Biology subjects

Endo, H.

Publications and source records attributed to Endo, H..

At least 19 recordsLinked to original sources

bioRxiv2026

Dietary phosphorus restriction enables multigenerational breeding of α-Klotho-deficient rats

Severe -Klotho deficiency causes early mortality and reproductive impairment, limiting the maintenance and physiological analysis of rat models. We generated rats carrying a CRISPR/Cas9-mediated -Klotho deletion spanning exons 1-5 and evaluated dietary phosphorus restriction primarily in the Wistar-Imamichi background. Maternal low-phosphorus (LP) feeding from mating through lactation was associated with higher overall survival to weaning (92.6% versus 85.8% under normal-phosphorus conditions) and a higher proportion of KO animals among weaned survivors (34/113 versus 23/145). Maternal LP feeding also reduced plasma phosphorus in KO pups. Continued LP feeding after weaning supported growth, gonadal development, and natural KO x KO breeding. Across 15 litters, 74 of 85 offspring survived to weaning, and KO colonies were maintained to at least the fifth generation. We additionally characterized 24-h metabolic rhythms in LP-maintained KO animals using indirect calorimetry. These profiles remained heterogeneous under a light-dark cycle. In conclusion, dietary phosphorus restriction provides a reliable strategy for the multigenerational maintenance of severe -Klotho-deficient rats, establishing a maintainable model to investigate residual metabolic and physiological phenotypes.

physiology↗

bioRxiv2026

Long read multi-omics sequencing reveals DNA-to-RNA evolutionary remodeling trajectories of recurrent astrocytoma

Astrocytoma recurrence is shaped by genetic, epigenetic and transcriptional evolution, but how DNA remodeling is propagated into full-length RNA isoforms and coding consequences remains poorly resolved. Here we applied paired PacBio HiFi whole-genome sequencing and Kinnex full-length RNA sequencing to matched primary and recurrent astrocytoma from six patients, with matched blood controls. Recurrent tumors preserved core glioma driver identity while acquiring patient-specific remodeling across somatic variants, copy number, structural variation, loss of heterozygosity, haplotype imbalance and DNA methylation. Long-read transcriptomics revealed extensive recurrence-associated gene-expression, isoform-usage, differential transcript-usage and predicted ORF/protein-fate remodeling beyond gene-level expression. A denominator-aware integration framework showed that copy-number changes provide broad RNA-dosage links, whereas expressed somatic variants, allele/haplotype-specific transcript usage, methylation-linked isoform remodeling and structural variants generate more focused DNA-RNA-ORF chains. These findings establish longitudinal long-read multi-omics as a framework for prioritizing patient-specific remodeling trajectories and identifying targets for precision medicine in recurrent astrocytoma.

cancer biology↗

bioRxiv2026

Standardizing image-derived fish length-frequency distributions to reference measurements using bin-specific error matrices

Artificial intelligence (AI)-based image analysis can efficiently estimate fish length, but differences in devices, imaging conditions, operators, and AI models limit comparability among surveys. We propose a standardization framework that estimates a bin-specific error matrix from paired reference measurements and AI-derived lengths and applies it to standardize (correct) AI-derived length-frequency distributions. The Richardson-Lucy expectation-maximization algorithm was used, with the number of iterations selected via cross-validation. Simulations based on empirical length-frequency data from 110 species showed that standardization reduced relative bias and distributional discrepancy; median relative-bias and root mean square error ratios were below 1, and the performance was more affected by the amount of paired data than by the number of cross-validation folds. In real data from 957 Japanese jack mackerel, standardized AI-derived distributions approached human-observer histograms, although discrepancies remained in the range of 160-230 mm. The proposed framework provides a practical approach for improving the comparability of image-derived length-frequency data using paired calibration data, without retraining the underlying AI model.

ecology↗

bioRxiv2026

Metatranscriptome data support the existence of two distinct morphotypes in a single parmalean species in natural environments

Parmales (Bolidophyceae), the closest relatives of diatoms, includes isolates exhibiting one of two distinct morphotypes: a silicified non-flagellated form (S-type) and a naked flagellated form (F-type). Although alternation of these two forms for a single isolate has not been formally established, previous studies hypothesized that these morphotypes represent alternating stages of a single parmalean. In this study, we investigated the global expression patterns of S- and F-type marker genes by integrating parmalean Metagenome-Assembled Genomes (MAGs) and the metatranscriptomic dataset from Tara Oceans. We detected the expression of both S- and F-type marker genes from individual environmental MAGs. This finding provides the first metatranscriptomic evidence that natural parmalean genomes possess the potential to manifest both morphotypes. Furthermore, our analysis revealed different geographical expression patterns between the two forms. The expression of F-type markers showed a broad distribution, whereas that of S-type markers was more restricted, suggesting distinct niches for the two morpho-phases. Moreover, S-type gene expression appears to require specific environmental triggers that lead to a higher population density, whereas F-type expression is rather constitutively maintained. Overall, our results support the hypothesis of a life cycle involving morphological switching and reconcile the long-standing discrepancy between the ubiquity of parmaleans in molecular surveys and the limited geographical range for the observation of silicified cells. Based on these patterns, we propose a threshold-based model in which F-type-dominated populations persist under conditions unfavorable for growth and a morphological switch to the S-type is triggered once environmental conditions exceed a critical threshold for growth.

microbiology↗

bioRxiv2026

Rapid diversification of a natural Heterosigma akashiwo virus population during a host bloom

Despite the ecological importance of viruses, our understanding of their evolutionary dynamics in natural environments remains limited. This gap is particularly pronounced for giant dsDNA viruses of the phyla Nucleocytoviricota and Mirusviricota. Most knowledge on their population genetic dynamics is derived from a small number of laboratory-based experiments, whereas patterns in nature are rarely observed. To overcome this limitation, we traced genetic structure and transcription status of Heterosigma akashiwo virus (HaV) using high-frequency, time-resolved sampling during a host bloom in a coastal area of Japan, by integrating cell counting, metabarcoding, metagenomic and metatranscriptomic sequencing. Our study revealed that HaV dominated the giant virus community in most samples, with the relative abundances of up to 56%. Despite the high abundances, the HaV population exhibited a relatively low level of microdiversity but with a high pN/pS ratio compared to other giant viruses in the study site. Microdiversity increased during the early sampling period, reached a maximum at mid-sampling, and decreased during the later period, consistent with rapid diversification during viral expansion, possibly driven by both in situ mutations and the succession of pre-existing minor variants. Several accessory genes, including a glycosyltransferase and an endonuclease, were highly expressed, providing functional evidence consistent with host interaction-driven selective pressure during the bloom. Together, these results indicate that HaV population dynamics during algal blooms are shaped by host-driven selection acting on standing genetic variation.

ecology↗

bioRxiv2025

Multiscale modeling of blood circulation with cerebral autoregulation and network pathway analysis for hemodynamic redistribution in the vascular network with anatomical variations and stenosis conditions

Cerebral hemodynamics is fundamentally regulated through the Circle of Willis (CoW), which redistribute flow via communicating arteries to stabilize perfusion under anatomical variations and vascular stenosis. In this study, a multiscale circulation model was developed by coupling a multiscale systemic hemodynamic framework with cerebral arterial network reconstructed from medical imaging. The model integrates a cerebral autoregulation mechanism (CAM) and enables quantitative simulation of flow redistribution across the CoW under normal, anatomically varied, and pathologically narrowing (stenosis) conditions. Baseline simulations at normal states reproduced physiological flow distributions in which the communicating arteries remained nearly inactive, showing negligible across-flow and agreement with clinical measurements, while two anatomical variations revealed distinct collateral activation patterns: the anterior communicating artery (ACoA) acted as the earliest and most sensitive functional collateral pathway, whereas the posterior communicating arteries (PCoAs) exhibited structure-dependent engagement. Progressive stenosis modelling further demonstrated the transition from a complete CoW to a fetal-type posterior cerebral artery (PCA) configuration, with early ACoA flow reversal followed by the ipsilateral PCoA activation, in agreement with experimental and transcranial Doppler observations. We further present a path-based quantitative analysis of source-to-sink flow contributions to quantitatively illustrates how the cerebral vascular network dynamically reconfigures collateral pathways in response to structural changes. Overall, the proposed framework provides a physiologically interpretable and image-informed tool for investigating cerebral flow regulations through the functional collaterals within the CoW, offering potential for clinical applications in the diagnosis, prognosis, and treatment planning of cerebrovascular diseases.

biophysics↗

bioRxiv2025

ALKBH1 drives codon-biased, pro-oncogenic translation and tumor microenvironment remodeling in glioma via tRNA wobble oxidation

Gliomas rely on translational plasticity to sustain heterogeneity, stemness, and immune evasion. Here we identify the tRNA dioxygenase ALKBH1 as a central regulator of codon-biased translation and tumor microenvironment remodeling. LC-MS/MS profiling of patient tumors revealed enrichment of ALKBH1-mediated wobble cytidine oxidation modifications in high-grade gliomas. Genetic perturbation demonstrated that ALKBH1 overexpression slows proliferation in vitro but worsens survival in vivo by promoting glioma stem-like and neuronal states and suppressing anti-tumor immunity. Ribosome profiling showed that ALKBH1 establishes an A/T-ending codon-biased translational program, enhancing decoding of rare leucine codons (TTA/TTG) and driving synthesis of pro-stemness transcripts. Single-cell RNA-seq analyses further revealed that ALKBH1 promotes glioma heterogeneity and induces neuronal cell clusters and rewires intercellular communication ECM-related signaling while dampening immune pathways and reducing immune infiltration. These findings establish a mechanistic link between tRNA oxidation, codon bias, and glioma aggressiveness, positioning ALKBH1 as a potential therapeutic target for glioma.

cancer biology↗

bioRxiv2025

Divergent evolution of insecticidal protein families across bacteria and ferns

Insecticidal Cry proteins produced by the bacterial insect pathogen Bacillus thuringiensis possess conserved three domains (3D). Two other families of insecticidal proteins--Prb proteins from bacterial symbionts of entomopathogenic nematodes and a marine bacterial pathogen, and IPD113 proteins from ferns--are two-domain (2D) proteins structurally resembling domains I and II of Cry proteins. Despite the structural resemblance, the amino acid sequence identity among these families is only [~]10%, supporting the prevailing view that they evolved independently through convergent evolution. However, the possibility of remote homology and ancient horizontal gene transfer (HGT) has remained largely unexplored. Here, we present evidence supporting divergent evolution of these protein families. We found that proteins containing Cry-like two domains are distributed far more broadly across bacteria, eukaryotes, and archaea than previously recognized. Phylogenetic analyses separated the structurally similar proteins into five clades including Cry, IPD113, Prb, and 2D/3D-mixed clades. Domain-level trees revealed intermixing within domain II, with nematocidal Cry proteins frequently clustering with IPD113 and 2D/3D-mixed clades, suggesting domain swapping events across these clades. Conserved amino acid motifs and domain core structures across clades further support a shared evolutionary origin. Phylogenetic and structural analyses suggest a bacterial origin of the fern IPD113 gene and its horizontal transfer via fungal symbionts, as well as multiple HGT events into diverse terrestrial and marine eukaryotes and archaea. This work redefines the evolutionary landscape of the insecticidal protein families, revealing their unexpectedly wide taxonomic distribution, possibly shaped through bacterial ecological networks and close biological interactions such as symbiosis.

molecular biology↗

bioRxiv2025

Whole-Brain Millisecond-Scale Effective Connectivity Atlas of Auditory and Visual Naming

Neurobiological models suggest that speech relies on interactions among distant cortical regions interconnected by white matter pathways. Prior studies have shown that speech-related functional coactivation--simultaneous high-gamma augmentation across distributed regions--reflects underlying neural interactions, as validated by electrical stimulation mapping. However, it remains unclear at the whole-brain level when, for how long, and in which directions cortical regions transmit information, and how dynamic information flows contribute to speech. Here, we investigated the causal roles of directional neural information flow during auditory and visual naming using intracranial EEG from 9,526 artifact-free nonepileptic sites across 127 patients. Information flow, estimated by transfer entropy-based effective connectivity, was classified as excitatory when high-gamma acceleration in one region predicted subsequent acceleration in another, and inhibitory when deceleration predicted downstream deceleration. Following stimulus onset, excitatory flows emerged from modality-specific sensory cortices and propagated to higher-order regions, later becoming bidirectional as functional coactivation developed. Each excitatory flow event was transient (<500 ms), typically followed by inhibitory flows and decreased coactivation, during which excitatory flows often emerged along new pathways. During auditory naming, faster response times were associated with stronger excitatory flows in left perisylvian regions; during visual naming, faster responses were linked to stronger flows in bilateral basal temporal cortices. Stronger excitatory flows at specific time points predicted a higher probability of stimulation-induced symptoms (Spearmans rho: 0.54-0.81; p<0.00001), whereas associations with inhibitory flows peaked later. Excitatory flows near visual naming response onset were particularly associated with stimulation-induced speech arrest and face sensorimotor symptoms, whereas functional coactivation alone failed to reveal comparable associations. These findings demonstrate that transient acceleration of directional neural interactions through white matter supports successive stages of speech processing. As activity within one pathway decelerates, excitatory flow accelerates along another, enabling functional transitions critical for naming. By establishing the causal contribution of temporally precise, anatomically specific white matter pathways, this study substantiates and extends existing neurobiological models of speech. To facilitate replication and dynamic whole-brain visualization, we provide open access to the full dataset (62.15 GB) and analysis code.

neuroscience↗

bioRxiv2025

Temporal dynamics of mRNA translation dysregulation and codon decoding during murine stroke evolution.

Ischemic stroke imposes acute oxidative and metabolic stress, yet how this reshapes mRNA translation remains poorly defined. We generated a time-resolved RNA-seq and ribosome-profiling atlas of mouse ischemic cortex at 1, 6 and 24 hours. Stroke produced early discordance between mRNA abundance and ribosome occupancy, revealing translational efficiency changes not captured by transcriptomics. The hyperacute phase was marked by a transient shift toward G/C-ending codon usage and a burst of 3' untranslated region ribosome footprints consistent with stop-codon readthrough-like termination stress. Machine-learning analyses linked this response to stop-proximal ribosome queuing, 3' untranslated region frame usage, local RNA structure and transcript architecture rather. From 6 to 24 hours, ischemic cortex developed progressive A-site pausing and altered coding-frame occupancy. Hidden Markov modeling localized a subset of frame-disruption events to discrete coding-sequence windows and machine learning revealed reproducible codon, amino-acid, nucleotide-composition and RNA-structure features associated with frameshifting. ORF-level analyses showed that many frame changes coincided with differential open reading frame usage. Late injury was characterized by increased upstream open reading frame engagement and 5' untranslated region ribosome occupancy, inversely correlating with coding-sequence translation. These data identify staged translational remodeling after stroke that could not be captured via traditional mRNA or protein expression analysis.

molecular biology↗

bioRxiv2025

Dynamic Causal White Matter Atlas of Auditory and Visual Speech Networks at Millisecond Resolution: Intracranial Evidence from 125 Patients

Background and ObjectivesSince the era of Penfield, invasive neurophysiology has laid a lasting foundation for functional neuroscience by elucidating brain regions necessary for speech. However, whole-brain investigations have yet to distinguish the millisecond-scale dynamics and specific white matter pathways that support rapid naming in the auditory and visual domains. MethodsIn this observational study, we constructed a whole-brain Dynamic Causal Tractography atlas using intracranial neurophysiological data from 125 neurosurgical patients. The resulting video atlas captured local cortical high-gamma activity and cortico-cortical coactivation via white matter tracts during rapid and delayed auditory and picture naming. Direct electrical stimulation was employed to assess the causal significance of the observed neural dynamics. ResultsThe atlas revealed white matter coactivation intensity patterns at specific 5-millisecond time windows that best aligned with sensorimotor and language symptoms elicited by electrical stimulation (Spearmans {rho} = 0.58-0.91; p = 4.8 x 10cc to 1.6 x 10c{superscript 2}c). Rapid auditory naming was associated with deactivation of the right rostral middle frontal gyrus and increased coactivation along the left arcuate fasciculus, linked to stimulation-induced receptive and expressive aphasia. In contrast, delayed auditory naming correlated with a late surge in bifrontal coactivation. Rapid picture naming involved early coactivation between cortices connected via the bilateral inferior longitudinal fasciculi--associated with stimulation-induced visual distortions--coinciding with transient co-inactivation of Brocas area. DiscussionThese findings delineate dissociable white matter-mediated mechanisms supporting rapid naming in the auditory and visual domains. Reduced inhibitory monitoring by the right dorsolateral prefrontal cortex may facilitate efficient lexical retrieval via left perisylvian pathways during auditory naming. In contrast, excessive bifrontal interaction may underlie delayed auditory naming. Rapid visual object recognition appears to rely on early occipitotemporal coactivation with minimal involvement of Brocas area. The resulting atlas--accompanied by a publicly available dataset (61.2 GB) and analysis code--serves as a valuable resource for students and trainees studying the network dynamics underlying speech, as well as for presurgical language mapping in patients undergoing cortical or subcortical intervention.

neuroscience↗

bioRxiv2025

Giant viruses specific to deep oceans show persistent presence and activity

Giant viruses (GVs) of the phyla Nucleocytoviricota and Mirusviricota are large double-stranded DNA viruses that infect diverse eukaryotic hosts and impact biogeochemical cycles. Their diversity and ecological roles have been well studied in the photic layer of the ocean, but less is known about their activity, population dynamics, and adaptive strategies in the aphotic layers. Here, we conducted eight seasonal time-series samplings of the surface and mesopelagic layers at a coastal site in Muroto, Japan, and integrated 18S metabarcoding, metagenomic, and metatranscriptomic data to investigate deep-sea GVs and their potential hosts. The analysis identified 48 GV genomes including six that were exclusively detected in the mesopelagic layer. Notably, these mesopelagic-specific GVs showed persistent activity across seasons. To investigate the global deep-sea-specific GV distribution, we compiled GV reference genomic data from the OceanDNA MAG project and other resources, and analyzed 1,890 marine metagenomes. This revealed 101 deep-sea-specific GVs, distributed across the GV phylogenetic tree, indicating that adaptation to deep-sea environments has occurred in multiple lineages. One clade enriched with deep-sea-specific GVs included one GV identified in our Muroto sampling, which displayed a wide geographic distribution. Seventy-six KEGG orthologs and 74 Pfam domains were specifically enriched in deep-sea-specific GVs, encompassing functions related to the ubiquitin system, energy metabolism, and nitrogen acquisition. These findings support the scenario that distinct GV lineages have adapted to hosts in aphotic marine environments by altering their gene repertoire to thrive in this unique habitat. IMPORTANCEGiant viruses are widespread in the ocean surface and are key in shaping marine ecosystems by infecting phytoplankton and other protists. However, little is known about their activity and adaptive strategies in deep-sea environments. In this study, we performed metagenomic and metatranscriptomic analyses of seawater samples collected from a coastal site in Japan and discovered giant virus genomes showing persistent transcriptional activity across seasons in the deep-sea water. Using a global marine dataset, we further uncovered the widespread existence of deep-sea-specific giant viruses and characterized their unique gene repertoire, which likely facilitates adaptation to the limited availability of light and organic compounds in the aphotic zone. These findings expand our understanding of giant virus ecology in the dark ocean.

genomics↗

bioRxiv2025

Metabolic reprogramming of protists within the microbiome of sinking particles

Protists play a crucial role in the biological carbon pump, yet their metabolic activity and function in sinking particles, which drive the aggregation and degradation of organic carbon, remains poorly characterized. Here, we examined transcriptional dynamics of protists in sinking and suspended particles collected by marine snow catcher in the Oyashio region to explore active lineages and their function during the sinking export. We found taxon-specific metabolic variations, with suspended particles showing up-regulated transcripts from diatoms, haptophytes, and chlorophytes, while sinking particles exhibited those from diatoms, ciliates, and dinoflagellates. Our data further revealed niche-dependent cellular metabolic reprogramming. The small diatoms Minidiscus variabilis and Thalassiosira oceanica upregulated more genes in suspended particles, while the chain-forming Thalassiosira rotula overexpressed more genes in sinking particles. The activity of both phototrophic and heterotrophic protists in sinking particles suggests the export of fresh organic carbon, with heterotrophic protists driving its degradation. Notably, the dinoflagellates Karlodinium veneficum and Karenia brevis exhibited significantly upregulated genes related to feeding and carbon metabolism in sinking particles. Additionally, the activity of RNA viruses was positively correlated with carbon flux. Overall, our study highlights the critical role of large-celled diatoms, heterotrophic dinoflagellate, ciliates and RNA viruses in organic carbon aggregation and degradation.

microbiology↗

bioRxiv2025

Non-DNA-damaging DNA-PK activation improving hearing and prolonging life due to NAD+ and SIRT upregulation

Emerging evidence strongly supports a close relationship between age-related hearing loss and frailty, highlighting the importance of early detection and intervention. Recently, we invented a mitochondria-homing drug named mitochonic acid 5 (MA-5), that increases the adenosine triphosphate (ATP) levels, rescue mitochondrial function, and protect tissue damages. Currently, the phase I clinical trial has been finished in Japan (jRCT2031210495) and the phase 2 clinical trial has already been approved by PMDA. Here we show that MA-5 improved various types of hearing loss in mouse models. Structural chemical bioanalysis revealed that MA-5 is a mixture of equal amount of S- and R- enantiomer and both S- and R- enantiomer increase ATP by binding mitochondrial protein, mitofilin. However, S-enantiomer significantly increased the NAD+ levels by binding to the NAD+-producing key enzyme nicotinamide phosphoribosyltransferase (NAMPT). Moreover, the S-enantiomer increased the sirtuin 1 protein by suppressing polyubiquitination induced by tripartite motif containing 28 (TRIM28) phosphorylation which was triggered by DNA-dependent protein kinase (DNA-PK) activation in the absence of DNA damage. Transcriptomic signatures showed that the signature of MA-5 shows an inverse correlation with aging and mortality and is oriented in the same direction as the OSKM-related iPSCs, suggesting the modification of aging pathways. Oral administration of MA-5 to mitochondrial disease model mouse showed increased survival. Our findings suggest that, in addition to enhancing ATP levels, the coordinated regulation of NAD+ metabolism, SIRT protein expression, and DNA-PK activity-constituting a novel therapeutic triad may contribute to the amelioration of hearing impairment and mitochondrial dysfunction, thereby improving life prognosis.

cell biology↗

bioRxiv2025

Visualization of functional and effective connectivity underlying auditory descriptive naming

ObjectiveWe visualized functional and effective connectivity within specific white matter networks in response to auditory descriptive questions. MethodsWe investigated 40 Japanese-speaking patients with focal epilepsy and estimated connectivity measures using cortical high-gamma dynamics and MRI tractography. ResultsHearing a wh-interrogative at question onset enhanced inter-hemispheric functional connectivity, with left-to-right callosal facilitatory flows between the superior-temporal gyri, contrasted by functional connectivity diminution with right-to-left callosal suppressive flows between dorsolateral prefrontal regions. Processing verbs associated with concrete objects or adverbs increased left intra-hemispheric connectivity, with bidirectional facilitatory flows through extensive white matter pathways. Questions beginning with what, compared to where, induced greater neural engagement in the left posterior inferior-frontal gyrus at question offset, linked to enhanced functional connectivity and bidirectional facilitatory flows to the temporal lobe neocortex via the arcuate fasciculus. During overt responses, inter-hemispheric functional connectivity was enhanced, with bidirectional callosal flows between Rolandic areas, and individuals with higher IQ scores exhibited less prolonged neural engagement in the left posterior middle frontal gyrus. ConclusionsVisualization of directional neural interactions within white matter networks during overt naming is feasible. SignificancePhrase order may influence network dynamics in listeners, even when presented with auditory descriptive questions conveying similar meanings.

neuroscience↗

bioRxiv2025

Remote Cortical Network for Frontal Cognitive Symptoms derived from Tau Accumulation in Progressive Supranuclear Palsy

Progressive Supranuclear Palsy (PSP) is a neurodegenerative disorder characterized by impaired movement and frontal cognitive dysfunctions. While motor symptoms have been linked with subcortical tau deposits, network mechanisms underlying the frontal cognitive symptoms remain unclear because pathological tau accumulation is quite limited within the frontal cortex and heterogeneously distributed primarily in the subcortical regions. Here, we combined tau-PET using a high-contrast probe we have recently developed with normative connectome to resolve this issue. Tau-deposition sites were connected to a common cortical network that could not be identified through similar analyses based on atrophy detected by structural MRI. This network was predominantly overlapped with canonical action-mode and frontoparietal networks, which jointly support adaptive and goal-directed behavior. Critically, while the degree of subcortical primary tau deposition correlated with motor symptoms, only the degree of connectivity from tau-deposition sites to the derived cortical network explained the frontal cognitive deficits of individual patients. These findings suggest a novel mechanism that frontal cognitive impairments, but not motor deficits, in PSP are derived from remote effects of tau deposits, independent of atrophy, through the convergent connectivity to the identified common cortical network.

neuroscience↗

bioRxiv2024

Temperature-driven biogeography of marine giant viruses infecting the picoeukaryote Micromonas

Climate shapes the biogeography of microbial and viral communities in the ocean. Among abiotic factors, temperature is one of the main drivers of microbial community distribution. However, we lack knowledge on how temperature shapes the life history traits, population dynamics, and the biogeography of marine viruses. This study integrates mathematical modeling with in situ observations to investigate the temperature-driven biogeography of marine viruses. We focused on prasinoviruses, a group of giant viruses that infect the picoeukaryote Micromonas, a widespread phytoplankton with thermotypes adapted from poles to tropics. Analyzing the Tara Oceans and Polar Circle databases, we found that temperature is the primary determinant of Micromonas virus (MicV) distribution in the surface ocean. Phylogenetic reconstruction of MicV-s revealed that these viruses form several groups with cryophile or cryo-mesophile preferences. We applied a mechanistic model to describe temperature-driven population dynamics, allowing us to predict the global presence and absence of MicV-s. Lysis and infection emerged as reliable predictors of MicV distribution, indicating that temperature-driven cellular mechanisms significantly shape viral community structure and distribution. This study provides new insights into the role of temperature in regulating viral populations, emphasizing the importance of integrating modeling with observations to understand marine viral ecology.

ecology↗

bioRxiv2024

Type 2 diabetes remodels collateral circulation and promotes leukocyte adhesion following ischemic stroke

AbstractType 2 diabetes mellitus (T2DM) is associated with impaired leptomeningeal collateral compensation and poor stroke outcome. Neutrophils tethering and rolling on endothelium after stroke can also independently reduce flow velocity. However, the chronology and topological changes in collateral circulation in T2DM is not yet defined. Here, we describe the spatial and temporal blood flow dynamics and vessel remodeling in pial arteries and veins and leukocyte- endothelial adhesion following middle cerebral artery (MCA) stroke using two-photon microscopy in awake control and T2DM mice. Relative to control mice prior to stroke, T2DM mice already exhibited smaller pial vessels with reduced flow velocity. Following stroke, T2DM mice displayed persistently reduced blood flow in pial arteries and veins, resulting in a poor recovery of downstream penetrating arterial flow and a sustained deficit in microvascular flow. There was also persistent increase of leukocyte adhesion to the endothelium of veins, coincided with elevated neutrophils infiltration into brain parenchyma in T2DM mice compared to control mice after stroke. Our data suggest that T2DM-induced increase in chronic inflammation may contribute to the remodeling of leptomeningeal collateral circulation and the observed hemodynamics deficiency that potentiates poor stroke outcome. HighlightsO_LIBlood flow and leukocyte imaging in awake mice by two-photon microscopy before and after stroke under physiological conditions C_LIO_LIT2DM induces collateral remodeling prior to stroke C_LIO_LIT2DM reduces blood flow and impedes recovery in pial arteries and veins after ischemic stroke C_LIO_LIPoor recovery of penetrating arterial flow and sustained deficit in microvascular flow after ischemic stroke in T2DM mice C_LIO_LIT2DM increases persistent leukocyte adhesion to endothelium of veins and elevates neutrophils infiltration into the brain parenchyma after ischemic stroke. C_LI

neuroscience↗