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A cortical-hippocampal communication undergoes rebalancing after new learning.
bioRxiv : the preprint server for biology Pub Date : 2025-03-29 DOI: 10.1101/2025.03.26.645547
Arron F Hall, Dong V Wang
{"title":"A cortical-hippocampal communication undergoes rebalancing after new learning.","authors":"Arron F Hall, Dong V Wang","doi":"10.1101/2025.03.26.645547","DOIUrl":"https://doi.org/10.1101/2025.03.26.645547","url":null,"abstract":"<p><p>The brain's ability to consolidate a wide range of memories while maintaining their distinctiveness across experiences remains poorly understood. Sharp-wave ripples, neural oscillations that occur predominantly within CA1 of the hippocampus during immobility and sleep, have been shown to play a critical role in the consolidation process. More recently, evidence has uncovered functional heterogeneity of pyramidal neurons within distinct sublayers of CA1 that display unique properties during ripples, potentially contributing to memory specificity. Despite this, it remains unclear exactly how ripples shift the activity of CA1 neuronal populations to accommodate the consolidation of specific memories and how sublayer differences manifest. Here, we studied interactions between the anterior cingulate cortex (ACC) and CA1 neurons during ripples and discovered a reorganization of their communication following learning. Notably, this reorganization appeared specifically for CA1 superficial (CA1sup) sublayer neurons. Utilizing a generalized linear model decoder, we demonstrate the pre-existence of ACC-to-CA1sup communication, which is suppressed during new learning and subsequent sleep suggesting that ACC activity may reallocate the contribution of CA1sup neurons during memory acquisition and consolidation. Further supporting this notion, we found that optogenetic stimulations of the ACC preferentially suppressed CA1sup interneurons while activating a unique subset of CA1 interneurons. Overall, these findings highlight a possible role of the ACC in rebalancing CA1 neuronal populations' contribution to ripple contents surrounding learning.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
fpocketR : A platform for identification and analysis of ligand-binding pockets in RNA.
bioRxiv : the preprint server for biology Pub Date : 2025-03-29 DOI: 10.1101/2025.03.25.645323
Seth D Veenbaas, Simon Felder, Kevin M Weeks
{"title":"<i>fpocketR</i> : A platform for identification and analysis of ligand-binding pockets in RNA.","authors":"Seth D Veenbaas, Simon Felder, Kevin M Weeks","doi":"10.1101/2025.03.25.645323","DOIUrl":"https://doi.org/10.1101/2025.03.25.645323","url":null,"abstract":"<p><p>Small molecules that bind specific sites in RNAs hold promise for altering RNA function, manipulating gene expression, and expanding the scope of druggable targets beyond proteins. Identifying binding sites in RNA that can engage ligands with good physicochemical properties remains a significant challenge. <i>fpocketR</i> is a software package for identifying, characterizing, and visualizing ligand-binding sites in RNA. <i>fpocketR</i> was optimized, through comprehensive analysis of currently available RNA-ligand complexes, to identify pockets in RNAs able to bind small molecules possessing favorable properties, generally termed drug-like. Here, we demonstrate use of <i>fpocketR</i> to analyze RNA-ligand interactions and novel pockets in small and large RNAs, to assess ensembles of RNA structure models, and to identify pockets in dynamic RNA systems. <i>fpocketR</i> performs best with RNA structures visualized at high (≤3.5 Å) resolution, but also provides useful information with lower resolution structures and computational models. <i>fpocketR</i> is a powerful, freely available tool for discovery and analysis of ligand-binding pockets in RNA molecules.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CHD7 binds to insulators during neuronal differentiation.
bioRxiv : the preprint server for biology Pub Date : 2025-03-29 DOI: 10.1101/2025.03.28.646031
Jingyun Qiu, Azadeh Jadali, Edward Martinez, Zhichao Song, Julie Z Ni, Kelvin Y Kwan
{"title":"CHD7 binds to insulators during neuronal differentiation.","authors":"Jingyun Qiu, Azadeh Jadali, Edward Martinez, Zhichao Song, Julie Z Ni, Kelvin Y Kwan","doi":"10.1101/2025.03.28.646031","DOIUrl":"https://doi.org/10.1101/2025.03.28.646031","url":null,"abstract":"<p><p>Spiral ganglion neurons (SGNs) are crucial for hearing, and the loss of SGNs causes hearing loss. Stem cell-based therapies offer a promising approach for SGN regeneration and require understanding the mechanisms governing SGN differentiation. We investigated the chromatin remodeler CHD7 in neuronal differentiation using immortalized multipotent otic progenitor (iMOP) cells. We demonstrated that CHD7 knockdown impaired neuronal differentiation. Genome-wide analysis revealed CHD7 binding at diverse <i>cis</i> -regulatory elements, with notable enrichment at sites marked by the insulator-binding protein CTCF between topologically associating domains (TADs). Insulators marked by the enrichment of CHD7 and CTCF resided near genes critical for neuronal differentiation, including <i>Mir9-2</i> . Targeting these regulatory regions in iMOPs with CRISPR interference (CRISPRi) and activation (CRISPRa) increased miR-9 transcription, irrespective of the method. Blocking the CHD7 and CTCF marked sites suggested that the elements function as insulators to regulate gene expression. The study highlights CHD7 activity at insulators and underscores an unreported mechanism for promoting neuronal differentiation.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Crucial roles of mesenchymal Gata2 in murine epididymal development.
bioRxiv : the preprint server for biology Pub Date : 2025-03-29 DOI: 10.1101/2025.03.26.645498
Allyssa Fogarty, Shuai Jia, Jillian Wilbourne, Claire DuPuis, Fei Zhao
{"title":"Crucial roles of mesenchymal <i>Gata2</i> in murine epididymal development.","authors":"Allyssa Fogarty, Shuai Jia, Jillian Wilbourne, Claire DuPuis, Fei Zhao","doi":"10.1101/2025.03.26.645498","DOIUrl":"https://doi.org/10.1101/2025.03.26.645498","url":null,"abstract":"<p><p>Androgens drive the morphogenesis and differentiation of the Wolffian duct (WD) into the epididymis, an essential organ for male reproduction, by binding to the androgen receptor (AR). However, it remains unclear whether other transcriptional programs operate beyond the central androgen/AR signaling in promoting WD development. We discovered that mesenchyme-specific deletion of the transcription factor <i>Gata2</i> resulted in defective epididymal coiling in the corpus and caudal regions. The defective coiling in the absence of mesenchymal <i>Gata2</i> did not result from androgen signaling deficiency, as there were no abnormalities in testicular morphology, androgen production, or AR/ <i>Ar</i> expression, and dihydrotestosterone supplementation did not restore epididymal coiling in cultured WDs. Instead, <i>Gata2</i> deletion reduced the expression of the mesenchyme- derived factor <i>Inhba</i> and epithelial proliferation, both of which play critical roles in epididymal coiling. The epididymal defect persisted into adulthood, with the uncoiled corpus and caudal epididymis exhibiting abnormal epithelial morphology and lumen environments, resulting in an unfavorable environment for sperm storage. Our results demonstrate the androgen-independent role of mesenchymal GATA2 in promoting epididymal development through <i>Inhba</i> induction and highlight the importance of proper fetal development in male reproduction.</p><p><strong>Significance statement: </strong>Testicular androgens drive the maintenance and differentiation of the Wolffian duct into a coiled and functional epididymis during male sexual differentiation. Our study, however, reveals that the Wolffian duct failed to develop into a coiled and functional epididymis in the absence of mesenchymal <i>Gata2.</i> This defect is not due to androgen signaling deficiency but rather to reduced expression of the mesenchyme-derived factor <i>Inhba</i> and decreased epithelial proliferation. Our results demonstrate the crucial role of GATA2-mediated transcriptional programs beyond the central androgen/androgen receptor signaling in Wolffian duct development.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Wnt/Beta-Catenin Signaling Is Active in Neuroendocrine Prostate Cancer.
bioRxiv : the preprint server for biology Pub Date : 2025-03-29 DOI: 10.1101/2025.03.25.645248
Yingli Shi, Shu Yang, Lin Li, Siyuan Cheng, Jeyaluxmy Sivalingam, Elahe Mahdavian, Xiuping Yu
{"title":"Wnt/Beta-Catenin Signaling Is Active in Neuroendocrine Prostate Cancer.","authors":"Yingli Shi, Shu Yang, Lin Li, Siyuan Cheng, Jeyaluxmy Sivalingam, Elahe Mahdavian, Xiuping Yu","doi":"10.1101/2025.03.25.645248","DOIUrl":"https://doi.org/10.1101/2025.03.25.645248","url":null,"abstract":"<p><p>Wnt/beta-Catenin signaling plays a critical role in prostate cancer (PCa) progression, yet its precise contributions in neuroendocrine prostate cancer (NEPCa) remain incompletely understood. In this study, we utilized TRAMP/Wnt-reporter mice to monitor Wnt/beta-Catenin activity and investigated transcriptional alterations associated with NEPCa development. RNA sequencing and pathway enrichment analyses identified neuroactive ligand-receptor interaction, MAPK, calcium, and cAMP signaling as key pathways enriched in NEPCa. Although Wnt signaling was not among the top-enriched pathways, elevated Axin2 expression and increased Wnt-reporter activity suggest its involvement in NEPCa progression. We observed upregulated expression of Wnt3, Wnt6, Dvl2, Dvl3, and Lef1 in NEPCa, coupled with reduced expression of Yap1 and Frat1, which are involved in beta-Catenin degradation. Pharmacological inhibition of Wnt/beta-Catenin signaling using FC101 significantly suppressed PCa growth, underscoring its potential as a therapeutic target. These findings reveal that Wnt/beta-Catenin signaling is active in NEPCa through multiple mechanisms and highlight the need for further investigation into the regulatory interplay between Wnt and YAP1 in prostate cancer.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nano-organization of synapses defines synaptic release properties at cortical neuron dendritic spines.
bioRxiv : the preprint server for biology Pub Date : 2025-03-29 DOI: 10.1101/2025.02.13.637710
Haani Jafri, Samantha J Thomas, Sung Hoon Yang, Rachel E Cain, Matthew B Dalva
{"title":"Nano-organization of synapses defines synaptic release properties at cortical neuron dendritic spines.","authors":"Haani Jafri, Samantha J Thomas, Sung Hoon Yang, Rachel E Cain, Matthew B Dalva","doi":"10.1101/2025.02.13.637710","DOIUrl":"10.1101/2025.02.13.637710","url":null,"abstract":"<p><p>Visualization of the submicron organization of excitatory synapses has revealed an unexpectedly ordered architecture consisting of nanocolumns of synaptic proteins that group into nanomodules which scale in number as spine size increases. How these features are related to synaptic function has remained unclear. Here, using super-resolution followed by live-cell line-scan imaging, we find that the size of the smallest miniature calcium and glutamate events are the same, regardless of whether spines have one or two nanopuncta of PSD-95, and that miniature synaptic response in all spines are best fit by a three term Poisson. Two nanomodule spines exhibit more large events without a significant change in event frequency, with the number of the largest events increasing disproportionately. These data support a model where nanomodules define sites of synaptic release and where the nanoarchitecture of synaptic proteins specifies subtypes of excitatory synapses, with increasing numbers of nanomodules increasing coordinated multivesicular release.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The spontaneous neoantigen-specific CD4 + T cell response to a growing tumor is functionally and phenotypically diverse. 针对生长中肿瘤的自发新抗原特异性 CD4 + T 细胞反应在功能和表型上具有多样性。
bioRxiv : the preprint server for biology Pub Date : 2025-03-29 DOI: 10.1101/2025.03.25.645281
Ryan Q Griswold, Spencer E Brightman, Karla Soria Zavala, Manuel Azaid Ordaz-Arias, Navid Djassemi, Rukman R Thota, Martin S Naradikian, Hannah Dose, Suzie Alarcon, Vijayanand Pandurangan, Bjoern Peters, Aaron M Miller, Ezra E W Cohen, Stephen P Schoenberger
{"title":"The spontaneous neoantigen-specific CD4 <sup>+</sup> T cell response to a growing tumor is functionally and phenotypically diverse.","authors":"Ryan Q Griswold, Spencer E Brightman, Karla Soria Zavala, Manuel Azaid Ordaz-Arias, Navid Djassemi, Rukman R Thota, Martin S Naradikian, Hannah Dose, Suzie Alarcon, Vijayanand Pandurangan, Bjoern Peters, Aaron M Miller, Ezra E W Cohen, Stephen P Schoenberger","doi":"10.1101/2025.03.25.645281","DOIUrl":"https://doi.org/10.1101/2025.03.25.645281","url":null,"abstract":"&lt;p&gt;&lt;p&gt;CD4 &lt;sup&gt;+&lt;/sup&gt; T cells play critical roles in the positive and negative regulation of cellular immunity through the many functional subsets they comprise. The progressive growth of immunogenic tumors which nonetheless generate mutation-specific T cells suggests that effective immune control may be avoided or suppressed at the level of the neoantigen-specific CD4 &lt;sup&gt;+&lt;/sup&gt; T cell response. We used a tetramer specific for a validated neoantigen, CTLC &lt;sub&gt;H129&gt;Q&lt;/sub&gt; /I-E &lt;sup&gt;k&lt;/sup&gt; , to characterize the ontogeny of natural CD4 &lt;sup&gt;+&lt;/sup&gt; T cell responses to an aggressive and poorly immunogenic Major Histocompatibility Complex Class II (MHCII)-deficient tumor, SCC VII, during progressive growth or following therapeutic peptide vaccination. We find that the natural CD4 &lt;sup&gt;+&lt;/sup&gt; T cell response to a growing tumor is phenotypically and functionally diverse, with distinct subsets including type 1 helper (T &lt;sub&gt;h&lt;/sub&gt; 1), T follicular helper (T &lt;sub&gt;fh&lt;/sub&gt; )-like, and regulatory T cell (T &lt;sub&gt;reg&lt;/sub&gt; ) lineages appearing as early as 9 days after tumor implantation. Therapeutic vaccination using the CLTC &lt;sub&gt;H129&gt;Q&lt;/sub&gt; peptide in adjuvant plus α-PD-1 sharply reduces the frequency of CLTC &lt;sub&gt;H129&gt;Q&lt;/sub&gt; -specific T &lt;sub&gt;reg&lt;/sub&gt; frequency in both tumor and tumor-draining lymph node (tdLN). Single cell transcriptomic analysis of CLTC-specific CD4 &lt;sup&gt;+&lt;/sup&gt; T cells recapitulated and extended the diversity of the response, with TCRs of varying affinity found within each functional subset. The TCR affinity differences did not strictly correlate with function, however, as even the lowest affinity TCRs isolated from T &lt;sub&gt;reg&lt;/sub&gt; can mediate therapeutic efficacy against established tumors in the setting of adoptive cellular therapy (ACT). These findings offer unprecedented insight into the functional diversity of a natural neoantigen-specific CD4 &lt;sup&gt;+&lt;/sup&gt; T cell response and show how immunotherapeutic intervention influences the phenotype, magnitude, and efficacy of the anti-tumor immune response.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is already known on this topic: &lt;/strong&gt;Little is known about the ontogeny, architecture, development of the CD4 &lt;sup&gt;+&lt;/sup&gt; NeoAg-specific repertoire induced by progressively-growing tumor. This study was performed to address this topic and contribute new information to aid in its understanding.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What this study adds: &lt;/strong&gt;This study reveals that the NeoAg-specific CD4 &lt;sup&gt;+&lt;/sup&gt; T cell response to a growing tumor is phenotypically and functionally diverse, featuring a range of functional T cells subsets including T &lt;sub&gt;H&lt;/sub&gt; 1, T &lt;sub&gt;FH&lt;/sub&gt; , and T &lt;sub&gt;reg&lt;/sub&gt; expressing a range of functional TCR avidities, and demonstrates how an immunotherapeutic NeoAg vaccine can alter their relative composition within the tumor and tumor-draining lymph node.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;How this study might affect research practice or policy: &lt;/strong&gt;This study offers new insights into the diversity o","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Androgen Deprivation-Induced TET2 Activation Fuels Prostate Cancer Progression via Epigenetic Priming and Slow-Cycling Cancer Cells.
bioRxiv : the preprint server for biology Pub Date : 2025-03-29 DOI: 10.1101/2025.03.26.645495
Lin Li, Siyuan Cheng, Yaru Xu, Su Deng, Ping Mu, Xiuping Yu
{"title":"Androgen Deprivation-Induced TET2 Activation Fuels Prostate Cancer Progression via Epigenetic Priming and Slow-Cycling Cancer Cells.","authors":"Lin Li, Siyuan Cheng, Yaru Xu, Su Deng, Ping Mu, Xiuping Yu","doi":"10.1101/2025.03.26.645495","DOIUrl":"https://doi.org/10.1101/2025.03.26.645495","url":null,"abstract":"<p><p>Advanced prostate cancer (PCa) frequently develops resistance to androgen deprivation therapy through various mechanisms including lineage plasticity. Slow-cycling cells (SCCs) have emerged as key players in adaptive responses to therapy, yet their role in PCa remains unclear. Through in silico analysis of single-cell RNA sequencing (scRNA-seq) data, we discovered that SCCs are enriched during pivotal stages of PCa progression, including the transition from androgen-dependent to castration-resistant states and the emergence of neuroendocrine PCa (NEPC). Using a tetracycline-inducible H2BeGFP reporter system, we confirmed SCC enrichment following androgen deprivation in both <i>in vitro</i> and <i>in vivo</i> models. Furthermore, we identified TET2 as a key regulator of SCCs, with its expression upregulated by androgen deprivation and positively correlated with SCC signature scores in PCa. Genome-wide 5-hydroxymethylcytosine (5hmC) profiling revealed increased hydroxymethylation after androgen deprivation, while TET2 knockdown reduced 5hmC levels at specific loci. Functional studies demonstrated that TET2 governs SCC maintenance, cell cycle progression, and DNA damage repair. Targeting TET2, either alone or in combination with an ATM inhibitor, significantly suppressed tumor growth, highlighting TET2 as a promising therapeutic target. Our study provides the first single-nucleotide resolution map of 5hmC dynamics in PCa, identifies a cell state driving epigenetic rewiring, and underscores the transformative potential of novel therapeutic strategies for advanced PCa.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
RNA sequence analysis of somatic mutations in aging and Parkinson's Disease.
bioRxiv : the preprint server for biology Pub Date : 2025-03-29 DOI: 10.1101/2025.03.26.645360
Shixiang Sun, Daisy Sproviero, César Payán-Gómez, Jan H J Hoeijmakers, Alexander Y Maslov, Pier G Mastroberardino, Jan Vijg
{"title":"RNA sequence analysis of somatic mutations in aging and Parkinson's Disease.","authors":"Shixiang Sun, Daisy Sproviero, César Payán-Gómez, Jan H J Hoeijmakers, Alexander Y Maslov, Pier G Mastroberardino, Jan Vijg","doi":"10.1101/2025.03.26.645360","DOIUrl":"https://doi.org/10.1101/2025.03.26.645360","url":null,"abstract":"<p><p>Parkinson's Disease (PD) is an age-related neurodegenerative disorder that has been associated with increased DNA damage. To test if PD is associated with increased somatic mutations, we analyzed RNA-seq data in whole blood from 5 visits of the Parkinson's Progression Markers Initiative for clonally amplified somatic variants. Comprehensive analysis of RNA-sequencing data revealed a total of 5,927 somatic variants (2.4 variants per sample on average). Mutation frequencies were significantly elevated in PD subjects as compared to agematched controls at the time of the last visit. This was confirmed by RNA analysis of substantia nigra. By contrast, the fraction of carriers with clonal hematopoiesis, was significantly reduced in old PD patients as compared to old healthy controls. These results indicate that while the overall mutation rate is higher in PD, specific clonally amplified mutations are protective against PD, as has been found for Alzheimer's Disease.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A systematic review of climate-change driven range shifts in mosquito vectors. 气候变化驱动的蚊媒分布区转移系统回顾。
bioRxiv : the preprint server for biology Pub Date : 2025-03-28 DOI: 10.1101/2025.03.25.645279
Kelsey Lyberger, Anna Rose Robinson, Lisa Couper, Isabel Delwel, Caroline Glidden, Crystal Qian, Aja Burslem, Faith Fernandez, Benjamen Gao, Gabriella Garcia, Julio Gomez, Caspar Griffin, Stephanie Jackson, Annalisa King, Olivia Manes, Andrew Song, Edward Tran, Erin A Mordecai
{"title":"A systematic review of climate-change driven range shifts in mosquito vectors.","authors":"Kelsey Lyberger, Anna Rose Robinson, Lisa Couper, Isabel Delwel, Caroline Glidden, Crystal Qian, Aja Burslem, Faith Fernandez, Benjamen Gao, Gabriella Garcia, Julio Gomez, Caspar Griffin, Stephanie Jackson, Annalisa King, Olivia Manes, Andrew Song, Edward Tran, Erin A Mordecai","doi":"10.1101/2025.03.25.645279","DOIUrl":"https://doi.org/10.1101/2025.03.25.645279","url":null,"abstract":"<p><p>As global temperatures rise, concerns about shifting mosquito ranges-and accompanying changes in the transmission of malaria, dengue, and other diseases-are mounting. However, systematic evidence for climate-driven changes in mosquito ranges remains limited. We conducted a systematic review of studies documenting expansions or contractions in medically important mosquito species. In total, 178 studies on six continents identified range expansions in 118 mosquito species. While over a third of these studies cited warming as a driver, fewer than 10% performed statistical tests of the role of climate. Instead, most expansions were linked to human-aided dispersal (e.g., trade, travel), land-use changes, and urbanization. Although several studies reported poleward or upward expansions consistent with climate warming, none demonstrated warm-edge contractions driven by rising temperatures, which are theoretically predicted in some settings. Rather than expanding into newly suitable areas, many expansions appear to be filling preexisting thermally suitable habitats. Our findings highlight the need for long-term mosquito monitoring, rigorous climate-attribution methods, and better documentation of confounding factors like land-use change and vector control efforts to disentangle climate-driven changes from other anthropogenic factors.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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