Biology subjects

Ray, N.

Publications and source records attributed to Ray, N..

13 recordsLinked to original sources

bioRxiv2026

Human-wildlife conflict shows shared spatial predictors across ecological and geographic contexts

Human-wildlife conflict (HWC) is a global challenge for biodiversity conservation, food security, and human well-being. Effective management towards human-wildlife coexistence, recognized as a priority in Target 4 of the Kunming-Montreal Global Biodiversity Framework, requires understanding the drivers of HWC. However, the strong influence of local human and ecological context means that most HWC research focuses on individual case studies, limiting transferability of patterns across contexts. Here, we link local contexts and transferable drivers by testing whether HWC exhibits an intermediate level of organization, in which local predictor profiles are structured by broader ecological, geographic, and taxonomic contexts. After compiling ~11,000 conflict incidents, we construct and compare random forest models across 29 mammalian HWC scenarios spanning diverse species, conflict types, biomes, and continents to identify contexts in which predictor profiles converge. While predictors varied among individual conflicts, HWC scenarios were organized by shared context: conflicts occurring within the same biome tended to have similar predictor profiles, with continent and taxonomic group providing additional structure. Proximity to protected areas was the most consistently important predictor of HWC globally. The likelihood of conflict increased with human population density across nearly all scales and contexts, while distance to roads was also an important predictor in many contexts. Together, these results demonstrate an intermediate level of organization in HWC that reconciles case-specific variation with broader patterns across biomes, continents, and taxonomic groups. This framework provides a basis for scaling mitigation strategies beyond individual case studies while avoiding one-size-fits-all approaches.

ecology↗

bioRxiv2026

Distinct nigral and brainstem pathology markers map onto separable subthalamic electrophysiological signatures in Parkinson's disease

Subthalamic local field potentials (LFPs) are increasingly used as physiomarkers of the symptomatic state in Parkinsons disease, but their relationship to the underlying neurodegenerative pathology remains unclear. Here, we combined OFF-medication subthalamic LFP recordings with quantitative MRI markers of nigral and brainstem pathology in 33 people with Parkinsons disease. Distinct pathological markers mapped onto dissociable electrophysiological components. Substantia nigra pars compacta susceptibility was associated with increased occupancy, duration and rate of low-{beta} bursts, whereas nigral free water was associated with greater low-frequency aperiodic offset and a steeper slope. Pedunculopontine nucleus free-water- corrected axial diffusivity was selectively associated with high-frequency aperiodic activity, and this relationship strengthened with increasing nigral susceptibility, consistent with dopaminergic-state- dependent influences of extranigral pathology on subthalamic physiology. Only low-frequency aperiodic offset was also associated with contralateral bradykinesia. These findings indicate that the subthalamic LFP is not a unitary readout of dopamine loss or motor state, but an integrated physiological signal in which pathology across interconnected systems is expressed through separable oscillatory and aperiodic components. Chronically implanted devices may therefore provide physiological readouts of underlying disease biology alongside control signals for adaptive therapy.

neuroscience↗

bioRxiv2026

Baicalin ameliorates behavioral and physiological deficits in Gtf2i-duplication mice and modulates synaptic activity in 7q11.23 Duplication Syndrome patient-derived neurons

7q11.23 Duplication Syndrome (7Dup) is a type of syndromic autism spectrum disorder caused by duplication of a typically 1.5-1.8 Mb segment in section q11.23 of chromosome 7, including 25-27 genes. Previous work has highlighted the GTF2I gene as playing a major role in the phenotype of 7Dup patients. Accordingly, mice with Gtf2i duplication (Gtf2i+/dup) are commonly used as an animal model of 7Dup. We previously reported deficits in several behavioral and physiological modalities, which were associated with Gtf2i dosage in mice conducting a battery of social discrimination tests. Here, we report the effect of treating Gtf2i+/dup mice with Baicalin, a naturally occurring flavonoid added to the mices drinking water (0.15 mg/ml), on these deficits. We found that Baicalin treatment ameliorated the higher surface temperature observed in Gtf2i+/dup males and the lower tail temperature observed in Gtf2i+/dup females during the social behavior tests. It also prevented the increased defecation rate exhibited by Gtf2i+/dup mice during the social preference test. We further analyzed the effect of Baicalin treatment on cortical neurons differentiated from 7Dup patient-derived IPSCs. Using whole cell patch clamp and calcium imaging, we found an increased rate of excitatory postsynaptic currents in Baicalin-treated cells, without a change in their firing rate, indicating a stronger synaptic activity in the Baicalin-treated cells. Altogether, our results reveal that Baicalin administration alleviates some of the behavioral and physiological effects of Gtf2i duplication in mice, and affects neuronal activity in cultured 7Dup human neurons. Thus, Baicalin administration has the potential to serve as a treatment for 7Dup patients.

neuroscience↗

bioRxiv2025

Notch and Wnt signalling interact for proper prosensory and non-sensory domain formation

The prosensory domain (PSD) of the developing inner ear develops into the sensory hair cells, supporting cells, and neurons necessary for hearing and balance. Although Notch-Jag1 signalling is known to maintain Sox2 expression in this domain, the mechanisms by which Notch sustains prosensory identity have remained unclear. Here, we show that this function does not require canonical RBPJ{kappa}-dependent transcription. Using chick in ovo electroporation, Notch reporter assays, and conditional mouse mutants, we find that canonical Notch signalling is active during neurogenesis but not within the Sox2-positive PSD. Jag1 loss leads to a gradual loss of Sox2, yet RBPJ{kappa} mutants retain Sox2, indicating a non- canonical Notch pathway. We further reveal that the non-sensory determinant Lmx1a is regulated by Wnt/{beta}-catenin signalling and that manipulating Wnt activity shifts the balance between Lmx1a and Sox2 expression. Finally, we show that NICD can directly interact with {beta}-catenin in the cytoplasm, suggesting that NICD sequesters {beta}-catenin to suppress Wnt activity and stabilise Sox2 in the PSD. Collectively, these findings support a model where prosensory maintenance occurs through non-canonical Notch signalling acting together with Wnt, forming a combined WNTCH regulatory module that coordinates sensory and non-sensory fate specification.

developmental biology↗

bioRxiv2025

Contrasting behavioral and physiological effects of Gtf2i duplication and deletion in mouse models of the 7q11.23 Duplication and Williams-Beuren Syndromes

7q11.23 Microduplication Syndrome (7Dup) and Williams-Beuren Syndrome (WBS) are two ASD-related syndromes characterized by both common and contrasting symptoms, caused by either duplication or deletion of a 1.5-1.8 Mb segment in section q11.23 of Human chromosome 7, respectively. Notably, WBS patients show reduced social fear and are considered hyper-social, while 7Dup patients suffer from social anxiety and withdrawal. Previous work suggests that the GTF2I gene, one of the genes included in this segment, has a major role in the social symptoms of both syndromes. Here, we combine video and thermal imaging in multiple social behavior tests to screen for behavioral and physiological variables showing variations in mice models with either a duplication (Gtf2i+/dup) or a deletion (Gtf2i+/del) of the gene. Our analyses of social behavior, micturition, and defecation patterns identify several differences between wild-type and mutant littermates, some of which show contrasting variations associated with Gtf2i dosage. Interestingly, thermal imaging revealed that Gtf2i dosage dictates the mices surface temperature profile during the tests, with Gtf2i+/dup males exhibiting higher surface temperature than their wild-type littermates, while Gtf2i+/del males and females show the opposite tendency. These results suggest that the two mouse models exhibit opposite changes in either their emotional state or thermoregulation capabilities, in correlation with Gtf2i dosage.

neuroscience↗

bioRxiv2025

Multi-ancestry Transcriptome-Wide Association Study Reveals Shared and Population-Specific Genetic Effects in Alzheimer's Disease

Alzheimers disease (AD) risk differs across ancestral populations, yet most genetic studies have focused on non-Hispanic White (NHW) cohorts. We conducted a multi-population transcriptome-wide association study (TWAS) using whole-blood RNA-seq and genotype data from NHW (n=235), African American (AA; n=224), and Hispanic (HISP; n=292) MAGENTA participants. Using SuShiE for multi-population cis-eQTL fine-mapping, we identified credible sets for 8,748 genes, improving fine-mapping precision relative to analyses using fewer populations. cis-eQTL effects were largely shared across populations, with a subset showing population-specific regulation. We performed population-stratified TWAS of AD and inverse variance-weighted meta-analysis, followed by gene-level TWAS fine-mapping (MA-FOCUS), prioritizing nine genes (FDR<0.05, PIP>0.8), including established AD loci (BIN1, PTK2B, DMPK) with broadly consistent effects across populations. At BIN1, fine-mapped cis-eQTL variants used in the TWAS prediction model highlighted rs11682128, which is only modestly correlated with the GWAS index SNP rs6733839 (r2 {approx} 0.34), demonstrating how integrating eQTL fine-mapping with TWAS can refine signals beyond sentinel GWAS variants. We also identified an association between COG4 expression and AD in NHW, implicating Golgi-related pathways. Using independent SuShiE-derived models from TOPMed MESA (PBMC), several signals replicated directionally across ancestries, with the strongest statistical support in NHW. Overall, multi-population eQTL fine-mapping improves model interpretability and helps resolve shared and population-specific regulatory mechanisms relevant to AD.

genomics↗

bioRxiv2025

Small- and large-scale patches shape benthic microbial community structure and function in streams at the subcontinental scale

Streams and rivers process dissolved and particulate matter as water moves along the land-to-ocean continuum, making important contributions to global biogeochemical cycles. Yet, predicting stream and river microbial metabolism associated with biogeochemical transformations at broad spatial scales remains challenging. Here, we used data from the National Ecological Observatory Network program to investigate whether ecological relationships among microbial community structure and function and environmental conditions observed at small scales hold at the subcontinental scale. We found that microbial communities were best explained by site-specific conditions. However, when field replicates were averaged, stream physico-chemical characteristics such as pH and temperature emerged as driving factors. This indicates that water quality acted as an environmental filter on microbial communities at the subcontinental scale, but was masked by small-scale patches that created high spatial heterogeneity. Our findings underscore the importance of considering multiple spatial scales to fully understand benthic microbial communities role in stream biogeochemistry. SCIENTIFIC SIGNIFICANCE STATEMENTMicrobial communities in streams process materials as water flows toward the ocean. As microbial communities are influenced by environmental conditions, it remains challenging to predict stream microbial metabolism at large spatial scales. In this study, we used the National Ecological Observatory Network (NEON) public database to investigate the drivers of microbial community structure and functions in stream sediments across the USA. This unique dataset revealed high variability in microbial communities among streams that were best explained by local conditions, then by water quality and streambed habitat type. However, stream physico-chemical characteristics emerged as strong predictors of microbial communities when field replicates were averaged and considered as single, large microbial communities. These findings indicate multiple spatial scales must be considered to fully understand benthic microbial communities.

ecology↗

bioRxiv2025

Higher methanotroph abundance and bottom-water methane in ponds with floating photovoltaic arrays

Floating photovoltaic (FPV) arrays alter the methane (CH4) cycling dynamics of waterbodies on which they are deployed. Here, we investigated dissolved CH4 dynamics and associated CH4 cycling microbial communities (methanogens and methanotrophs) in the second year of FPV deployment (70% aerial coverage) in experimental ponds. We found that bottom-water CH4 concentrations were twice as high in ponds with FPV compared to those without, while surface water CH4 concentrations were orders of magnitude lower than bottom-waters, but did not differ between treatments. There was no change in the relative abundances of putative sediment methanogens or methanotrophs, but FPV restructured methanogen communities. FPV promoted late-summer methanotroph blooms in the water column, with abundances surpassing 1,000,000 cells mL-1. We conclude that prolonged periods of CH4 production in low oxygen FPV ponds favored blooms of methanotrophs, that may mitigate diffusive CH4 emissions to the atmosphere by consuming dissolved CH4.

ecology↗

bioRxiv2025

ENPP1 inhibitor with ultralong drug-target residence time as an innate immune checkpoint blockade cancer therapy

Only one in five patients is estimated to respond to immune checkpoint inhibitors, which primarily target adaptive immunity. To date, no FDA-approved immunotherapies directly activate the innate anti-cancer immunity--an essential driver of lymphocyte recruitment and potentiator of responses to existing cancer immunotherapies. ENPP1, the dominant hydrolase that degrades extracellular cGAMP and suppresses downstream STING-mediated innate immune signaling, has emerged as a promising therapeutic target. However, existing ENPP1 inhibitors have been optimized for prolonged systemic residence time rather than effective target inhibition within tumors. Here, we report the characterization of STF-1623, a highly potent ENPP1 inhibitor with an exceptionally long tumor residence time despite rapid systemic clearance, enabled by its high ENPP1 binding affinity and slow dissociation rate. We show that membrane-bound ENPP1 on tumor cells, not the abundant soluble ENPP1 in serum, drives tumor progression. Consequently, STF-1623 unleashes anti-tumor immunity and synergizes with ionizing radiation, anti-PD-L1 and anti-PD-1, and a DNA damaging agent to produce robust anti-tumor and anti-metastatic effects across multiple syngeneic mouse tumor models, all without detectable toxicity. Conceptually, this work establishes that a noncovalent small molecule inhibitor of ENPP1 with ultralong drug-target engagement offers a safe and precise strategy to activate STING within tumors, fulfilling an unmet need of innate immunotherapies in cancer. One Sentence SummaryA small molecule blocks ENPP1, reviving immune attack on tumors and enhancing immune therapy with minimal side effects in preclinical cancer models.

cancer biology↗

bioRxiv2024

DeePosit: an AI-based tool for detecting mouse urine and fecal depositions from thermal video clips of behavioral experiments

In many mammals, including rodents, social interactions are often accompanied by active urination (micturition), which is considered a mechanism for spatial scent marking. Urine and fecal deposits contain a variety of chemosensory signals that convey information about the individuals identity, genetic strain, social rank, and physiological or hormonal state. Furthermore, scent marking has been shown to be influenced by the social context and by the individuals internal state and experience. Therefore, analyzing scent-marking behavior during social interactions can provide valuable insight into the structure of mammalian social interactions in health and disease. However, conducting such analyses has been hindered by several technical challenges. For example, the widely used void spot assay lacks temporal resolution and is prone to artifacts, such as urine smearing. To solve these issues, recent studies employed thermal imaging for the spatio-temporal analysis of urination activity. However, this method involved manual analysis, which is time-consuming and susceptible to observer bias. Moreover, defecation activity was hardly analyzed by previous studies. In the present study, we integrate thermal imaging with an open-source algorithm based on a transformer-based video classifier for automatic detection and classification of urine and fecal deposits made by male and female mice during various social behavior assays. Our results reveal distinct dynamics of urination and defecation in a test-, strain- and sex-dependent manner, indicating two separate processes of scent marking in mice. We validate this algorithm, termed by us DeePosit, and show that its accuracy is comparable to that of a human annotator and that it is efficient in various setups and conditions. Thus, the method and tools introduced here enable efficient and unbiased automatic spatio-temporal analysis of scent marking behavior in the context of behavioral experiments in small rodents.

animal behavior and cognition↗

bioRxiv2024

Distinct prelimbic cortex neuronal responses to emotional states of others drive emotion recognition in adult male mice

The ability to perceive the emotional states of others, termed emotion recognition, allows individuals to adapt their conduct to the social environment. The brain mechanisms underlying this capacity, known to be impaired in individuals with autism spectrum disorder (ASD), remain, however, elusive. Using the emotional state preference paradigm, we show that adult mice can discern emotional states of conspecifics in a sex-specific manner, behavior impaired in an ASD mouse model. Fiber photometry revealed inhibition of pyramidal neurons in the prelimbic medial prefrontal cortex (PrL) during investigation of aroused individuals, as opposed to transient excitation towards non-aroused conspecifics. Augmenting this differential neuronal response enhanced emotion recognition, while abolishing this response eliminated such behavior, as demonstrated via optogenetic stimulation. Chronic electrophysiological recordings at the single-cell level indicated social stimulus-specific responses in PrL neurons at the onset and conclusion of social investigation bouts, potentially regulating the initiation and termination of social interactions. The dysregulated activity of these neurons may thus contribute to deficits in social behavior observed in ASD.

neuroscience↗

bioRxiv2023

Impaired emotion recognition in Cntnap2-deficient mice is associated with hyper-synchronous prefrontal cortex neuronal activity

Individuals diagnosed with autism spectrum disorder (ASD) show difficulty in recognizing emotions in others, a process termed emotion recognition. While human fMRI studies linked multiple brain areas to emotion recognition, the specific mechanisms underlying impaired emotion recognition in ASD are not clear, partially due to the lack of appropriate tests in animal models. Here, we employed an emotional state preference (ESP) task to show that Cntnap2-knockout (KO) mice, an established ASD model, do not distinguish between conspecifics according to their emotional state. We assessed brain-wide local-field potential (LFP) signals during various social behavior tasks and found that Cntnap2-KO mice exhibited higher LFP theta and gamma rhythmicity than did C57BL/6J mice, even at rest. Specifically, Cntnap2-KO mice showed increased theta coherence, especially between the prelimbic cortex (PrL) and the hypothalamic paraventricular nucleus, during social behavior. Moreover, we observed significantly increased Granger causality of theta rhythmicity between these two brain areas, across all types of social behavior. Finally, optogenetic stimulation of PrL pyramidal neurons in C57BL/6J mice impaired their social discrimination abilities, including ESP behavior. Together, these results suggest that increased activity of PrL pyramidal neurons and their augmented synchronization with specific brain regions are involved in the impaired emotion recognition exhibited by Cntnap2-KO mice.

neuroscience↗

bioRxiv2021

Constructing and validating a transferable epidemic risk index in data scarce environments using open data: a case study for dengue in the Philippines

Epidemics are among the most costly and destructive natural hazards globally. To reduce the impacts of infectious disease outbreaks, the development of a risk index for infectious diseases can be effective, by shifting infectious disease control from emergency response to early detection and prevention. In this study, we introduce a methodology to construct and validate an epidemic risk index using only open data, with a specific focus on scalability. The external validation of our risk index makes use of distance sampling to correct for underreporting of infections, which is often a major source of biases, based on geographical accessibility to health facilities. We apply this methodology to assess the risk of dengue in the Philippines. The results show that the computed dengue risk correlates well with standard epidemiological metrics, i.e. dengue incidence (p = 0.002). Here, dengue risk constitutes of the two dimensions susceptibility and exposure. Susceptibility was particularly associated with dengue incidence (p = 0.047) and dengue case fatality rate (CFR) (p = 0.029). Exposure had lower correlations to dengue incidence (p = 0.211) and CFR (p = 0.163). Highest risk indices were seen in the south of the country, mainly among regions with relatively high susceptibility to dengue outbreaks. Our findings reflect that the modelled epidemic risk index is a strong indication of sub-national dengue disease patterns and has therefore proven suitability for disease risk assessments in the absence of timely epidemiological data. The presented methodology enables the construction of a practical, evidence-based tool to support public health and humanitarian decision-making processes with simple, understandable metrics. The index overcomes the main limitations of existing indices in terms of construction and actionability. Author summaryO_LIWhy Was This Study Done? - Epidemics are among the most costly and destructive natural hazards occurring globally; currently, the response to epidemics is still focused on reaction rather than prevention or preparedness. - The development of an epidemic risk index can support identifying high-risk areas and can guide prioritization of preventive action and humanitarian response. - While several frameworks for epidemic risk assessment exist, they suffer from several limitations, which resulted in limited uptake by local health actors - such as governments and humanitarian relief workers - in their decision-making processes C_LIO_LIWhat Did the Researchers Do and Find? - In this study, we present a methodology to develop epidemic risk indices, which overcomes the major limitations of previous work: strict data requirements, insufficient geographical granularity, validation against epidemiological data. - We take as a case study dengue in the Philippines and develop an epidemic risk index; we correct dengue incidence for underreporting based on accessibility to healthcare and show that it correlates well with the risk index (Pearson correlation coefficient 0.69, p-value 0.002). C_LIO_LIWhat Do These Findings Mean? - Our methodology enables the development of disease-specific epidemic risk indices at a sub-national level, even in countries with limited data availability; these indices can guide local actors in programming prevention and response activities. - Our findings on the case study show that the epidemic risk index is a strong indicator of sub-national dengue disease patterns and is therefore suitable for disease risk assessments in the absence of timely and complete epidemiological data. C_LI

ecology↗