bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fast evolutionary turnover and overlapping variances of sex-biased gene expression patterns defy a simple binary classification of sexes
Authors: Xie Chen , Künzel Sven , Tautz Diethard 
Published: May 2024

AbstractThe phenotypic differences between the sexes are generated by genes with sex-biased expression. These range from a few major regulators to large numbers of organ-specific effector genes in sexually mature individuals. We explore the variation and evolutionary patterns of these genes in a large dataset from natural populations of sub-species and species of mice across an evolutionary distance of two million years. Within these short phylogenetic distances, we find a faster evolutionary turnover of sex-biased gene expression compared to non-sex-biased genes and a faster adaptive protein evolution for the genes that are sex-biased in a given taxon. We show that sex-biased genes occur only in a subset of the co-expression modules of each organ and the turnover of genes between the taxa occurs often within the main modules. Given that our dataset is the first in animals that was generated in a combined population genetic and phylogenetic context, we were interested to study the within-group variances for sex-biased gene expression in somatic and gonadal tissues and their evolutionary turnover. To visualize the individual variances, we have developed a sex-biased gene expression index (SBI) that represents the cumulative expression of all sex-biased genes for each individual in each organ. We find that SBI distributions can range from close to binary patterns to overlapping patterns between the sexes. They do not correlate between organs of the same individuals, thus supporting a mosaic model of sex-determination of individuals. Comparison with data from humans shows fewer sex-biased genes compared to mice and strongly overlapping SBI distributions between the sexes. We conclude that sex-biased genes are subject to fast evolution, with no long-term stability for male or female expression characteristics.
SASH1 impairs melanin synthesis and metastasis by down-regulating the TGF-β signaling pathway
Authors: Cui Hongzhou , Wang Qiong , Liang Honggang , Zhang Yingjie , Liang Bo , Wang Wenjun , Ge Shanshan , He Hongxia , Ren Xiaoli , Su Zhenxing , Guo Shuping 
Published: May 2024

AbstractDyschromatosis universalis hereditaria (DUH) is a rare genetic dermatosis characterized by widespread hyperpigmentation and depigmentation. In our previous study, we identified SH3 domain-containing protein 1 (SASH1) mutations associated with the DUH phenotype in Chinese families and predict SASH1/THBS1/TGF-β1 signaling to mediate melanin production and melanocyte transport. We detected SASH1/THBS1/TGF-β1 pathway genes expression and evaluated cell phenotypes and melanin synthesis in A375 and PIG1 cell lines by regulating the expression of SASH1 and THBS1 respectively. Finally, we validated the results of the cellular experiments in nude mice. Results showed that SASH1 inhibited the proliferation, migration, invasion, EMT ability and melanin synthesis via TGF-β1 signaling, and THBS1 reversed the elevation of TGF-β1 caused by SASH1 knockdown. We demonstrated that SASH1 further inhibits TGF-β1 through its regulatory effect on THBS1, thereby inhibiting melanin synthesis and metastasis, which may advance the utilization of TGF-β1 for therapeutic purposes.Plain Language SummaryDyschromatosis universalis hereditaria(DUH) is a genetic disease showing uneven pigment pattern, which greatly affects the appearance. In our previous study, we had reported a SASH1 mutation in a Chinese DUH pedigree. In this study, we mainly focus on the effect of SASH1 gene on pigment synthesis and metabolism at the cell and animal level. The results show SASH1 inhibits the melanin synthesis of melanocytes, it can also hinder cell migration, invasion, and EMT. More than that, SASH1 reduced TGF-β1 mRNA, protein expression and promoter activity, and THBS1 could discharge this effect. In mice, SASH1 inhibits the tumor growth via TGF-β1 signaling. We detected a novel SASH1/THBS1/TGF-β1 pathway in cell phenotypes and melanin synthesis.
Multiplexed detection, partitioning, and persistence of wild type and vaccine strains of measles, mumps, and rubella viruses in wastewater
Authors: Wu Jingjing , Wang Michael X. , Kalvapalle Prashant , Nute Michael , Treangen Todd J. , Ensor Katherine , Hopkins Loren , Poretsky Rachel , Stadler Lauren B. 
Published: May 2024

AbstractWastewater surveillance of vaccine-preventable diseases may provide early warning of outbreaks and identify areas to target for immunization. To advance wastewater monitoring of measles, mumps, and rubella viruses, we developed and validated a multiplexed RT-ddPCR assay for the detection of their RNA. Because the measles-mumps-rubella (MMR) vaccine is an attenuated live virus vaccine, we also developed an assay that distinguishes between wild-type and vaccine strains of measles in wastewater and validated it using a wastewater sample collected from a facility with an active measles outbreak. We also evaluated the partitioning behavior the viruses in between the liquid and solid fractions of influent wastewater. We found that assaying the liquid fraction of the wastewater resulted in more sensitive detection of the viruses despite the fact that the viral RNA was enriched in the solid fraction due to the low solids content of the influent wastewater. Finally, we investigated the stability of measles, mumps, and rubella RNA in wastewater samples spiked with viruses over 28 days at two different concentrations and two temperatures (4°C and room temperature) and observed limited viral decay. Our study supports the feasibility of wastewater monitoring for measles, mumps, and rubella viruses for population-level surveillance.
Active fluctuations of cytoplasmic actomyosin networks facilitate dynein-driven intracellular transport along microtubules
Authors: Torisawa Takayuki , Saito Kei , Furuta Ken’ya , Kimura Akatsuki 
Published: May 2024

SummaryInside cells, molecular motors transport cargoes within the actively fluctuating environment known as the cytoplasm. How fluctuations in the cytoplasm affect motor-driven transport is not fully understood. In this study, we investigated the role of fluctuations for transport along microtubules usingC. elegansearly embryos, focusing on transport driven by cytoplasmic dynein. An artificial motor-cargo complex showed faster transportin vivothanin vitro, suggesting anin vivoacceleration mechanism. We also found that endogenous early endosome transport by dynein is significantly enhanced by the fluctuations in the cytoplasm, which is attributed to the activity of actomyosin networks. Anin vitroforce measurement of dynein suggests that the asymmetric force response would play a key role in the acceleration. This study provides insights into a regulatory mechanism of molecular motors within actively fluctuating cytoplasm, potentially utilizing random force originating from fluctuating dynamics in the cytoplasm to increase transport efficiency.
In-Silo Federated Learning vs. Centralized Learning for Segmenting Acute and Chronic Ischemic Brain Lesions
Authors: Kim Joon , Lee Hoyeon , Park Jonghyeok , Park Sang Hyun , Lee Myungjae , Sunwoo Leonard , Kim Chi Kyung , Kim Beom Joon , Ryu Wi-Sun 
Published: May 2024

AbstractPurposeTo investigate the efficacy of federated learning (FL) compared to industry-level centralized learning (CL) for segmenting acute infarct and white matter hyperintensity.Materials and MethodsThis retrospective study included 13,546 diffusion-weighted images (DWI) from 10 hospitals and 8,421 fluid-attenuated inversion recovery images (FLAIR) from 9 hospitals for acute (Task I) and chronic (Task II) lesion segmentation. The mean ages (SD) for the training datasets were 68.1 (12.8) for Task I and 67.4 (13.0) for Task II. The frequency of male participants was 51.5% and 60.4%, respectively. We trained with datasets from 9 and 3 institutions for Task I and Task II, respectively, and externally tested them in datasets from 1 and 9 institutions each. For FL, the central server aggregated training results every four rounds with FedYogi (Task I) and FedAvg (Task II). A batch clipping strategy was tested for the FL models. Performances were evaluated with the Dice similarity coefficient (DSC).ResultsIn Task I, the FL model employing batch clipping trained for 360 epochs achieved a DSC of 0.754±0.183, surpassing an equivalent CL model (DSC 0.691±0.229; p<0.001) and comparable to the best-performing CL model at 940 epochs (DSC 0.755±0.207; p=0.701). In Task II, no significant differences were observed amongst FL model with clipping, without clipping, and CL model after 48 epochs (DSCs of 0.761±0.299, 0.751±0.304, 0.744±0.304). Few-shot FL showed significantly lower performance. Task II reduced training times with batch clipping (3.5 to 1.75 hours).ConclusionComparisons between CL and FL in identical settings suggest the feasibility of FL for medical image segmentation.
Evidence from metagenomic study indicate that subclinical mastitis may have a different pathological origin than clinical mastitis
Authors: Bhar Subhrajit , Bose Tungadri 
Published: May 2024

ABSTRACTBovine mastitis is one of the main causes of low milk production, resulting in significant economic losses for the dairy industry. Therefore, the industry will benefit from the development of strategies for the timely diagnosis of bovine mastitis, especially the sub-clinical sub-type. Here, we analysed the milk metagenome of healthy cows and cows suffering from various forms of mastitis, viz. clinical, sub-clinical and chronic/ recurrent sub-types. We identifiedNeisseria,EubacteriumandStreptococcusas the key drivers of the change in microbial community structure from a healthy state to a clinical mastitis state. Our results also indicate that the microbiota composition and the probable cause of clinical and recurrent bovine mastitis may not be the same as that of sub-clinical mastitis. Further, the sensory protein load in the sub-clinical mastitis sub-group differed significantly from the other studied categories, whereinAchromobacter,Dickeya,PectobacteriumandRaoultellawere identified as the discriminatory features. We also propose ML-based classifiers to screen for bovine mastitis using milk metagenomic samples. The principles elucidated here through the study of mastitis in cows can be applied to other animals and hopefully will benefit the entire dairy industry.
Merging Metabolic Modeling and Imaging for Screening Therapeutic Targets in Colorectal Cancer
Authors: Tavakoli Niki , Fong Emma J. , Coleman Abigail , Huang Yu-Kai , Bigger Mathias , Doche Michael E. , Kim Seungil , Lenz Heinz-Josef , Graham Nicholas A. , Macklin Paul , Finley Stacey D. , Mumenthaler Shannon M. 
Published: May 2024

AbstractCancer-associated fibroblasts (CAFs) play a key role in metabolic reprogramming and are well-established contributors to drug resistance in colorectal cancer (CRC). To exploit this metabolic crosstalk, we integrated a systems biology approach that identified key metabolic targets in a data-driven method and validated them experimentally. This process involved a novel machine learning-based method to computationally screen, in a high-throughput manner, the effects of enzyme perturbations predicted by a computational model of CRC metabolism. This approach reveals the network-wide effects of metabolic perturbations. Our results highlighted hexokinase (HK) as a crucial target, which subsequently became our focus for experimental validation using patient-derived tumor organoids (PDTOs). Through metabolic imaging and viability assays, we found that PDTOs cultured in CAF-conditioned media exhibited increased sensitivity to HK inhibition, confirming the model predictions. Our approach emphasizes the critical role of integrating computational and experimental techniques in exploring and exploiting CRC-CAF crosstalk.
An atlas of expressed transcripts in the prenatal and postnatal human cortex
Authors: Bamford Rosemary A. , Leung Szi Kay , Chundru V. Kartik , Jeffries Aaron R. , Davies Jonathan P. , Franklin Alice , Chen Xinmu , McQuillin Andrew , Bass Nicholas ,   APEX consortium, Walker Emma , O’Neill Paul , Pishva Ehsan , Dempster Emma L. , Hannon Eilis , Wright Caroline F. , Mill Jonathan 
Published: May 2024

ABSTRACTAlternative splicing is a post-transcriptional mechanism that increases the diversity of expressed transcripts and plays an important role in regulating gene expression in the developing central nervous system. We used long-read transcriptome sequencing to characterise the structure and abundance of full-length transcripts in the human cortex from donors aged 6 weeks post-conception to 83 years old. We identified thousands of novel transcripts, with dramatic differences in the diversity of expressed transcripts between prenatal and postnatal cortex. A large proportion of these previously uncharacterised transcripts have high coding potential, with corresponding peptides detected in proteomic data. Novel putative coding sequences are highly conserved and overlapde novomutations in genes linked with neurodevelopmental disorders in individuals with relevant clinical phenotypes. Our findings underscore the potential of novel coding sequences to harbor clinically relevant variants, offering new insights into the genetic architecture of human disease. Our cortical transcript annotations are available as a resource to the research community via an online database.
Transcriptomic landscape of mammalian ventral pallidum at single-cell resolution
Authors: Yang Lite , Fang Lisa Z , Lynch Michelle R , Xu Chang S , Hahm Hannah , Zhang Yufen , Heitmeier Monique R , Costa Vincent , Samineni Vijay K , Creed Meaghan C 
Published: May 2024

AbstractThe ventral pallidum (VP) is critical for motivated behaviors. While contemporary work has begun to elucidate the functional diversity of VP neurons, the molecular heterogeneity underlying this functional diversity remains incompletely understood. We used snRNA-seq andin situhybridization to define the transcriptional taxonomy of VP cell types in mice, macaques, and baboons. We found transcriptional conservation between all three species, within the broader neurochemical cell types. Unique dopaminoceptive and cholinergic subclusters were identified and conserved across both primate species but had no homolog in mice. This harmonized consensus VP cellular atlas will pave the way for understanding the structure and function of the VP and identified key neuropeptides, neurotransmitters, and neuro receptors that could be targeted within specific VP cell types for functional investigations.TeaserGenetic identity of ventral pallidum cell types is conserved across rodents and primates at the transcriptional level
A Recurrent Neural Network for Rhythmic Timing
Authors: Zemlianova Klavdia , Bose Amitabha , Rinzel John 
Published: May 2024

AbstractDespite music’s omnipresence, the specific neural mechanisms responsible to perceive and anticipate temporal patterns in music are unknown. To study potential mechanisms for keeping time in rhythmic contexts, we train a biologically constrained RNN on seven different stimulus tempos (2 – 8Hz) on a synchronization and continuation task, a standard experimental paradigm. Our trained RNN generates a network oscillator that uses an input current (context parameter) to control oscillation frequency and replicates key features of neural dynamics observed in neural recordings of monkeys performing the same task. We develop a reduced three-variable rate model of the RNN and analyze its dynamic properties. By treating our understanding of the mathematical structure for oscillations in the reduced model as predictive, we confirm that the dynamical mechanisms are found also in the RNN. Our neurally plausible reduced model reveals an E-I circuit with two distinct inhibitory sub-populations, of which one is tightly synchronized with the excitatory units.
Sex specific emergence of trisomicDyrk1a-related skeletal phenotypes in the development of a Down syndrome mouse model
Authors: LaCombe Jonathan M. , Sloan Kourtney , Thomas Jared R. , Blackwell Matthew P. , Crawford Isabella , Wallace Joseph M. , Roper Randall J. 
Published: May 2024

AbstractSkeletal insufficiency affects all individuals with Down syndrome (DS) or Trisomy 21 (Ts21) and may alter bone strength throughout development due to a reduced period of bone formation and early attainment of peak bone mass compared to typically developing individuals. Appendicular skeletal deficits also appear in males before females with DS. In femurs of male Ts65Dn DS model mice, cortical deficits were pronounced throughout development, but trabecular deficits andDyrk1aoverexpression were transitory until postnatal day (P) 30 when there were persistent trabecular and cortical deficits andDyrk1awas trending overexpression. Correction of DS-related skeletal deficits by a purported DYRK1A inhibitor or through genetic means beginning at P21 was not effective at P30, but germline normalization ofDyrk1aimproved male bone structure by P36. Trabecular and cortical deficits in female Ts65Dn mice were evident at P30 but subsided by P36, typifying periodic developmental skeletal normalizations that progressed to more prominent bone deficiencies. Sex-dependent differences in skeletal deficits with a delayed impact of trisomicDyrk1aare important to find temporally specific treatment periods for bone and other phenotypes associated with Ts21.Summary StatementAnalyzing developing bone and gene expression in Ts65Dn Down syndrome model mice revealed timepoints during development when trisomicDyrk1aoverexpression linked to appendicular skeletal abnormalities.Dyrk1awas not always overexpressed.
Improving the Z3EV promoter system to create the strongest yeast promoter
Authors: Higuchi Rina , Fujita Yuri , Moriya Hisao 
Published: May 2024

SummaryPromoters for artificial control of gene expression are central tools in genetic engineering. In the budding yeastS. cerevisiae, a variety of constitutive and controllable promoters with different strengths have been constructed using endogenous gene promoters, synthetic transcription factors and their binding sequences, and artificial sequences. However, there have been few attempts to construct the highest-strength promoter in yeast cells. In this study, by incrementally increasing the binding sequences of the synthetic transcription factor Z3EV, we were able to construct a promoter (P36) with approximately 1.4 times the strength of theTDH3promoter. This is stronger than any previously reported promoter. Although the P36 promoter exhibits some leakage in the absence of induction, the expression induction by β-estradiol is maintained. When combined with a multicopy plasmid, it can express up to approximately 50% of total protein as a heterologous protein. This promoter system can be used to gain knowledge about the cell physiology resulting from the ultimate overexpression of excess proteins and is expected to be a useful tool for heterologous protein expression in yeast.
Genome-wide sweeps create fundamental ecological units in the human gut microbiome
Authors: Yu Xiaoqian Annie , Strachan Cameron R. , Herbold Craig W. , Lang Michaela , Gasche Christoph , Makristathis Athanasios , Segata Nicola , Pollak Shaul , Tett Adrian , Polz Martin F. 
Published: May 2024

AbstractThe human gut microbiome is shaped by diverse selective forces originating from the host and associated environmental factors, and in turn profoundly influences health and disease. While the association of microbial lineages with various conditions has been shown at different levels of phylogenetic differentiation, it remains poorly understood to what extent unifying adaptive mechanisms sort microbial lineages into ecologically differentiated populations. Here we show that a pervasive mechanism differentiating bacteria in the microbiome are genome-wide selective sweeps, leading to population structure akin to global epidemics across geographically and ethnically diverse human populations. Such sweeps arise when an adaptation allows a clone to outcompete others within its niche followed by re-diversification, and manifest as clusters of closely related genomes on long branches in phylogenetic trees. This structure is revealed by excluding recombination events that mask the clonal descent of the genomes, and we find that genome-wide sweeps originate under a wide regime of recombination rates in at least 66 taxa from 25 bacterial families. Estimated ages of divergence suggest sweep clusters can spread globally within decades, and this process has occurred repeatedly throughout human history. We show, as an example, that the ecological differentiation of sweep clusters forms populations highly associated with age and colorectal cancer. Our analysis elucidates an evolutionary mechanism for the observation of stably inherited strains with differential associations and provides a theoretical foundation for analyzing adaptation among co-occurring microbial populations.
A Peptide Derived from Sorting Nexin 1 Inhibits HPV16 Entry, Retrograde Trafficking, and L2 Membrane Spanning
Authors: Li Shuaizhi , Williamson Zachary L. , Christofferson Matthew A. , Jeevanandam Advait , Campos Samuel K. 
Published: May 2024

AbstractHigh risk human papillomavirus (HPV) infection is responsible for 99% of cervical cancers and 5% of all human cancers worldwide. HPV infection requires the viral genome (vDNA) to gain access to nuclei of basal keratinocytes of epithelium. After virion endocytosis, the minor capsid protein L2 dictates the subcellular retrograde trafficking and nuclear localization of the vDNA during mitosis. Prior work identified a cell-permeable peptide termed SNX1.3, derived from the BAR domain of sorting nexin 1 (SNX1), that potently blocks the retrograde and nuclear trafficking of EGFR in triple negative breast cancer cells. Given the importance of EGFR and retrograde trafficking pathways in HPV16 infection, we set forth to study the effects of SNX1.3 within this context. SNX1.3 inhibited HPV16 infection by both delaying virion endocytosis, as well as potently blocking virion retrograde trafficking and Golgi localization. SNX1.3 had no effect on cell proliferation, nor did it affect post-Golgi trafficking of HPV16. Looking more directly at L2 function, SNX1.3 was found to impair membrane spanning of the minor capsid protein. Future work will focus on mechanistic studies of SNX1.3 inhibition, and the role of EGFR signaling and SNX1-mediated endosomal tubulation, cargo sorting, and retrograde trafficking in HPV infection.