bluuebunny/crossref_metadata_2025_split huggingface dataset:
SPEAR: a proteomics approach for simultaneous protein expression and redox analysis
Authors: Doron Shani , Lampl Nardy , Savidor Alon , Katina Corine , Gabashvili Alexandra , Levin Yishai , Rosenwasser Shilo 
Published: June 2021

AbstractOxidation and reduction of protein cysteinyl thiols serve as molecular switches, which is considered the most central mechanism for redox regulation of biological processes, altering protein structure, biochemical activity, subcellular localization, and binding affinity. Redox proteomics allows for the global identification of redox-modified cysteine (Cys) sites and quantification of their oxidation/reduction responses, serving as a hypothesis-generating platform to stimulate redox biology mechanistic research. Here, we developed Simultaneous Protein Expression and Redox (SPEAR) analysis, a new redox-proteomics approach based on differential labeling of oxidized and reduced cysteines with light and heavy isotopic forms of commercially available isotopically-labeled N-ethylmaleimide (NEM). The presented method does not require enrichment for labeled peptides, thus enabling simultaneous quantification of Cys oxidation state and protein abundance. Using SPEAR, we were able to quantify the in-vivo oxidation state of thousands of cysteines across theArabidopsisproteome under steady-state and oxidative stress conditions. Functional assignment of the identified redox-sensitive proteins demonstrated the widespread effect of oxidative conditions on various cellular functions and highlighted the enrichment of chloroplast-targeted proteins. SPEAR provides a simple, straightforward, and cost-effective means of studying redox proteome dynamics. The presented data provide a global quantitative view of cysteine oxidation of well-known redox-regulated active sites and many novel redox-sensitive sites whose role in plant acclimation to stress conditions remains to be further explored.
Glial AP1 promotes early TBI recovery but chronically drives tauopathy
Authors: Byrns China N. , Saikumar Janani , Bonini Nancy M. 
Published: June 2021

AbstractThe emergence of degenerative disease after traumatic brain injury is often described as an acceleration of normal age-related processes. Whether similar molecular processes occur in injury and in age is unclear. Here we identify a functionally dynamic and lasting transcriptional response in glia, mediated by the conserved transcription factor AP1. In the early post-TBI period, glial AP1 is essential for recovery, ensuring brain integrity and animal survival. In sharp contrast, chronic AP1 activation promotes human tau pathology, tissue loss, and mortality. We show a similar process activates in healthy brains with age. Importantly, AP1 activity is present in moderate human TBI, decades after injury, and associates with microglial activation and tauopathy. Our data provide key molecular insight into glia, highlighting that the same molecular process drives dynamic and contradictory glia behavior in TBI, first acting to protect but chronically promoting disease.
Insight into the ecology of vaginal bacteria through integrative analyses of metagenomic and metatranscriptomic data
Authors: France M. T. , Fu L. , Rutt L. , Yang H. , Humphrys M. , Narina S. , Gajer P. , Ma B. , Forney L. J. , Ravel J. 
Published: June 2021

AbstractVaginal bacterial communities dominated by Lactobacillus species are associated with a reduced risk to various adverse health outcomes. However, somewhat unexpectedly many healthy women have microbiota that are not dominated by lactobacilli. To determine the factors that drive vaginal community composition we characterized the genetic composition and transcriptional activities of vaginal microbiota in healthy women. We demonstrated that the abundance of a species is not always indicative of its transcriptional activity and that impending changes in community composition can be predicted from metatranscriptomic data. Functional comparisons highlight differences in the metabolic activities of these communities, notably in their degradation of host-produced mucin but not glycogen. Degradation of mucin by communities not dominated by Lactobacillus may play a role in their association with adverse health outcomes. Finally, we show that the transcriptional activities of L. crispatus, L. iners, and G. vaginalis vary with the taxonomic composition of the communities in which they reside. Notably, L. iners and G. vaginalis both demonstrated lower expression of their cholesterol-dependent cytolysins when co-resident with Lactobacillus spp. and higher expression when co-resident with other facultative and obligate anaerobes. The pathogenic potential of these species may depend on the communities in which they reside and thus could be modulated by interventional strategies. Our results provide insight to the functional ecology of vaginal microbiota and reveal strategies for management of these ecosystems.
A Dynamic Efficient Sensory Encoding Approach to Adaptive Tuning in Neural Models of Visual Motion Processing
Authors: Steinmetz Scott T. , Layton Oliver W. , Powell Nate V. , Fajen Brett R. 
Published: June 2021

ABSTRACTThis paper introduces a self-tuning mechanism for capturing rapid adaptation to changing visual stimuli by a population of neurons. Building upon the principles of efficient sensory encoding, we show how neural tuning curve parameters can be continually updated to optimally encode a time-varying distribution of recently detected stimulus values. We implemented this mechanism in a neural model that produces human-like estimates of self-motion direction (i.e., heading) based on optic flow. The parameters of speed-sensitive units were dynamically tuned in accordance with efficient sensory encoding such that the network remained sensitive as the distribution of optic flow speeds varied. In two simulation experiments, we found that model performance with dynamic tuning yielded more accurate, shorter latency heading estimates compared to the model with static tuning. We conclude that dynamic efficient sensory encoding offers a plausible approach for capturing adaptation to varying visual environments in biological visual systems and neural models alike.
Pressure and curvature control of contact inhibition in epithelia growing under spherical confinement
Authors: Di Meglio Ilaria , Trushko Anastasiya , Guillamat Pau , Blanch-Mercader Carles , Roux Aurélien 
Published: June 2021

SummaryMorphogenesis requires spatiotemporal regulation of cell shape and proliferation, both regulated by biochemical and mechanical cues. In epithelia, this regulation is called contact inhibition, but disentangling biochemical from mechanical cues remains challenging. Here, we show that epithelia growing under confinement accumulate pressure that inhibits proliferation above a threshold value, which depends on the β-catenin pathway. Before inhibition of proliferation, cell aspect ratio abruptly increased upon reaching confluency. This shape transition occurred at low, constant pressure and was mainly controlled by cell density and contractility, correlating with YAP/TAZ pathway inhibition. In our system, epithelia spontaneously buckle: we observed that folding transiently reactivates both the YAP/TAZ pathway and cell proliferation. Altogether, our results support that different mechanical cues part of contact inhibition regulate cell proliferation through different mechanosensing pathways. Proliferation is regulated by sustained, tissue-level pressure through the β-catenin pathway, and by local curvature and pressure changes through the YAP/TAZ pathway.
Mapping QTLs for phenotypic and morpho-physiological traits related to grain yield under late sown conditions conditions in wheat (Triticum aestivum L.)
Authors: Pankaj Yaswant Kumar , Pal Lalit , Nagarajan Ragupathi , Gill Kulvinder Singh , Kumar Vishnu , Sangwan Sonali , Panigrahi Sourav , Kumar Rajeev 
Published: June 2021

AbstractThe elevating temperature makes heat stress one of the major issues for wheat production globally. To elucidate genetic basis and map heat tolerance traits, a set of 166 doubled haploid lines (DHLs) derived from the cross between PBW3438/IC252874 was used. The population was evaluated under Normal sown (NS) and late sown (LS) conditions, by exposing to heat stress during rabi season. The canopy temperature (CT) showed positive correlations with grain yield, whereas Soil plant analysis development (SPAD) was not significantly correlated and associated with GY in both the normal and late sown conditions. Composite interval mapping (CIM) identified total 12 Quantitative trait loci (QTLs) viz., 2 (Normal sown), 10 (late sown) mapped on linkage groups 1A, 1D, 2B, 2D, 3B, 4D, 5B and 6D, during both the crop seasons 2017-18 and 2018-19. Combining the results of these QTLs revealed a major stable QTL for grain yield (GY) on chromosome 3B with 11.84% to 21.24% explaining phenotypic variance under both sowing conditions. QTL for CT and SPAD was detected on chromosome 1A while QTL for GY on chromosome 3B and 5B. The identified QTLs in the genomic regions could be targeted for genetic improvement and marker assisted selection for heat tolerance in wheat. The tools like SPAD and CT could be exploited to screen the large number of breeding lines.
Characterization of endogenous Rubus yellow net virus in raspberries
Authors: Ho Thien , Broome Janet C. , Buhler Jason P. , O’Donovan Wendy , Tian Tongyan , Diaz-Lara Alfredo , Martin Robert R. , Tzanetakis Ioannis E. 
Published: June 2021

AbstractRubus yellow net virus (RYNV) belongs to genus Badnavirus. Badnavirids are found in plants as endogenous, inactive sequences, and/or in episomal (infectious and active) forms. To assess the state of RYNV infections, we sequenced the genomes of various Rubus cultivars and mined eight additional published whole genome sequencing datasets. Sequence analysis revealed the presence of a diverse array of endogenous RYNV (endoRYNV) sequences that differ significantly in their structure; some lineages have nearly complete, yet non-functional genomes whereas others have rudimentary, small sequence fragments. We developed assays to genotype the six main endoRYNV lineages as well as the only known episomal lineage in commercial Rubus. This study discloses the widespread presence of endoRYNVs in commercial raspberries, likely because breeding programs have been using a limited pool of germplasm that harbored endoRYNVs.
Whole Genome Sequence and CAZyme distribution of the cellulase hyper producing filamentous fungus Penicillium janthinellum NCIM 1366
Authors: Christopher Meera , Sreeja-Raju Athiraraj , Kooloth-Valappil Prajeesh , Abraham Amith , Gokhale Digambar Vitthal , Sukumaran Rajeev K. 
Published: June 2021

AbstractPenicillium janthinellum NCIM 1366, capable of secreting cellulases that are highly efficient in the hydrolysis of lignocellulosic biomass, was sequenced to understand its cellulolytic machinery. De novo sequencing and assembly revealed a 37.6 Mb genome encoding 11,848 putative proteins, 93% of which had significant BLAST-P hits. The majority of the top hits (those with over 60% UniProt identity) belonged to P. brasilianum. Carbohydrate active enzymes (CAZymes) and other enzymes involved in lignocellulose degradation were also predicted from this strain and compared with those of the industrial workhorse of cellulase production-Trichoderma reesei RUT-C30. The comparison showed that the fungus encodes a far higher number of CAZYmes (422) as compared to T. reesei RUT-C30 (244), which gives a plausible explanation for its overall effectiveness in biomass hydrolysis. An analysis of the secreted CAZymes and annotated ligninases identified 216 predicted proteins which may be directly involved in the breakdown of lignocellulose.
Metagenome-based comparisons of decay rates and host-specificity of fecal microbial communities for improved microbial source tracking
Authors: Suttner Brittany , Lindner Blake G. , Kim Minjae , Conrad Roth E. , Rodriguez Luis M. , Orellana Luis H. , Johnston Eric R. , Hatt Janet K. , Zhu Kevin J. , Brown Joe , Konstantinidis Konstantinos T. 
Published: June 2021

ABSTRACTFecal material in the environment is a primary source of pathogens that cause waterborne diseases and affect over a billion people worldwide. Microbial source tracking (MST) assays based on single genes (e.g., 16S rRNA) do not always provide the resolution needed to attribute fecal contamination sources. In this work, we used dialysis bag mesocosms simulating a freshwater habitat that were spiked separately with cow, pig, or human feces to monitor the decay of host-specific fecal signals over time with metagenomics, traditional qPCR, and culture-based methods. Sequencing of the host fecal communities used as inocula recovered 79 non-redundant metagenome-assembled genomes (MAGs) whose abundance patterns showed that the majority of the fecal community signal was not detectable in the mesocosm metagenomes after four days. Several MAGs showed high host specificity, and thus are promising candidates for biomarkers for their respective host type. Traditional qPCR methods varied in their correlation with MAG decay kinetics. Notably, the human-specific Bacteroides assay, HF183/BFDRev, consistently under-estimated fecal pollution due to not being present in all hosts and/or primer mismatches. This work provides new insights on the persistence and decay kinetics of host-specific gut microbes in the environment and identifies several MAGs as putative biomarkers for improved MST.SYNOPSISWe track cow, pig, and human fecal pollution in lake water over time with metagenomics and benchmark these novel protocols against standard culture-based and qPCR tests for water quality monitoring.
Multi-Parameter Quantitative Imaging of Tumor Microenvironments Reveals Perivascular Immune Niches Associated with Anti-Tumor Immunity
Authors: Stoltzfus Caleb R , Sivakumar Ramya , Kunz Leo , Pope BE Olin , Menietti Elena , Speziale Dario , Adelfio Roberto , Bacac Marina , Colombetti Sara , Perro Mario , Gerner Michael Y 
Published: June 2021

AbstractTumors are populated by a multitude of immune cell types with varied phenotypic and functional properties, which can either promote or inhibit anti-tumor responses. Appropriate localization and function of these cells within tumors is critical for protective immunity, with CD8 T cell infiltration being a biomarker of disease outcome and therapeutic efficacy. Recent multiplexed imaging approaches have revealed highly complex patterns of localization for these immune cell subsets and the generation of distinct tumor microenvironments (TMEs), which can vary among cancer types, individuals, and within individual tumors. While it is recognized that TMEs play a pivotal role in disease progression, a better understanding of their composition, organization, and heterogeneity, as well as how distinct TMEs are reshaped with immunotherapy, is necessary. Here, we performed spatial analysis using multi-parameter confocal imaging, histocytometry, and CytoMAP to study the microanatomical organization of immune cells in two widely used preclinical cancer models, the MC38 colorectal and KPC pancreatic murine tumors engineered to express human carcinoembryonic antigen (CEA). Immune responses were examined in either unperturbed tumors or after immunotherapy with a CEA T cell bispecific (CEA-TCB) surrogate antibody and anti-PD-L1 treatment. CEA-TCB mono and combination immunotherapy markedly enhanced intra-tumoral cellularity of CD8 T cells, dominantly driven by the expansion of TCF1− PD1+ effector T cells and with more minor increases in TCF1+PD1+ resource CD8 T cells. The majority of infiltrating T cells, particularly resource CD8 T cells, were colocalized with dendritic cells (DCs) or activated MHCII+ macrophages, but largely avoided the deeper tumor nest regions composed of cancer cells and non-activated macrophages. These myeloid cell – T cell aggregates were found in close proximity to tumor blood vessels, generating perivascular immune niches. This perivascular TME was present in untreated samples and markedly increased after CEA-TCB therapy, with its relative abundance positively associated with response to therapy. Together, these studies demonstrate the utility of advanced spatial analysis in cancer research by revealing that blood vessels are key organizational hubs of innate and adaptive immune cells within tumors, and suggesting the likely relevance of the perivascular immune TME in disease outcome.
Simple models highlight differences in the walking biomechanics of young children and adults
Authors: Rose Vivian L. , Arellano Christopher J. 
Published: June 2021

AbstractAdults conserve metabolic energy during walking by minimizing the step-to-step transition work performed by the legs during double support and by utilizing spring-like mechanisms in their legs, but little is known as to whether children utilize these same mechanisms. To gain a better understanding, we studied how children (5-6 years) and adults modulate the mechanical and metabolic demands of walking at their preferred speed, across slow (75%), preferred (100%), and fast (125%) step frequencies. We quantified the 1) positive mass-specific work done by the trailing leg during step-to-step transitions and 2) the leg’s spring-likebehavior during single support. On average, children walked with a 36% greater net cost of transport (COT; J/kg/m) than adults (p=0.03), yet both groups increased their net COT at varying step frequencies. After scaling for speed, children generated ∼2-fold less trailing limb positive scaled mechanical work during the step-to-step transition (p=0.02). Unlike adults, children did not modulate their trailing limb positive work to meet the demands of walking at 75% and 125% of their preferred step frequency. In single support, young children operated their stance limb with much greater compliance than adultsvs. 11.35;p=.023). Our observations suggest that the mechanics of walking in children 5-6 years are fundamentally distinct from the mechanics of walking in adults and may help to explain a child’s higher net COT. These insights have implications for the design of assistive devices for children and suggest that children cannot be simply treated as scaled down versions of adults.
Fast and powerful statistical method for context-specific QTL mapping in multi-context genomic studies
Authors: Lu Andrew , Thompson Mike , Grace Gordon M , Dahl Andy , Ye Chun Jimmie , Zaitlen Noah , Balliu Brunilda 
Published: June 2021

AbstractRecent studies suggest that context-specific eQTLs underlie genetic risk factors for complex diseases. However, methods for identifying them are still nascent, limiting their comprehensive characterization and downstream interpretation of disease-associated variants. Here, we introduce FastGxC, a method to efficiently and powerfully map context-specific eQTLs by leveraging the correlation structure of multi-context studies. We first show via simulations that FastGxC is orders of magnitude more powerful and computationally efficient than previous approaches, making previously year-long computations possible in minutes. We next apply FastGxC to bulk multi-tissue and single-cell RNA-seq data sets to produce the most comprehensive tissue- and cell-type-specific eQTL maps to date. We then validate these maps by establishing that context-specific eQTLs are enriched in corresponding functional genomic annotations. Finally, we examine the relationship between context-specific eQTLs and human disease and show that FastGxC context-specific eQTLs provide a three-fold increase in precision to identify relevant tissues and cell types for GWAS variants than standard eQTLs. In summary, FastGxC enables the construction of context-specific eQTL maps that can be used to understand the context-specific gene regulatory mechanisms underlying complex human diseases.
Profiling a single-stranded DNA region within an rDNA segment that is a loading site for bacterial condensin
Authors: Yano Koichi , Noguchi Hideki , Niki Hironori 
Published: June 2021

AbstractBacterial condensin preferentially loads to single-stranded DNA (ssDNA) in vitro and loads onto rDNA in vivo to support proper chromosome compaction. Thus, the actively transcribing rDNA would provide the ssDNA region for the topological loading of bacterial condensin. We attempted to detect the ssDNA region in the rrnI gene in situ. Non-denaturing sodium bisulfite treatment catalyzed the conversion of cytosines to thymines via uracils (CT-conversion) at locally melted DNA of a bacterial genome. Using next-generation sequencing, we generated an average of 11,000 reads covering each cytosine on the PCR-amplified rDNA segment to obtain the actual CT-conversion rate. In principle, the CT-conversion rate is an accurate guide to detect the formation of the ssDNA segment. We expected that an increment of the CT-conversion rate would reflect a trend toward ssDNA accumulation at a given site within the rDNA. We detected multiple ssDNA segments throughout the rDNA. The deletion mutations of the rDNA that affect the bacterial-condensin loading hindered the ssDNA formation only at the 100–500 bp segment downstream of the promoter. These data support the idea that the ssDNA segment plays a crucial role as the bacterial condensin-loading site and suggest the mechanism of condensin loading onto rDNA.
Probabilistic modeling methods for cell-free DNA methylation based cancer classification
Authors: Halla-aho Viivi , Lähdesmäki Harri 
Published: June 2021

AbstractBackgroundcfMeDIP-seq is a low-cost method for determining the DNA methylation status of cell-free DNA and it has been successfully combined with statistical methods for accurate cancer diagnostics. We investigate the diagnostic classification aspect by applying statistical tests and dimension reduction techniques for feature selection and probabilistic modeling for the cancer type classification, and we also study the effect of sequencing depth.MethodsWe experiment with a variety of statistical methods that use different feature selection and feature extraction methods as well as probabilistic classifiers for diagnostic decision making. We test the (moderated) t-tests and the Fisher’s exact test for feature selection, principal component analysis (PCA) as well as iterative supervised PCA (ISPCA) for feature generation, and GLMnet and logistic regression methods with sparsity promoting priors for classification. Probabilistic programming language Stan is used to implement Bayesian inference for the probabilistic models.Results and conclusionsWe compare overlaps of differentially methylated genomic regions as chosen by different feature selection methods, and evaluate probabilistic classifiers by evaluating the area under the receiver operating characteristic (AUROC) scores on discovery and validation cohorts. While we observe that many methods perform equally well as, and occasionally considerably better than, GLMnet that was originally proposed for cfMeDIP-seq based cancer classification, we also observed that performance of different methods vary across sequencing depths, cancer types and study cohorts. Overall, methods that seem robust and promising include Fisher’s exact test and ISPCA for feature selection as well as a simple logistic regression model with the number of hyper and hypomethylated regions as features.