions when screening defence systems for their efficacy against various phages.
Nematicidal and antifeedant activity of ethyl acetate extracts from culture filtrates ofArabidopsis thalianafungal endophytes
Authors: Díaz-González Sandra , Andrés María Fe , González-Sanz Carlos , Sacristán Soledad , González-Coloma Azucena
Published: January 2025

Endophytic fungi produce a diverse range of bioactive secondary metabolites with potential applications in biopesticide development. This study investigates the nematicidal and antifeedant properties of ethyl acetate extracts from endophytic fungi isolated from wildArabidopsis thalianapopulations in Spain. The extracts were tested against the plant-parasitic nematodeMeloidogyne javanica, and two common insect pests,Myzus persicaeandSpodoptera littoralis. Nine of the 13 extracts demonstrated significant nematicidal and/or antifeedant activity, indicating their potential as biopesticides. The active extracts were derived from six genera:Alternaria(3 isolates),Dydimella(1),Dothiora(1),Pleiochaeta(1),Penicillium(1), andFusarium(2). Five extracts exhibited nematicidal activity above 90%, with three reducing the total number ofM. javanicasecond-stage juveniles hatched from egg masses by 22–37%. Four extracts showed strong settling inhibition (>70%) againstM. persicae, and three exhibited feeding inhibition againstS. littoralis. Chemical analysis by GC-MS and LC-MS revealed a wide array of unique secondary metabolites in the active extracts, reflecting substantial chemical diversity, regardless of the fungal origin. This study highlights the potential of fungal endophytes fromA. thalianaas sources of novel biopesticides, paving the way for future research focused on harnessing these fungi for biopesticide development.
The olivocerebellar system differentially encodes the effect sensory events exert on behavior
Authors: Scheer Irina , Prsa Mario
Published: January 2025

Inferior olive neurons convey information about sensorimotor events via climbing fibers to the cerebellum, but their functional significance remains unclear. We directly imaged, with two-photon microscopy, climbing fiber axonal terminals in the cerebellum during a task that successively exposed mice to a force perturbation, a movement instruction and reward; each followed by multiple modes of motor activity. Climbing fiber activations by the sensory events were either generic or informative about the consequences the encoded event has on behavior. The number of informative cells and the information strength are regulated by event modality and functional complexity of the cell’s activity. We observed an additional, previously unreported activation of climbing fibers: they carried probabilistic information on the behavioral context during idle waiting periods preceding stimulus presentation. Our findings reveal properties of olivary neurons that are key for defining their function in the cerebellum-dependent control of behavior. They suggest that the inferior olive flexibly instructs the cerebellum of any process that may shape an animal’s action.
ERGA-BGE Reference Genome ofPhyllidia flava(Nudibranchia: Phyllidiidae), a Relict Species Endemic to the Mediterranean Sea
Authors: Galià-Camps Carles , Pontes Miquel , Marcussen Thomas , Struck Torsten H. , Oomen Rebekah , Böhne Astrid , Monteiro Rita , Aguilera Laura , Gut Marta , Ferreira Francisco Câmara , Cruz Fernando , Gómez-Garrido Jèssica , Alioto Tyler S. , De Panis Diego
Published: January 2025

Phyllidia flava, the only Mediterranean representative of the otherwise Indo-Pacific family Phyllididae, is a radula-less dorid nudibranch that feeds exclusively on toxic sponges, from which it derives defensive and camouflage compounds. Although not currently listed as endangered, this relict species remains vulnerable due to its restricted distribution and the rising temperatures of the Mediterranean Sea. A total of 13 contiguous chromosomal pseudomolecules were assembled, resulting in a chromosome-level genome spanning 1.9 Gb. This assembly comprises 2,032 contigs and 62 scaffolds, with contig and scaffold N50 values of 2.4 Mb and 169.7 Mb, respectively. This reference genome will serve as a valuable resource for conservation efforts, provide a robust calibration point for studying nudibranch phylogenetics based on the Tethys Ocean closure, and lay the groundwork for research into toxic prey diet specialisation.
Identification of two glycosyltransferases required for synthesis of membrane glycolipids inClostridioides difficile
Authors: Zbylicki Brianne R. , Cochran Sierra , Weiss David S. , Ellermeier Craig D.
Published: January 2025

Clostridioides difficileinfections cause over 12,000 deaths and an estimated one billion dollars in healthcare costs annually in the United States. The cell membrane is an essential structure that is important for protection from the extracellular environment, signal transduction, and transport of nutrients. The polar membrane lipids ofC. difficileare ∼50% glycolipids, a higher percentage than most other organisms. The glycolipids ofC. difficileconsist of monohexosyldiradylglycerol (MHDRG) (∼14%), dihexosyldiradylglycerol (DHDRG) (∼15%), trihexosyldiradylglycerol (THDRG) (∼5%), and a unique glycolipid aminohexosyl-hexosyldiradylglycerol (HNHDRG) (∼16%). Previously, we found HexSDF are required for synthesis of HNHDRG. The enzymes required for synthesis of MHDRG, DHDRG, and THDRG are not known. In this study, we identified the glycosyltransferases UgtA (CDR20291_0008), which is required for synthesis of all glycolipids, and UgtB (CDR20291_1186), which is required for synthesis of DHDRG and THDRG. We propose a model where UgtA synthesizes only MHDRG, HexSDF synthesize HNHDRG from MHDRG, and UgtB synthesizes DHDRG and potentially THDRG from MHDRG. We also report that glycolipids are important for critical cell functions, including sporulation, cell size and morphology, maintaining membrane fluidity, colony morphology, and resistance to some membrane targeting antimicrobials.

Importance

Clostridioides difficileinfections are the leading cause of healthcare associated diarrhea.C. difficileposes a risk to public health due to its ability to form spores and cause recurrent infections. Glycolipids make up ∼50% of the polar lipids in theC. difficilemembrane, a higher percentage than other common pathogens and include a unique glycolipid not present in other organisms. Here, we identify glycosyltransferases required for synthesis of glycolipids inC. difficileand demonstrate the important role glycolipids play inC. difficilephysiology.
Robustness of working memory to prefrontal cortex microstimulation
Authors: Soldado-Magraner Joana , Minai Yuki , Yu Byron M. , Smith Matthew A.
Published: January 2025

Delay period activity in the dorso-lateral prefrontal cortex (dlPFC) has been linked to the maintenance and control of sensory information in working memory. The stability of working memory related signals found in such delay period activity is believed to support robust memory-guided behavior during sensory perturbations, such as distractors. Here, we directly probed dlPFC’s delay period activity with a diverse set of activity perturbations, and measured their consequences on neural activity and behavior. We applied patterned microstimulation to the dlPFC of monkeys implanted with multi-electrode arrays by electrically stimulating different electrodes in the array while the monkeys performed a memory-guided saccade task. We found that the microstimulation perturbations affected spatial working memory-related signals in individual dlPFC neurons. However, task performance remained largely unaffected. These apparently contradictory observations could be understood by examining different dimensions of the dlPFC population activity. In dimensions where working memory related signals naturally evolved over time, microstimulation impacted neural activity. In contrast, in dimensions containing working memory related signals that were stable over time, microstimulation minimally impacted neural activity. This dissociation explained how working memory-related information could be stably maintained in dlPFC despite the activity changes induced by microstimulation. Thus, working memory processes are robust to a variety of activity perturbations in the dlPFC.

Significance statement

Memory-guided behavior is remarkably robust to sensory perturbations such as distractions. The dorso-lateral prefrontal cortex (dlPFC) is believed to underlie this robustness, given that it stably maintains working memory-related information in the presence of distractors. Here, we sought to understand the extent to which dlPFC circuits can robustly maintain working memory information during memory-guided behavior. We found that behavior was robust to microstimulation perturbations in dlPFC, and that working memory signals were stably maintained in dlPFC despite widespread changes in the neural activity caused by the perturbations. Our findings indicate that working memory is robust to direct activity perturbations in the dlPFC, an ability that may be due to the processes that mediate similar robustness in the face of distraction.
Recombinant production inEscherichia coliof functionally active α-hemolysin from the human pathogenStaphylococcus aureus
Authors: Díaz-Varela Jaime L. , Sabia Vittoria , Heras-Márquez Diego , Laxalde-Fernández Diego , Martínez-del-Pozo Álvaro , García-Linares Sara
Published: January 2025

Staphylococcus aureusis a human opportunistic pathogen capable of causing multiple infections in both humans and animals. It secretes a group of exotoxins, known as hemolysins, which are released to enhance its pathogenicity. All of them exhibit cytolytic activity on a variety of host cell types, but α-hemolysin stands out for being the most thoroughly studied variant. In this work, we show the production and purification ofS. aureusα-hemolysin following a straightforward protocol and in sufficient quantity to consider it as a potential procedure for future biotechnological approaches. Functional and structural characterization has indeed revealed that the protein is fully functional, confirming the key role of cholesterol in the necessary protein-lipid interaction. Furthermore, it has also been shown that the purified toxin can be assembled into single-particle individual pores within soluble lipid platforms in the form of cholesterol-containing nanodiscs.
A Propidium Iodide-basedIn VitroScreen of the “Bug Box” AgainstBabesia duncaniReveals Potent Inhibitors
Authors: Dews Emmett A. , Teixeira José E. , Huston Christopher D. , Meyers Marvin J. , Hyson Peter R.
Published: January 2025

Incidence and endemic range of human babesiosis are expanding. Standard therapy for human babesiosis consists of antimicrobials developed for other indications. While these treatments are adequate in immunocompetent hosts, infections in the immunocompromised can be severe, relapsing, and drug-resistant despite use of multi-drug regimens. Existing drugs are ineffective because they cannot safely achieve and maintain adequate serum concentrations to inhibit Babesia. Discovery of improved agents against Babesia spp. is of growing importance and efficient techniques for high throughput compound screening can assist in this effort.

We developed a high throughputin vitrodrug screening assay forBabesia duncanithat is conducted in 384 well plates and makes use of the fluorescent DNA stain propidium iodide (PI) with relative fluorescence measured by a microplate reader. A Z’ factor of >0.81 was calculated which suggests an excellent ability to detect inhibitory compounds. A screen of the 41-compound library Structural Genomics Consortium Bug Box was conducted yielding five hits: trimethoprim, atovaquone, SDDC M7, diphenyleneiodonium chloride, and panobinostat. Panobinostat, a histone deacetylase complex (HDAC) inhibitor, was selected for further evaluation given that its target had not been previously explored inB. duncani.Follow up dose-response testing of structurally related compounds revealed multiple potential leads including nanatinostat and quisinostat, both of which were potent at the nanomolar level and showed favorable selectivity index in cytotoxicity studies. High throughput screening using PI and 384 well plates is an advance in drug discovery for babesiosis and HDAC inhibitors show promise as lead compounds worthy of further investigation.
Exploring the Suitability of Piecewise-Linear Dynamical System Models for Cognitive Neural Dynamics
Authors: Wu Jiemin , Asamoah Boateng , Kong Zhaodan , Ditterich Jochen
Published: January 2025

Dynamical system models have proven useful for decoding the current brain state from neural activity. So far, neuroscience has largely relied on either linear models or nonlinear models based on artificial neural networks. Piecewise linear approximations of nonlinear dynamics have proven useful in other technical applications, providing a clear advantage over network-based models, when the dynamical system is not only supposed to be observed, but also controlled. Here we explore whether piecewise-linear dynamical system models (recurrent Switching Linear Dynamical System or rSLDS models) could be useful for modeling brain dynamics, in particular in the context of cognitive tasks. We first generate artificial neural data based on a nonlinear computational model of perceptual decision-making and demonstrate that piecewise-linear dynamics can be successfully recovered from these observations. We then demonstrate that the piecewise-linear model outperforms a linear model in terms of predicting future states of the system and associated neural activity. Finally, we apply our approach to a publicly available dataset recorded from monkeys performing perceptual decisions. Much to our surprise, the piecewise-linear model did not provide a significant advantage over a linear model for these particular data, although linear models that were estimated from different trial epochs showed qualitatively different dynamics. In summary, we present a dynamical system modeling approach that could prove useful in situations, where the brain state needs to be controlled in a closed-loop fashion, for example, in new neuromodulation applications for treating cognitive deficits. Future work will have to show under what conditions the brain dynamics are sufficiently nonlinear to warrant the use of a piecewise-linear model over a linear one.
Visuospatial computations vary by category and stream and continue to develop in adolescence
Authors: Yao Jewelia K. , Choo Justin , Finzi Dawn , Grill-Spector Kalanit
Published: January 2025

Reading, face recognition, and navigation are supported by visuospatial computations in category-selective regions across ventral, lateral, and dorsal visual streams. However, the nature of visuospatial computations across streams and their development in adolescence remain unknown. Using fMRI and population receptive field (pRF) modeling in adolescents and adults, we estimate pRFs in high-level visual cortex and determine their development. Results reveal that pRF location, size, and visual field coverage vary across category, stream, and hemisphere in both adolescents and adults. While pRF location is mature by adolescence, pRF size and visual field coverage continue to develop – increasing in face-selective and decreasing in place-selective regions – alongside similar development of category selectivity. These findings provide a timeline for differential development of visual functions and suggest that visuospatial computations in high-level visual cortex continue to be optimized to accommodate both category and stream demands through adolescence.
Causal Spike Timing Dependent Plasticity Prevents Assembly Fusion in Recurrent Networks
Authors: Yang Xinruo , Doiron Brent
Published: January 2025

The organization of neurons into functionally related assemblies is a fundamental feature of cortical networks, yet our understanding of how these assemblies maintain distinct identities while sharing members remains limited. Here we analyze how spike-timing-dependent plasticity (STDP) shapes the formation and stability of overlapping neuronal assemblies in recurrently coupled networks of spiking neuron models. Using numerical simulations and an associated mean-field theory, we demonstrate that the temporal structure of the STDP rule, specifically its degree of causality, critically determines whether assemblies that share neurons maintain segregation or merge together after training is completed. We find that causal STDP rules, where potentiation/depression occurs strictly when presynaptic spikes precede/proceed postsynaptic spikes, allow assemblies to remain distinct even with substantial overlap in membership. This stability arises because causal STDP effectively cancels the symmetric correlations introduced by common inputs from shared neurons. In contrast, acausal STDP rules lead to assembly fusion when overlap exceeds a critical threshold, due to unchecked growth of common input correlations. Our results provide theoretical insight into how spike-timing-dependent learning rules can support distributed representation where individual neurons participate in multiple assemblies while maintaining functional specificity.
Neurite density but not myelination of specific fiber tracts links polygenic scores to general intelligence
Authors: Stammen Christina , Penate Javier Schneider , Metzen Dorothea , Hönscher Maurice J. , Fraenz Christoph , Schlüter Caroline , Güntürkün Onur , Kumsta Robert , Genç Erhan
Published: January 2025

White matter is fundamental for efficient and accurate information transfer throughout the human brain and thus crucial for intelligence. Previous studies often demonstrated associations between fractional anisotropy (FA) as a metric of white matter “microstructural integrity” and intelligence, but it is still unclear, whether this relation is due to greater axon density, parallel, homogenous fiber orientation distributions, or greater myelination since all of these measures influence FA. Using neurite orientation dispersion and density imaging (NODDI) and myelin water fraction (MWF) imaging data, we analyzed the microstructural architecture of intelligence in more detail in a sample of 500 healthy young adults. Furthermore, we were interested whether specific white matter microstructural indices play intermediary roles in the pathway that links genetic disposition for intelligence to phenotype. Thus, we conducted for the first time mediation analyses investigating whether neurite density (NDI), orientation dispersion (ODI), and MWF of 64 white matter fiber tracts mediate the effects of polygenic scores for intelligence (PGSGI) on general intelligence. By doing so, we showed that NDI, but not ODI or MWF of white matter fiber tracts was significantly associated with general intelligence and that the NDI of six fiber tracts mediated the relation between genetic variability andg. These findings are a crucial step forward in decoding the neurogenetic underpinnings of general intelligence, as they identify that neurite density of specific fiber tracts relates polygenic variation tog, whereas orientation dispersion and myelination did not.
An extended Stokes’ theorem for spiral paths: applications to rotational flows inTrachelospermum jasminoidesstems and flowers
Authors: Tozzi Arturo
Published: January 2025

The traditional Stokes’ theorem connects the macroscopic circulation along a closed boundary to the microscopic circulation across the surface it encloses. However, it proves inadequate for addressing complex geometries such as helicoidal paths, non-planar flow patterns and dynamic systems with open boundaries. We introduce an extension of Stokes’ theorem (EST) that provides a robust tool for interdisciplinary research in spiral/helicoidal dynamics, facilitating the evaluation of rotational forces and circulation in both natural and engineered systems with open boundaries. We apply EST to model the rotational dynamics of flower petals and the helical forces within the stems ofTrachelospermum jasminoides, known as star jasmine. For the flower, we demonstrate the equivalence between the line integral along the petal boundary and the surface integral over the enclosed disk, effectively capturing the uniform rotational stress generated by tangential forces. EST enables the analysis of external factors such as wind or pollinator interactions, while providing valuable insights to deepen our understanding of floral mechanics and petal growth patterns. For the stem, linking microscopic circulatory forces to macroscopic flow patterns, we demonstrate the interaction of torsional and bending stresses caused by the helical geometry. This finding has significant implications for understanding plant growth biomechanics and structural stability as well as for quantifying nutrient and water transport within stems, where spiral dynamics play a pivotal role. In summary, EST streamlines the analysis of rotational and translational forces in systems governed by spiral and helicoidal dynamics, including physical and biological phenomena such as phyllotaxis and plant growth.
Multitrace deformations and the nonlinear stability of anti–de Sitter space
Authors: Serantes Alexandre , Travieso Mayo David , Mas Javier
Published: January 2025

We investigate the nonlinear stability of global anti–de Sitter space in the presence of multitrace deformations utilizing an Einstein-Klein-Gordon system with a top-down scalar potential. Our numerical simulations show that marginal and irrelevant deformations retain the nonlinear instability originally found by Bizoń and Rostworowski, while relevant deformations disrupt it. We show that the nonlinear impact of multitrace deformations is in one-to-one correspondence with how they affect the resonant character of the global anti–de Sitter normal mode eigenfrequency spectrum.

Published by the American Physical Society
2025