bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exogenous Nitro-Oleic Acid inhibits primary root growth by reducing the mitosis in the meristem inArabidopsis thaliana
Authors: Di Fino Luciano M. , Cerrudo Ignacio , Salvatore Sonia R. , Schopfer Francisco J. , García-Mata Carlos , Laxalt Ana M. 
Published: June 2020

ABSTRACTNitric oxide (NO) is a second messenger that regulates a broad range of physiological processes in plants. NO-derived molecules called reactive nitrogen species (RNS) can react with unsaturated fatty acids generating nitrated fatty acids (NO2-FA). NO2-FA work as signaling molecules in mammals where production and targets have been described under different stress conditions. Recently, NO2-FAs were detected in plants, however their role(s) on plant physiological processes is still poorly known. Here we show that exogenous application of nitro-oleic acid (NO2-OA) inhibits Arabidopsis primary root growth; this inhibition is not likely due to nitric oxide (NO) production or impaired auxin or cytokinin root responses. Deep analyses showed that roots incubated with NO2-OA had a lower cell number in the division area. Although this NO2-FA did not affect the signaling mechanisms maintaining the stem cell niche, plants incubated with NO2-OA showed a reduction of cell division in the meristematic area. Therefore, this work shows that NO2-OA inhibits mitotic processes subsequently reducing primary root growth.
Multiple epigenetic layers accompany the spatial distribution of ribosomal genes in Arabidopsis
Authors: Kutashev Konstantin O. , Franek Michal , Diamanti Klev , Komorowski Jan , Olšinová Marie , Dvořáčková Martina 
Published: June 2020

Abstract45S ribosomal genes in A. thaliana (rDNA) are located in tandem arrays on termini of chromosomes 2 and 4 (NOR2 and NOR4) and encode rRNA, crucial structural elements of the ribosome. Inactive rDNA genes accumulate in the condensed chromocenters in the nucleus and at the nucleolar periphery, while nucleolus delimits the active genes. We show that a subset of nucleolar rDNA assembles into condensed foci marked by H3.1 and H3.3 histones and that progressive rDNA condensation is connected with rDNA transcriptional activity, cell ploidy and rDNA copy number. Interestingly, some nucleolar foci are reminiscent of perinucleolar chromocenters, containing the NOR4 region. We further demonstrate that rDNA promoter is a key regulatory region of the rDNA repeat and describe large involvement of repressive epigenetic mark H3K9me2 and H2A.W histone variant in rDNA activity regulation. In addition, we found euchromatic H3.3 histone enrichment at the rDNA transcription start site in actively dividing tissues, despite its accumulation in nucleolar foci containing condensed rDNA repeats.
Electrophysiological validation of premotor interneurons monosynaptically connected to the aCC motoneuron in theDrosophilalarval CNS
Authors: Giachello Carlo N. G. , Zarin Aref Arzan , Kohsaka Hiroshi , Fan Yuen Ngan , Nose Akinao , Landgraf Matthias , Baines Richard A. 
Published: June 2020

AbstractMapping the wired connectivity of a nervous system is a prerequisite for full understanding of function. In this respect, such endeavours can be likened to genome sequencing projects. These projects similarly produce impressive amounts of data which, whilst a technicaltour-de-force, remain under-utilised without validation. Validation of neuron synaptic connectivity requires electrophysiology which has the necessary temporal and spatial resolution to map synaptic connectivity. However, this technique is not common and requires extensive equipment and training to master, particularly when applied to the small CNS of theDrosophilalarva. Thus, validation of connectivity in this CNS has been more reliant on behavioural analyses and, in particular, activity imaging using the calcium-sensor GCaMP. Whilst both techniques are powerful, they each have significant limitations for this purpose. Here we use electrophysiology to validate an array of driver lines reported to label specific premotor interneurons that theDrosophilaconnectome project suggests are monosynaptically connected to an identified motoneuron termed the anterior corner cell (aCC). Our results validate this proposition for four selected lines. Thus, in addition to validating the connectome with respect to these four premotor interneurons, our study highlights the need to functionally validate driver lines prior to use.
Single cell RNA sequence analysis of human bone marrow samples reveals new targets for isolation of skeletal stem cells using DNA-coated gold nanoparticles
Authors: Matthews Elloise , Lanham Stuart , White Kate , Kyriazi Maria-Eleni , Alexaki Konstantina , El-Sagheer Afaf H. , Brown Tom , Kanaras Antonios G. , West Jonathan , MacArthur Ben D. , Stumpf Patrick S. , Oreffo Richard O.C. 
Published: June 2020

AbstractThere is a wealth of data indicating human bone marrow derived stromal cells (HBMSCs) contain the skeletal stem cell (SSC) with the potential to differentiate along the stromal osteogenic, adipogenic and chondrogenic lineages. However, despite these advances, current methods to isolate skeletal stem cells (SSCs) from human tissues have proved challenging as no single specific marker has been identified limiting understanding of SSC fate, immunophenotype and the widespread clinical application of these cells. While a number of cell surface markers can enrich for SSCs, none of the proposed markers, alone, provide a platform to isolate single cells with the ability to form bone, cartilage, and adipose tissue in humans. The current study details the application of oligonucleotide-coated nanoparticles, spherical nucleic acids (SNAs), to rapidly isolate human cells using mRNAs signatures detected in SSCs in real time, to identify stem and progenitor skeletal populations using single cell RNA sequencing. Based on scRNA-seq of samples from 11 patients, this method was able to identify novel targets for SSC enrichment, which were assessed in a total of 80 patients. This methodology was able to isolate potential SSCs found at a frequency of <1 in 1,000,000 in human bone marrow, with a capacity for tri-lineage differentiationin vitro. The current approach provides new targets and a platform to advance SSC isolation, enrichment with significant therapeutic impact therein.
Chromatin potential identified by shared single cell profiling of RNA and chromatin
Authors: Ma Sai , Zhang Bing , LaFave Lindsay , Chiang Zachary , Hu Yan , Ding Jiarui , Brack Alison , Kartha Vinay K. , Law Travis , Lareau Caleb , Hsu Ya-Chieh , Regev Aviv , Buenrostro Jason D. 
Published: June 2020

SummaryCell differentiation and function are regulated across multiple layers of gene regulation, including the modulation of gene expression by changes in chromatin accessibility. However, differentiation is an asynchronous process precluding a temporal understanding of the regulatory events leading to cell fate commitment. Here, we developed SHARE-seq, a highly scalable approach for measurement of chromatin accessibility and gene expression within the same single cell. Using 34,774 joint profiles from mouse skin, we develop a computational strategy to identifycis-regulatory interactions and define Domains of Regulatory Chromatin (DORCs), which significantly overlap with super-enhancers. We show that during lineage commitment, chromatin accessibility at DORCs precedes gene expression, suggesting changes in chromatin accessibility may prime cells for lineage commitment. We therefore develop a computational strategy (chromatin potential) to quantify chromatin lineage-priming and predict cell fate outcomes. Together, SHARE-seq provides an extensible platform to study regulatory circuitry across diverse cells within tissues.
WNT inhibition creates a BRCA-like state in Wnt-addicted cancer
Authors: Kaur Amanpreet , Sepramaniam Sugunavathi , Lim Jun Yi Stanley , Patnaik Siddhi , Harmston Nathan , Lee May Ann , Petretto Enrico , Virshup David M. , Madan Babita 
Published: June 2020

ABSTRACTWnt signaling maintains diverse adult stem cell compartments and is implicated in chemotherapy resistance in cancer. PORCN inhibitors that block Wnt secretion have proven effective in Wnt-addicted preclinical cancer models and are in clinical trials. In a survey for potential combination therapies, we found that Wnt inhibition synergizes with the PARP inhibitor olaparib in Wnt-addicted cancers. Mechanistically, we find that multiple genes in the homologous recombination and Fanconi anemia repair pathways, includingBRCA1,FANCD2, andRAD51are dependent on Wnt/β-catenin signaling in Wnt-high cancers, and treatment with a PORCN inhibitor creates a BRCA-like state. This coherent regulation of DNA repair genes occurs via a Wnt/β-catenin/MYBL2 axis. Importantly, this pathway also functions in intestinal crypts, where high expression of BRCA and Fanconi anemia genes is seen in intestinal stem cells, with further upregulation in Wnt high APCminmutant polyps. Our findings suggest a general paradigm that Wnt/β-catenin signaling enhances DNA repair in stem cells and cancers to maintain genomic integrity. Conversely, interventions that block Wnt signaling may sensitize cancers to radiation and other DNA damaging agents.
Model of intracellular ATP production reproduces common electrophysiological signatures of anesthesia
Authors: Joo Pangyu , Lee Heonsoo , Wang Shiyong , Kim Seunghwan , Hudetz Anthony G. 
Published: June 2020

AbstractAccumulating evidence suggest that general anesthetics with diverse chemical structure reduce cerebral metabolism with consequent reduction of intracellular adenosine triphosphate (ATP) levels. How cerebral hypometabolism is associated with the typical electroencephalographic (EEG) changes under general anesthesia remains largely unknown.,. We hypothesized that the deficit in ATP production would reduce high-frequency activity, increase low-frequency activity, and cause burst suppression, which are common dose-dependent anesthetic effects on the EEG. To test the hypothesis, we developed a novel neural network model consisting of leaky integrate-and-fire neurons with additional dependency on ATP dynamics. The effect of varying rate of ATP production on neuronal and population activity patterns was simulated under various excitatory/inhibitory balance conditions. A decrease of ATP production suppressed neuronal spiking and enhanced synchronization of neurons over a range of excitatory/inhibitory synaptic strength ratios. As anticipated, the initially asynchronous fast activity was replaced by globally desynchronized slow oscillation and, on further decrease of ATP production, changed into burst suppression with enhanced global synchronization. This study substantiates a novel biophysical mechanism for anesthetic-induced EEG changes through a relationship between energy production and synchronization of neural network.
Comparative analysis of the molecular mechanism of heat shock proteins from pathogenic and non-pathogenicE.coli
Authors: Bhattacharjee Sanchari , Saha Mohana , Dasgupta Rakhi , Bagchi Angshuman 
Published: June 2020

AbstractCells can withstand the effects of temperature stress by activating small heat shock proteins IbpA and IbpB. Lon protease employing Ser679 – Lys722 catalytic dyad proteolyze IbpA and IbpB in their free forms, at physiological temperature i.e. without any temperature stress. However, the proteolytic activity of IbpA and IbpB is affected when the catalytic dyad residue of Lon protease is mutated. The mutation S679A in Lon protease brings about some changes so that the proteolytic interactions between the small heat shock proteins with that of the mutant Lon protease are lost which makes a difference in the interaction pattern of mutant Lon protease with their substrates. In the present study, we made an attempt through in-silico approach to figure out the underlying aspects of the interactions between the small heat shock proteins IbpA and IbpB with mutant Lon protease inEscherichia coli. We have tried to decipher the molecular details of the mechanism of interaction of proteolytic machinery of small heat shock proteins and mutant Lon protease with S679A mutation at physiological temperature in absence cellular temperature stress. Our study may therefore be helpful to decode the mechanistic details of the correlation with IbpA, IbpB and S679A mutant Lon protease inE. coli.
A designed high-affinity peptide that hijacks microtubule-based transport
Authors: Cross Jessica A. , Chegkazi Magda S. , Steiner Roberto A. , Woolfson Derek N. , Dodding Mark P. 
Published: June 2020

ABSTRACTTechnologies that manipulate and augment the transport of vesicles and organelles by motor proteins along microtubules offer new routes to understanding its mechanistic basis, and could lead to therapeutics. Many cargoes for the kinesin-1 family of microtubule motors utilize adaptor proteins that harbor linear peptide motifs that are recognized by the tetratricopeptide repeats of kinesin light chains (KLCTPRs). These motifs bind with micromolar affinities at independent but overlapping sites. Here, we employ a fragment-linking peptide design strategy to generate an extended synthetic ligand (KinTag) with low nanomolar affinity for KLCTPRs. The X-ray crystal structure of the KLCTPR:KinTag complex demonstrates interactions as designed. Moreover, KinTag functions in cells to promote the transport of lysosomes with a high efficiency that correlates with its enhanced affinity. Together, these data demonstrate a new strategy for peptide design and its application to reveal that the more tightly a motor holds its cargo, the greater is the extent of cargo transport.
Multiscale Simulation Reveals Passive Proton Transport Through SERCA on the Microsecond Timescale
Authors: Li Chenghan , Yue Zhi , Espinoza-Fonseca L. Michel , Voth Gregory A. 
Published: June 2020

ABSTRACTThe sarcoplasmic reticulum Ca2+-ATPase (SERCA) transports two Ca2+ions from the cytoplasm to the reticulum lumen at the expense of ATP hydrolysis. In addition to transporting Ca2+, SERCA facilitates bidirectional proton transport across the sarcoplasmic reticulum to maintain the charge balance of the transport sites and to balance the charge deficit generated by the exchange of Ca2+. Previous studies have shown the existence of a transient water-filled pore in SERCA that connects the Ca2+-binding sites with the lumen, but the capacity of this pathway to sustain passive proton transport has remained unknown. In this study, we used the multiscale reactive molecular dynamics (MS-RMD) method and free energy sampling to quantify the free energy profile and timescale of the proton transport across this pathway while also explicitly accounting for the dynamically coupled hydration changes of the pore. We find that proton transport from the central binding site to the lumen has a microsecond timescale, revealing a novel passive cytoplasm-to-lumen proton flow beside the well-known inverse proton countertransport occurring in active Ca2+transport. We propose that this proton transport mechanism is operational and serves as a functional conduit for passive proton transport across the sarcoplasmic reticulum.SIGNIFICANCEMultiscale reactive molecular dynamics combined with free energy sampling was applied to study proton transport through a transient water pore connecting the Ca2+-binding site to the lumen in SERCA. This is the first computational study of this large biomolecular system that treats the hydrated excess proton and its transport through water structures and amino acids explicitly. When also correctly accounting for the hydration fluctuations of the pore, it is found that a transiently hydrated channel can transport protons on a microsecond timescale. These results quantitatively support the hypothesis of the proton intake into the sarcoplasm via SERCA, in addition to the well-known proton pumping by SERCA to the cytoplasm along with Ca2+transport.
Skeletal Muscle Remodeling in Immobilized Patients: Determined Using a Parameter Estimation Histomorphometric Approach
Authors: Formosa Brent , Liyanaarachchi Asiri , Silvers Samantha , Gatti Domenico L. , Larsson Lars , Arslanturk Suzan , Jena Bhanu P. 
Published: June 2020

AbstractSkeletal muscle biopsy commonly used for light microscopic, electron microscopic and biochemical and transcriptional evaluation remains the gold standard for establishing the etiology of a myopathy. While most myopathies exhibit one or more phenotypes, early stages or several metabolic myopathies often exhibit normal muscle morphology, making diagnosis difficult. In such cases where standard staining techniques fail to offer definitive diagnostic information, a combination of expensive and time-consuming electron microscopy and biochemical testing is required to provide definitive diagnosis. As a step toward overcoming these limitations in diagnostic pathology of skeletal muscle tissue, here we report the application of parameter estimation machine learning approaches on immunofluorescent images of human skeletal muscle tissue acquired using fluorescent microscopy. The machine learning morphometric approach enables the recognition of fine cellular changes in skeletal muscle tissue, allowing determination of skeletal muscle remodeling as a consequence of immobilization.
Wild emmer introgressions alter root-to-shoot growth dynamics in response to water stress
Authors: Bacher Harel , Zhu Feiyu , Gao Tian , Liu Kan , Dhatt Balpreet K , Awada Tala , Zhang Chi , Distelfeld Assaf , Yu Hongfeng , Peleg Zvi , Walia Harkamal 
Published: June 2020

AbstractWater deficit is a major limiting factor for wheat (Triticumsp.) development and productivity. One approach to increase water stress adaptation in wheat is incorporating novel alleles from the drought-adapted wheat progenitor, wild emmer (T. turgidumssp.dicoccoides). We explored this idea in the context of vegetative growth by examining the phenotypic consequence of a series of wild emmer (acc. Zavitan) introgressions into elite durum wheat (cv. Svevo) under water-limited conditions. Using image-based phenotyping we cataloged divergent (from Svevo) growth responses to water stress ranging from high plasticity to high stability among the introgression lines. We identified an introgression line (IL20) that exhibits a highly plastic response to water stress by shifting its root-to-shoot biomass ratio for detailed characterization. By combining genotypic information with root transcriptome analysis, we propose several candidate genes (including a root-specific kinase) that can confer the shoot-to-root carbon resource allocation in IL20 under water stress. Discovery of high plasticity trait in IL20 in response to water stress highlights the potential of wild introgressions for enhancing stress adaptation via mechanisms that may be absent or rare in elite breeding material.
Optimizing spectral quality with quantum dots to enhance crop yield in controlled environments
Authors: Parrish Charles H. , Hebert Damon , Jackson Aaron , Ramasamy Karthik , McDaniel Hunter , Giacomelli Gene A. , Bergren Matthew R. 
Published: June 2020

AbstractBioregenerative life-support systems (BLSS) involving plants will be required to realize self-sustaining human settlements beyond Earth. To improve plant photosynthetic efficiency in BLSS, the quality of the solar spectrum can be modified by lightweight, luminescent films. CuInS2/ZnS quantum dot (QD) films with peak emissions at 600 and 660 nm were used to redshift ultraviolet and blue photons to increase biomass accumulation in red romaine lettuce. Plant growth parameters, except spectral quality, were held constant among three equivalent production environments. Lettuce grown under the 600 and 660 nm-emitting QD films respectively increased edible dry mass (13% and 9%), edible fresh mass (11% each), and total leaf area (8% and 13%) compared to under a control film that contained no QDs. Spectral modifications by the luminescent QD films improved photosynthetic efficiency in lettuce and could enhance crop productivity in greenhouses on Earth or in space, where further improvements are expected from greater availability of ultraviolet photons for conversion.
TBK1 interacts with tau and enhances neurodegeneration in tauopathy
Authors: Abreha Measho H. , Ojelade Shamsideen , Dammer Eric B. , McEachin Zachary T. , Duong Duc M. , Gearing Marla , Bassell Gary J. , Lah James J. , Levey Allan I. , Shulman Joshua M. , Seyfried Nicholas T. 
Published: June 2020

ABSTRACTOne of the defining pathological features of Alzheimer’s Disease (AD) is the deposition of neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau in the brain. Aberrant activation of kinases in AD has been suggested to enhance phosphorylation and toxicity of tau, making the responsible tau-directed kinases attractive therapeutic targets. The full complement of tau interacting kinases in AD brain and their activity in disease remains incompletely defined. Here, immunoaffinity enrichment coupled with mass spectrometry (MS) identified TANK-binding kinase 1 (TBK1) as a tau-interacting partner in human AD cortical brain tissues. We validated this interaction in both human AD and familial frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) caused by mutations inMAPT(R406W) postmortem brain tissues as well as human cell lines. Further, we document increased TBK1 activity in both AD and FTDP-17 and map the predominant TBK1 phosphorylation sites on tau based onin vitrokinase assays coupled to MS. Lastly, in aDrosophilatauopathy model, activating expression of a conserved TBK1 ortholog triggers tau hyperphosphorylation and enhanced neurodegeneration, whereas knockdown had the reciprocal effect, suppressing tau toxicity. Collectively, our findings suggest that increased TBK1 activity may promote tau hyperphosphorylation and neuronal loss in AD and related tauopathies.
Quantitative differences between intra-host HCV populations from persons with recently established and persistent infections
Authors: Baykal Pelin Icer , Lara James , Zelikovsky Alex , Khudyakov Yury , Skums Pavel 
Published: June 2020

SummaryBackgroundDetection of incident hepatitis C virus (HCV) infections is crucial for identification of outbreaks and development of public health interventions. However, there is no single diagnostic assay for distinguishing recent and persistent HCV infections. HCV exists in each infected host as a heterogeneous population of genomic variants, whose evolutionary dynamics remain incompletely understood. Genetic analysis of such viral populations can be applied to the detection of incident HCV infections and used to understand intra-host viral evolution.MethodsWe studied intra-host HCV populations sampled using next-generation sequencing from 98 recently and 256 persistently infected individuals. Genetic structure of the populations was evaluated using 245,878 viral sequences from these individuals and a set of selected parameters measuring their diversity, topological structure, complexity, strength of selection, epistasis, evolutionary dynamics, and physico-chemical properties.FindingsDistributions of the viral population parameters differ significantly between recent and persistent infections. A general increase in viral genetic diversity from recent to persistent infections is frequently accompanied by decline in genomic complexity and increase in structuredness of the HCV population, likely reflecting a high level of intra-host adaptation at later stages of infection. Using these findings, we developed a Machine Learning classifier for the infection staging, which yielded a detection accuracy of 95.22%, thus providing a higher accuracy than other genomic-based models.InterpretationThe detection of a strong association between several HCV genetic factors and stages of infection suggests that intra-host HCV population develops in a complex but regular and predictable manner in the course of infection. The proposed models may serve as a foundation of cyber-molecular assays for staging infection, that could potentially complement and/or substitute standard laboratory assays.FundingAZ and PS were supported by NIH grant 1R01EB025022. PIB was supported by GSU MBD fellowship.