bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene-set Enrichment with Regularized Regression
Authors: Fang Tao , Davydov Iakov , Marbach Daniel , Zhang Jitao David 
Published: June 2019

AbstractMotivationCanonical methods for gene-set enrichment analysis assume independence between gene-sets. In practice, heterogeneous gene-sets from diverse sources are frequently combined and used, resulting in gene-sets with overlapping genes. They compromise statistical modelling and complicate interpretation of results.ResultsWe rephrase gene-set enrichment as a regression problem. Given some genes of interest (e.g.a list of hits from an experiment) and gene-sets (e.g.functional annotations or pathways), we aim to identify a sparse list of gene-sets for the genes of interest. In a regression framework, this amounts to identifying a minimum set of gene-sets that optimally predicts whether any gene belongs to the given genes of interest. To accommodate redundancy between gene-sets, we propose regularized regression techniques such as theelastic net.We report that regression-based results are consistent with established gene-set enrichment methods but more parsimonious and interpretable.AvailabilityWe implement the model ingerr(gene-set enrichment with regularized regression), an R package freely available athttps://github.com/TaoDFang/gerrand submitted toBioconductor.Code and data required to reproduce the results of this study are available athttps://github.com/TaoDFang/GeneModuleAnnotationPaper.ContactJitao David Zhang (jitao_david.zhang@roche.com), Roche Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. Grenzacherstrasse 124, 4070 Basel, Switzerland.
Computational design and interpretation of single-RNA translation experiments
Authors: Aguilera Luis U. , Raymond William , Fox Zachary R. , May Michael , Djokic Elliot , Morisaki Tatsuya , Stasevich Timothy J. , Munsky Brian 
Published: June 2019

AbstractAdvances in fluorescence microscopy have introduced new assays to quantify live-cell translation dynamics at single-RNA resolution. We introduce a detailed, yet efficient sequence-based stochastic model that generates realistic synthetic data for several such assays, including Fluorescence Correlation Spectroscopy (FCS), ribosome Run-Off Assays (ROA) after Harringtonine application, and Fluorescence Recovery After Photobleaching (FRAP). We simulate these experiments under multiple imaging conditions and for thousands of human genes, and we evaluate through simulations which experiments are most likely to provide accurate estimates of elongation kinetics. Finding that FCS analyses are optimal for both short and long length genes, we integrate our model with experimental FCS data to capture the nascent protein statistics and temporal dynamics for three human genes: KDM5B, β-actin, and H2B. Finally, we introduce a new open-source software package, RNA Sequence to NAscent Protein Simulator (RSNAPSIM), to easily simulate the single-molecule translation dynamics of any gene sequence for any of these assays and for different assumptions regarding synonymous codon usage, tRNA level modifications, or ribosome pauses. RSNAPSIM is implemented in Python and is available at: https://github.com/MunskyGroup/rSNAPsim.git.Author summaryTranslation is an essential step in which ribosomes decipher mRNA sequences to manufacture proteins. Recent advances in time-lapse fluorescence microscopy allow live-cell quantification of translation dynamics at the resolution of single mRNA molecules. Here, we develop a flexible computational framework to reproduce and interpret such experiments. We use this framework to explore how well different single-mRNA translation experiment designs would perform to estimate key translation parameters. We then integrate experimental data from the most flexible design with our stochastic model framework to reproduce the statistics and temporal dynamics of nascent protein elongation for three different human genes. Our validated computational method is packaged with a simple graphical user interface that (1) starts with mRNA sequences, (2) generates discrete, codon-dependent translation models, (3) provides visualization of ribosome movement as trajectories or kymographs, and (4) allows the user to estimate how optical single-mRNA translation experiments would be affected by different genetic alterations (e.g., codon substitutions) or environmental perturbations (e.g., tRNA titrations or drug treatments).
Chd1 regulates repair of promoter-proximal DNA breaks to sustain hypertranscription in embryonic stem cells
Authors: Bulut-Karslioglu Aydan , Jin Hu , Guzman-Ayala Marcela , Williamson Andrew JK , Hejna Miroslav , Whetton Anthony D , Song Jun S. , Ramalho-Santos Miguel 
Published: June 2019

AbstractStem and progenitor cells undergo a global elevation of nascent transcription, or hypertranscription, during key developmental transitions involving rapid cell proliferation. The chromatin remodeler Chd1 binds to genes transcribed by RNA Polymerase (Pol) I and II and is required for hypertranscription in embryonic stem (ES) cellsin vitroand the early post-implantation epiblastin vivo. Biochemically, Chd1 has been shown to facilitate transcription at least in part by removing nucleosomal barriers to elongation, but its mechanism of action in stem cells remains poorly understood. Here we report a novel role for Chd1 in the repair of promoter-proximal endogenous double-stranded DNA breaks (DSBs) in ES cells. An unbiased proteomics approach revealed that Chd1 interacts with several DNA repair factors including Atm, Parp1, Kap1 and Topoisomerase 2β. We show that wild-type ES cells display high levels of phosphorylated H2A.X and Kap1 at chromatin, notably at rDNA in the nucleolus, in a Chd1-dependent manner. Loss of Chd1 leads to an extensive accumulation of DSBs at Chd1-bound Pol II-transcribed genes and rDNA. Genes prone to DNA breaks in Chd1 KO ES cells tend to be longer genes with GC-rich promoters, a more labile nucleosomal structure and roles in chromatin regulation, transcription and signaling. These results reveal a vulnerability of hypertranscribing stem cells to endogenous DNA breaks, with important implications for developmental and cancer biology.
Non-invasive recording from the human olfactory bulb
Authors: Iravani Behzad , Arshamian Artin , Ohla Kathrin , Wilson Donald A. , Lundström Johan N. 
Published: June 2019

ABSTRACTCurrent methods can, in a non-invasive manner, assess neural activity in all areas of the human brain but the olfactory bulb (OB). The OB is intimately involved in a long list of olfactory tasks, has been suggested to fulfill a role comparable to that of V1 and the thalamus in the visual system, and have been closely linked to a wide range of neuropathologies. Here we present a method for non-invasive recording of signals from the human OB with millisecond precision. We demonstrate that signals obtained via recordings from EEG electrodes at the nasal bridge represent responses from the olfactory bulb - recordings we term Electrobulbogram (EBG). The EBG is localized to the OB, is reliable, and follows response patterns demonstrated in non-human animal models. The EBG will aid future olfactory-related translational work but can also easily be implemented as an everyday clinical tool to detect pathology-related changes in human central olfactory processing in neurodegenerative diseases.
GATA2 controls lymphatic endothelial cell junctional integrity and lymphovenous valve morphogenesis throughmiR-126
Authors: Mahamud Md. Riaj , Geng Xin , Ho Yen-Chun , Cha Boksik , Kim Yuenhee , Ma Jing , Chen Lijuan , Myers Greggory , Camper Sally , Mustacich Debbie , Witte Marlys , Choi Dongwon , Hong Young-Kwon , Chen Hong , Varshney Gaurav , Engel James Douglas , Wang Shusheng , Kim Tae-Hoon , Lim Kim-Chew , Srinivasan R. Sathish 
Published: June 2019

ABSTRACTMutations in the transcription factor GATA2 cause lymphedema. GATA2 is necessary for the development of lymphatic valves (LVs) and lymphovenous valves (LVVs), and for the patterning of lymphatic vessels. Here, we report that GATA2 is not necessary for valvular endothelial cell (VEC) differentiation. Instead, GATA2 is required for VEC maintenance and morphogenesis. GATA2 is also necessary for the expression of cell junction molecules VE-Cadherin and Claudin5 in lymphatic vessels. We identifiedmiR-126as a target of GATA2, andmiR-126−/−embryos recapitulate the phenotypes of mice lacking GATA2. Primary human lymphatic endothelial cells (HLECs) lacking GATA2 (GATA2ΔHLEC) have altered expression of Claudin5 and VE-Cadherin, and blockingmiR-126activity in HLECs phenocopies these changes in expression. Importantly, overexpression ofmiR-126in GATA2ΔHLECsignificantly rescues the cell junction defects. Thus, our work defines a new mechanism of GATA2 and uncoversmiR-126as a novel regulator of mammalian lymphatic vascular development.Non-standard abbreviationsLECs, lymphatic endothelial cells;LVs, lymphatic valves;LV-ECs, lymphatic valve-forming endothelial cells;LVVs, lymphovenous valves;LVV-ECs, lymphovenous valve-forming endothelial cells;HLEC, primary human LECs;OSS, Oscillatory shear stress;IHC, immunohistochemistry.
Importance of the Landlocked Pond SmeltHypomesus nipponensisas a food resource of the Little TernSternula albifronson inland Andong Lake of Korea: A video image analysis
Authors: Shin Dong-Man , Han Jeong-Ho 
Published: June 2019

AbstractWe carried out the diet study of the little tern on the sandy islet in inland Andong Lake, Korea, during the beeding season (April to July 2018). To identify its diet and examine the importance of the main prey species as a food resource, we set two remote-control video cameras with 4K-resolution on the islet. One thousand two hundred seventy-five still images that the tern had prey in its bill were identified at the species level and measured on a monitor. Then, they were classified to five length-categories and compared among months and breeding stages. Freshwater fishes dominated the diet (100%; eleven species overall), where the landlocked pond smeltHypomesus nipponensis(80.8%) and largemouth bassMicropterus salmoides(13.7%) were the primary and next essential prey species, respectively. The average prey item length was 51.04 ± 20.89 mm and significantly differed among months and breeding stages (P< 0.001, respectively). 50–75 mm prey length category was the most frequent in the diet (42.2%). In April and May, larger fish >50 mm constituted the greater part of their diet (93.1%, 66.3%, respectively), whereas the diet in June and July consisted of smaller fishes <50 mm (56.2%, 68.8% respectively). The occurrence frequency of prey length categories also varied significantly among the breeding stages (P< 0.001): 1–25 mm and 50–75 mm were overrepresented and underrepresented, respectively, at the chicks in the nest stage. On the other hand, 50–75 mm was preferred for the pre-laying and incubation stages. In terms of the survival condition of pond smelts, the before- and after water surface temperatures of the day when terns flew away showed a significant difference (P= 0.004), where a threshold looks like between 29.11°C and 30.04°C. These results support the prey abundance hypothesis that, when cold-water pond smelts might wholly swim down into the deeper lake in the hot summer, the terns might also leave their colony for another foraging place with higher prey availability.
Recombinant rotaviruses rescued by reverse genetics reveal the role of NSP5 hyperphosphorylation in the assembly of viral factories
Authors: Papa Guido , Venditti Luca , Arnoldi Francesca , Schraner Elisabeth M. , Potgieter Christiaan , Borodavka Alexander , Eichwald Catherine , Burrone Oscar R. 
Published: June 2019

ABSTRACTRotavirus (RV) replicates in round-shaped cytoplasmic viral factories although how they assemble remains unknown.During RV infection, NSP5 undergoes hyperphosphorylation, which is primed by the phosphorylation of a single serine residue. The role of this post-translational modification in the formation of viroplasms and its impact on the virus replication remains obscure. Here we investigated the role of NSP5 during RV infection by taking advantage of a modified fully tractable reverse genetics system. An NSP5 trans-complementing cell line was used to generate and characterise several recombinant rotaviruses (rRVs) with mutations in NSP5. We demonstrate that a rRV lacking NSP5, was completely unable to assemble viroplasms and to replicate, confirming its pivotal role in rotavirus replication.A number of mutants with impaired NSP5 phosphorylation were generated to further interrogate the function of this post-translational modification in the assembly of replication-competent viroplasms. We showed that the rRV mutant strains exhibit impaired viral replication and the ability to assemble round-shaped viroplasms in MA104 cells. Furthermore, we have investigated the mechanism of NSP5 hyper-phosphorylation during RV infection using NSP5 phosphorylation-negative rRV strains, as well as MA104-derived stable transfectant cell lines expressing either wt NSP5 or selected NSP5 deletion mutants. Our results indicate that NSP5 hyper-phosphorylation is a crucial step for the assembly of round-shaped viroplasms, highlighting the key role of the C-terminal tail of NSP5 in the formation of replication-competent viral factories. Such a complex NSP5 phosphorylation cascade may serve as a paradigm for the assembly of functional viral factories in other RNA viruses.IMPORTANCERotavirus (RV) double-stranded RNA genome is replicated and packaged into virus progeny in cytoplasmic structures termed viroplasms. The non-structural protein NSP5, which undergoes a complex hyperphosphorylation process during RV infection, is required for the formation of these virus-induced organelles. However, its roles in viroplasm formation and RV replication have never been directly assessed due to the lack of a fully tractable reverse genetics (RG) system for rotaviruses. Here we show a novel application of a recently developed RG system by establishing a stable trans-complementing NSP5-producing cell line required to rescue rotaviruses with mutations in NSP5. This approach allowed us to provide the first direct evidence of the pivotal role of this protein during RV replication. Furthermore, using recombinant RV mutants we shed light on the molecular mechanism of NSP5 hyperphosphorylation during infection and its involvement in the assembly and maturation of replication-competent viroplasms.
SweHLA: the high confidence HLA typing bio-resource drawn from 1 000 Swedish genomes
Authors: Nordin Jessika , Ameur Adam , Lindblad-Toh Kerstin , Gyllensten Ulf , Meadows Jennifer R.S. 
Published: June 2019

AbstractThere is a need to accurately call human leukocyte antigen (HLA) genes from existing short-read sequencing data, however there is no single solution that matches the gold standard of lab typing. Here we aimed to combine results from available software, minimising the biases of applied algorithm and HLA reference. The result is a robust HLA population resource for the published 1 000 Swedish genomes, and a framework for future HLA interrogation. HLA 2-field alleles were called using four imputation and inference methods for the classical eight genes (class I: HLA-A, -B, -C; class II: HLA-DPA1, -DPB1, -DQA1, -DQB1, -DRB1). A high confidence population set (SweHLA) was determined using an n-1 concordance rule for class I (four software) and class II (three software) alleles. Results were compared across populations and individual programs benchmarked to SweHLA. Per allele, 875 to 988 of the 1 000 samples were genotyped in SweHLA; 920 samples had at least seven loci. While a small fraction of reference alleles were common to all software (class I=1.9% and class II=4.1%), this did not affect the overall call rate. Gene-level concordance was high compared to European populations (>0.83%), with COX and PGF the dominant SweHLA haplotypes. We noted that 15/18 discordant alleles (delta allele frequency > 2) were previously reported as disease-associated. These differences could in part explain across-study genetic replication failures, reinforcing the need to use multiple software. SweHLA demonstrates a way to use existing NGS data to generate a population resource agnostic to individual HLA software biases.
Eco-evolutionary spatial dynamics of non-linear social dilemmas
Authors: Gokhale Chaitanya S. , Park Hye Jin 
Published: June 2019

AbstractSpatial dynamics can promote the evolution of cooperation. While dispersal processes have been studied in simple evolutionary games, real-world social dilemmas are much more complicated. The public good, in many cases, does not increase linearly as per the investment in it. When the investment is low, for example, every additional unit of the investment may help a lot to increase the public good, but the effect vanishes as the number of investments increase. Such non-linear behaviour is the norm rather than an exception in a variety of social as well as biological systems. We take into account the non-linearity in the payoffs of the public goods game as well as the natural demographic effects of population densities. Population density has also been shown to impact the evolution of co-operation. Coupling these non-linear games and population size effect together with an explicitly defined spatial structure brings us one step closer to the complexity of real eco-evolutionary spatial systems. We show how the non-linearity in payoffs, resulting in synergy or discounting of public goods can alter the effective rate of return on the cooperative investment. Synergy or discounting in public goods accumulation affects the resulting spatial structure, not just quantitatively but in some cases, drastically changing the outcomes. In cases where a linear payoff structure would lead to extinction, synergy can support the coexistence of cooperators and defectors. The combined eco-evolutionary trajectory can thus be qualitatively different in cases on non-linear social dilemmas.
Public–private equity joint ventures and risk transfers in motorways of the sea
Authors: Juan Carmen , Olmos Fernando 
Published: June 2019

PurposeThe purpose of this paper is to present a new scheme of public–private partnership (PPP) within the framework of motorways of the sea (MoS) similar to that of an equity joint venture along with a methodology for valuing risk transfers arising from options embedded in the clauses included in such agreement.Design/methodology/approachThe architecture of the proposed PPP is an adaptation to the scope of a MoS of collaborative schemes commonly used in industry such as equity joint ventures. The methodology for valuing options involved making use of a valuation tree of optimal cashflows along with algorithm designs from the field of financial and real options.FindingsThe proposed structure of public–private equity joint venture (PPEJV) increases the stability of private–public collaboration as compared with standard PPPs, so as to achieve the desired modal shift. The analyzed case study shows how the methodology provides valuable numerical information for both negotiating partners and policy makers.Practical implicationsThis study provides a quantitative tool for policy makers to redefine the role that public agents and public funds should play in a future sustainable mobility model.Originality/valueThe originality of the authors’ contribution to the field of PPPs in transport is triple. First, there is no precedent in the literature on PPPs of an architecture similar to that of the proposed PPEJV. Second, unlike the usual practice in the valuation of financial or real options, no prior structure is assumed for modelling the behaviour of cashflows. Third, the type of options addressed is not usual neither in the real options literature in general nor in the valuation of guarantee mechanisms included in PPPs in particular.
Comparisons of students’ perceptions on BIM practice among Australia, China and UK
Authors: Jin Ruoyu , Zou Patrick Xiaowei , Li Bo , Piroozfar Poorang , Painting Noel 
Published: June 2019

PurposeUniversity students are the future driving forces in and leaders of the architectural, engineering and construction (AEC) industry advancement. Although BIM pedagogical studies have been performed in different institutions, there has not been sufficient research providing a global perspective of BIM education and students’ perceptions toward BIM practice and application following their learning progress. The purpose of this paper is to adopt student samples from Swinburne University of Technology (SUT, Australia), Wenzhou University (WZU, China) and University of Brighton (UK) as three case studies to investigate the BIM practice and application-related perceptions and motivations.Design/methodology/approachBased on the thorough understanding of the BIM pedagogical delivery including teaching contents and assessment methods among the three institutions, a questionnaire survey approach was adopted to collect AEC students’ perceptions of BIM. Within each selected case, statistical analysis was conducted to investigate both the overall sample and subgroup differences regarding students’ opinions on BIM’s functions (e.g. as a 3D visualization tool) and BIM usefulness in various industry professions, their motivation in BIM-related jobs and their perceptions of challenges encountered in BIM practice and application. Multiple factors influencing BIM learners’ perceptions were discussed, such as pedagogical assessment approach, and individual factors (e.g. disciplines).FindingsThe results showed that students were able to discern the latest industry practices and critical thinking in BIM movements. For example, SUT students perceived more challenges from the government legislation or incentive policies, which was consistent with Australia’s BIM policy movement. WZU students tended to have less positive views on BIM usefulness. The results also indicated fewer differences regarding perceived challenges among students from these three institutions.Originality/valueThis study contributed to the body of knowledge in managerial BIM by focusing on learners’ perceptions from the perspective of students’ understanding, motivation and individual views of BIM, which were insightful to both BIM educators and employers. By initiating the framework of BIM learning process and its influence factors, the current study serves as a point of reference to continue the future work in strengthening the connection between institutional BIM education and industry practical needs worldwide.