bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduction of a Stochastic Model of Gene Expression: Lagrangian Dynamics Gives Access to Basins of Attraction as Cell Types and Metastabilty
Authors: Ventre Elias , Espinasse Thibault , Bréhier Charles-Edouard , Calvez Vincent , Lepoutre Thomas , Gandrillon Olivier 
Published: September 2020

AbstractDifferentiation is the process whereby a cell acquires a specific phenotype, by differential gene expression as a function of time. This is thought to result from the dynamical functioning of an underlying Gene Regulatory Network (GRN). The precise path from the stochastic GRN behavior to the resulting cell state is still an open question. In this work we propose to reduce a stochastic model of gene expression, where a cell is represented by a vector in a continuous space of gene expression, to a discrete coarse-grained model on a limited number of cell types. We develop analytical results and numerical tools to perform this reduction for a specific model characterizing the evolution of a cell by a system of piecewise deterministic Markov processes (PDMP). Solving a spectral problem, we find the explicit variational form of the rate function associated to a large deviations principle, for any number of genes. The resulting Lagrangian dynamics allows us to define a deterministic limit of which the basins of attraction can be identified to cellular types. In this context the quasipotential, describing the transitions between these basins in the weak noise limit, can be defined as the unique solution of an Hamilton-Jacobi equation under a particular constraint. We develop a numerical method for approximating the coarse-grained model parameters, and show its accuracy for a symmetric toggle-switch network. We deduce from the reduced model an approximation of the stationary distribution of the PDMP system, which appears as a Beta mixture. Altogether those results establish a rigorous frame for connecting GRN behavior to the resulting cellular behavior, including the calculation of the probability of jumps between cell types.
Aging selectively dampens oscillation of lipid abundance in white and brown adipose tissue
Authors: Held Ntsiki M. , Buijink M. Renate , Elfrink Hyung L. , Kooijman Sander , Janssens Georges E. , Vaz Frédéric M. , Michel Stephan , Houtkooper Riekelt H. , van Weeghel Michel 
Published: September 2020

AbstractLipid metabolism is under the control of the circadian system and circadian dysregulation has been linked to obesity and dyslipidemia. These factors and outcomes have also been associated to, or affected by, the process of aging. Here, we investigated whether murine white (WAT) and brown (BAT) adipose tissue lipids exhibit rhythmicity and if this is affected by aging. To this end, we have measured the 24 hour lipid profiles of WAT and BAT using a global lipidomics analysis of >1100 lipids. We observed rhythmicity in nearly all lipid classes including glycerolipids, glycerophospholipids, sterol lipids and sphingolipids. Overall, ~22% of the analyzed lipids were considered rhythmic in WAT and BAT. Despite a general accumulation of lipids upon aging the fraction of oscillating lipids decreased in both tissues to 14% and 18%, respectively. Diurnal profiles of lipids in BAT appeared to depend on the lipid acyl chain length and this specific regulation was lost in aged mice. Our study revealed how aging affects the rhythmicity of lipid metabolism and could contribute to the quest for targets that improve diurnal lipid homeostasis to maintain cardiometabolic health during aging.
Infra Red Thermography Reveals Transpirational Cooling in Pearl Millet (Pennisetum glaucum) Plants Under Heat Stress
Authors: Shanker Arun K. , Bhanu Divya , Sarkar Basudev , Yadav S.K. , Jyothilakshmi N. , Maheswari M. 
Published: September 2020

AbstractAn infra red thermographic analysis of well watered control and well watered heat stressed pearl millet (Pennisetum glaucum) was conducted at ICAR – Central Research Institute for Dryland Agriculture as a part of high resolution phenomics studies to identify the individual quantitative physiological parameters by plant phenotyping that form the basis for more complex abiotic stress tolerant traits. It was seen that the temperature gradient increased gradually from ground level to the top in the control non heat stressed plant. In contrast, it was seen that in the heat stressed plant the temperature increased up to the middle of the plant and then started to decrease at the top of the plant in comparison with the non heat stressed control plant. Our results indicate that the lowering of temperatures in the top of the heat stressed plant may be a mechanism by which the heat stressed plant acclimates to stress by regulating its transpiration thereby bringing in a cooling effect to counter stress.
Relationship of taxonomic error to frequency of observation
Authors: Stribling James B. , Leppo Erik W. 
Published: September 2020

AbstractBiological nomenclature is the entry point to a wealth of information related to or associated with living entities. When applied accurately and consistently, communication between and among researchers and investigators is enhanced, leading to advancements in understanding and progress in research programs. Based on freshwater benthic macroinvertebrate taxonomic identifications, inter-laboratory comparisons of >900 samples taken from rivers, streams, and lakes across the U.S., including the Great Lakes, provided data on taxon-specific error rates. Using the error rates in combination with frequency of observation (FREQ; as a surrogate for rarity), six uncertainty/frequency classes (UFC) are proposed for approximately 1,000 taxa. The UFC, error rates, FREQ each are potentially useful for additional analyses related to interpreting biological assessment results and/or stressor response relationships, as weighting factors for various aspects of ecological condition or biodiversity analyses and helping set direction for taxonomic research and refining identification tools.
Cis-Regulatory Differences Explaining Evolved Levels of Endometrial Invasibility in Eutherian Mammals
Authors: Suhail Yasir , Maziarz Jamie D. , Dighe Anasuya , Wagner Gunter , Kshitiz  
Published: September 2020

AbstractEutherian (placental) mammals exhibit great differences in the degree of placental invasion into the maternal endometrium, with humans being on the most invasive end. Previously, we have shown that these differences in invasiveness is largely controlled by the stromal fibroblasts of the maternal endometrium, with secondary effect on stroma of other tissues resulting in correlated differences in cancer malignancy. Here, we present a statistical investigation of the second dogma linking the phenotypic and transcriptional differences to the genomic changes across species, revealing the regulatory genomic sequence differences underlying these inter-species differences. We show that gain or loss of specific transcription factor binding site sequences are connected to the inter-species gene-expression differences in a statistically significant manner, with a particularly larger effect on stromal genes related to invasibility. We also uncover transcriptional factors differentially regulating genes related to pro- and anti- invasible property of stroma. This work extends the understanding of inter-species differences in stromal invasion to the causal genomic sequence differences paving new avenues to target stromal characteristics to regulate placental, or cancer invasion.
Neuroendocrine and behavioral measures of stress-reactivity in male goal-tracker and sign-tracker rats
Authors: Lopez Sofia A. , Mubarak Eman , Yang Charlotte , Parsegian Aram , Klumpner Marin , Campus Paolo , Flagel Shelly B. 
Published: September 2020

AbstractEnvironmental cues attain the ability to guide behavior via learned associations. As predictors, cues can elicit adaptive behavior and lead to valuable resources (e.g., food). For some individuals, however, cues are transformed into incentive stimuli and elicit motivational states that can be maladaptive. The goal-tracker/sign-tracker animal model captures individual differences in cue-motivated behaviors, with reward-associated cues serving as predictors of reward for both phenotypes but becoming incentive stimuli to a greater degree for sign-trackers. While these distinct phenotypes are characterized based on Pavlovian conditioned approach behavior, they exhibit differences on a number of behaviors relevant to psychopathology. To further characterize the neurobehavioral endophenotype associated with individual differences in cue-reward learning, neuroendocrine and behavioral profiles associated with stress and anxiety were investigated in male goal-tracker, sign-tracker, and intermediate responder rats. It was revealed that baseline corticosterone increases with Pavlovian learning, but to the same degree, regardless of phenotype. No significant differences in behavior were observed between goaltrackers and sign-trackers during an elevated plus maze or open field test, nor were there differences in corticosterone response to the open field test or physiological restraint. Upon examination of central markers associated with stress-reactivity, we found that sign-trackers have greater glucocorticoid receptor mRNA expression in the ventral hippocampus, with no phenotypic differences in the dorsal hippocampus or prelimbic cortex. These findings demonstrate that goal-trackers and sign-trackers do not differ on stress- and anxiety-related behaviors, and suggest that differences in neuroendocrine measures between these phenotypes can be attributed to distinct cue-reward learning styles.Significance StatementWhile the goal-tracker/ sign-tracker animal model derives from individual differences in Pavlovian conditioned approach behavior, other traits, including some of relevance to addiction and post-traumatic stress disorder, have been shown to co-exist with the propensity to sign-track. The extent to which this model encompasses differences in aversive arousal and associated neuroendocrine measures, however, remains largely unexplored. Here we show that behavioral and corticosterone response to stress-related paradigms do not differ between goal-trackers and sign-trackers. However, glucocorticoid receptor expression in the ventral hippocampus does differ between phenotypes, suggesting that this central marker that is typically associated with stress-responsivity, may, in fact, play an important role in appetitive motivation.
Identification of genetic factors controlling phosphorus utilization efficiency in wheat by genome-wide association study with principal component analysis
Authors: Safdar Luqman Bin , Umer Muhammad Jawad , Almas Fakhrah , Uddin Siraj , Safdar Qurra-tul-Ain , Blighe Kevin , Quraishi Umar Masood 
Published: September 2020

ABSTRACTDespite the economic importance of P utilization efficiency, information on genetic factors underlying this trait remains elusive. To address that, we performed a genome-wide association study in a spring wheat diversity panel ranging from landraces to elite varieties. We evaluated the phenotype variation for P utilization efficiency in controlled conditions and genotype variation using wheat 90K SNP array. Phenotype variables were transformed into a smaller set of uncorrelated principal components that captured the most important variation data. We identified two significant loci associated with both P utilization efficiency and the 1st principal component on chromosomes 3A and 4A:qPE1-3AandqPE2-4A. Annotation of genes at these loci revealed 53 wheat genes, among which 6 were identified in significantly enriched pathways. The expression pattern of these 6 genes indicated thatTraesCS4A02G481800, involved in pyruvate metabolism and TCA cycle, had a significantly higher expression in the P efficient variety under limited P conditions. Further characterization of these loci and candidate genes can help stimulate P utilization efficiency in wheat.KEY MESSAGEWe report two new loci for P utilization efficiency on chromosomes 3A and 4A of wheat. The prioritized candidate genes at these loci can be investigated by molecular biology techniques to improve P efficiency in wheat and grass relatives.
Electrophysiological Indicators of Sleep-associated Memory Consolidation in 5- to 6-Year-Old Children
Authors: Joechner Ann-Kathrin , Wehmeier Sarah , Werkle-Bergner Markus 
Published: September 2020

AbstractIn adults, the synchronised interplay of sleep spindles (SP) and slow oscillations (SO) supports memory consolidation. Given tremendous developmental changes in SP and SO morphology, it remains elusive whether across childhood the same mechanisms as identified in adults are functional. Based on topography and frequency, we characterise slow and fast SPs and their temporal coupling to SOs in 24 pre-school children. Further, we ask whether slow and fast SPs and their modulation during SOs are associated with behavioural indicators of declarative memory consolidation as suggested by the literature on adults. Employing an individually tailored approach, we reliably identify an inherent, development-specific fast centro-parietal SP type, nested in the adult-like slow SP frequency range, along with a dominant slow frontal SP type. Further, we provide evidence that the modulation of fast centro-parietal SPs during SOs is already present in pre-school children. However, the temporal coordination between fast centro-parietal SPs and SOs is weaker and less precise than expected from research on adults. While we do not find evidence for a critical contribution of SP–SO coupling for memory consolidation, crucially, slow frontal and fast centro-parietal SPs are each differentially related to sleep-associated consolidation of items of varying quality. While a higher number of slow frontal SPs is associated with stronger maintenance of medium-quality memories, a higher number of fast centro-parietal SPs is linked to a greater gain of low-quality items. Our results demonstrate two functionally relevant inherent SP types in pre-school children although SP–SO coupling is not yet fully mature.
Stable 3D Head Direction Signals in the Primary Visual Cortex
Authors: Guitchounts Grigori , Lotter William , Dapello Joel , Cox David 
Published: September 2020

AbstractVisual signals influence the brain’s computation of spatial position and orientation. Accordingly, the primary visual cortex (V1) is extensively interconnected with areas involved in computing head direction (HD) information. Predictive coding theories posit that higher cortical areas send sensory or motor predictions to lower areas, but whether this includes cognitive variables like the HD signal—and whether HD information is present in V1—is unknown. Here we show that V1 encodes the yaw, roll, and pitch of the head in freely behaving rats, either in the presence or absence of visual cues. HD tuning was modulated by lighting and movement state, but was stable on a population level for over a week. These results demonstrate the presence of a critical spatial orientation signal in a primary cortical sensory area and support predictive coding theories of brain function.
Soil characteristics constrain the response of bacterial and fungal communities and hydrocarbon degradation genes to phenanthrene soil contamination and phytoremediation with poplars
Authors: Correa-García Sara , Rheault Karelle , Tremblay Julien , Séguin Armand , Yergeau Etienne 
Published: September 2020

AbstractRhizodegradation is a promising cleanup technology where microorganisms degrade soil contaminants in the rhizosphere. A symbiotic relationship is expected to occur between plant roots and soil microorganisms in contaminated soils that enhance natural microbial degradation in soils. However, little is known about how this initial microbiota influences the rhizodegradation outcome in a context of different soil microbiotas. Recent studies have hinted that soil initial diversity has a determining effect on the outcome of contaminant degradation. To test this hypothesis, we planted (P) or not (NP) balsam poplars (Populus balsamifera) in two soils of contrasting diversity (agricultural and forest) that were contaminated or not with 50 mg kg-1of phenanthrene (PHE). The DNA from the rhizosphere of the P and the bulk soil of the NP pots was extracted and the bacterial genes encoding for the 16S rRNA, the PAH ring-hydroxylating dioxygenase alpha subunits (PAH-RHDα) of gram-positive (GP) and gram-negative (GN) bacteria, and the fungal ITS region were sequenced to characterize the microbial communities. and the abundance of the PAH-RHDα genes were also quantified by real-time quantitative PCR. Plant presence had a significant effect on PHE degradation only in the forest soil, whereas both NP and P agricultural soils degraded the same amount of PHE. Bacterial communities were principally affected by the soil type, and upon contamination the dominant PAH degrading community was similarly constrained by soil type. Our results highlight the crucial importance of soil microbial and physicochemical characteristics in the outcome of rhizoremediation.
Deletion of Mcpip1 in Mcpip1AlbKOmice recapitulates the phenotype of human primary biliary cholangitis
Authors: Kotlinowski Jerzy , Hutsch Tomasz , Czyzynska-Cichon Izabela , Wadowska Marta , Pydyn Natalia , Jasztal Agnieszka , Kij Agnieszka , Dobosz Ewelina , Lech Maciej , Miekus Katarzyna , Pośpiech Ewelina , Fu Mingui , Jura Jolanta , Koziel Joanna , Chlopicki Stefan 
Published: September 2020

AbstractBackground & AimsPrimary biliary cholangitis (PBC) is an autoimmune disease characterized by progressive destruction of the intrahepatic bile ducts. The immunopathology of PBC involves excessive inflammation; therefore, negative regulators of inflammatory response, such as Monocyte Chemoattractant Protein-1-Induced Protein-1 (MCPIP1,aliasRegnase1) may play important roles in the development of PBC. The aim of this work was to verify whether Mcpip1 expression protects against development of PBC.MethodsGenetic deletion ofZc3h12awas used to characterize the role of Mcpip1 in the pathogenesis of PBC. 6-52-week-old Mcpip1fl/fland Mcpip1AlbKOmice were used for immunohistochemical, biochemical and molecular tests.ResultsWe found that Mcpip1 deficiency in the liver recapitulates most of the features of human PBC, in contrast to mice with Mcpip1 deficiency in myeloid cells (Mcpip1LysMKOmice), which present with robust myeloid cell-driven systemic inflammation. In Mcpip1AlbKOlivers, intrahepatic bile ducts displayed proliferative changes with inflammatory infiltration, bile duct destruction, and fibrosis leading to cholestasis. In plasma, increased concentrations of IgG, IgM, and AMA autoantibodies (anti-PDC-E2) were detected. Interestingly, the phenotype of Mcpip1AlbKOmice was robust in 6-week-old and 52-week-old mice, but milder in 12-24-week-old mice, suggesting early prenatal origin of the phenotype and age-dependent progression of the disease. Hepatic transcriptome analysis of 6-week-old and 24-week-old Mcpip1AlbKOmice showed 812 and 8 differentially expressed genes (DEGs), respectively, compared with age-matched control mice, and revealed a distinct set of genes compared to those previously associated with development of PBC.ConclusionsThe phenotype of Mcpip1AlbKOmice recapitulates most of the features of human PBC, and demonstrates early prenatal origin and age-dependent progression of PBC. Therefore, Mcpip1AlbKOmice provide a unique model for the study of PBC.Lay summaryDeletion of hepatic Mcpip1 in Mcpip1AlbKOmice leads to development of PBC that recapitulates phenotype of human patients. These animals, show early prenatal origin and age-dependent progression of the disease. Thus, Mcpip1AlbKOmice provide a unique model for studying PBC.
TRPV1 feed-forward sensitisation depends on COX2 upregulation in primary sensory neurons
Authors: Li Tianci , Wang Gaoge , Chin Hui Vivian Chin , Saad Daniel , de Sousa Valente Joao , Montanara Paolo La , Nagy Istvan 
Published: September 2020

ABSRTRACTIncreased activity and excitability (sensitisation) of a series of molecules including the transient receptor potential ion channel, vanilloid subfamily, member 1 (TRPV1) in pain-sensing (nociceptive) primary sensory neurons are pivotal for developing pathological pain experiences in tissue injuries. TRPV1 sensitisation is induced and maintained by two major mechanisms; post-translational and transcriptional changes in TRPV1 induced by inflammatory mediators produced and accumulated in injured tissues, and TRPV1 activation-induced feed-forward signalling. The latter mechanism includes synthesis of TRPV1 agonists within minutes, and upregulation of various receptors functionally linked to TRPV1 within a few hours, in nociceptive primary sensory neurons. Here, we report that a novel mechanism, which contributes to TRPV1 activation-induced TRPV1-sensitisation within ~30 minutes in at least ~30% of TRPV1-expressing cultured murine primary sensory neurons, is mediated through upregulation in cyclooxygenase 2 (COX2) expression and increased synthesis of a series of COX2 products. These findings highlight the importance of feed-forward signalling in sensitisation, and the value of inhibiting COX2 activity to control pain, in nociceptive primary sensory neurons in tissue injuries.
RNA LEVER Mediates Long-Range Regulation of ε-globin by Keeping PRC2 in Check
Authors: Teo Wei Wen , Cao Xinang , Wu Chan-Shuo , Tan Hong Kee , Zhou Qiling , Yang Henry , Chai Li , Tenen Daniel G. 
Published: September 2020

SummaryPolycomb Repressive Complex 2 (PRC2) is an epigenetic regulator required for gene silencing during embryonic development. Previous studies have reported that PRC2 interacts with RNA in a promiscuous manner, but the biological functions of such interaction are unknown. Here we present a seesaw mechanism for the regulation of ε-globin through inactivatingEZH2 by an upstream non-codingRNA (LEVER). We show that LEVER, a non-coding RNA identified by RNA immunoprecipitation sequencing (RIP-seq) of the PRC2 core subunit EZH2 and Nanopore sequencing, binds PRC2 and thereby prevents the accumulation of H3K27 methylation along the genomic region where LEVER RNA is transcribed. The open chromatin within the LEVER locus in turn competes for the chromatin interaction between the ε-globin promoter and the Locus Control Region (LCR), working as a negative regulatory element of ε-globin expression. Hence, LEVER RNA negatively regulates ε-globin by sequestering PRC2 from repressing the LEVER locus, which is a competitor of the ε-globin-LCR interaction.
rab-27acts in an intestinal secretory pathway to inhibit axon regeneration inC. elegans
Authors: Lin-Moore Alexander T. , Oyeyemi Motunrayo J. , Hammarlund Marc 
Published: September 2020

ABSTRACTInjured axons must regenerate to restore nervous system function, and regeneration is regulated in part by external factors from non-neuronal tissues. Many of these extrinsic factors act in the immediate cellular environment of the axon to promote or restrict regeneration, but the existence of long-distance signals regulating axon regeneration has not been clear. Here we show that the Rab GTPaserab-27inhibits regeneration of GABAergic motor neurons inC. elegansthrough activity in the intestine. Re-expression of RAB-27, but not the closely related RAB-3, in the intestine ofrab-27mutant animals is sufficient to rescue normal regeneration. Several additional components of an intestinal neuropeptide secretion pathway also inhibit axon regeneration, including NPDC1/cab-1, SNAP25/aex-4, and KPC3/aex-5. Together these data indicate that RAB-27-dependent neuropeptide secretion from the intestine inhibits axon regeneration, and point to distal tissues as potent extrinsic regulators of regeneration.