bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of intercellular coupling and delay on the synchronization of genetic oscillators
Authors: Dey Supravat , Tracey Lee , Singh Abhyudai 
Published: October 2020

AbstractLiving cells encode diverse biological clocks for circadian timekeeping and formation of rhythmic structures during embryonic development. A key open question is how these clocks synchronize across cells through intercellular coupling mechanisms. To address this question, we leverage the classical motif for genetic clocks the Goodwin oscillator where a gene product inhibits its own synthesis via time-delayed negative feedback. More specifically, we consider an interconnected system of two identical Goodwin oscillators (each operating in a single cell), where state information is conveyed between cells via a signaling pathway whose dynamics is modeled as a first-order system. In essence, the interaction between oscillators is characterized by an intercellular coupling strength and an intercellular time delay that represents the signaling response time. Systematic stability analysis characterizes the parameter regimes that lead to oscillatory dynamics, with high coupling strength found to destroy sustained oscillations. Within the oscillatory parameter regime we find both in-phase and anti-phase oscillations with the former more likely to occur for small intercellular time delays. Finally, we consider the stochastic formulation of the model with low-copy number fluctuations in biomolecular components. Interestingly, stochasticity leads to qualitatively different behaviors where in-phase oscillations are susceptible to the inherent fluctuations but not the anti-phase oscillations. In the context of the segmentation clock, such synchronized in-phase oscillations between cells are critical for the proper generation of repetitive segments during embryo development that eventually leads to the formation of the vertebral column.
Leptin receptor expression in the dorsomedial hypothalamus stimulates breathing during NREM sleep indb/dbmice
Authors: Pho Huy , Berger Slava , Freire Carla , Kim Lenise J , Shin Mi-Kyung , Streeter Stone R , Hosamane Nishitha , Cabassa Meaghan E , Anokye-Danso Frederick , Dergacheva Olga , Amorim Mateus , Fleury-Curado Thomaz , Jun Jonathan J , Schwartz Alan R , Ahima Rexford S , Mendelowitz David , Polotsky Vsevolod Y 
Published: October 2020

ABSTRACTObesity can lead to recurrent upper airway obstruction (obstructive sleep apnea, OSA) during sleep as well as alveolar hypoventilation. We have previously shown that leptin stimulates breathing and treats OSA in leptin-deficientob/obmice and leptin-resistant diet-induced obese mice. Our previous data also suggest that leptin’s respiratory effects may occur in the dorsomedial hypothalamus (DMH). We selectively expressed leptin receptorLepRbin the DMH neurons of obeseLepRb-deficientdb/dbmice (LepRb-DMH mice), which hypoventilate at baseline, and showed that intracerebroventricular injection of leptin in these animals increased inspiratory flow, tidal volume and minute ventilation during NREM sleep without any effect on the quality of NREM sleep or CO2production. Leptin had no effect on upper airway obstruction inLepRb-DMHanimals. We conclude that leptin stimulates breathing and treats obesity related hypoventilation acting on LepRb-positive neurons in the DMH.
Syncmers are more sensitive than minimizers for selecting conservedk-mers in biological sequences
Authors: Edgar Robert C. 
Published: October 2020

AbstractMinimizers are widely used to select subsets of fixed-length substrings (k-mers) from biological sequences in applications ranging from read mapping to taxonomy prediction and indexing of large datasets. The minimizer of a string ofwconsecutivek-mers is thek-mer with smallest value according to an ordering of allk-mers. Syncmers are a family of alternative methods which selectk-mers by inspecting the position of the smallest-valued substring of lengths<kwithin thek-mer. For example, a closed syncmer selected if its smallests-mer is at the start of end of thek-mer. At least one closed syncmer must be found in every window of length (k–s)k-mers. Unlike a minimizer, a syncmer is identified by its sequence alone, and is therefore synchronized in the following sense: if a givenk-mer is selected from one sequence, it will also be selected from any other sequence. Also, minimizers can be deleted by mutations in flanking sequence, which cannot happen with syncmers. Experiments on minimizers with parameters used in the minimap2 read mapper and Kraken taxonomy prediction algorithm respectively show that syncmers can simultaneously achieve both lower density and higher conservation compared to minimizers.
Identification and transcriptional regulation of the mir-218-1 alternative promoter
Authors: Rheinheimer Brenna A. , Vrba Lukas , Futscher Bernard W , Heimark Ronald L 
Published: October 2020

AbstractBackgroundmiRNAs are small, endogenous non-coding RNAs approximately 22 nucleotides in length that account for approximately 1% of the genome and play key regulatory roles in multiple signaling pathways. mir-218-1 is an intronic miRNA located within intron 15 of theSLIT2gene. Public datasets showed enrichment of H3K4me3 within intron 4 of the SLIT2 gene. Therefore, we sought to determine the genomic location and transcriptional regulatory elements of the mir-218-1 candidate alternative promoter in pancreatic ductal adenocarcinoma.MethodsExpression of mir-218 was evaluated in a panel of pancreatic ductal adenocarcinoma cell lines. The mir-218-1 candidate alternative promoter was characterized by chromatin immunoprecipitation, Sequenom, and luciferase assays. Transcriptional regulation of the mir-218-1 candidate alternative promoter was assessed using chromatin immunoprecipitation and an inhibitor to NF-kB.ResultsWe found that expression of mir-218-1 does not correlate with SLIT2 expression and that mir-218-1 has a novel transcriptional start site separate from the SLIT2 promoter. This novel transcriptional start site showed transcriptional activity and was regulated by NF-kB.Conclusionsmir-218-1 is transcribed from an independent and novel transcriptional start site located within intron 4 of the SLIT2 gene in pancreatic ductal adenocarcinoma. Additionally, mir-218-1 expression is regulated by Nf-kB at this alternative transcriptional start site in pancreatic cancer.
Continuous Rate Modelling of bacterial stochastic size dynamics
Authors: Nieto Cesar , Vargas-Garcia Cesar , Pedraza Juan 
Published: October 2020

AbstractBacterial division is an inherently stochastic process. However, theoretical tools to simulate and study the stochastic transient dynamics of cell-size are scarce. Here, we present a general theoretical approach based on the Chapman-Kolmogorov formalism to describe these stochastic dynamics including continuous growth and division events as jump processes. Using this approach, we analyze the effect of different sources of noise on the dynamics of the size distribution. Oscillations in the distribution central moments were found as consequence of the discrete translation invariance of the system with period of one doubling time, these oscillations are found in both the central moments of the size distribution and the auto-correlation function and do not disappear including stochasticity on division times or size heterogeneity on the population but only after include noise in either growth rate or septum position.
A preferential role for ventromedial prefrontal cortex in assessing “the value of the whole” in multi-attribute object evaluation
Authors: Pelletier Gabriel , Aridan Nadav , Fellows Lesley K. , Schonberg Tom 
Published: October 2020

ABSTRACTEveryday decision-making commonly involves assigning values to complex objects with multiple value-relevant attributes. Drawing on object recognition theories, we hypothesized two routes to multi-attribute evaluation: assessing the value of the whole object based on holistic attribute configuration or summing individual attribute-values. In two samples of healthy human participants undergoing eye-tracking and fMRI while evaluating novel pseudo-objects, we found evidence for both forms of evaluation. Fixations to, and transitions between attributes differed systematically when value of pseudo-objects was associated with individual attributes or attribute configurations. Ventromedial prefrontal cortex (vmPFC) and perirhinal cortex were engaged when configural processing was required. These results converge with our recent findings that individuals with vmPFC lesions were impaired in decisions requiring configural evaluation, but not when evaluating “the sum of the parts”. This suggests that multi-attribute decision-making engages distinct evaluation mechanisms relying on partially dissociable neural substrates, depending on the relationship between attributes and value.SIGNIFICANCE STATEMENTDecision neuroscience has only recently begun to address how multiple choice-relevant attributes are brought together during evaluation and choice among complex options. Object recognition research makes a crucial distinction between individual attribute and holistic/configural object processing, but how the brain evaluates attributes and whole objects remains unclear. Using fMRI and eye-tracking, we found that the vmPFC and the perirhinal cortex contribute to value estimation specifically when it emerged from the whole objects i.e. predicted by the unique configuration of attributes, and not when value was predicted by the sum of individual attributes. This novel perspective on the interactions between subjective value and object processing mechanisms bridges an important gap between the fields of object recognition and reward-guided decision-making.
Experimental Estimate of Soil Nutrient Exchange in an Afrotropical Forest: The Role of Dung Beetle Community Complexity
Authors: Stanbrook Roisin 
Published: October 2020

AbstractDespite recognition of its importance, little is known about functional aspects of soil fauna. Here, we investigate the effect that different dung beetle functional groups have on macronutrient movement (N, P, K, and C) from dung into soil over 112-day period. We report a large overall effect where more macronutrients are moved into soil over time when beetles are present compared to a control treatment. We also report a large effect of beetle functional groupings on the amount of macronutrient movement, with larger dung beetles moving more nutrients over time. We provide the first experimental evidence that dung beetle body size directly influences macronutrient recycling and discuss the importance of dung beetle functional characteristics in maintaining soil fertility.
Epigenetic clock and DNA methylation analysis of porcine models of aging and obesity
Authors: Schachtschneider Kyle M. , Schook Lawrence B , Meudt Jennifer J. , Shanmuganayagam Dhanansayan , Zoller Joseph A. , Haghani Amin , Li Caesar Z. , Zhang Joshua , Yang Andrew , Raj Ken , Horvath Steve 
Published: October 2020

AbstractDNA-methylation profiles have been used successfully to develop highly accurate biomarkers of age, epigenetic clocks, for many species. Using a custom methylation array, we generated DNA methylation data from n=238 porcine tissues including blood, bladder, frontal cortex, kidney, liver and lung, from domestic pigs (Sus scrofa domesticus) and minipigs (Wisconsin Miniature Swine™). We present 4 epigenetic clocks for pigs that are distinguished by their compatibility with tissue type (pan-tissue and blood clock) and species (pig and human). Two dual-species human-pig pan-tissue clocks accurately measure chronological age and relative age, respectively. We also characterized CpGs that differ between minipigs and domestic pigs. Strikingly, several genes implicated by our epigenetic studies of minipig status overlap with genes (ADCY3, TFAP2B, SKOR1, andGPR61) implicated bygeneticstudies of body mass index in humans. In addition, CpGs with different levels of methylation between the two pig breeds were identified proximal to genes involved in blood LDL levels and cholesterol synthesis, of particular interest given the minipig’s increased susceptibility to cardiovascular disease compared to domestic pigs. Thus, inbred differences of domestic and minipigs may potentially help to identify biological mechanisms underlying weight gain and aging-associated diseases. Our porcine clocks are expected to be useful for elucidating the role of epigenetics in aging and obesity, and the testing of anti-aging interventions.
Single molecule dynamics of DNA receptor ComEA, membrane permease ComEC and taken up DNA in competentBacillus subtiliscells
Authors: Burghard-Schrod Marie , Kilb Alexandra , Krämer Kai , Graumann Peter L. 
Published: October 2020

AbstractIn competent gram-negative and gram-positive bacteria, double stranded DNA is taken up through the outer cell membrane and/or the cell wall, and is bound by ComEA, which inBacillus subtilisis a membrane protein. DNA is converted to single stranded DNA, and transported through the cell membrane via ComEC. We show that inBacillus subtilis, the C-terminus of ComEC, thought to act as a nuclease, is not only important for DNA uptake, as judged from a loss of transformability, but also for the localization of ComEC to the cell pole and its mobility within the cell membrane. Using single molecule tracking, we show that only 13% of ComEC molecules are statically localised at the pole, while 87% move throughout the cell membrane. These experiments suggest that recruitment of ComEC to the cell pole is mediated by a diffusion/capture mechanism. Mutation of a conserved aspartate residue in the C-terminus, likely affecting metal binding, strongly impairs transformation efficiency, suggesting that this periplasmic domain of ComEC could indeed serve a catalytic function as nuclease. By tracking fluorescently labeled DNA, we show that taken up DNA has a similar mobility within the periplasm as ComEA, suggesting that most taken up molecules are bound to ComEA. We show that DNA can be highly mobile within the periplasm, indicating that this subcellular space can act as reservoir for taken up DNA, before its entry into the cytosol.ImportanceBacteria can take up DNA from the environment and incorporate it into their chromosome in case similarity to the genome exists. This process of “natural competence” can result in the uptake of novel genetic information leading to horizontal gene transfer. We show that fluorescently labelled DNA moves within the periplasm of competentBacillus subtiliscells with similar dynamics as DNA receptor ComEA, and thus takes a detour to get stored before uptake across the cell membrane into the cytosol by DNA permease ComEC. The latter assembles at a single cell pole, likely by a diffusion-capture mechanism, and requires its large C-terminus, including a conserved residue thought to confer nuclease function, for proper localization, function and mobility within the membrane.
The Association of Late-Life Self-Reported Vision and Hearing Impairments with Cognitive Function: A 3-Year Longitudinal Mediation Analysis Through Social Isolation
Authors: Yorgason Jeremy B. , Tanner Corinna Trujillo , Richardson Stephanie , Hill Melanie S. , Stagg Brian , Wettstein Markus , Ehrlich Joshua R. 
Published: October 2020

AbstractBackground and ObjectivesVision impairment (VI), hearing impairment (HI), and dual sensory impairment (DSI), are prevalent among older adults and have been associated with cognitive impairment in later life. Knowledge about mediating pathways that account for the association between sensory impairment and cognitive impairment is scarce. Mediators of this association could serve as possible future intervention targets. We examined longitudinal associations between sensory impairment and cognitive functioning indirectly through social isolation.Research Design and MethodsData were taken from a nationally representative panel study, The National Health and Aging Trends Study, an annual survey of Medicare beneficiaries age ≥ 65. Participants (N = 6,286) from Rounds 5, 6, and 7 (2015, 2016, 2017), with complete data on self-reported VI and/or HI status at baseline. Structural equation models were estimated to test longitudinal direct and indirect associations.ResultsAdjusting for covariates, cross-sectional results indicated that all sensory impairments (VI, HI, and DSI) were negatively associated with all cognitive functioning measures through social isolation. Longitudinally, only VI was indirectly associated with word-recall scores across 1 and 2 years through social isolation, as well as across 2 years for orientation.Discussion and ImplicationsAs social isolation is both a consequence of sensory impairment and a risk factor for cognitive impairment, it provided a starting point from which to study the process of cognitive decline among those with sensory impairments. Awareness of the association of sensory impairment with social isolation, as well as its longitudinal implications for cognitive health, may enhance our ability to intervene.
Widely used mutants ofeiger, encoding theDrosophilaTumor Necrosis factor, carry additional mutations in the NimrodC1 phagocytosis receptor
Authors: Kodra Albana , de la Cova Claire , Gerhold Abigail R. , Johnston Laura A. 
Published: October 2020

AbstractThe process of apoptosis in epithelia involves activation of caspases, delamination of cells, and degradation of cellular components. Corpses and cellular debris are then rapidly cleared from the tissue by phagocytic blood cells. In studies of theDrosophilaTNF, Eiger (Egr) and cell death in wing imaginal discs, the epithelial primordia of fly wings, we noticed that dying cells persisted longer inegr3mutant wing discs than in wild type discs, raising the possibility that their phagocytic engulfment by hemocytes was impaired. Further investigation revealed that lymph glands and circulating hemocytes fromegr3mutant larvae were completely devoid of NimC1 staining, a marker of phagocytic hemocytes. Genome sequencing uncovered mutations in theNimC1coding region that are predicted to truncate the NimC1 protein before its transmembrane domain, and provide an explanation for the lack of NimC staining. The work that we report here demonstrates the presence of theseNimC1mutations in the widely usedegr3mutant, its sister allele,egr1, and its parental strain,Regg1GS9830. As theegr3andegr1alleles have been used in numerous studies of immunity and cell death, it may be advisable to re-evaluate their associated phenotypes.
Epithelial HVEM promotes basement membrane synthesis and intraepithelial T cell survival and migration
Authors: Takahashi Daisuke , Wang Qingyang , Seo Goo-Young , Shui Jr-wen , Mikulski Zbigniew , Marcovecchio Paola , Takahashi Masumi , Surh Charles D. , Cheroutre Hilde , Kronenberg Mitchell 
Published: October 2020

SummaryIntraepithelial T cells (IET) provide continuous surveillance of the intestinal epithelium, but little was known about how epithelial-derived signals regulate the IET population. We show that epithelial expression of the herpes virus entry mediator (HVEM), a member of the TNF receptor superfamily (TNFRSF), maintained the survival of small intestine IET, especially innate-like TCRαβ+cells lacking CD4 and CD8β. Patrolling movement of all CD8α+IET also was impaired in the absence of HVEM. HVEM-deficient epithelial cells exhibited downregulation of synthesis of basement membrane components, including collagen IV. Collagen IV supported IET survivalin vitrovia interactions with β1integrins expressed by the IET; absence of β1integrins decreased some IET subsets. Therefore, these data define a circuit whereby epithelial cells regulate intestine resident T lymphocyte populations through basement membrane synthesis.
DDX3X and DDX3Y are redundant in protein synthesis
Authors: Venkataramanan Srivats , Calviello Lorenzo , Wilkins Kevin , Floor Stephen N. 
Published: October 2020

AbstractDDX3 is a DEAD-box RNA helicase that regulates translation and is encoded by the X- and Y-linked paralogs DDX3X and DDX3Y. While DDX3X is ubiquitously expressed in human tissues and essential for viability, DDX3Y is male-specific and shows lower and more variable expression than DDX3X in somatic tissues. Heterozygous genetic lesions in DDX3X mediate a class of developmental disorders called DDX3X syndrome, while loss of DDX3Y is implicated in male infertility. One possible explanation for female-bias in DDX3X syndrome is that DDX3Y encodes a polypeptide with different biochemical activity. In this study, we use ribosome profiling and in vitro translation to demonstrate that the X- and Y-linked paralogs of DDX3 play functionally redundant roles in translation. We find that transcripts that are sensitive to DDX3X depletion or mutation are rescued by complementation with DDX3Y. Our data indicate that DDX3X and DDX3Y proteins can functionally complement each other in human cells. DDX3Y is not expressed in a large fraction of the central nervous system. These findings suggest that expression differences, not differences in paralog-dependent protein synthesis, underlie the sex-bias of DDX3X-associated diseases.
Phenotypic Differences in Adult and Fetal Dermal Fibroblast Responses to Mechanical Tension
Authors: Short Walker D. , Parikh Umang M. , Templeman Natalie , Olutoye Oluyinka O. , Blum Alexander , Colchado Daniel , Padon Benjamin , Kaul Aditya , Li Hui , Vangapandu Hima V. , Jung Olivia S. , Bommekal Pranav , Kogan Phillip , Fahrenholtz Monica M. , Coarfa Cristian , Balaji Swathi 
Published: October 2020

ABSTRACTObjectiveFetal regenerative wound healing is characterized by hyaluronan(HA)-rich microenvironment and fibroblasts that produce pericellular matrices(PCM) abundant in high molecular weight HA. Recent studies showed that while small wounds in fetal skin heal regeneratively, large wounds heal with fibrosis. We posit large wounds generate higher mechanical tension which alters HA metabolism in the fetal fibroblasts and lead to a pro-fibrotic phenotype.ApproachC57BL/6J murine fetal (FFB; E14.5) and adult (AFB; 8wk) dermal fibroblasts were subjected to +/-10% tonic strain. Changes in PCM, HA enzymes and molecular weight, and fibrotic gene expression were measured.ResultsFFB pericellular matrix reduced upon exposure to increased tension, and the HA profile shifted from high to lower molecular weight. Under static conditions, AFB had higher expression of HA synthases (HAS) 1 and 2 and degradation enzymes KIAA1199, HYAL1, and TMEM2 than FFB, suggesting more HA turnover in AFB. Tension resulted in an increase in HAS1, HAS3, KIAA1199, and HYAL2 expression and a decrease in HAS2 and TMEM2 expression in FFB. CD26, a marker associated with scar production, increased in FFB under tension, along with altered fibrotic gene expression profile and reorganized cytoskeletal f-actin and increased α-SMA that resembled AFB.InnovationThis study elucidates the differences in how biomechanical tension alters HA metabolism and fibrotic phenotype of FFB vs AFB, providing further understanding of the fetal regenerative wound healing phenotype.ConclusionUnderstanding the intrinsic differences in HA metabolism and fibrotic phenotype among FFB and AFB in response to wound mechanical stimuli may yield new insights to promote regenerative wound healing.