bluuebunny/crossref_metadata_2025_split huggingface dataset:
LINbase: A Web service for genome-based identification of microbes as members of crowdsourced taxa
Authors: Tian Long , Huang Chengjie , Heath Lenwood S. , Vinatzer Boris A. 
Published: August 2019

AbstractThe development of next generation and third generation DNA sequencing technologies in combination with new efficient algorithms allows scientists to economically, quickly, and precisely identify microbes at all taxonomic levels and even attribute pathogen isolates to specific disease outbreaks. However, current taxonomic practice has not kept up with the sequencing revolution and continues to rely on cumbersome journal publications to describe new species. Here we introduce a Web service that allows any user to genomically circumscribe any monophyletic group of bacteria as a taxon and associate with each taxon a name and short description. Any other user can immediately identify their unknown microbe as a member of any of these crowdsourced taxa using gene or genome sequences. The Web service is called LINbase. It leverages the previously described concept of Life Identification Numbers (LINs), which are codes assigned to individual organisms based on genome similarity. Most genomes currently in LINbase were imported from GenBank, but users have the option to upload their own genome sequences as well. Importantly, LINbase allows users to share the precise identity of their sequenced genomes without sharing the actual genome sequences, making not yet published or private genome sequences discoverable by the scientific community stimulating collaboration between academia and industry. LINbase is available at http://www.LINbase.org.
Sub-Nanometer Precision using Bayesian Grouping of Localizations
Authors: Fazel Mohamadreza , Wester Michael J. , Rieger Bernd , Jungmann Ralf , Lidke Keith A. 
Published: August 2019

AbstractSingle-molecule localization microscopy super-resolution methods such as DNA-PAINT and (d)STORM can generate multiple observed localizations over the time course of data acquisition from each dye or binding site that are not a priori assigned to those specific dyes or binding sites. We describe a Bayesian method of grouping and combining localizations from multiple blinking/binding events that can improve localization precision to better than one nanometer. The known statistical distribution of the number of binding/blinking events per dye/docking strand along with the precision of each localization event are used to estimate the true number and location of emitters in closely-spaced clusters.
Receptor-Like Kinase Phosphorylation of Arabidopsis Heterotrimeric G-Protein Gα - Subunit AtGPA1
Authors: Jia Haiyan , Song Gaoyuan , Werth Emily G. , Walley Justin W. , Hicks Leslie M. , Jones Alan M. 
Published: August 2019

AbstractAs molecular on-off switches, heterotrimeric G protein complexes, comprised of a Gα subunit and an obligate Gβγ dimer, transmit extracellular signals received by G protein– coupled receptors (GPCRs) to cytoplasmic targets that respond to biotic and abiotic stimuli. Signal transduction is modulated by phosphorylation of GPCRs and G protein complexes. In Arabidopsis thaliana, the Gα subunit AtGPA1 is phosphorylated by the receptor-like kinase (RLK) BRI1-ASSOCIATED Kinase 1 (BAK1), but the extent that other RLKs phosphorylates AtGPA1 is unknown. We mapped 22 trans-phosphorylation sites on AtGPA1 by 12 RLKs hypothesized to act in the Arabidopsis G protein signaling pathway. Cis-phosphorylation sites on these RLKs were also identified. BRI1, BAK1, and SERK1 have been reported as Ser/Thr and Tyr dual specificity kinases. We identified 4 more dual specificity kinases: IOS1, PSY1R, PEPR1, and AT2G37050. Multiple sites are present in the core AtGPA1 functional units, including pSer52 and pThr53 of the conserved P-loop that directly binds nucleotide/phosphate, pThr164 and pSer175 from αE helix in the intramolecular domain interface for nucleotide exchange and GTP hydrolysis, and pThr193 or pThr194 in Switch I (SwI) that coordinates nucleotide exchange and protein partner binding. Several AtGPA1 S/T phosphorylation sites are nucleotide-dependent phosphorylation patterns, such as S52/T53 in the P-loop and T193 and/or T194 in SwI.
Days Gained Response Discriminates Treatment Response in Patients with Recurrent Glioblastoma Receiving Bevacizumab-based Therapies
Authors: Singleton Kyle W. , Porter Alyx B. , Hu Leland S. , Johnston Sandra K , Bond Kamila M. , Rickertsen Cassandra R. , De Leon Gustavo , Whitmire Scott A. , Clark-Swanson Kamala R. , Mrugala Maciej M. , Swanson Kristin R. 
Published: August 2019

AbstractPurposeAccurate assessments of patient response to therapy are a critical component of personalized medicine. In glioblastoma multiforme (GBM), the most aggressive form of brain cancer, tumor growth dynamics are heterogenous across patients, complicating assessment of treatment response. This study aimed to analyze Days Gained (DG), a burgeoning model-based dynamic metric, for response assessment in patients with recurrent GBM who received bevacizumab-based therapies.Experimental DesignDays Gained response scores were calculated using volumetric tumor segmentations for patients receiving bevacizumab with and without concurrent cytotoxic therapy (N=62). Kaplan-Meier and Cox proportional hazards analyses were implemented to examine DG prognostic relationship to overall (OS) and progression-free survival (PFS) from the onset of treatment for recurrent GBM.ResultsIn patients receiving concurrent bevacizumab and cytotoxic therapy, Kaplan-Meier analysis showed significant differences in OS and PFS at previously identified DG cutoffs consistent with previous DG analyses using gadolinium-enhanced T1 weighted MR imaging. DG scores for bevacizumab monotherapy only approached significance for PFS. Cox regression showed that increases of 25 DG were significantly associated with a 12.5% reduction in OS hazard for concurrent therapy patients and a 4.4% reduction in PFS hazard for bevacizumab monotherapy.ConclusionDays Gained has significant meaning in recurrent therapy as a metric of treatment response, even in the context of anti-angiogenic therapies. This provides further evidence supporting the use of DG as an adjunct response metric that quantitatively connects treatment response and clinical outcomes.
Moderate amounts of epistasis are not evolutionarily stable in small populations
Authors: Sydykova Dariya K. , LaBar Thomas , Adami Christoph , Wilke Claus O. 
Published: August 2019

AbstractHigh mutation rates select for the evolution of mutational robustness where populations inhabit flat fitness peaks with little epistasis, protecting them from lethal mutagenesis. Recent evidence suggests that a different effect protects small populations from extinction via the accumulation of deleterious mutations. In drift robustness, populations tend to occupy peaks with steep flanks and positive epistasis between mutations. However, it is not known what happens when mutation rates are high and population sizes are small at the same time. Using a simple fitness model with variable epistasis, we show that the equilibrium fitness has a minimum as a function of the parameter that tunes epistasis, implying that this critical point is an unstable fixed point for evolutionary trajectories. In agent-based simulations of evolution at finite mutation rate, we demonstrate that when mutations can change epistasis, trajectories with a subcritical value of epistasis evolve to decrease epistasis, while those with supercritical initial points evolve towards higher epistasis. These two fixed points can be identified with mutational and drift robustness, respectively.
Single Cell RNA-sequencing reveals cellular heterogeneity, stage transition and antigenic variation during stress adaptation in synchronized Plasmodium falciparum
Authors: Rawat Mukul , Srivastava Ashish , Gupta Ishaan , Karmodiya Krishanpal 
Published: August 2019

AbstractThe malaria parasite has a complex life cycle exhibiting phenotypic and morphogenic variations in two different hosts. Phenotypic cell-to-cell variability can be an important determinant of cellular adaptation, stress tolerance and immune evasion in the host. To investigate cellular heterogeneity, we performed single cell RNA-sequencing (scRNA-seq) of 4949 and 6873 synchronized Plasmodium cells in control and under temperature stress condition (phenocopying the cyclic bouts of fever experienced during malarial infection). High-resolution clustering of scRNA-seq datasets and a combination of gene signatures allow identification of cellular heterogeneity and stage transition during stress adaptation. We identified a subset of parasites primed for gametogenesis and another subset primed for stress adaptation. Interestingly, temperature stress inducted the process of gametogenesis by upregulation of master regulator (AP2-G) of sexual conversion. Moreover, pseudotime analysis indicated bifurcation for cell-fate decision to gametogenesis at two different stages of intra-erythrocytic cycle. Furthermore, we identified a rare population of cells, which is only emerged during the stress condition, showing the reactive state of the pathogen against the temperature stress condition. Interestingly, genes associated with the gametogenesis, chaperon activity and maintenance of cellular homeostasis showed maximum variation under temperature stress condition. We also developed an online exploratory tool (website: http://bit.ly/plasmo_sync), which will provide new insights into gene function under normal and physiological stress condition. Thus, our study suggests that the variability and versatility of the maintenance of cellular homeostasis should enable cells to survive under different stress conditions, and may act as an important stimulator of development of drug-resistance in Plasmodium falciparum.
Variations of gut microbiome profile under different storage conditions and preservation periods: A multi-dimensional evaluation
Authors: Ma Junli , Sheng Lili , Xi Chuchu , Gu Yu , Hong Ying , Zheng Ningning , Chen Linlin , Wu Gaosong , Li Yue , Yan Juan , Han Ruiting , Li Bingbing , Qiu Huihui , Zhong Jing , Jia Wei , Li Houkai 
Published: August 2019

ABSTRACTGut dysbiosis contributes to the development of various human diseases. There are thousands of publications per year for investigating the role of gut microbiota in development of various diseases. However, emerging evidence has indicated data inconsistency between different studies frequently, but gained very little attention by scientists. There are many factors that can cause data variation and inconsistency during the process of microbiota study, in particular, sample storage conditions and subsequent sequencing process. Here, we systemically evaluated the impacts of six fecal sample storage conditions (including −80 °C, −80 °C with 70% ethanol (ET_-80 °C), 4°C with 70% ethanol (ET_4°C), and three commercial storage reagents including OMNIgene•GUT OMR-200 (GT), MGIEasy (MGIE), and Longsee (LS)), storage periods (1, 2 weeks or 6 months), and sequencing platform on gut microbiome profile using 16S rRNA gene sequencing. Our results suggested that −80°C is acceptable for fecal sample storage, and the addition of 70% ethanol offers some benefits. Meanwhile, we found that samples in ET_4 °Cand GT reagents are comparable, both introduced multi-dimensional variations. The use of MGIE resulted in the least alteration, while the greatest changes were observed in samples stored in LS reagents during the whole experiment. Finally, we also confirmed that variations caused by storage condition were larger than that of storage time and sequencing platform.IMPORTANCEIn the current study, we performed a multi-dimensional evaluation on the variations introduced by types of storage conditions, preservation period and sequencing platform on the basis of data acquired from 16S rRNA gene sequencing. The efficacy of preservation methods was comprehensively evaluated by DNA yield and quality, α and β diversity, relative abundance of the dominant bacteria and functional bacteria associated with SCFAs producing and BAs metabolism. Our results confirmed that variations introduced by storage condition were larger than that of storage periods and sequencing platform. Collectively, our study provided a comprehensive view to the impacts of storage conditions, storage times, and sequencing platform on gut microbial profile.
Vibrio choleraeOmpR represses the ToxR regulon in response to membrane intercalating agents that are prevalent in the human gastrointestinal tract
Authors: Kunkle DE , Bina TF , Bina XR , Bina JE 
Published: August 2019

ABSTRACTMultidrug efflux systems belonging Resistance-Nodulation-Division (RND) superfamily are ubiquitous in Gram-negative bacteria. RND efflux systems are often associated with multiple antimicrobial resistance but also contribute to the expression of diverse bacterial phenotypes including virulence, as documented in the intestinal pathogenVibrio cholerae, the causative agent of the severe diarrheal disease cholera. Transcriptomic studies with RND efflux-negativeV. choleraesuggested that RND-mediated efflux was required for homeostasis, as loss of RND efflux resulted in the activation of transcriptional regulators, including multiple environmental sensing systems. In this report we investigated six RND efflux responsive regulatory genes for contributions toV. choleraevirulence factor production. Our data showed thatV. choleraegene VC2714, encoding a homologue ofEscherichia coliOmpR, was a virulence repressor. The expression ofompRwas elevated in an RND-null mutant andompRdeletion partially restored virulence factor production in the RND-negative background. Virulence inhibitory activity in the RND-negative background resulted from OmpR repression of the key ToxR regulon virulence activatoraphB, andompRoverexpression in WT cells also repressed virulence throughaphB.We further show thatompRexpression was not altered by changes in osmolarity, but instead was induced by membrane intercalating agents that are prevalent in the host gastrointestinal tract, and which are substrates of theV. choleraeRND efflux systems. Our collective results indicate thatV. cholerae ompRis anaphBrepressor and regulates the expression of the ToxR virulence regulon in response to novel environmental cues.
Loss of BubR1 Acetylation instigates Replication Stress leading to Complex Chromosomal Rearrangement in tumors
Authors: Park Jiho , Yeu Song-Yion , Paik Sangjin , Lee Junyeob , Jang Jinho , Lee Semin , Koh Young-Il , Lee Hyunsook 
Published: August 2019

AbstractChromosome number and structure instability is the hallmark of cancer. Equal chromosome segregation is guaranteed by the spindle assembly checkpoint (SAC), thus defective SAC leads to chromosome instability. However, aneuploidy alone is not oncogenic, and whether compromised SAC is associated with structure instability remains elusive. BubR1 is a core component of SAC, which is acetylated at lysine 250 in mitosis. Previously, we showed that deficiency of BubR1 acetylation in mice (K243R/+) leads to spontaneous tumorigenesis via chromosome mis-segregation. Here, we asked whether loss of BubR1 acetylation is associated with chromosome structure instability by examiningK243R/+mice intercrossed top53-deficient mice. Genome-wide sequencing and spectral karyotyping of the double mutant mouse tumors revealed that BubR1 acetylation deficiency leads to complex chromosome rearrangements, including Robertsonian-like whole-arm translocations and premature sister-chromatid separations (PMSCS). In primary MEFs, replication stress was markedly increased in telomeres and centromeres, suggesting that the replication stress underlies the significant increase of DNA damage and subsequent chromosome rearrangements. Furthermore, defects in BubR1 acetylation at K250 were detected in human cancers as well. Collectively, we propose that chromosome mis-segregation by the loss of BubR1 acetylation causes chromosome structure instability, leading to massive chromosome rearrangements through the induction of replication stress.
Selective Sweep at a QTL in a Randomly Fluctuating Environment
Authors: Chevin Luis-Miguel 
Published: August 2019

AbstractAdaptation is mediated by phenotypic traits that are often near continuous, and undergo selective pressures that may change with the environment. The dynamics of allelic frequencies at underlying quantitative trait loci (QTL) depend on their own phenotypic effects, but also possibly on other polymorphic loci affecting the same trait, and on environmental change driving phenotypic selection. Most environments include a substantial component of random noise, characterized by both its magnitude and its temporal autocorrelation, which sets the timescale of environmental predictability. I investigate the dynamics of a mutation affecting a quantitative trait in an autocorrelated stochastic environment that causes random fluctuations of an optimum phenotype. The trait under selection may also exhibit background polygenic variance caused by many polymorphic loci of small effects elsewhere in the genome. In addition, the mutation at the QTL may affect phenotypic plasticity, the phenotypic response of given genotype to its environment of development or expression. Stochastic environmental fluctuations increases the variance of the evolutionary process, with consequences for the probability of a complete sweep at the QTL. Background polygenic variation critically alters this process, by setting an upper limit to stochastic variance of population genetics at the QTL. For a plasticity QTL, stochastic fluctuations also influences the expected selection coefficient, and alleles with the same expected trajectory can have very different stochastic variances. Finally, a mutation may be favored through its effect on plasticity despite causing a systematic mismatch with optimum, which is compensated by evolution of the mean background phenotype.
Single-cell RNA sequencing reveals functional heterogeneity and sex differences of glioma-associated brain macrophages
Authors: Ochocka Natalia , Segit Pawel , Walentynowicz Kacper Adam , Wojnicki Kamil , Cyranowski Salwador , Swatler Julian , Mieczkowski Jakub , Kaminska Bozena 
Published: August 2019

AbstractMicroglia are resident myeloid cells in the central nervous system (CNS) that control homeostasis and protect CNS from damage and infections. Microglia and peripheral myeloid cells accumulate and adapt tumor supporting roles in human glioblastomas that show prevalence in men. Cell heterogeneity and functional phenotypes of myeloid subpopulations in gliomas remain elusive. Single-cell RNA sequencing (scRNA-seq) of CD11b+myeloid cells in naïve and GL261 glioma-bearing mice revealed distinct profiles of microglia, infiltrating monocytes/macrophages and CNS border-associated macrophages. We demonstrated an unforeseen molecular heterogeneity among myeloid cells in naïve and glioma-bearing brains, validated selected marker proteins and showed distinct spatial distribution of identified subsets in experimental gliomas. We found higher expression of MHCII encoding genes in glioma-activated male microglia, which was corroborated in bulk and scRNA-seq data from human diffuse gliomas. Sex-specific gene expression in glioma-activated microglia may be relevant to sex differences in incidence and outcomes of glioma patients.
Lack of regularity between letters impacts word recognition performance
Authors: Beier Sofie , Bernard Jean-Baptiste 
Published: August 2019

AbstractPhysical inter-letter dissimilarity has been suggested as a solution to increase perceptual differences between letter shapes and hence a solution to improve reading performance. However, the deleterious effects of font tuning suggest that low inter-letter regularity (due to the enhancement of specific letter features to make them more differentiable) may impair word recognition performance. The aim of the present investigation was 1) to validate our hypothesis that reducing inter-letter regularity impairs reading performance, as suggested by font tuning, and 2) to test whether some forms of non-regularities could impair visual word recognition more. To do so, we designed four new fonts. For each font we induced one type of increased perceptual difference: for the first font, the letters have longer extender length; for the second font, the letters have different slants; and for the third font, the letters have different font cases. We also designed a fourth font where letters differ on all three aspects (worst regularity across letters). Word recognition performance was measured for each of the four fonts in comparison to a traditional sans serif font (best regularity across letters) through a lexical decision task. Results showed a significant decrease in word recognition performance only for the fonts with mixed-case letters, suggesting that fonts with low regularity, such as mixed-case letters, should be avoided in the definition of new “optimal” fonts. Letter recognition performance measured for the five different fonts through a trigram recognition task showed that this effect is not consistently due to poor letter identification.
Health care service providers’ experiences, understanding and conceptions of voluntary medical male circumcision in KwaZulu-Natal, South Africa
Authors: Nxumalo Celenkosini Thembelenkosini , Mchunu Gugu Gladness 
Published: August 2019

ABSTRACTBackgroundThere is compelling evidence that voluntary medical male circumcision reduces the chances of heterosexual transmission of HIV infection. Health care workers are among the key influencers in terms of scale up of VMMC as they are often involved in mobilization for uptake. Adequate knowledge and competence are essential to ensuring that the delivery of VMMC services is line with the recommended comprehensive package of HIV prevention services.AimThe aim of this study was to analyse health care service providers’ conceptions, experiences and understanding of VMMC in KwaZulu-Natal, South Africa.MethodsThe study employed a qualitative approach using a phenomenographic design. Ethical clearance to conduct the study was obtained from the University of KwaZulu-Natal’s Biomedical Research Ethics Committee (BE627/18).Data were collected from a purposive sample of 15 health care worker who were doctors, nurses and clinical associates working in six different rural clinics in KwaZulu-Natal, South Africa. Individual in-depth interviews were used collect data guided by a semi-structured interview schedule. An audiotape was used to record the interviews, which were then transcribed verbatim, and analysed thematically.ResultsCategories of description in healthcare providers’ experiences, conceptions and understanding of voluntary medical male circumcision emerged. The findings of this study revealed that health care workers conceptions, experiences and understanding of VMMC were influenced by stereotypical cultural, religious and traditional beliefs. The challenges of implementing VMMC were shortage of staff and poor training of health care workers on VMMC.ConclusionTailored messaging targeting health care workers misconceptions and poor understanding of VMMC in necessary. In addition, resource allocation for training and infrastructure could significantly improve the quality of VMMC services and uptake thereof.