bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic profiles of stress susceptibility and resilience in the amygdala and hippocampus
Authors: Long Kimberly L. P. , Muroy Sandra E. , Sorooshyari Siamak K. , Ko Mee Jung , Jaques Yanabah , Sudmant Peter , Kaufer Daniela 
Published: February 2023

AbstractA single, severe episode of stress can bring about myriad responses amongst individuals, ranging from cognitive enhancement to debilitating and persistent anxiety; however, the biological mechanisms that contribute to resilience versus susceptibility to stress are poorly understood. The dentate gyrus (DG) of the hippocampus and the basolateral nucleus of the amygdala (BLA) are key limbic regions that are susceptible to the neural and hormonal effects of stress. Previous work has also shown that these regions contribute to individual variability in stress responses; however, the molecular mechanisms underlying the role of these regions in susceptibility and resilience are unknown. In this study, we profiled the transcriptomic signatures of the DG and BLA of rats with divergent behavioral outcomes after a single, severe stressor. We subjected rats to three hours of immobilization with exposure to fox urine and conducted a behavioral battery one week after stress to identify animals that showed persistent, high anxiety-like behavior. We then conducted bulk RNA sequencing of the DG and BLA from susceptible, resilient, and unexposed control rats. Differential gene expression analyses revealed that the molecular signatures separating each of the three groups were distinct and non-overlapping between the DG and BLA. In the amygdala, key genes associated with insulin and hormonal signaling corresponded with vulnerability. Specifically,Inhbb, Rab31, andNcoa3were upregulated in the amygdala of stress-susceptible animals compared to resilient animals. In the hippocampus, increased expression ofCartpt -which encodes a key neuropeptide involved in reward, reinforcement, and stress responses - was strongly correlated with vulnerability to anxiety-like behavior. However, few other genes distinguished stress-susceptible animals from control animals, while a larger number of genes separated stress-resilient animals from control and stress-susceptible animals. Of these,Rnf112, Tbx19, andUBALD1distinguished resilient animals from both control and susceptible animals and were downregulated in resilience, suggesting that an active molecular response in the hippocampus facilitates protection from the long-term consequences of severe stress. These results provide novel insight into the mechanisms that bring about individual variability in the behavioral responses to stress and provide new targets for the advancement of therapies for stress-induced neuropsychiatric disorders.
Long-term epidemiology and evolution of swine influenza viruses in Vietnam
Authors: Cheung Jonathan , Bui Anh Ngoc , Younas Sonia , Edwards Kimberly M. , Nguyen Huy Quang , Pham Ngoc Thi , Bui Vuong Nghia , Peiris Malik , Dhanasekaran Vijaykrishna 
Published: February 2023

AbstractSwine influenza virus (SwIV) surveillance in Hanoi, Vietnam from 2013–2019 found gene pool enrichment from imported swine from Asia and North America. Long-term maintenance, persistence and reassortment of SwIV lineages was observed. Co-circulation of H1-δ1a viruses with other SwIV genotypes raises concern due to its zoonotic potential.
Rapid lethality of mice lacking the phagocyte oxidase and Caspase1/11 followingMycobacterium tuberculosisinfection
Authors: Thomas Sean M. , Olive Andrew J. 
Published: February 2023

AbstractImmune networks that control antimicrobial and inflammatory mechanisms have overlapping regulation and functions to ensure effective host responses. Genetic interaction studies of immune pathways that compare host responses in single and combined knockout backgrounds are a useful tool to identify new mechanisms of immune control during infection. For disease caused by pulmonaryMycobacterium tuberculosisinfections, which currently lacks an effective vaccine, understanding genetic interactions between protective immune pathways may identify new therapeutic targets or disease-associated genes. Previous studies suggested a direct link between the activation of NLRP3-Caspase1 inflammasome and the NADPH-dependent phagocyte oxidase complex during Mtb infection. Loss of the phagocyte oxidase complex alone resulted in increased activation of Caspase1 and IL1β production during Mtb infection, resulting in failed disease tolerance during the chronic stages of disease. To better understand this interaction, we generated mice lacking bothCybb, a key subunit of the phagocyte oxidase, andCaspase1/11. We found thatex vivoMtb infection ofCybb-/-Caspase1/11-/-macrophages resulted in the expected loss of IL1β secretion but an unexpected change in other inflammatory cytokines and bacterial control. Mtb infectedCybb-/-Caspase1/11-/-mice rapidly progressed to severe TB, succumbing within four weeks to disease characterized by high bacterial burden, increased inflammatory cytokines, and the recruitment of granulocytes that associated with Mtb in the lungs. These results uncover a key genetic interaction between the phagocyte oxidase complex and Caspase1/11 that controls protection against TB and highlight the need for a better understanding of the regulation of fundamental immune networks during Mtb infection.
Human Tear Film Protein Sampling Using Soft Contact Lenses
Authors: Roden Robert K. , Zuniga Nathan , Wright Joshua C. , Parkinson David H. , Patil Leena M. , Jiang Fangfang , Burlett Rebecca S. , Rogers Joshua J. , Pittman Jarett T. , Roper Connor O. , Virgin Kenneth L. , Ackroyd P. Christine , Price John C. , Christensen Kenneth A. 
Published: February 2023

AbstractHuman tear protein biomarkers are useful for detecting both ocular and systemic diseases. Unfortunately, existing tear film sampling methods (Schirmer strips [SS] and microcapillary tubes [MCT]) have significant drawbacks. Here we present an alternative tear protein sampling method using soft contact lenses (SCLs). First, we optimized SCL protein samplingin vitro, then performedin vivostudies in 6 human subjects. Using Etafilcon A SCLs and 4M guanidine-HCl for protein removal, we sampled an average of 60±31 μg of protein per eye. We also performed objective and subjective assessments of all sampling methods. Proteomic analysis by mass spectrometry (MS) revealed the majority of proteins were sampled by all methods. However, smaller subsets of unique and shared proteins were identified, particularly for SS and MCT. Additionally, SCLs had reduced levels of reflex tear protein zymogen granule protein 16 homolog B (ZG16B) versus SS and MCT. These experiments demonstrate SCLs as an accessible tear sampling method which may minimize reflex tearing and potentially aid biomarker discovery.Abstract Figure
Evaluation of Kernel Low-Rank Compressed Sensing in preclinical Diffusion Magnetic Resonance Imaging
Authors: Alves Rodrigues De Souza Diego , Mathieu Hervé , Deloulme Jean-Christophe , Barbier Emmanuel L. 
Published: February 2023

AbstractCompressed Sensing (CS) is widely used to accelerate clinical diffusion MRI acquisitions, but it remains under-utilized in preclinical settings. In this study, we optimized and compared several CS reconstruction methods for diffusion imaging.Different undersampling patterns and two reconstruction approaches were evaluated: conventional CS, based on Berkeley Advanced Reconstruction Toolbox (BART-CS) toolbox, and a new Kernel Low-Rank (KLR)-CS, based on Kernel Principal Component Analysis and low-resolution-phase maps. 3D CS acquisitions were performed at 9.4T using a 4-element cryocoil on mice (wild type and aMAP6knockout). Comparison metrics were error and Structural Similarity Index Measure (SSIM) on fractional anisotropy (FA) and mean diffusivity (MD), as well as reconstructions of the anterior commissure and fornix. Acceleration factors (AF) up to 6 were considered.In the case of retrospective undersampling, the proposed KLR-CS outperformed BART-CS up to AF=6 for FA and MD maps and tractography. For instance, for AF=4, the maximum errors were respectively 8.0% for BART-CS and 4.9% for KLR-CS, considering both FA and MD in the corpus callosum. Regarding undersampled acquisitions, these maximum errors became respectively 10.5% for BART-CS and 7.0% for KLR-CS. This difference between simulations and acquisitions arose mainly from repetition noise, but also from differences in resonance frequency drift, signal-to-noise ratio, and in reconstruction noise. Despite this increased error, fully sampled and AF=2 yielded comparable results for FA, MD and tractography, and AF=4 showed minor faults. Altogether, KLR-CS based on low-resolution-phase maps seems a robust approach to accelerate preclinical diffusion MRI.
Functional binding of PD1 ligands predicts response to anti-PD1 treatment in cancer patients
Authors: Kaufman Bar , Abramov Orli , Yevko Anna , Apple Daria , Shlapobersky Mark , Greenshpan Yariv , Shaco-Levy Ruthy , Roubinov Keren , Liboff Alejandro , Elkabets Moshe , Porgador Angel 
Published: February 2023

AbstractAccurate predictive biomarkers of response to immune checkpoint inhibitors (ICIs) are required for better stratifying cancer patients to ICI treatments. Here, we present a new concept for a bioassay to predict the response to anti-PD1 therapies, which is based on measuring the binding functionality of PDL1 and PDL2 to their receptor, PD1. In detail, we developed a cell-based reporting system, called the Immuno-checkpoint Artificial Reporter with overexpression of PD1 (IcAR-PD1) and evaluated the PDL1 and PDL2 binding functionality in tumor cell lines, patient-derived xenografts, and in fixed-tissue tumor samples obtained from cancer patients. In a retrospective clinical study, we found that the functionality of PDL1 and PDL2 predicts response to anti-PD1, and functionality of PDL1 binding is a more effective predictor than PDL1 protein expression alone. Our findings suggest that assessing the functionality of ligand binding is superior to staining of protein expression for predicting response to ICIs.TeaserPositive clinical response of cancer patients to anti-PD1 therapy can be predicted by measuring the binding activity of PDL1 and PDL2.
Pathogen genetics identifies avirulence/virulence loci associated with barley chromosome 6H resistance in thePyrenophora teresf.teres– barley interaction
Authors: Li Jinling , Wyatt Nathan A. , Skiba Ryan M. , Kariyawasam Gayan K. , Richards Jonathan K. , Effertz Karl , Rehman Sajid , Brueggeman Robert S. , Friesen Timothy L. 
Published: February 2023

AbstractBarley net form net blotch (NFNB) is a foliar disease caused byPyrenophora teresf.teres. Barley line CIho5791, which harbors the chromosome 6H broad spectrum resistance geneRpt5, displays dominant resistance toP. teresf.teres. To genetically characterizeP. teresf.teresavirulence/virulence on the barley line CIho5791, we generated aP. teresf.teresmapping population using a cross between the Moroccan CIho5791-virulent isolate MorSM40-3, and the avirulent reference isolate 0-1. Genetic maps were generated for all 12 chromosomes (Ch) and quantitative trait locus (QTL) mapping identified two significant QTL associated withP. teresf.teresavirulence/virulence on CIho5791. The most significant QTL mapped toP. teresf.teresCh1 where the virulent allele was contributed by MorSM40-3. A second QTL mapped to Ch8, however, this virulent allele was contributed by 0-1. The Ch1 and Ch8 loci accounted for 27 and 15% of the disease variation, respectively and the avirulent allele at the Ch1 locus was shown to be epistatic over the virulent allele at the Ch8 locus. Additionally, we used 177 sequencedP. teresf.teresisolates in a genome wide association study that identified the same Ch1 and Ch8 loci as the two most significant associations. Within the identified genomic regions, we identified several genes that encoded small secreted proteins, one or more of which may be responsible for overcoming the CIho5791 resistance. Results presented here demonstrate the complexity of avirulence/virulence in theP. teresf.teres- barley interaction.
PI3Kδ inhibition potentiates glucocorticoids in B-lymphoblastic leukemia by decreasing receptor phosphorylation and enhancing gene regulation
Authors: Zimmerman Jessica A.O. , Fang Mimi , Pufall Miles A. 
Published: February 2023

ABSTRACTGlucocorticoids, including dexamethasone and prednisone, are the cornerstone of B-lymphoblastic leukemia (B-ALL) therapy. Because response to glucocorticoids alone predicts overall outcomes for B-ALL, enhancing glucocorticoid potency is a route to improving outcomes. However, systematic toxicities prevent the use of higher dose and more potent glucocorticoids. We therefore took a functional genomic approach to identify targets to enhance glucocorticoid activity specifically in B-ALL cells. Here we show that inhibition of the lymphoid-restricted PI3Kδ, signaling through the RAS/MAPK pathway, enhances both prednisone and dexamethasone activity in almost allex vivoB-ALL specimens tested. This potentiation is most synergistic at sub-saturating doses of glucocorticoids, approaching the EC50. Potentiation correlates with global enhancement of glucocorticoid-induced gene regulation, including regulation of effector genes that drive B-ALL cell death. Idelalisib reduces phosphorylation of the glucocorticoid receptor (GR) at MAPK1/ERK2 targets S203 and S226, and ablation of these phospho-acceptor sites enhances glucocorticoid potency. We further show that phosphorylation of S226 reduces the affinity of GR for DNAin vitro, which impairs DNA binding. We therefore propose that PI3Kδinhibition improves glucocorticoid efficacy in B-ALL in part by decreasing GR phosphorylation, increasing DNA binding affinity, and enhancing downstream gene regulation. The overall enhancement of GR function suggests that idelalisib will provide benefit to most patients with B-ALL by improving outcomes for patients whose disease is less responsive to glucocorticoid-based therapy, including high-risk disease, and allowing less toxic glucocorticoid-sparing strategies for patients with standard-risk disease.
Mechanically activated bone cells drive vessel formation via an extracellular vesicle mediated mechanism
Authors: Shen N. , Maggio M. , Woods I. , Lowry M. , Eichholz K.F , Stavenschi E. , Hokamp K. , Roche F.M. , O’Driscoll L. , Hoey D.A. 
Published: February 2023

AbstractBlood vessel formation is an important initial step for bone formation during development as well as during remodelling and repair in the adult skeleton. This results in a heavily vascularized tissue where endothelial cells and skeletal cells are constantly in crosstalk to facilitate homeostasis, a process that is mediated by numerous environment signals, including mechanical loading. Breakdown in this communication can lead to disease and/or poor fracture repair. Therefore, this study aimed to determine the role of mature bone cells in regulating angiogenesis, how this is influenced by a dynamic mechanical environment, and understand the mechanism by which this could occur. Herein, we demonstrate that both osteoblasts and osteocytes coordinate endothelial cell proliferation, migration, and blood vessel formation via a mechanically dependent paracrine mechanism. Moreover, we identified that this process is mediated via the secretion of extracellular vesicles (EVs), as isolated EVs from mechanically stimulated bone cells elicited the same response as seen with the full secretome, while the EV depleted secretome did not elicit any effect. Despite mechanically activated bone cell derived EVs (MA-EVs) driving a similar response to VEGF treatment, MA-EVs contain minimal quantities of this angiogenic factor. Lastly, a miRNA screen identified mechanoresponsive miRNAs packaged within MA-EVs which are linked with angiogenesis. Taken together, this study has highlighted an important mechanism in osteogenic-angiogenic coupling in bone and has identified the mechanically activated bone cell derived EVs as a therapeutic to promote angiogenesis and potentially bone repair.
Clinorotation inhibits myotube formation by fluid motion, not by simulated microgravity
Authors: Mansour Janet , Berwanger Carolin , Jung Marcel , Eichinger Ludwig , Fabry Ben , Clemen Christoph S. 
Published: February 2023

AbstractTo study processes related to weightlessness in ground-based cell biological research, a theoretically assumed microgravity environment is typically simulated using a clinostat – a small laboratory device that rotates cell culture vessels with the aim of averaging out the vector of gravitational forces. Here, we report that the rotational movement during fast clinorotation induces complex fluid motions in the cell culture vessel, which can trigger unintended cellular responses. Specifically, we demonstrate that suppression of myotube formation by 2D-clinorotation at 60 rpm is not an effect of the assumed microgravity but instead is a consequence of fluid motion. Therefore, cell biological results from fast clinorotation cannot be attributed to microgravity unless alternative explanations have been rigorously tested and ruled out. We consider two control experiments mandatory, i) a static, non-rotating control, and ii) a control for fluid motion. These control experiments are also highly recommended for other rotation speed settings and experimental conditions. Finally, we discuss strategies to minimize fluid motion in clinorotation experiments.
Stabilisation of β-Catenin-WNT signalling by USP10 in APC-truncatedcolorectal cancer drives cancer stemness and enables super-competitor signalling
Authors: Reissland Michaela , Hartmann Oliver , Tauch Saskia , Prieto-Garcia Cristian , Schulte Clemens , Solvie Daniel , Loebbert Sinah , Jacomin Anne-Claire , Pesic Marina , Bugter Jeroen M. , Schuelein-Voelk Christina , Fuss Carmina T. , Pahor Nikolet , Ade Carsten , Buck Viktoria , Potente Michael , Li Vivian , Beliu Gerti , Wiegering Armin , Bitman-Lotan Eliya , Grossmann Tom , Rosenfeldt Mathias , Eilers Martin , Maric Hans , Maurice Madelon M. , Greten Florian , Dikič Ivan , Orian Amir , Gallant Peter , Diefenbacher Markus E. 
Published: February 2023

SummaryThe contribution of deubiquitylating enzymes to β-Catenin stabilisation in intestinal stem cells and colorectal cancer (CRC) is poorly understood. Here, we report the deubiquitylase USP10 as an APC-truncation- specific enhancer of β-Catenin stability, potentiating WNT signalling in CRC and cancer stem cells. Mechanistically, interaction studies in various CRC cell lines and in vitro binding studies, together with computational modelling, revealed that USP10 binding to β-Catenin is mediated via the unstructured N-terminus of USP10 and requires the absence of full-length APC. Notably, loss of USP10 in CRISPR engineered intestinal organoids reduces tumorigenic properties of CRC and blocks the super competitor-signalling of APC-mutated CRC. Furthermore, reduction of USP10 induces the expression of differentiation genes, and opposes the APC-truncated phenotype in an intestinal hyperplasia model ofD.melanogaster.Taken together, our findings reveal USP10s role in intestinal tumourigenesis by stabilising β-Catenin, leading to aberrant WNT signalling, enhancing cancer cell stemness and implicate the DUB USP10 as a cancer specific therapeutic vulnerability inApctruncated CRC.
Proteins with anti-apoptotic action in the hemolymph of caterpillars of the Megalopygidae family acts by maintaining the structure of the cellular cytoskeleton
Authors: de Carvalho Nathalia Delazeri , Rofatto Henrique Krambeck , de Senna Villar Karina , Magnelli Roberta Fiusa , da Silva Junior PI , Mendonça Ronaldo Zucatelli 
Published: February 2023

ABSTRACTBrazil has a very large biological variety, which is an almost inexhaustible source of substances of pharmacological and biotechnological interest. Several studies have demonstrated the presence of bioactive peptides in insect hemolymph and their potential use as therapeutic agents. However, few data are available regarding molecules extracted from insects with anti-apoptotic action. The objective of this work was to identify and isolate proteins from the hemolymph of caterpillars of theMegalopygidaefamily with pharmacological and biotechnological interest. Two species of this family were studied,Podalia sp and Megalopyge albicolis. Cytotoxicity tests on Vero and Sf-9 cells revealed that the hemolymph of both caterpillars was cytotoxic only at concentrations greater than 5%v/v. In the anti-apoptotic activity assays, it was verified that the supplementation of cell cultures with only 1% of hemolymph v/v is sufficient to inhibit cell death by apoptosis induced by different inducers such as terbutyl, actinomycin D, hydrogen peroxide, or even by nutrient depletion. For this study, cells were stained with trypan blue, crystal violet, and fluorescent markers to cytoskeleton (actin and tubulin), mitochondria membrane electric potential (JC-1), and apoptosis marker (acridine orange and ethidium). The protein responsible for anti-apoptotic action was isolated through gel filtration chromatography, using an AKTA purifier high-resolution liquid chromatography system. The hemolymph was fractionated into 3 pools forPodalia spand 6 pools forM. abicolis. In the antiapoptotic tests, semi-purified hemolymph from both caterpillars showed anti-apoptotic effect in VERO and SF-9 cells, pre-treated with only 1% v/v of hemolymph and induced to death by different and apoptotic inductors. Was observed that the molecule with anti-apoptotic effect is present in pool 3 in both hemolymphs. This protector effect blocked and attenuated the disruption of the cytoskeleton (actin filaments), being that the protective effect also was observed on the integrity of the mitochondrial membrane of SF-9 cells pre-treated with both hemolymphs and treated with the apoptosis inducer Terbutil at concentrations of 25 to 100μM. By acting on the mitochondrial pathway of death by apoptosis, a pathway that can cause disorders and diseases neurodegenerative such as Parkinson’s and Alzheimer’s diseases, substances present in the hemolymph of these and others caterpillars could be good candidates in studies for the treatment of these diseases.