bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maintenance of High Inbreeding Depression in Selfing Populations: Effects of Coupling of Early- and Late-Acting Mutations
Authors: Sakai Satoki 
Published: August 2019

ABSTRACTHigh estimates of inbreeding depression have been obtained in many plant populations with high selfing rates. However, deleterious mutations might be purged from such populations as a result of selfing. I developed a simulation model assuming the presence of mutations at two sets of loci, namely, early- and late-acting loci, and the selective abortion of embryos coupled with ovule overproduction. In the model, early-acting loci are expressed during embryo initiation, and less vigorous embryos are aborted. Late-acting loci are expressed after selective abortion ends; the surviving embryos (seeds) compete, and some of them form the next generation. If mutations are allowed to occur in both early- and late-acting loci, they increase in frequency in populations with high selfing rates in both sets of loci. However, this phenomenon does not occur if mutations occur in only the early- or late-acting loci. Consistent results are observed even if the total number of loci in which mutations are allowed to occur is the same among simulations with both early- and late-acting loci or only early- or late-acting loci, indicating that the presence of both sets of loci is the causal factor. Thus, the coupling effects of early- and late-acting mutations promote the maintenance of these mutations in populations with high selfing rates.
The Alzheimer’s disease associated bacterial protease RgpB from P. gingivalis activates the alternative β-secretase meprin β thereby increasing Aβ generation
Authors: Armbrust Fred , Colmorgen Cynthia , Pietrzik Claus U. , Becker-Pauly Christoph 
Published: August 2019

AbstractAlzheimer’s disease (AD) is the most common type of dementia and characterized by tau hyperphosphorylation, oxidative stress, reactive microglia and amyloid-β (Aβ) deposits. A recent study revealed that Porphyromonas gingivalis infection is associated with amyloid β generation in Alzheimer’s disease. Increased Aβ levels, tau degradation and neuronal toxicity were observed as a consequence of ginigipain R (RgpB) activity, a cysteine protease constitutively secreted by P. gingivalis. Of note, we previously identified RgpB as a potent activator of the metalloproteinase meprin β. Interestingly, meprin β is an alternative β-secretase of the amyloid precursor protein (APP), which together with the γ-secretase leads to the generation of aggregation-prone N-terminally truncated Aβ2-x peptides. Importantly, identification of a risk gene variant of meprin β (rs173032) for Alzheimer’s disease using whole-exome sequencing of the BDR cohort further supports the impact of this alternative β-secretase. Thus, we wondered if increased Aβ levels as a consequence of P. gingivalis colonization into the brain might be due to meprin β activation by RgpB. Here, we demonstrate that i) upon incubation with RgpB the proteolytic activity of meprin β at the cell surface of transfected HEK cells or of endogenously expressed enzyme in SH-SY5Y neuroblastoma cells was significantly increased, and that ii) RgpB-mediated increase in meprin β activity leads to massive generation of Aβ-peptides. In conclusion, our findings would further explain the pathogenesis of P. gingivalis in AD brain.
The global phylogenetic landscape and nosocomial spread of the multidrug-resistant opportunistStenotrophomonas maltophilia
Authors: Gröschel Matthias I , Meehan Conor J , Barilar Ivan , Diricks Margo , Gonzaga Aitor , Steglich Matthias , Conchillo-Solé Oscar , Scherer Isabell-Christin , Mamat Uwe , Luz Christian F. , De Bruyne Katrien , Utpatel Christian , Yero Daniel , Gibert Isidre , Daura Xavier , Kampmeier Stefanie , Rahman Nurdyana Abdul , Kresken Michael , van der Werf Tjip S , Alio Ifey , Streit Wolfgang R. , Zhou Kai , Schwartz Thomas , Rossen John W A , Farhat Maha R , Schaible Ulrich E , Nübel Ulrich , Rupp Jan , Steinmann Joerg , Niemann Stefan , Kohl Thomas A 
Published: August 2019

AbstractRecent studies portend a rising global spread and adaptation of human- or healthcare-associated pathogens. Here, we analysed an international collection of the emerging, multidrug-resistant, opportunistic pathogenStenotrophomonas maltophiliafrom 22 countries to infer population structure and clonality at a global level. We show that theS. maltophiliacomplex is divided into 23 monophyletic lineages, most of which harboured strains of all degrees of human virulence. Lineage Sm6 comprised the highest rate of human-associated strains, linked to key virulence and resistance genes. Transmission analysis identified potential outbreak events of genetically closely related strains isolated within days or weeks in the same hospitals.One Sentence SummaryTheS. maltophiliacomplex comprises genetically diverse, globally distributed lineages with evidence for intra-hospital transmission.
Stable Engraftment of a Human Gut Bacterial Microbiome in Double Humanized BLT-mice
Authors: Daharsh Lance , Ramer-Tait Amanda E. , Li Qingsheng 
Published: August 2019

AbstractBackgroundHumanized mice featuring a functional human immune system are an important pre-clinical model for examining immune responses to human-specific pathogens. This model has been widely utilized to study human diseases that are otherwise impossible or difficult to investigate in humans or with other animal models. However, one limitation of using humanized mice is their native murine gut microbiome, which significantly differs from the one found in humans. These differences may be even greater for mice housed and bred in specific pathogen free conditions. Given the importance of the gut microbiome to human health and disease, these differences may profoundly impact the ability to translate the results from humanized mice studies to human disease. Further, there is a critical need for improved pre-clinical models to study the complex in vivo relationships of the gut microbiome, immune system, and human disease. We therefore created double humanized mice with both a functional human immune system and stable human-like gut microbiome.ResultsSurgery was performed on NOD.Cg-PrkdcscidII2rgtm1Wjl/SzJ (NSG) mice to create bone-marrow, liver, thymus (BLT) humanized mice. After immune reconstitution, mice were treated with broad spectrum antibiotics to deplete murine gut bacteria and then transplanted with fecal material from healthy human donors. Characterization of 173 fecal samples obtained from 45 humanized mice revealed that double humanized mice had unique 16S rRNA gene profiles consistent with those of the individual human donor samples. Importantly, transplanted human-like gut microbiomes were stable in mice for the duration of the study, up to 14.5 weeks post-transplant. Microbiomes of double humanized mice also harbored predicted functional capacities that more closely resembled those of the human donors compared to humanized mice.ConclusionsHere, we describe successful engraftment of a stable human microbiome in BLT humanized mice to further improve this preclinical humanized mouse model. These double humanized mice represent a unique and tractable new model to study the complex relationships between the human gut microbiome, human immune system, and human disease in vivo.
Variant calling for cpn60 barcode sequence-based microbiome profiling
Authors: Vancuren Sarah J. , Santos Scott J. Dos , Hill Janet E. ,   the Maternal Microbiome Legacy Project Team
Published: August 2019

AbstractAmplification and sequencing of conserved genetic barcodes such as the cpn60 gene is a common approach to determining the taxonomic composition of microbiomes. Exact sequence variant calling has been proposed as an alternative to previously established methods for aggregation of sequence reads into operational taxonomic units (OTU). We investigated the utility of variant calling for cpn60 barcode sequences and determined the minimum sequence length required to provide species-level resolution. Sequence data from the 5’ region of the cpn60 barcode amplified from the human vaginal microbiome (n=45), and a mock community were used to compare variant calling to de novo assembly of reads, and mapping to a reference sequence database in terms of number of OTU formed, and overall community composition. Variant calling resulted in microbiome profiles that were consistent in apparent composition to those generated with the other methods but with significant logistical advantages. Variant calling is rapid, achieves high resolution of taxa, and does not require reference sequence data. Our results further demonstrate that 150 bp from the 5’ end of the cpn60 barcode sequence is sufficient to provide species-level resolution of microbiota.
Genome-wide discovery of hidden genes mediating known drug-disease association using KDDANet
Authors: Yu Hua , Lu Lu , Chen Ming , Li Chen , Zhang Jin 
Published: August 2019

AbstractMany of genes mediating Known Drug-Disease Association (KDDA) are escaped from experimental detection. Identifying of these genes (hidden genes) is of great significance for understanding disease pathogenesis and guiding drug repurposing. Here, we presented a novel computational tool, called KDDANet, for systematic and accurate uncovering the hidden genes mediating KDDA from the perspective of genome-wide functional gene interaction network. KDDANet demonstrated the competitive performances in both sensitivity and specificity of identifying genes in mediating KDDA in comparison to the existing state-of-the-art methods. Case studies on Alzheimer’s disease (AD) and obesity uncovered the mechanistic relevance of KDDANet predictions. Furthermore, when applied with multiple types of cancer-omics datasets, KDDANet not only recapitulated known genes mediating KDDAs related to cancer, but also revealed novel candidates that offer new biological insights. Importantly, KDDANet can be used to discover the shared genes mediating multiple KDDAs. KDDANet can be accessed at http://www.kddanet.cn and the code can be freely downloaded at https://github.com/huayu1111/KDDANet.
The Ficus erecta genome to identify the Ceratocystis canker resistance gene for breeding programs in common fig (F. carica)
Authors: Shirasawa Kenta , Yakushiji Hiroshi , Nishimura Ryotaro , Morita Takeshige , Jikumaru Shota , Ikegami Hidetoshi , Toyoda Atsushi , Hirakawa Hideki , Isobe Sachiko 
Published: August 2019

AbstractFicus erecta, a wild relative of common fig (F. carica), is a donor of Ceratocystis canker resistance in fig breeding programs. Interspecific hybridization followed by recurrent backcrossing is an effective method to transfer the resistance trait from wild to cultivated fig; however, this is time consuming and labor-intensive for trees, especially for gynodioecious plants such as fig. In this study, genome resources were developed for F. erecta to facilitate fig breeding programs. The genome sequence of F. erecta was determined using single-molecule real-time sequencing technology. The resultant assembly spanned 331.6 Mb with 538 contigs and an N50 length of 1.9 Mb, from which 51,806 high-confidence genes were predicted. Pseudomolecule sequences corresponding to the chromosomes of F. erecta were established with a genetic map based on single nucleotide polymorphisms from double-digest restriction-site associated DNA sequencing. Subsequent linkage analysis and whole genome resequencing identified a candidate gene for the Ceratocystis canker resistance trait. Genome-wide genotyping analysis enabled selection of female lines that possessed resistance and effective elimination of donor genome from progeny. The genome resources provided in this study will accelerate and enhance disease resistance breeding programs in fig.
Brain permeable AMPK activator R481 raises glycemia by autonomic nervous system activation and amplifies the counterregulatory response to hypoglycemia in rats
Authors: Cruz Ana M. , Malekizadeh Yasaman , Vlachaki Walker Julia M. , Weightman Potter Paul G. , Pye Katherine , Shaw Simon J. , Ellacott Kate L.J. , Beall Craig 
Published: August 2019

ABSTRACTAMP-activated protein kinase (AMPK) is a critical cellular and whole body energy sensor activated by energy stress, including hypoglycemia, which is frequently experienced by people with diabetes. Previous studies using direct delivery of an AMPK activator to the ventromedial hypothalamus (VMH) in rodents increased hepatic glucose production. Moreover, recurrent glucoprivation in the hypothalamus leads to blunted AMPK activation and defective hormonal responses to subsequent hypoglycemia. These data suggest that amplifying AMPK activation may prevent or reduce frequency hypoglycemia in diabetes. We used a novel brain-permeable AMPK activator, R481, which potently increased AMPK phosphorylation in vitro. R481 significantly increased peak glucose levels during glucose tolerance tests in rats, which were attenuated by treatment with AMPK inhibitor SBI-0206965 and completely abolished by blockade of the autonomic nervous system. This occurred without altering insulin sensitivity measured by hyperinsulinemic-euglycemic clamps. Endogenous insulin secretion was not altered by R481 treatment. During hyperinsulinemic-hypoglycemic clamp studies, R481 treatment reduced exogenous glucose requirements and amplified peak glucagon levels during hypoglycemia. These data demonstrate that peripheral administration of the brain permeable AMPK activator R481 amplifies the counterregulatory response to hypoglycemia in rats, which could have clinical relevance for prevention of hypoglycemia.
Adaptation and correlated fitness responses over two time scales in Drosophila suzukii populations evolving in different environments
Authors: Olazcuaga Laure , Foucaud Julien , Gautier Mathieu , Deschamps Candice , Loiseau Anne , Leménager Nicolas , Facon Benoit , Ravigné Virginie , Hufbauer Ruth A. , Estoup Arnaud , Rode Nicolas O. 
Published: August 2019

AbstractThe process of local adaptation involves differential changes in fitness over time across different environments. While experimental evolution studies have extensively tested for patterns of local adaptation at a single time point, there is relatively little research that examines fitness more than once during the time course of adaptation. We allowed replicate populations of the fruit pest Drosophila suzukii to evolve in one of eight different fruit media. After five generations, populations with the highest initial levels of maladaptation had mostly gone extinct, whereas experimental populations evolving on cherry, strawberry and cranberry media had survived. We measured the fitness of each surviving population in each of the three fruit media after five and after 26 generations of evolution. After five generations, adaptation to each medium was associated with increased fitness in the two other media. This was also true after 26 generations, except when populations that evolved on cranberry medium developed on cherry medium. These results suggest that, in the theoretical framework of a fitness landscape, the fitness optima of cherry and cranberry media are the furthest apart. Our results show that studying how fitness changes across several environments and across multiple generations provides insights into the dynamics of local adaptation that would not be evident if fitness were analyzed at a single point in time. By allowing a qualitative mapping of an experimental fitness landscape, our approach will improve our understanding of the ecological factors that drive the evolution of local adaptation in D. suzukii.
BANDITS: Bayesian differential splicing accounting for sample-to-sample variability and mapping uncertainty
Authors: Tiberi Simone , Robinson Mark D 
Published: August 2019

AbstractAlternative splicing is a biological process during gene expression that allows a single gene to code for multiple proteins. However, splicing patterns can be altered in some conditions or diseases. Here, we present BANDITS, a R/Bioconductor package to perform differential splicing, at both gene and transcript-level, based on RNA-seq data. BANDITS uses a Bayesian hierarchical structure to explicitly model the variability between samples, and treats the transcript allocation of reads as latent variables. We perform an extensive benchmark across both simulated and experimental RNA-seq datasets, where BANDITS has extremely favorable performance with respect to the competitors considered.
Clathrin’s adaptor interaction sites are repurposed to stabilize microtubules during mitosis
Authors: Rondelet Arnaud , Lin Yu-Chih , Singh Divya , Porfetye Arthur T. , Thakur Harish C. , Hecker Andreas , Brinkert Pia , Schmidt Nadine , Bendre Shweta , Müller Franziska , Widlund Per O. , Bange Tanja , Hiller Michael , Vetter Ingrid R. , Bird Alexander W. 
Published: August 2019

SUMMARYClathrin plays an important role to ensure mitotic spindle stability and efficient chromosome alignment, independently of its well-characterized functions in vesicle trafficking. While clathrin clearly localizes to the mitotic spindle and kinetochore-fiber microtubule bundles, the mechanisms by which clathrin stabilizes microtubules have remained elusive. Here we show that clathrin adaptor interaction sites on clathrin heavy chain (CHC) are repurposed during mitosis to directly recruit the microtubule-stabilizing protein GTSE1 to the mitotic spindle. Structural analyses reveal that multiple clathrin-box motifs on GTSE1 interact directly with different clathrin adaptor interaction sites on CHC, in a manner structurally analogous to that which occurs between adaptor proteins and CHC near membranes. Specific disruption of this interaction in cells releases GTSE1 from spindles and causes defects in chromosome alignment. Surprisingly, this disruption causes destabilization of astral microtubules, but not kinetochore-microtubule attachments, and the resulting chromosome alignment defect is due to a failure of chromosome congression independent of kinetochore-microtubule attachment stability. Finally, we show that GTSE1 recruited to the spindle by clathrin stabilizes microtubules and promotes chromosome congression by inhibiting the activity of the microtubule depolymerase MCAK. This work thus uncovers a novel role of clathrin to stabilize non-kinetochore-fiber microtubules to support chromosome congression. This role is carried out via clathrin adaptor-type interactions of CHC with GTSE1, defining for the first time an important repurposing of this endocytic interaction mechanism during mitosis.
Prognostic value of Red Blood Cell Distribution Width in Acute Kidney Injury Patients: A Systematic Review and Meta-analysis
Authors: Liu Zhengsheng , Wang Shanshan , Yao Xiongbo , Xing Jinchun 
Published: August 2019

AbstractBackgroundThe conflicting result with regard to Red Cell Distribution Width (RDW) with Acute Kidney Injury (AKI) has been reported. This systematic review and meta-analysis were aimed to investigate RDW and prognostic value in AKI patients.Methods/Main ResultsThis meta-analysis included 1251 cases and 1663 controls with a total of 7 enrolled published papers. The results of RDW levels were significantly associated with patients of AKI (WMD=1.127, 95% CI=0.426-1.827; P=0.002), with statistically significant heterogeneity (I2 =95.80%, Pheterogeneity =0.000, random-effects model).ConclusionsIn conclusion, the results of this present meta-analysis suggest that the RDW value is a positive prognostic indicator in patients with AKI. However, these results were obtained on the basis of RCS or small sample sizes studies. Further functional studies with additional data would be needed to validate our findings.
ORAL HEALTH BEHAVIOUR PERCEPTION SCALE APPLIED AMONG A SAMPLE OF PORTUGUESE ADOLESCENTS
Authors: Veiga Nélio Jorge , Amaral Odete , Correia Maria José , Coelho Inês 
Published: August 2019

AbstractIntroductionThe application of a scale can be particularly useful for the epidemiological studies comparing different populations and for analysis of the influence of distinct aspects of oral health on the development of certain health conditions. The aim of this study consists in the creation of a scale to classify the level of perception of the oral health behaviors applicable to the sample of Portuguese adolescents.Materials and methodsAn observational cross-sectional study was designed with a total of 649 adolescents between the ages of 12 and 18 years old from five public schools in the Viseu and Guarda districts, in Portugal. Data was collected by the application of a self-administered questionnaire and, after analysis of data collection, the newly Universidade Católica Portuguesa (UCP) oral health perception scale was created.ResultsAnalyzing the sample included in the present study, we verified, by the UCP oral health perception scale created, that 67.9% of the sample presented a poor perception of their oral health behaviors, 23.9% intermediate/sufficient and only 8.2% presented what is considered in the scale as having a good classification in terms of oral health behaviors perception respecting the assumptions defined for the elaboration of the present scale.ConclusionsFor this purpose, through the scale to classify the level of oral health behaviors applicable to the sample of portuguese adolescents, it is possible to compare the data of several samples and understand what are the most frequent oral or eating habits among adolescents.
Incorporating evaporative water loss into bioenergetic models of hibernation to test for relative influence of host and pathogen traits on white-nose syndrome
Authors: Haase Catherine G. , Fuller Nathan W. , Hranac C. Reed , Hayman David T. S. , McGuire Liam P. , Norquay Kaleigh J. O. , Silas Kirk A. , Willis Craig K. R. , Plowright Raina K. , Olson Sarah H. 
Published: August 2019

AbstractHibernation consists of extended durations of torpor interrupted by periodic arousals. The ‘dehydration hypothesis’ proposes that hibernating mammals arouse to replenish water lost through evaporation during torpor. Arousals are energetically expensive, and increased arousal frequency can alter survival throughout hibernation. Yet we lack a means to assess the effect of evaporative water loss (EWL), determined by animal physiology and hibernation microclimate, on torpor bout duration and subsequent survival. White-nose syndrome (WNS), a devastating disease impacting hibernating bats, causes increased frequency of arousals during hibernation and EWL has been hypothesized to contribute to this increased arousal frequency. WNS is caused by a fungus, which grows well in humid hibernaculum environments and damages wing tissue important for water conservation. Here, we integrated the effect of EWL on torpor expression in a hibernation energetics model, including the effects of fungal infection, to determine the link between EWL and survival. We collected field data forMyotis lucifugus, a species that experiences high mortality from WNS, to gather parameters for the model. In saturating conditions we predicted healthy bats experience minimal mortality. Infected bats, however, suffer high fungal growth in highly saturated environments, leading to exhaustion of fat stores before spring. Our results suggest that host adaptation to humid environments leads to increased arousal frequency from infection, which drives mortality across hibernaculum conditions. Our modified hibernation model provides a tool to assess the interplay between host physiology, hibernaculum microclimate, and diseases such as WNS on winter survival.