bluuebunny/crossref_metadata_2025_split huggingface dataset:
Macular Oxygen Saturation in Glaucoma Using Retinal Oximetry of Visible Light Optical Coherence Tomography
Authors: Wang Jingyu , Sadlak Natalie , Fiorello Marissa G. , Desai Manishi , Yi Ji 
Published: December 2023

AbstractPurposeOxygen saturation (sO2) plays a critical role in retinal pathophysiology, especially at the macula, which undergoes significant energy consumption. While macular damage has been suggested to be involved in early-stage glaucoma, there has been no report to date on non-invasive macular sO2in glaucoma. Therefore, we conducted this study to compare macular sO2associated with other clinical measurements between normal and glaucoma subjects and evaluate whether there are significant differences.MethodThis is a cross-sectional study. We used visible light optical coherence tomography (VIS-OCT) for retinal oximetry in perifoveal vessels. The subjects from groups of normal, suspect/pre-perimetric glaucoma (GS/PPG) and perimetric glaucoma (PG) were scanned using VIS-OCT in the macular region with a sampling density of 512×256 in an area of 5×5 mm2. 48 eyes (16 normal, 17 GS/PPG and 15 PG) were included for the analysis. For each eye, we measured the sO2of arterioles (AsO2), venules (VsO2), and calculated the difference between arterioles and venules (A-V sO2=AsO2-VsO2), oxygen extraction (OE=(AsO2-VsO2)/AsO2×100%). Additionally, we included Zeiss Cirrus OCT scans and 24-2 visual field test (VFT) for clinical benchmark. One-way ANOVA was used to compare the differences among the three groups. Spearman correlation tests were used for correlation sO2markers to standard metrics including the thickness of ganglion cell layer and inner plexiform layer (GCL+IPL), circumpapillary retinal nerve fiber layer (cpRNFL) and mean deviation (MD) in VFT.ResultSignificant differences were found among three groups for all VIS-OCT, Zeiss OCT, and VFT variables. Macular AsO2, A-V sO2, OE decreased, and VsO2increased along with severity. Macular AsO2and A-V sO2were statistically correlated with GCL+IPL and cpRNFL in all eyes, as well as only PG eyes. Within PG eyes, the correlation between AsO2and GCL+IPL is dominant in more damaged lower hemifield.ConclusionThe GS/PPG and PG subjects had significantly higher macular VsO2, lower A-V sO2and OE indicating less oxygen consumption. The sO2measured by retinal oximetry of VIS-OCT can be a potential metric for the early diagnosis of glaucoma.
Druggable causal genes of bipolar disorder identified through Mendelian Randomization analysis offer a route to intervention in integrated stress response
Authors: Ting Zhai 
Published: December 2023

AbstractBipolar disorder (BD) is known to be comorbid with many medical and psychiatric conditions and they may share inflammatory and stress-related aetiologies, which could give rise to this association. Psychosomatic illnesses are characterized by widespread immune signaling in the central nervous system, oxidative stress, and increased immune trafficking into the brain. The integrated stress response (ISR) responds to a variety of different stress conditions that lead to alterations in cellular homeostasis. However, as a causative mechanism underlying the cognitive deficits and neurodegeneration in a broad range of brain disorders, the impact of ISR on BD is understudied, particularly for the ISR’s central regulatory switch lies in eIF2 ternary complex formation. We aimed to prioritize eIF2-associated genes for follow-up studies using the summary data-based Mendelian Randomization (SMR) and Bayesian colocalization (COLOC) methods to integrate the summary-level data of the GWAS on BD and the expression quantitative trait locus (eQTL) study in blood. We utilized the GWAS data including 41917 BD cases and 371549 controls from the Psychiatric Genomics Consortium and the eQTL data from 31,684 participants of predominantly European ancestry from the eQTLGen consortium. Plus, we use Graph DB to alt drug targets. The SMR analysis identified EIF2B5 gene that were associated with BD due to no linkage but pleiotropy or causality. The COLOC analysis strongly suggested that EIF2B5 and the trait of BD were affected by shared causal variants, and thus were colocalized. Utilizing data in EpiGraphDB we find other putative causal BD genes (EIF2AK4 and GSK3B) to prioritise potential alternative drug targets.
An Endogenous Aryl Hydrocarbon Receptor Ligand Induces Preeclampsia-like Phenotypes: Transcriptome, Phosphoproteome, and Cell Functions
Authors: Zhao Ying-jie , Zhou Chi , Wei Ying-ying , Zhang Si-yan , Mishra Jay S. , Li Hui-hui , Lei Wei , Wang Kai , Kumar Sathish , Zheng Jing 
Published: December 2023

ABSTRACTBackgroundPreeclampsia (PE) is one hypertensive disorder and a leading cause of maternal and fetal mortality and morbidity during human pregnancy. Aryl hydrocarbon receptor (AhR) is a transcription factor, which regulates vascular functions. Exogenous and endogenous AhR ligands can induce hypertension in animals. However, if dysregulation of endogenous AhR ligands contributes to the pathophysiology of PE remains elusive.MethodsWe measured AhR activities in human maternal and umbilical vein sera. We also applied physiological, cellular, and molecular approaches to dissect the role of endogenous AhR ligands in vascular functions during pregnancy using pregnant rats and primary human umbilical vein endothelial cells (HUVECs) as models.ResultsPE elevated AhR activities in human umbilical vein sera. Exposure of pregnant rats to an endogenous AhR ligand, 2-(1’H-indole-3’-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) increased blood pressure and proteinuria, while decreased uteroplacental blood flow and reduced fetal and placental weights, all of which are hallmarks of PE. ITE dampened vascular growth and fetal sex-specifically altered immune cell infiltration in rat placentas. ITE also decreased cell proliferation and cell monolayer integrity in HUVECsin vitro. RNA sequencing analysis revealed that ITE dysregulated transcriptome in rat placentas and HUVECs in a fetal sex-specific manner. Bottom-up phosphoproteomics showed that ITE disrupted phosphoproteome in HUVECs. These ITE-dysregulated genes and phosphoproteins were enriched in biological functions and pathways which are highly relevant to diseases of heart, liver, and kidney, vascular functions, inflammation responses, cell death, and kinase inhibition.ConclusionsDysregulation of endogenous AhR ligands during pregnancy may lead to the development of PE with underlying impaired vascular functions, fetal sex-specific immune cell infiltration and transcriptome, and phosphoproteome. Thus, this study has provided a novel mechanism for the development of PE and potentially other forms of hypertensive pregnancies. These AhR ligand-activated genes and phosphoproteins might represent promising therapeutic and fetal sex-specific targets for PE-impaired vascular functions.
Olfactory ensheathing cells from adult female rats are hybrid glia that promote neural repair
Authors: Phelps Patricia E. , Ha Sung Min , Khankan Rana R. , Mekonnen Mahlet A. , Juarez Giovanni , Ingraham Dixie Kaitlin L. , Chen Yen-Wei , Yang Xia 
Published: December 2023

AbstractOlfactory ensheathing cells (OECs) are unique glial cells found in both central and peripheral nervous systems where they support continuous axonal outgrowth of olfactory sensory neurons to their targets. Previously we reported that following severe spinal cord injury, OECs transplanted near the injury site modify the inhibitory glial scar and facilitate axon regeneration past the scar border and into the lesion. To better understand the mechanisms underlying the reparative properties of OECs, we used single-cell RNA-sequencing of OECs from adult rats to study their gene expression programs. Our analyses revealed five diverse OEC subtypes, each expressing novel marker genes and pathways indicative of progenitor, axonal regeneration, secreted molecules, or microglia-like functions. We found substantial overlap of OEC genes with those of Schwann cells, but also with microglia, astrocytes, and oligodendrocytes. We confirmed established markers on cultured OECs, and localized select top genes of OEC subtypes in olfactory bulb tissue. We also show that OECs secrete Reelin and Connective tissue growth factor, extracellular matrix molecules which are important for neural repair and axonal outgrowth. Our results support that OECs are a unique hybrid glia, some with progenitor characteristics, and that their gene expression patterns indicate functions related to wound healing, injury repair and axonal regeneration.
Comprehensive Assessment of Ischemic Stroke in Nonhuman Primates: Neuroimaging, Behavioral, and Serum Proteomic Analysis
Authors: Li Ge , Lan Lan , He Tingting , Tang Zheng , Liu Shuhua , Li Yunfeng , Huang Zhongqiang , Guan Yalun , Li Xuejiao , Zhang Yu , Lai Hsin-Yi 
Published: December 2023

AbstractIschemic strokes, prevalence and impactful, underscore the necessity of advanced research models closely resembling human physiology. O integrating n ur study in nonhuman primates (NHPs) offers a comprehensive exploration of ischemic stroke, integrating neuroimaging data, behavioral outcomes, and serum proteomics to elucidate the complex interplay of factors involved in stroke pathophysiology. We observed a consistent pattern in infarct volume, peaking at 1-month post-middle cerebral artery occlusion (MCAO) and stabilizing thereafter. This trend was closely correlated with notable changes in motor function and working memory performance. Using diffusion tensor imaging (DTI), we detected significant alterations in fractional anisotropy (FA) and mean diffusivity (MD) values, indicative of microstructural changes in the brain. These findings were strongly correlated with the observed neurological and cognitive deficits, highlighting the sensitivity of DTI metrics in stroke assessment. Behaviorally, the monkeys exhibited a reliance on their unaffected limb for compensatory movements, a response commonly observed in stroke impairment. This adaptation, alongside the consistent findings in DTI metrics, suggests a substantial impact of stroke on motor function and spatial perception. Proteomic analysis through MS/MS functional enrichment revealed two distinct groups of proteins with significant changes post-MCAO. Notably, MMP9, THBS1, MB, PFN1, and YWHAZ emerged as potential biomarkers and therapeutic targets in ischemic stroke. Our findings underscore the complex nature of stroke and the potential of an integrated approach, combining neuroimaging, behavioral studies, and proteomics, for advancing our understanding and treatment of this condition.
Cryptic female choice in response to male pheromones inDrosophila melanogaster
Authors: Doubovetzky Nicolas , Kohlmeier Philip , Bal Sanne , Billeter Jean-Christophe 
Published: December 2023

AbstractFemales control the paternity of their offspring by selectively mating with males they perceive to be of high quality. In species where females mate with multiple males in succession, females may bias offspring paternity by favoring the sperm of one male over another, a process known as cryptic female choice (CFC). While evidence of CFC exists in multiple taxa, the mechanisms underlying this process have remained difficult to unravel. Understanding CFC requires demonstration of a female-driven post mating bias in sperm use and paternity, and a causal link between this bias and male cues. Here, we show that in the vinegar flyDrosophila melanogaster,mated females eject the ejaculate of their first mate faster when exposed to the pheromones of an attractive male than in the presence of an unattractive one. Using transgenic males expressing fluorescent sperm, we show that exposure to attractive males between mating causes twice-mated females to bias sperm storage towards the second male, affecting paternity. Using pheromonal bioassays in combination with genetic manipulation of sensory systems, we show that females modulate ejaculate ejection latency in response to male pheromones heptanal and 11-cis-Vaccenyl acetate (cVA) sensed via olfactory receptor neurons OR35a, Or22a, Or65a and OR67d, demonstrating that polyandrous females use male pheromonal cues to modulate ejaculate ejection timing. We provide the first demonstration to our knowledge of a CFC mechanism allowing a female to increase or decrease the share of paternity of her first mate depending on the sensing of the quality of potential mates in her environment. These findings showcase that paternity can be influenced by events that go beyond copulation and highlights the importance of post-copulatory sexual selection.One Sentence SummaryWe show that females bias sperm use and paternity towards specific males in response to male pheromones.
Gap junction mediated bioelectric coordination is required for slow muscle development, organization, and function
Authors: Lukowicz-Bedford RM , Eisen JS , Miller AC 
Published: December 2023

AbstractBioelectrical signaling, intercellular communication facilitated by membrane potential and electrochemical coupling, is emerging as a key regulator of animal development. Gap junction (GJ) channels can mediate bioelectric signaling by creating a fast, direct pathway between cells for the movement of ions and other small molecules. In vertebrates, GJ channels are formed by a highly conserved transmembrane protein family called the Connexins. Theconnexingene family is large and complex, presenting a challenge in identifying the specific Connexins that create channels within developing and mature tissues. Using the embryonic zebrafish neuromuscular system as a model, we identify aconnexinconserved across vertebrate lineages,gjd4,which encodes the Cx46.8 protein, that mediates bioelectric signaling required for appropriate slow muscle development and function. Through a combination of mutant analysis andin vivoimaging we show thatgjd4/Cx46.8 creates GJ channels specifically in developing slow muscle cells. Using genetics, pharmacology, and calcium imaging we find that spinal cord generated neural activity is transmitted to developing slow muscle cells and synchronized activity spreads viagjd4/Cx46.8 GJ channels. Finally, we show that bioelectrical signal propagation within the developing neuromuscular system is required for appropriate myofiber organization, and that disruption leads to defects in behavior. Our work reveals the molecular basis for GJ communication among developing muscle cells and reveals how perturbations to bioelectric signaling in the neuromuscular system may contribute to developmental myopathies. Moreover, this work underscores a critical motif of signal propagation between organ systems and highlights the pivotal role played by GJ communication in coordinating bioelectric signaling during development.
Tryptophan Metabolites And Their Predicted Microbial Sources In Fecal Samples Of Healthy Individuals
Authors: Chappell Cynthia L. , Hoffman Kristi L. , Lorenzi Philip L. , Tan Lin , Petrosino Joseph F. , Gibbs Richard A. , Muzny Donna M. , Doddapaneni Harsha , Ross Matthew C. , Menon Vipin K. , Surathu Anil , Javornik Cregeen Sara J. , Reyes Anaid G. , Okhuysen Pablo C. 
Published: December 2023

ABSTRACTGut microbiota produce tryptophan metabolites (TMs) important to homeostasis. However, measuring TM levels in stool and determining their microbial sources can be difficult. Here, we measured TMs from the indole pathway in fecal samples from 21 healthy adults with the goal to: 1) determine fecal TM concentrations in healthy individuals; 2) link TM levels to bacterial abundance using 16S and whole genome shotgun (WGS) sequencing data; and 3) predict likely bacterial sources of TM production. Within our samples, we identified 151 genera (16S) and 592 bacterial species (WGS). Eight TMs were found in ≥17 fecal samples, including four in all persons. To our knowledge, we are the first to report fecal levels for indole-3-lactate, indole-3-propionate, and 3-indoleacrylate levels in healthy persons. Overall, indole, indole-3-acetate (IAA), and skatole accounted for 86% of the eight TMs measured. Significant correlations were found between seven TMs and 29 bacterial species. Predicted multiple TM sources support the notion of a complex network of TM production and regulation. Further, the data suggest key roles forCollinsella aerofaciensand IAA, a metabolite reported to maintain intestinal homeostasis through enhanced barrier integrity and anti-inflammatory/antioxidant activities. These findings extend our understanding of TMs and their relationship to the microbial species that act as effectors and/or regulators in the healthy intestine and may lead to novel strategies designed to manipulate tryptophan metabolism to prevent disease and/or restore health to the dysbiotic gut.IMPORTANCETryptophan metabolites (TMs) of bacterial origin are increasingly recognized as important signaling molecules among gut microbiota and with the host. However, few reports exist for fecal TM levels in healthy humans, and reported levels vary widely. Further, the specific bacterial species producing TMs and the combinations of fecal TMs in healthy individuals are not well known. Our research combines 16S and whole genome shotgun sequencing of gut bacteria with a sensitive method (LC/MS) for measuring TMs and a reported method to predict which species are likely TM contributors. To our knowledge, this combination of analyses has not been reported elsewhere and will add significantly to the existing literature. Understanding TM levels and their sources in the healthy intestine are fundamental to elucidating how TMs contribute to maintaining homeostasis. Such knowledge of gut microbiota and their metabolic products will inform novel strategies to maintain intestinal health and prevent or treat dysbioses.
Intronic miR-6741-3p is involved in oral squamous cell carcinoma pathogenesis by targeting the oncogeneSRSF3
Authors: More Dhanashree Anil , Singh Nivedita , Mishra Radha , Muralidharan Harsha Pulakkat , Gopinath Kodaganur Srinivas , Gopal Champaka , Kumar Arun 
Published: December 2023

AbstractEpigenetic silencing through methylation is one of the major mechanisms for downregulation of tumor suppressor miRNAs in various malignancies. The aim of this study was to identify novel tumor suppressor miRNAs which are silenced by DNA hypermethylation and investigate the role of at least one of these in oral squamous cell carcinoma (OSCC) pathogenesis.We treated cells from an OSCC cell line SCC131 with 5-Azacytidine, a DNA methyltransferase inhibitor, to reactivate tumor suppressor miRNA genes silenced/downregulated due to DNA methylation. At 5-day post-treatment, total RNA was isolated from the 5-Azacytidine and vehicle control-treated cells. The expression of 2,459 mature miRNAs was analysed between 5-Azacytidine and control-treated OSCC cells by the microRNA microarray analysis.Of the 50 miRNAs which were found to be upregulated following 5-Azacytidine treatment, we decided to work with miR-6741-3p in details for further analysis, as it showed a mean fold expression of >4.0. The results of qRT-PCR, Western blotting, and dual-luciferase reporter assay indicated that miR-6741-3p directly targets the oncogeneSRSF3at the translational level only. The tumor-suppressive role of miR-6741-3p was established by variousin vitroandin vivoassays.Our results revealed that miR-6741-3p plays a tumor-suppressive role in OSCC pathogenesis, in part, by directly regulatingSRSF3. Based on our observations, we propose that miR-6741-3p may serve as a potential biological target in tumor diagnostics, prognostic evaluation, and treatment of OSCC and perhaps other malignancies.
Development of KASP markers for the potato virus Y resistance geneRychcusing whole-genome resequencing data
Authors: Asano Kenji , Endelman Jeffrey B. 
Published: December 2023

AbstractPotato virus Y is the most important potato virus worldwide, affecting tuber yield and quality. The resistance geneRychc, derived from the potato wild relativeSolanum chacoense, provides broad spectrum and durable resistance to the virus and has been used to develop resistant cultivars. Several DNA markers have been developed and have contributed to the efficient selection of resistant individuals. In this study, we developed Kompetitive Allele Specific PCR markers forRychcusing whole-genome resequencing data for a diverse set of 25 PVY susceptible cultivars and aRychc-positive clone. Marker Ry_4099 targets two variants in the 3’-UTR and was able to discriminate all five allele dosages in a tetraploid test population. Marker Ry_3331 targets two variants in Exon 4 and, although it only provides presence/absence information, it discriminates between the two known resistant alleles ofRychc. These markers will greatly contribute to efficient development of resistant cultivars.
Identifying functional multi-host shuttle plasmids to advance synthetic biology applications inMesorhizobiumandBradyrhizobium
Authors: Meaney Jordyn S. , Panchal Aakanx K. , Wilcox Aiden J. , diCenzo George C. , Karas Bogumil J. 
Published: December 2023

ABSTRACTAmmonia availability has a crucial role in agriculture as it ensures healthy plant growth and increased crop yields. Since diazotrophs are the only organisms capable of reducing dinitrogen to ammonium, they have a great ecological importance and potential to mitigate the environmental and economic costs of synthetic fertilizer use. Rhizobia are especially valuable being that they can engage in nitrogen-fixing symbiotic relationships with legumes, and they demonstrate great diversity and plasticity in genomic and phenotypic traits. However, few rhizobial species have improved genetic tractability for synthetic biology applications. This study established a basic genetic toolbox with antibiotic resistance markers, multi-host shuttle plasmids and a streamlined protocol for biparental conjugation withMesorhizobiumandBradyrhizobiumspecies. We identified tworepABCorigins of replication fromSinorhizobium meliloti(pSymB) andRhizobium etli(p42d) that were stable across all three strains of interest. Furthermore, the NZP2235 genome was sequenced and phylogenetic analysis determined its reclassification toMesorhizobium huakuii. These tools will enable the use of plasmid-based strategies for more advanced genetic engineering projects and ultimately contribute towards the development of more sustainable agriculture practices by means of novel nitrogen-fixing organelles, elite bioinoculants or symbiotic association with non-legumes.GRAPHICAL ABSTRACT