bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA840 accelerates leaf senescence by targeting the overlapping 3’UTRs ofPPRandWHIRLY3inArabidopsis thaliana
Authors: Yujun Ren , Wanzhen Wang , Wei Lan , Dirk Schenke , Daguang Cai , Ying Miao 
Published: October 2020

AbstractMicroRNAs (miRNAs) negatively regulate gene expression by cleaving the target mRNA and/or impairing its translation, thereby playing a crucial role in plant development and environmental stress responses. In Arabidopsis,MIR840is located within the overlapping 3’UTR ofPPRandWHIRLY3 (WHY3),both being predicted targets of miR840. Gain- and loss-of-function of miR840 in Arabidopsis resulted in opposite senescent phenotypes. Highest expression ofpri-miR840is observed at senescence initiation, and is negatively correlated with a significant reduction ofPPRtranscripts but not ofWHY3.AlthoughWHY3transcript levels were not significantly affected by miR840 overexpression, its protein synthesis was strongly reduced. Mutating the cleavage sites or replacing the target sequences abolishes the miR840-mediated degradation ofPPRtranscripts and inhibition ofWHY3translation. In support for this, concurrent knock-down of bothPPRandWHY3in the WT resulted in the senescent phenotype resembling that of the miR840-overexpressing mutant. This indicates that both PRR and WHY3 are targets in the miR840-regulated senescent pathway. Moreover, single knockout mutant ofPPRorWHY3shows a convergent up-regulated subset of senescence-associated genes, which are also found among those induced by miR840 overexpression. Our data provide evidences for a regulatory role of miR840 in plant senescence.HighlightMicroRNA840 (miR840) has a unique miRNA-target configuration regulatingPPRandWHIRLY3genes in Arabidopsis. MiR840 is highly expressed at the onset of plant senescent stage. BothPPRandWHIRLY3transcripts are specifically targetedin vivowithin their 3’UTR region by mature miR840 or its star strandin vivo.Interestingly,PPRexpression is mainly repressed on mRNA transcript level by cleavage, while WHIRLY3 is predominantly translationally inhibited. We conclude that miR840 enhances plant senescenceviapost transcriptional gene silencing ofPPRandWHIRLY3, which appear to be novel negative joint regulators of plant senescence.Footnote: The author(s) responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the intructions for Authors is: Ying Miao (ymiao@fafu.edu.cn)
Bayesian inference: The comprehensive approach to analyzing single-molecule experiments
Authors: Kinz-Thompson Colin D. , Ray Korak Kumar , Gonzalez Ruben L. 
Published: October 2020

ABSTRACTBiophysics experiments performed at single-molecule resolution contain exceptional insight into the structural details and dynamic behavior of biological systems. However, extracting this information from the corresponding experimental data unequivocally requires applying a biophysical model. Here, we discuss how to use probability theory to apply these models to single-molecule data. Many current single-molecule data analysis methods apply parts of probability theory, sometimes unknowingly, and thus miss out on the full set of benefits provided by this self-consistent framework. The full application of probability theory involves a process called Bayesian inference that fully accounts for the uncertainties inherent to single-molecule experiments. Additionally, using Bayesian inference provides a scientifically rigorous manner to incorporate information from multiple experiments into a single analysis and to find the best biophysical model for an experiment without the risk of overfitting the data. These benefits make the Bayesian approach ideal for analyzing any type of single-molecule experiment.
Mice hypomorphic forPitx3define a minimal dopamine neuron population sufficient for entraining behavior and metabolism to scheduled feeding
Authors: Scarpa Lori L. , Wanken Brad , Smidt Marten , Mistlberger Ralph E. , Steele Andrew D. 
Published: October 2020

SummaryPitx3akmice lack a functioning retina and nearly all dopamine neurons of the substantia nigra (SN). del Rio-Marten et al (2019) reported that entrainment of circadian rhythms to daily light-dark and feeding schedules is absent in these mice. With food limited to 12h/day, food anticipatory circadian rhythms failed to emerge, and metabolic rhythms failed to synchronize with locomotor and feeding rhythms. The authors propose that retinal innervation of the suprachiasmatic nucleus clock is required for development of cyclic metabolic homeostasis, but methodological issues limit interpretation of the results. Using standardized feeding schedules and procedures for distinguishing free-running from entrained circadian rhythms, we confirm that behavioral and metabolic rhythms inPitx3akmice do not entrain to LD cycles, but we find no desynchrony between these rhythms nor a deficit in entrainment to daily feeding schedules. SN dopamine neurons surviving inPitx3akmice may define a mininum population sufficient for food entrainment.
Ultrasound activates mechanosensitive TRAAK K+channels directly through the lipid membrane
Authors: Sorum Ben , Rietmeijer Robert A. , Gopakumar Karthika , Adesnik Hillel , Brohawn Stephen G. 
Published: October 2020

SummaryUltrasound modulates the electrical activity of excitable cells and offers advantages over other neuromodulatory techniques; for example, it can be non-invasively transmitted through skull and focused to deep brain regions. However, the fundamental cellular, molecular, and mechanistic bases of ultrasonic neuromodulation are largely unknown. Here, we demonstrate ultrasound activation of the mechanosensitive K+channel TRAAK with sub-millisecond kinetics to an extent comparable to canonical mechanical activation. Single channel recordings reveal a common basis for ultrasonic and mechanical activation with stimulus-graded destabilization of long-duration closures and promotion of full conductance openings. Ultrasonic energy is transduced to TRAAK directly through the membrane in the absence of other cellular components, likely increasing membrane tension to promote channel opening. We further demonstrate ultrasonic modulation of neuronally expressed TRAAK. These results suggest mechanosensitive channels underlie physiological responses to ultrasound and provides a framework for developing channel-based sonogentic actuators for acoustic neuromodulation of genetically targeted cells.
Connectome Gradient Dysfunction in Major Depression and Its Association with Gene Expression Profiles
Authors: Xia Mingrui , Liu Jin , Mechelli Andrea , Sun Xiaoyi , Ma Qing , Wang Xiaoqin , Wei Dongtao , Chen Yuan , Liu Bangshan , Huang Chu-Chung , Zheng Yanting , Wu Yankun , Chen Taolin , Cheng Yuqi , Xu Xiufeng , Gong Qiyong , Si Tianmei , Qiu Shijun , Lin Ching-Po , Cheng Jingliang , Tang Yanqing , Wang Fei , Qiu Jiang , Xie Peng , Li Lingjiang , He Yong ,   DIDA-Major Depressive Disorder Working Group
Published: October 2020

AbstractBackgroundPatients with major depressive disorder (MDD) exhibit concurrent deficits in sensory processing and high-order cognitive functions such as self-awareness and rumination. Connectome mapping studies have suggested a principal primary-to-transmodal gradient in functional brain networks, supporting the spectrum from sensation to cognition. However, whether this principal connectome gradient is disrupted in patients with MDD and how this disruption is associated with gene expression profiles remain unclear.MethodsUsing a large cohort of resting-state functional magnetic resonance imaging data from 2,234 participants (1,150 patients with MDD and 1,084 healthy controls) recruited at 10 sites, we investigated MDD-related alterations in the principal connectome gradient. We further used Neurosynth and postmortem gene expression data to assess the cognitive functions and transcriptional profiles related to the gradient alterations in MDD, respectively.ResultsRelative to controls, patients with MDD exhibited abnormal global topography of the principal primary-to-transmodal gradient, as indicated by reduced explanation ratio, gradient range, and gradient variation (Cohen’sd= −0.16∼-0.21). Focal alterations of gradient scores were mostly in the primary systems involved in sensory processing and in the transmodal systems implicated in high-order cognition. The transcriptional profiles explained 53.9% of the spatial variance in the altered gradient patterns, with the most correlated genes enriched in transsynaptic signaling and calcium ion binding.ConclusionsThese results highlight the dysfunction of the core connectome hierarchy in MDD and its linkage with gene expression profiles, providing insights into the neurobiological and molecular genetic underpinnings of sensory-cognitive deficits in this disorder.
Attribution of Cancer Origins to Endogenous, Exogenous, and Actionable Mutational Processes
Authors: Cannataro Vincent L. , Mandell Jeffrey D. , Townsend Jeffrey P. 
Published: October 2020

AbstractMutational processes in tumors leave tell-tale genomic signatures composed of “passenger” mutations and mutations that have quantifiable effects on the proliferation and survival of cancer cell lineages. We identify the contributions of mutational processes to each oncogenic variant, quantifying responsibility for origination of changes at oncogenic variant sites contributing to tumorigenesis in 23 cancer types. We demonstrate that the variants driving melanomas and lung cancers are predominantly attributable to the actionable, preventable, exogenous mutational processes of ultraviolet light and tobacco exposure, whereas gliomas and prostate adenocarcinomas are largely attributable to endogenous processes associated with aging. Preventable mutations associated with pathogen exposure and APOBEC activity account for a large proportion of the cancer effect within head and neck, bladder, cervical, and breast cancers. These attributions complement epidemiological approaches—revealing the burden of cancer driven by single-nucleotide variants caused by either endogenous or exogenous, non-actionable or actionable processes, and crucially inform cancer prevention.
EGF-Activated Grb7 Confers to STAT3-Mediated EPHA4 Gene Expression in Regulating Lung Cancer Progression
Authors: Chu Pei-Yu , Tai Yu-Ling , Wang Ming-Yang , Lee Hsinyu , Kuo Wen Hung , Shen Tang-Long 
Published: October 2020

AbstractGrowth factor receptor bound protein-7 (Grb7) is a multi-domain signaling adaptor protein that regulates various cellular functions acting as an adaptor protein in relaying signal transduction. Although several studies indicated that Grb7 amplifies EGFR-mediated signaling in cancers, the detailed regulatory mechanism of whether and how Grb7 is involved in EGFR-mediated lung cancer progression remains unclear. Here, we demonstrate that EGF-regulated Grb7 phosphorylation promotes lung cancer progression through phosphorylation of STAT3. Intrinsically, EGF/EGFR signal is required for the formation of Grb7/STAT3 complex as well as its nuclear accumulation. Once in the nucleus, STAT3 interacts withEPHA4promoter, which in turn affects the gene expression level ofEPHA4through transcriptional regulation. Functionally, EphA4 together with EGFR promotes cancer migration, proliferation, and anchorage-independent growth. Our study reveals a novel mechanism in which Grb7 contribute to lung cancer malignancies through its interaction with STAT3 that leads to sequential regulation ofEPHA4gene expression in an EGF/EGFR signal-dependent manner.
A role of DAO1 in oxidation of IAA amino acid conjugates revealed through metabolite, high throughput transcript and protein level analysis
Authors: Karel Müller , Petre Dobrev I. , Aleš Pěnčík , Petr Hošek , Zuzana Vondráková , Roberta Filepová , Kateřina Malínská , Lenka Helusová , Tomáš Moravec , Retzer Katarzyna , Karel Harant , Ondřej Novák , Klára Hoyerová , Jan Petrášek 
Published: October 2020

SummaryAuxin metabolism is, together with auxin transport, a key determinant of auxin signalling output in plant cells, yet details on the underlying mechanisms and factors involved are still largely unknown. Processes involved in the auxin metabolism are subject to regulation based on numerous signals, including auxin concentration itself. Altered auxin availability and the subsequent changes of auxin metabolite profiles can therefore elucidate the function and regulatory role of individual elements in the auxin metabolic machinery.After analysing auxin metabolism in auxin dependent tobacco BY-2 cell line grown in presence or absence of synthetic auxin 2,4-D we found that both conditions were similarly characterized by very low levels of endogenous indole-3-acetic acid (IAA) and its metabolites. However, metabolic profiling after exogenous application of IAA uncovered that the concentration of N-(2-oxindole-3-acetyl)-L-aspartic acid (oxIAA-Asp), the most abundantly formed auxin metabolite in the control culture, dramatically decreased in auxin-starved conditions. To describe the molecular mechanism behind this regulation, we analysed transcriptome and proteome changes caused by auxin starvation. While no changes in the expression of auxin biosynthetic machinery were observed, many genes related to auxin conjugation and degradation showed differential expression. Selected putative auxin glycosylating enzymes as well as members of the Gretchen Hagen 3 gene family involved in auxin amino acid conjugation showed both up- and down-regulation. Contrarily to that, all tobacco homologs ofArabidopsis thalianaDIOXYGENASE FOR AUXIN OXIDATION 1 (DAO1), known to be responsible for the formation of oxIAA from IAA, showed significant downregulation at both transcript and protein levels. To validate the role of DAO1 in auxin metabolism, we performed auxin metabolite profiling in BY-2 mutants carrying either siRNA-silenced or CRISPR-Cas9-mutatedNtDAO1, as well as indao1-1 Arabidopsis thalianaplants. Both mutants showed not only expectedly lower levels of oxIAA, but also significantly lower abundance of oxidated amino acid conjugates of IAA (oxIAA-Asp). Our results thus represent the first direct evidence on DAO1 activity on IAA amino acid conjugates.Statement of significanceHere we present an analysis of auxin metabolism on metabolite, transcript and protein levels in tobacco BY-2 cell line, collectively identifying oxidation of IAA amino acid conjugates as a new role of DIOXYGENASE FOR AUXIN OXIDATION 1 within an auxin-level-responsive metabolic system.
Actin-based protrusions lead microtubules during stereotyped axon initiation in spinal neuronsin vivo
Authors: Moore Rachel E. , Pop Sînziana , Alleyne Caché , Clarke Jonathan DW 
Published: October 2020

ABSTRACTIn vitro, developing neurons progress through well-defined stages to form an axon and multiple dendrites.In vivo, neurons are derived from progenitors within a polarised neuroepithelium and it is not clear how axon initiation observedin vitrorelates to what occurs in a complex, three-dimensionalin vivoenvironment. Here we show that the position of axon initiation in embryonic zebrafish spinal neurons is extremely consistent across neuronal sub-types. We investigated what mechanisms may regulate axon positioningin vivoand found that microtubule organising centres are located distant from the site of axon initiation in contrast to that observedin vitro, and that microtubule plus-ends are not enriched in the axon during axon initiation. F-actin accumulation precedes axon formation and nascent axons form but are not stabilised in the absence of microtubules. Laminin depletion removes a spatial cue for axon initiation but axon initiation remains robust.
Immunoglobulins, MHC and T Cell receptors genes in Cetaceans
Authors: Gambón-Deza Francisco 
Published: October 2020

AbstractCetaceans correspond to mammals that have returned to the marine environment. Adaptive changes are very significant with the conversion of the limbs into flippers. It is studied the changes that have occurred in immunoglobulins, MHC class I and II and T cell receptors genes. Constant regions of immunoglobulins are similar to those of the rest of mammals. An exception is the IgD gene, which is composed of three CH domains but CH1 similar to CH1 of immunoglobulin M. In the IGHV locus, it exist a decrease in the number of VH genes with the absence of genes within Clan I. The number of Vλgenes is greater than that of Vκ. In the genes for T lymphocyte receptors, it exists a decrease in the number of Vαgenes with loss of significant clades and subclades. In Vβand Vγ, there is also the loss of clades. These declines of Vα, Vβand Vγare not present Artiodactyla, and they are specific to Cetaceans. In MHC present tree evolutive lines of class I genes. These species have DQ, DR, DO and DM genes, but they are no present DP genes.
Identification of a new orthonairovirus associated with human febrile illness in China
Authors: Ma Jun , Lv Xiao-Long , Zhang Xu , Han Shu-Zheng , Wang Ze-Dong , Li Liang , Sun He-Ting , Ma Li-Xin , Cheng Zheng-Lei , Shao Jian-Wei , Chen Chen , Zhao Ying-Hua , Sui Liyan , Liu Lin-Na , Qian Jun , Wang Wei , Liu Quan 
Published: October 2020

AbstractThe genusOrthonairovirusof the familyNairoviridaeincludes the important tick-transmitted pathogens, Crimean-Congo hemorrhagic fever virus (CCHFV) and Nairobi sheep disease virus (NSDV), as well as many other poorly characterized viruses isolated from ticks, birds, and mammals1,2. Here we identified a novel orthonairovirus, designated Sōnglǐng virus (SGLV), from patients who reported being bitten by a tick in China. The genome of SGLV shared similar structural features with orthonairoviruses, with 46.5–65.7% sequence identify. Phylogenetic analysis showed that SGLV belonged to theTamdy orthonairovirusand formed a unique clade in theNairoviridaefamily. Electron microscopy revealed typical morphological characteristics of orthonairoviruses. The isolated SGLVs from the blood samples of patients could induce cytopathic effects in human hepatoma cells. SGLV infection was confirmed in 42 patients in 2017-2018, with the main clinical manifestations of headache, fever, depression, fatigue and dizziness. Serological assays showed that 69% patients generated virus-specific antibody responses in the acute phase. In contrast, neither SGLV viral RNA nor specific antibodies against SGLV were detected in healthy individuals. SGLV was also detected inIxodes crenulatus, Haemaphysalis longicornis, Haemaphysalis concinna, andIxodes persulcatusin northeastern China. Collectively, a newly discovered orthonairovirus was shown to be associated with human febrile illness in northeastern China.
Trade-Offs Between Antibacterial Resistance and Fitness Cost in the Production of Metallo-β-Lactamase by Enteric Bacteria Manifest as Sporadic Emergence of Carbapenem Resistance in a Clinical Setting
Authors: Cheung Ching Hei Phoebe , Alorabi Mohammed , Hamilton Fergus , Takebayashi Yuiko , Mounsey Oliver , Heesom Kate J. , Williams Philip B. , Williams O. Martin , Albur Maha , MacGowan Alasdair P. , Avison Matthew B. 
Published: October 2020

AbstractMeropenem is a clinically important antibacterial reserved for treatment of multi-resistant infections. In meropenem-resistant bacteria of the family Enterobacteriales, NDM-1 is considerably more common than IMP-1, despite both metallo-β-lactamases (MBLs) hydrolysing meropenem with almost identical kinetics. We show thatblaNDM-1consistently confers meropenem resistance in wild-type Enterobacteriales, butblaIMP-1does not. The reason is higherblaNDM-1expression because of its stronger promoter. However, the cost of meropenem resistance is reduced fitness ofblaNDM-1positive Enterobacteriales because of amino acid starvation. In parallel, from a clinical case, we identified multipleEnterobacterspp. isolates carrying a plasmid-encodedblaNDM-1having a modified promoter region. This modification lowered MBL production to a level associated with zero fitness cost but, consequently, the isolates were not meropenem resistant. However, we identified aKlebsiella pneumoniaeisolate from this same clinical case carrying the sameblaNDM-1plasmid. This isolate was meropenem resistant despite low-level NDM-1 production because of aramRmutation, reducing envelope permeability. Overall, therefore, we show how the resistance/fitness trade-off for MBL carriage can be resolved. The result is sporadic emergence of meropenem resistance in a clinical setting.
Decoding subjective emotional arousal from EEG during an immersive Virtual Reality experience
Authors: Hofmann Simon M. , Klotzsche Felix , Mariola Alberto , Nikulin Vadim V. , Villringer Arno , Gaebler Michael 
Published: October 2020

AbstractImmersive virtual reality (VR) enables naturalistic neuroscientific studies while maintaining experimental control, but dynamic and interactive stimuli pose methodological challenges. We here probed the link between emotional arousal, a fundamental property of affective experience, and parieto-occipital alpha power under naturalistic stimulation: 37 young healthy adults completed an immersive VR experience, which included rollercoaster rides, while their EEG was recorded. They then continuously rated their subjective emotional arousal while viewing a replay of their experience. The association between emotional arousal and parieto-occipital alpha power was tested and confirmed by (1) decomposing the continuous EEG signal while maximizing the comodulation between alpha power and arousal ratings and by (2) decoding periods of high and low arousal with discriminative common spatial patterns and a Long Short-Term Memory recurrent neural network.We successfully combine EEG and a naturalistic immersive VR experience to extend previous findings on the neurophysiology of emotional arousal towards real-world neuroscience.
Endpoint PCR coupled with capillary electrophoresis (celPCR) provides sensitive and quantitative measures of environmental DNA in singleplex and multiplex reactions
Authors: Thalinger Bettina , Pütz Yannick , Traugott Michael 
Published: October 2020

AbstractThe use of sensitive methods is key for the detection of target taxa, from trace amounts of environmental DNA (eDNA) in a sample. In this context, digital PCR (dPCR) enables direct quantification and is commonly perceived as more sensitive than endpoint PCR. However, endpoint PCR coupled with capillary electrophoresis (celPCR) potentially embodies a viable alternative as it quantitatively measures signal strength in Relative Fluorescence Units (RFU). Provided comparable levels of sensitivity are reached, celPCR permits the development of cost-efficient multiplex PCRs, enabling the simultaneous detection of several target taxa.Here, we compared the sensitivity of singleplex and multiplex celPCR to dPCR for species-specific primer pairs amplifying mitochondrial DNA (COI) of fish species occurring in European freshwaters by analysing dilution series of DNA extracts and field-collected water samples. Both singleplex and multiplex celPCR and dPCR displayed comparable sensitivity with reliable positive amplifications starting at two to 10 target DNA copies per µl DNA extract. celPCR was suitable for quantifying target DNA and direct inference of DNA concentrations from RFU was possible after accounting for primer effects. Furthermore, multiplex celPCRs and dPCRs were successfully used for the detection and quantification of fish-eDNA in field-collected water samples, confirming the results of the dilution series experiment and exemplifying the high sensitivity of the two approaches.The possibility of detection and quantification via multiplex celPCR is appealing for the cost-efficient screening of high sample numbers. The present results confirm the sensitivity of this approach thus enabling its application for future eDNA-based monitoring efforts.