bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative Vectors for Regulated Expression of SARS-CoV-2 Proteins Implicated in RNA Metabolism
Authors: Bresson Stefan , Robertson Nic , Sani Emanuela , Turowski Tomasz W , Shchepachev Vadim , Kompauerova Michaela , Spanos Christos , Helwak Aleksandra , Tollervey David 
Published: July 2020

ABSTRACTInfection with SARS-CoV-2 is expected to result in substantial reorganization of host cell RNA metabolism. We identified 14 proteins that were predicted to interact with host RNAs or RNA binding proteins, based on published data for SARS-CoV and SARS-CoV-2. Here, we describe a series of affinity-tagged and codon-optimized expression constructs for each of these 14 proteins. Each viral gene was separately tagged at the N-terminus with Flag-His8, the C-terminus with His8-Flag, or left untagged. The resulting constructs were stably integrated into the HEK293 Flp-In TREx genome. Each viral gene was expressed under the control of an inducible Tet-On promoter, allowing expression levels to be tuned to match physiological conditions during infection. Expression time courses were successfully generated for most of the fusion proteins and quantified by western blot. A few fusion proteins were poorly expressed, whereas others, including Nsp1, Nsp12, and N protein, were toxic unless care was taken to minimize background expression. All plasmids can be obtained from Addgene and cell lines are available. We anticipate that availability of these resources will facilitate a more detailed understanding of coronavirus molecular biology.
Integrative Modeling of Membrane-associated Protein Assemblies
Authors: Roel-Touris Jorge , Jiménez-García Brian , Bonvin Alexandre M.J.J. 
Published: July 2020

AbstractHistorically, membrane protein systems have been considered as one of the most challenging systems to study with experimental structural biology techniques. Over the past years, increased number of experimental structures of membrane proteins have become available thanks in particular to advances in solid-state NMR spectroscopy and cryo-electron microscopy. This has opened the route to modeling the complexes that those membrane proteins form by methods such as docking. Most approaches developed to date are, however, not capable of incorporating the topological information provided by the membrane into the modeling process. Here, we present an integrative computational protocol for the modeling of membrane-associated protein assemblies, specifically complexes consisting of a membrane-embedded protein and a soluble partner. It combines efficient, artificial intelligence-based rigid-body docking by LightDock with a flexible final refinement with HADDOCK to remove potential clashes at the interface. We make use of an equilibrated coarse-grained lipid bilayer to represent the information encoded in the membrane in the form of artificial beads, which allows to target the docking towards the binding-competent regions. We demonstrate the performance of this membrane-driven protocol on eighteen membrane-associated complexes, whose interface lies between the membrane and either the cytosolic or periplasmic regions. In addition, we evaluate how different membrane definitions impact the performance of the docking protocol and provide a comparison, in terms of success rate, to another state-of-the-art docking software, ZDOCK. Finally, we discuss the quality of the generated models and propose possible future developments. Our membrane docking protocol should allow to shed light on the still rather dark fraction of the interactome consisting of membrane proteins.
Comparative regulomics reveals pervasive selection on gene dosage following whole genome duplication
Authors: Gillard Gareth B. , Grønvold Lars , Røsæg Line L. , Holen Matilde Mengkrog , Monsen Øystein , Koop Ben F. , Rondeau Eric B. , Gundappa Manu Kumar , Mendoza John , Macqueen Daniel J. , Rohlfs Rori V. , Sandve Simen R. , Hvidsten Torgeir R. 
Published: July 2020

AbstractWhole genome duplication (WGD) events have played a major role in eukaryotic genome evolution, but the consequence of these extreme events in adaptive genome evolution is still not well understood. To address this knowledge gap we used a comparative phylogenetic model and transcriptomic data from seven species to infer selection on gene expression in duplicated genes (ohnologs) following the salmonid WGD 80-100 million years ago. We find rare cases of tissue-specific expression evolution but pervasive expression evolution affecting many tissues, reflecting strong selection on maintenance of genome stability following genome doubling. Although ohnolog expression levels have evolved mostly asymmetrically, by diverting one ohnolog copy down a path towards pseudogenization, strong evolutionary constraints have frequently also favoured symmetric shifts in gene dosage of both copies, likely to achieve gene dose reduction while avoiding accumulation of ‘toxic mutations’. Mechanistically, ohnolog regulatory divergence is dictated by the number of bound transcription factors in promoters, with transposable elements being one source of novel binding sites driving tissue-specific gains in expression. Our results imply pervasive adaptive expression evolution following WGD to overcome the immediate challenges posed by genome doubling and to exploit the long-term genetic opportunities for novel phenotype evolution.
Nutrient supplementation experiments with saltern microbial communities implicate utilization of DNA as a source of phosphorus
Authors: Hua Zhengshuang , Ouellette Matthew , Makkay Andrea M. , Papke R. Thane , Zhaxybayeva Olga 
Published: July 2020

AbstractAll environments including hypersaline ones harbor measurable concentrations of dissolved extracellular DNA (eDNA) that can be utilized by microbes as a nutrient. However, it remains poorly understood which eDNA components are used, and who in a community utilizes it. For this study, we incubated a saltern microbial community with combinations of carbon, nitrogen, phosphorus, and DNA, and tracked the community response in each microcosm treatment via 16S rRNA andrpoBgene sequencing. We show that microbial communities used DNA only as a phosphorus source, and provision of other sources of carbon and nitrogen was needed to exhibit a substantial growth. The taxonomic composition of eDNA in the water column changed with the availability of inorganic phosphorus or supplied DNA, hinting at preferential uptake of eDNA from specific organismal sources. Especially favored for growth was eDNA from the most abundant taxa, suggesting some haloarchaea prefer eDNA from closely related taxa. Additionally, microcosms’ composition shifted substantially depending on the provided nutrient combinations. These shifts allowed us to predict supplemented nutrients from microbial composition with high accuracy, suggesting that nutrient availability in an environment could be assessed from a taxonomic survey of its microbial community.
Unique genomic features of crAss-like phages, the dominant component of the human gut virome
Authors: Yutin Natalya , Benler Sean , Shmakov Sergei A. , Wolf Yuri I. , Tolstoy Igor , Rayko Mike , Antipov Dmitry , Pevzner Pavel A. , Koonin Eugene V. 
Published: July 2020

AbstractCrAssphage is the most abundant virus identified in the human gut virome and the founding member of a large group of bacteriophages that infect bacteria of the phylum Bacteroidetes and have been discovered by metagenomics of both animal-associated and environmental habitats. By analysis of circular contigs from human gut microbiomes, we identified nearly 600 genomes of crAss-like phages. Phylogenetic analysis of conserved genes demonstrates the monophyly of crAss-like phages, which can be expected to become a new order of viruses, and of 5 distinct branches, likely, families within that order. Two of these putative families have not been identified previously. The phages in one of these groups have large genomes (145-192 kilobases) and contain an unprecedented high density of self-splicing introns and inteins. Many crAss-like phages encode suppressor tRNAs that enable readthrough of UGA or UAG stop-codons, mostly, in late phage genes, which could represent a distinct anti-defense strategy. Another putative anti-defense mechanism that might target an unknown defense system in Bacteroidetes inhibiting phage DNA replication involves multiple switches of the phage DNA polymerase type between A and B families. Thus, comparative genomic analysis of the expanded assemblage of crAss-like phages reveals several unusual features of genome architecture and expression as well as phage biology that were not apparent from the previous crAssphage analyses.
Antifeedant activities of L-arabinose to caterpillars of the cotton bollwormHelicoverpa armigera(Hübner)
Authors: Sun Longlong , Hong Zhenzhen , Ma Ying , Hou Wenhua , Liu Long , Zhao Xincheng , Yan Fengming , Yin Xinming , Wang Chenzhu , Tang Qingbo 
Published: July 2020

ABSTRACTExploring botanical biopesticide is one of the eco-friendly approaches for pest control in current crop protection. L-arabinose, a plant-specific and less absorptive pentose, is known for its selective inhibitory effect on the sucrose digestion in mammals. In this study, we investigated the effects of L-arabinose on the feeding preference, the peripheral gustatory perception, the larval development, as well as the activity of intestinal sucrase of an insect pest species, the cotton bollwormHelicoverpa armigera(Hübner) (Lepidoptera: Noctuidae), in an attempt to explore the antifeedant activities of this pentose. The results showed that L-arabinose deterred the feeding preferences ofH. armigeracaterpillars for its two host plants and two phagostimulants, the tobacco, the pepper, the sucrose and the fructose. Gustatory receptor neurons (GRNs) sensitive to L-arabinose were not found in the peripheral maxillary sensilla ofH. armigeracaterpillars, but the sensitivities of GRNs sensitive to sucrose, fructose and tobacco saps were suppressed by the additions of L-arabinose. Exposure ofH. armigeracaterpillars to dietary L-arabinose resulted in a prolonged larval developmental duration, a suppressed activity of intestinal sucrase and a reduced glucose level in midgut.In vitro, L-arabinose inhibited activities of the intestinal sucrase ofH. armigeracaterpillars in an uncompetitive manner. Taken together, these findings demonstrate that L-arabinose is a behavioral, gustatory and physiological inhibitor to caterpillars of the extremely generalist pest speciesH. armigera, suggesting the great potential of L-arabinose to be an effective antifeedant.
Impacts of supportive HR practices and organisational climate on the attitudes of HR managers towards gender diversity – a mediated model approach
Authors: Biswas Kumar , Boyle Brendan , Bhardwaj Sneh 
Published: July 2020

PurposeUsing the theoretical lens of the behavioural perspective on HRM, this study examined a mediated model to understand the extent to which organisational factors such as supportive human resource management policies and practices (SHRPP) and organisational climate (OC) can influence the affective attitudes of HR managers towards promoting women into organisational leadership roles. Survey data collected from 182 human resource managers in Bangladesh were analysed using partial least squares–based structural equation modelling (PLS-SEM) and the PROCESS macro to test mediating effects. The results reveal that the adoption of SHRPP is positively associated with OC, which in turn shapes the attitudes of HR managers leading to implementing unbiased promotional practices for organisational leadership roles.Design/methodology/approachQuantitative survey data collected from 182 human resource managers in Bangladesh were analysed using PLS-SEM and PROCESS macro.FindingsThe results reveal that the adoption of SHRPP is positively associated with OC which in turn shapes the attitudes of HR managers leading to implementing unbiased promotional practices for organisational leadership roles.Research limitations/implicationsSelf-report, cross-sectional survey data may contribute to the methodological bias such as common method bias (CMB). Harman's single-factor test revealed that no single component explained a major portion of the total variance. Furthermore, partial correlational analysis using a marker variable coupled with an assessment of social desirability indicates that common method variance is unlikely to have any CMB risks to the validity of the study results.Practical implicationsFrom a practical point of view, the findings of this study suggest that supportive HR practices may create a positive organisational climate that leads to creating a healthy work environment ensuring an equal opportunity for everyone to grow and excel irrespective of their socio-cultural backgrounds and gender identity; thus, facilitating the organisation to take advantage of creativity and innovation offered by their talents, a critical factor for the organisation to survive and flourish in the dynamic market.Social implicationsThe study findings provide insights into why organisations should adopt fair and transparent HR policies to create a congenial work climate impacting on positive social attitudes towards acceptance of a gender-balanced empowered society.Originality/valueTo the best of author's knowledge, this is the first study that examined a mediated model to understand how organisational factors such as SHRPP and OC can impact on the affective attitudes of HR managers towards promoting women in the organisational leadership roles.
Work to family, family to work conflicts and work family balance as predictors of job satisfaction of Malaysian academic community
Authors: Rahman Md. Mizanur , Ali Noor Azman , Jantan Amer Hamzah , Mansor Zuraina Dato' , Rahaman Md. Saidur 
Published: July 2020

PurposeThe purpose of this study is to confirm that work to family conflict (W to FC), family to work conflict (F to WC) and work family balance (WFB) are the predictors of job satisfaction (JS) for Malaysian academic community. To achieve the fundamental objective, the authors first test the direct (structural model) effects of W to FC and F to WC on JS. Secondly, using mediation model, the indirect effects of WFB were calculated through W to FC, F to WC and JS.Design/methodology/approachUsing convenience sampling, the data was collected from 280 academic people who work at private universities in Malaysia. Structural equation modelling technique was applied to complete the data analyses procedures.FindingsThe findings revealed that W to FC and F to WC have negative significant effects on JS. Besides, WFB partially mediates only the relationship between W to FC and JS while no mediation effect was found for F to WC and JS.Research limitations/implicationsAll the research variables in this study were individual-level variables, thus it is suggested to use some organizational and national level variables such as religion and culture as they might be good intervening variables for predicting JS.Practical implicationsUsing the findings of this research, the Malaysian private universities community can take some necessary initiatives to mitigate work family conflict (W-FC) and ensure WFB and JS that might enhance the standard of higher education in Malaysia.Originality/valueTo the best of the authors’ knowledge, this is the first attempt to test the mediation effect of WFB in the relationship between both directions of W-FC and JS of employees from the perspective of Malaysia (a collectivist community).
The outcome of pregnancy in women with cystic fibrosis: a UK population‐based descriptive study
Authors: Ashcroft A , Chapman SJ , Mackillop L 
Published: July 2020

ObjectiveTo estimate the incidence of cystic fibrosis in pregnancy and to explore obstetric and neonatal outcomes.DesignA population‐based descriptive study using the methodology of the UK Obstetric Surveillance System (UKOSS).SettingAll consultant‐led maternity units in the UK.PopulationAll pregnant women with a diagnosis of cystic fibrosis who booked for antenatal care in a UK obstetric unit between March 2015 and February 2017.MethodsProspective case collection identified using UKOSS monthly notification.Main outcome measuresIncidence, maternal morbidity, maternal mortality, gestation at delivery, neonatal mortality, neonatal morbidity.ResultsWe report 71 pregnancies over a 2‐year period. There was one early miscarriage, four terminations and three sets of twins, resulting in the live birth of 69 infants. There were no maternal deaths. One infant died following spontaneous preterm birth at 29 weeks’ gestation. The mean gestation at delivery was 36.2 completed weeks. The mean birthweight centile for gestational age was the 61st centile. We report a positive correlation between both maternal lung function (FEV1) and mean gestation at delivery, and between FEV1 and mean birthweight centile for gestational age.ConclusionsPregnancy outcomes are generally good in women with cystic fibrosis. Successful pregnancy is possible even in those women with FEV1 <60% predicted, although such women have higher chance of preterm delivery and a smaller baby.Tweetable abstractPregnant women with cystic fibrosis who have poorer lung function at the beginning of pregnancy have a higher risk of having a premature or smaller baby.
Disclosing Physician Ratings: Performance Effects and the Difficulty of Altering Ratings Consensus
Authors: EYRING HENRY 
Published: July 2020

ABSTRACTI examine effects of a health care system's policy to publicly disclose patient ratings of its physicians. I find evidence that this policy leads to performance improvement by the disclosed, subjective ratings and also by undisclosed, objective measures of quality. These effects are consistent with multitasking theory, in that physicians respond to the disclosure by providing more of a shared input—time with patients—that benefits performance by ratings and underlying quality. I also find, as predicted by information cascade theory, that the ratings become jammed to some degree near initially disclosed values. Specifically, raters observe the pattern of initial ratings and follow suit by providing similar ratings. Finally, I find evidence that physicians anticipate rating jamming and so concentrate their effort on earlier performance in order to set a pattern of high ratings that later ratings follow. These results demonstrate that the disclosure of subjective ratings can benefit performance broadly but can also shift effort toward earlier performance.
Comparison of enzymatic and microwave‐assisted alkaline extraction approaches for the generation of oligosaccharides from American Cranberry (Vaccinium macrocarpon) Pomace
Authors: Spadoni Andreani Eugenio , Karboune Salwa 
Published: July 2020

AbstractCranberry pomace obtained from industrial juice production was characterized by proximate composition analysis and monosaccharide profile of the dietary fiber. Extraction of carbohydrates from pomace was investigated using microwave‐assisted alkaline method and five commercial biocatalysts (pure endo‐galactanase and four multienzyme biocatalysts). The extracts obtained from microwave‐assisted approach had average total sugars yield of 21.3% and contained mostly oligosaccharides in the degree of polymerization range of 7 to 10. All multienzyme biocatalysts led to yields similar or higher than microwave‐assisted approach (23.4% to 42.0%), but mainly generated shorter oligosaccharides with a degree of polymerization of 2 to 5. Compared to cranberry pomace dietary fiber, microwave‐assisted extracts were enriched in pectic oligosaccharides, whereas the enzymatic extracts were enriched in glucans and had less rhamnose and galactose. Pomace ground for 5 min or more by ball mill assumed a powdery consistence. Longer milling did not affect particle size but increased their roughness. Such physical changes had no effect on the efficiency of multienzymatic treatment.Practical ApplicationThe increased production of cranberries and cranberry products will continuously generate more pomace, a potentially valuable material for the generation of added‐value products. Up to 60% to 70% of cranberry pomace is composed of plant cell wall material. The properties of naturally occurring plant cell wall polysaccharides and their corresponding oligosaccharides have been of a great interest, and many of them find application as functional food ingredients. Despite the fact that the cranberry pomace is rich in plant cell polysaccharides, it has been mainly explored as a source of phenolic antioxidants. This study reveals the efficiency of cranberry pomace as a source of nondigestible oligosaccharides. The use of microwave‐assisted extraction and different biocatalysts for the enzymatic extraction led to oligosaccharides with well‐defined monosaccharide composition and molecular weight distribution. The study of the effects of these extraction techniques on the yield and the characteristics of generated oligosaccharides would allow the modulation of their properties. As an overall, the findings of this study would contribute to lay the scientific ground for the development of innovative process for the isolation of nondigestible oligosaccharides as functional ingredients from cranberry pomace by products.
DLL3 expression is a predictive marker of sensitivity to adjuvant chemotherapy for pulmonary LCNEC
Authors: Ogawa Hiroyuki , Sakai Yasuhiro , Nishio Wataru , Fujibayashi Yusuke , Nishikubo Megumi , Nishioka Yuki , Tane Shinya , Kitamura Yoshitaka , Sudo Tamotsu , Sakuma Toshiko , Yoshimura Masahiro 
Published: July 2020

BackgroundThe mammalian Notch family ligands delta‐like 3 (DLL3) is reported to be a potential therapeutic target for large cell neuroendocrine carcinomas (LCNEC). The effect of DLL3 expression on LCNEC prognosis has not yet been elucidated.MethodsWe reviewed the medical records of 70 LCNEC patients undergoing surgical resection between 2001 and 2015 using a prospectively maintained database. We performed immunohistochemistry for DLL3 and investigated the correlation between the sensitivity of LCNEC to platinum‐based adjuvant chemotherapy.ResultsDLL3 expression was positive in 26 (37.1%) LCNEC patients. A total of 23 patients (32.9%) received platinum‐based adjuvant chemotherapy. Among patients with DLL3 expression‐positive tumors, no difference was found in the five‐year overall survival (OS) or recurrence‐free survival (RFS) between patients with and without adjuvant chemotherapy (surgery + chemotherapy vs. surgery alone, five‐year OS: 58.3% vs. 35.7% P = 0.36, five‐year RFS: 41.7% vs. 35.7% P = 0.74). In contrast, among patients with DLL3‐negative tumors, significantly greater five‐year OS and RFS rates were observed for patients with adjuvant chemotherapy than for those without it (surgery + chemotherapy vs. surgery alone: five‐year OS: 90.0% vs. 26.9% P<0.01, five‐year RFS: 80.0% vs. 21.7% P < 0.01). A multivariate analysis for the RFS revealed that adjuvant chemotherapy was a significant independent prognostic factor among patients with DLL3‐negative tumors (hazard ratio [HR]: 0.05, 95% confidence interval [CI]: 0.01–0.41, P < 0.01), although it was not a factor among patients with DLL3‐positive tumors (HR: 0.73, 95% CI: 0.23–2.27, P = 0.58).ConclusionsOur results revealed that DLL3 is a predictive marker of sensitivity to platinum‐based adjuvant chemotherapy for LCNEC.Key pointsSignificant findings of the studyDLL3 was a predictive marker of sensitivity to platinum‐based adjuvant chemotherapy for LCNEC. Among patients with DLL3 expression‐negative LCNEC, platinum‐based adjuvant chemotherapy significantly improved the OS and RFS, although it did not do so among patients with DLL3 expression‐positive LCNEC.What this study addsOur results suggest that DLL3 expression‐positive LCNEC may be better treated with other types of adjuvant chemotherapy, such as the anti‐DLL3 therapies if these effects are confirmed by ongoing clinical research.