bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zfp36l1establishes the high affinity CD8 T cell response by directly linking TCR affinity to cytokine sensing
Authors: Petkau Georg , Mitchell Twm J. , Evans Marian Jones , Matheson Louise , Salerno Fiamma , Turner Martin 
Published: May 2023

AbstractHow individual T cells compete for and respond to IL2 at the molecular level, and, as a consequence, how this shapes population dynamics and the selection of high affinity clones is still poorly understood. Here we describe how the RNA binding protein ZFP36L1, acts as a sensor of TCR affinity to promote clonal expansion of high affinity CD8 T cells. As part of an incoherent feed forward loop ZFP36L1 has a non-redundant role in suppressing negative regulators of cytokine signalling and mediating a selection mechanism based on competition for IL2. We suggest that ZFP36L1 acts as a sensor of antigen affinity and establishes dominance of high affinity T cells by installing a hierarchical response to IL2.
The renal capsule, a vibrant and adaptive cell environment of the kidney in homeostasis and aging
Authors: Korin Ben , Avraham Shimrit , Moncada Reuben , Ho Terence , Tleugabulova Mayra Cruz , Menon Hari , Darmanis Spyros , Liang Yuxin , Modrusan Zora , Chalouni Cecile , Victoria Charles , Rangell Linda , Havnar Charles , Ewart Will , Jones Charles , Jiang Jian , Dunlap Debra , Dohse Monika , McKay Andrew , Webster Joshua D , Durinck Steffen , Shaw Andrey S 
Published: May 2023

AbstractThe kidney is a complex organ that governs many physiological parameters. It is roughly divided into three parts, the renal pelvis, medulla, and cortex. Covering the cortex is the renal capsule, a serosal tissue that provides protection and forms a barrier for the kidney. Serosal tissues of many organs have been recently shown to play a vital role in homeostasis and disease. Analyses of the cells that reside in these tissues have identified distinct cell types with unique phenotypes. Here, we characterized this niche and found that it is mainly comprised of fibroblasts and macrophages, but also includes other diverse cell types. Characterizing renal capsule-associated macrophages, we found that they consist of a distinct subset (i.e., TLF+macrophages) that is nearly absent in the kidney parenchyma. Injury, disease, and other changes that involve the kidney, affected the cell composition of the renal capsule, indicating its dynamic response to changes within the organ parenchyma. Lastly, we studied age-related changes in the renal capsule and found that aging affected the cell composition and inflammatory phenotype of macrophages, increased CD8 T cells and other lymphocyte counts, and promoted a senescence-associated phenotype in fibroblasts. Taken together, our data illustrate the complexity and heterogeneity of the renal capsule and its underlying changes during aging and disease, improving our understanding of the kidney serosa that may be valuable for novel renal therapies.
Diazo-carboxyl click chemistry enables rapid and sensitive quantification of carboxylic acid metabolites
Authors: Li Cong , Cheng Kunlun , Zhao Qijin , Jin Li , Wang Xuelian , Liufu Tongling , Zhao Xutong , Li Xiaochuan , Wang Xiao , Lyu Jia , Huang Dong , Li Pingping , Chen Xiao-Wei , Wang Zhaoxia , Hu Xinli , Quan Li , Chen Zhixing 
Published: May 2023

AbstractCarboxylic acids are central metabolites in bioenergetics, signal transduction and post-translation protein regulation. Unlike its genomic and transcriptomic counterparts, the quest for metabolomic profiling in trace amounts of biomedical samples is prohibitively challenging largely due to the lack of sensitive and robust quantification schemes for carboxylic acids. Based on diazo-carboxyl click chemistry, here we demonstrate DQmB-HA method as a rapid derivatization strategy for the sensitive analysis of hydrophilic, low-molecular-weight carboxylic acids. To the investigated metabolites, DQmB-HA derivatization method renders 5 to 2,000-fold higher response on mass spectrometry along with improved chromatographic separation on commercial UHPLC-MS machines. Using this method, we present the near-single-cell analysis of carboxylic acid metabolites in mouse egg cells before and after fertilization. Malate, fumarate and β-hydroxybutyrate were found to decrease in mouse zygotes. We also showcase the kinetic profiling of TCA-cycle intermediates inside adherent cells cultured in one well of 96-well plates during drug treatment. FCCP and AZD3965 were shown to have overlapped but different effects on the isotope labeling of carboxylic acids. Finally, we apply DQmB-HA method to plasma or serum samples (down to 5 μL) from mice and humans collected on pathological and physiological conditions. The measured changes of succinate, β-hydroxybutyrate, and lactate in blood corroborate previous literatures in ischemia-reperfusion injury mouse model, acute fasting-refeeding mouse model, and human individuals diagnosed with mitochondrial dysfunction diseases, respectively. Overall, DQmB-HA method offers a sensitive, rapid and user-friendly quantification scheme for carboxylic acid metabolites, paving the road toward the ultimate goals of single-cell metabolomic analysis and bedside monitoring of biofluid samples.
A Superior “Thumb” Drive: Optimizing DNA Stability for DNA Data Storage
Authors: Liu Jiun-You 
Published: May 2023

AbstractDNA digital data storage is an emerging technology with the potential to keep up with increasing demands in space, energy, and materials used for information storage. To make DNA storage systems more practical and cost-effective, it is crucial to determine how the physical and chemical properties of DNA affect its performance. Thus far, scientists have experimented with various DNA storage mediums and encoding techniques to maintain DNA stability. In this study, we first review existing strategies for maintaining DNA stability under various environmental constraints, organized according to the application of the storage system (Archival Storage, Working Storage, and Dynamic Storage). Then, we report on our own quantitative evaluation of the tradeoffs between storage density and DNA stability to identify the optimal system configurations for distinct storage scenarios.
Early warning signals are hampered by a lack of critical transitions in empirical lake data
Authors: O’Brien Duncan A. , Deb Smita , Gal Gideon , Thackeray Stephen J. , Dutta Partha S. , Matsuzaki Shin-ichiro S. , May Linda , Clements Christopher F. 
Published: May 2023

AbstractQuantifying the potential for abrupt non-linear changes in ecological communities is a key managerial goal, leading to a significant body of research aimed at identifying indicators of approaching regime shifts. Most of this work has built on the theory of bifurcations, with the assumption that critical transitions are a common feature of complex ecological systems. This has led to the development of a suite of often inaccurate early warning signals (EWSs), with more recent techniques seeking to overcome their limitations by analysing multivariate time series or applying machine learning. However, it remains unclear whether regime shifts and/or critical transitions are common occurrences in natural systems, and – if they are present – whether classic and second-generation EWS methods predict rapid community change. Here, using multitrophic data on nine lakes from around the world, we both identify the type of transition a lake is exhibiting, and the reliability of classic and second generation EWSs methods to predict whole ecosystem change. We find few instances of critical transitions in our lake dataset, with different trophic levels often expressing different forms of abrupt change. The ability to predict this change is highly technique dependant, with multivariate EWSs generally classifying correctly, classical rolling window univariate EWSs performing not better than chance, and recently developed machine learning techniques performing poorly. Our results suggest that predictive ecology should start to move away from the concept of critical transitions and develop methods suitable for predicting change in the absence of the strict bounds of bifurcation theory.
Centromere Innovations Within a Mouse Species
Authors: Gambogi Craig W. , Pandey Nootan , Dawicki-McKenna Jennine M. , Arora Uma P. , Liskovykh Mikhail A. , Ma Jun , Lamelza Piero , Larionov Vladimir , Lampson Michael A. , Logsdon Glennis A. , Dumont Beth L. , Black Ben E. 
Published: May 2023

AbstractMammalian centromeres direct faithful genetic inheritance and are typically characterized by regions of highly repetitive and rapidly evolving DNA. We focused on a mouse species,Mus pahari,that we found has evolved to house centromere-specifying CENP-A nucleosomes at the nexus of a satellite repeat that we identified and term π-satellite (π-sat), a small number of recruitment sites for CENP-B, and short stretches of perfect telomere repeats. OneM. paharichromosome, however, houses a radically divergent centromere harboring ∼6 Mbp of a homogenized π-sat-related repeat, π-satB, that contains >20,000 functional CENP-B boxes. There, CENP-B abundance drives accumulation of microtubule-binding components of the kinetochore, as well as a microtubule-destabilizing kinesin of the inner centromere. The balance of pro and anti-microtubule-binding by the new centromere permits it to segregate during cell division with high fidelity alongside the older ones whose sequence creates a markedly different molecular composition.TeaserChromatin and kinetochore alterations arise in response to evolutionarily rapid changes to underlying repetitive centromere DNA.
Gene-by-environment interactions influence the fitness cost of gene copy-number variation in yeast
Authors: Robinson DeElegant , Vanacloig-Pedros Elena , Cai Ruoyi , Place Michael , Hose James , Gasch Audrey P 
Published: May 2023

ABSTRACTVariation in gene copy number can alter gene expression and influence downstream phenotypes; thus copy-number variation (CNV) provides a route for rapid evolution if the benefits outweigh the cost. We recently showed that genetic background significantly influences how yeast cells respond to gene over-expression (OE), revealing that the fitness costs of CNV can vary substantially with genetic background in a common-garden environment. But the interplay between CNV tolerance and environment remains unexplored on a genomic scale. Here we measured the tolerance to gene OE in four genetically distinctSaccharomyces cerevisiaestrains grown under sodium chloride (NaCl) stress. OE genes that are commonly deleterious during NaCl stress recapitulated those commonly deleterious under standard conditions. However, NaCl stress uncovered novel differences in strain responses to gene OE. West African strain NCYC3290 and North American oak isolate YPS128 are more sensitive to NaCl stress than vineyard BC187 and laboratory strain BY4743. Consistently, NCYC3290 and YPS128 showed the greatest sensitivities to gene OE. Although most genes were deleterious, hundreds were beneficial when overexpressed – remarkably, most of these effects were strain specific. Few beneficial genes were shared between the NaCl-sensitive isolates, implicating mechanistic differences behind their NaCl sensitivity. Transcriptomic analysis suggested underlying vulnerabilities and tolerances across strains, and pointed to natural CNV of a sodium export pump that likely contributes to strain-specific responses to OE of other genes. Our results reveal extensive strain-by-environment interaction in the response to gene CNV, raising important implications for the accessibility of CNV-dependent evolutionary routes under times of stress.
Go west: population genomics reveals unexpected population fluctuations and little gene flow in Western Hemisphere populations of the predatory lady beetle,Hippodamia convergens
Authors: Sethuraman Arun , Nunziata Schyler O. , Jones Angela , Obrycki John , Weisrock David W. 
Published: May 2023

AbstractThe convergent lady beetle,Hippodamia convergens, is used extensively in augmentative biological control of aphids, thrips, and whiteflies across its native range in North America, and was introduced into South America in the 1950s. OverwinteringH. convergenspopulations from its native western range in the United States are commercially collected and released across its current range in the eastern U.S., with little knowledge of the effectiveness of augmentative biological control usingH. convergens. Here we use a novel ddRADseq-based SNP/haplotype discovery approach to estimate its range-wide population diversity, differentiation, and recent evolutionary history. Our results indicate (1) significant population differentiation among eastern U.S., western U.S., and South American populations ofH. convergens, with (2) little to no detectable recent admixture between them, despite repeated population augmentation, and (3) continued recent population size expansion across its range. These results contradict previous findings using microsatellite markers. In light of these new findings, the implications for the effectiveness of augmentative biological control usingH. convergensare discussed. Additionally, because quantifying the non-target effects of augmentative biological control is a difficult problem in migratory beetles, our results could serve as a foundation cornerstone in improving and predicting the efficacy of future releases ofH. convergensacross its range.
Default Values And Read-Across Proposal For Dermal Absorption Based On Human Skin In Vitro Studies Dataset With Pesticides
Authors: Sarti D. , Wagner J. , Palma F. , Kalvan H. , Giachini M. , Lautenschalaeger D. , Lupianhez V. , Pires J. , Sales M. , Faria P. , Bertomeu L. , Le Bras M. 
Published: May 2023

AbstractThe skin is the main route of exposure to plant protection products for operators, workers, residents, and bystanders. Assessing dermal absorption is key for evaluating pesticide exposure risks. However, conductingin vitrodermal absorption studies using human skin is resource-intensive. Therefore, establishing realistic regulatory default values is essential for non-dietary risk assessment and ensuring safety. This project analysed 468in vitrodermal absorption studies with human skin compiled by ProHuma. Combined with a prior database by Aggarwal et al. (2015), the dataset comprised 759 GLP-compliant studies covering 25 formulation types and 248 active substances at various concentrations. The assessment confirmed earlier findings that dermal absorption shows no correlation with molecular weight or log Pow and does not increase linearly with dilution. Based on the comprehensive ProHuma/ECPA dataset, dermal absorption default values are proposed: 2% for solid concentrates, 5% for liquid concentrates, 30% for solid dilutions, and 34% for liquid dilutions. These values, derived conservatively using the 95th percentile, better represent formulations and agricultural use cases, reducing the need for unnecessary studies. The project also suggests read-across between different formulation types. By proposing more realistic default values and read-across approaches, it streamlines decision-making and supports safety in agriculture.
Hyperactivity in mice induced by opioid agonists with partial intrinsic efficacy and biased agonism; alone and in combination with morphine
Authors: Acevedo-Canabal Agnes , Grim Travis W. , Schmid Cullen L. , McFague Nina , Stahl Edward L. , Kennedy Nicole M. , Bannister Thomas D. , Bohn Laura M. 
Published: May 2023

AbstractOpioid analgesics like morphine and fentanyl induce mu-opioid receptor (MOR)-mediated hyperactivity in mice. Here we show that morphine, fentanyl, SR-17018, and oliceridine have submaximal intrinsic efficacy in the mouse striatum using35S-GTPγS binding assays. While all of the agonists act as partial agonists for stimulating G protein coupling in striatum, morphine, fentanyl and oliceridine are fully efficacious in stimulating locomotor activity; meanwhile, the noncompetitive biased agonists, SR-17018 and SR-15099 produce submaximal hyperactivity. Moreover, the combination of SR-17018 and morphine attenuates hyperactivity while antinociceptive efficacy is increased. The combination of oliceridine with morphine increases hyperactivity which is maintained over time. These findings provide evidence that noncompetitive agonists at MOR can be used to suppress morphine-induced hyperactivity while enhancing antinociceptive efficacy; moreover, they demonstrate that intrinsic efficacy measured at the receptor level is not directly proportional to drug efficacy in the locomotor activity assay.
Dynamically stiffening biomaterials reveal age- and sex-specific differences in pulmonary arterial adventitial fibroblast activation
Authors: Mueller Mikala C. , Du Yanmei , Walker Lori A. , Magin Chelsea M. 
Published: May 2023

ABSTRACTRespiratory diseases like pulmonary arterial hypertension (PAH) frequently exhibit sexual dimorphism. Female PAH patients are more susceptible to the disease but have increased survival rates. This phenomenon is known as the estrogen paradox, and the underlying mechanisms are not fully understood. During PAH progressionin vivo, human pulmonary arterial adventitial fibroblasts (hPAAFs) differentiate into an activated phenotype. These cells produce excess, aberrant extracellular matrix proteins that stiffen the surrounding pulmonary arterial tissues. Here, we employed dynamic poly(ethylene glycol)-alpha methacrylate (PEGαMA)-based biomaterials to study how the age and sex of human serum influenced hPAAF activation in response to microenvironmental stiffeningin vitro. Results showed female and male cells responded differently to increases in microenvironmental stiffness and serum composition. Male hPAAFs were less activated than female cells on soft hydrogels and more responsive to increases in microenvironmental stiffness regardless of serum composition. Female hPAAF activation followed this pattern only when cultured in younger (age < 50) female serum or when older (age ≥ 50) female serum was supplemented with estradiol. Otherwise, female hPAAF activation was relatively high on both soft and stiffened hydrogels, with little difference in activation between the two conditions. Collectively, these results suggest that it may be possible to model the estrogen paradox observed in PAHin vitroand that it is critical for researchers to report cell sex and serum source when conductingin vitroexperimentation.
IMMUNE RESPONSE TO SARS CoV2 INFECTION BY TLR3, TLR4 AND TLR7 GENE EXPRESSION
Authors: Marignac Veronica L. Martinez , Oertlin Gloria S. , Favant Jose Luis , Fleischman Erika , Salinas Mercedes , Marchetti Gaston , Gassali Zaida , Richard Silvina M. 
Published: May 2023

AbstractToll-like receptors (TLRs) may be involved both in the initial failure of viral clearance and in the subsequent development of severe clinical manifestations of COVID-19, essentially ARDS (acute respiratory distress syndrome) with fatal respiratory failure. We present the gene expression of TLR 3, 4, and 7 in nasopharyngeal total RNA samples from 150 individuals positive for SARS Cov2 (DET) by molecular techniques of isothermal amplification (Neokit SA) and 152 SARS Cov2 non detectable (ND) ambulatory and hospitalized patients with a non-defined respiratory disease, and we compared with the symptomatology developed by all those patients. We analyzed 4 cohorts: 1-SARS Cov2 genome detected patients with severe to high symptomatology (n=107); 2-SARS Cov2 genome detected patients low to mild symptomatology (n=43); 3-SARS Cov2 genome non detected patients with severe to high symptomatology (n=109); and 4-SARS Cov2 genome non detected patients low to mild symptomatology (n=41).Our results not only contradict few previous study, it also corrects for sample size bias, showing no significant differences of expression for TLR3, TLR4 and TLR7 between SARS Cov2 DET and ND total cohort of patients (Non Paired T –Test p Value>0.1). When compared severity of symptoms -presence of symptoms from the COVID-19 12 WHO diagnosis symptoms- and gene expression, here we found significant positive correlation between severe symptomatology, and the number of symptoms and death for TLR4 and TLR7 for both DET and ND COVID-19 patients. When the cohort was construct with low/middle and severe symptoms, the Correlation Coefficient showed that expression of TLR4 and TLR7 was significantly amplified in those ND patients with severe symptomatology (p Value= 0.00311) as well as for TLR3 in ND low to mild symptoms cohort of patients. We also showed and discussed the results obtained of these genes expression and the sex and age of patients. In summary, our data suggest that although our innate immune system with TLRs contributes to the elimination of viruses, it can also be associated with harm to the host due to persistent inflammation and tissue destruction. We confirmed that principally TLR4 and TLR7 could be involved not only in the pathogenesis of COVID□19 but also in other respiratory diseases with same symptomatology. We agree with previous studies that treatments focus on TLR4 and TLR7 expression in inflammatory respiratory diseases could be a start point against severe symptoms development.
Factors associated with within-individual variability of lung function for people with cystic fibrosis: a longitudinal registry study
Authors: Palma Marco , Keogh Ruth H , Carr Siobhán B , Szczesniak Rhonda , Taylor-Robinson David , Wood Angela M , Muniz-Terrera Graciela , Barrett Jessica K 
Published: May 2023

AbstractLung function is a key outcome used in the evaluation of disease progression in cystic fibrosis. The variability of individual lung function measurements over time (within-individual variability) has been shown to predict subsequent lung function changes. Nevertheless, the association between within-individual lung function variability and demographic and genetic covariates is not quantified. We performed a longitudinal analysis of data from a cohort of 7099 adults with cystic fibrosis (between 18 and 49 years old) from the UK cystic fibrosis registry, containing annual review data between 1996 and 2020. A mixed-effects location-scale model is used to quantify mean FEV1(forced expiratory volume in 1 second) trajectories and FEV1within-individual variability as a function of sex, age at annual review, age at diagnosis, genotype and birth cohort. Mean FEV1decreased with age and lung function variability showed an approximately quadratic trend by age. Males showed higher FEV1mean and variability than females across the whole age range. Individuals who died during follow-up showed on average higher lung function variability than those who survived. This work opens new avenues for further research to understand the role of within-individual lung function variability in disease progression and prediction of key outcomes such as mortality.