bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pheno-Morphological Characterization and Genetic Diversity Assessment of Grain and Vegetable Soybean (Glycine max. (L.) Merrill) Lines for Breeding Advancements
Authors: Saha Madhumita , Chavan Mohan , Onkarappa T , Ravikumar R L , Das Uddalak 
Published: December 2024

AbstractThis study presents for the first time, a thorough pheno-morphological characterization of ten soybean [Glycine max(L.) Merrill] lines (four grain type and six vegetable type). The vegetable soybean, also called asEdamame, and the grain type soybean, which underpin considerable genetic variation across traits such as flowering and pod-setting times, plant height, and seed size. Analyses of variance and clustering reveal obvious differentiation between vegetable and grain-type soybeans, particularly in traits such as height at the R7 stage, pod length, and branching patterns. The vegetable type exhibited faster plant development throughout reproductive stages and tended to be taller than the grain type. The study found characteristics, including test weight, plant height, and pods per plant, had higher phenotypic and genotypic coefficient of variation and, therefore, may serve as good candidates for selection breeding since these characteristics are based on a strong genetic constitution and to a lesser extent on environmental influences. The traits like number of pods per plant and test weight had high heritability and genetic advance and thus held great promise for improvement of productivity through selection. Important PCA explained traits were the plant height at the R7 stage, number of branches, and number of pods per cluster, which have high values for the breeding program. Hierarchical clustering also clumped the genotypes from other morphological characteristics which grouped them into clear distinct classification for the genetic diversity of this germplasm. In relation to this, one realizes that these soybean lines have genetic variability for significant breeding programs concerning increases in yield, adaptability, and resistance to stresses: biotic and abiotic.
RGnet: Recessive Genotype Network in a Large Mendelian Disease Cohort
Authors: Ai Fandi , Kang Lu , Zeng Jiayi , He Mingmin , Zhong Mingjun , Cheng Jing , Lu Yu , Yuan Huijun , Bu Fengxiao 
Published: December 2024

AbstractRecessive genotypes, including compound heterozygotes and homozygotes formed by rare variants that impact gene function, affect both alleles and were linked to numerous diseases and traits. However, the underlying patterns and interconnections of these recessive genotypes in large cohorts have rarely been studied. To address this gap, the Recessive Genotype Network (RGnet) was developed. This network model maps variant and genotype features to visualize and analyze recessive genotype patterns within large cohorts. Additionally, it uses permutation-based analyses to assess the enrichment of these genotypes in relation to specific phenotypes. Demonstrated through its application to the genetic deafness geneSLC26A4in 22,125 cases affected by hearing loss, RGnet successfully identified pathogenic variants with high connectivity, providing a reliable method for exploring the pathogenic mechanisms underlying recessive disorders or traits.Availability and ImplementationRGnet is available from GitHub athttps://github.com/jiayiiiZeng/RGnetContactbufengxiao@wchscu.cnSupplementary informationSupplementary data are available at Bioinformatics online.
CrGEF1, CrGAP1, and CrGDI2 function as key regulators of ROP-GTPase mediated modulation of alkaloid biosynthesis inCatharanthus roseus
Authors: Sharma Anuj , Mohan Sruthi , Gupta Priyanka , Parihar Durgesh , Nagegowda Dinesh A. 
Published: December 2024

ABSTRACTROP-GTPase Regulatory Proteins (RGRPs) have been shown to control plant morphogenesis, development and immunity, however, their role in specialized metabolism is hitherto not known. Here, we demonstrate that specific RGRPs control monoterpene indole alkaloid (MIA) biosynthesis by interacting with distinct Rho of Plants (ROP) inCatharanthus roseus. Among the five Guanine nucleotide Exchange Factors (GEFs), four GTPase-activating proteins (GAPs), and two GDP dissociation inhibitors (GDIs) identified in theC. roseusgenome, only CrGEF1, CrGAP1, and CrGDI2 specifically interacted with CrROP3 and CrROP5. These RGRPs displayed distinct cytosolic and/or membrane localization patterns, with their transcripts predominantly expressed in aerial tissues. Functional studies revealed thatCrGEF1acts as a positive regulator of MIA biosynthesis, as its silencing led to a reduction in MIA production, while overexpression enhanced MIA levels. Conversely, CrGAP1 and CrGDI2 function as negative regulators, with their silencing resulting in increased MIA production and their overexpression causing reduced MIA levels. Notably, terminal truncated forms of these RGRPs showed interaction with CrROP3 or CrROP5 but failed to influence MIA biosynthesis, underscoring the importance of these domains in their regulatory functions. Overall, our findings uncover a previously unexplored mechanism by which distinct RGRPs coordinate with specific ROPs to regulate transcription factors and fine-tune MIA biosynthesis inC. roseus.SignificancePlants fine-tune their metabolic pathways to adapt to environmental and physiological cues, balancing primary and specialized metabolism. Here, we uncover a feedback regulatory mechanism by which ROP-GTPase regulatory proteins (RGRPs) control alkaloid biosynthesis inCatharanthus roseus. We found that CrGEF1, CrGAP1, and CrGDI2 specifically interact with ROP-GTPases CrROP3 and CrROP5, modulating the monoterpene indole alkaloid (MIA) pathway. This RGRP-ROP module plays a crucial role in dynamically regulating MIA levels, where CrGEF1 promotes MIA production while CrGAP1 and CrGDI2 act as negative regulators. These findings highlight the importance of RGRP-ROP circuitry in control of alkaloid biosynthesis inC. roseus, and specialized metabolism in plants.
Retrotransposon LINE1 trans-inhibiting differentiation maintains embryonic stem cell identity
Authors: Ren Likun , Teng Yue , Xu Wenqiu , Hou Jingya , Lu Mengyue , Shi Feitong , Ren Jie , Zheng Caihong , Cai Jun 
Published: December 2024

AbstractLong Interspersed Nuclear Elements-1s (LINE1s) are one of the >17% most abundant Retrotransposons in mammalian genomes. LINE1 RNA is high expression during early embryonic development, meanwhile is under tight epigenetic control. Some studies have confirmed LINE1 play a critical role in early embryo development and ESC identity. Previous studies focused on the role of LINE1 in cis-regulation, however, the function of L1 RNA in tans-regulation remains largely unknown. In this study, we performed a high-throughput proximity MARGI (pxMARGI) experiment found transposon LINE1 RNA trans-regulated prefer to young LINE1 subfamily, and in hybrid and non-hybrid two different manner repress ESC to dual progress of 2C-like cells and differentiation. In differentiation process, LINE1 RNA as a scaffold recruit polycomb core subunits combine three core pluripotent factors maintain ESC identity. In 2C process, LINE1 RNA in a sequence-specific manner recruit Kap1 to old L1 subfamily, and recruit ELL3 to RE 5‘UTR maintain ESC self-renewal. Our data point to LINE1 transcriptions more detail trans-regulation mechanism to orchestrate developmental progression for the self-renewal of embryonic stem cells (ESCs). LINE1 RNA may be potential biomarker for noninvasive embryo selection.
Cell-Cell Fusion in NSCLC Confers a Fitness Benefit Under Drug Selection
Authors: Shultes Paulameena V. , Tadele Dagim S. , Durmaz Arda , Weaver Davis T. , Barker-Clarke Rowan , Dinh Mina N. , Liu Siqing , Alemu Endalkachew A. , Rayner Simon , Scott Jacob G. 
Published: December 2024

ABSTRACTCell-cell fusion has been implicated in various physiological and pathological processes, including cancer progression. This study investigated the role of cell-cell fusion in non-small cell lung cancer (NSCLC), focusing on its contribution to chemoresistance and tumor evolution. By co-culturing drug-sensitive and drug-resistant NSCLC cell lines, we observed spontaneous cell-cell fusion events, particularly under gefitinib selection. These fused cells exhibited enhanced fitness and a higher degree of chemoresistance compared to parental lines across a panel of 12 chemotherapeutic agents. Further analysis, including fluorescence imaging and cell cycle analysis, confirmed nuclear fusion and increased DNA content in the fused cells. Bulk RNA sequencing revealed genomic heterogeneity in fused cells, including enrichment of gene sets associated with cell cycle progression and epithelial-mesenchymal transition, hallmarks of cancer malignancy. These findings demonstrate that cell-cell fusion contributes significantly to therapeutic resistance and the promotion of aggressive phenotypes in NSCLC, highlighting its potential as a therapeutic target.
Structure of the ciliary tip central pair reveals the unique role of the microtubule-seam binding protein SPEF1
Authors: Legal Thibault , Joachimiak Ewa , Parra Mireya , Peng Wang , Tam Amanda , Black Corbin , Valente-Paterno Melissa , Brouhard Gary , Gaertig Jacek , Wloga Dorota , Bui Khanh Huy 
Published: December 2024

AbstractMotile cilia are unique organelles with the ability to autonomously move. Force generated by beating cilia propels cells and moves fluids. The ciliary skeleton is made of peripheral doublet microtubules and a central pair (CP) with a distinct structure at the tip. In this study, we present a high-resolution structure of the CP in the ciliary tip of the ciliateTetrahymena thermophilaand identify several tip proteins that bind and form unique patterns on both microtubules of the tip CP. Two of those proteins that contain tubulin polymerization-promoting protein (TPPP)-like domains, TLP1 and TLP2, bind to high curvature regions of the microtubule. TLP2, which contains two TPPP-like domains, is an unusually long protein that wraps laterally around half a microtubule and forms the bridge between the two microtubules. Moreover, we found that the conserved protein SPEF1 binds to both microtubule seams.In vitro, human SPEF1 not only binds to the microtubule seam but also crosslinks two parallel microtubules. Single-molecule microtubule dynamics assays indicate that SPEF1 stabilizes microtubulesin vitro. Together, these data show that the proteins in the tip CP maintain stable microtubule structure and probably play important roles in maintaining the integrity of the axoneme.
Expanding GABAergic Neuronal Diversity in iPSC-Derived Disease Models
Authors: Hu Ruiqi , Boshans Linda L. , Zhu Bohan , Cai Peiwen , Tao Yiran , Youssef Mark , Girrbach Gizem Inak , Song Yingnan , Wang Xuran , Tsankov Alexander , Buxbaum Joseph D. , Ma Sai , Yang Nan 
Published: December 2024

AbstractGABAergic interneurons play a critical role in maintaining neural circuit function, and their dysfunction is implicated in various neurodevelopmental and psychiatric disorders. Traditional approaches for differentiating human pluripotent stem cells (PSCs) into neuronal cells often face challenges such as incomplete neural differentiation, prolonged culture periods, and variability across PSC lines. To address these limitations, we developed a new strategy that integrates overexpression of transcription factors ASCL1 and DLX2 with dual-SMAD and WNT inhibition, efficiently driving the differentiation of human PSCs into diverse, region-specific GABAergic neuronal types. Using single-cell sequencing, we characterized the cellular heterogeneity of GABAergic induced neurons (iNs) generated with the patterning factors (patterned iNs) and those derived solely with transcription factors (PSC-derived iNs), uncovering the regulatory mechanisms that govern their fate specification. Patterned iNs exhibited gene expression features corresponding to multiple brain regions, particularly ganglionic eminence (GE) and neocortex, while GABAergic PSC-derived iNs predominantly resembled hypothalamic and thalamic neurons. Both iN types were enriched for genes relevant to neurodevelopmental and psychiatric disorders, with patterned iNs more specifically linked to neural lineage genes, highlighting their utility for disease modeling. We further applied this protocol to investigate the impact of an ADNP syndrome-associated mutation (p.Tyr719* variant) on GABAergic neuron differentiation, revealing that this mutation disrupts GABAergic fate specification and synaptic transmission. Overall, this study expands the toolkit for disease modeling by demonstrating the complementary advantages of GABAergic PSC-derived iNs and patterned iNs in representing distinct GABAergic neuron subtypes, brain regions, and disease contexts. These approaches offer a powerful platform for elucidating the molecular mechanisms underlying various neurodevelopmental and psychiatric disorders.
Tabula Sapiens reveals transcription factor expression, senescence effects, and sex-specific features in cell types from 28 human organs and tissues
Authors: Quake Stephen R ,   The Tabula Sapiens Consortium
Published: December 2024

AbstractThe Tabula Sapiens is a reference human cell atlas containing single cell transcriptomic data from more than two dozen organs and tissues. Here we report Tabula Sapiens 2.0 which includes data from nine new donors, doubles the number of cells in Tabula Sapiens, and adds four new tissues. This new data includes four donors with multiple organs contributed, thus providing a unique data set in which genetic background, age, and epigenetic effects are controlled for. We analyzed the combined Tabula Sapiens data for expression of transcription factors, thereby providing putative cell type specificity for nearly every human transcription factor and as well as new insights into their regulatory roles. We analyzed the molecular phenotypes of senescent cells across the entire data set, providing new insight into both the universal attributes of senescence as well as those aspects of human senescence that are specific to particular organs and cell-types. Similarly, we analyzed sex-specific gene expression across all of the identified cell types and discovered which cell types and genes have the most distinct sex based gene expression profiles. Finally, to enable accessible analysis of the voluminous medical records of Tabula Sapiens donors, we created a web application powered by a large language model that allows users to ask general questions about the health history of the donors.
Trehalose supports the growth ofAedes aegypticells and modifies gene expression and dengue virus replication
Authors: Marten Andrew D. , Haslitt Douglas P. , Martin Chad A. , Swanson Daniel H. , Kalera Karishma , Johnson Ulysses G. , Swarts Benjamin M. , Conway Michael J. 
Published: December 2024

AbstractTrehalose is a non-reducing disaccharide that is the major sugar found in insect hemolymph fluid. Trehalose provides energy, and promotes growth, metamorphosis, stress recovery, chitin synthesis, and insect flight. Trehalase is the only enzyme responsible for the hydrolysis of trehalose, which makes it an attractive molecular target. Here we show thatAedes aegypti(Aag2) cells express trehalase and that they can grow on trehalose-containing cell culture media. Trehalase activity was confirmed by treating Aag2 cells with trehalase inhibitors, which inhibited conversion of trehalose to glucose and reduced cell proliferation. Cell entry of a fluorescent trehalose probe was dependent on trehalose concentration, suggesting that trehalose moves across the cell membrane via passive transport. Culturing Aag2 cells with trehalose-containing cell culture media led to significant changes in gene expression, intracellular lipids, and dengue virus replication and specific infectivity, and increased their susceptibility to trehalase inhibitors. These data describe anin vitromodel that can be used to rapidly screen novel trehalase inhibitors and probes and underscores the importance of trehalose metabolism inAe. aegyptiphysiology and transmission of a mosquito-borne virus.
Tmbim5 loss causes muscle atrophy in zebrafish without exacerbating mcu or slc8b1 knockout phenotypes
Authors: Wasilewska Iga , Adamek-Urbańska Dobrochna , Baranykova Sofiia , Majewski Łukasz , Methner Axel 
Published: December 2024

AbstractMitochondria generate ATP by creating a proton gradient across the inner membrane. This gradient also drives calcium uptake by the mitochondrial calcium uniporter (MCU) complex, while NCLX, encoded bySLC8B1,facilitates efflux. Mcu deficiency in various species does not result in obvious phenotypes, suggesting the existence of additional calcium transport systems. We here generated zebrafish lacking Tmbim5, a potential bidirectional mitochondrial calcium transporter, and Slc8b1, the probable NCLX ortholog.tmbim5knockout fish exhibited impaired growth, muscle atrophy, increased brain cell death, and reduced mitochondrial membrane potential, but no significant changes in steady-state mitochondrial calcium levels. Slc8b1-deficient fish had increased larval mortality but were otherwise normal. Double knockouts oftmbim5/mcuandtmbim5/slc8b1were viable with normal Mendelian distribution, indicating robust compensatory mechanisms maintain calcium homeostasis.tmbim5knockout rescued the increased mortality in Slc8b1-deficient fish, and the NCLX inhibitor CGP-37157 lost its effect on behavior in Tmbim5-deficient but not Slc8b1-deficient zebrafish, implying shared, possibly antagonistic pathways. These findings suggest alternative pathways for mitochondrial calcium transport compensate for the loss of these proteins, enabling zebrafish survival.
Intermittent suppressive posaconazole therapy is ineffective at mitigating cardiac and digestive tract pathologies in an experimental model of chronic Chagas disease
Authors: Jayawardhana Shiromani , Olmo Francisco , Fortes Francisco Amanda , Khan Archie A. , Lewis Michael D. , Taylor Martin C. , Kelly John M. 
Published: December 2024

ABSTRACTInfections withTrypanosoma cruzicause Chagas disease, a chronic condition that can give rise to debilitating cardiac and/or gastrointestinal damage. However, it is unclear why only ∼30% of individuals progress to symptomatic pathology, why this can take decades to become apparent, and why there is such a wide range of disease outcomes. Disease pathology is a long-term cumulative process resulting from collateral damage caused by inflammatory immune responses that continually eliminate transient parasite infections in the heart and/or gastrointestinal tract. The guiding principle behind anti-parasitic drug development is that sterile cure is required to prevent progression to symptomatic pathology. Evidence suggests that the cumulative damage required to reach the symptomatic threshold is determined by a number of factors, including host and parasite genetics, which govern the intensity and location(s) of infection. Therefore, an alternative therapeutic strategy could involve long-term intermittent treatment, which may not confer sterile cure, but is able to suppress the parasite burden to a level where the disease does not become symptomatic within the life-time of the infected individual. To test this hypothesis, we used an experimental murine model that displays both cardiac and digestive tract pathology. Mice were given intermittent treatment with posaconazole, under conditions that reduced the parasite burden by >99%, but did not confer sterile clearance. Our results show that this did not provide long-term protection against the key cardiac or gastrointestinal manifestations of Chagas disease, and that sterile cure should remain the single goal of the drug development community.
A computational Evo-Devo approach for elucidating the roles of PLETHORA transcription factors in regulating root development
Authors: Rodríguez Herrera Joel , Galván Alcaraz Kenia Aislinn , Albarrán Hernández Ramsés Uriel , Villa Núñez Juan Pablo , Rodríguez Alonso Gustavo , Shishkova Svetlana 
Published: December 2024

AbstractPLETHORA (PLT) transcription factors play essential roles in regulating various developmental processes in plants, including embryogenesis, rhizotaxis, phyllotaxis, and most prominently, root development, by regulating cell proliferation and differentiation along the root. Despite their important roles in plant development, PLT transcription factors have mainly been studied inArabidopsis thalianaand only a few crop species.A. thalianahas sixPLTgenes, which are expressed in overlapping domains and have partially redundant activities, with numerous shared target genes. Here we identified putativePLTorthologs across Viridiplantae, including representatives of all extant plant clades, reconstructing the molecular phylogeny of PLTs and integrating synteny and microsynteny analyses. We suggest that PLTs arose by neofunctionalization prior to the divergence of Spermatophyta and that they might regulate their target genes in a context-specific manner given the presence of intrinsically disordered regions at their N- and C-termini. After identifying direct PLT targets in public databases, we inferred a gene regulatory network driven by PLTs in the root apical meristem in six angiosperm species. Our results suggest that the direct PLT targets regulate ribosome and ribonucleoprotein biogenesis as well as RNA processing, among other basic cellular processes. The central relevance of these processes may account for the high conservation and stability of PLT-driven gene regulatory networks across angiosperms.
Prophage induction contributes to alterations in the gut phageome during intestinal inflammation
Authors: Sinha Anshul , Qian Amy , Boutin Tommy , Maurice Corinne F. 
Published: December 2024

SummaryBacteriophages (phages) are abundant members of the gut microbiota and regulators of bacterial communities. During homeostasis, gut phage communities are longitudinally stable and lysogenic replication is dominant. In chronic gut inflammatory disorders, such as inflammatory bowel diseases (IBDs), there are alterations in phage diversity, which may result from changes in phage replication cycle dynamics. Here, we used a combination ofin vitro, simplified community, and whole-community bioinformatics approaches to investigate whether prophage induction contributes to these alterations. We identified several compounds associated with gut inflammation that induced prophages in commensal gut bacterial isolates. Analysing data from two mouse models of colitis, we observed that shifts in the composition of temperate phages occur over the course of inflammation, supporting a switch from lysogenic to lytic replication. Collectively, our observations support the idea that prophage induction contributes to alterations in the phageome associated with inflammation.