bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosomal replication origins inCandida albicansare genetically defined irrespective of their chromosomal context
Authors: Mitra Sreyoshi 
Published: October 2020

AbstractInitiation of DNA replication occurs at specialized regions along chromosomes called origins. The knowledge of replication origins is imperative to understand regulation of DNA replication. The properties of replication origins in the pathogenic budding yeastCandida albicansremain enigmatic in the absence of the knowledge of authentic chromosomal origins. Earlier, we identified centromere proximal (pCEN) chromosomal origins on chromosomes 5 and 7 ofC. albicans. Here, we identify another centromere-distal (dCEN) chromosomal origin by two-dimensional agarose gel electrophoresis corresponding to a previously reported autonomously replicating sequence (ARS), CARS2. We show that all the identified chromosomal origins are bound byC. albicanshomologs of conserved pre-replication complex proteins Orc2 and Mcm2. Previous reports from our lab and others have shown that there is a strong inter-relationship between centromere function and pericentric origin activity, suggesting that these origins are epigenetically regulated. However, we find that short intergenic regions corresponding to each of these origins functions as an ARS element in circular plasmids. Further, we use the novel strategy ofin vivogap repair to demonstrate that circular ARS plasmids can exist independentlyin vivoinC. albicans.Taken together, these results show that DNA sequence underlies the function of both centromere proximal and centromere distal chromosomal origins inC. albicans.
In Pursuit of a Better Broiler: Growth, Efficiency and Mortality of 16 Strains of Broiler Chickens
Authors: Torrey Stephanie , Mohammadigheisar Mohsen , dos Santos Midian Nascimento , Rothschild Daniel , Dawson Lauren , Liu Zhenzhen , Kiarie Elijah , Edwards A. Michelle , Mandell Ira , Karrow Niel , Tulpan Dan , Widowski Tina 
Published: October 2020

ABSTRACTTo meet the growing consumer demand for chicken meat, the poultry industry has selected broiler chickens for increasing efficiency and breast yield. While this high productivity means affordable and consistent product, it has come at a cost to broiler welfare. There has been increasing advocacy and consumer pressure on primary breeders, producers, processors and retailers to improve the welfare of the billions of chickens processed annually. Several small-scale studies have reported better welfare outcomes for slower growing strains compared to fast growing, conventional strains. However, these studies often housed birds with range access or used strains with vastly different growth rates. Additionally, there may be traits other than growth, such as body conformation, that influence welfare. As the global poultry industries consider the implications of using slower growing strains, there was a need for a comprehensive, multidisciplinary examination of broiler chickens with a wide range of genotypes differing in growth rate and other phenotypic traits. To meet this need, our team designed a study to benchmark data on conventional and slower growing strains of broiler chickens reared in standardized laboratory conditions. Over a two-year period, we studied 7,528 broilers from 16 different genetic strains. In this paper, we compare the growth, efficiency and mortality of broilers to one of two target weights (TW): 2.1 kg (TW1) and 3.2 kg (TW2). We categorized strains by their growth rate to TW2 as conventional (CONV), fastest slow strains (FAST), moderate slow strains (MOD) and slowest slow strains (SLOW). When incubated, hatched, housed, managed and fed the same, the categories of strains differed in body weights, growth rates, feed intake and feed efficiency. At 48 days of age, strains in the CONV category were 835-1264 g heavier than strains in the other categories. By TW2, differences in body weights and feed intake resulted in a 22 to 43-point difference in feed conversion ratios. Categories of strains did not differ in their overall mortality rates.
Microbiome signatures in a fast and slow progressing gastric cancer murine model and their contribution to gastric carcinogenesis
Authors: Bali Prerna , Coker Joanna , Lozano-Pope Ivonne , Zengler Karsten , Obonyo Marygorret 
Published: October 2020

AbstractGastric cancer is the third most common cancer in the world andHelicobacter spp. being one of the main factors responsible for development of cancer. AlongsideHelicobacterthe microbiota of the stomach mucosa may also play an important role in gastric cancer progression. Previously we had established that MyD88 deficient mice rapidly progressed to neoplasia when infected withH. felis. Thus, in order to assess the role of microbiota in gastric cancer progression we measured the changes in microbial diversity of the stomach in mice with different genotypic backgrounds (Wild type (WT), MyD88 deficient (MyD88−/−), mice deficient in the Toll/IL-1R (TIR) domain-containing adaptor-inducing interferon-β (TRIF,Triflps2), and MyD88 and Trif deficient (MyD88−/−and Trif−/−)double knockout (DKO) mice), both in uninfected andHelicobacterinfected mice and its correlation of these changes with gastric cancer progression. We observed that there was an overall reduction in microbial diversity post infection withH. felisacross all genotypes.Campylobacteraleswere observed in all infected mice, with marked reduction in abundance at 3 and 6 months in MyD88−/−mice. This low abundance ofH. pyloricould facilitate dominance of other organisms of microbiome likeLactobacilliales. A sharp increase inLactobacillialesin infected MyD88−/−and DKO mice at 3 and 6 months was observed as compared to Trif−/−and WT mice suggesting its possible role in gastric cancer progression. This was further reinforced upon comparison ofLactobacillusratio with histological data suggesting thatLactobacillalesis closely associated withHelicobacterinfection and gastric cancer progression. Thus, this study firstly suggests that difference in genotypes could define the stomach microbiome and make it more susceptible to development of gastric cancer uponHelicobacterinfections. Secondly the increase inLactobacillalescould contribute to faster development of gastric cancer and serve as a probable bio marker for fast progressing form of gastric cancer.
Multi-omics integration analysis identifies novel genes for alcoholism with potential link to neurodegenerative diseases
Authors: Kapoor Manav , Chao Michael , Johnson Emma C. , Novikova Gloriia , Lai Dongbing , Meyers Jacquelyn , Schulman Jessica , Nurnberger John I , Porjesz Bernice , Liu Yunlong ,   COGA collaborators, Tatiana Foroud, Edenberg Howard J. , Marcora Edoardo , Agrawal Arpana , Goate Alison 
Published: October 2020

AbstractSignificanceIdentification of causal variants and genes underlying genome-wide association study (GWAS) loci is essential to understanding the biology of alcohol use disorder (AUD).MethodsIntegration of “multi-omics” data is often necessary to nominate candidate causal variants and genes and prioritize them for follow up studies. Here, we used Mendelian randomization to integrate AUD and drinks per week (DPW) GWAS summary statistics with the gene expression and methylation quantitative trait loci (eQTLs and mQTLs) in the largest brain and myeloid datasets. We also used AUD-related single cell epigenetic data to nominate candidate causal variants and genes associated with DPW and AUD.ResultsOur multi-omics integration analyses prioritized unique as well as shared genes and pathways among AUD and DPW. The GWAS variants associated with both AUD and DPW showed significant enrichment in the promoter regions of fetal and adult brains. The integration of GWAS SNPs with mQTLs from fetal brain prioritized variants on chromosome 11 in both AUD and DPW GWASs. The co-localized variants were found to be overlapping with promoter marks forSPI1,specifically in human microglia, the myeloid cells of the brain. The co-localized SNPs were also strongly associated withSPI1mRNA expression in myeloid cells from peripheral blood. The prioritized variant at this locus is predicted to alter the binding site for a transcription factor, RXRA, a key player in the regulation of myeloid cell function. Our analysis also identifiedMAPTas a candidate causal gene specifically associated with DPW. mRNA expression ofMAPTwas also correlated with daily amounts of alcohol intake in post-mortem brains (frontal cortex) from alcoholics and controls (N = 92). Results may be queried and visualized in an online public resource of these integrative analysis (https://lcad.shinyapps.io/alc_multiomics/). These results highlight overlap between causal genes for neurodegenerative diseases, alcohol use disorder and alcohol consumption.In conclusionintegrating GWAS summary statistics with multi-omics datasets from multiple sources identified biological similarities and differences between typical alcohol intake and disordered drinking highlighting molecular heterogeneity that might inform future targeted functional and cross-species studies. Interestingly, overlap was also observed with causal genes for neurodegenerative diseases.
Multiomics data collection, visualization, and utilization for guiding metabolic engineering
Authors: Roy Somtirtha , Radivojevic Tijana , Forrer Mark , Marti Jose Manuel , Jonnalagadda Vamshi , Backman Tyler , Morrell William , Plahar Hector , Kim Joonhoon , Hillson Nathan , Martin Hector Garcia 
Published: October 2020

AbstractBiology has changed radically in the past two decades, growing from a purely descriptive science into also a design science. The availability of tools that enable the precise modification of cells, as well as the ability to collect large amounts of multimodal data, open the possibility of sophisticated bioengineering to produce fuels, specialty and commodity chemicals, materials, and other renewable bioproducts. However, despite new tools and exponentially increasing data volumes, synthetic biology cannot yet fulfill its true potential due to our inability to predict the behavior of biological systems. Here, we present a set of tools that, combined, provide the ability to store, visualize and leverage these data to predict the outcome of bioengineering efforts.
Structural studies onM. tuberculosisdecaprenyl phosphoryl-β-D-ribose epimerase-2 enzyme involved in cell wall biogenesis
Authors: Gangwar Shanti P. , Bandyopadhyay Arkita , Saxena Ajay K. 
Published: October 2020

AbstractTheMycobacteriumDprE2 is a NADH-dependent enzyme and converts the decaprenylphosphoryl-β-D-ribose (DPX) to decaprenylphosphoryl-β-D-arabinofuranose (DPA). The FAD-containing oxidoreductaseMtbDprE1and NADH-dependent reductaseMtbDprE2enzymes catalyses together the epimerization reaction, which coverts DPR to DPA. Here,MtbDprE2enzyme was purified and structurally characterized using circular dichroism, molecular modelling and dynamics simulation techniques. TheMtbDprE2was purified, which eluted as oligomer from size exclusion column. The circular dichroism analysis yielded ~ 47.6% α-helix, ~ 19.8% β-sheet and ~ 32.6% random coil structures inMtbDprE2enzyme and showed highly thermostability. The molecular modelling ofMtbDprE2and its complex with NADH showed that it contains two domains (i) the large domain consists of central twisted seven β-sheets decorated by eight α-helices and (ii) a small domain contains two short α-helices connect by loop. Overall, theMtbDprE2adopts a typical short-chain dehydrogenase rossmann fold and NADH binds to Asp69, Ser147, Tyr160, Lys164 of catalytic triad and Gly16, Ser19, Glu20, Ile21 of Gly-rich motif ofMtbDprE2. 1 ns dynamics simulation was performed on apo and NADH boundMtbDprE2, which indicated the small conformational change in ligand binding site, which resulted more closed pocket than open pocket observed in apo enzyme. Small conformational changes were observed in active site residues and orientation between large and small domains ofMtbDprE2upon NADH binding. Current knowledge ofMtbDprE2structure and its NADH binding mechanism will contribute significantly in development of specific inhibitors againstM. tuberculosis.
Avoiding tensional equilibrium in cells migrating on a matrix with cell-scale stiffness-heterogeneity
Authors: Ebata Hiroyuki , Kidoaki Satoru 
Published: October 2020

AbstractIntracellular stresses affect various cell functions, including proliferation, differentiation and movement, which are dynamically modulated in migrating cells through continuous cell-shaping and remodeling of the cytoskeletal architecture induced by spatiotemporal interactions with extracellular matrix stiffness. When cells migrate on a matrix with cell-scale stiffness-heterogeneity, which is a common situation in living tissues, what intracellular stress dynamics (ISD) emerge? In this study, to explore this issue, finite element method-based traction force microscopy was applied to cells migrating on microelastically patterned gels. Two model systems of microelastically patterned gels (stiff/soft stripe and stiff triangular patterns) were designed to characterize the effects of a spatial constraint on cell-shaping and of the presence of different types of cues to induce competing cellular taxis (usual and reverse durotaxis) on the ISD, respectively. As the main result, the prolonged fluctuation of traction stress on a whole-cell scale was markedly enhanced on single cell-size triangular stiff patterns compared with homogeneous gels. Such ISD enhancement was found to be derived from the interplay between the nomadic migration of cells to regions with different degrees of stiffness and domain shape-dependent traction force dynamics, which should be an essential factor for keeping cells far from tensional equilibrium.
Quantitative assessment of NCLDV–host interactions predicted by co-occurrence analyses
Authors: Meng Lingjie , Endo Hisashi , Blanc-Mathieu Romain , Chaffron Samuel , Hernández-Velázquez Rodrigo , Kaneko Hiroto , Ogata Hiroyuki 
Published: October 2020

AbstractNucleocytoplasmic DNA viruses (NCLDVs) are highly diverse and abundant in marine environments. However, knowledge of their hosts is limited because only a few NCLDVs have been isolated so far. Taking advantage of the recent large-scale marine metagenomics census,in silicohost prediction approaches are expected to fill the gap and further expand our knowledge of virus–host relationships for unknown NCLDVs. In this study, we built co-occurrence networks of NCLDVs and eukaryotic taxa to predict virus–host interactions usingTaraOceans sequencing data. Using the positive likelihood ratio to assess the performance of host prediction for NCLDVs, we benchmarked several co-occurrence approaches and demonstrated an increase in the odds ratio of predicting true positive relationships four-fold compared with random host predictions. To further refine host predictions from high-dimensional co-occurrence networks, we developed a phylogeny-informed filtering method, Taxon Interaction Mapper, and showed it further improved the prediction performance by twelve-fold. Finally, we inferred virophage – NCLDV networks to corroborate that co-occurrence approaches are effective for predicting interacting partners of NCLDVs in marine environments.ImportanceNCLDVs can infect a wide range of eukaryotes although their life cycle is less dependent on hosts compared with other viruses. However, our understanding of NCLDV– host systems is highly limited because few of these viruses have been isolated so far. Co-occurrence information has been assumed to be useful to predict virus–host interactions. In this study, we quantitatively show the effectiveness of co-occurrence inference for NCLDV host prediction. We also improve the prediction performance with a phylogeny-guided method, which leads to a concise list of candidate host lineages for three NCLDV families. Our results underpin the usage of co-occurrence approach for metagenomic exploration of the ecology of this diverse group of viruses.
α-Synuclein strains influence multiple system atrophy via central and peripheral mechanisms
Authors: Torre Murazabal T. , Van der Perren A. , Coens A. , Barber Janer A. , Camacho-Garcia S. , Stefanova N. , Melki R. , Baekelandt V. , Peelaerts W. 
Published: October 2020

AbstractMultiple system atrophy (MSA) is a progressive neurodegenerative disease with prominent autonomic and motor features. Different disease subtypes are distinguished by their predominant parkinsonian or cerebellar signs. The pathognomonic feature of MSA is the presence of α-synuclein (αSyn) protein deposits in glial cells of the central and peripheral nervous system. It is unclear why MSA, that invariably presents with αSyn pathology, is clinically so heterogeneous, why it progresses at varying rates and how neuroinflammation affects disease progression. Recently, it was shown that different strains of αSyn can assemble in unique disease environments but also that a variety of strains might exist in the brain of MSA patients. We therefore investigated if different αSyn strains might influence MSA disease progression. To this aim, we injected two recombinant strains of αSyn in MSA transgenic mice and found that they significantly impact MSA disease progression in a strain-dependent way via oligodendroglial, neurotoxic and immune-related mechanisms. Neurodegeneration and brain atrophy were accompanied by unique microglial and astroglial responses and the recruitment of central and peripheral immune cells. The differential activation of microglial cells correlated with the structural features of αSyn strains bothin vitroandin vivo. By injecting αSyn strains in MSA mice we could more closely mimic a comprehensive MSA phenotype in an experimental setting. This study therefore shows that i) MSA phenotype is governed by both the αSyn strain nature and the host environment and ii) αSyn strains can directly trigger a detrimental immune response related to disease progression in MSA.
Similarity-based information fusion grey model for remaining useful life prediction of aircraft engines
Authors: Yang Xiaoyu , Fang Zhigeng , Li Xiaochuan , Yang Yingjie , Mba David 
Published: October 2020

PurposeOnline health monitoring of large complex equipment has become a trend in the field of equipment diagnostics and prognostics due to the rapid development of sensing and computing technologies. The purpose of this paper is to construct a more accurate and stable grey model based on similar information fusion to predict the real-time remaining useful life (RUL) of aircraft engines.Design/methodology/approachFirst, a referential database is created by applying multiple linear regressions on historical samples. Then similarity matching is conducted between the monitored engine and historical samples. After that, an information fusion grey model is applied to predict the future degradation trajectory of the monitored engine considering the latest trend of monitored sensory data and long-term trends of several similar referential samples, and the real-time RUL is obtained correspondingly.FindingsThe results of comparative analysis reveal that the proposed model, which is called similarity-based information fusion grey model (SIFGM), could provide better RUL prediction from the early degradation stage. Furthermore, SIFGM is still able to predict system failures relatively accurately when only partial information of the referential samples is available, making the method a viable choice when the historical whole life cycle data are scarce.Research limitations/implicationsThe prediction of SIFGM method is based on a single monotonically changing health indicator (HI) synthesized from monitoring sensory signals, which is assumed to be highly relevant to the degradation processes of the engine.Practical implicationsThe SIFGM can be used to predict the degradation trajectories and RULs of those online condition monitoring systems with similar irreversible degradation behaviors before failure occurs, such as aircraft engines and centrifugal pumps.Originality/valueThis paper introduces the similarity information into traditional GM(1,1) model to make it more suitable for long-term RUL prediction and also provide a solution of similarity-based RUL prediction with limited historical whole life cycle data.
Pedagogical strategies and challenges of multigrade schoolteachers in Albay, Philippines
Authors: Bongala Judy Vargas , Bobis Vanessa Baraero , Castillo John Paul Ramos , Marasigan Arlyne Canales 
Published: October 2020

PurposeThis paper aims to examine the pedagogical strategies and challenges of selected multigrade (MG) schoolteachers in Albay, Philippines.Design/methodology/approachThis study utilized a case study design using a validated semi-structured instrument with in-depth interviews to ten MG teachers, observation and document analysis. Qualitative data analyses such as content and thematic analyses were used in analyzing the data.FindingsThe results show that MG teachers use a variety of overlapping and supplementary instructional strategies such as (1) teaching one topic to all grades and at varying levels of difficulty using differentiated activity, (2) “jump-jump strategy”/teaching one grade while others work independently and (3) peer teaching or tutoring. However, there are several pedagogical challenges that MG teachers are faced with: (1) conflict between the medium of instructions and grade grouping, (2) problems with lesson planning, (3) unfocused instruction, (4) insufficient learners' materials, (5) absence of training prior to MG teaching and (6) the negative perception of the effectiveness of MG instructions.Research limitations/implicationsThe research is limited within the context of the participants and focuses on the pedagogical strategies and challenges in the implementation of MG teaching.Practical implicationsThe results of this study can serve as a reference on how to support and strengthen MG instruction.Originality/valueThis study provides a research-based overview of MG schools from the grassroots level and adds to the limited studies of MG education in the Philippines.
Learning from the ambiguous past with project reviews
Authors: Christiansen John K. , Mouritsen Jan 
Published: October 2020

PurposeKnowledge is supposedly a good ally of the future. Postproject reviews aim to create knowledge and improvements based on the past, but what happens when those observations are ambiguous? Based on intriguing observations on developing structured postproject reviews, implications of the ambiguities of the past are analyzed and discussed.Design/methodology/approachThe present research departed from an interactive clinical action research approach (Schein, 1987), employing several rounds of interaction over 11 months. The studied company had a clear objective to improve its project evaluations and learn from three past projects to improve future ones by developing a framework to facilitate project evaluation.FindingsDespite top management support and a benevolent organizational climate, the development process encountered problems. The list of issues to consider grew ever more extensive, and the expected data refinement and accompanying insights did not happen. Participants debated what to observe, and there was uncertainty about how to link the elements and confusion and disagreement about what was learned.Research limitations/implicationsLearning from past projects was more problematic and difficult than predicted based on the postproject review literature. The past did purvey multiple interpretations.Practical implicationsLearning from the past is not effective if the goal is generating causal knowledge, scoring forms and checklists for future use. Postproject reviews provide an opportunity to decide what the past should be about rather than identifying what it was about.Originality/valueThe past might appear stable, but, when examined, ambiguity emerges. Research on knowledge generation from postproject reviews assumes that a project’s past is more or less stable and agreed upon. However, this study addresses the critical role of ambiguity about the past and the challenges when organizations try to learn from history through project reviews and evaluation processes.