bluuebunny/crossref_metadata_2025_split huggingface dataset:
Xenogeneic regulation of the ClpCP protease ofBacillus subtilisby a phage-encoded adaptor-like protein
Authors: Mulvenna Nancy , Hantke Ingo , Burchell Lynn , Nicod Sophie , Turgay Kürşad , Wigneshweraraj Sivaramesh 
Published: March 2019

AbstractSPO1 phage infection ofBacillus subtilisresults in a comprehensive remodelling of processes leading to conversion of the bacterial cell into a factory for phage progeny production. A cluster of 26 genes in the SPO1 genome, called the host takeover module, encodes for potentially cytotoxic proteins for the specific shut down of various host processes including transcription, DNA synthesis and cell division. However, the properties and bacterial targets of many genes of the SPO1 host takeover module remain elusive. Through a systematic analysis of gene products encoded by the SPO1 host takeover module we identified eight gene products which attenuatedB. subtilisgrowth. Out of the eight gene products that attenuated bacterial growth, a 25 kDa protein, called Gp53, was shown to interact with the AAA+ chaperone protein ClpC of the ClpCP protease ofB. subtilis. Results reveal that Gp53 functions like a phage encoded adaptor protein and thereby appears to alter the substrate specificity of the ClpCP protease to modulate the proteome of the infected cell to benefit efficient SPO1 phage progeny development. It seems that Gp53 represents a novel strategy used by phages to acquire their bacterial prey.Significance statementViruses of bacteria (phages) represent the most abundant living entities on the planet, and many aspects of our fundamental knowledge of phage–bacteria relationships remain elusive. Many phages encode specialised small proteins, which modulate essential physiological processes in bacteria in order to convert the bacterial cell into a ‘factory’ for phage progeny production – ultimately leading to the demise of the bacterial cell. We describe the identification of several antibacterial proteins produced by a prototypical phage that infectsBacillus subtilisand describe how one such protein subverts the protein control system of its host to benefit phage progeny development. The results have broad implications for our understanding of phage–bacteria relationships and the therapeutic application of phages and their gene products.
Transduction of gluconeogenic enzymes prolongs cone photoreceptor survival and function in models of retinitis pigmentosa
Authors: Chinchore Yashodhan , Begaj Tedi , Guillermeir Christelle , Steinhauser Matthew L. , Punzo Claudio , Cepko Constance L. 
Published: March 2019

AbstractThe hereditary nature of many retinal degenerative disorders makes them potentially amenable to corrective gene therapies. Numerous clinical trials are ongoing with the goal to rectify the genetic defect in the afflicted cell types. However, the personalized nature of these approaches excludes many patients for whom the underlying mutation is not mapped, or the number of affected individuals is too few to develop a commercially viable therapy (vide infra). Thus, a therapy that can delay visual impairment irrespective of the underlying genetic etiology can satisfy this unmet medical need. Here, we demonstrate the utility of such an approach in retinitis pigmentosa (RP) by promoting survival of cone photoreceptors by targeting metabolic stress. These cells are not primarily affected by the inherited mutation, but their non-autonomous demise leads to a decline in daylight vision, greatly reducing the quality of life. We designed adeno-associated virus (AAV) vectors that promote gluconeogenesis- a pathway found in the liver which produces glucose in response to hypoglycemia. Retinal transduction with these vectors resulted in improved cone survival and delayed a decline in visual acuity in three different RP mouse models. Because this approach extended visual function independent of the primary mutation, therapies emanating from this approach could be used as a treatment option for a genetically heterogenous cohort of patients.
Ciliary Genesarl13b,ahi1andcc2d2aDifferentially Modify Expression of Visual Acuity Phenotypes but do not Enhance Retinal Degeneration due to Mutation ofcep290 in Zebrafish
Authors: Lessieur Emma M. , Song Ping , Nivar Gabrielle C. , Piccillo Ellen M. , Fogerty Joseph , Rozic Richard , Perkins Brian D. 
Published: March 2019

ABSTRACTMutations in the gene Centrosomal Protein 290 kDa (CEP290) result in multiple ciliopathies ranging from the neonatal lethal disorder Meckel-Gruber Syndrome to multi-systemic disorders such as Joubert Syndrome and Bardet-Biedl Syndrome to nonsyndromic diseases like Leber Congenital Amaurosis (LCA) and retinitis pigmentosa. Results from model organisms and human genetics studies, have suggest that mutations in genes encoding protein components of the transition zone (TZ) and other cilia-associated proteins can function as genetic modifiers and be a source forCEP290pleiotropy. We investigated the zebrafishcep290fh297/fh297mutant, which encodes a nonsense mutation (p.Q1217*). This mutant is viable as adults, exhibits scoliosis, and undergoes a slow, progressive cone degeneration. Thecep290fh297/fh297mutants showed partial mislocalization of the transmembrane protein rhodopsin but not of the prenylated proteins rhodopsin kinase (GRK1) or the rod transducin subunit GNB1. Surprisingly, photoreceptor degeneration did not trigger proliferation of Müller glia, but proliferation of rod progenitors in the outer nuclear layer was significantly increased. To determine if heterozygous mutations in other cilia genes could exacerbate retinal degeneration, we bredcep290fh297/fh297mutants toarl13b, ahi1,andcc2d2amutant zebrafish lines. Whilecep290fh297/fh297mutants lacking a single allele of these genes did not exhibit accelerated photoreceptor degeneration, loss of one alleles ofarl13borahi1reduced visual performance in optokinetic response assays at 5 days post fertilization. Our results indicate that thecep290fh297/fh297mutant is a useful model to study the role of genetic modifiers on photoreceptor degeneration in zebrafish and to explore how progressive photoreceptor degeneration influences regeneration in adult zebrafish.Nonstandard abbreviationsBBSBardet-Biedl SyndromeCOScone outer segmentsDpfDays post fertilizationGNB1rod transducin β subunitGRK1rhodopsin kinaseJTBSJoubert SyndromeLCALeber Congenital AmaurosisMKSMeckel SyndromeNPHPnephronophthisisOKRoptokinetic responsePNApeanut agglutinin lectinROSrod outer segmentsRP2Retinitis Pigmentosa 2
Determination of glucosinolate contents in Brassica germplasm collections and inter- & intra-leaves distribution pattern using UPLC-MS/MS Multiple Reaction Monitoring scan mode
Authors: Assefa Awraris Derbie , Choi Susanna , Lee Jae-Eun , Sung Jung-Sook , Hur On-Sook , Ro Na-Young , Lee Ho-Sun , Noh Jaejong , Hwang Aejin , Ko Ho-Cheol , Chung Yun-Jo , Rhee Ju-Hee 
Published: March 2019

AbstractIntact glucosinolate (GSL) profile (five aliphatic; three aromatic, and one indolic glucosinolate) in the leaves of 50 germplasm collections and commercial cultivars of Brassica rapa, Brassica juncea, and Brassica oleracea collected from six different countries and grown under uniform cultural conditions were compared by UPLC-MS/MS. Total GSLs content ranged from 36.80 to 2383.12 μmol/kg DW. Aliphatic GSLs predominated among the entire samples representing from 23.0 to 98.9% of the total GSLs content, where gluconapin and glucobrassicanapin contributed the greatest proportion. Other GSLs such as, progoitrin (PRO), glucotropaeolin (TRO), and glucobarbarin (BAR) were found in relatively low concentrations. Principal Component Analysis (PCA) yielded three principal components with eigenvalue ≥ 1, representing 70.33% of the total variation across the entire data set. Accessions IT260822 & IT32750, and commercial cultivar, “Hangamssam2”, were well distinguished from other samples in the PCA plot due to their significantly high amount of BAR, glucobrassicin (GBC), and glucoerucin (ERU), respectively. The inter- and intra-leaf variations of GSLs were examined in three kimichi cabbage varieties. The GSLs content varied significantly among leaves in different positions (outer, middle, and inner) and sections within the leaves (top, middle, bottom, green/red, and white). Higher GSL contents were observed in the proximal half & white section of the leaves and inner positions (younger leaves) in most of the samples. GBC, gluconasturtiin (NAS), and glucoberteroin (BER) should be studied profusely in Brassica plants as some of their degradation products of GBC and NAS are useful in cancer chemopreventive functions, whereas BER takes part in the process of suppressing aging of the skin. GSLs are regarded as allelochemicals; hence, the data related to the patterns of GSLs within the leaf and between leaves at different position could be useful to understand the defense mechanism of Brassica plants. The observed variability could be useful for breeders to develop Brassica crops with high GSL content or specific profiles of GSLs as required.
Hydrology-informed metapopulation modeling of liver fluke transmission in the Lawa Lake complex of northeast Thailand
Authors: León Tomás M. , Plermkamon Vichian , Kuntiyawichai Kittiwet , Sripa Banchob , Spear Robert C. 
Published: March 2019

AbstractWhile hydrologic processes are intuitively understood to influence transmission dynamics of water-related diseases, limited research exists that explicitly links hydrologic and infectious disease data. In the case of the life cycle of liver flukes, hydrology influences several transmission processes that mediate infection risk for multiple hosts. Northeast Thailand is a hotspot for liver fluke transmission and has strong seasonal flooding patterns. A metapopulation model linking local hydrologic processes with transmission of the liver fluke Opisthorchis viverrini in a lake system in northeast Thailand was developed and parameterized using infection data from 2008-2016. A rainfall-runoff model and other hydrologic data were used to assess level of connectivity between villages and the influence of upstream communities on parasite distribution in the study area. Disease transmission was modeled with metapopulations representing six village clusters around the lake using known prevalence data from humans, cats and dogs, snails, and fish. The metapopulation model improved upon the single-village model in its match to historical data patterns for the six village clusters with the introduction of the new time-variable parameters. Results suggest there are three unique hydrologic-epidemiologic regimes within the Lawa Lake system in response to upstream watersheds and risk of overland flooding that contribute to risk for O. viverrini infection. While available data may be insufficient to specifically characterize exact transmission dynamics, the practical implications of such findings are the importance of addressing connectivity for any intermediate host-based intervention. Similar approaches using hydrologic data to assess the impacts of water on pathogen transmission dynamics and inform mechanistic disease transmission models could be applied across other water-related disease systems.
7q11.23 Syndromes Reveal BAZ1B as a Master Regulator of the Modern Human Face and Validate the Self-Domestication Hypothesis
Authors: Zanella Matteo , Vitriolo Alessandro , Andirko Alejandro , Martins Pedro Tiago , Sturm Stefanie , O’Rourke Thomas , Laugsch Magdalena , Malerba Natascia , Skaros Adrianos , Trattaro Sebastiano , Germain Pierre-Luc , Merla Giuseppe , Rada-Iglesias Alvaro , Boeckx Cedric , Testa Giuseppe 
Published: March 2019

AbstractSymmetrical 7q11.23 dosage alterations cause craniofacial and cognitive/behavioral phenotypes that provide a privileged entry point into the evolution of the modern human face and (pro-) sociality. We undertook a functional dissection of chromatin remodeler BAZ1B in neural crest stem cells (NCSCs) from a uniquely informative cohort of typical and atypical patients harboring 7q11.23 Copy Number Variants (CNVs). Our results reveal a key contribution of BAZ1B to NCSCin vitroinduction and migration, coupled with a crucial involvement in neural crest (NC)-specific transcriptional circuits and distal regulation. By intersecting our experimental data with new paleogenetic analyses comparing modern and archaic humans, we uncover a modern-specific enrichment for regulatory changes both in BAZ1B and its experimentally defined downstream targets, thereby providing the first empirical validation of the self-domestication hypothesis and positioning BAZ1B as a master regulator of the modern human face.One Sentence SummaryBAZ1B dosage shapes the modern human face.
Network analysis allows to unravel breast cancer molecular features and to identify novel targets
Authors: Savino Aurora , Avalle Lidia , Monteleone Emanuele , Miglio Irene , Griffa Alberto , Accetta Giulia , Provero Paolo , Poli Valeria 
Published: March 2019

AbstractThe behaviour of complex biological systems is determined by the orchestrated activity of many components interacting with each other, and can be investigated by networks. In particular, gene co-expression networks have been widely used in the past years thanks to the increasing availability of huge gene expression databases. Breast cancer is a heterogeneous disease usually classified either according to immunohistochemical features or by expression profiling, which identifies the 5 subtypes luminal A, luminal B, basal-like, HER2-positive and normal-like. Basal-like tumours are the most aggressive subtype, for which so far no targeted therapy is available.Making use of the WGCNA clustering method to reconstruct breast cancer transcriptional networks from the METABRIC breast cancer dataset, we developed a platform to address specific questions related to breast cancer biology. In particular, we obtained gene modules significantly correlated with survival and age of onset, useful to understand how molecular features and gene expression patterns are organized in breast cancer. We next generated subtype-specific gene networks and in particular identified two modules that are significantly more connected in basal-like breast cancer with respect to all other subtypes, suggesting relevant biological functions. We demonstrate that network centrality (kWithin) is a suitable measure to identify relevant genes, since we could show that it correlates with clinical features and that it provides a mean to select potential upstream regulators of a module with high reliability. Finally, we showed the feasibility of adding meaning to the networks by combining them with independently obtained data related to activated pathways.In conclusion, our platform allows to identify groups of genes highly relevant in breast cancer and possibly amenable to drug targeting, due to their ability to regulate survival-related gene networks. This approach could be successfully extended to other BC subtypes, and to all tumor types for which enough expression data are available.
Comparison of single nucleotide variants identified by Illumina and Oxford Nanopore technologies in the context of a potential outbreak of Shiga Toxin ProducingEscherichia coli
Authors: Greig David R , Jenkins Claire , Gharbia Saheer , Dallman Timothy J 
Published: March 2019

AbstractBackgroundWe aimed to compare Illumina and Oxford Nanopore Technology (ONT) sequencing data from the two isolates of STEC O157:H7 to determine whether concordant single nucleotide variants were identified and whether inference of relatedness was consistent with the two technologies.ResultsFor the Illumina workflow, the time from DNA extraction to availability of results, was approximately 40 hours in comparison to the ONT workflow where serotyping, Shiga toxin subtyping variant identification were available within seven hours. After optimisation of the ONT variant filtering, on average 95% of the discrepant positions between the technologies were accounted for by methylated positions found in the described 5-Methylcytosine motif sequences, CC(A/T)GG. Of the few discrepant variants (6 and 7 difference for the two isolates) identified by the two technologies, it is likely that both methodologies contain false calls.ConclusionsDespite these discrepancies, Illumina and ONT sequences from the same case were placed on the same phylogenetic location against a dense reference database of STEC O157:H7 genomes sequenced using the Illumina workflow. Robust SNP typing using MinION-based variant calling is possible and we provide evidence that the two technologies can be used interchangeably to type STEC O157:H7 in a public health setting.
MultiCapsNet: a interpretable deep learning classifier integrate data from multiple sources
Authors: Wang Lifei , Miao Xuexia , Zhang Jiang , Cai Jun 
Published: March 2019

AbstractRecent advances in experimental biology have generated huge amount of data. Due to differences present in detection targets and detection mechanisms, the produced data comes with different formats and lengths. There is an urgent call for computational methods to integrate these diverse data. Deep learning model is an ideal tool to cope with complex datasets, but its inherent ‘black box’ nature needs more interpretability. Here, we present MultiCapsNet, a deep learning model built on CapsNet and scCapsNet. The MultiCapsNet model possesses the merits of both easier data integration and higher model interpretability. In the first example, we use the labeled variant call dataset, which is originally used to test the models for automating somatic variant refinement. We divide the 71 features listed in the dataset into eight groups according to data source and data property. Then, the data from those eight groups with different formats and lengths are integrated by our MultiCapsNet to predict the labels associated with each variant call. The performance of our MultiCapsNet matches the previous deep learning model well, given much less parameters than those needed by the previous model. After training, the MultiCapsNet model provides importance scores for each data source directly, while the previous deep learning model needs an extra importance determination step to do so. Despite that our MultiCapsNet model is substantially different from the previous deep learning model and the source importance measuring methods are also different, the importance score correlation between these two models is very high. In the second example, the prior knowledge, including information for protein-protein interactions and protein-DNA interactions, is used to determine the structure of MultiCapsNet model. The single cell RNA sequence data are decoupled into multiple parts according to the structure of MultiCapsNet model that has been integrated with prior knowledge, with each part represents genes influenced by a transcription factor or involved in a protein-protein interaction network and then could be viewed as a data source. The MultiCapsNet model could classify cells with high accuracy as well as reveal the contribution of each data source for cell type recognition. The high ranked contributors are often relevant to the contributed cell type.
Variation analysis driven by small-sample data for compliant aero-structure assembly
Authors: Mei Biao , Zhu Weidong , Ke Yinglin , Zheng Pengyu 
Published: March 2019

Purpose
Assembly variation analysis generally demands probability distributions of variation sources. However, due to small production volume in aircraft manufacturing, especially prototype manufacturing, the probability distributions are hard to obtain, and only the small-sample data of variation sources can be consulted. Thus, this paper aims to propose a variation analysis method driven by small-sample data for compliant aero-structure assembly.

Design/methodology/approach
First, a hybrid assembly variation model, integrating rigid effects with flexibility, is constructed based on the homogeneous transformation and elasticity mechanics. Then, the bootstrap approach is introduced to estimate a variation source based on small-sample data. The influences of bootstrap parameters on the estimation accuracy are analyzed to select suitable parameters for acceptable estimation performance. Finally, the process of assembly variation analysis driven by small-sample data is demonstrated.

Findings
A variation analysis method driven by small-sample data, considering both rigid effects and flexibility, is proposed for aero-structure assembly. The method provides a good complement to traditional variation analysis methods based on probability distributions of variation sources.

Practical implications
With the proposed method, even if probability distribution information of variation sources cannot be obtained, accurate estimation of the assembly variation could be achieved. The method is well suited for aircraft assembly, especially in the stage of prototype manufacturing.

Originality/value
A variation analysis method driven by small-sample data is proposed for aero-structure assembly, which can be extended to deal with other similar applications.
Towards human resource development at Hanoi Open University
Authors: Nguyen Hong Thi Thuy 
Published: March 2019

Purpose
The purpose of this paper is to investigate the roles of human resource development (HRD) in open universities. The study also intends to assess the current situation of HRD at Hanoi Open University (HOU) with an end view of proposing some suggested recommendations to enhance HRD to improve the training quality and effectiveness at HOU.

Design/methodology/approach
The study’s first two parts refer to HRD’s role in open universities. The third one summarizes the existing research literature on HRD used as theoretical base for the author to evaluate the current HRD at HOU in the fourth part. The fifth part involves the methodology to gather the data on HRD practices at HOU while the next two important parts deal with the study’s findings and recommendations for better HRD at HOU. The final part summaries the study’s main points. Referring methodology, the survey data were analyzed through frequency, percentage and weighted mean as statistical tools.

Findings
The study’s findings show that HRD practices at HOU are not as effective as expected in terms of human resource quality, human resource structure and human resource management. There is a shortage of full-time well-qualified employees, inadequate and imbalance working positions, and un-synchronous, fragmented personnel management.

Originality/value
The study’s values are not only useful for building policies on HRD but also for developing strategies to train and foster capable and adequate staff in open universities’ academic environment and in HOU as well.