bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early-life experience determines the social stability of adult communities in female mice
Authors: Doludda Birte , Bogado Lopes Jadna , Zocher Sara , Kempermann Gerd , Overall Rupert W 
Published: December 2023

AbstractEarly social interactions critically shape lifelong individual behaviour but their development and stability have been difficult to study in laboratory settings. Our experimental platform allows the automated real-time and longitudinal study of social structure in mice living in a shared environment, providing previously inaccessible behavioural measures. These include estimates of directed agonistic activity for the reconstruction of social hierarchies and their dynamics over the life-course. In an all-female colony of genetically identical mice, pairwise inter-individual interactions revealed stable dominance hierarchies that already emerged early in life. Older animals introduced into a new colony exhibited a steeper hierarchy compared to adolescent mice or mature mice that had been co-housed throughout life. Our longitudinal analysis of social dominance hierarchies highlights the critical role of early-life experience.One-Sentence SummaryAutomated tracking of mouse colonies revealed differences in social structure dependent on the animals’ early-life experience.
Lack of Purple Acid PhosphataseSlPAP26bcompromises the phosphorus starvation response in tomato independent of SlPHR1 and SlPHL1
Authors: Akash  , Srivastava Rajat , Roychowdhury Abhishek , Sharma Kapil , Cerny Martin , Kerchev Pavel , Kumar Rahul 
Published: December 2023

AbstractThe scarcity of soil phosphorus (P), an essential macronutrient, often limits plant growth and development. Enhanced secretion of intracellular and secretory acid phosphatases is essential to maintain cellular inorganic P (Pi) homeostasis in plants. Herein, using transcriptomics and proteomics approach, we observed upregulation of several purple acid phosphatases (PAPs), includingSlPAP1,SlPAP10b,SlPAP12,SlPAP15,SlPAP17b,SlPAP26a, andSlPAP26bin Pi-deficient tomato seedlings. Higher transcript levels ofSlPAP17bandSlPAP26bin the older senescing leaves than the younger leaves indicated active involvement of these PAPs in Pi remobilization. Subsequent detailed characterization ofSlPAP17b,SlPAP26a, andSlPAP26brevealed a prominent role ofSlPAP26bin Pi homeostasis. Silencing ofSlPAP26bled to an exacerbated P starvation response as these plants exhibited smaller shoots, lower soluble Pi, total P levels, and higher sucrose than their EV controls under Pi deprivation.SlPAP26b-silenced plants also showed misregulation of P starvation inducible genes such as phosphate transporters and glycerolipid remodellers, even under Pi-sufficient conditions. WhereasSlPAP26blevels were induced by external sucrose, its expression was found to be independent of the Myb class master regulators of P starvation response, SlPHR1 and SlPHL1. Altogether, this study identifies a prominent role ofSlPAP26bin the Pi compensation network in tomato seedlings.
JUN mediates senescence and immune cell recruitment to prevent prostate cancer progression
Authors: Redmer Torben , Raigel Martin , Sternberg Christina , Ziegler Roman , Probst Clara , Lindner Desiree , Aufinger Astrid , Limberger Tanja , Trachtova Karolina , Kodajova Petra , Högler Sandra , Schlederer Michaela , Stoiber Stefan , Oberhuber Monika , Bolis Marco , Neubauer Heidi A. , Miranda Sara , Tomberger Martina , Harbusch Nora S. , Garces de los Fayos Alonso Ines , Sternberg Felix , Moriggl Richard , Theurillat Jean-Philippe , Tichy Boris , Bystry Vojtech , Persson Jenny L. , Mathas Stephan , Aberger Fritz , Strobl Birgit , Pospisilova Sarka , Merkel Olaf , Egger Gerda , Lagger Sabine , Kenner Lukas 
Published: December 2023

AbstractBackgroundProstate cancer develops through malignant transformation of the prostate epithelium in a stepwise, mutation-driven process. Although activator protein-1 transcription factors such as JUN have been implicated as potential oncogenic drivers, the molecular programs contributing to prostate cancer progression are not fully understood.MethodsWe analyzed JUN expression in clinical prostate cancer samples across different stages and investigated its functional role in aPten-deficient mouse model. We performed histopathological examinations, transcriptomic analyses and explored the senescence-associated secretory phenotype in the tumor microenvironment.ResultsElevated JUN levels characterized early-stage prostate cancer and predicted improved survival in human and murine samples. Immune-phenotyping ofPten-deficient prostates revealed high accumulation of tumor-infiltrating leukocytes, particularly innate immune cells, neutrophils and macrophages as well as high levels of STAT3 activation and IL-1β production.Jundepletion in aPten-deficient background prevented immune cell attraction which was accompanied by significant reduction of active STAT3 and IL-1β and accelerated prostate tumor growth. Comparative transcriptome profiling of prostate epithelial cells revealed a senescence-associated gene signature, upregulation of pro-inflammatory processes involved in immune cell attraction and of chemokines such as IL-1β, CCL3 and CCL8 inPten-deficient prostates. Strikingly, JUN depletion reversed both, senescence and senescence-associated immune cell infiltration and consequently accelerated tumor growth.ConclusionsOur results suggest that JUN acts as tumor-suppressor and decelerates the progression of prostate cancer by transcriptional regulation of senescence- and inflammation-associated genes. This study opens avenues for novel treatment strategies that could impede disease progression and improve patient outcomes.
qDATA - an R application implementing a practical framework for analyzing quantitative Real-Time PCR data
Authors: Ionascu Adrian , Ecovoiu Alexandru Al. , Chifiriuc Mariana Carmen , Ratiu Attila Cristian 
Published: December 2023

AbstractGene expression assays that are based on quantitative real-time PCR (qRT-PCR) method are still very popular, therefore, we developed qDATA, a modern open-source R based bioinformatics application that offers a quick and intuitive analysis of raw cycle threshold (Ct) values. The application relies on a straightforward specific data input consisting in Ct values and a few other mandatory fields specifying the experimental and control groups, as well as the target and house-keeping genes. Afterwards, it automatically performs descriptive statistics, normality and statistical testing on 2-ΔCt(or ΔCt) and 2-ΔΔCtterms calculated with Livak’s method. Each computation is indicated in dedicated tabs that display their output consisting in dynamic data tables and publishing quality graphs. We also detail a qRT-PCR data analysis framework that depends on performing exhaustive ΔCt calculations within discrete biological replicates (BRs). The Livak formula is used for the complete sets of available data. These prerequisites arguably lead to an improved data analysis and statistical relevance. In order to maximize the relevance of the results we recommend using at least three BRs and three technical replicates. The efficiency of our computing approach was tested with qDATA using input Ct values corresponding to immune related gene expression evaluated in experimental infection ofDrosophila melanogasterand summer versus winterApis melliferaworkers, respectively. Our results reveal that our working strategy is very reliable and highlight the efficacy and performance of qDATA application.
OCA-B promotes pathogenic maturation of stem-like CD4+T cells and autoimmune demyelination
Authors: Hughes Erik P. , Syage Amber R. , Mehrabad Elnaz Mirzaei , Lane Thomas E. , Spike Benjamin T. , Tantin Dean 
Published: December 2023

AbstractStem-like T cells selectively contribute to autoimmunity, but the activities that promote their pathogenicity are incompletely understood. Here, we identify the transcription coregulator OCA-B as a driver of the pathogenic maturation of stem-like CD4+T cell to promote autoimmune demyelination. Using a human multiple sclerosis (MS) patient dataset, we show thatPOU2AF1, the gene encoding OCA-B, is elevated in CD4+T cells from secondary-progressive MS patient lesions. We show that T cell-intrinsic OCA-B loss protects mice from experimental autoimmune encephalomyelitis (EAE) while preserving responses to viral CNS infection. In EAE models driven by antigen reencounter, OCA-B deletion nearly eliminates CNS infiltration, proinflammatory cytokine production and clinical disease. CNS OCA-B-expressing CD4+T of mice with EAE express an encephalitogenic gene program and preferentially confer disease. In a relapsing-remitting EAE model, OCA-B loss protects mice specifically at relapse. During remission, OCA-B promotes the expression ofTcf7,Slamf6, andSellin proliferating CNS T cell populations. At relapse timepoints, OCA-B loss results in both the accumulation of an immunomodulatory CD4+T cell population expressingCcr9andBach2, and loss of pro-inflammatory gene expression from Th17 cells. These results identify OCA-B as a driver of pathogenic CD4+T cells.
Gene expression shifts in Emperor penguin adaptation to the extreme Antarctic environment
Authors: Paris Josephine R. , Fernandes Flávia A. Nitta , Pirri Federica , Greco Samuele , Gerdol Marco , Pallavicini Alberto , Benoiste Marine , Cornec Clément , Zane Lorenzo , Haas Brian , Le Bohec Céline , Trucchi Emiliano 
Published: December 2023

AbstractGene expression can accelerate ecological divergence by rapidly tweaking the response of an organism to novel environments, with more divergent environments exerting stronger selection and supposedly, requiring faster adaptive responses. Organisms adapted to extreme environments provide ideal systems to test this hypothesis, particularly when compared to related species with milder ecological niches. The Emperor penguin (Aptenodytes forsteri) is the only warm-blooded vertebrate breeding in the harsh Antarctic winter, in stark contrast with the less cold-adapted sister species, the King penguin (A. patagonicus). Assembling the firstde novotranscriptomes and analysing multi-tissue (brain, kidney, liver, muscle, skin) RNAseq data from natural populations of both species, we quantified the shifts in tissue-enhanced genes, co-expression gene networks, and differentially expressed genes characterising Emperor penguin adaptation to extreme Antarctic ecology. Our analyses revealed the crucial role played by muscle and liver in temperature homeostasis, fasting and whole-body energy metabolism (glucose/insulin regulation, lipid metabolism, fatty acid beta-oxidation, and blood coagulation). Repatterning at the regulatory level appears as more important in the brain of the Emperor penguin, showing the lowest signature of differential gene expression but the largest co-expression gene network shift. Nevertheless, over-expressed genes related to mTOR signalling in the brain and the liver support their central role in cold and fasting responses. Besides contributing to understanding the genetics underlying complex traits, like body energy reservoir management, our results provide a first insight into the role of gene expression in adaptation to one of the most extreme environmental conditions endured by an endotherm.
MAIT cells drive chronic inflammation in a genetically diverse murine model of spontaneous colitis
Authors: Loh Liyen , Orlicky David , Spengler Andrea , Levens Cassandra , Celli Sofia , Domenico Joanne , Klarquist Jared , Onyiah Joseph , Matsuda Jennifer , Kuhn Kristine , Gapin Laurent 
Published: December 2023

AbstractBackground & aimsLymphocytes that produce IL-17 can confer protective immunity during infections by pathogens, yet their involvement in inflammatory diseases is a subject of debate. Although these cells may perpetuate inflammation, resulting in tissue damage, they are also capable of contributing directly or indirectly to tissue repair, thus necessitating more detailed investigation. Mucosal-Associated-Invariant-T (MAIT) cells are innate-like T cells, acquiring a type III phenotype in the thymus. Here, we dissected the role of MAIT cellsin vivousing a spontaneous colitis model in a genetically diverse mouse strain.MethodsMultiparameter spectral flow cytometry and scRNAseq were used to characterize MAIT and immune cell dynamics and transcriptomic signatures respectively, in the collaborative-cross strain, CC011/Unc and CC011/Unc-Traj33-/-.ResultsIn contrast to many conventional mouse laboratory strains, the CC011 strain harbors a high baseline population of MAIT cells. We observed an age-related increase in colonic MAIT cells, Th17 cells, regulatory T cells, and neutrophils, which paralleled the development of spontaneous colitis. This progression manifested histological traits reminiscent of human IBD. The transcriptomic analysis of colonic MAIT cells from CC011 revealed an activation profile consistent with an inflammatory milieu, marked by an enhanced type-III response. Notably, IL-17A was abundantly secreted by MAIT cells in the colons of afflicted mice. Conversely, in the MAIT cell-deficient CC011-Traj33−/− mice, there was a notable absence of significant colonic histopathology. Furthermore, myeloperoxidase staining indicated a substantial decrease in colonic neutrophils.ConclusionsOur findings suggest that MAIT cells play a pivotal role in modulating the severity of intestinal pathology, potentially orchestrating the inflammatory process by driving the accumulation of neutrophils within the colonic environment.
A low-cost, AI-powered Measurement Verification and Reporting System for growing trees with smallholder farmers
Authors: Amoah Edward Idun , McCloskey Peter , Ouedrago Rimnoma Serge , Chelal John , Akuleut Chelsea , Mwambumba Binti Ibrahan , Meli Brian Kipchirchir , Oyudi Christabel Akinyi , Kibwamga Edna Santa , Cleophas Eunice Kwamboka , Ochola Fredrick Odhiambo , Wangiru Catherine Njeri , Morang’a Kelvin , Mushira Lyon Wilson , Maboke Maureen Kalegi , Titus Nancy Syonthi , Oltimbao Serah Lanoi , Odawa Sheilah Awour , Hughes David Peter 
Published: December 2023

AbstractLimited access to low-cost tools to measure, report, and verify (MRV) tree growth with smallholder farmers limits the scaling of tree planting efforts in developing countries. Artificial Intelligence (AI) offers the potential for low-cost, reliable, and accessible measurement and verification tools to be developed for an MRV platform to scale tree planting efforts in developing countries. Here, we present an AI-powered non-contact tree diameter measurement and verification tool. We have developed an AI-powered algorithm that accurately estimates the diameter of a tree from an image of the tree with a reference object. This non-contact measurement method utilizes semantic segmentation and image processing techniques to analyze an image of the tree with the reference object. The performance of the proposed method was evaluated on 142 trees with tape-measured diameters at breast height ranging from 5 to 60 cm. A regression analysis between predicted and measured diameter values had an R2and an RMSE of 0.97 and 2.23 cm, respectively. Thus, using a smartphone application, the non-contact method developed here can empower anyone to accurately measure and report tree growth by just taking pictures of the trees with the reference object. The images submitted with on-farm measurements serve as data for future verification operations using the AI-powered algorithm. With the reference object serving as a unique tree identifier, a tree’s survival and diameter measurements can be tracked over time. The MRV system described here, with the developed AI-powered non-contact tree diameter measurement and verification tool, can empower organizations to plant, grow, and monitor trees with anyone, including smallholder farmers.
Multivariate Pattern Analysis of EEG Reveals Neural Mechanism of Naturalistic Target Processing in Attentional Blink
Authors: Jahanian Mansoure , Joanisse Marc , Wang Boyu , Mohsenzadeh Yalda 
Published: December 2023

AbstractThe human brain has inherent limitations in consciously processing visual information. When individuals monitor a rapid sequence of images for detecting two targets, they often miss the second target (T2) if it appears within a short time frame of 200-500ms after the first target (T1), a phenomenon known as the attentional blink (AB). The neural mechanism behind AB remains unclear, largely due to the use of simplistic visual items such as letters and digits in conventional AB experiments, which differ significantly from naturalistic vision. This study employed advanced multivariate pattern analysis (MVPA) of human EEG data to explore the neural representations associated with target processing within a naturalistic paradigm under conditions where AB does or does not occur. Our MVPA analysis successfully decoded the identity of target images from EEG data. Moreover, in the AB condition, characterized by a limited time between targets, T1 processing coincided with T2 processing, resulting in the suppression of late representational markers of both T1 and T2. Conversely, in the condition with longer inter-target interval, neural representations endured for a longer duration. These findings suggest that the attentional blink can be attributed to the suppression of neural representations in the later stages of target processing.Significance StatementWithin a naturalistic paradigm, we investigated the phenomenon known as attentional blink, where individuals struggle to identify a second target in a rapid sequence when the first target precedes it too closely. Attentional blink is purported to reflect an apparent bottleneck in the attention system’s ability to rapidly redirect attentional resources; however, the mechanism underlying this phenomenon remains hotly debated. Our findings reveal that during a rapid presentation of natural images, a short temporal gap between targets results in reduced neural representations of targets and the occurrence of attentional blink. Conversely, when a greater temporal gap exists between targets, neural representations are preserved. This study provides valuable insights into how the human brain perceives the ever-changing visual world around us.
Digital telomere measurement by long-read sequencing distinguishes healthy aging from disease
Authors: Sanchez Santiago E. , Gu Jessica , Golla Anudeep , Martin Annika , Shomali William , Hockemeyer Dirk , Savage Sharon A. , Artandi Steven E. 
Published: December 2023

AbstractTelomere length is an important biomarker of organismal aging and cellular replicative potential, but existing measurement methods are limited in resolution and accuracy. Here, we deploy digital telomere measurement by nanopore sequencing to understand how distributions of human telomere length change with age and disease. We measure telomere attrition andde novoelongation with unprecedented resolution in genetically defined populations of human cells, in blood cells from healthy donors and in blood cells from patients with genetic defects in telomere maintenance. We find that human aging is accompanied by a progressive loss of long telomeres and an accumulation of shorter telomeres. In patients with defects in telomere maintenance, the accumulation of short telomeres is more pronounced and correlates with phenotypic severity. We apply machine learning to train a binary classification model that distinguishes healthy individuals from those with telomere biology disorders. This sequencing and bioinformatic pipeline will advance our understanding of telomere maintenance mechanisms and the use of telomere length as a clinical biomarker of aging and disease.
Acetylation of WCC is dispensable for the core circadian clock but differentially regulates acute light responses inNeurospora
Authors: Wang Bin , Edamo Mark E. , Zhou Xiaoying , Wang Ziyan , Gerber Scott A. , Kettenbach Arminja N. , Dunlap Jay C. 
Published: December 2023

AbstractIn theNeurosporacircadian system, the White Collar Complex (WCC) formed by WC-1 and WC-2 drives expression of thefrequency(frq) gene whose product FRQ feedbacks to inhibit transcriptional activity of WCC. Phosphorylation of WCC has been extensively studied, but the extent and significance of other post-translational modifications (PTM) has been poorly studied. To this end, we used mass-spectrometry to study alkylation sites on WCC, resulting in discovery of nine acetylation sites. Mutagenesis analysis showed most of the acetylation events individually do not play important roles in period determination. Moreover, mutating all the lysines falling in either half of WC-1 or all the lysine residues in WC-2 to arginines did not abolish circadian rhythms. In addition, we also found nine mono-methylation sites on WC-1, but like acetylation, individual ablation of most of the mono-methylation events did not result in a significant period change. Taken together, the data here suggest that acetylation or mono-methylation on WCC is not a determinant of the pace of the circadian feedback loop. The finding is consistent with a model in which repression of WCC’s circadian activity is controlled mainly by phosphorylation. Interestingly, light-induced expression of some light-responsive genes has been modulated in certainwc-1acetylation mutants, suggesting that WC-1 acetylation events differentially regulate light responses.
Editing cis-regulatory elements towards generating rice stomatal morphological variation for adaptation to broad and dynamic environments
Authors: Karavolias Nicholas G. , Patel-Tupper Dhruv , Cruz Ana Gallegos , Litvak Lilian , Lieberman Samantha E. , Tjahjadi Michelle , Niyogi Krishna K. , Cho Myeong-Je , Staskawicz Brian J. 
Published: December 2023

AbstractCis-regulatory element editing can generate quantitative trait variation while mitigating against extreme phenotypes and harmful pleiotropy associated with coding sequence mutations. Here, we applied a multiplexed guide RNA design approach, informed by bioinformatic datasets, to generate genotypic variation in the promoter ofOsSTOMAGEN,a positive regulator of stomatal density in rice. Engineered genotypic variation corresponded to broad and continuous variation in stomatal density, ranging from 70% to 120% of wild-type stomatal density. This near-isogenic panel of stomatal variants was leveraged in physiological assays to establish discrete relationships between stomatal morphological variation and stomatal conductance, carbon assimilation, and intrinsic water use efficiency in steady-state and fluctuating light conditions. Additionally, promoter alleles were subjected to vegetative drought regimes to assay the effects of the edited alleles on developmental response to drought. Notably, the capacity for drought-responsive stomatal density reprogramming instomagenand two cis-regulatory edited alleles was reduced. Collectively our data demonstrate that cis-regulatory element editing can generate near-isogenic trait variation that can be leveraged for establishing relationships between anatomy, physiology, and crop improvement along diverse environmental clines.