bluuebunny/crossref_metadata_2025_split huggingface dataset:
α-Arrestins maintain phospholipid balance and Atg18 distribution to permit efficient autophagy
Authors: Bowman Ray W. , Davis Sydnie , Jordahl Eric M. , Chera Karandeep , Ozbaki-Yagan Nejla , Franks Jonathan , Hawbaker Sarah , Chiang Annette , Acar Omer , Beer-Stoltz Donna , O’Donnell Allyson F. 
Published: August 2022

AbstractCells selectively reorganize their membrane proteome in response to stressors via selective protein trafficking. The α-arrestins, a family of conserved protein trafficking adaptors, bind to select membrane proteins and interact with the ubiquitin ligase Rsp5. The α-arrestins recruit Rsp5 to its membrane protein substrates, permitting their ubiquitination and endocytosis. To identify new α-arrestin functions, we performed a genetic screen to isolate mutants that alter α-arrestin-mediated resistance to rapamycin, a drug that inhibits TORC1. Interestingly, loss of many of the ATG genes, which encode the machinery needed for the self-degradative process of autophagy, disrupted α-arrestins’ ability to promote growth on rapamycin. Herein we define a genetic network linking α-arrestins to autophagy. We show autophagy impairment in the absence of select α-arrestins, with increased autophagosome lifetimes and delayed/reduced delivery of autophagosomes to the vacuole. The α-arrestin mutants that impeded autophagy had vacuole morphology defects and increased vacuolar retention of Atg18, a member of the PROPPIN family that is needed to maintain vacuole shape and facilitate lipid transfer to expanding autophagosomes. Atg18 binds phosphatidylinositol 3 phosphate (PI3P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2), and we observed increased PI3P on the vacuole membrane in α-arrestin mutants. The levels of Vps34 and Fab1, the kinases responsible for the generation of PI3P and PI(3,5)P2, respectively, were also elevated at vacuole membranes in cells lacking α-arrestins. We posit that altered phospholipids in the vacuolar membrane form the basis for the Atg18-Atg2 mislocalization and autophagy defect. These data demonstrate a previously unappreciated link between the α-arrestins and autophagy, expanding the functional impact of these trafficking adaptors in responding to nutrient stress.Author SummaryCells survive nutrient starvation by degrading parts of themselves through the process of autophagy. During autophagy, cells make a double membrane, known as an autophagosome (AP), around bits of cytoplasm or organelles. The AP and its engulfed material are delivered to the vacuole, an organelle that helps break down proteins and lipids. These materials can then be used as building blocks to generate the essential components needed for the cell to survive starvation. For cells to undergo efficient autophagy, they need α-arrestins, a group of proteins important for deciding where membrane proteins localize. In cells lacking α-arrestins, the AP forms slowly, likely due to a problem in growing the AP membrane. This results in less material being delivered to the vacuole via APs when cells do not have α-arrestins. This study defines a new role for α-arrestins in promoting AP formation and starvation survival.
Elucidating the systemic response of wheat plants under waterlogging based on transcriptomic and metabolic approaches
Authors: Cid Geeisy , Francioli Davide , Kolb Steffen , Tandron Moya Yudelsy Antonia , von Wirén Nicolaus , Hajirezaei Mohammad-Reza 
Published: August 2022

AbstractExtreme weather conditions lead to significant imbalances in crop productivity, which in turn affect food security. Flooding events cause serious problems to many crop species such as wheat. Although metabolic readjustments under flooding are important for plant regeneration, underlying processes remain poorly understood. Here, we investigated the systemic response of wheat to waterlogging using metabolomics and transcriptomics. A 12-day exposure to excess water triggered nutritional imbalances and disruption of metabolite synthesis and translocation, reflected by reduction of plant biomass and growth performance. Metabolic and transcriptomic profiling in roots, xylem, and leaves indicated anaerobic fermentation processes as a local response occurring in roots. Differentially expressed genes and ontological categories revealed that carbohydrate metabolism plays an important role as a systemic response. Analysis of the translocation rate of specific compounds in the xylem showed how waterlogging alters the composition of xylem exudates and thus the root to shoot communication. Interestingly, among all metabolites determined in our study, alanine was the most abundant transported in the xylem. Our results suggest an important role of this amino acid not only as amino-nitrogen source but also as the major root-to-shoot translocated and systemically acting metabolite crucial for balancing C/N between roots and shoots during waterlogging.The relevance of this study relies on the basis to characterize the important role of alanine asHighlightMetabolic and transcriptomic changes in wheat highlight alanine as the major root-to-shoot translocated and systemically acting metabolite crucial for balancing C/N between roots and shoots.
Statistical characterization of tactile scenes in three-dimensional environments reveals filter properties of somatosensory cortical neurons
Authors: Zweifel Nadina O. , Solla Sara A. , Hartmann Mitra J. Z. 
Published: August 2022

AbstractNatural scenes statistics have been studied extensively using collections of natural images and sound recordings. These studies have yielded important insights about how the brain might exploit regularities and redundancies in visual and auditory stimuli. In contrast, natural scenes for somatosensation have remained largely unexplored. Here we use three-dimensional scans of natural and human-made objects to quantify natural scene statistics at the scale of the human fingertip. Using measurements of distance, slope, and curvature from the object surfaces, we show that the first order statistics follow similar trends as have been observed for images of natural and human-made environments. In addition, independent component analysis of curvature measurements reveals Gabor-like basis vectors similar to those found in natural images. A simple neural model using these filters showed responses that accurately capture the statistics of responses in primate primary somatosensory cortex.
Behavioural foundation of a massive mitochondrial introgression in the fire salamander,Salamandra salamandra
Authors: Chiocchio Andrea , de Rysky Erica , Carere Claudio , Nascetti Giuseppe , Bisconti Roberta , Canestrelli Daniele 
Published: August 2022

AbstractPatterns of mito-nuclear discordance across secondary contact zones have been reported in a wide range of animal and plant organisms. They consist of a spatial mismatch between nuclear and mitochondrial genomes, in terms of the geographic location and/or extension of the secondary contact zone between distinct evolutionary lineages. Several theoretical and empirical studies have identified massive mitochondrial introgression as the putative source of these mismatches. Yet, we still lack a clear understanding of the potential phenotypic underpinnings of these instances of massive introgression. In this study, we addressed the hypothesis that mtDNA variation across a contact zone could be associated with variation at phenotypic traits affecting dispersal propensity. We analyzed patterns of behavioural and genetic variation across a mtDNA secondary contact zone of the fire salamanderSalamandra salamandrain central Italy, which is over 600 km displaced from its nuclear counterpart. We found distinct behavioral profiles associated with the two mitotypes co-occurring in the mtDNA secondary contact zone. Counterintuitively, we found a ‘slow-thorough’ dispersal profile associated with the massively introgressed mitotype. This dispersal profile was characterized by shy, less active and less exploratory personality traits, and this pattern was consistent across life-stages and contexts (i.e., aquatic larvae and terrestrial juveniles). Our results provide experimental evidence supporting the intriguing hypothesis that personality traits associated with distinct mitotypes could promote differential mitochondrial introgression within alternative nuclear backgrounds.
Brown adipocytes local response to thyroid hormone is required for adaptive thermogenesis in adult male mice
Authors: Zekri Yanis , Guyot Romain , Suñer Inés Garteizgogeascoa , Canaple Laurence , Gautier-Stein Amandine , Vily-Petit Justine , Aubert Denise , Richard Sabine , Flamant Frédéric , Gauthier Karine 
Published: August 2022

AbstractThyroid hormone (T3) and its nuclear receptors (TR) are important regulators of energy expenditure and adaptive thermogenesis, notably through their action in the brown adipose tissue (BAT). However, T3 acts in many other peripheral and central tissues which are also involved in energy expenditure. The general picture of how T3 regulates BAT thermogenesis is currently not fully established, notably due to the absence of extensive omics analyses and the lack of specific mice model. Here, we first used transcriptome and cistrome analyses to establish the list of T3/TR direct target genes in brown adipocytes. We then developed a novel model of transgenic mice, in which T3-signaling is specifically suppressed in brown adipocytes at adult stage. We addressed the capacity of these mice to mount a thermogenic response when challenged by either a cold exposure or a high-fat diet, and analyzed the associated changes in BAT transcriptome. We conclude that T3 plays a crucial role in the thermogenic response of the BAT, controlling the expression of genes involved in lipid and glucose metabolism and regulating BAT proliferation. The resulting picture provides an unprecedented view on the pathways by which T3 activates energy expenditure through an efficient adaptive thermogenesis in the BAT.Significance StatementThyroid hormones (TH) increase energy expenditure by regulating the expression of target genes in many metabolic tissues. Among them, brown adipose tissue (BAT) dissipates biochemical energy into heat production to notably prevent hypothermia during cold exposure. Hypothyroid mice display inefficient BAT thermogenesis suggesting that TH are crucial for this process. Here, we eliminated TH signaling specifically in brown adipocytes and expose the mice to different physiological stressors. We showed that TH signaling is crucial for BAT thermogenesis as it controls the expression of genes involved in proliferation and in the metabolism of lipids and glucose, the main energy resources for BAT thermogenesis. This study provides an unprecedented view on the pathways by which T3 activates energy expenditure the BAT.
Brain de novo transcriptome assembly of a toad species showing polymorphic anti-predatory behavior
Authors: Chiocchio Andrea , Libro Pietro , Martino Giuseppe , Bisconti Roberta , Castrignanò Tiziana , Canestrelli Daniele 
Published: August 2022

AbstractUnderstanding the genomic underpinnings of antipredatory behaviors is a hot topic in eco-evolutionary research. Yellow-bellied toad of the genus Bombina are textbook examples of the deimatic display, a time-structured behavior aimed at startling predators. Here, we generated the first de novo brain transcriptome of the Apennine yellow-bellied toad Bombina pachypus, a species showing inter-individual variation in the deimatic display. Through Rna-Seq experiments on a set of individuals showing distinct behavioral phenotypes, we generated 316,329,573 reads, which were assembled and annotated. The high-quality assembly was confirmed by assembly validators and by aligning the contigs against the de novo transcriptome with a mapping percentage higher than 91.0%. The homology annotation with DIAMOND (blastx) led to 77,391 contigs annotated on Nr, Swiss Prot and TrEMBL, whereas the domain and site protein prediction made with InterProScan led to 4747 GO-annotated and 1025 KEGG-annotated contigs. The B. pachypus transcriptome described here will be a valuable resource for further studies on the genomic underpinnings of behavioral variation in amphibians.
Blocking necroptosis reduces inflammation and tumor incidence in a mouse model of diet-induced hepatocellular carcinoma
Authors: Mohammed Sabira , Thadathil Nidheesh , Tran Albert L , Van Der Veldt Michael , Georgescu Constantin , Haritha Nair H , Ohene-Marfo Phoebe , Oh Sangphil , Nicklas Evan H , Wang Dawei , Luo Wenyi , Janknecht Ralf , Miller Benjamin F , Wren Jonathan D. , Freeman Willard , Deepa Sathyaseelan S 
Published: August 2022

AbstractBackground & AimsNonalcoholic fatty liver disease (NAFLD) is one of the etiologies that contribute to hepatocellular carcinoma (HCC), and chronic inflammation is one of the proposed mediators of HCC. As necroptosis is a cell death pathway that induces inflammation, we tested whether necroptosis- induced inflammation contributes to the progression of NAFLD to HCC in a mouse model of diet- induced HCC.MethodsMale and female wild-type (WT) mice or mouse models where necroptosis is blocked (Ripk3-/- or Mlkl-/- mice) were fed a control diet or choline-deficient low fat diet (CD-LFD) or CD-high fat diet (CD-HFD) for 6 months. Changes in inflammation, immune cell infiltration, activation of oncogenic pathways, and tumor incidence were assessed by gene expression analysis, western blotting, and flow cytometry. RNA sequencing (RNA-seq) was performed to assess the changes in liver transcriptome.ResultsBlocking necroptosis by deleting either Ripk3 or Mlkl reduced markers of inflammation [proinflammatory cytokines (TNFα, IL-6, and IL-1β), F4/80+ve macrophages, CCR2+ve infiltrating monocytes], inflammation associated oncogenic pathways (JNK, PD-L1/PD-1, β-catenin), and HCC in male mice. In female mice, blocking necroptosis reduced HCC independent of inflammation. Blocking necroptosis reduced cell senescence markers in males and females, suggesting a novel cross-talk between necroptosis and cell senescence.ConclusionsOur data show that hepatic necroptosis promotes recruitment and activation of liver macrophages leading to chronic inflammation, which in turn trigger oncogenic pathways leading to the progression of NAFLD to HCC in male mice. In female mice necroptosis contributes to HCC independent of inflammation. Thus, our study suggests that necroptosis is a valid target for NAFLD-mediated HCC.SynopsisNecroptosis is a cell death pathway that mediate inflammation. Blocking necroptosis attenuated chronic inflammation by reducing recruitment and activation of liver macrophages, which in turn reduced activation of oncogenic pathways and progression of NAFLD to HCC in mice.Graphical Abstract
The solution path of the Li-Stephens haplotype copying model
Authors: Jin Yifan , Terhorst Jonathan 
Published: August 2022

AbstractThe Li-Stephens (LS) haplotype copying model forms the basis of a number of important statistical inference procedures in genetics. LS is a probabilistic generative model which supposes that a sampled chromosome is an imperfect mosaic of other chromosomes found in a population. In the frequentist setting which is the focus of this paper, the output of LS is a “copying path” through chromosome space. The behavior of LS depends crucially on two user-specified parameters, θ and ρ, which are respectively interpreted as the rates of mutation and recombination. However, because LS is not based on a realistic model of ancestry, the precise connection between these parameters and the biological phenomena they represent is unclear. Here, we offer an alternative perspective, which considers θ and ρ as tuning parameters, and seeks to understand their impact on the LS output. We derive an algorithm which, for a given dataset, efficiently partitions the (θ, ρ) plane into regions where the output of the algorithm is constant, thereby enumerating all possible solutions to the LS model at one go. We extend this approach to the “diploid LS” model commonly used for phasing. We demonstrate the usefulness of our method by studying the effects changing of θ and ρ when using LS for common bioinformatic tasks. Our findings indicate that using the conventional (i.e., population-scaled) values for θ and ρ produces near optimal results for imputation, but may systematically inflate switch error in the case of phasing diploid genotypes.
FAK-SFK Signaling Integrates ECM Rigidity Sensing and Engagement of ERBB2 to Activate YAP and Promote Invasive Growth and Metastasis in Breast Cancer
Authors: Wang Xiaobo , Wang Shimin 
Published: August 2022

AbstractWe have examined the mechanism through which fibrotic extracellular matrices promote tumor progression and metastasis in HER2+ breast cancer. We found that integrin-mediated mechano-transduction and engagement of ERBB2/ERBB3 cooperate to induce activation of YAP and invasive growth in stiff 3D Matrigel-Collagen I. Mechanistic studies revealed that joint activation of SRC Family Kinases (SFKs) by FAK and ERBB2/3 results in tyrosine phosphorylation and inactivation of LATS1/2 and MOB1. The ensuing activation of YAP enables HER2+ breast cancer cells to proliferate and invade in 3D Matrigel-Collagen I. In addition, tyrosine phosphorylation of LATS1/2 and MOB1 and activation of YAP are required for v-SRC-mediated transformation of fibroblasts. Finally, preclinical studies indicated that FAK-SRC signaling is required for primary tumor growth and lung metastasis in the MMTV-Neumouse model of HER2+ breast cancer. Congruently, administration of dasatinib significantly increased the capacity of lapatinib to inhibit primary tumor growth and lung colonization in MMTV-Neu mice. These findings indicate that integrin-mediated mechano-transduction functions as a rheostat to regulate ERBB2 signaling to YAP and suggest that co-targeting ERBB2 and SFKs may exhibit therapeutic efficacy in HER2+ breast cancer.Significance statementStromal stiffness, which ensues from increased deposition and crosslinking of linear collagens, promotes oncogenesis and tumor progression in the breast. Moreover, tumor fibrosis is increased in the more aggressive subtypes of breast cancer, such as Triple Negative (TN) and HER2+ breast cancer. However, the mechanisms through which extracellular matrix stiffness regulates intracellular signaling are poorly understood. In this study, we show that the Focal Adhesion Kinase (FAK)-SRC Family Kinase (SFK) complex integrates the sensing of matrix rigidity by integrins and the activation of ERBB2/3 to promote activation of YAP and that YAP is required for breast cancer growth and invasion. Mechanistic studies demonstrate that SFKs can phosphorylate and inhibit LATS1 and MOB1, leading to activation of YAP. Simultaneous inhibition of ERBB2/3 with lapatinib and SFKs with dasatinib profoundly inhibits primary tumor growth and metastasis in a mouse model of HER2+ breast cancer. These findings suggest that the therapeutic efficacy of combinatorial blockade of ERBB2 and integrin-mediated mechano-transduction should be tested in biomarker-driven clinical trials.
Successful reproduction of a large EEG study across software packages
Authors: Kabbara Aya , Forde Nina , Maumet Camille , Hassan Mahmoud 
Published: August 2022

AbstractAs an active field of research and with the development of state-of-the-art algorithms to analyze EEG datasets, the parametrization of Electroencephalography (EEG) analysis workflows has become increasingly flexible and complex, with a great variety of methodological options and tools to be selected at each step. This high analytical flexibility can be problematic as it can yield to variability in research outcomes. Therefore, growing attention has been recently paid to understand the potential impact of different methodological decisions on the reproducibility of results.In this paper, we aim to examine how sensitive the results of EEG analyses are to variations in preprocessing with different software tools. We reanalyzed the shared EEG data (N=500) from (Williams et al. 2021) using three of the most commonly used EEG software tools: EEGLAB, Brainstorm and FieldTrip. After reproducing the same original preprocessing workflow in each software, the resulting evoked-related potentials (ERPs) were qualitatively and quantitatively compared in order to examine the degree of consistency/discrepancy between softwares. Our findings show a good degree of convergence in terms of the general profile of ERP waveforms, peak latencies and effect size estimates related to specific signal features. However, considerable variability was also observed in the magnitude of the absolute voltage observed with each software package as reflected by the similarity values and observed statistical differences at particular channels and time instants. In conclusion, we believe that this study provides valuable clues to better understand the impact of the software tool on the analysis of EEG results.
Electrical potential spiking of kombucha zoogleal mats
Authors: Adamatzky Andrew 
Published: August 2022

AbstractA kombucha is a sugared tea fermented by a symbiotic community of over twenty species of bacteria and yeasts. The community produces and inhabits cellulosic gelatinous zoogleal mats. We studied electrical activity of the kombucha mats using pairs of differential electrodes. We discovered that the mats produce action like spikes of electrical potential. The spikes are often grouped in the trains of spikes. Characteristics of the spikes and trains of spikes are presented. We demonstrated that electrical responses of kombucha mats to chemical, electrical and optical stimulation are distinctive and therefore the mats can be used as sensors, or even unconventional computing devices.
Most High Throughput Expression Data Sets Are Underpowered
Authors: Trostle Alexander J. , Wang Jiasheng , Li Lucian , Wan Ying-Wooi , Liu Zhandong 
Published: August 2022

AbstractResearchers handicap their high-throughput sequencing experiments when they do not perform enough biological replicates. Given that biological tissues can be highly variable, too few replicates will lead to false negatives, false positives, irreproducibility, and failure to detect real biological signatures. We propose that at least six biological replicates per condition becomes the standard for high-throughput expression datasets.
Sex andAPOEGenotype Influence Respiratory Function Under Hypoxic and Hypoxic-Hypercapnic Conditions
Authors: Taylor Chase E. , Mendenhall Laura E. , Sunshine Michael D. , Wilson Jessica N. , Calulot Chris M. , Sun Ramon C. , Johnson Lance A. , Alilain Warren J. 
Published: August 2022

ABSTRACTThe apolipoprotein(APOE)gene has been studied due to its influence on Alzheimer’s disease (AD) development and work in anAPOEmouse model recently demonstrated impaired respiratory motor plasticity following spinal cord injury (SCI). Individuals with AD often co-present with obstructive sleep apnea (OSA) characterized by cessations in breathing during sleep. Despite the prominence ofAPOEgenotype and sex as factors in AD progression, little is known about the impact of these variables on respiratory control. Ventilation is tightly regulated across many systems, with respiratory rhythm formation occurring in the brainstem but modulated in response to chemoreception. Alterations within these modulatory systems may result in disruptions of appropriate respiratory control and ultimately, disease. Using mice expressing two different humanizedAPOEalleles, we characterized how sex and the presence ofAPOE3orAPOE4influences ventilation during baseline breathing (normoxia) and during respiratory challenge. We show that sex andAPOEgenotype influence breathing during hypoxic challenge, which may have clinical implications in the context of AD and OSA. Additionally, female mice, while responding robustly to hypoxia, were unable to recover to baseline respiratory levels, emphasizing sex differences in disordered breathing.