bluuebunny/crossref_metadata_2025_split huggingface dataset:
AP2rx7passenger mutation affects the vitality and function of immune cells in P2X4ko and other transgenic mice
Authors: Er-Lukowiak Marco , Duan Yinghui , Rassendren Francois , Ulmann Lauriane , Nicke Annette , Ufer Friederike , Friese Manuel A. , Koch-Nolte Friedrich , Magnus Tim , Rissiek Björn 
Published: June 2020

AbstractAmong laboratory mouse strains many genes are differentially expressed in the same cell population. As consequence, gene targeting in 129-derived embryonic stem cells (ESCs) and backcrossing the modified mice onto the C57BL/6 (B6) background can introduce passenger mutations in the close proximity of the targeted gene. Here, we demonstrate that several 129-originating transgenic mice in whichP2rx7-neighboring genes were targeted carry aP2rx7passenger mutation that affects the vitality and function of T cells. By the example ofP2rx4tm1Rasswe demonstrate that CD4+and CD8+T cells derived from these mice express higher levels of P2X7 when compared to corresponding cell populations in B6-WT mice. The increased T cell sensitivity towards the P2X7 activators adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD+) rendered these cells more vulnerable towards NAD-induced cell death (NICD) compared to their B6-WT counterparts. The enhanced NICD sensitivity significantly affected the outcome of functional assays e.g. cytokine production and cell migration. For P2rx4tm1Rass, we demonstrate that the expression of P2X7 is diminished in several innate immune cell populations, possibly as a side effect ofP2rx4targeting, and independent of theP2rx7passenger mutation. These results need to be considered when working with P2rx4tm1Rassmice or other 129-based transgenic strains that targetP2rx7neighboring genes and might have implications for other mouse models.
Beyond sharing unpleasant affect – evidence for pain-specific opioidergic modulation of empathy for pain
Authors: Rütgen Markus , Wirth Eva-Maria , Riečanský Igor , Hummer Allan , Windischberger Christian , Petrovic Predrag , Silani Giorgia , Lamm Claus 
Published: June 2020

AbstractThe neural mechanisms underpinning empathy for pain are still a matter of debate. One of the major questions is whether empathy-related pain responses indicate domain-general vs. pain-specific affective responses. Using fMRI and psychopharmacological experiments, we investigated if placebo analgesia reduces first-hand and empathic experiences of affective touch, and compared them to the effects on pain. Placebo analgesia also affected the first-hand and empathic experience of unpleasant touch, implicating domain-general effects. However, and in contrast to pain and pain empathy, administering an opioid antagonist did not block these effects. Moreover, placebo analgesia reduced neural activity related to both modalities in the bilateral insular cortex, while it specifically modulated activity in the anterior midcingulate cortex for pain and pain empathy. These findings provide causal evidence that one of the major neurochemical systems for pain regulation is involved in pain empathy, and crucially substantiate the role of shared representations in empathy.
Visualizing ATP Dynamics in Live Mice
Authors: Koitabashi Norimichi , Ogasawara Riki , Yasui Ryuto , Sugiura Yuki , Matsuda Hinako , Nonaka Shigenori , Izumi Takashi , Kurabayashi Masahiko , Suematsu Makoto , Yanagita Motoko , Imamura Hiromi , Yamamoto Masamichi 
Published: June 2020

ABSTRACTAnalysis of the dynamics of adenosine triphosphate (ATP) is vital to quantitatively define the actual roles of ATP in biological activities. Here, we applied a genetically encoded Förster resonance energy transfer biosensor “GO-ATeam” and created a transgenic mouse model that allows systemic ATP levels to be quantitatively, sensitively, noninvasively, and spatiotemporally measured under physiological and pathological conditions. We used this model to readily conduct intravital imaging of ATP dynamics under three different conditions: during exercise, in all organs and cells; during myocardial infarction progression; and in response to the application of cardiotoxic drugs. These findings provide compelling evidence that the GO-ATeam mouse model is a powerful tool to investigate the multifarious functions of cellular ATPin vivowith unprecedented spatiotemporal resolution in real-time. This will inform predictions of molecular and morphological responses to perturbations of ATP levels, as well as the elucidation of physiological mechanisms that control ATP homeostasis.One Sentence SummaryIntravital real-time imaging of ATP dynamics in multiple organs using GO-ATeam mice, can be used to quantitatively, sensitively, noninvasively, and spatiotemporally measure systemic ATP levels and provide a platform for preclinical pharmacological studies.
Phylogenetic Analysis of St. Louis Encephalitis Virus within Two Southwestern United State Counties: a case for a bulk introduction event into the southwest United States
Authors: Ridenour Chase , Cocking Jill , Poidmore Samuel , Erickson Daryn , Brock Breezy , Valentine Michael , Young Steven J , Henke Jennifer A , Hung Kim Y , Wittie Jeremy , O’Neill Heidie M Hornstra , Sheridan Krystal , Centner Heather , Lemmer Darrin , Fofanov Viacheslav , Smith Kirk , Will James , Townsend John , Keim Paul S. , Engelthaler David M. , Hepp Crystal M 
Published: June 2020

AbstractSt. Louis Encephalitis Virus (SLEV) has been seasonally detected within theCulex spp. populations within Maricopa County, Arizona and Coachella Valley, California since an outbreak in Maricopa County in 2015. Previous work revealed that the outbreak was caused by an importation of SLEV genotype III, which had only been detected within Argentina in prior years. However, little is known about when the importation occurred or the population dynamics since its arrival into the southwestern United States. In this study, we wanted to determine if the annual detection of SLEV in Maricopa and Riverside counties is due to enzootic cycling or new importations. To address this question, we analyzed 143 SLEV genomes (138 sequenced as part of this study) using the Bayesian phylogenetic analysis software, BEAST, to estimate the date of arrival into the American Southwest and characterize the underlying population structure of SLEV. Phylogenetic clustering showed that SLEV variants circulating in Arizona and California form two distinct populations with little evidence of transmission among the two populations since the onset of the outbreak. Interestingly, the SLEV variants in Coachella Valley appear to be annually imported from a nearby source, whereas the Arizona population is locally sourced each year. Finally, the earliest representatives of SLEV genotype III in the southwestern US formed a polytomy that includes both California and Arizona samples. We propose that the initial outbreak could have resulted from an introductory population of SLEV, perhaps in one or more bird flocks migrating north in 2013, rather than a single variant introduced by one bird.
Syndecan-4-/-mice have smaller muscle fibers, increased Akt/mTOR/S6K1 and Notch/HES-1 pathways, and alterations in extracellular matrix components
Authors: Rønning Sissel Beate , Carlson Cathrine Rein , Aronsen Jan Magnus , Pisconti Addolorata , Høst Vibeke , Lunde Marianne , Liland Kristian Hovde , Sjaastad Ivar , Kolset Svein Olav , Christensen Geir , Pedersen Mona Elisabeth 
Published: June 2020

AbstractBackgroundExtracellular matrix (ECM) remodeling is essential for skeletal muscle development and adaption in response to environmental cues such as exercise and injury. The cell surface proteoglycan syndecan-4 has been reported to be essential for muscle differentiation, but few molecular mechanisms are known. Syndecan-4-/-mice are unable to regenerate damaged muscle, and display deficient satellite cell activation, proliferation, and differentiation. A reduced myofiber basal lamina has also been reported in syndecan-4-/-muscle, indicating possible defects in ECM production. To get a better understanding of the underlying molecular mechanisms, we have here investigated the effects of syndecan-4 genetic ablation on molecules involved in ECM remodeling and muscle growth, both under steady state conditions and in response to exercise.MethodsTibialis anterior (TA) muscles from sedentary and exercised syndecan-4-/-and WT mice were analyzed by immunohistochemistry, real-time PCR and western blotting.ResultsCompared to WT, we found that syndecan-4-/-mice had reduced body weight, reduced muscle weight, muscle fibers with a smaller cross-sectional area, and reduced expression of myogenic regulatory transcription factors. Sedentary syndecan-4-/-had also increased mRNA levels of syndecan-2, decorin, collagens, fibromodulin, biglycan, and LOX. Some of these latter ECM components were reduced at protein level, suggesting them to be more susceptible to degradation or less efficiently translated when syndecan-4 is absent. At the protein level, TRPC7 was reduced, whereas activation of the Akt/mTOR/S6K1 and Notch/HES-1 pathways were increased. Finally, although exercise induced upregulation of several of these components in WT, a further upregulation of these molecules was not observed in exercised syndecan-4-/-mice.ConclusionsAltogether our data suggest an important role of syndecan-4 in muscle development.
Forecasting virus diffusion with simple Bayesian forecast combination
Authors: Franses Philip Hans 
Published: June 2020

AbstractThere are various diffusion models for S shaped processes like virus diffusion and these models are typically not nested. In this note it is proposed to combine the forecasts using a simple Bayesian forecast combination algorithm. An illustration to daily data on cumulative Covid-19 cases in the Netherlands shows the ease of use of the algorithm and the accuracy of the thus combined forecasts.
The influence of Schizotypy on Event-Related Oscillations in Sensory Gating during early Infant Development
Authors: Smith Eleanor S. , Crawford Trevor J. , Reid Vincent M. 
Published: June 2020

AbstractMaternal schizotypic personality is thought to influence childhood risk for mental health and is a personality dimension elevated among schizophrenia-spectrum patients and their first-degree relatives, in whom neuro-oscillatory deficits have been observed. The current study investigated whether 6-month-old infants (n=46), and a subset of their biological mothers (n=34), who identified as either schizotypic (n=14) non-schizotypic (n=14), or an intermediate group (n=6), displayed reduced evoked-oscillatory activity. All mothers completed the Oxford-Liverpool Inventory of Feelings and Experiences as an index of schizotypy dimensionality. An auditory paired-tone paradigm was used to probe oscillatory activity, revealing that although the infants’ evoked-oscillations displayed differences betweenStimulus 1and2, there were no group differences between infants of schizotypic and control mothers. Their mothers, however, displayed differences, with reduced amplitudes towardStimulus 1in schizotypic mothers; consistent with literature on early sensory processes, showing sensory gating is impaired in schizophrenia-spectrum disorders.
RNA-seq analyses: Benchmarking differential expression analyses tools reveals the effect of higher number of replicates on performance
Authors: Salifu Samson Pandam , Nyarko Hannah Nyarkoah , Doughan Albert , Msatsi Haward Keteyo , Mensah Isabel , Bukari Abdul-Rahman Adamu 
Published: June 2020

AbstractThe introduction of several differential gene expression analysis tools has made it difficult for researchers to settle on a particular tool for RNA-seq analysis. This coupled with the appropriate determination of biological replicates to give an optimum representation of the study population and make biological sense. To address these challenges, we performed a survey of 8 tools used for differential expression in RNA-seq analysis. We simulated 39 different datasets (from 10 to 200 replicates, at an interval of 5) using compcodeR with a maximum of 100 replicates. Our goal was to determine the effect of varying the number of replicates on the performance (F1-score, recall and precision) of the tools. EBSeq and edgeR-glmRT recorded the highest (0.9385) and lowest (0.6505) average F1-score across all replicates, respectively. We also performed a pairwise comparison of all the tools to determine their concordance with each other in identifying differentially expressed genes. We found the greatest concordance to be betweenlimma voom treatandlimma voom ebayes. Finally, we recommend employing edgeR-glmRT for RNA-seq experiments involving 10-50 replicates and edgeR-glmQLF for studies with 55 to 200 replicates.Author summaryDownstream analysis of RNA-seq data in R often poses several challenges to researchers as it is a daunting task to choose a specific differential expression analysis tool over another. Researchers also find it challenging to determine the number (replicates) of samples to use in order to give comparable and accurate results. In this paper, we surveyed eight differential expression analysis tools using different number of replicates of simulated RNA-seq count data. We measured the performance of each tool and based on the recorded F1-scores, recall and precision, we made the following recommendations; consider edgeR-glmRT and edgeR-glmQLF for replicates of 10-50 and 55-200 respectively.
Molecular Basis of Sex Difference in Neuroprotection induced by Hypoxia Preconditioning in Zebrafish
Authors: Das Tapatee , Soren Kalyani , Yerasi Mounica , Kamle Avijeet , Kumar Arvind , Chakravarty Sumana 
Published: June 2020

ABSTRACTHypoxia, the major cause of ischemia, leads to debilitating disease in infants via birth asphyxia and cerebral palsy, whereas in adults via heart attack and stroke. A widespread, natural protective phenomenon termed ‘Hypoxic Preconditioning’ occurs when prior exposures to hypoxia eventually results in robust hypoxia resistance. Accordingly, we have developed a novel model of sex-specific hypoxic preconditioning in adult zebrafish to mimic the tolerance of mini stroke(s) in human, which appears to protect against the severe damage inflicted by a major stroke event. Remarkable difference in the progression pattern of neuroprotection between preconditioning hypoxia followed by acute hypoxia (PH) group, and acute hypoxia (AH) group were observed with noticeable sex difference. Since gender difference has been reported in stroke, it was pertinent to investigate whether any such sex difference also exists in PH’s protective mechanism against acute ischemic stroke. In order to elucidate the neural molecular mechanisms behind sex difference in neuroprotection induced by PH, a high throughput proteomics approach utilizing iTRAQ was performed, followed by protein enrichment analysis using Ingenuity Pathway Analysis. Out of thousands of altered proteins in zebrafish brain, the ones having critical role either in neuroglial proliferation/differentiation or neurotrophic functions, were validated by analyzing their expression levels in PH, AH and normoxia groups. Results indicate that female zebrafish brains are more protected against the severity of AH. The study also sheds light on the involvement of many signaling pathways underlying sex difference in pre-conditioning induced neuroprotective mechanism, which can be further validated for the therapeutic approach.
Slippery flowers as a mechanism of defence against nectar-thieving ants
Authors: Takeda Kazuya , Kadokawa Tomoki , Kawakita Atsushi 
Published: June 2020

AbstractBackground and AimsThe great diversity of floral characters among animal-pollinated plants is commonly understood as the result of coevolutionary interactions between plants and pollinators. Floral antagonists, such as nectar thieves, also have the potential to exert selection on floral characters, but adaptation against floral antagonists has attracted comparatively little attention. We found that the corollas of hornet-pollinatedCodonopsis lanceolata(Campanulaceae) and the tepals of bee-pollinatedFritillaria koidzumiana(Liliaceae) are slippery to nectar-thieving ants living in the plant’s habitat; because the flowers of both species have exposed nectaries, slippery perianths may function as a defence against nectar-thieving ants.MethodsWe conducted a behavioural experiment and observed perianth surface microstructure by scanning electron microscopy to investigate the mechanism of slipperiness. Field experiments were conducted to test whether slippery perianths prevent floral entry by ants, and whether ant presence inside flowers affects pollination.Key ResultsScanning electron microscopy observations indicated that the slippery surfaces were coated with epicuticular wax crystals. The perianths lost their slipperiness when wiped with hexane. Artificial bridging of the slippery surfaces using non-slippery materials allowed ants to enter flowers more frequently. Experimental introduction of live ants to theCodonopsisflowers evicted hornet pollinators and shortened the duration of pollinator visits. However, no differences were found in the fruit or seed sets of flowers with and without ants.ConclusionsSlippery perianths, most likely based on epicuticular wax crystals, prevent floral entry by ants that negatively affect pollinator behaviour. Experimental evidence of floral defence based on slippery surfaces is rare, but such a mode of defence may be widespread amongst flowering plants.
Evaluating the efficacy of RT-qPCR SARS-CoV-2 direct approaches in comparison to RNA extraction
Authors: Israeli Ofir , Beth-Din Adi , Paran Nir , Stein Dana , Lazar Shirley , Weiss Shay , Milrot Elad , Atiya-Nasagi Yafit , Yitzhaki Shmuel , Laskar Orly , Schuster Ofir 
Published: June 2020

ABSTRACTSARS-CoV-2 genetic identification is based on viral RNA extraction prior to RT-qPCR assay, however recent studies support the elimination of the extraction step. Herein, we assessed the RNA extraction necessity, by comparing RT-qPCR efficacy in several direct approaches vs. the gold standard RNA extraction, in detection of SARS-CoV-2 from laboratory samples as well as clinical Oro-nasopharyngeal SARS-CoV-2 swabs. Our findings show advantage for the extraction procedure, however a direct no-buffer approach might be an alternative, since it identified up to 70% of positive clinical specimens.
Igf signalling uncouples retina growth from body size by modulating progenitor cell division
Authors: Becker Clara , Lust Katharina , Wittbrodt Joachim 
Published: June 2020

AbstractBalancing the relative growth of body and organs is of key importance for coordinating size and function. This is of particular relevance in post-embryonically growing organisms, facing this challenge life-long. We addressed this question in the neuroretina of medaka fish(Oryzias latipes),where growth and size regulation are crucial for functional homeostasis of the visual system. We find that a central growth regulator, Igf1 receptor, is necessary and sufficient for proliferation control in the postembryonic retinal stem cell niche, the ciliary marginal zone (CMZ). Targeted activation of Igf1r signalling in the CMZ uncouples neuroretina growth from body size control, increasing layer thickness while preserving the structural integrity of the retina. The retinal expansion is driven exclusively by enhanced proliferation of progenitor cells while stem cells do not respond to Igf1r modulation. Our findings position Igf signalling as key module controlling retinal size and structure with far reaching evolutionary implications.
Multi-Dimensional Immuno-Profiling ofDrosophilaHemocytes by Single Cell Mass Cytometry
Authors: Balog József Á. , Honti Viktor , Kurucz Éva , Kari Beáta , Puskás László G. , Andó István , Szebeni Gábor J. 
Published: June 2020

AbstractSingle cell mass cytometry (SCMC) combines features of traditional flow cytometry (FACS) with mass spectrometry and allows the measurement of several parameters at the single cell level, thus permitting a complex analysis of biological regulatory mechanisms. We optimized this platform to analyze the cellular elements, the hemocytes, of theDrosophilainnate immune system. We have metal-conjugated six antibodies against cell surface antigens (H2, H3, H18, L1, L4, P1), against two intracellular antigens (3A5, L2) and one anti-IgM for the detection of L6 surface antigen, as well as one anti-GFP for the detection of crystal cells in the immune induced samples. We investigated the antigen expression profile of single cells and hemocyte populations in naive, in immune induced states, in tumorous mutants (hopTumbearing a driver mutation andl(3)mbn1carrying deficiency of a tumor suppressor) as well as in stem cell maintenance defectivehdcΔ84mutant larvae. Multidimensional analysis enabled the discrimination of the functionally different major hemocyte subsets, lamellocytes, plasmatocytes, crystal cell, and delineated the unique immunophenotype of the mutants. We have identified sub-populations of L2+/P1+ (l(3)mbn1), L2+/L4+/P1+ (hopTum)transitional phenotype cells in the tumorous strains and a sub-population of L4+/P1+ cells upon immune induction. Our results demonstrated for the first time, that mass cytometry, a recent single cell technology combined with multidimensional bioinformatic analysis represents a versatile and powerful tool to deeply analyze at protein level the regulation of cell mediated immunity ofDrosophila.
Feedback control of Wnt signaling based on histidine cluster co-aggregation between Naked/NKD and Axin
Authors: Gammons Melissa , Renko Miha , Flack Joshua E. , Mieszczanek Juliusz , Bienz Mariann 
Published: June 2020

ABSTRACTFeedback control is a universal feature of cell signaling pathways. Naked/NKD is a widely conserved feedback regulator of Wnt signaling which controls animal development and tissue homeostasis. Naked/NKD destabilizes Dishevelled, which assembles Wnt signalosomes to inhibit the β-catenin destruction complex via recruitment of Axin. Here, we discover that the molecular mechanism underlying Naked/NKD function relies on its assembly into ultrastable decameric core aggregates via its conserved C-terminal histidine cluster (HisC). HisC aggregation is facilitated by Dishevelled and depends on accumulation of Naked/NKD during prolonged Wnt stimulation. Naked/NKD HisC cores co-aggregate with a conserved histidine cluster within Axin, to destabilize it along with Dishevelled, possibly via the autophagy receptor p62 which binds to HisC aggregates. Consistent with this, attenuated Wnt responses are observed in CRISPR-engineered flies and human epithelial cells whose HisC has been deleted. Thus, HisC aggregation by Naked/NKD provides context-dependent feedback control of prolonged Wnt responses.