Biology subjects

Gomez, A.

Publications and source records attributed to Gomez, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Systematic Functional Interrogation of Neurodevelopmental Disorder Risk Variants

Neurodevelopmental disorders (NDDs) are highly polygenic, yet the functional consequences of most associated non-coding variants remain unclear. We used a massively parallel reporter assay (MPRA) to test 727 NDD-associated non-coding variants in human neural progenitors, identifying 38 expression-modulating variants (emVars) with regulatory activity. These emVars were predicted to alter transcription factor binding motifs linked to neurodevelopmental signaling and cellular metabolism. We mapped emVars to candidate target genes using expression quantitative trait loci and activity-by-contact (ABC) models. We then used CRISPR droplet sequencing (CROP-seq) in human pluripotent stem cell-derived neurons to identify endogenous target genes and characterize their downstream transcriptional effects. CROP-seq preferentially supported ABC predictions, identified additional regulatory relationships, and revealed convergence on developmentally regulated programs involving neuronal connectivity, synaptic function, and mitochondrial biology. Together, these results connect NDD risk variants to endogenous target genes and shared neurodevelopmental transcriptional programs.

genomics↗

bioRxiv2026

Genomes of three Sympatric Species of an Adaptive Radiation: Cyprinodon variegatus, C. desquamator, and C. brontotheroides

Speciation is a central process in evolutionary biology that involves the formation of reproductive barriers between diverging populations. This process can occur through multiple ecological, behavioral, and genetic mechanisms that ultimately lead to changes within a population leading to the formation of distinct species. The relatively young adaptive radiation of Cyprinodon pupfishes in the lakes of San Salvador Island provides a powerful system to study the drivers of speciation in species that exist both sympatrically and allopatrically. The three species; C. variegatus, C. desquamator, and C. brontotheroides, can be found in many lakes on the island, exhibit distinct morphological adaptations relating to feeding, and, when in sympatry, the three species have overlapping habitats and breeding grounds. Species boundaries are maintained by asymmetric mate choice by both males and females, which reinforce extreme fitness costs of hybridization. Here we present high-quality annotated reference genomes for these three species generated using PacBio hifi sequencing. The assemblies resulted in a genome size of approximately 1.2 Gb for each species with most sequences scaffolding into 24 chromosomes with BUSCO analysis indicating a >99% level of completion. The annotation of these three genomes generated over 21,500 protein coding genes with BUSCO analysis indicating a >86 completion. These genomes provide a key resource for studying the genomic architecture of ecological specialization, reproductive isolation in sympatry, and rapid speciation and will facilitate future comparative and population genomic studies on adaptive radiations.

genomics↗

bioRxiv2026

Cytokinesis genes regulate ring canal patterning and follicle cell differentiation in Drosophila

Stable intercellular bridges that form through incomplete cytokinesis are present in a wide variety of cell types but their function in somatic cell differentiation is not well understood. Using super-resolution confocal microscopy, we identified a stepwise process of ring canal development in the follicle cells of the Drosophila ovary. Using a custom-trained deep learning model to aid in 3D image segmentation and follicle cell quantification, we found that ring canals are more heterogeneous at the early prefollicle stages compared to the more differentiated later stages. In addition, we found that depletion of the septin, peanut, caused cytokinetic defects but did not disrupt ring canal formation, whereas depletion of the ESCRT III gene, shrub, increased ring canal number in prefollicle cells and caused proliferation and differentiation phenotypes. Our findings identify cytokinesis and ring canal formation as a point of regulation in the patterning of proliferation and differentiation in the Drosophila follicle stem cell lineage.

cell biology↗

bioRxiv2026

A distributed pallial circuit links sensory and bodily representations to aversive motivational value in the goldfish dorsomedial pallium

Understanding how neural circuits transform sensory and bodily signals into motivational states and adaptive behavior is a central problem in neuroscience. In teleost fish, the dorsomedial telencephalon (Dm) is a key pallial region implicated in both sensory processing and aversive behavior, yet whether these functions arise from a functionally uniform region or from interactions among specialized pallial domains has remained unknown. Here we show that the teleost dorsomedial telencephalon exhibits a previously unrecognized functional organization in which distinct but interconnected pallial domains perform complementary computations that progressively transform multimodal sensory and bodily representations into aversive motivational value and adaptive behavioral control. Wide-field voltage-sensitive dye imaging revealed that tactile, auditory, and gustatory stimuli evoke spatially organized, modality-specific activity exclusively within the caudal subdivision of Dm (Dmc), whereas the rostral subdivision (Dmr) showed little or no sensory responsiveness. In contrast, focal intracerebral microstimulation demonstrated that activation of Dmr, but not Dmc, is sufficient to generate robust, flexible, and reversible conditioned place avoidance, identifying Dmr as a pallial node causally involved in the assignment of negative motivational value. Anatomical tracing revealed a circuit in which sensory and bodily-related inputs converge onto Dmc, are relayed intrapallially to Dmr, where they are transformed into an aversive motivational signal before being conveyed to hypothalamic and brainstem centers involved in autonomic and behavioral regulation. Immunohistochemical analyses confirmed the pallial identity of both subdivisions and their distinct rostrocaudal organization, while providing no evidence that Dm corresponds to a classical pallial amygdaloid territory. This functional architecture more closely resembles the distributed organization of mammalian corticolimbic networks than either a unitary pallial amygdala or a neocortical sensory hierarchy, suggesting that the transformation of sensory and bodily representations into motivational control may represent a conserved organizational feature of the pallium that emerged early during vertebrate evolution. Short abstract / Significance statementThis study shows that the teleost dorsomedial pallium is organized into complementary functional domains that dissociate multimodal sensory representation from negative motivational processing while forming an interconnected pallial circuit associated with adaptive behavioral control. Our findings reveal a distributed pallial organization resembling mammalian corticolimbic architectures and provide a new framework for understanding the evolution of vertebrate pallial function.

neuroscience↗

bioRxiv2026

Spatiotemporal distribution of Delta-like protein 1 during mouse pituitary ontogeny and its relationship with differentiating endocrine cell populations

Delta-like protein 1 (DLK1) is a transmembrane protein involved in the regulation of cellular differentiation and stem cell maintenance in several tissues, including the pituitary gland. Although DLK1 expression has been reported in the adult pituitary, its spatiotemporal distribution during mouse pituitary development remains incompletely characterized. The aim of this study was to analyse the distribution of DLK1 during embryonic and postnatal development of the mouse pituitary gland and to characterize its relationship with hormone-producing cell populations. Immunohistochemistry was performed in Swiss albino mice from embryonic day 9.5 (e9.5) to postnatal day 15 (p15). Double immunofluorescence was used at e18.5 and p15 to examine the association of DLK1 immunoreactivity with ACTH-, TSH-, GH-, FSH- and PRL-producing cells. DLK1 immunoreactivity was detected from the earliest stages of pituitary development in Rathke's pouch and the ventral diencephalon. During embryonic development, DLK1-ir cells were widely distributed throughout adenohypophyseal and neurohypophyseal primordia. As development progressed, DLK1 immunoreactivity became progressively regionalized within the anterior, intermediate and tuberal lobes, as well as in the median eminence of the hypothalamus and the posterior pituitary lobe. Cells displaying overlapping immunoreactivity for DLK1 and all hormone-producing cell populations analysed were observed at e18.5 and p15. Semiquantitative analysis at p15 indicated that approximately 32% of adenohypophyseal cells were DLK1-immunoreactive. These findings provide a detailed description of the spatiotemporal distribution of DLK1 during mouse pituitary ontogeny and suggest that DLK1 immunoreactivity is associated with differentiating endocrine cell populations throughout pituitary development.

Developmental Biology↗

bioRxiv2026

Altered Brain Extracellular Matrix Structure and Sex-Specific Learning/Memory Dysfunction in Mice Lacking the Functional Amyloid Cystatin-Related Epididymal Spermatogenic (CRES)

Cystatin-related epididymal spermatogenic (CRES) is a member of a reproductive subgroup of family 2 cystatins and part of a functional amyloid-containing extracellular matrix (ECM) with host defense functions in the epididymal lumen. CRES and the endogenous epididymal amyloid matrix exhibit high plasticity, forming distinct amyloid structures, with antimicrobial functions tailored to specific bacterial strains. We recently demonstrated that CRES/CRES amyloid is also present in the mammalian brain ECM. In this study, we utilized a CRES knockout (KO) mouse model to determine if the loss of CRES altered the structure of the hippocampal and cortical ECM and impacted brain function. We report that CRES KO male and female mice exhibited sex-specific structural changes in both the loose/interstitial and perineuronal net (PNN) ECM. Additionally, young CRES KO males but not females displayed deficits in learning, memory and executive functioning when compared to WT controls. In contrast, older CRES KO males did not exhibit behavioral deficits, a finding that correlated with the observation of a similar PNN ECM structure when compared to WT mice. Our data suggest that CRES functions as a regulatory or structural component of the brain ECM, contributing to its sex-specific structural organization and plasticity, affecting sex-specific behaviors of learning and memory.

neuroscience↗

bioRxiv2026

Diet-dependent effects of kombucha on the gut microbiome and its neuroactive potential: Associations with reduced anxiety and depressive-like behaviors in mice

Fermented foods are increasingly recognized for their health-boosting potential, yet the mechanisms involved are not fully resolved. Here, we tested whether kombucha reshapes the gastrointestinal microbiome and whether these changes are associated with stress-related behaviors under contrasting dietary backgrounds. Male C57BL/6 mice were fed either a total Western diet (TWD) or a control diet (CTRL) supplemented with kombucha or water three times weekly for seven weeks. Depressive-like and anxiety-related behaviors were evaluated using the forced swimming (FST) and marble burying tests (MBT). Ileum, cecum, and colon microbiomes were profiled via 16S rRNA, ITS2, and shotgun metagenomics, while feces and whole brains were profiled by LC-MS metabolomics. Serum cytokines were measured by ELISA. Results highlight diet-dependent effects of Kombucha on behavioral, microbial and metabolic outcomes. Kombucha reduced immobility in the FST under both diets, whereas fewer marbles buried were observed only under TWD. Kombucha intake enriched Bifidobacterium pseudolongum in the ileum under CTRL and TWD diets, while cecal microbial functions related to amino acid metabolism were stimulated mainly under CTRL. Only CTRL mice receiving kombucha showed higher fecal acetate and butyrate together with lower fecal levels of neurochemically relevant amino acids, including glutamine, phenylalanine, tryptophan, and tyrosine. Under TWD, kombucha was associated with lower spleen weight and altered brain tryptophan/kynurenine profiles. These findings identify kombucha as a food intervention that can remodel gastrointestinal microbial and neuroactive metabolism in a diet depending manner. Associations with reduced depressive and anxiety-related behaviors are promising but warrant further exploration. Key HighlightsO_LIKombucha supplementation reshaped the mice gastrointestinal microbiome and its neuroactive potential C_LIO_LIKombucha intake was associated reduced depressive and anxious like behaviors C_LIO_LIThe potential of kombucha to modulate microbial, metabolic and behavioral outcomes may be dependent on subject dietary background C_LI

microbiology↗

bioRxiv2026

Haplotype-resolved genome of autotetraploid alfalfa (Medicago sativa) Regen-SY27x uncovers large scale structural variation and resistance gene dynamics

Polyploid genome assembly presents unique challenges due to extensive heterozygosity and complex haplotype structure. We report a haplotype-resolved, chromosome-scale assembly of Regen-SY27x, a genotype of autotetraploid alfalfa (Medicago sativa), which is widely used for genetic modification because of its excellent regenerative capacity in tissue culture. Using PacBio HiFi long reads, Omni-C scaffolding, and linkage map guided phasing, we generated a 3.2 GB assembly comprising four haplotypes with high contiguity and completeness. Kmer-based validation confirmed accurate haplotype separation, while linkage map integration and dotplot analysis identified and corrected chimeric scaffolds. Gene annotation yielded 221,688 protein-coding genes, with more than 99% assigned to pseudochromosomes. Repetitive elements accounted for 62.7% of the genome, dominated by long terminal repeat retrotransposons and a high fraction of Helitrons. The spatial enrichment of Helitrons within gene-dense distal chromosome arms underscores their pivotal role as key drivers of genomic innovation and gene family expansion. We identified 3,696 nucleotide-binding leucine-rich repeat R genes, with Toll/interleukin-1 receptor-like and Rx-type subclasses forming large tandem clusters across haplotypes. Comparative analyses revealed strong macrosyntenic conservation among Regen-SY27x and the publicly available Chinese alfalfa genomes but extensive structural variation both within Regen-SY27x haplotypes and between Regen-SY27x and the Chinese genotypes with tens of thousands of duplications, inversions, and translocations detected. These results demonstrate that a single autotetraploid individual captures extensive structural diversity, but individuals from different populations vary greatly. The Regen-SY27x assembly provides a foundational genomic resource for investigating polyploid genome evolution and identifying genetic variation relevant to biological and agronomic improvement in alfalfa. Article SummaryThis study presents the first chromosome-scale, haplotype-resolved genome assembly of the US alfalfa germplasm, Regen-SY27x, a key alfalfa genotype used widely for genetic engineering. We integrated HiFi long reads, Omni-CTM scaffolding, and linkage map-guided phasing to reconstruct all four haplotypes of this complex autotetraploid. Our results identified 221,688 protein-coding genes and reveal immense intra-individual structural variations dominated by small duplications. This high-quality reference serves as a foundational tool for the alfalfa community, enabling researchers to link complex structural diversity with agronomic traits and further enhance the biotechnological potential of this essential forage crop.

genomics↗

bioRxiv2026

SENSORY MAPS IN THE TELENCEPHALIC PALLIUM OF GOLDFISH.

The functional organization of the teleost telencephalic pallium remains poorly understood, particularly regarding the presence of modality-specific sensory domains and their topographic arrangement. Here, we used in vivo wide-field voltage-sensitive dye imaging to map sensory-evoked neural activity across the dorsal surface of the telencephalic pallium of adult goldfish. Somatosensory, auditory, gustatory, and visual stimulation revealed distinct, modality-specific domains primarily located within the dorsomedial (Dm) and dorsolateral (Dl) pallium. Within Dm, somatosensory and auditory stimuli activated partially overlapping territories in the caudal subregion (Dm4), exhibiting clear somatotopic and tonotopic organization along the mediolateral axis. Gustatory stimulation selectively engaged Dm3, where different tastants activated spatially distinct but partially overlapping domains. A more rostral subregion (Dm2) responded only to high-intensity somatosensory stimulation, suggesting involvement in processing negatively valenced inputs. Visual stimulation activated a circumscribed area within the dorsolateral pallium (Dld2),that closely matched cytoarchitectural boundaries. Pharmacological blockade of ionotropic glutamate receptors markedly reduced sensory-evoked responses, indicating that these maps depend on glutamatergic synaptic transmission. Together, these findings show that the goldfish pallium contains distinct, spatially organized sensory representations and a refined internal functional architecture. This organization suggests that pallial topographic sensory maps may not be exclusive to mammals and birds. Based on these results, we propose that dorsomedial and dorsolateral pallial regions may be functionally comparable to components of the mammalian mesocortical network, more than to the pallial amygdala or the neocortex. This framework provides a new perspective on pallial organization in teleosts and contributes to understanding the evolutionary origins of the vertebrate pallium. HIGHLIGHTSO_LIVoltage-sensitive dye imaging was used to map sensory responses in the goldfish pallium. C_LIO_LIDistinct sensory areas for somatosensory, auditory, gustatory, and visual modalities were identified. C_LIO_LISome sensory regions in Dm show topographically organized maps. C_LIO_LIFunctional segregation suggests a complex, non-diffuse pallial organization. C_LIO_LIFindings support a novel hypothesis linking Dm and Dld to mammalian mesocortical regions. C_LI

neuroscience↗

bioRxiv2026

The City Nature Challenge increases urban biodiversity knowledge and public engagement with blue spaces

Global biodiversity is declining at an unprecedented rate due to rapid environmental change and increasing human pressures. Ongoing urban expansion fragments natural systems, while urban design increasingly seeks to mitigate these impacts through the integration of blue-green infrastructure. Effective biodiversity monitoring is therefore essential to evaluate ecological conditions within these novel socio-ecological systems. Although urban biodiversity monitoring is challenged by its high landscape heterogeneity, dense human populations provide opportunities for large-scale data collection through public participation in citizen science. Using data from 25 City Nature Challenge (CNC) projects across the United Kingdom (2020-2025), we assessed the effects of the four-day bioblitz on species inventories, participation in biological recording, and spatial patterns of recording effort. CNC events doubled public participation in iNaturalist recording relative to baseline activity, leading to the documentation of numerous previously unrecorded species through increased observer effort and broader use of urban blue-green spaces. These results show that CNC events enhance urban biodiversity datasets by increasing the number of observers and reducing spatial and observer biases, providing a cost-effective tool for enriching urban biodiversity data. In addition to generating ecological data, CNC events could have public health benefits through increased exposure to urban blue-green spaces.

ecology↗

bioRxiv2026

Engineering the Self-assembly of Bacterial Microcompartment Shell Proteins via Charged Mutations

AbstractProtein self-assembly is a fundamental biological process of great importance for the design and synthesis of biomaterials. Developing the ability to precisely manipulate protein assembly would greatly expand both our understanding of the process and our biotechnological capabilities. Within bacteria, proteins that self-organize to form bacterial microcompartments (MCPs) offer an excellent model system for studying protein self-assembly and advancing biomaterial design capabilities. MCPs consist of irregular polyhedral shells that encase an enzyme core, functioning as enzymatic nanoreactors. In isolation, the abundant shell proteins of the 1,2-propanediol utilization (Pdu) MCP, PduA and PduJ, have a high propensity to self-assemble into tubular structures, analogous in form to carbon nanotubes. Here, we design and characterize tubular structures formed by hexameric PduA and PduJ proteins. We demonstrate that altering hexamer charge offers a systematic strategy for modulating the higherorder assembly of PduA and PduJ across multiple contexts by integrating molecular dynamics simulations with heterologous overexpression, cell-free, and in vivo Salmonella enterica serovar Typhimurium LT2 experiments. First, using molecular simulation, we find that tube chirality and radius play critical roles in determining structural stability and flexibility. Next, overexpression and cell-free experiments show that increasing the overall negative charge of assembling subunits consistently promotes self-assembly into tubular structures. We find that this holds true in the native MCP system, as these same mutations promote the formation of tubular MCP structures in S. enterica LT2. Our results collectively reveal that both electrostatic interactions and fields generated by charges on proteins can be leveraged to control protein-based nanostructures.

biochemistry↗

bioRxiv2025

Priority effects drive fungal and nematode emergence from insect larvae

Priority effects, in which species arrival history influences community assembly, are increasingly recognized to affect host-parasite systems. However, priority effects across disparate groups of parasitic organisms are poorly understood despite the wide range of taxonomic groups involved. In California oak woodland, we investigated how priority effects between two insect-parasitic fungi (Metarhizium and Beauveria) influenced emergence of nematodes from insect larvae. Field and laboratory results indicated that both fungi were common, but priority effects prevented them from co-emerging from the same larva. Metarhizium- and Beauveria-infected insects did not differ in the species composition of emerging nematodes, but larvae without fungal emergence had distinct nematode communities, with Oscheius almost always emerging without fungi. Experiments indicated that none of the commonly found nematodes (Acrobeloides, Mesorhabditis, Oscheius, and Rhabditis) were entomopathogenic, but that Oscheius could exclude Beauveria if arrived early. This time-dependent exclusion was likely caused by an Ochrobactrum bacterium that Oscheius nematodes carried. Together, these findings suggest that fungi enter insects as primary arrivers, while nematodes come as secondary arrivers to exploit fungus-killed insects, with priority effects influencing both groups. We suggest that this system is a promising natural microcosm for understanding priority effects across disparate groups in host-parasite systems.

ecology↗

bioRxiv2025

Pupation substrate and prepupal handling affect eclosion rate, timing, and adult morphology in black soldier flies (Hermetia illucens; Diptera: Stratiomyidae)

On farms, the conditions experienced by black soldier fly (BSF) prepupae may impact their development and survival, altering production goals by changing the fitness of breeding adults. Few studies have addressed the impact of environmental variables (such as substrate type or moisture content), or stressors like handling, on the development and survival of BSF as they transition from prepupae through adulthood. This study examined the effects of pupation substrate (corn cob grits, potting soil, vermiculite, wood chips, and frass), moisture content (20%, 60%, and 100%), and handling during the prepupal period (daily handling, no handling) on eclosion rate and timing, morphology (mass, head width, thorax length), and abdominal window fullness of adult BSF. Handling delayed adult emergence by over three days, reduced eclosion rates by 30.6%, reduced head width and wet mass in adult males, and reduced window fullness and head width in adult females. Frass resulted in the lowest eclosion rate (72.1 {+/-} 2.4%) while corn cob grits (82.2 {+/-} 2.3%) and wood chips (81.5 {+/-} 2.2%) had the highest. Wood chips also resulted in the highest wet and dry mass, head width, and thorax length for adult males and females. Wood chips may be the best pupation substrate for BSF as it enhances body size and has a good eclosion rate. Significant prepupal handling delays adult emergence, reduces eclosion/survival rates, and reduces adult body size; however, more research is necessary to determine if the less chronic handling regimes that are likely present on farms produce similar effects.

zoology↗

bioRxiv2025

BASP1 Couples Ca2+ Signaling and Actin Polymerization to Mitochondrial Fission Essential for Neurite Outgrowth

Actin-mediated mitochondrial fission is essential for cellular homeostasis, yet the mechanisms by which actin is recruited to mitochondria and how it couples the outer and inner mitochondrial membranes (IMM) remain poorly understood. Using a phosphoproteomic screen in a rat model of -synucleinopathy, we identified BASP1 as a calcineurin-dependent substrate that is constitutively dephosphorylated under pathological Ca2+ elevations and phosphorylated under neuroprotective calcineurin inhibition. Immunoprecipitation and mass spectrometry of phosphomutant BASP1 expressed in neurons revealed that dephosphorylation promotes interactions with actin and IMM proteins. Dephosphorylated BASP1 recruits actin to mitochondria, while subsequent phosphorylation enables actin-mediated mitochondrial fission and neurite elongation. Constitutive dephosphorylation, as it occurs in -synucleinopathy, impairs mitochondrial fission, inhibits neurite growth and promotes -synuclein aggregation. Our findings position BASP1 as a Ca2+-CaN-regulated hub that coordinates actin remodeling and couples mitochondrial membranes to drive fission, revealing a mechanistic axis linking mitochondrial dysfunction to neuronal morphogenesis and -synuclein pathobiology.

cell biology↗

bioRxiv2025

Single-cell mass accumulation reveals bacterioplankton growth rate in native seawater

AO_SCPLOWBSTRACTC_SCPLOWThe growth of marine microbial communities drives biogeochemical cycling of carbon and other elements, yet the growth rates of individual species within complex ocean ecosystems remain poorly understood. In particular, the coexistence of a large diversity of copiotrophic bacteria, which are capable of fast growth but typically remain at low abundance, has been interpreted as a feast or famine existence. Here we show that contrary to the notion of infrequent growth, Vibrio bacteria exhibited consistent growth rates in coastal ocean samples, despite representing only a small fraction of the total community. These observations were enabled by a suspended microchannel resonator (SMR), which we adapted to function as a single-cell chemostat. By maintaining a continuous supply of native seawater around each trapped cell, we prevented nutrient depletion and used the SMRs high mass precision to resolve growth rates that are otherwise undetectable. Vibrio species displayed significantly larger cell mass and faster growth than other community members across samples collected at different temporal intervals from days to years. Surprisingly, their growth was consistently limited by carbon, contrary to the expectation that heterotrophic bacteria in the euphotic zone would be limited by nitrogen and phosphorus due to competition with algae. The correlation between cell mass and growth rate of Vibrionaceae in seawater followed established growth laws derived from laboratory conditions, suggesting that growth physiology observed in pure cultures is applicable to wild bacterial populations. Overall, our findings suggest that rare species may play a disproportionately large role in the marine carbon cycle, with rapid biomass turnover driven by a combination of high growth rates balanced by intense predation.

microbiology↗

bioRxiv2025

The Functional Epididymal Amyloid Cystatin-Related Epididymal Spermatogenic (CRES) is a Component of the Mammalian Brain Extracellular Matrix

CRES is the defining member of a reproductive subgroup of family 2 cystatins of cysteine protease inhibitors. We previously showed that CRES and other subgroup members are part of a highly plastic amyloid-containing extracellular matrix (ECM) with host defense functions in the mouse epididymal lumen. Based on parallels between the epididymis and the brain, we hypothesized that CRES and CRES amyloids might also function within the brain including the ECM. Here we show that CRES is produced by hippocampal neurons and astrocytes in the male and female mouse and human brain. Further, approximately 50% of hippocampal astrocytes from aged mice, like the aged human donor samples, had significantly reduced levels of CRES compared to younger mice, suggesting an age-related decline in CRES could contribute to altered brain function. Immunofluorescence experiments showed CRES colocalized with the ECM markers phosphacan and wisteria floribunda agglutinin indicating that CRES is part of the ECM. CRES monomer and high molecular weight SDS-resistant forms were found in insoluble fractions of the hippocampus, cortex, cerebellum, and midbrain and bound to the protein aggregation disease (PAD) ligand, which preferentially binds amyloids but not protein monomers, suggesting a population of CRES exists in the brain as an amyloid structure. Collectively, our studies demonstrate that CRES/CRES amyloid is present in the mammalian brain and may contribute to ECM structure and function. Significance StatementWe previously established that the cystatin-related epididymal spermatogenic (CRES) protein is part of an amyloid-containing extracellular matrix (ECM) that protects the male germline in the epididymal lumen. Here we demonstrate that CRES is present within the mouse and human brain. Using cell biological and biochemical approaches, we show that CRES is found in hippocampal astrocytes and specific neuronal populations, including those that possess perineuronal nets, and colocalized with ECM markers suggesting it is part of the ECM. Biochemical analyses suggested a population of CRES is present as an ordered amyloid structure. Our studies reveal CRES is present in the male and female mammalian brain and may contribute to brain structure and function as a biological amyloid. Keyword: hippocampus, mouse, human, plasticity

neuroscience↗

bioRxiv2025

PULPO: Pipeline of understanding large-scale patterns of oncogenomic signatures

Short Structured AbstractO_ST_ABSSummaryC_ST_ABSPULPO v1.0 is a novel, fully automated pipeline designed for the preprocess and extraction of mutational signatures from raw Optical Genome Mapping (OGM) data. Built using Snakemake and executed within an isolated, Conda-managed environment, PULPO transforms complex cytogenetic alterations, captured at ultra-high resolution, into Catalogue of somatic mutations in Cancer (COSMIC)-based mutational signatures. This innovative approach not only enables researchers to work directly from raw OGM inputs but also streamlines the traditionally complex process of signature extraction, making advanced oncogenomic analyses accessible to users with varying levels of bioinformatics expertise. By facilitating the integration of comprehensive structural variants (SVs) and copy number variants (CNVs) data with established signature catalogs, PULPO paves the way for improved diagnostic accuracy and personalized therapeutic strategies. Availability and ImplementationThe pipeline is open source and freely available under the MIT License at https://github.com/OncologyHNJ/PULPO.

bioinformatics↗

bioRxiv2025

Just add water: Urban blue spaces increase avian richness and functional diversity

Urban blue spaces are highly valuable for both people and nature, providing key ecosystem services, including flood alleviation, pollution absorption, microclimate regulation, benefits to human health and wellbeing, and habitat provision. Crucially, urban blue spaces support biodiversity, including threatened species, and despite often being small, may have disproportionate effects on their surrounding environment, acting as critical habitats within urban systems. However, research on the role of urban blue spaces within ecological contexts remains limited. Here, we assessed urban bird communities across green and blue spaces to quantify the ecological effects of urban water bodies. We surveyed birds along 22 paired 1 km transects in the city of Kingston Upon Hull, UK, recording species and abundance across both winter and breeding seasons. Our findings indicate that blue spaces significantly increase bird species richness during summer (P = 0.016), though not in winter. However, we found that the taxonomic distinctiveness of bird communities is consistently greater around blue spaces across both seasons (P < 0.05). Similarly, functional diversity based on species-level ecological traits was more varied around water (P = 0.01). In addition, we show that urban blue spaces could be important for avian conservation, supporting more red and amber-listed species than green spaces during the summer (P = < 0.05). Overall, our results show that urban blue spaces play a critical ecological role within cities by enhancing the complexity of avian communities, which in turn could improve human wellbeing and contribute to urban sustainability.

ecology↗