bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short-term social isolation acts on hypothalamic neurons to promote social behavior in a sex- and context-dependent manner
Authors: Zhao Xin , Chae Yurim , Smith Destiny , Chen Valerie , DeFelipe Dylan , Sokol Joshua W , Sadangi Archana , Tschida Katherine 
Published: November 2023

AbstractSocial animals, including both humans and mice, are highly motivated to engage in social interactions. Short-term social isolation promotes social behavior, but the neural circuits through which it does so remain incompletely understood. Here, we sought to identify neurons that promote social behavior in single-housed female mice, which exhibit increased rates of social investigation, social ultrasonic vocalizations (USVs), and mounting during same-sex interactions that follow a period of short-term (3-day) isolation. We first used immunostaining for the immediate early gene Fos to identify a population of neurons in the preoptic hypothalamus (POA) that increase their activity in single-housed females following same-sex interactions (POAsocialneurons) but not in single-housed females that did not engage in social interactions. TRAP2-mediated chemogenetic silencing of POAsocialneurons in single-housed females significantly attenuates the effects of short-term isolation on social investigation, USV production, and mounting. In contrast, caspase-mediated ablation of POAsocialneurons in single-housed females robustly attenuates mounting but does not decrease social investigation or USV production. Optogenetic activation of POAsocialneurons in group-housed females promotes social investigation and USV production but does not recapitulate the effects of short-term isolation on mounting. To understand whether a similar population of POAsocialneurons promotes social behavior in single-housed males, we performed Fos immunostaining in single-housed males following either same-sex or opposite-sex social interactions. These experiments revealed a population of POA neurons that increase Fos expression in single-housed males following opposite-sex, but not same-sex, interactions. Chemogenetic silencing of POAsocialneurons in single-housed males during interactions with females reduces mounting but does not affect social investigation or USV production. These experiments identify a population of hypothalamic neurons that promote social behavior following short-term isolation in a sex- and social context-dependent manner.
Short communication: Accounting for nuclear and mito genome in dairy cattle breeding - a simulation study
Authors: Mafra Fortuna Gabriela , Zumbach B.J. , Johnsson M. , Pocrnic I. , Gorjanc G. 
Published: November 2023

AbstractMitochondria play a significant role in numerous cellular processes through proteins encoded by both nuclear genome (nDNA) and mito genome (mDNA). While the variation in nDNA is influenced by mutations and recombination of parental genomes, the variation in mDNA is solely driven by mutations. In addition, mDNA is inherited in a haploid form, from the dam. Cattle populations show significant variation in mDNA between and within breeds. Past research suggests that variation in mDNA accounts for 1-5% of the phenotypic variation in dairy traits. Here we simulated a dairy cattle breeding program to assess the impact of accounting for mDNA variation in pedigree-based and genome-based genetic evaluations on the accuracy of estimated breeding values for mDNA and nDNA components. We also examined the impact of alternative definitions of breeding values on genetic gain, including nDNA and mDNA components that both impact phenotype expression, but mDNA is inherited only maternally. We found that accounting for mDNA variation increased accuracy between +0.01 and +0.05 for different categories of animals, especially for young bulls (+0.05) and females without genotype data (between +0.01 and +0.03). Different scenarios of modelling and breeding value definition impacted genetic gain. The standard approach of ignoring mDNA variation achieved competitive genetic gain. Modelling, but not selecting on mDNA expectedly reduced genetic gain, while optimal use of mDNA variation recovered the genetic gain.
Antagonistic conflict between transposon-encoded introns and guide RNAs
Authors: Žedaveinytė Rimantė , Meers Chance , Le Hoang C. , Mortman Edan E. , Tang Stephen , Lampe George D. , Pesari Sanjana R. , Gelsinger Diego R. , Wiegand Tanner , Sternberg Samuel H. 
Published: November 2023

ABSTRACTTnpB nucleases represent the evolutionary precursors to CRISPR-Cas12 and are widespread in all domains of life, presumably due to the critical roles they play in transposon proliferation. IS605-family TnpB homologs function in bacteria as programmable homing endonucleases by exploiting transposon-encoded guide RNAs to cleave vacant genomic sites, thereby driving transposon maintenance through DSB-stimulated homologous recombination. Whether this pathway is conserved in other genetic contexts, and in association with other transposases, is unknown. Here we uncover molecular mechanisms of transposition and RNA-guided DNA cleavage by IS607-family elements that, remarkably, also encode catalytic, self-splicing group I introns. After reconstituting and systematically investigating each of these biochemical activities for a candidate ‘IStron’ derived fromClostridium botulinum, we discovered sequence and structural features of the transposon-encoded RNA that satisfy molecular requirements of a group I intron and TnpB guide RNA, while still retaining the ability to be faithfully mobilized at the DNA level by the TnpA transposase. Strikingly, intron splicing was strongly repressed not only by TnpB, but also by the secondary structure of ωRNA alone, allowing the element to carefully control the relative levels of spliced products versus functional guide RNAs. Our results suggest that IStron transcripts have evolved a sensitive equilibrium to balance competing and mutually exclusive activities that promote transposon maintenance while limiting adverse fitness costs on the host. Collectively, this work explains how diverse enzymatic activities emerged during the selfish spread of IS607-family elements and highlights molecular innovation in the multi-functional utility of transposon-encoded noncoding RNAs.
Season-specific dominance broadly stabilizes polymorphism under symmetric and asymmetric multivoltinism
Authors: Brud Evgeny 
Published: November 2023

AbstractSeasonality causes intraannual fitness changes in multivoltine populations (defined as having multiple generations per year). While it is well-known that seasonally balanced polymorphism is established by overdominance in geometric mean fitness, an unsettled aspect of the deterministic theory is the relative contribution of various season-specific dominance mechanisms to the potential for polymorphism. In particular, the relative importance of seasonally-reversing and non-reversing schemes remains unclear. Here I analyze the parameter space for the discrete generation two-season multivoltine model and conclude that, in general, a substantial fraction of stabilizing schemes are non-reversing with the season (∼25-50%). In addition, I derive the approximate equilibrium allele frequency cycle under bivoltinism, and find that the amplitude of allelic oscillation is maximized by non-reversing dominance if the selection coefficients are roughly symmetric. Lastly, I derive conditions for the intralocus evolution of dominance. These predict a long-term trend toward maximally beneficial reversal. Overall, the results counter the disproportionate emphasis placed on dominance reversal as a stabilizing mechanism and clarify that non-reversing dominance is expected to frequently characterize seasonally fluctuating alleles under both weak and strong selection, especially in their early history. I conclude that seasonally alternating selection regimes are easily able to maintain allelic variation without restrictive assumptions on either selection coefficients or dominance parameters.
Particulate organic matter drives spatial variation in denitrification potential at the field scale
Authors: Stuchiner Emily R. , Jernigan Wyatt A. , Zhang Ziliang , Eddy William C. , DeLucia Evan H. , Yang Wendy H. 
Published: November 2023

AbstractHigh spatiotemporal variability in soil nitrous oxide (N2O) fluxes challenges quantification and prediction of emissions to evaluate the climate change mitigation outcomes of sustainable agricultural practices. Triggers for large, short-lived N2O emission pulses, such as rainfall and fertilization, alter soil oxygen (O2) and nitrate (NO3−) availability to favor N2O production via denitrification. However, the organic C (OC) needed to fuel denitrification may exhibit subfield variation that constrains the potential for high denitrification rates to occur, leading to spatial variation in N2O hot moments. We tested the hypothesis that the particulate organic matter (POM) fraction of soil organic matter controls subfield variation in denitrification potential by regulating availability of dissolved organic C (DOC), the form of OC used by denitrifiers. Among 20 soil samples collected across a maize field in central Illinois, USA, we found that potential denitrification rate was best predicted by POM C concentration (R2= 0.35). Using multiple linear regression analysis that included other soil properties as explanatory variables, we found that POM C fraction of bulk soil (mg POM C g−1SOC) was the most important predictor based on regression coefficient size (P < 0.01). Our results, which provide support for our hypothesis, suggest that consideration of the link between C and N cycling may be a key to predicting spatiotemporal variation in soil N2O emissions when denitrification is the dominant N2O source process.
scSemiProfiler: Advancing Large-scale Single-cell Studies through Semi-profiling with Deep Generative Models and Active Learning
Authors: Wang Jingtao , Fonseca Gregory , Ding Jun 
Published: November 2023

AbstractSingle-cell sequencing is a crucial tool for dissecting the cellular intricacies of complex diseases. Its prohibitive cost, however, hampers its application in expansive biomedical studies. Traditional cellular deconvolution approaches can infer cell type proportions from more affordable bulk sequencing data, yet they fall short in providing the detailed resolution required for single-cell-level analyses. To overcome this challenge, we introduce “scSemiProfiler”, an innovative computational framework that marries deep generative models with active learning strategies. This method adeptly infers single-cell profiles across large cohorts by fusing bulk sequencing data with targeted single-cell sequencing from a few rigorously chosen representatives. Extensive validation across heterogeneous datasets verifies the precision of our semi-profiling approach, aligning closely with true single-cell profiling data and empowering refined cellular analyses. Originally developed for extensive disease cohorts, “scSemiProfiler” is adaptable for broad applications. It provides a scalable, cost-effective solution for single-cell profiling, facilitating in-depth cellular investigation in various biological domains.
Genetic labeling of embryonically-born dentate granule neurons in young mice using thePenkCremouse line
Authors: Mortessagne Pierre , Cartier Estelle , Balia Maddalena , Fèvre Murielle , Corailler Fiona , Herry Cyril , Abrous Djoher Nora , Battefeld Arne , Pacary Emilie 
Published: November 2023

ABSTRACTThe dentate gyrus (DG) of the hippocampus is a mosaic of dentate granule neurons (DGNs) accumulated throughout life. While many studies focused on the morpho-functional properties of adult-born DGNs, much less is known about DGNs generated during development, and in particular those born during embryogenesis. One of the main reasons for this gap is the lack of methods available to specifically label and manipulate embryonically-born DGNs. Here, we have assessed the relevance of thePenkCremouse line as a genetic model to target this embryonically-born population. In young animals,PenkCreexpression allows to tag neurons in the DG with positional, morphological and electrophysiological properties characteristic of DGNs born during the embryonic period. In addition, PenkCre+ cells in the DG are distributed in both blades along the entire septo-temporal axis. This model thus offers new possibilities to explore the functions of this underexplored population of embryonically-born DGNs.
Fast and efficient root phenotyping via pose estimation
Authors: Berrigan Elizabeth M. , Wang Lin , Carrillo Hannah , Echegoyen Kimberly , Kappes Mikayla , Torres Jorge , Ai-Perreira Angel , McCoy Erica , Shane Emily , Copeland Charles D. , Ragel Lauren , Georgousakis Charidimos , Lee Sanghwa , Reynolds Dawn , Talgo Avery , Gonzalez Juan , Zhang Ling , Rajurkar Ashish B. , Ruiz Michel , Daniels Erin , Maree Liezl , Pariyar Shree , Busch Wolfgang , Pereira Talmo D. 
Published: November 2023

AbstractImage segmentation is commonly used to estimate the location and shape of plants and their external structures. Segmentation masks are then used to localize landmarks of interest and compute other geometric features that correspond to the plant’s phenotype. Despite its prevalence, segmentation-based approaches are laborious (requiring extensive annotation to train), and error-prone (derived geometric features are sensitive to instance mask integrity). Here we present a segmentation-free approach which leverages deep learning-based landmark detection and grouping, also known as pose estimation. We use a tool originally developed for animal motion capture called SLEAP (Social LEAP Estimates Animal Poses) to automate the detection of distinct morphological landmarks on plant roots. Using a gel cylinder imaging system across multiple species, we show that our approach can reliably and efficiently recover root system topology at high accuracy, few annotated samples, and faster speed than segmentation-based approaches. In order to make use of this landmark-based representation for root phenotyping, we developed a Python library (sleap-roots) for trait extraction directly comparable to existing segmentation-based analysis software. We show that landmark-derived root traits are highly accurate and can be used for common downstream tasks including genotype classification and unsupervised trait mapping. Altogether, this work establishes the validity and advantages of pose estimation-based plant phenotyping. To facilitate adoption of this easy-to-use tool and to encourage further development, we makesleap-roots, all training data, models, and trait extraction code available at:https://github.com/talmolab/sleap-rootsandhttps://osf.io/k7j9g/.
Re-drawing Köppen-Geiger classes with microclimate: implications for nature and society
Authors: Klinges David H. , Maclean Ilya M. D. , Scheffers Brett R. 
Published: November 2023

AbstractScientists have long categorized the planet’s climate using the Köppen-Geiger (KG) classification to understand climate change impacts, biogeographical realms, agricultural suitability, and conservation. However, global KG maps primarily rely on macroclimate data collected by weather stations, which may not represent microclimatic conditions experienced by most life on Earth. Few studies have explored microclimate at broad scales, largely due to data and computational constraints. Here, we predicted KG classes separately from macroclimate and microclimate for over 32 million locations across six continents. Microclimate reclassified 38% of the total area, and microclimate KG classes were both more spatially variable, and encompassed a broader range of latitudes, relative to macroclimate KG classes. By redrawing the lines of climate classes, our study prompts a reevaluation of the importance of meteorological drivers of ecology across scales, shedding light on how natural, agricultural, and social systems experience and respond to global change.
Multi-parametric MRI can detect enhanced myelination in theGli1-/-mouse brain
Authors: Lee Choong H. , Holloman Mara , Salzer James L. , Zhang Jiangyang 
Published: November 2023

AbstractThis study investigated the potential of combining multiple MR parameters to enhance the characterization of myelin in the mouse brain. We collectedex vivomulti-parametric MR data at 7 Tesla from control andGli1−/−mice; the latter exhibit enhanced myelination at postnatal day 10 (P10) in the corpus callosum and cortex. The MR data included relaxivity, magnetization transfer, and diffusion measurements, each targeting distinct myelin properties. This analysis was followed by and compared to myelin basic protein (MBP) staining of the same samples. Although a majority of the MR parameters included in this study showed significant differences in the corpus callosum between the control andGli1−/−mice, only T2, T1/T2,and radial diffusivity (RD) demonstrated a significant correlation with MBP values. Based on data from the corpus callosum, partial least square regression suggested that combining T2, T1/T2, and inhomogeneous magnetization transfer ratio could explain approximately 80% of the variance in the MBP values. Myelin predictions based on these three parameters yielded stronger correlations with the MBP values in the P10 mouse brain corpus callosum than any single MR parameter. In the motor cortex, combining T2, T1/T2,and radial kurtosis could explain over 90% of the variance in the MBP values at P10. This study demonstrates the utility of multi-parametric MRI in improving the detection of myelin changes in the mouse brain.
A Synthetic Cytotoxic T cell Platform for Rapidly Prototyping TCR Function
Authors: Sharma Govinda , Round James , Teng Fei , Ali Zahra , May Chris , Yung Eric , Holt Robert A. 
Published: November 2023

AbstractCurrent tools for functionally profiling T cell receptors with respect to cytotoxic potency and cross-reactivity are hampered by difficulties in establishing model systems to test these proteins in the contexts of different HLA alleles and against broad arrays of potential antigens. We have implemented and validated a granzyme-activatable sensor of T cell cytotoxicity in a novel universal prototyping platform which enables facile recombinant expression of any combination of TCR-, peptide-, and class I MHC-coding sequences and direct assessment of resultant responses. This system consists of an engineered cell platform based on the immortalized natural killer cell line, YT-Indy, and the MHC-null antigen-presenting cell line, K562. These cells were engineered using contemporary gene-editing techniques to furnish the YT-Indy/K562 pair with appropriate protein domains required for recombinant TCR expression and function in a non-T cell chassis, integrate a fluorescence-based target-centric early detection reporter of cytotoxic function, and deploy a set of protective genetic interventions designed to preserve antigen-presenting cells for subsequent capture and downstream characterization. Our data show successful reconstitution of the surface TCR complex in the YT-Indy cell line at biologically relevant levels. We also demonstrate successful induction and highly sensitive detection of antigen-specific response in multiple distinct model TCRs, with significant responses (p < 0.05 and Cohen’sd>1.9) in all cases. Additionally, we monitored destruction of targets in co-culture and found that our survival-optimized system allowed for complete preservation after 24-hour exposure to cytotoxic effectors. With this bioplatform, we anticipate investigators will be empowered to rapidly express and characterize T cell receptor responses, generate new knowledge regarding the patterns of T cell receptor recognition, and optimize novel therapeutic T cell receptors for improved cytotoxic potential and reduced cross-reactivity to undesired antigenic targets.
Linked regulation of genome integrity and senescence-associated inflammation by p53
Authors: Miller Karl N. , Li Brightany , Pierce-Hoffman Hannah R. , Patel Shreeya , Lei Xue , Rajesh Adarsh , Teneche Marcos G. , Havas Aaron P. , Gandhi Armin , Macip Carolina Cano , Lyu Jun , Victorelli Stella G. , Woo Seung-Hwa , Lagnado Anthony B. , LaPorta Michael A. , Liu Tianhui , Dasgupta Nirmalya , Li Sha , Davis Andrew , Korotkov Anatoly , Hultenius Erik , Gao Zichen , Altman Yoav , Porritt Rebecca A. , Garcia Guillermina , Mogler Carolin , Seluanov Andrei , Gorbunova Vera , Kaech Susan M. , Tian Xiao , Dou Zhixun , Chen Chongyi , Passos João F. , Adams Peter D. 
Published: November 2023

AbstractGenomic instability and inflammation are distinct hallmarks of aging, but the connection between them is poorly understood. Understanding their interrelationship will help unravel new mechanisms and therapeutic targets of aging and age-associated diseases. Here we report a novel mechanism directly linking genomic instability and inflammation in senescent cells through a mitochondria-regulated molecular circuit driven by p53 and cytoplasmic chromatin fragments (CCF). We show, through activation or inactivation of p53 by genetic and pharmacologic approaches, that p53 suppresses CCF accumulation and the downstream inflammatory senescence-associated secretory phenotype (SASP), without affecting cell cycle arrest. p53 activation suppressed CCF formation by promoting DNA repair, and this is reflected in maintenance of genomic integrity, particularly in subtelomeric regions, as shown by single cell genome resequencing. Activation of p53 in aged mice by pharmacological inhibition of MDM2 reversed signatures of aging, including age- and senescence-associated transcriptomic signatures of inflammation and age-associated accumulation of monocytes and macrophages in liver. Remarkably, mitochondria in senescent cells suppressed p53 activity by promoting CCF formation and thereby restricting ATM-dependent nuclear DNA damage signaling. These data provide evidence for a mitochondria-regulated p53 signaling circuit in senescent cells that controls DNA repair, genome integrity, and senescence- and age-associated inflammation. This pathway is immunomodulatory in mice and a potential target for healthy aging interventions by small molecules already shown to activate p53.
Inbreeding depression leads to reduced fitness in declining populations of wild maize
Authors: Schulz Aimee J , Hufnagel David E , Gepts Paul , Hufford Matthew B 
Published: November 2023

AbstractCrop wild relatives can serve as a source of variation for the genetic improvement of modern varieties. However, the realization of this genetic potential depends critically on the conservation of wild populations. In this study, five populations ofZea maysssp.parviglumis, the closest relative of domesticated maize, were collected in Jalisco, Mexico and planted in a common garden. Eleven traits related to plant fitness were measured and evaluated in the context of genetic diversity and genetic load. Plants whose seed were sourced from larger, less disturbed populations had greater genetic diversity, lower genetic load, and possessed phenotypes associated with higher fitness, while plants sourced from smaller, heavily impacted populations had traits characteristic of lower fitness and increased genetic load. For example, plants from larger populations germinated more quickly, reached anthesis sooner, demonstrated a higher level of photosynthetic activity, and produced more above-ground biomass, suggesting a direct correlation between the fitness of a population, genetic diversity, and genetic load. These results emphasize the importance of preserving the habitat of populations ofZea maysssp.parviglumisto limit inbreeding depression and maintain the genetic diversity and adaptive potential of this germplasm.