bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mixture distributions in a stochastic gene expression model with delayed feedback
Authors: Bokes Pavol , Borri Alessandro , Palumbo Pasquale , Singh Abhyudai 
Published: November 2019

AbstractNoise in gene expression can be substantively affected by the presence of production delay. Here we consider a mathematical model with bursty production of protein, a one-step production delay (the passage of which activates the protein), and feedback in the frequency of bursts. We specifically focus on examining the steady-state behaviour of the model in the slow-activation (i.e. large-delay) regime. Using a quasi-steady-state (QSS) approximation, we derive an autonomous ordinary differential equation for the inactive protein that applies in the slow-activation regime. If the differential equation is monostable, the steady-state distribution of the inactive (active) protein is approximated by a single Gaussian (Poisson) mode located at the globally stable steady state of the differential equation. If the differential equation is bistable (due to cooperative positive feedback), the steady-state distribution of the inactive (active) protein is approximated by a mixture of Gaussian (Poisson) modes located at the stable steady states; the weights of the modes are determined from a WKB approximation to the stationary distribution. The asymptotic results are compared to numerical solutions of the chemical master equation.
Extracellular electron transfer-dependent anaerobic oxidation of ammonium by anammox bacteria
Authors: Shaw Dario R. , Ali Muhammad , Katuri Krishna P. , Gralnick Jeffrey A. , Reimann Joachim , Mesman Rob , van Niftrik Laura , Jetten Mike S. M. , Saikaly Pascal E. 
Published: November 2019

AbstractAnaerobic ammonium oxidation (anammox) by anammox bacteria contributes significantly to the global nitrogen cycle, and plays a major role in sustainable wastewater treatment. Anammox bacteria convert ammonium (NH4+) to dinitrogen gas (N2) using nitrite (NO2−) or nitric oxide (NO) as the electron acceptor. In the absence of NO2−or NO, anammox bacteria can couple formate oxidation to the reduction of metal oxides such as Fe(III) or Mn(IV). Their genomes contain homologs ofGeobacterandShewanellacytochromesinvolved in extracellularelectron transfer (EET). However, it is still unknown whether anammox bacteria have EET capability and can couple the oxidation of NH4+with transfer of electrons to carbon-based insoluble extracellular electron acceptors. Here we show using complementary approaches that in the absence of NO2−, freshwater and marine anammox bacteria couple the oxidation of NH4+with transfer of electrons to carbon-based insoluble extracellular electron acceptors such as graphene oxide (GO) or electrodes poised at a certain potential in microbial electrolysis cells (MECs). Metagenomics, fluorescencein-situhybridization and electrochemical analyses coupled with MEC performance confirmed that anammox electrode biofilms were responsible for current generation through EET-dependent oxidation of NH4+.15N-labelling experiments revealed the molecular mechanism of the EET-dependent anammox process. NH4+was oxidized to N2via hydroxylamine (NH2OH) as intermediate when electrode was the terminal electron acceptor. Comparative transcriptomics analysis supported isotope labelling experiments and revealed an alternative pathway for NH4+oxidation coupled to EET when electrode is used as electron acceptor compared to NO2−as electron acceptor. To our knowledge, our results provide the first experimental evidence that marine and freshwater anammox bacteria can couple NH4+oxidation with EET, which is a significant finding, and challenges our perception of a key player of anaerobic oxidation of NH4+in natural environments and engineered systems.
Mitochondrial substitution rates estimation for molecular clock analyses in modern birds based on full mitochondrial genomes
Authors: Arcones Angel , Ponti Raquel , Vieites David R. 
Published: November 2019

AbstracttiMitochondrial DNA (mtDNA) is a very popular resource in the study of evolutionary processes in birds, and especially to infer divergence times between lineages. These inferences rely on rates of substitution in the mtDNA genes that, ideally, are specific for the studied taxa. But as such values are often unavailable many studies fixed rate values generalised from other studies, such as the popular “standard molecular clock”. However the validity of these universal rates across all bird lineages and for the different mtDNA has been severely questioned. Thus, we here performed the most comprehensive calibration of the mtDNA molecular clock in birds, with the inclusion of complete mitochondrial genomes for 622 bird species and 25 reliable fossil calibrations. The results show variation in the rates between lineages and especially between markers, contradicting the universality of the standard clock. Moreover, we provide especific rates for every mtDNA marker (except D-loop) in each of the sampled avian orders, which should help improve future estimations of divergence times between bird species or populations.
Mechano-calcium and mechano-electric feedbacks in the human cardiomyocyte analyzed in a mathematical model
Authors: Balakina-Vikulova Nathalie A. , Panfilov Alexander , Solovyova Olga , Katsnelson Leonid B. 
Published: November 2019

AbstractExperiments on animal hearts (rat, rabbit, guinea pig, etc.) have demonstrated that mechano-calcium feedback (MCF) and mechano-electric feedback (MEF) are very important for myocardial self-regulation because they adjust the cardiomyocyte contractile function to various mechanical loads and to mechanical interactions between heterogeneous myocardial segments in the ventricle walls. Inin vitroexperiments on these animals, MCF and MEF manifested themselves in several basic classical phenomena (e.g. load dependence, length dependence of isometric twitches, etc.), and in the respective responses of calcium transients and action potentials. However, it is extremely difficult to study simultaneously the electrical, calcium, and mechanical activities of the human heart musclein vitro. Mathematical modeling is a useful tool for exploring these phenomena. We have developed a novel model to describe electromechanical coupling and mechano-electric feedbacks in the human cardiomyocyte. It combines the ‘ten Tusscher – Panfilov’ electrophysiological model of the human cardiomyocyte with our module of myocardium mechanical activity taken from the ‘Ekaterinburg – Oxford’ model and adjusted to human data. Using it, we simulated isometric and afterloaded twitches and effects of MCF and MEF on excitation-contraction coupling. MCF and MEF were found to affect significantly the duration of the calcium transient and action potential in the human cardiomyocyte model in response to both smaller afterloads as compared to bigger ones and various mechanical interventions applied during isometric and afterloaded twitches.
Intravenous indocyanine green dye is insufficient for robust immune cell labelling in the human retina
Authors: Bell Oliver H. , Carreño Ester , Williams Emily L. , Wu Jiahui , Copland David A. , Bora Monalisa , Kobayter Lina , Fruttiger Marcus , Sim Dawn A. , Lee Richard W.J. , Dick Andrew D. , Chu Colin J. 
Published: November 2019

AbstractIt is not currently possible to reliably visualise and track immune cells in the human central nervous system or eye. Previous work demonstrated that indocyanine green (ICG) dye could label immune cells and be imaged after a delay during disease in the mouse retina. We report a pilot study investigating if ICG can similarly label immune cells within the human retina. Twelve adult participants receiving ICG angiography as part of routine standard of care were recruited. Baseline retinal images were obtained prior to ICG administration then repeated over a period ranging from 2 hours to 9 days. Matched peripheral blood samples, in addition to human and mouse macrophage cultures as controls, were analysed by flow cytometry. Differences between the delayed near infrared ICG imaging and 488 nm autofluorescence was observed across pathologies, likely arising from the retinal pigment epithelium (RPE). Only one subject demonstrated ICG signal on peripheral blood myeloid cells and only three distinct cell-sized signals appeared over time within the retina of three participants. No significant increase in immune cell activation markers were detected after ICG administration. ICG accumulated in the endosomes of macrophage cultures and was detectable above a minimum concentration, suggesting cell labelling is possible. ICG can label RPE and may be used as an additional biomarker for cell health across a range of retinal disorders. Standard clinical doses of intravenous ICG do not lead to robust immune cell labelling in human blood or retina and further optimisation in dose and route are required.
Insulin signal transduction is impaired in the type 2 diabetic retina
Authors: Jiang Youde , Liu Li , Li Hainan , Wang Jie-Mei , Steinle Jena J. 
Published: November 2019

AbstractRates of type 2 diabetes are reaching epidemic levels. Yet, the tissue specific alterations due to insulin resistance are only recently being investigated. The goal of the present study was to evaluate retinal insulin signal transduction in a common mouse model of type 2 diabetes, the db/db mouse. Retinal lysates from five month old male db/db and db/+ (control) mice were collected and processed for Western blotting or ELISA analyses for insulin receptor, insulin receptor substrate-1 (IRS-1), Akt, tumor necrosis factor alpha (TNFα) and caspase 3 levels. Data demonstrate increased TNFα and IRS-1 phosphorylation on serine 307. This led to decreased Akt phosphorylation on serine 473 and increased cleavage of caspase 3. Taken together, the data suggest dysfunctional insulin signaling in the retina of the db/db mouse.
A field experiment to assess passage of juvenile salmonids across beaver dams during low flow conditions in a tributary to the Klamath River, California, USA
Authors: Pollock Michael Moritz , Witmore Shari , Yokel Erich 
Published: November 2019

ABSTRACTAcross Eurasia and North America, beaver (Castorspp), their dams and their human-built analogues are becoming increasingly common restoration tools to facilitate recovery of streams and wetlands, providing a natural and cost-effective means of restoring dynamic fluvial ecosystems. Although the use of beaver ponds by numerous fish and wildlife species is well documented, debate continues as to the benefits of beaver dams, primarily because dams are perceived as barriers to the movement of fishes, particularly migratory species such as salmonids. In this study, through a series of field experiments, we tested the ability of juvenile salmonids to cross constructed beaver dams (aka beaver dam analogues). Two species, coho salmon (Oncorhynchus kisutch) and steelhead trout (O. mykiss), were tracked using passive integrated transponder tags (PIT tags) as they crossed constructed beaver dams. We found that when we tagged and moved late-summer parr from immediately upstream of the dams to immediately downstream of them, most of them were detected upstream within 36 hours of displacement. By the end of a 21-day field experiment, 91% of the displaced juvenile coho and 54% of the juvenile steelhead trout were detected on antennas upstream of the dams while <1% of the coho and 15% of the steelhead trout were detected on antennas in the release pool below the dams. A similar but shorter 4-day pilot experiment with only steelhead trout produced similar results. In contrast, in a non-displacement experiment, juveniles of both species that were captured, tagged and released in a pool 50 m below the dams showed little inclination to move upstream. Finally by measuring hydraulic conditions at the major flowpaths over and around the dams, we provide insight into conditions under which juvenile salmonids are able to cross these constructed beaver dams, which should help guide future restoration efforts.
An Escherichia coli Chassis for Production of Electrically Conductive Protein Nanowires
Authors: Ueki Toshiyuki , Walker David J.F. , Woodard Trevor L. , Nevin Kelly P. , Nonnenmann Stephen S. , Lovley Derek R. 
Published: November 2019

AbstractGeobacter sulfurreducens’ pilin-based electrically conductive protein nanowires (e-PNs) are a revolutionary electronic material. They offer novel options for electronic sensing applications and have the remarkable ability to harvest electrical energy from atmospheric humidity. However, technical constraints limit mass cultivation and genetic manipulation of G. sulfurreducens. Therefore, we designed a strain of Escherichia coli to express e-PNs by introducing a plasmid that contained an inducible operon with E. coli genes for type IV pili biogenesis machinery and a synthetic gene designed to yield a peptide monomer that could be assembled into e-PNs. The e-PNs expressed in E. coli, and harvested with a simple filtration method, had the same diameter (3 nm) and conductance as e-PNs expressed in G. sulfurreducens. These results, coupled with the robustness of E. coli for mass cultivation and the extensive E. coli toolbox for genetic manipulation, greatly expands opportunities for large-scale fabrication of novel e-PNs.
ACTOR: a latent Dirichlet model to compare expressed isoform proportions to a reference panel
Authors: McCabe Sean D. , Nobel Andrew B. , Love Michael I. 
Published: November 2019

AbstractThe relative proportion of RNA isoforms expressed for a given gene has been associated with disease states in cancer, retinal diseases, and neurological disorders. Examination of relative isoform proportions can help determine biological mechanisms, but such analyses often require a per-gene investigation of splicing patterns. Leveraging large public datasets produced by genomic consortia as a reference, one can compare splicing patterns in a dataset of interest with those of a reference panel in which samples are divided into distinct groups (tissue of origin, disease status, etc). We propose ACTOR, a latent Dirichlet model with Dirichlet Multinomial observations to compare expressed isoform proportions in a dataset to an independent reference panel. We use a variational Bayes procedure to estimate posterior distributions for the group membership of one or more samples. Using the Genotype-Tissue Expression (GTEx) project as a reference dataset, we evaluate ACTOR on simulated and real RNA-seq datasets to determine tissue-type classifications of genes. ACTOR is publicly available as an R package at https://github.com/mccabes292/actor.
Combining hypoxia-activated prodrugs and radiotherapy in silico: Impact of treatment scheduling and the intra-tumoural oxygen landscape
Authors: Hamis Sara , Kohandel Mohammad , Dubois Ludwig J , Yaromina Ala , Lambin Philippe , Powathil Gibin G 
Published: November 2019

AbstractHypoxia-activated prodrugs (HAPs) present a conceptually elegant approach to not only overcome, but better yet, exploit intra-tumoural hypoxia. Despite being successful in vitro and in vivo, HAPs are yet to achieve successful results in clinical settings. It has been hypothesised that this lack of clinical success can, in part, be explained by the insufficiently stringent clinical screening selection of determining which tumours are suitable for HAP treatments.Taking a mathematical modelling approach, we investigate how tumour properties and HAP-radiation scheduling influence treatment outcomes in simulated tumours. The following key results are demonstrated in silico: (i) HAP and ionising radiation (IR) monotherapies may attack tumours in dissimilar, and complementary, ways. (ii) HAP-IR scheduling may impact treatment efficacy. (iii) HAPs may function as IR treatment intensifiers. (iv) The spatio-temporal intra-tumoural oxygen landscape may impact HAP efficacy. Our in silico framework is based on an on-lattice, hybrid, multiscale cellular automaton spanning three spatial dimensions. The mathematical model for tumour spheroid growth is parameterised by multicellular tumour spheroid (MCTS) data.Author SummaryWhen cancer patients present with solid tumours, the tumours often contain regions that are oxygen-deprived or, in other words, hypoxic. Hypoxic cancer cells are more resistant to conventional anti-cancer therapies, such as chemotherapy and radiotherapy, and therefore tumour hypoxia may complicate treatments. Hypoxia-activated prodrugs constitute a conceptually elegant approach to not only overcome, but better yet, exploit tumour hypoxia. Hypoxia-activated prodrugs are drugs that act as Trojan horses, they are theoretically harmless vehicles that are converted into warheads when they reach their targets: hypoxic tumour cells. Despite being conceptually clever and successful in experimental settings, hypoxia-activated prodrugs are yet to achieve successful results in clinical trials. It has been hypothesised that this lack of clinical success can, in part, be explained by an insufficiently stringent clinical screening selection of determining which tumours are suitable for hypoxia-activated prodrug treatments.In this article, we investigate how simulated tumours with different oxygen landscapes respond to anti-cancer treatments that include hypoxia-activated prodrugs, either alone or in combination with radiotherapy. Our simulation framework is based on a mathematical model that describes how individual cancer cells in a tumour divide and respond to treatments. We demonstrate that the efficacy of hypoxia-activated prodrugs depends on both the treatment scheduling, and on the oxygen landscape of the specific, simulated tumour.
Quantitative Delineation of Herpesviruses in Bats for use in Ecological Studies
Authors: Sjodin Anna R. , Willig Michael R. , Anthony Simon J. 
Published: November 2019

AbstractPublic health concerns about recent viral epidemics have motivated researchers to seek transdisciplinary understanding of infection in wildlife hosts. With its deep history devoted to explaining the abundance and distribution of organisms, ecology can augment current methods for studying viral dynamics. However, datasets allowing ecological explorations of viral communities are lacking, and common methods for delineating viral operational taxonomic units (OTUs), or “species”, are subjective. Here, we comprehensively sampled 1,086 bats from two Puerto Rican caves and tested them for infection with herpesviruses. Using percent identity of nucleotides and a machine learning algorithm, we categorized herpesviruses into 41 OTUs, representing approximately 80% of all herpesviruses in the host community. Although 13 OTUs were detected in multiple host species, OTUs generally exhibited host specificity by infecting a core host species at a significantly higher prevalence than in all other species combined. Only two OTUs showed significantly different prevalence between host sexes. This work is the first exploration of viral community ecology in a community of wildlife hosts.
RepeatModeler2: automated genomic discovery of transposable element families
Authors: Flynn Jullien M. , Hubley Robert , Goubert Clément , Rosen Jeb , Clark Andrew G. , Feschotte Cédric , Smit Arian F. 
Published: November 2019

AbstractThe accelerating pace of genome sequencing throughout the tree of life is driving the need for improved unsupervised annotation of genome components such as transposable elements (TEs). Because the types and sequences of TEs are highly variable across species, automated TE discovery and annotation are challenging and time-consuming tasks. A critical first step is the de novo identification and accurate compilation of sequence models representing all the unique TE families dispersed in the genome. Here we introduce RepeatModeler2, a new pipeline that greatly facilitates this process. This new program brings substantial improvements over the original version of RepeatModeler, one of the most widely used tools for TE discovery. In particular, this version incorporates a module for structural discovery of complete LTR retroelements, which are widespread in eukaryotic genomes but recalcitrant to automated identification because of their size and sequence complexity. We benchmarked RepeatModeler2 on three model species with diverse TE landscapes and high-quality, manually curated TE libraries:Drosophila melanogaster(fruit fly),Danio rerio(zebrafish), andOryza sativa(rice). In these three species, RepeatModeler2 identified approximately three times more consensus sequences matching with >95% sequence identity and sequence coverage to the manually curated sequences than the original RepeatModeler. As expected, the greatest improvement is for LTR retroelements. The program had an extremely low false positive rate when applied to simulated genomes devoid of TEs. Thus, RepeatModeler2 represents a valuable addition to the genome annotation toolkit that will enhance the identification and study of TEs in eukaryotic genome sequences. RepeatModeler2 is available as source code or a containerized package under an open license (https://github.com/Dfam-consortium/RepeatModeler,https://github.com/Dfam-consortium/TETools).SignificanceGenome sequences are being produced for more and more eukaryotic species. The bulk of these genomes is composed of parasitic, self-mobilizing transposable elements (TEs) that play important roles in organismal evolution. Thus there is a pressing need for developing software that can accurately identify the diverse set of TEs dispersed in genome sequences. Here we introduce RepeatModeler2, an easy-to-use package for the curation of reference TE libraries which can be applied to any eukaryotic species. Through several major improvements over the previous version, RepeatModeler2 is able to produce libraries that recapitulate the known composition of three model species with some of the most complex TE landscapes. Thus RepeatModeler2 will greatly enhance the discovery and annotation of TEs in genome sequences.
Chronic cortisol exposure in early development leads to neuroendocrine dysregulation in adulthood
Authors: Hartig Ellen I. , Zhu Shusen , King Benjamin L. , Coffman James A. 
Published: November 2019

AbstractObjectiveChronic early life stress can affect development of the neuroendocrine stress system, leading to its persistent dysregulation and consequently increased disease risk in adulthood. One contributing factor is thought to be epigenetic programming in response to chronic cortisol exposure during early development. We have previously shown that zebrafish embryos treated chronically with cortisol develop into adults with constitutively elevated whole body cortisol and aberrant immune gene expression. The objective of the experiments reported here was to further characterize the phenotype of those adults.ResultsWe find that adult zebrafish derived from cortisol-treated embryos have aberrant cortisol levels, tissue distribution, and dynamics, which correlate with differential activity of key glucocorticoid-responsive regulatory genes klf9 and fkbp5 in blood and brain.