bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of genetic bases of male fertility inPyricularia oryzaeby Genome Wide Association Study (GWAS)
Authors: Lassagne Alexandre , Adreit Henri , Malagnac Fabienne , Charriat Florian , Dumartinet Thomas , Parinello Hugues , Gonzalez Anne-Alicia , Tharreau Didier , Fournier Elisabeth 
Published: April 2024

AbstractThe reproductive system of an organism impacts the emergence and evolution of adaptive variants in response to selective constraints. The understanding of the sexual mode of reproduction in pathogens helps to understand their life history. In filamentous Ascomycete fungi, mating type system and the production of gametes are required to reproduce sexually. In the phytopathogenic AscomycetePyricularia oryzae, studies of the genetic determinants of sexual reproduction are still limited to the mating type system. This study focuses on identifying the genes involved in male fertility through the production of male gametes known as microconidia. We performed a GWAS analysis coupled with a local score approach on a wild recombinant population ofPyricularia oryzaephenotyped for microconidia production. We identified one genomic region significantly associated with the quantity of microconidia produced. This region contained nine candidate genes, some of them annotated with functions associated to sexual reproduction in model fungi such asNeurospora crassa,Podospora anserinaandSordaria macrospora. The most promising candidate gene contains a Jumonji domain. Proteins belonging to the Jumonji family are conserved among Eukaryotes and are known to be involved in chromatin regulation.
BRWD1 establishes epigenetic states for germinal center initiation, maintenance, and function
Authors: Wright Nathaniel E. , Kennedy Domenick E. , Ai Junting , Veselits Margaret L. , Attaway Mary , Yoon Young me , Durkee Madeleine S. , Veselits Jacob , Maienschein-Cline Mark , Mandal Malay , Clark Marcus R. 
Published: April 2024

ABSTRACTGerminal center (GC) B cells segregate into three subsets that compartmentalize the antagonistic molecular programs of selection, proliferation, and somatic hypermutation. In bone marrow, the epigenetic reader BRWD1 orchestrates and insulates the sequential stages of cell proliferation andIgkrecombination. We hypothesized BRWD1 might play similar insulative roles in the periphery. InBrwd1-/-follicular B cells, GC initiation and class switch recombination following immunization were inhibited. In contrast, inBrwd1-/-GC B cells there was admixing of chromatin accessibility across GC subsets and transcriptional dysregulation including induction of inflammatory pathways. This global molecular GC dysregulation was associated with specific defects in proliferation, affinity maturation, and tolerance. These data suggest that GC subset identity is required for some but not all GC-attributed functions. Furthermore, these data demonstrate a central role for BRWD1 in orchestrating epigenetic transitions at multiple steps along B cell developmental and activation pathways.
Intrinsic diving reflex enhances cognitive performance by alleviating microvascular dysfunction in vascular cognitive impairment
Authors: Tambo Willians , Powell Keren , Wadolowski Steven , Sciubba Daniel , Brines Michael , Li Chunyan 
Published: April 2024

AbstractVascular cognitive impairment (VCI) stands as the second-most prominent contributor to cognitive decline, lacking efficacious interventions. Chronic cerebral hypoperfusion (CCH) triggers microvascular dysfunction, which plays a critical role in VCI pathophysiology, emerging as a pivotal therapeutic target. While interventions addressing facets of microvascular dysfunction like angiogenesis and blood-brain barrier functionality show promise, the evaluation of microvascular constriction, another key component, remains unexplored. The diving reflex (DR) represents an oxygen-conserving response, characterized by robust vasodilation and potentially also inducing angiogenesis. In this investigation, we studied DR’s functionality and underlying mechanisms within a rat bilateral common carotid artery occlusion induced CCH model. Remarkably, progressive hippocampal microvascular constriction exhibited strong correlations with short-term memory impairment during both early (R2=0.641) and late phases (R2=0.721) of CCH. Implementation of DR led to a significant reduction in microvascular constriction within the hippocampus (∼2.8-fold) and striatum (∼1.5-fold), accompanied by enhanced vasodilatory capacity and heightened expression of vasoactive neuropeptides. Furthermore, DR attenuated microvascular degeneration across various brain subregions affected by CCH, concomitant with increased levels of multiple angiogenic factors. The reinforced microvascular integrity facilitated by DR corresponded with significantly improved short-term recognition memory and long-term spatial memory functions observed during the late phase of CCH. The comprehensive and synergistic effects of DR on various aspects of microvascular function and cognitive preservation highlight its potential as a disease-modifying therapeutic strategy in VCI.
Exploring the PET in vivo generator134Ce as a theranostic match for225Ac
Authors: Bauer David , De Gregorio Roberto , Pratt Edwin C. , Bell Abram , Michel Alexa , Lewis Jason S. 
Published: April 2024

AbstractPurposeThe radionuclide pair cerium-134/lanthanum-134 (134Ce/134La) was recently proposed as a suitable diagnostic counterpart for the therapeutic alpha-emitter actinium-225 (225Ac). The unique properties of134Ce offer perspectives for developing innovative in vivo investigations not possible with225Ac. In this work,225Ac- and134Ce-labeled tracers were directly compared using internalizing and slow-internalizing cancer models to evaluate their in vivo comparability, progeny meandering, and potential as a matched theranostic pair for clinical translation. Despite being an excellent chemical match,134Ce/134La has limitations to the setting of quantitative positron emission tomography imaging.MethodsThe precursor PSMA-617 and a macropa-based tetrazine-conjugate (mcp-PEG8-Tz) were radiolabelled with225Ac or134Ce and compared in vitro and in vivo using standard (radio)chemical methods. Employing biodistribution studies and positron emission tomography (PET) imaging in athymic nude mice, the radiolabelled PSMA-617 tracers were evaluated in a PC3/PIP (PC3 engineered to express a high level of prostate-specific membrane antigen) prostate cancer mouse model. The225Ac and134Ce-labeled mcp-PEG8-Tz were investigated in a BxPC-3 pancreatic tumour model harnessing the pretargeting strategy based on a trans-cyclooctene-modified 5B1 monoclonal antibody.ResultsIn vitro and in vivo studies with both225Ac and134Ce-labelled tracers led to comparable results, confirming the matching pharmacokinetics of this theranostic pair. However, PET imaging of the134Ce-labelled precursors indicated that quantification is highly dependent on tracer internalization due to the redistribution of134Ce’s PET-compatible daughter134La. Consequently, radiotracers based on internalizing vectors like PSMA-617 are suited for this theranostic pair, while slow-internalizing225Ac-labelled tracers are not quantitatively represented by134Ce PET imaging.ConclusionWhen employing slow-internalizing vectors,134Ce might not be an ideal match for225Ac due to the underestimation of tumour uptake caused by the in vivo redistribution of134La. However, this same characteristic makes it possible to estimate the redistribution of225Ac’s progeny noninvasively. In future studies, this unique PET in vivo generator will further be harnessed to study tracer internalization, trafficking of receptors, and the progression of the tumour microenvironment.TOC GraphicRedistribution of progeny. Investigating the225Ac and134Ce decay chain. This figure was created with BioRender.
Genome-Wide Transcriptome Dynamics in Auxin Homeostasis During Fruit Development in Strawberry (F. xananassa)
Authors: Jang Yoon Jeong , Kim Taehoon , Lin Makou , Kim Jeongim , Begcy Kevin , Liu Zhongchi , Lee Seonghee 
Published: April 2024

AbstractThe plant hormone auxin plays a crucial role in regulating important functions in strawberry fruit development. Although a few studies have described the complex auxin biosynthetic and signaling pathway in wild diploid strawberry (Fragaria vesca), the molecular mechanisms underlying auxin biosynthesis and crosstalk in octoploid strawberry fruit development are not fully characterized. To address this knowledge gap, comprehensive transcriptomic analyses were conducted at different stages of fruit development and compared between the achene and receptacle to identify developmentally regulated auxin biosynthetic genes and transcription factors during the fruit ripening process. Similar to wild diploid strawberry, octoploid strawberry accumulates high levels of auxin in achene compared to receptacle. Consistently, genes functionating in auxin biosynthesis and conjugation, such as TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS (TAAs), YUCCA (YUCs), and GRETCHEN HAGEN 3 (GH3s) were found to be primarily expressed in the achene, with low expression in the receptacle. Interestingly, several genes involved in auxin transport and signaling like PIN-FORMED (PINs), AUXIN/INDOLE-3-ACETIC ACID proteins (Aux/IAAs), TRANSPORT INHIBITOR RESPONSE 1 / AUXIN-SIGNALING F-BOX (TIR/AFBs) and AUXIN RESPONSE FACTOR (ARFs) were more abundantly expressed in the receptacle. Moreover, by examining DEGs and their transcriptional profiles across all six developmental stages, we identified key auxin-related genes co-clustered with transcription factors from the NAM-ATAF1,2-CUC2/ WRKYGQK motif (NAC/WYKY), BASIC REGION/ LEUCINE ZIPPER motif (bZIP), and APETALA2/Ethylene Responsive Factor (AP2/ERF) groups. These results elucidate the complex regulatory network of auxin biosynthesis and its intricate crosstalk within the achene and receptacle, enriching our understanding of fruit development in octoploid strawberries.
Role of miRNA 383 in regulating the mitochondrial machinery and carcinogenesis
Authors: Maurya Ashutosh Kumar , Raji Grace R. , Kumar V.B. Sameer 
Published: April 2024

AbstractMicroRNAs are a class of small non-coding RNAs, which regulate the expression pattern of various genes in a mechanism similar to RNAi. Along with their importance in normal physiology, microRNAs play crucial role in cancer initiation and progression. Various microRNAs have been reported to be associated with the important hallmarks of the cancer including altered mitochondrial machinery. With our in-silico analysis we found that miR 383 has targets on crucial mitochondrial genes involved in electron transport chain. So, next we checked the role of miR 383 in modulation of the mitochondrial machinery and effect of this alteration in the process of carcinogenesis. The results suggested that miR 383 contribute to carcinogenesis, possibly by modulating the mitochondrial machinery via targeting ND4L and ATP6 genes involved in the complex 1 & 5 of electron transport chain.
MicroRNA 106b: Role in the reprograming of mitochondrial machinery and carcinogenesis in hepatic cells
Authors: Maurya Ashutosh Kumar , Edatt Lincy , Kumar V.B. Sameer 
Published: April 2024

AbstractCancer is a disease of unregulated cell growth. The process of initiation and progression of cancer is called carcinogenesis and the factors possessing ability to induce carcinogenesis are called carcinogens. Along with the coding sequence, the non-coding sequence also play very crucial role in the process of carcinogenesis. MicroRNAs are small non-coding RNAs having targets on both the classes of genes important in cancer i.e., oncogenes and tumour suppressor genes, thus act as key play in carcinogenesis. Dysfunctional mitochondrial metabolism has been widely reported in cancer and this malfunctioning could be brought in by suppression of the expression pattern of important mitochondrial genes by microRNAs. Our in-silico analysis revealed that miR 106b possess targets on several important mitochondrial genes involved in various complexes of electron transport chain. Further, we checked the role of miR 106b in reprogramming of the mitochondrial mechanism and carcinogenesis. The results suggested that miR 106b contributes to carcinogenesis in hepatic cells by modulating the mitochondrial metabolism.
The mechanical and sensory signature of plant-based and animal meat
Authors: St. Pierre Skyler R. , Darwin Ethan C. , Adil Divya , Aviles Magaly C. , Date Archer , Dunne Reese A. , Lall Yanav , Vallecillo María Parra , Medina Valerie A. Perez , Linka Kevin , Levenston Marc E. , Kuhl Ellen 
Published: April 2024

AbstractEating less meat is associated with a healthier body and planet. Yet, we remain reluctant to switch to a plant-based diet, largely due to the sensory experience of plant-based meat. Food scientists characterize meat using a double compression test, which only probes one-dimensional behavior. Here we use tension, compression, and shear tests–combined with constitutive neural networks–to automatically discover the behavior of eight plant-based and animal meats across the entire three-dimensional spectrum. We find that plant-based sausage and hotdog, with stiffnesses of 95.9±14.1kPa and 38.7±3.0kPa, successfully mimic their animal counterparts, with 63.5±45.7kPa and 44.3±13.2 kPa, while tofurky is twice as stiff, and tofu is twice as soft. Strikingly, a complementary food tasting survey produces in nearly identical stiffness rankings for all eight products (ρ=0.833, p=0.015). Probing the fully three-dimensional signature of meats is critical to understand subtle differences in texture that may result in a different perception of taste.Our data and code are freely available athttps://github.com/LivingMatterLab/CANN
Deep learning-driven imaging of cell division and cell growth across an entire eukaryotic life cycle
Authors: Ramakanth Shreya , Kennedy Taylor , Yalcinkaya Berk , Neupane Sandhya , Tadic Nika , Buchler Nicolas E. , Argüello-Miranda Orlando 
Published: April 2024

AbstractThe life cycle of biomedical and agriculturally relevant eukaryotic microorganisms involves complex transitions between proliferative and non-proliferative states such as dormancy, mating, meiosis, and cell division. New drugs, pesticides, and vaccines can be created by targeting specific life cycle stages of parasites and pathogens. However, defining the structure of a microbial life cycle often relies on partial observations that are theoretically assembled in an ideal life cycle path. To create a more quantitative approach to studying complete eukaryotic life cycles, we generated a deep learning-driven imaging framework to track microorganisms across sexually reproducing generations. Our approach combines microfluidic culturing, life cycle stage-specific segmentation of microscopy images using convolutional neural networks, and a novel cell tracking algorithm, FIEST, based on enhancing the overlap of single cell masks in consecutive images through deep learning video frame interpolation. As proof of principle, we used this approach to quantitatively image and compare cell growth and cell cycle regulation across the sexual life cycle ofSaccharomyces cerevisiae. We developed a fluorescent reporter system based on a fluorescently labeled Whi5 protein, the yeast analog of mammalian Rb, and a new High-Cdk1 activity sensor, LiCHI, designed to report during DNA replication, mitosis, meiotic homologous recombination, meiosis I, and meiosis II. We found that cell growth preceded the exit from non-proliferative states such as mitotic G1, pre-meiotic G1, and the G0 spore state during germination. A decrease in the total cell concentration of Whi5 characterized the exit from non-proliferative states, which is consistent with a Whi5 dilution model. The nuclear accumulation of Whi5 was developmentally regulated, being at its highest during meiotic exit and spore formation. The temporal coordination of cell division and growth was not significantly different across three sexually reproducing generations. Our framework could be used to quantitatively characterize other single-cell eukaryotic life cycles that remain incompletely described. An off-the-shelf user interfaceYeastvisionprovides free access to our image processing and single-cell tracking algorithms.
bayesTPC: Bayesian inference for Thermal Performance Curves in R
Authors: Sorek Sean , Smith John W. , Huxley Paul J. , Johnson Leah R. 
Published: April 2024

1AbstractReliable predictions of arthropod responses to climatic warming are important because many of these species perform important roles that can directly impact human society.Thermal performance curves (TPCs) provide useful information on the physiological constraints that limit the capacity of temperature-sensitive organisms (like arthropods) to exist and grow.NLS pipelines for fitting TPCs are widely available, but these approaches rely on assumptions that can yield unreliable parameter estimates.We presentbayesTPC, anRpackage for fitting TPCs to trait responses using the nimble language and machinery as the underlying engine for Markov Chain Monte Carlo.bayesTPCaims to support the adoption of Bayesian approaches in thermal physiology, and promote TPC fitting that adequately quantifies uncertainty.
Dispersed Transcription Start Sites Modulate uORF-Mediated Regulation in Arabidopsis
Authors: Wu Hsin-Yen Larry , Hsu Polly Yingshan 
Published: April 2024

ABSTRACTIn eukaryotic mRNAs, upstream open reading frames (uORFs) in the 5′ untranslated regions (5′ UTRs) often attenuate the translation of downstream main ORFs (mORFs). While some uORFs are beneficial by playing important regulatory roles, uORFs are generally disfavored in evolution. Here we studied how uORF repression is suppressed in Arabidopsis. We found that the heterogeneous distribution of transcription start sites (TSSs) results in heterogeneous 5′ UTRs that selectively exclude uORFs from mRNAs. Thus, only a subset of the transcripts from “uORF-containing” genes truly contain uORFs. Importantly, the fraction of uORFs remaining within transcripts determines uORF overall repressiveness. Interestingly, uORFs that encode conserved peptides are almost exclusively preserved within mRNAs, implying coevolution between TSSs and functional uORFs. Consistent with TSSs determining uORF presence, a sharp transition of AUG frequency between promoters and 5′ UTRs was observed, and this pattern differentiates between genes lacking and carrying translated uORFs. Remarkably, while 55% of the genes are predicted to contain uORFs, upon accounting for the heterogeneous TSSs, only 9% of the transcripts within the mRNA pool genuinely contain uORFs. Our results highlight a profound effect of TSS distribution in determining uORF repressiveness, a factor that was previously overlooked. As a warning note, the TSS heterogeneity should be taken into consideration when studying various 5′ UTR features, such as RNA structures and protein binding motifs, in post-transcriptional gene regulation. The uORFs and other features preferentially preserved in 5′ UTRs (i.e., downstream of TSSs) are more likely to be functional as the result of natural selection.
Taking advantage of reference-guided assembly in a slowly-evolving lineage: application to Testudo graeca
Authors: Mira-Jover Andrea , Graciá Eva , Giménez Andrés , Fritz Uwe , Rodríguez-Caro Roberto Carlos , Bourgeois Yann 
Published: April 2024

ABSTRACTBackgroundObtainingde novochromosome-level genome assemblies greatly enhances conservation and evolutionary biology studies. For many research teams, long-read sequencing technologies (that produce highly contiguous assemblies) remain unaffordable or unpractical. For the groups that display high synteny conservation, these limitations can be overcome by a reference-guided assembly using a close relative genome. Of chelonians, terrestrial tortoises are considered one of the most endangered taxa, which calls for more genomic resources. Here we make the most of high synteny conservation in chelonians to produce the first chromosome-level genome assembly of genusTestudowith one of the most iconic tortoise species in the Mediterranean basin:T. graeca.ResultsWe used high quality, paired-end Illumina sequences to build a reference-guided assembly with the chromosome level assembly ofGopherus evgoodei.We reconstructed a 2.29 Gb haploid genome with a scaffold N50 of 107.598 Mb and 5.37% gaps. We sequenced 25998 protein-coding genes, and a 41.2% fraction was determined as repetitive in our assembled genome. Demographic history reconstruction based on the genome revealed two events (population decline and recovery) consistent with previously suggested phylogeographic patterns for the species. This outlines the value of genomes like this for phylogeographic studies.ConclusionsOur results highlight the value of using close relatives to producede novodraft assemblies in species where such resources are unavailable. OurTestudo graecaannotated genome paves the way to delve deeper into the species’ evolutionary history and provides a valuable resource to increase making direct conservation efforts on their threatened populations.
A roadmap for implanting microelectrode arrays to evoke tactile sensations through intracortical microstimulation
Authors: Downey John E , Schone Hunter R , Foldes Stephen T , Greenspon Charles , Liu Fang , Verbaarschot Ceci , Biro Daniel , Satzer David , Moon Chan Hong , Coffman Brian A , Youssofzadeh Vahab , Fields Daryl , Hobbs Taylor G , Okorokova Elizaveta , Tyler-Kabara Elizabeth C , Warnke Peter C , Gonzalez-Martinez Jorge , Hatsopoulos Nicholas G , Bensmaia Sliman J , Boninger Michael L , Gaunt Robert A , Collinger Jennifer L 
Published: April 2024

AbstractIntracortical microstimulation (ICMS) is a method for restoring sensation to people with paralysis as part of a bidirectional brain-computer interface to restore upper limb function. Evoking tactile sensations of the hand through ICMS requires precise targeting of implanted electrodes. Here we describe the presurgical imaging procedures used to generate functional maps of the hand area of the somatosensory cortex and subsequent planning that guided the implantation of intracortical microelectrode arrays. In five participants with cervical spinal cord injury, across two study locations, this procedure successfully enabled ICMS-evoked sensations localized to at least the first four digits of the hand. The imaging and planning procedures developed through this clinical trial provide a roadmap for other brain-computer interface studies to ensure successful placement of stimulation electrodes.