bluuebunny/crossref_metadata_2025_split huggingface dataset:
The SHAPE of logistic growth shows that serial passaging biases fixation probability
Authors: Dench Jonathan 
Published: August 2018

AbstractThe forward time simulation tool rSHAPE (R-package for Simulated Haploid Asexual Population Evolution) was designed to complement the theoretical and empirical study of evolution. Included with rSHAPE are functions to programmatically build, run, and initially process results of an evolutionary experiment defined by the range of experimental conditions. As experimental evolution often studies both the emergence and fate ofde novomutants, I validated rSHAPE by confirming its ability to replicate seminal theoretical expectations concerning changes in fitness through time and the fixation probability of mutants. As an example of how rSHAPE can support both theoretical and empirical research, I applied rSHAPE to study how the laboratory protocol of serial passaging, common in microbial experimental evolution, affects the fixation probability ofde novomutants. Unlike related theoretical work which modelled growth as effectively exponential (Wahlet al., 2002), this study considered populations experiencing logistic growth which is common to microbes undergoing serial passaging. In contrast to exponential growth, when a population undergoes logistic growth the probability of a mutant arising and eventually fixing depends upon when a mutant arises during a growth phase. Users can download software and documentation for rSHAPE through CRAN athttps://cran.r-project.org/web/packages/rSHAPE/index.html, or via GitHub athttps://www.github.com/Jdench/SHAPE_library/.
CCCP experimental evolution ofEscherichia coliselects for mutations that increase EmrA activity or that downregulate other PMF-driven drug efflux pumps
Authors: Griffith Jessie M. , Basting Preston J. , Bischof Katarina M. , Wrona Erintrude P. , Kunka Karina S. , Tancredi Anna C. , Moore Jeremy P. , Hyman Miriam R. L. , Slonczewski Joan L. 
Published: August 2018

ABSTRACTExperimental evolution was conducted withEscherichia coliK-12 W3110 in the presence of carbonyl cyanide m-chlorophenylhydrazone (CCCP), an uncoupler of the proton motive force (PMF). Cultures were serially diluted daily 1:100 in broth medium containing 20-150 μM CCCP at pH 6.5 or at pH 8.0. After 1,000 generations, all populations showed 5- to 10-fold increase in CCCP resistance. Sequenced isolates showed mutations inemrABor in its negative repressormprA; the EmrAB-TolC multidrug efflux pump confers resistance to CCCP and nalidixic acid. Deletion ofemrAabolished the CCCP resistance of these strains. One CCCP-evolved isolate lackedemrAormprAmutations; this strain (C-B11-1) showed mutations in drug efflux regulatorscecR(ybiH) (upregulates drug pumps YbhG and YbhFSR) andgadE(upregulates drug pumpmdtEF). AcecR∷kanRdeletion conferred partial resistance to CCCP. A later evolved descendant of the C-B11 population showed mutations inybhR(MDR efflux). Another isolate showedacrB(MDR efflux pump). TheacrBisolate was sensitive to chloramphenicol and tetracycline, which are effluxed by AcrAB. Other mutant genes in CCCP-evolved strains includeadhE(alcohol dehydrogenase),rng(ribonuclease G), andcyaA(adenylate cyclase). Overall, experimental evolution revealed a CCCP fitness advantage for mutations increasing its own efflux via EmrA; and for mutations that may decrease proton-driven pumps that efflux other drugs not present (cecR, gadE, acrB, ybhR). These results are consistent with our previous report of drug sensitivity associated with evolved tolerance to a partial uncoupler (benzoate or salicylate).IMPORTANCEThe genetic responses of bacteria to depletion of proton motive force, and their effects on drug resistance, are poorly understood. Our evolution experiment reveals genetic mechanisms of adaptation to the PMF uncoupler CCCP, including selection for and against various multidrug efflux pumps. The results have implications for our understanding of the gut microbiome, which experiences high levels of organic acids that decrease PMF. Organic acid uncouplers may select against multidrug resistance in evolving populations of enteric bacteria.
Keystone mutualists can facilitate transition between alternative ecosystem states in the soil
Authors: Duhamel Marie , Wan Joe , Bogar Laura M. , Segnitz R. Max , Duncritts Nora C. , Peay Kabir G. 
Published: August 2018

AbstractSymbioses between plants and microbial organisms can fundamentally alter the structure of ecosystems, from their species diversity to rates of nutrient cycling. Yet, many aspects of how differences in the prevalence of microbial symbioses arise are unclear. This is a key knowledge gap, as if co-variation in plant and microbial distributions are primarily determined by extrinsic abiotic factors then symbioses should exert little independent control over ecosystems. To examine the potential for alternative symbiotic communities to arise under similar conditions we examined biogeochemical cycling and microbial community structure in a coastal landscape where historical patterns of vegetation transition are known, allowing us to eliminate abiotic determinism. We found that alternative states in microbial community structure and ecosystem processes emerged under different plant species. Greenhouse studies further demonstrated that plant selection of symbiotic microbes is central to emergence of these alternative states and occurs independent of soil abiotic conditions. Moreover, we provide evidence that transition between states may be highly dependent on the presence of a small set of ruderal symbionts that are rare in mature systems but may act as keystone mutualists. Because differences between these alternative states can be directly linked to plant-microbe symbioses, independent of initial conditions, our results suggesting that biotic feedbacks between keystone symbiotic microbes and plants play a foundational role in the diversity and function of soils.
eTumorRisk, an algorithm predicts cancer risk based on comutated gene networks in an individual’s germline genome
Authors: Zou Jinfeng , Wang Edwin 
Published: August 2018

AbstractEarly cancer detection has potentials to reduce cancer burden. A prior identification of the high-risk population of cancer will facilitate cancer early detection. Traditionally, cancer predisposition genes such as BRCA1/2 have been used for identifying high-risk population of developing breast and ovarian cancers. However, such high-risk genes have only a few. Moreover, the complexity of cancer hints multiple genes involved but also prevents from identifying such predictors for predicting high-risk subpopulation. Therefore, we asked if the germline genomes could be used to identify high-risk cancer population. So far, none of such predictive models has been developed. Here, by analyzing of the germline genomes of 3,090 cancer patients representing 12 common cancer types and 25,701 non-cancer individuals, we discovered significantly differential co-mutated gene pairs between cancer and non-cancer groups, and even between cancer types. Based on these findings, we developed a network-based algorithm, eTumorRisk, which enables to predict individuals’ cancer risk of six genetic-dominant cancers including breast, colon, brain, leukemia, ovarian and endometrial cancers with the prediction accuracies of 74.1-91.7% and have 1-3 false-negatives out of the validating samples (n=14,701). The eTumorRisk which has a very low false-negative rate might be useful in screening of general population for identifying high-risk cancer population.
Effective Machine-Learning Assembly For Next-Generation Sequencing With Very Low Coverage
Authors: Ranjard Louis , Wong Thomas K. F. , Rodrigo Allen G. 
Published: August 2018

ABSTRACTIn short-read DNA sequencing experiments, the read coverage is a key parameter to successfully assemble the reads and reconstruct the sequence of the input DNA. When coverage is very low, the original sequence reconstruction from the reads can be difficult because of the occurrence of uncovered gaps. Reference guided assembly can then improve these assemblies. However, when the available reference is phylogenetically distant from the sequencing reads, the mapping rate of the reads can be extremely low. Some recent improvements in read mapping approaches aim at modifying the reference according to the reads dynamically. Such approaches can significantly improve the alignment rate of the reads onto distant references but the processing of insertions and deletions remains challenging. Here, we introduce a dynamic programming algorithm to update the reference sequence according to previously aligned reads. Substitutions, insertions and deletions are performed in the reference sequence dynamically. We evaluate this approach to assemble a western-grey kangaroo mitochondrial amplicon. Our results show that more reads can be aligned and that this method produces assemblies of length comparable to the truth while limiting error rate when classic approaches fail to recover the correct length. Our method allows us to assemble the first full mitochondrial genome for the western-grey kangaroo. Finally, we discuss how the core algorithm of this method could be improved and combined with other approaches to analyse larger genomic sequences.
A new schizophrenia model: immune activation is associated with induction of the tryptophan catabolite pathway and increased eotaxin levels which together determine memory impairments and schizophrenia symptom dimensions
Authors: Sirivichayakul Sunee , Kanchanatawan Buranee , Thika Supaksorn , Carvalho André F. , Maes Michael 
Published: August 2018

AbstractObjectiveRecently, we reported that stable-phase schizophrenia is characterized by two interrelated symptom dimensions: PHEMN (psychotic, hostility, excitation, mannerism and negative symptoms); and DAPS (depressive, anxiety and physio-somatic symptoms) and that Major Neuro-Cognitive psychosis (MNP) is the full blown phenotype of schizophrenia (largely overlapping with deficit schizophrenia). Herein we examined the effects of immune activation in association with tryptophan catabolite (TRYCAT) patterning and memory disorders on PHEMN/DAPS dimensions and MNP.MethodSerum levels of macrophage inflammatory protein-1 (MIP-1), soluble interleukin (IL)-1 receptor antagonist (sIL-1RA), IL-10, eotaxin, IgA/IgM responses to TRYCATs, and Consortium to Establish a Registry for Alzheimer’s disease (CERAD) tests were assessed in 40 controls and 80 schizophrenia patients.ResultsSchizophrenia and MNP were predicted by significantly increased levels of IL-10, eotaxin and TRYCATs. A large part of the variance in both PHEMN/DAPS symptom dimensions (42.8%) was explained by cytokine levels and TRYCATs combined. The MTP+sTL-1R A+IL-10 composite score and eotaxin explained each around 19% of the variance in symptom dimensions, and approximately 18% of memory deficits. Moreover, MIP+sIL-1RA+IL-10 was significantly associated with elevations in picolinic acid, xanthurenic acid and 3-OH-kynurenine. Partial Least Squares path modeling shows that the highly significant effects of MIP+sIL-1RA+IL-10 on symptomatology are mediated by the effects of noxious TRYCATs on memory deficits.ConclusionsCurrent findings indicate that in schizophrenia, immune activation may underpin activation of indoleamine-2,3-dioxygenase and kynurenine monooxygenase, while impairments in episodic and semantic memory may be caused by the neurotoxic effects of TRYCATs and eotaxin. The combined effects of immune activation, eotaxin and memory defects determine to a large extent PHEMN/DAPS symptoms and the MNP phenotype. These findings indicate that schizophrenia phenomenology is largely mediated by multiple neuro-immune pathways and that immune activation, increased production of eotaxin and neurotoxic TRYCATs (picolinic acid, xanthurenic acid and 3-HO-kynurenine) are new drug targets in schizophrenia and MNP.
Glycine promotes longevity inCaenorhabditis elegansin a methionine cycle-dependent fashion
Authors: Liu Yasmine J. , Janssens Georges E. , Kamble Rashmi , Gao Arwen W. , Jongejan Aldo , Weeghel Michel van , MacInnes Alyson W. , Houtkooper Riekelt H. 
Published: August 2018

AbstractThe deregulation of metabolism is a hallmark of aging. As such, changes in the expression of metabolic genes and the profiles of amino acid levels are features associated with aging animals. We previously reported that the levels of most amino acids decline with age inCaenorhabditis elegans (C. elegans).Glycine, in contrast, substantially accumulates in agingC. elegans. In this study we show that this is coupled to a decrease in gene expression of enzymes important for glycine catabolism. We further show that supplementation of glycine significantly prolongsC. eleganslifespan and ameliorates specific transcriptional changes that are associated with aging. Glycine feeds into the methionine cycle. We find that mutations in components of this cycle, methionine synthase(metr-1)and S-adenosylmethionine synthetase(sams-1), completely abrogate glycine-induced lifespan extension. Strikingly, the beneficial effects of glycine supplementation are conserved when we supplement with serine, also driving the methionine cycle. RNA sequencing of serine- and glycine-supplemented worms reveals similar transcriptional profiles including widespread gene suppression. Taken together, these data uncover a novel role of glycine in the deceleration of aging through its function in the methionine cycle.Author summaryThere are a growing number of studies showing that amino acids function as signal metabolites that influence aging and health. Although contemporary -OMICs studies have uncovered various associations between metabolite levels and aging, in many cases the directionality of the relationships is unclear. In a recent metabolomics study, we found that glycine accumulates in agedC. eleganswhile other amino acids decrease. The present study shows that glycine supplementation prolongs longevity and drives a genome-wide inhibition effect onC. elegansgene expression. Glycine as a one-carbon donor fuels the methyl pool of one-carbon metabolism composed of folates and methionine cycle. We find that glycine-mediated longevity effect is fully dependent on methionine cycle, and that all of these observations are conserved with supplementation of the other one-carbon amino acid, serine. These results provide a novel role for glycine as a promoter of longevity and bring new insight into the role of one-carbon amino acids in the regulation of aging that may ultimately be beneficial for humans.
Excess of rare missense variants in hearing loss genes in sporadic Meniere disease
Authors: Gallego-Martinez Alvaro , Requena Teresa , Roman-Naranjo Pablo , Lopez-Escamez Jose A. ,   Meniere Disease Consortium (MeDiC)
Published: August 2018

AbstractMeniere’s disease (MD) is a clinical spectrum of rare disorders characterized by vertigo attacks, associated with sensorineural hearing loss (SNHL) and tinnitus involving low to medium frequencies. Although it shows familial aggregation with incomplete phenotypic forms and variable expressivity, most cases are considered sporadic. The aim of this study was to investigate the burden for rare variation in SNHL genes in patients with sporadic MD.We conducted a targeted-sequencing study including SNHL and familial MD genes in 890 MD patients to compare the frequency of rare variants in cases using three independent public datasets as controls.Patients with sporadic MD showed a significant enrichment of missense variants in SNHL genes that was not found in the controls. The list of genes includesGJB2, USH1G, SLC26A4, ESRRBandCLDN14. A rare synonymous variant with unknown significance was found in theMARVELD2gene in several unrelated patients with MD.There is a burden of rare variation in certain SNHL genes in sporadic MD. Furthermore, the physical interaction of specific gene variants at protein level can explain the additive effect of rare variants in different genes in MD. This study will contribute to design a gene panel for the genetic diagnosis of MD.
Petite Integration Factor 1 (PIF1) helicase deficiency increases weight gain in Western diet-fed female mice without increased inflammatory markers or decreased glucose clearance
Authors: Belmonte Frances R. , Dedousis Nikolaos , Sipula Ian , Desai Nikita A. , Singhi Aatur D. , Chu Yanxia , Zhang Yingze , Bannwarth Sylvie , Paquis-Flucklinger Véronique , Harrington Lea , Jurczak Michael J. , O’Doherty Robert M. , Kaufman Brett A. 
Published: August 2018

AbstractPetite Integration Factor 1 (PIF1) is a multifunctional helicase present in nuclei and mitochondria. PIF1 knock out (KO) mice exhibit accelerated weight gain and decreased wheel running on a normal chow diet. In the current study, we investigated whether Pif1 removal alters whole body metabolism in response to weight gain. PIF1 KO and wild type (WT) C57BL/6J mice were fed a Western diet (WD) rich in fat and carbohydrates before evaluation of their metabolic phenotype. Compared with weight gain-resistant WT female mice, WD-fed PIF1 KO females, but not males, showed accelerated adipose deposition, decreased locomotor activity, and reduced whole-body energy expenditure without increased dietary intake. Surprisingly, PIF1 KO females were protected against obesity-induced alterations in fasting blood glucose and glucose clearance. WD-fed PIF1 KO females developed mild hepatic steatosis and associated changes in liver gene expression that were absent in weight-matched, WD-fed female controls, linking hepatic steatosis to Pif1 ablation rather than increased body weight. WD-fed PIF1 KO females also showed decreased gene expression of inflammatory markers in adipose tissue. Collectively, these data separated weight gain from inflammation and impaired glucose homeostasis. They also support a role for Pif1 in weight gain resistance and liver metabolic dysregulation during nutrient stress.
Dexidisruption depletes gut microbial metabolites and accelerates autoimmune diabetes
Authors: Davison LJ , Wallace MD , Preece C , Hughes K , Todd JA , Davies B , O’ Callaghan CA 
Published: August 2018

AbstractNon-coding genetic variants in the CLEC16A gene on human chromosome 16p13.13 are associated with risk of autoimmune diseases, including type 1 diabetes and multiple sclerosis. In this region, we previously identifiedDEXI, a candidate causal gene of unknown function, which alters the risk of type 1 diabetes, where the T1D predisposing allele is associated with lowerDEXIexpression. Here, we demonstrate by CRISPR mutagenesisin vivoand deep phenotyping that disruptedDexiexpression accelerates diabetes in the non-obese diabetic (NOD) mouse, a spontaneous model of autoimmune pancreatic beta-cell destruction. Mutant mice have increased serum IgM and IgA concentrations compared to wild-type NOD mice, as well as changes in both the gut microbiome and molecular metabolites associated with microbial metabolism. These findings suggest that the mechanism by whichDEXIalters diabetes risk involves the composition and function of the microbiome and its impact on host metabolites. Such metabolites, including short chain fatty acids such as butyrate, have been shown to alter the activity of the immune cells involved in beta-cell destruction and susceptibility of the beta cells to autoimmune attack.One Sentence Summary:Disruption of theDexigene leads to accelerated diabetes in the non-obese diabetic (NOD) mouse, accompanied by changes in serum immunoglobulins, gut microbiome and microbial metabolites.
Multimodal integration and vividness in the angular gyrus during episodic encoding and retrieval
Authors: Tibon Roni , Fuhrmann Delia , Levy Daniel A. , Simons Jon S. , Henson Richard 
Published: August 2018

AbstractMuch evidence suggests that the angular gyrus (AnG) is involved in episodic memory, but its precise role is yet to be determined. We examined two possible accounts, within the same experimental paradigm: the CoBRA account (Shimamura, 2011), which suggests that the AnG acts as a convergence zone that binds multimodal episodic features; and the Subjectivity account (Yazar et al., 2012), which implicates AnG involvement in subjective mnemonic experience (such as vividness or confidence). fMRI was employed during both encoding and retrieval of paired-associates. During study, female and male human participants memorised picture-pairs of common objects (in the unimodal task) or of an object-picture and an environmental sound (in the crossmodal task). At test, they performed a cued-recall task, and further indicated the vividness of their memory. During retrieval, BOLD activation in the AnG was greatest for vividly remembered associates, consistent with the Subjectivity account. During encoding, the same effect of vividness was found, but this was further modulated by task: Greater activations were associated with subsequent recall in the crossmodal than the unimodal task. Thus, encoding data suggests an additional role to the AnG in cross-modal integration, consistent with its role at retrieval proposed by CoBRA. These results resolve some of the puzzles in the literature and indicate that the AnG can play different roles during encoding and retrieval, determined by the cognitive demands posed by different mnemonic tasks.Significance StatementWe offer new insights into the multiplicity of processes that are associated with angular gyrus (AnG) activation during encoding and retrieval of newly formed memories. We used fMRI while human participants learned and subsequently recalled pairs of objects presented to the same sensory modality or to different modalities. We were able to show that the AnG is involved when vivid memories are created and retrieved, as well as when encoded information is integrated across different sensory modalities. These findings provide novel evidence for the contribution of the AnG to our subjective experience of remembering, alongside its role in integrative processes that promote subsequent memory.