bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic information in the frontal cortex-striatal pathway
Authors: Alsolami Ibrahim , Handa Takashi , Fukai Tomoki 
Published: June 2021

SUMMARYAcross the cortico-basal ganglia circuit, the medial frontal cortex (MFC) communicates with the dorsal striatum (DS) during learning and planning. How these two brain regions communicate with each other is, however, not fully understood. Here we report the presence of synergistic information during information transfer across the frontal cortex-striatal pathway. Synergistic information emerges from the positive interaction of DS and MFC neurons and provides the DS with additional cortical information. This information is held latent in neuronal signals. To reveal it, we simultaneously record neuronal activities from the MFC and DS of rats trained on an outcome-based decision-making task and determined whether past neuronal activities of the DS positively influence communication rates. We detect a neuronal synergy that enables the MFC to boost its communication rate to the DS. Our results suggest that past neuronal activities of the DS help decode MFC signals. This ability is not attributed to the inherent autocorrelation of DS spiking activities.
Infectiousness in omicron variant strain and bA.2 variant in Japan
Authors: Kurita Junko , Sugawara Tamie , Ohkusa Yasushi 
Published: June 2021

AbstractBackgroundOmicron variant strain dominated since the beginning of 2022. Its infectivity was supposes to be higher than Delta variant strain or strains in past.ObjectWe estimated prevalence of omicron variant strain, particularly bA.2 variant and COVID-19 vaccine effectiveness of the third dose in Japan as well as controlling for waning of second dose of vaccine, other mutated strains, the Olympic Games, and countermeasures.MethodThe effective reproduction number R(t) was regressed on shares of omicron variant strain and bA.2 and vaccine coverage of the third dose, as well as along with data of temperature, humidity, mobility, share of the other mutated strains, and an Olympic Games and countermeasures. The study period was February, 2020 through February 21, 2022, as of March 15, 2022.ResultsEstimation results indicated that waning of the second dose vaccine e with 150 days prior was the most appropriate specification. Moreover, bA.2 of omicron variant strain has higher infectively than other variant strain or traditional strain.DiscussionBecause of data limitation since emerging bA.2, the estimated its infectively will change over time.
Deconvolution of the epigenetic age discloses distinct inter-personal variability in epigenetic aging patterns
Authors: Shahal Tamar , Segev Elad , Konstantinovsky Thomas , Marcus Yonit , Shefer Gabi , Pasmanik-Chor Metsada , Buch Assaf , Ebenstein Yuval , Zimmet Paul , Stern Naftali 
Published: June 2021

BackgroundThe epigenetic age can now be extrapolated from one of several epigenetic clocks, which are based on age-related changes in DNA methylation levels at specific multiple CpG sites. Accelerated aging, calculated from the discrepancy between the chronological age and the epigenetic age, has shown to predict morbidity and mortality rate. We assumed that deconvolution of epigenetic age to its components could shed light on the diversity of epigenetic, and by inference, on inter-individual variability in the causes of biological aging.ResultsUsing the Horvath original epigenetic clock, we identified several CpG sites linked to distinct genes that quantitatively explain much of the interpersonal variability in epigenetic aging, with CpG sites related to secretagogin and malin being the most variable. We show that equal epigenetic age in different subjects can result from variable contribution size of the same CpG sites to the total epigenetic age. In a healthy cohort, the most variable CpG sites are responsible for accelerated and decelerated epigenetic aging, relative to chronological age.ConclusionsOf the 353 CpG sites that form the basis for the Horvath epigenetic age, we have found the CpG sites that are responsible for accelerated and decelerated epigenetic aging in healthy subjects. However, the relative contribution of each site to aging varies between individuals, leading to variable personal aging patterns. Our findings pave the way to form personalized aging cards allowing the identification of specific genes related to CpG sites, as aging markers, and perhaps treatment of these targets in order to hinder undesirable age drifting.
The challenge of structural heterogeneity in the native mass spectrometry studies of the SARS-CoV-2 spike protein interactions with its host cell-surface receptor
Authors: Yang Yang , Ivanov Daniil G. , Kaltashov Igor A. 
Published: June 2021

AbstractNative mass spectrometry (MS) enjoyed tremendous success in the past two decades in a wide range of studies aiming at understanding the molecular mechanisms of physiological processes underlying a variety of pathologies and accelerating the drug discovery process. However, the success record of native MS has been surprisingly modest with respect to the most recent challenge facing the biomedical community – the novel coronavirus infection (COVID-19). The major reason for the paucity of successful studies that use native MS to target various aspects of SARS-CoV-2 interaction with its host is the extreme degree of structural heterogeneity of the viral protein playing a key role in the host cell invasion. Indeed, the SARS-CoV-2 spike protein (S-protein) is extensively glycosylated, presenting a formidable challenge for native mass spectrometry (MS) as a means of characterizing its interactions with both the host cell-surface receptor ACE2 and the drug candidates capable of disrupting this interaction. In this work we evaluate the utility of native MS complemented with the experimental methods using gas-phase chemistry (limited charge reduction) to obtain meaningful information on the association of the S1 domain of the S-protein with the ACE2 ectodomain, and the influence of a small synthetic heparinoid on this interaction. Native MS reveals the presence of several different S1 oligomers in solution and allows the stoichiometry of the most prominent S1/ACE2 complexes to be determined. This enables meaningful interpretation of the changes in native MS that are observed upon addition of a small synthetic heparinoid (the pentasaccharide fondaparinux) to the S1/ACE2 solution, confirming that the small polyanion destabilizes the protein/receptor binding.
Mycobacterium tuberculosis DosS binds H2S through its Fe3+ heme iron to regulate the Dos dormancy regulon
Authors: Sevalkar Ritesh R. , Glasgow Joel N. , Pettinati Martín , Marti Marcelo A. , Reddy Vineel P. , Basu Swati , Alipour Elmira , Kim-Shapiro Daniel B. , Estrin Dario A. , Lancaster Jack R. , Steyn Adrie J.C. 
Published: June 2021

AbstractMycobacterium tuberculosis (Mtb) senses and responds to host-derived gasotransmitters NO and CO via heme-containing sensor kinases DosS and DosT and the response regulator DosR. Hydrogen sulfide (H2S) is an important signaling molecule in mammals, but its role in Mtb physiology is unclear. We have previously shown that exogenous H2S can modulate expression of genes in the Dos dormancy regulon via an unknown mechanism(s). Here, we tested the hypothesis that Mtb senses and responds to H2S via the DosS/T/R system. Using UV-Vis and EPR spectroscopy, we show that H2S binds directly to the ferric (Fe3+) heme of DosS (KD = 5.64 µM) but not the ferrous (Fe2+) form. No interaction with DosT was detected. Thus, the mechanism by which DosS senses H2S is different from that for sensing NO and CO, which bind only the ferrous forms of DosS and DosT. Steered Molecular Dynamics simulations show that H2S, and not the charged HS- species, can enter the DosS heme pocket. We also show that H2S increases DosS autokinase activity and subsequent phosphorylation of DosR, and H2S-mediated increases in Dos regulon gene expression is lost in Mtb lacking DosS. Finally, we demonstrate that physiological levels of H2S in macrophages can induce Dos regulon genes via DosS. Overall, these data reveal a novel mechanism whereby Mtb senses and responds to a third host gasotransmitter, H2S, via DosS-Fe3+. These findings highlight the remarkable plasticity of DosS and establish a new paradigm for how bacteria can sense multiple gasotransmitters through a single heme sensor kinase.Significance StatementHydrogen sulfide (H2S) is an important signaling molecule in eukaryotes and bacteria, and along with CO and NO, is an important part of host defense against Mycobacterium tuberculosis (Mtb). However, the mechanism(s) by which Mtb senses and responds to H2S is unknown. Here, we report that the Mtb heme sensor kinase DosS, a known sensor of CO and NO, is also a sensor of H2S. We found that H2S binds DosS in its ferric (Fe3+) state, which is considered as its inactive state, to induce the Dos dormancy regulon during infection. These data highlight the unusual capacity of Mtb to sense multiple gasotransmitters through a single sensing protein.
A turquoise fluorescence lifetime-based biosensor for quantitative imaging of intracellular calcium
Authors: van der Linden Franka H. , Mahlandt Eike K. , Arts Janine J.G. , Beumer Joep , Puschhof Jens , de Man Saskia M.A. , Chertkova Anna O. , Ponsioen Bas , Clevers Hans , van Buul Jaap D. , Postma Marten , Gadella Theodorus W.J. , Goedhart Joachim 
Published: June 2021

AbstractThe most successful genetically encoded calcium indicators (GECIs) employ an intensity or intensiometric readout. Despite a large calcium-dependent change in fluorescence intensity, the quantification of calcium concentrations with GECIs is problematic, which is further complicated by the sensitivity of all GECIs to changes in the pH in the biological range. Here, we report on a novel sensing strategy in which a conformational change directly modifies the fluorescence quantum yield and fluorescence lifetime of a circular permutated turquoise fluorescent protein. The fluorescence lifetime is an absolute parameter that enables straightforward quantification, eliminating intensity-related artifacts. A new engineering strategy that optimizes lifetime contrast led to a biosensor that shows a 3-fold change in the calcium-dependent quantum yield and a fluorescence lifetime change of 1.3 ns. Additionally, the response of the calcium sensor is insensitive to pH between 6.2-9. As a result, the turquoise GECI enables robust measurements of intracellular calcium concentrations by fluorescence lifetime imaging. We demonstrate quantitative imaging of calcium concentration with the turquoise GECI in single endothelial cells and human-derived organoids.Abstract Figure
Multi-omics-based label-free metabolic flux inference reveals obesity-associated dysregulatory mechanisms in liver glucose metabolism
Authors: Uematsu Saori , Ohno Satoshi , Tanaka Kaori Y. , Hatano Atsushi , Kokaji Toshiya , Ito Yuki , Kubota Hiroyuki , Hironaka Ken-ichi , Suzuki Yutaka , Matsumoto Masaki , Nakayama Keiichi I. , Hirayama Akiyoshi , Soga Tomoyoshi , Kuroda Shinya 
Published: June 2021

SUMMARYGlucose homeostasis is maintained by modulation of metabolic flux. Enzymes and metabolites regulate the involved metabolic pathways. Dysregulation of glucose homeostasis is a pathological event in obesity. Analyzing metabolic pathways and the mechanisms contributing to obesity-associated dysregulation in vivo is challenging. Here, we introduce OMELET: Omics-Based Metabolic Flux Estimation without Labeling for Extended Trans-omic Analysis. OMELET uses metabolomic, proteomic, and transcriptomic data to identify changes in metabolic flux, and to quantify contributions of metabolites, enzymes, and transcripts to the changes in metabolic flux. By evaluating the livers of fasting ob/ob mice, we found that increased metabolic flux through gluconeogenesis resulted primarily from increased transcripts, whereas that through the pyruvate cycle resulted from both increased transcripts and changes in substrates of metabolic enzymes. With OMELET, we identified mechanisms underlying the obesity-associated dysregulation of metabolic flux in liver.HighlightsWe created OMELET to infer metabolic flux and its regulation from multi-omic data.Gluconeogenic and pyruvate cycle fluxes increased in fasting ob/ob mice.Transcripts increases mediated the increase in gluconeogenic fluxes in ob/ob mice.Increases in transcripts and substrates enhanced pyruvate cycle flux in ob/ob mice.
SARS-CoV-2 activates ER stress and Unfolded protein response
Authors: Rosa-Fernandes Livia , Lazari Lucas C. , da Silva Janaina Macedo , de Morais Gomes Vinicius , Machado Rafael Rahal Guaragna , dos Santos Ancely Ferreira , Araujo Danielle Bastos , Coutinho João Vitor Paccini , Arini Gabriel Santos , Angeli Claudia B. , de Souza Edmarcia E. , Wrenger Carsten , Marinho Claudio R. F. , Oliveira Danielle B. L. , Durigon Edison L. , Labriola Leticia , Palmisano Giuseppe 
Published: June 2021

ABSTRACTCoronavirus disease-2019 (COVID-19) pandemic caused by the SARS-CoV-2 coronavirus infection is a major global public health concern affecting millions of people worldwide. The scientific community has joint efforts to provide effective and rapid solutions to this disease. Knowing the molecular, transmission and clinical features of this disease is of paramount importance to develop effective therapeutic and diagnostic tools. Here, we provide evidence that SARS-CoV-2 hijacks the glycosylation biosynthetic, ER-stress and UPR machineries for viral replication using a time-resolved (0-48 hours post infection, hpi) total, membrane as well as glycoproteome mapping and orthogonal validation. We found that SARS-CoV-2 induces ER stress and UPR is observed in Vero and Calu-3 cell lines with activation of the PERK-eIF2α-ATF4-CHOP signaling pathway. ER-associated protein upregulation was detected in lung biopsies of COVID-19 patients and associated with survival. At later time points, cell death mechanisms are triggered. The data show that ER stress and UPR pathways are required for SARS-CoV-2 infection, therefore representing a potential target to develop/implement anti-CoVID-19 drugs.
Wuschel2enables highly efficient CRISPR/Cas-targeted genome editing during rapidde novoshoot regeneration in sorghum
Authors: Che Ping , Wu Emily , Simon Marissa K. , Anand Ajith , Lowe Keith , Gao Huirong , Sigmund Amy L. , Yang Meizhu , Albertsen Marc C. , Gordon-Kamm William , Jones Todd J. 
Published: June 2021

SummaryFor many important crops, including sorghum, the use of CRISPR/Cas technology is limited not only by the delivery of the gene-modification components into a plant cell, but more critically, by the ability to regenerate a fertile plant from the engineered cell through conventional tissue culture methods. Here, we report thatWuschel2 (Wus2)-enabled sorghum (Sorghum bicolorL.) transformation increases not only the efficiency of transgenic plant recovery, but also increases the observed efficiency of CRISPR/Cas-targeted genome editing within the population of T0 plants. UsingAgrobacterium-mediated transformation, we have demonstratedWus2-induced direct somatic embryo formation and regeneration, bypassing genotype-dependent callus formation and significantly shortening the tissue culture cycle time. This method also increased regeneration capacity, resulting in higher transformation efficiency across different sorghum genotypes. Subsequently, advanced excision systems and “altruistic” transformation technology have been developed to generate high-quality morphogenic gene-free and/or selectable marker-free sorghum events. Finally, we demonstrated up to an additional 6.8-fold increase in CRISPR/Cas9-mediated gene dropout frequency usingWus2-enabled,Agrobacterium-mediated transformation (compared to the control treatment with noWus2), across various targeted loci in different sorghum genotypes.Wus2-enabled genome editing may be applicable to other crops and increasingly popularin plantatransformation strategies.
Transregulation of an odorant binding protein by a proto-Y chromosome affects male courtship in house fly
Authors: Delclos Pablo J , Adhikari Kiran , Mai Alexander B , Hassan Oluwatomi , Oderhowho Alexander A , Sriskantharajah Vyshnika , Trinh Tammie , Meisel Richard P 
Published: June 2021

ABSTRACTY chromosomes have male-limited inheritance, which favors the fixation of alleles that affect spermatogenesis, courtship, and other male-specific traits. Y-linked male-beneficial alleles can also have female-deleterious (sexually antagonistic) effects because they never experience direct selection in females. However, determining the mechanisms underlying these male-beneficial effects is challenging because it can require studying Y-linked alleles while they still segregate as polymorphism. We used a Y chromosome polymorphism in the house fly,Musca domestica, to address this challenge. Two common male-determining Y chromosomes (YMand IIIM) segregate as stable polymorphisms in natural house fly populations, and they differentially affect multiple traits, including male courtship performance. We performed a meta-analysis of RNA-seq data and identified differentially expressed genes encoding odorant binding proteins (in theObp56hfamily) as candidate causal agents in the courtship differences. TheObp56hgenes are not found on either the YMor IIIMchromosomes, suggesting that they must be regulated intransby one of the house fly sex chromosomes. Using a network analysis and allele-specific expression measurements, we identified multiple genes on the house fly IIIMchromosome that could serve astransinhibitors ofObp56hgene expression. One of those genes is homologous toD. melanogaster CG2120, which encodes a transcription factor that binds both up- and down-stream ofObp56h. We found that up-regulation ofCG2120inD. melanogasternervous tissues reduces copulation latency, consistent with this transcription factor acting as a negative regulator ofObp56hexpression. We propose the namespeed date(spdt) forCG2120, with the house fly homolog namedMd-spdt. The expression ofspdtacrossD. melanogasterdevelopment and tissues suggests that evolution of higher expression in neurons may be constrained by pleiotropic or sexual antagonistic effects. We hypothesize that acis-regulatory allele that increases expression ofMd-spdton the IIIMchromosome exists because Y-linkage of this allele releases it from those constraints. This provides evidence for a molecular mechanism by which a Y-linked gene can evolve a male-beneficial function regardless of the negative effects on females.
Biorational Management And Mycosis Studies Of Grape Thrips [Rhipiphorothrips cruentatus H.]
Authors: reddy Ankireddy Jawahar , Saindane Y. S. , Datkhile R. V. , Deore B. V. 
Published: June 2021

ABSTRACTField experiment was conducted to test the bioefficacy of various biorational insecticides against grapevine thrips at AICRP on Fruits, Department of Horticulture, MPKV, Rahuri, during 2017-18. Results revealed that standard check emamectin benzoate 5% SG consistently proved to be the most promising by recording the least thrips population (3.10/shoot). Among biorational insecticides neem oil 2% (4.09/shoot) proved as best treatment followed by, karanj oil (4.51/shoot) and neemazol (5.08/shoot). While entomopathogenic fungi Lecanicillium lecanii recorded less population (4.24/shoot) and emerged as best treatment as compared to the Metarhizium anisopliae (4.87/shoot) and Beauveria bassiana (5.34/shoot). However chlli methanolic extract (6.29/shoot), garlic methanolic extract (6.78/shoot), chilli water extract (6.85/shoot) and garlic water extract (7.08/shoot) are the least effective treatments.Incremental Cost Benefit Ratio (ICBR) in respect of different treatments ranged between 1.30 to 7.92. The highest ICBR of 1:7.92 was recorded in the treatment with emamectin benzoate 5 SG, and it was followed by Lecanicillium lecanii (1:6.34) and Metarhizium anisopliae (1:5.32). Although neem oil and karanj oil has great reduction of thrips population, but has less incremental cost benefit ratio i.e. 2.81 and 3.04, respectively, due to high dose and its cost.The mycosis test of three entomopathogenic fungi viz. Beauveria bassiana, Metarhizium anisopliae, Lecanicillium lecanii were studied on grape thrips. Mycosis by Beauveria bassiana was confirmed the pathogenicity of entomopathogenic fungi on grape thrips. Highly pronounced mycosis was observed by Metarhizium anisopliae on the dead bodies of thrips. Mycosis test of Lecanicillium lecanii was also proved on grape thrips (plate - 1, 2 and 3).
Regulation of the Molecular Shuttle Service: A Multiscale Model of Aquaporin 2 Recycling
Authors: Leberecht Christoph , Schroeder Michael , Labudde Dirk 
Published: June 2021

ABSTRACTThe response of cells to their environment is driven by a variety of proteins and messenger molecules. In eukaryotes their distribution, which is regulated by a vesicular transport system, is important for a tight cellular response. The recycling of aquaporin 2 between membrane and storage region is a crucial part of the body water homeostasis and its malfunction can lead to Diabetes insipidus. To understand the regulation of this system, we aggregated pathways and mechanisms from literature and derived three models in a hypothesis-driven approach. Furthermore, we combined the models to a single system to gain insight into key regulatory mechanisms. To achieve this we developed a multiscale computational framework for the modeling and simulation of cellular systems. The analysis of the system rationalises that the compartmentalization of cAMP in renal principal cells is a result of the protein kinase A signalosome and can only occur if specific cellular components are observed in conjunction. Endocytotic and exocytotic processes are inherently connected and can be regulated by the same protein kinase A signal.
In vivo imaging of mammary epithelial cell dynamics in response to lineage-biased Wnt/β-catenin activation
Authors: Lloyd-Lewis Bethan , Gobbo Francesca , Perkins Meghan , Jacquemin Guillaume , Faraldo Marisa M , Fre Silvia 
Published: June 2021

AbstractReal-time, in vivo imaging provides an essential window into the spatiotemporal cellular and molecular events contributing to tissue development and pathology. By coupling longitudinal intravital imaging with genetic lineage tracing, here we captured the earliest cellular events underlying the impact of active Wnt/β-catenin signaling on the organization and differentiation of the mammary epithelium. This enabled us to interrogate how Wnt/β-catenin regulates the dynamics of distinct subpopulations of mammary epithelial cells in vivo and in real time. We show that β-catenin stabilization, when targeted to either of the mammary luminal or basal epithelial lineages, invariably leads to cellular rearrangements that precipitate the formation of hyperplastic lesions that undergo squamous transdifferentiation. These results enhance our understanding of the earliest stages of hyperplastic lesion formation in vivo, and reveal that in mammary neoplastic development, β-catenin activation dictates a hair-follicle/epidermal differentiation program independently of the targeted cell of origin.