bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic mapping of the early responses to salt stress inArabidopsis thaliana
Authors: Awlia Mariam , Alshareef Nouf , Saber Noha , Korte Arthur , Oakey Helena , Panzarová Klára , Trtílek Martin , Negrão Sónia , Tester Mark , Julkowska Magdalena M. 
Published: October 2020

AbstractSalt stress decreases plant growth prior to significant ion accumulation in the shoot. However, the processes underlying this rapid reduction in growth are still unknown. To understand the changes in salt stress responses through time and at multiple physiological levels, examining different plant processes within a single setup is required. Recent advances in phenotyping has allowed the image-based estimation of plant growth, morphology, colour and photosynthetic activity. In this study, we examined the salt stress-induced responses of 191 Arabidopsis accessions from one hour to seven days after treatment using high-throughput phenotyping. Multivariate analyses and machine learning algorithms identified that quantum yield measured in the light-adapted state (Fv′/Fm′) greatly affected growth maintenance in the early phase of salt stress, while maximum quantum yield (QY max) was crucial at a later stage. In addition, our genome-wide association study (GWAS) identified 770 loci that were specific to salt stress, in which two loci associated with QY max and Fv′/Fm′ were selected for validation using T-DNA insertion lines. We characterised an unknown protein kinase found in the QY max locus, which reduced photosynthetic efficiency and growth maintenance under salt stress. Understanding the molecular context of the identified candidate genes will provide valuable insights into the early plant responses to salt stress. Furthermore, our work incorporates high-throughput phenotyping, multivariate analyses and GWAS, uncovering details of temporal stress responses, while identifying associations across different traits and time points, which likely constitute the genetic components of salinity tolerance.
Glucose-lactose mixture feeds in industry-like conditions: a gene regulatory network analysis on the hyperproducingTrichoderma reeseistrain Rut-C30
Authors: Pirayre Aurélie , Duval Laurent , Blugeon Corinne , Firmo Cyril , Perrin Sandrine , Jourdier Etienne , Margeot Antoine , Bidard Frédérique 
Published: October 2020

AbstractBackgroundThe degradation of cellulose and hemicellulose molecules into simpler sugars such as glucose is part of the second generation biofuel production process. Hydrolysis of lignocellulosic substrates is usually performed by enzymes produced and secreted by the fungusTrichoderma reesei. Studies identifying transcription factors involved in the regulation of cellulase production have been conducted but no overview of the whole regulation network is available. A transcriptomic approach with mixtures of glucose and lactose, used as a substrate for cellulase induction, was used to help us decipher missing parts in the network.ResultsExperimental results confirmed the impact of sugar mixture on the enzymatic cocktail composition. The transcriptomic study shows a temporal regulation of the main transcription factors and a lactose concentration impact on the transcriptional profile. A gene regulatory network (GRN) built using the BRANE Cut software reveals three sub-networks related toia positive correlation between lactose concentration and cellulase production,iia particular dependence of the lactose onto theβ-glucosidase regulation andiiia negative regulation of the development process and growth.ConclusionsThis work is the first investigating a transcriptomic study regarding the effects of pure and mixed carbon sources in a fed-batch mode. Our study expose a co-orchestration ofxyr1,clr2andace3for cellulase and hemicellulase induction and production, a fine regulation of theβ-glucosidase and a decrease of growth in favor of cellulase production. These conclusions provide us with potential targets for further genetic engineering leading to better cellulase-producing strains.
Niche evolution of the Neotropical tree genusOtobain the context of global biogeography of the nutmeg family, Myristicaceae
Authors: Frost Laura , Santamaría-Aguilar Daniel A. , Singletary Daisy , Lagomarsino Laura P. 
Published: October 2020

AbstractAimPlant distributions are influenced by species’ ability to colonize new areas via long-distance dispersal and propensity to adapt to new environments via niche evolution. We useOtoba(Myristicaceae), an ecologically dominant tree genus found in low-to-mid elevation wet forests, as a system to understand the relative importance of these processes within the Neotropics, a region characterized by high species richness and a diversity of biomes.LocationNeotropics and globalTaxonOtobaand entire MyristicaceaeMethodsWe resolve the first phylogeny ofOtobausing targeted sequence capture phylogenomics. We pair this with the most densely sampled phylogeny of Myristicaceae to date, inferred using publicly available data. We then use phylogenetic comparative methods to infer biogeography and examine patterns of niche evolution.ResultsMyristicaceae has an Old World origin, with a single expansion event into the Americas. Divergence dates, fossil evidence, and a notable lack of long-distance dispersal are consistent with a Boreotropical origin of Neotropical Myristicaceae. Mirroring the rarity of dispersal at the family level,Otoba’s biogeography is marked by few biogeographic events: two expansions into Central America from a South American ancestor and a single dispersal event across the Andes. This limited movement contrasts with rapid climatic niche evolution, typically occurring across geographically proximate habitats.Main conclusionsContrasting with previous studies, long-distance dispersal does not need to be invoked to explain the pantropical distribution of Myristicaceae, nor the biogeography ofOtoba. This likely results from the family’s relatively large seeds that are dispersed by large-bodied vertebrates. Instead, rapid niche evolution inOtobahas facilitated its occurrence throughout mesic habitats of the northern Neotropics, including the Amazon rainforest and Andean montane forests.Otobaadds to a growing group of Neotropical plant clades in which climate adaptation following local migration is common, implying an important role of niche evolution in the assembly of the Neotropical flora.Significance statementSpecies distributions across the climatically and topographically heterogenous Neotropics are explained by a combination of local adaptation and dispersal. The relative importance of these mechanisms is clade dependent. We find that niche evolution in geographically proximal habitats is much more common than long-distance dispersal to preadapted regions in the tree genusOtoba, which includes both hyperdominant Amazonian species and narrow Andean endemics. The lack of long-distance dispersal is likely due toOtoba’s large seeds. Our results add to a growing body of literature demonstrating a key role of labile niche evolution across steep environmental gradients in Neotropical plant biogeography.
Modulation of early host innate immune response by a Fowlpox virus (FWPV) lateral body protein
Authors: Giotis Efstathios S , Laidlaw Stephen M , Bidgood Susanna R , Albrecht David , Burden Jemima J , Robey Rebecca C , Mercer Jason , Skinner Michael A 
Published: October 2020

AbstractThe avian pathogen, fowlpox virus (FWPV) has been successfully used as vaccine vector in poultry and humans but relatively little is known about its ability to modulate host antiviral immune responses in these hosts, which are replication permissive and non-permissive, respectively. FWPV is highly resistant to avian type I interferon (IFN) and able to completely block the host IFN-response. Microarray screening of host IFN-regulated gene expression in cells infected with 59 different, non-essential FWPV gene knock-out mutants revealed that FPV184 confers immunomodulatory capacity. We report thatFPV184-knockout virus (FWPVΔ184) induces the cellular IFN response as early as 2 hours post-infection. The wild-type, uninduced phenotype can be rescued by transient expression ofFPV184in FWPVΔ184-infected cells. Ectopic expression ofFPV184inhibited polyI:C activation of the chicken IFN-β promoter and IFN-α activation of the chicken Mx promoter. Confocal and correlative super-resolution light and electron microscopy demonstrated that FPV184 has a functional nuclear localisation signal domain and is packaged in the lateral bodies of the virions. Taken together, these results provide a paradigm for a late poxvirus structural protein packaged in the lateral bodies and capable of supressing IFN induction early during the next round of infection.
On-tissue spatially-resolved glycoproteomics guided by N-glycan imaging reveal global dysregulation of canine glioma glycoproteomic landscape
Authors: Malaker Stacy A. , Quanico Jusal , Romero Antonella Raffo , Kobeissy Firas , Aboulouard Soulaimane , Tierny Dominique , Bertozzi Carolyn R. , Fournier Isabelle , Salzet Michel 
Published: October 2020

AbstractHere we present an approach to identify N-linked glycoproteins and deduce their spatial localization using a combination of MALDI mass spectrometry N-glycan imaging and spatially-resolved glycoproteomic strategies. We subjected formalin-fixed, paraffin-embedded glioma biopsies to on-tissue PNGaseF digestion and MALDI imaging and found that the glycan HexNAc4-Hex5-NeuAc2 was found to be predominantly expressed in necrotic regions of high-grade canine gliomas, whereas high mannose HexNAc2-Hex5 was predominantly found in benign regions. To determine the underlying sialo-glycoprotein, various regions in adjacent tissue sections were subjected to microdigestion and the extracts were analyzed by LC-MS/MS without further glycopeptide enrichment. Results identified haptoglobin, which is involved in iron scavenging that presents aberrant fucosylation/sialylation in various cancers, as the protein associated with HexNAc4-Hex5-NeuAc2. Additionally, we identified several high-mannose (Hex2-HexNAc5) glycopeptides enriched in benign regions. To the best of our knowledge, this is the first report that directly links glycan imaging with intact glycopeptide identification. In total, our spatially-resolved glycoproteomics technique identified over 400 N-glycosylated, O-GalNAcylated, O-mannosylated, and S- and O-GlcNAcylated glycopeptides from over 30 proteins, demonstrating the diverse array of glycosylation present on the tissue slides and the sensitivity of our technique. While N-glycosylation and O-mannosylation were similar between benign and tumor/necrotic sections, S- and O-GlcNAc glycopeptides were significantly deceased in tumor/necrotic sections, whereas sialylated O-GalNAc glycopeptides were significantly upregulated. Ultimately, this proof-of-principle work demonstrates the capability of spatially-resolved glycoproteomics to complement MALDI-imaging technologies in understanding dysregulated glycosylation in cancer.
Antibody-drug conjugates targeting CD45 plus Janus kinase inhibitors effectively condition for allogeneic hematopoietic stem cell transplantation
Authors: Persaud Stephen P. , Ritchey Julie K. , Choi Jaebok , Ruminski Peter G. , Cooper Matthew L. , Rettig Michael P. , DiPersio John F. 
Published: October 2020

ABSTRACTDespite the curative potential of hematopoietic stem cell transplantation (HSCT), transplant conditioning-associated toxicities preclude broader clinical application. Antibody-drug conjugates (ADC) provide an attractive approach to HSCT conditioning that minimizes toxicity while retaining efficacy. Initial studies of ADC conditioning have largely involved syngeneic HSCT; however, for treatment of acute leukemias or tolerance induction for solid organ transplantation, strategies for allogeneic HSCT (allo-HSCT) are needed. Using murine allo-HSCT models, we show that combining CD45-targeted ADCs with the Janus kinase inhibitor baricitinib enables multilineage alloengraftment with >80-90% donor chimerism. Mechanistically, baricitinib impaired T and NK cell survival, proliferation and effector function, with NK cells being particularly susceptible due to inhibited IL-15 signaling. Unlike irradiated mice, CD45-ADC-conditioned mice did not manifest graft-versus-host alloreactivity when challenged with mismatched T cells. Our studies demonstrate novel allo-HSCT conditioning strategies that exemplify the promise of immunotherapy to improve the safe application of HSCT for treating hematologic diseases.
Projection in genomic analysis: A theoretical basis to rationalize tensor decomposition and principal component analysis as feature selection tools
Authors: Taguchi Y-h. , Turki Turki 
Published: October 2020

AbstractIdentifying differentially expressed genes is difficult because of the small number of available samples compared with the large number of genes. Conventional gene selection methods employing statistical tests have the critical problem of heavy dependence ofP-values on sample size. Although the recently proposed principal component analysis (PCA) and tensor decomposition (TD)-based unsupervised feature extraction (FE) has often outperformed these statistical test-based methods, the reason why they worked so well is unclear. In this study, we aim to understand this reason in the context of projection pursuit (PP) that was proposed a long time ago to solve the problem of dimensions; we can relate the space spanned by singular value vectors with that spanned by the optimal cluster centroids obtained from K-means. Thus, the success of PCA- and TD-based unsupervised FE can be understood by this equivalence. In addition to this, empirical threshold adjustedP-values of 0.01 assuming the null hypothesis that singular value vectors attributed to genes obey the Gaussian distribution empirically corresponds to threshold-adjustedP-values of 0.1 when the null distribution is generated by gene order shuffling. For this purpose, we newly applied PP to the three data sets to which PCA and TD based unsupervised FE were previously applied; these data sets treated two topics, biomarker identification for kidney cancers (the first two) and the drug discovery for COVID-19 (the thrid one). Then we found the coincidence between PP and PCA or TD based unsupervised FE is pretty well. Shuffling procedures described above are also successfully applied to these three data sets. These findings thus rationalize the success of PCA- and TD-based unsupervised FE for the first time.
Intracellular label-free detection of mesenchymal stem cell metabolism within a perivascular niche-on-a-chip
Authors: Perottoni Simone , Neto Nuno G. B. , Di Nitto Cesare , Raimondi Manuela Teresa , Monaghan Michael G. 
Published: October 2020

AbstractThe stem cell niche at the perivascular space in human tissue plays a pivotal role in dictating the overall fate of stem cells within it. Mesenchymal stem cells (MSCs), in particular, experience influential microenvironmental conditions, which induce specific metabolic profiles that affect processes such as cell differentiation and dysregulation of the immunomodulatory funtion. Reports focusing specifically on the metabolic status of MSCs under the effect of pathophysiological stimuli - in terms of flow velocities, shear stresses or oxygen tension – do not model heterogenous gradients, highlighting the need of more advanced models reproducing the metabolic niche. Organ-on-a-chip technology offers the most advanced tools for stem cell niche modelling thus allowing for controlled dynamic culture conditions while profiling tunable oxygen tension gradients. However, current systems for live cell detection of metabolic activity inside microfluidic devices require the integration of microsensors that allow for extracellular measurments only, giving innacurate and indirect information about the metabolic state of cells. Here, we present a metabolic toolbox coupling a miniatuirzedin vitrosystem for human-MSCs dynamic culture, that mimics microenvironmental conditions of the perivascular niche, with high-resolution imaging of intracellular metabolism. Using Fluorescence Lifetime Imaging Microscopy (FLIM) we monitor the spatial metabolic machinery and correlate it with experimentally validated intracellular oxygen concentration after designing the oxygen tension decay along the fluidic chamber byin silicomodels prediction. Our platform allows for the subjection of a metabolic profile to MSCs, mimicking the physiological niche in space and time, and its real-time monitoring representing a functional tool for modelling perivascular niches, relevant diseases and metabolic-related uptake of pharmaceuticals.
The mTORC1-mediated activation of ATF4 promotes protein and glutathione synthesis downstream of growth signals
Authors: Torrence Margaret E. , MacArthur Michael R. , Hosios Aaron M. , Valvezan Alexander J. , Asara John M. , Mitchell James R. , Manning Brendan D. 
Published: October 2020

AbstractThe mechanistic target of rapamycin complex 1 (mTORC1) stimulates a coordinated anabolic program in response to growth-promoting signals. Paradoxically, recent studies indicate that mTORC1 can activate the adaptive stress-responsive transcription factor ATF4 through mechanisms distinct from its canonical induction by the integrated stress response (ISR). However, how ATF4 functions in response to these distinct modes of regulation and its broader role as a downstream target of mTORC1 are unknown. Therefore, we directly compared ATF4-dependent transcriptional changes induced upon activation of mTORC1 or the ISR. The mTORC1-ATF4 pathway stimulated the expression of only a subset of the ATF4 target genes stimulated by the ISR, including genes involved in amino acid uptake, synthesis, and tRNA charging. We demonstrate that ATF4 is a metabolic effector of mTORC1 involved in both its established role in promoting protein synthesis and in a previously unappreciated function for mTORC1 in stimulating cellular cystine uptake and glutathione synthesis.
Sedimentation rate and organic matter dynamics shape microbiomes across a continental margin
Authors: Bhattacharya Sabyasachi , Mapder Tarunendu , Fernandes Svetlana , Roy Chayan , Sarkar Jagannath , Rameez Moidu Jameela , Mandal Subhrangshu , Sar Abhijit , Chakraborty Amit Kumar , Mondal Nibendu , Dam Bomba , Peketi Aditya , Chakraborty Ranadhir , Mazumdar Aninda , Ghosh Wriddhiman 
Published: October 2020

AbstractMarine sedimentation rate and bottom-water O2concentration control the remineralization/sequestration of organic carbon across continental margins; but whether/how they shape microbiome architecture (the ultimate effector of all biogeochemical phenomena), across shelf/slope sediments, is unknown. Here we reveal distinct microbiome structures and functions, amidst comparable pore-fluid chemistries, along ~3 m sediment-horizons underlying the seasonal (shallow coastal) and perennial (deep sea) oxygen minimum zones (OMZs) of the Arabian Sea, situated across the western-Indian margin (water-depths: 31 m and, 530 and 580 m, respectively). Along the perennial- and seasonal-OMZ sediment-cores microbial communities were predominated byGammaproteobacteria/AlphaproteobacteriaandEuryarchaeota/Firmicutesrespectively. As a perennial-OMZ signature, a cryptic methane production-consumption cycle was found to operate near the sediment-surface; overall diversity, as well as the relative abundances of simple-fatty-acids-requiring anaerobes (methanogens, anaerobic methane-oxidizers, sulfate-reducers and acetogens), peaked in the topmost sediment-layer and then declined via synchronized fluctuations until the sulfate-methane transition zone was reached. The entire microbiome profile was reverse in the seasonal-OMZ sediment-horizon. We discerned that in the perennial-OMZ sediments organic carbon deposited was higher in concentration, and marine components-rich, so it potentially degraded readily to simple fatty acids; lower sedimentation rate afforded higher O2exposure time for organic matter degradation despite perennial hypoxia in the bottom-water; thus, the resultant abundance of reduced metabolites sustained multiple inter-competing microbial processes in the upper sediment-layers. Remarkably, the whole geomicrobial scenario was opposite in the sediments of the seasonal/shallow-water OMZ. Our findings create a microbiological baseline for understanding carbon-sulfur cycling across distinct marine depositional settings and water-colum n oxygenation regimes.
Fitness Estimation for Genetic Evolution of Bacterial Populations
Authors: Sarkisov Sergey S. , Timofeyev Ilya , Azencott Robert 
Published: October 2020

AbstractIn this paper we develop and test algorithmic techniques to estimate genotypes fitnesses by analysis of observed daily frequency data monitoring the long-term evolution of bacterial populations. In particular, we develop a non-linear least squares approach to estimate selective advantages of emerging new mutant strains in locked-box stochastic models describing bacterial genetic evolution similar to the celebrated Lenski experiment on Escherichia Coli. Our algorithm first analyses emergence of new mutant strains for each individual trajectory. For each trajectory our analysis is progressive in time, and successively focuses on the first mutation event before analyzing the second mutation event. The basic principle applied here is to minimize (for each trajectory) the mean squared errors of predictionw(t) −W(t) where the observed white cell frequenciesw(t) are predicted byW(t), which is computed as the conditional expectation ofw(t) given the available information at time (t− 1). The pooling of all selective advantages estimates across all trajectories provides histograms on which we perform a precise peak analysis to compute final estimates of selective advantages. We validate our approach using ensembles of simulated trajectories.
Plectin Ensures Intestinal Epithelial Integrity and Protects Colon Against Colitis
Authors: Krausova Alzbeta , Buresova Petra , Sarnova Lenka , Oyman-Eyrilmez Gizem , Skarda Jozef , Wohl Pavel , Bajer Lukas , Sticova Eva , Bartonova Lenka , Pacha Jiri , Koubkova Gizela , Prochazka Jan , Spörrer Marina , Dürrbeck Christopher , Stehlikova Zuzana , Vit Martin , Ziolkowska Natalia , Sedlacek Radislav , Jirak Daniel , Kverka Miloslav , Wiche Gerhard , Fabry Ben , Korinek Vladimir , Gregor Martin 
Published: October 2020

ABSTRACTPlectin, a highly versatile cytolinker protein, provides tissues with mechanical stability through the integration of intermediate filaments (IFs) with cell junctions. Here, we hypothesize that plectin-controlled cytoarchitecture is a critical determinant of the intestinal barrier function and homeostasis. Mice lacking plectin in intestinal epithelial cells (IEC;PleΔIEC) spontaneously developed colitis characterized by extensive detachment of IECs from the basement membrane (BM), increased intestinal permeability, and inflammatory lesions. Moreover, plectin expression was reduced in colons of ulcerative colitis (UC) patients and negatively correlated with the severity of colitis. Mechanistically, plectin deficiency in IECs led to aberrant keratin filament (KF) network organization and formation of dysfunctional hemidesmosomes (HDs) and intercellular junctions. In addition, the hemidesmosomal α6β4 integrin (Itg) receptor showed attenuated association with KFs, and protein profiling revealed prominent downregulation of junctional constituents. Consistent with effects of plectin loss in the intestinal epithelium, plectin-deficient IECs exhibited remarkably reduced mechanical stability and limited adhesion capacityin vitro. Feeding mice with a low-residue liquid diet that reduced mechanical stress and antibiotic treatment successfully mitigated epithelial damage in thePleΔIECcolon.