bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide dynamics of RNA synthesis, processing and degradation without RNA metabolic labeling
Authors: Furlan Mattia , Galeota Eugenia , Del Gaudio Nunzio , Dassi Erik , Caselle Michele , de Pretis Stefano , Pelizzola Mattia 
Published: January 2019

AbstractThe kinetic rates of RNA synthesis, processing and degradation determine the dynamics of transcriptional regulation by governing both the abundance and the responsiveness to modulations of premature and mature RNA species. The study of RNA dynamics is largely based on the integrative analysis of total and nascent transcription, with the latter being quantified through RNA metabolic labeling. We describe here INSPEcT-, a computational method based on mathematical modeling of intronic and exonic expression, able to derive the dynamics of transcription from steady state or time course profiling of just total RNA, without requiring any information on nascent transcripts. Our approach closely recapitulates the kinetic rates obtained through RNA metabolic labeling, improves the ability to detect changes in transcripts half-lives, reduces the cost and complexity of the experiments, and can be adopted to study experimental conditions where nascent transcription cannot be readily profiled. Finally, we applied INSPEcT- to the characterization of post-transcriptional regulation landscapes in dozens of physiological and disease conditions. This approach was included in the INSPEcT Bioconductor package, which can now unveil RNA dynamics from steady state or time course data, with or without the profiling of nascent RNA.
Biotic interactions and climate in species distribution modelling
Authors: Bebber Daniel P. , Gurr Sarah J. 
Published: January 2019

SummarySpecies have preferred environmental niches 1 and their geographical distributions respond to global climate change 2. Predicting range shifts under climate change has profound implications for conservation of biodiversity 3, provision of ecosystem services, and in the management of invasive species 4. Species distribution modelling (SDM) has largely focussed on climate variations, but biotic interactions, such as predation and competition, can alter potential distributions 5,6 and affect migration rates 7. However, a lack of data on biotic interactions has restricted consideration of these factors for many species 1. Here, we compare the power of biotic and climatic factors as predictors of global distributions of hundreds of crop pests and pathogens (CPPs), for which host preferences are known. We show that host availability is a more important predictor of endobiotic pathogen distributions (fungi, oomycetes, bacteria, viruses and nematodes) than of epibiotic pest distributions (insect herbivores). Conversely, climatic variables are better predictors of epibiotic pest distributions. These results are robust to statistical controls for varying observational capacity among countries. Our findings demonstrate that life history affects global scale species distributions and that SDM should incorporate biotic interactions as well as climate.
Genetic Variability and Correlation Coefficients of Major Traits in Early Maturing Rice under Rainfed Lowland Environments of Nepal
Authors: Tiwari Dev Nidhi , Tripathi Santosh Raj , Tripathi Mahendra Prasad , Khatri Narayan , Bastola Bishwas Raj 
Published: January 2019

ABSTRACTGenetic variability is the fundamental requirement of any crop breeding program to develop superior cultivars. The objective of this study was to estimate the genetic variability and find out the correlation among the different quantitative traits of rainfed early lowland rice. The experiment was conducted consecutively two years during 2015 and 2016 in wet season across the four different locations in Regional Agricultural Research Station, Khajura, National Wheat Research Program, Bhairahawa, National Maize Research Program, Rampur and National Rice Research Program, Hardinath along the Terai region of Nepal representing sub-tropical agro-climate. Seven genotypes including Hardinath-1 as standard check variety were evaluated in the randomized complete block design with three replications. Various quantitative traits were measured to investigate the variability and correlation coefficients. All the genotypes and locations showed significant variations for all the traits considered. Genotypic coefficient of variation was lower than phenotypic coefficient of variation for all traits studied. The magnitudes of genotypic coefficient of variations were relatively higher for grain yield, 1000-grain weight and days to heading. The highest broad sense heritability of 94% was recorded in days to maturity and the lowest heritability of 16% was observed in plant height. Positive and highly significant correlations were found both in genotypic and phenotypic levels between days to heading and days to maturity (rg=0.9999**, rp=0.997**), days to heading and grain yield (rg =0.9999**, rp= 0.9276**), days to maturity and grain yield (rg =0.9796**, rp=0.9174**). However, negative and highly significant genetic correlation was observed between plant height and 1000 grain weight (rg = -0.9999**). Thus results indicated that days to heading, days to maturity, grain yield, 1000 grain weight demonstrated higher heritability and remarkable genetic advance could be considered for the most appropriate traits for improvement and selection of trait to achieve stable and high yielding early rice genotypes under rainfed environments.
Plasticity versus stability across the human cortical visual connectome
Authors: Haak Koen V. , Beckmann Christian F. 
Published: January 2019

AbstractWhether and how the balance between plasticity and stability varies across the brain is an important open question. Within a processing hierarchy, it is thought that plasticity is increased at higher levels of cortical processing, but direct quantitative comparisons between low- and high-level plasticity have not been made so far. Here, we addressed this issue for the human cortical visual system. By quantifying plasticity as the complement of the heritability of functional connectivity, we demonstrate a non-monotonic relationship between plasticity and hierarchical level, such that plasticity decreases from early to mid-level cortex, and then increases further of the visual hierarchy. This non-monotonic relationship argues against recent theory that the balance between plasticity and stability is governed by the costs of the “coding-catastrophe”, and can be explained by a concurrent decline of short-term adaptation and rise of long-term plasticity up the visual processing hierarchy.
Discovery of a redox-thiol switch regulating cellular energy metabolism
Authors: Gao Xing-Huang , Li Ling , Parisien Marc , Mcleod Matt , Wu Jing , Bederman Ilya , Gao Zhaofeng , Krokowski Dawid , Chirieleison Steven M , Diatchenko Luda , Abbott Derek , Yee Vivien , Hoppel Charles L. , Kibbey Richard G , Holyoak Todd , Willard Belinda , Arvan Peter , Hatzoglou Maria 
Published: January 2019

AbstractPreviously, we reported that increased synthesis of the gas hydrogen sulfide (H2S) during the Integrated Stress Response (ISR) induced proteome-wide cysteine-sulfhydration with the predominant modified pathway being enzymes of cellular energy metabolism (Gao, et al. 2015). Using pancreatic beta cells and quantitative proteomics in this study, we identified a Redox Thiol Switch from S-glutathionylation to S-sulfhydration and we named it, RTSGS. About half of the identified proteins are involved in energy metabolism, and one novel target was the mitochondrial phosphoenolpyruvate carboxykinase 2 (PCK2) whose catalytic Cys306was targeted by both modifications. The enzymatic activity of PCK2 was inhibited by S-glutathionylation, and this inhibition was largely reversed by S-sulfhydration. S-sulfhydration also reversed the S-glutathionylation-mediated inhibition of glucose flux, indicating a broad metabolic significance. We propose that a Redox Thiol Switch from S-glutathionylation to S-sulfhydration is a key mechanism to fine tune cellular energy metabolism in response to different levels of oxidative stress.
Analytical expressions and physical principles for single-cell mRNA distributions of the lac operon of Escherichia coli
Authors: Choudhary Krishna , Narang Atul 
Published: January 2019

ABSTRACTMechanistic models of stochastic gene expression are of considerable interest, but their complexity often precludes tractable analytical expressions for mRNA and protein distributions. The lac operon of E. coli is a model system with regulatory elements such as multiple operators and DNA looping that are shared by many operons. Although this system is complex, intuition suggests that fast DNA looping may simplify it by causing the repressor-bound states of the operon to equilibrate rapidly, thus ensuring that the subsequent dynamics are governed by slow transitions between the repressor-free and the equilibrated repressor-bound states. Here, we show that this intuition is correct by applying singular perturbation theory to a mechanistic model of lac transcription with the scaled time constant of DNA looping as the perturbation parameter. We find that at steady state, the repressor-bound states satisfy detailed balance and are dominated by the looped states; moreover, the interaction between the repressor-free and the equilibrated repressor-bound states is described by an extension of the Peccoud-Ycart two-state model in which both (repressor-free and repressor-bound) states support transcription. The solution of this extended two-state model reveals that the steady state mRNA distribution is a mixture of the Poisson and negative hypergeometric distributions which reflects mRNAs obtained by transcription from the repressor-bound and repressor-free states, respectively. Finally, we show that the physics revealed by perturbation theory makes it easy to derive the extended two-state model equations for complex regulatory architectures.
Quantitative Analysis of Global Protein Stability Rates in Tissues
Authors: McClatchy Daniel B. , Gao Yu , Lavallée-Adam Mathieu , Yates John R. 
Published: January 2019

AbstractProtein degradation is an essential mechanism for maintaining homeostasis in response to internal and external perturbations. Disruption of this process is implicated in many human diseases, but quantitation of global stability rates has not yet been achieved in tissues. We have developed QUAD (Quantification of Azidohomoalanine Degradation), a technique to quantitate global protein degradation using mass spectrometry. Azidohomoalanine (AHA) is pulsed into mouse tissues through their diet. The mice are then returned to a normal diet and the decrease of AHA abundance can be quantitated in the proteome. QUAD analysis reveals that protein stability varied within tissues, but discernible trends in the data suggest that cellular environment is a major factor dictating stability. Within a tissue, different organelles, post-translation modifications, and protein functions were enriched with different stability patterns. Surprisingly, subunits of the TRIC molecular chaperonin possessed markedly distinct stability trajectories in the brain. Further investigation revealed that these subunits also possessed different subcellular localization and expression patterns that were uniquely altered with age and in Alzheimer’s disease transgenic mice, indicating a potential non-canonical chaperonin. Finally, QUAD analysis demonstrated that protein stability is enhanced with age in the brain but not in the liver. Overall, QUAD allows the first global quantitation of protein stability rates in tissues, which may lead to new insights and hypotheses in basic and translational research.SummaryProtein degradation is an important component of the proteostasis network, but no techniques are available to globally quantitate degradation rates in tissues. In this study, we demonstrate a new method QUAD (Quantification of Azidohomoalanine Degradation) that can accurately quantitate degradation rates in tissues. QUAD analysis of mouse tissues reveal that unique degradation trends can define different tissue proteomes. Within a tissue, specific protein characteristics are correlated with different levels of protein stability. Further investigation of the TRIC chaperonin with strikingly different subunit stabilities suggests a non-canonical chaperonin in brain tissue. Consistent with the theory that the proteostasis network is compromised with age, we discovered that protein stability is globally enhanced in brains of old mice compared to young mice.
The relationship between spatial configuration and functional connectivity of brain regions revisited
Authors: Bijsterbosch Janine D. , Beckmann Christian F. , Woolrich Mark W. , Smith Stephen M. , Harrison Samuel J. 
Published: January 2019

AbstractIn our previous paper (Bijsterbosch et al., 2018), we showed that network-based modelling of brain connectivity interacts strongly with the shape and exact location of brain regions, such that cross-subject variations in the spatial configuration of functional brain regions are being interpreted as changes in functional connectivity. Here we show that these spatial effects on connectivity estimates actually occur as a result of spatial overlap between brain networks. This is shown to systematically bias connectivity estimates obtained from group spatial ICA followed by dual regression. We introduce an extended method that addresses the bias and achieves more accurate connectivity estimates.Impact statementWe show that functional connectivity network matrices as estimated from resting state functional MRI are biased by spatially overlapping network structure.
Neuropathological validation of the MDS-PSP criteria with PSP and other frontotemporal lobar degeneration
Authors: Gazzina Stefano , Respondek Gesine , Compta Yaroslau , Allinson Kieren S.J. , Spillantini Maria G. , Molina-Porcel Laura , Guasp-Verdaguer Mar , Moftakhar Shirin , Reich Stephen G. , Hall Deborah , Litvan Irene , Höglinger Günter U. ,   Movement Disorder Society-endorsed PSP Study Group, Rowe James B. 
Published: January 2019

ABSTRACTBackgroundProgressive supranuclear palsy (PSP) is clinically heterogeneous. Clinical diagnostic criteria were revised in 2017, to increase sensitivity and operationalize the diagnosis of PSP Richardson’s syndrome (PSP-RS) and “variant” syndromes (vPSP).ObjectivesTo determine the (1) sensitivity and specificity of the 1996 NINDS-SPSP and 2017 MDS-PSP criteria; (2) false positive rates in frontotemporal dementia with frontotemporal lobar degeneration (FTLD); and (3) clinical evolution of variant PSP syndromes (vPSP).MethodsRetrospective multicenter review of 108 neuropathologically-confirmed PSP patients and 81 patients with other forms of FTLD: 38 behavioral variant frontotemporal dementia (bvFTD), 14 non-fluent/agrammatic variant primary progressive aphasia (nfvPPA), and 29 corticobasal degeneration (CBD), Sensitivity and specificity of the MDS-PSP criteria were compared to the NINDS-SPSP criteria at baseline. In a subset of cases, the timing and frequency of clinical features were compared across groups over six years.ResultsSensitivity for recognition of probable and possible PSP pathology was higher by MDS-PSP criteria (72.2-100%) than NINDS-SPSP criteria (48.1-61.1%). Specificity was higher by NINDS-SPSP criteria (97.5-100%) than MDS-PSP criteria (53.1-95.1%). False positives by MDS-PSP criteria were few for bvFTD (10.5-18.4%) but common for CBD and nfvPPA (fulfilling “suggestive of’ PSP). Most vPSP cases developed PSP-RS-like features within six years, including falls and supranuclear gaze palsy, distinguishing frontal presentations of PSP from bvFTD, and speech/language presentations of PSP from nfvPPA.ConclusionsThe 2017 MDS-PSP criteria successfully identify PSP, including variant phenotypes. This independent validation of the revised clinical diagnostic criteria strengthens the case for novel therapeutic strategies against PSP to include variant presentations.
Chromosome-level assembly of the common lizard (Zootoca vivipara) genome
Authors: Yurchenko Andrey A. , Recknagel Hans , Elmer Kathryn R. 
Published: January 2019

ABSTRACTSquamate reptiles exhibit high variation in their traits and geographical distribution and are therefore fascinating taxa for evolutionary and ecological research. However, high-quality genomic recourses are very limited for this group of species, which inhibits some research efforts. To address this gap, we assembled a high-quality genome of the common lizard Zootoca vivipara (Lacertidae) using a combination of high coverage Illumina (shotgun and mate-pair) and PacBio sequence data, with RNAseq data and genetic linkage maps. The 1.46 Gbp genome assembly has scaffold N50 of 11.52 Mbp with N50 contig size of 220.4 Kbp and only 2.96% gaps. A BUSCO analysis indicates that 97.7% of the single-copy Tetrapoda orthologs were recovered in the assembly. In total 19,829 gene models were annotated in the genome using a combination of three ab initio and homology-based methods. To improve the chromosome-level assembly, we generated a high-density linkage map from wild-caught families and developed a novel analytical pipeline to accommodate multiple paternity and unknown father genotypes. We successfully anchored and oriented almost 90% of the genome on 19 linkage groups. This annotated and oriented chromosome-level reference genome represents a valuable resource to facilitate evolutionary studies in squamate reptiles.
TORC2 Affects Endocytosis through Plasma Membrane Tension
Authors: Riggi Margot , Macchione Mariano , Matile Stefan , Loewith Robbie , Roux Aurélien 
Published: January 2019

AbstractTarget Of Rapamycin complex 2 (TORC2) is a conserved protein kinase that regulates multiple plasma membrane (PM)-related processes including endocytosis. Direct, chemical inhibition of TORC2 arrests endocytosis but with kinetics that are relatively slow and therefore inconsistent with signaling being mediated solely through simple phosphorylation cascades. Here, we show that, in addition to regulation of the phosphorylation of endocytic proteins, TORC2 also controls endocytosis by modulating PM tension. Elevated PM tension, upon TORC2 inhibition, impinges on endocytosis at two different levels: first, by severing the bonds between the PM adaptor proteins Sla2 and Ent1 and the actin cytoskeleton; and, second, by hindering recruitment of Rvs167, an N-BAR-containing protein important for vesicle fission, to endocytosis sites. These results underline the importance of biophysical cues in the regulation of cellular and molecular processes.
Coherent coding of spatial position mediated by theta oscillations in hippocampus and prefrontal cortex
Authors: Zielinski Mark C. , Shin Justin D. , Jadhav Shantanu P. 
Published: January 2019

ABSTRACTInteractions between the hippocampus (area CA1) and prefrontal cortex (PFC) are crucial for memory-guided behavior. Theta oscillations (~8 Hz) underlie a key physiological mechanism for mediating these coordinated interactions, and theta oscillatory coherence and phase-locked spiking in the two regions have been shown to be important for spatial memory. Hippocampal place cell activity associated with theta oscillations encodes spatial position during behavior, and theta-phase associated spiking is known to further mediate a temporal code for space within CA1 place fields. Although prefrontal neurons are prominently phase-locked to hippocampal theta oscillations in spatial memory tasks, whether and how theta oscillations mediate processing of spatial information across these networks remains unclear. Here, we addressed these questions using simultaneous recordings of dorsal CA1 – PFC ensembles and population decoding analyses in male rats performing a continuous spatial working memory task known to require hippocampal-prefrontal interactions. We found that in addition to CA1, population activity in PFC can also encode the animal’s current spatial position on a theta-cycle timescale during memory-guided behavior. Coding of spatial position was coherent for CA1 and PFC ensembles, exhibiting correlated position representations within theta cycles. In addition, incorporating theta-phase information during decoding to account for theta-phase associated spiking resulted in a significant improvement in the accuracy of prefrontal spatial representations, similar to concurrent CA1 representations. These findings indicate a theta-oscillation mediated mechanism of temporal coordination for shared processing and communication of spatial information across the two networks during spatial memory-guided behavior.
Diffusion Tensor Imaging connectivity analysis: detecting structural alterations and their underlying substrates for Optic Ataxia in correlations with “How” stream Visual Pathways
Authors: Elumalai Ganesh , Maiti Panchanan , Vinodhanand Geethanjali , Camoya Brown Valencia Lasandra , Venkata Ghanta Nitya Akarsha Surya , Krishna Kurra Venkata Hari 
Published: January 2019

ABSTRACTOptic ataxia is a neurological condition that shows clinical manifestations of disturbances in visual guided hand movements on reaching for a target object. Previous studies failed to provide substantial evidences for the neural structural pathway damaged by this condition. Therefore, this study was aimed to identify the neural structural connectivity between “Visual cortex with Superior Parietal Lobule” and to correlate its functional importance, using “Diffusion Imaging fiber Tractography. The fibers were traced, and we confirmed its extension from “Visual cortex (Brodmann’s Areas 18 and 19) to Superior Parietal Lobule (Brodmann’s Area 7)”. This new observation gives an insight to understand the structural existence and functional correlations between “Visual cortex with Superior Parietal Lobule” which is involved in targeting the grasping hand movements towards a visually perceived object, called visuo-motor coordination pathway or “how” stream pathways in visual perception. The observational analysis used thirty-two healthy adults, ultra-high b-value, diffusion MRI datasets from an Open access research platform. The datasets range between 20–49 years, in both sexes, with mean age of 31.1 years. The confirmatory observational analysis process includes, datasets acquisition, pre-processing, processing, reconstruction, fiber tractography and analysis using software tools. All the datasets confirmed that the fiber structural extension between, Visual cortex to superior parietal lobe in both the sexes may be responsible for the visual spatial recognition of objects. These new fiber connectivity evidences justify the structural relevance of visual spatial recognition impairments, such as optic ataxia.