bluuebunny/crossref_metadata_2025 huggingface dataset:
Reasserting the Centre: The Brexit Doctrine and the Imperative Mandate in British Politics
Authors: Ward Joseph W
Published: May 2020

Despite the outpouring of scholarship on the motivations behind the 2016 EU referendum result and the preliminary impact of Brexit on British politics, comparatively little time has been spent analysing the government(s) entrusted with implementation. This article aims to address this gap in the literature, examining government management of the Brexit process as a case study through which to illustrate the continued relevance of the British Political Tradition in British politics. It argues that through Brexit implementation, the May government initiated a process of centralisation of both policy-making influence and administrative resources within Whitehall. This process was shielded externally by appeals to the referendum result as an imperative mandate parliament was obliged to implement. Although the political landscape of May’s premiership was characterised by flux, these internal shifts towards centralisation in the executive are proposed to have had a more sustained impact through the reassertion of aspects of Britain’s ‘power-hoarding’ constitutional settlement.
Individual Cortical Entropy Profile: Test–Retest Reliability, Predictive Power for Cognitive Ability, and Neuroanatomical Foundation
Authors: Liu Mianxin , Liu Xinyang , Hildebrandt Andrea , Zhou Changsong
Published: May 2020

The entropy profiles of cortical activity have become novel perspectives to investigate individual differences in behavior. However, previous studies have neglected foundational aspects of individual entropy profiles, that is, the test–retest reliability, the predictive power for cognitive ability in out-of-sample data, and the underlying neuroanatomical basis. We explored these issues in a large young healthy adult dataset (Human Connectome Project, N = 998). We showed the whole cortical entropy profile from resting-state functional magnetic resonance imaging is a robust personalized measure, while subsystem profiles exhibited heterogeneous reliabilities. The limbic network exhibited lowest reliability. We tested the out-of-sample predictive power for general and specific cognitive abilities based on reliable cortical entropy profiles. The default mode and visual networks are most crucial when predicting general cognitive ability. We investigated the anatomical features underlying cross-region and cross-individual variations in cortical entropy profiles. Cortical thickness and structural connectivity explained spatial variations in the group-averaged entropy profile. Cortical folding and myelination in the attention and frontoparietal networks determined predominantly individual cortical entropy profile. This study lays foundations for brain-entropy-based studies on individual differences to understand cognitive ability and related pathologies. These findings broaden our understanding of the associations between neural structures, functional dynamics, and cognitive ability.
Identification of an Elite Wheat-Rye T1RS·1BL Translocation Line Conferring High Resistance to Powdery Mildew and Stripe Rust
Authors: Han Guohao , Liu Shiyu , Wang Jing , Jin Yuli , Zhou Yilin , Luo Qiaoling , Liu Hong , Zhao He , An Diaoguo
Published: May 2020

Wheat-rye T1RS·1BL translocations have been widely used worldwide in wheat production for multiple disease resistance and superior yield traits. However, many T1RS·1BL translocations have successively lost their resistance to pathogens due to the coevolution of pathogen virulence with host resistance. Because of the extensive variation in rye (Secale cereale L.) as a naturally cross-pollinating relative of wheat, it still has promise to widen the variation of 1RS and to fully realize its application value in wheat improvement. In the present study, the wheat-rye breeding line R2207 was characterized by comprehensive analyses using genomic in situ hybridization (GISH), multicolor fluorescence in situ hybridization with multiple probes, multicolor GISH, and molecular marker analysis, and then was proven to be a cytogenetically stable wheat-rye T1RS·1BL translocation line. Based on the disease responses to different isolates of powdery mildew and genetic analysis, R2207 appears to possess a novel variation for resistance, which was confirmed to be located on the rye chromosome arm 1RS. Line R2207 also exhibited high levels of resistance to stripe rust at both seedling and adult stages, as well as enhanced agronomic performance, so it has been transferred into a large number of commercial cultivars using an efficient 1RS-specific kompetitive allele specific PCR marker for marker-assisted selection.
The Effects of Pre-Burn Center Intubation on Rates of Pneumonia, Early Extubation, and Death: A Systematic Review
Authors: Donnelly Jason
Published: May 2020

Airway burns cause delayed collapse of airways due to airway edema. Transferring clinicians are trained to intubate at the first suspicion of airway collapse, which can lead to vague reasons for intubation such as “airway protection.” Intubation, however, is not without risks, such as pneumonia and death. The objective of this research review is to compare pre-burn center intubations with those performed at burn centers and compare rates of pneumonia, mortality, and time to extubation. A systematic review of articles from MEDLINE and CINAHL Plus was performed to identify eligible trials and observational studies that compared pre-burn center intubations with those performed at burn centers between the years 2014 and 2018. Four studies met eligibility requirements. There were mixed results on the correlation of pre-burn center intubation with pneumonia and death; however, pre-burn center patients were more likely to have earlier extubation times, which points to potentially unnecessary intubations. Clinicians should be aware of the increased mortality and morbidity associated with intubation. Providers should use objective evidence-based tools such as the ABA (American Burn Association) and Denver criteria to determine the need for intubation to avoid unnecessary intubations and their potential complications.
Serinicoccus hydrothermalis sp. nov., isolated from shallow-sea hydrothermal systems off Kueishantao Island
Authors: Zhang Qingfeng , Ye Jianing , Yu Limei , Lin Dan , Tang Kai
Published: May 2020

A Gram-stain-positive, non-flagellated, non-gliding, coccoid bacterial strain, designated JLT9T, was isolated from the shallow-sea hydrothermal system off Kueishantao Island, Taiwan, ROC. Strain JLT9T was aerobic, chemoheterotrophic and grew optimally at 35 °C, at pH 6.0 and in the presence of 2.5 % (w/v) NaCl. Strain JLT9T exhibited highest 16S rRNA gene sequence similarity to

Serinicoccus marinus

DSM 15273T (98.83 %). Phylogenetic trees based on 16S rRNA gene sequences revealed that strain JLT9T belonged to the genus

Serinicoccus

, clustering with

Serinicoccus marinus

JC1078T,

Serinicoccus profundi

MCCC 1A05965T,

Serinicoccus sediminis

GP-T3-3T and

Serinicoccus chungangensis

CAU9536T. The digital DNA–DNA genome hybridization values between strain JLT9T and the closest related strain

S. marinus

DSM 15273T was 34.30 %. The DNA G+C content was 72.43 mol%. The dominant fatty acids were identified as iso-C15 : 0 (41.4 %) and iso-C16 : 0 (24.7 %). The polar lipids of strain JLT9T comprised diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, three unidentified glycolipid and an unidentified phospholipid. The predominant isoprenoid quinone was MK-8 (H4). The cell wall contained ornithine and serine, and no diaminopimelic acid. On the basis of phylogenetic data and several distinct phenotypic characteristics, strain JLT9T represents a novel species of the genus

Serinicoccus

, for which the name Serinicoccus hydrothermalis sp. nov. is proposed. The type strain is JLT9T (=CGMCC 1.15779T=JCM 31502T).
Sulfuriferula nivalis sp. nov., a sulfur oxidizer isolated from snow and emended description of Sulfuriferula plumbiphila
Authors: Kojima Hisaya , Mochizuki Jun , Fukui Manabu
Published: May 2020

A chemolithoautotrophic sulfur-oxidizing bacterium, strain SGTMT was isolated from snow collected in Japan. As electron donors for growth, SGTMT oxidized thiosulfate, tetrathionate and elemental sulfur. Heterotrophic growth was not observed. Growth of the novel isolate was observed at a temperature range of 5–28 °C, with optimum growth at 18 °C. SGTMT grew at a pH range of 4.3–7.4, with optimum growth at pH 6.1–7.1. Major components in the cellular fatty acid profile were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0. The complete genome of SGTMT consisted of a circular chromosome of approximately 3.4 Mbp and two plasmids. Phylogenetic analysis based on the 16S rRNA gene indicated that SGTMT represented a member of the genus

Sulfuriferula

, and its closest relative is

Sulfuriferula thiophila

mst6T with a sequence identity of 98 %. A comparative genome analysis showed dissimilarity between the genomes of SGTMT and

S. thiophila

mst6T, as low values of average nucleotide identity (74.9 %) and digital DNA–DNA hybridization (20.4%). On the basis of its genomic and phenotypic properties, SGTMT (=DSM 109609T=BCRC 81185T) is proposed as the type strain of a novel species, Sulfuriferula nivalis sp. nov. Some characteristics of another species in the same genus,

Sulfuriferula plumbiphila

, were also investigated to revise and supplement its description. The type strain of

S. plumbiphila

can grow on thiosulfate, tetrathionate and elemental sulfur. The strain showed optimum growth at pH 6.3–7.0 and shared major cellular fatty acids with the other species of the genus

Sulfuriferula

.
Bacillus aquiflavi sp. nov., isolated from yellow water of strongly flavored Chinese baijiu
Authors: Xie Jiuyan , Cheng Kun , Zhao Dong , Yang Guanrong , Qiao Zongwei , Qiu Shengqiang , Yu Xuejian , Liu Hongqiang , Li Ting , Feng Huijun , Yao Su , Zhai Lei
Published: May 2020

A Gram-stain-positive, strictly aerobic and rod-shaped bacterium, designated as 3 H-10T, was isolated from a yellow water sample collected from the manufacturing process of strong flavor Chinese baijiu in Yibin region of Sichuan province (PR China). Oval endospores were formed at the subtermini of cells with swollen sporangia. The isolate was able to grow at temperatures of 20–45 °C (optimum growth at 37 °C), at pH 6.0–10.0 (optimum growth at pH 8.0) and in the presence of 0–2 % (w/v) NaCl (optimum growth with 0 % NaCl). Ribose was the major cell-wall sugar, and meso-diaminopimelic acid (meso-DAP) was the diagnostic amino acid. The main polar lipids of 3 H-10T included diphosphatidylglycerol (DPG), phosphatidylglycerol (PG) and phosphatidylethanolamine (PE). MK-7 was predominant menaquinone and iso-C15 : 0 (60.7 %) was the major fatty acid. Comparisons of 16S rRNA gene sequence indicated that 3 H-10T was most closely related to

Bacillus mesophilus

SA4T (96.30 %),

Bacillus ginsengihumi

Gsoil 114T (96.27 %) and

Bacillus shackletonii

LMG 18435T (96.27 %). The average nucleotide identity (ANI) values between strain 3 H-10T and the three type strains mentioned above were 69.56, 70.19 and 70.67 %, respectively. The genomic DNA G+C content was 35.4 mol%. On the basis of its phenotypic, chemotaxonomic and phylogenetic properties, strain 3 H-10T represents a novel species of the genus

Bacillus

, for which the name Bacillus aquiflavi sp. nov. is proposed. The type strain is Bacillus aquiflavi 3 H-10T (=CICC 24755T=JCM 33703T).
Oleiharenicola lentus sp. nov., isolated from irrigation water
Authors: Chen Wen-Ming , Chen Tzu-Ying , Yang Che-Chia , Sheu Shih-Yi
Published: May 2020

Bacterial strain TWA-58T, isolated from irrigation water in Taiwan, was characterized using a polyphasic taxonomy approach. Phylogenetic analyses based on 16S rRNA gene sequences and coding sequences of 92 protein clusters indicated that strain TWA-58T formed a phylogenetic lineage in the genus

Oleiharenicola

of the family

Opitutaceae

. Strain TWA-58T was most closely related to

Oleiharenicola alkalitolerans

NVTT with a 96.7 % 16S rRNA gene sequence similarity. Strain TWA-58T showed 75.2 % average nucleotide identity, 70.9 % average amino acid identity and 21.0 % digital DNA–DNA hybridization identity with

O. alkalitolerans

NVTT. Cells were Gram-stain-negative, aerobic, motile, coccoid-shaped and formed transparent colonies. Optimal growth occurred at 25 °C, pH 6, and 0 % NaCl. The major fatty acids of strain TWA-58T were iso-C15 : 0 and anteiso-C15 : 0. The predominant hydroxy fatty acid was iso-C13 : 0 3-OH. The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and two unidentified aminophospholipids. The major isoprenoid quinone was MK-7. Genomic DNA G+C content of strain TWA-58T was 65.3 mol%. On the basis of phenotypic and genotypic properties and phylogenetic inference, strain TWA-58T should be classified in a novel species of the genus

Oleiharenicola

, for which the name Oleiharenicola lentus sp. nov. is proposed. The type strain is TWA-58T (=BCRC 81161T=LMG 31019T=KCTC 62872T).
Proposal for transfer of Defluviimonas alba to the genus Frigidibacter as Frigidibacter mobilis nom. nov
Authors: Liu Yang , Pei Tao , Zhang Jun , Yang Fan , Zhu Honghui
Published: May 2020

A polyphasic taxonomic study was undertaken to clarify the exact position of the type strain cai42T of the species

Defluviimonas alba

Pan et al. 2015. The results of the 16S rRNA gene sequence analysis indicated that the two sequences from cai42T shared 99.6 and 99.7 % similarity to that of the type strain SP32T of the species

Frigidibacter albus

and formed a coherent clade in the phylogenetic tree. Whole genomic comparison between cai42T and SP32T yielded a digital DNA–DNA hybridization estimate of 36.3 %, an average nucleotide identity of 88.8 % and an average amino acid identity of 89.8 %, clearly indicating that the two strains should belong to two genospecies of the same genus. The close relationship between the two strains was underpinned by the results of genome-based phylogenetic analysis. Although cai42T and SP32T shared similar physiological and biochemical properties, some striking differences, such as mobility, the temperature range for growth and the polar lipid components, could distinguish them as separate species. Therefore, the comparative phenotypic and genotypic analyses supported the incorporation of

Defluviimonas alba

into the genus

Frigidibacter

as Frigidibacter mobilis nom. nov. with the type strain cai42T (=CGMCC 1.12518T=LMG 27406T).
Genomic analysis of 40 prophages located in the genomes of 16 carbapenemase-producing clinical strains of Klebsiella pneumoniae
Authors: Bleriot Ines , Trastoy Rocío , Blasco Lucia , Fernández-Cuenca Felipe , Ambroa Antón , Fernández-García Laura , Pacios Olga , Perez-Nadales Elena , Torre-Cisneros Julian , Oteo-Iglesias Jesús , Navarro Ferran , Miró Elisenda , Pascual Alvaro , Bou German , Martínez-Martínez Luis , Tomas Maria
Published: May 2020

Klebsiella pneumoniae

is the clinically most important species within the genus

Klebsiella

and, as a result of the continuous emergence of multi-drug resistant (MDR) strains, the cause of severe nosocomial infections. The decline in the effectiveness of antibiotic treatments for infections caused by MDR bacteria has generated particular interest in the study of bacteriophages. In this study, we characterized a total of 40 temperate bacteriophages (prophages) with a genome range of 11.454–84.199 kb, predicted from 16 carbapenemase-producing clinical strains of

K. pneumoniae

belonging to different sequence types, previously identified by multilocus sequence typing. These prophages were grouped into the three families in the order Caudovirales (27 prophages belonging to the family Myoviridae, 10 prophages belonging to the family Siphoviridae and 3 prophages belonging to the family Podoviridae). Genomic comparison of the 40 prophage genomes led to the identification of four prophages isolated from different strains and of genome sizes of around 33.3, 36.1, 39.6 and 42.6 kb. These prophages showed sequence similarities (query cover >90 %, identity >99.9 %) with international Microbe Versus Phage (MVP) (http://mvp.medgenius.info/home) clusters 4762, 4901, 3499 and 4280, respectively. Phylogenetic analysis revealed the evolutionary proximity among the members of the four groups of the most frequently identified prophages in the bacterial genomes studied (33.3, 36.1, 39.6 and 42.6 kb), with bootstrap values of 100 %. This allowed the prophages to be classified into three clusters: A, B and C. Interestingly, these temperate bacteriophages did not infect the highest number of strains as indicated by a host-range assay, these results could be explained by the development of superinfection exclusion mechanisms. In addition, bioinformatic analysis of the 40 identified prophages revealed the presence of 2363 proteins. In total, 59.7 % of the proteins identified had a predicted function, mainly involving viral structure, transcription, replication and regulation (lysogenic/lysis). Interestingly, some proteins had putative functions associated with bacterial virulence (toxin expression and efflux pump regulators), phage defence profiles such as toxin–antitoxin modules, an anti-CRISPR/Cas9 protein, TerB protein (from terZABCDE operon) and methyltransferase proteins.
Antibiotic resistance in Pseudomonas aeruginosa and adaptation to complex dynamic environments
Authors: Sommer Lea M. , Johansen Helle K. , Molin Søren
Published: May 2020

Antibiotic resistance has become a serious threat to human health (WHO Antibacterial Agents in Clinical Development: an Analysis of the Antibacterial Clinical Development Pipeline, Including Tuberculosis. Geneva: World Health Organization; 2017), and the ability to predict antibiotic resistance from genome sequencing has become a focal point for the medical community. With this genocentric prediction in mind, we were intrigued about two particular findings for a collection of clinical

Pseudomonas aeruginosa

isolates (Marvig et al. Nature Genetics 2015;47:57–64; Frimodt-Møller et al. Scientific Reports 2018;8:12512; Bartell et al. Nature Communications 2019;10:629): (i) 15 out of 52 genes found to be frequently targeted by adaptive mutations during the initial infection stage of cystic fibrosis airways (‘candidate pathoadaptive genes’) (Marvig et al. Nature Genetics 2015;47:57–64) were associated with antibiotic resistance (López-Causapé et al. Fronters in Microbiology 2018;9:685; López-Causapé et al. Antimicrobal Agents and Chemotherapy 2018;62:e02583-17); (ii) there was a parallel lack of resistance development and linkage to the genetic changes in these antibiotic-resistance-associated genes (Frimodt-Møller et al. Scientific Reports 2018;8:12512; Bartell et al. Nature Communications 2019;10:629). In this review, we highlight alternative selective forces that potentially enhance the infection success of

P. aeruginosa

and focus on the linkage to the 15 pathoadaptive antibiotic-resistance-associated genes, thereby showing the problems we may face when using only genomic information to predict and inform about relevant antibiotic treatment.
On the progression of COVID19 in Portugal: A comparative analysis of active cases using non-linear regression
Authors: Milhinhos Ana , Costa Pedro M.
Published: May 2020

Portugal has been portrayed as a relatively successful case in the control of the COVID-19’s March 2020 outbreak in Europe due to the timely confinement measures taken. As other European Union member states, Portugal is now preparing the phased loosening of the confinement measures, starting in the beginning of May. Even so, the current data, albeit showing at least a reduction in infection rates, renders difficult to forecast scenarios in the imminent future. Using South Korea data as scaffold, which is becoming a paradigmatic case of recovery following a high number of infected people, we fitted Portuguese data to biphasic models using non-linear regression and compared the two countries. The results, which suggest good fit, show that recovery in Portugal can be much slower than anticipated, with a very high percentage of active cases (over 50%) remaining still active even months after the projected end of mitigation measures. This, together with the unknown number of asymptomatic carriers, may increase the risk of a much slower recovery if not of new outbreaks. Europe and elsewhere must consider this contingency when planning the relief of containment measures.
Estimation of COVID-19 case fatality ratio based on a bi-directional correction method
Authors: Hu Wanling , Liu Xiaoyun , Wang Tao , Zhou Changlong , Liu Dingfu , Zhang Yuanming , Hu Zhongli , Diao Ying
Published: May 2020

The case fatality rate (CFR) can be used to predict the number of potential deaths in the epidemic and thus can reflect the appropriateness and quality of medical measures developed by public health. When a new disease breaks out, it is particularly important to accurately estimate the CFR. However, while the epidemic is still developing, the crude CFR is often lower than the true value and the hospital CFR is often higher than the true value due to differences in occurrence time, patient number, and treatment plans. Therefore, this study proposes a bi-directional correction method to estimate the CFR. COVID-19 data from China were used to evaluate this method. The results show that this method provides more accurate results than both the crude CFR and hospital CFR. Additionally, this method was used to estimate the CFR of COVID-19 in other countries, with an aim to provide a reference for prevention and control decisions for the COVID-19 epidemic and for the evaluation of medical efforts.
Factors Influencing Mental Health During Covid-19 Outbreak: An Exploratory Survey Among Indian Population
Authors: Ahmad Absar , Rahman Ishrat , Agarwal Maitri
Published: May 2020

Purpose

Research on the impact of social distancing on mental health during epidemics is limited, especially in India. The purpose of this study is to scale the association between anxiety and socio-demographic factors during Covid19 lockdown among the general Indian population.

Design/methodology/approach

A descriptive cross-sectional nationwide study was designed to enrol the general population. The inclusion criteria for this study were Indian citizens aged 18 years and above. The study was conducted from 29th March to 12th April 2020, using an online google questionnaire. The anxiety among respondents was detected and measured using a Generalised Anxiety Disorder Scale which consists of 7 questions (in English), i.e. GAD-7.

Findings

Respondees were 392, and from these participants, the prevalence of anxiety was 25.3 per cent. Based on the bivariate logistic regression analysis, the predictors of anxiety were gender, religion, occupation as business/self-employed, marital status, family size, health status and sleep deprivation.

Conclusion

This study reports the prevalence of anxiety among Indian population who were grounded at their homes during lockdown due to coronavirus pandemic in the country.

Limitations

(1) The selection of participants through non-random sampling. (2) Because of the cross-sectional character of the study, causal conclusions cannot be drawn.

Originality/Value

This paper fulfils an identified need to study the mental health status of the population under situations like lockdown, thereby helping fill a persistent gap in Indian research on this issue.
The importance of the timing of quarantine measures before symptom onset to prevent COVID-19 outbreaks - illustrated by Hong Kong’s intervention model
Authors: Yuan Hsiang-Yu , Han Guiyuan , Yuan Hsiangkuo , Pfeiffer Susanne , Mao Axiu , Wu Lindsey , Pfeiffer Dirk
Published: May 2020

Background

The rapid expansion of the current COVID-19 outbreak has caused a global pandemic but how quarantine-based measures can prevent or suppress an outbreak without other more intrusive interventions has not yet been determined. Hong Kong had a massive influx of travellers from mainland China, where the outbreak began, during the early expansion period coinciding with the Lunar New Year festival; however, the spread of the virus has been relatively limited even without imposing severe control measures, such as a full city lockdown. Understanding how quarantine measures in Hong Kong were effective in limiting community spread can provide us with valuable insights into how to suppress an outbreak. However, challenges exist in evaluating the effects of quarantine on COVID-19 transmission dynamics in Hong Kong due to the fact that the effects of border control have to be also taken into account.

Methods

We have developed a two-layered susceptible-exposed-infectious-quarantined-recovered (SEIQR) meta-population model which can estimate the effects of quarantine on virus transmissibility after stratifying infections into imported and subsequent community infections, in a region closely connected to the outbreak’s source. We fitted the model to both imported and local confirmed case data with symptom onset from 18 January to 29 February 2020 in Hong Kong, together with daily transportation data and the transmission dynamics of COVID-19 from Wuhan and mainland China. After model fitting, epidemiological parameters and the timing of the start of quarantine for infected cases were estimated.

Results

The model estimated that the reproduction number of COVID-19 in Hong Kong was 0.76 (95% CI, 0.66 to 0.86), achieved through quarantining infected cases −0.57 days (95% CI, −4.21 − 3.88) relative to symptom onset, with an estimated incubation time of 5.43 days (95% CI, 1.30 − 9.47). However, if delaying the quarantine start by more than 1.43 days, the reproduction number would be greater than one, making community spread more likely. The model also determined the timing of the start of quarantine necessary in order to suppress an outbreak in the presence of population immunity.

Conclusion

The results suggest that the early quarantine for infected cases before symptom onset is a key factor to prevent COVID-19 outbreak.
Metabolomic and Proteomic Stratification of Equine Osteoarthritis
Authors: Anderson James R , Phelan Marie M , Caamaño-Gutiérrez Eva , Clegg Peter D , Rubio-Martinez Luis M , Peffers Mandy J
Published: May 2020

Osteoarthritis (OA) is characterised by loss of articular cartilage, synovial membrane dysfunction and subchondral sclerosis. Few studies have used a global approach to stratify equine synovial fluid (SF) molecular profiles according to OA severity. SF was collected from 58 metacarpophalangeal (MCP) and metatarsophalangeal joints of racing Thoroughbred horses (Hong Kong Jockey Club; HKJC) and 83 MCP joints of mixed breed horses from an abattoir and equine hospital (biobank). Joints were histologically and macroscopically assessed for OA severity. For proteomic analysis, native SF and SF loaded onto ProteoMiner™ equalisation columns, to deplete high abundant proteins, were analysed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and label-free quantification. Validation of selected differentially expressed proteins was undertaken using clinical SF collected during diagnostic investigations. Native SF metabolites were analysed using 1D1H Nuclear Magnetic Resonance (NMR). 1,834 proteins and 40 metabolites were identified in equine SF. Afamin levels decreased with synovitis severity and four uncharacterised proteins decreased with OA severity. Gelsolin and lipoprotein binding protein decreased with OA severity and apolipoprotein A1 levels increased for mild and moderate OA. Within the biobank, glutamate levels decreased with OA severity and for the HKJC cohort, 2-aminobutyrate, alanine and creatine increased with severity. Proteomic and metabolomic integration was undertaken using linear regression via Lasso penalisation modelling, incorporating 29 variables (R2=0.82) with principal component 2 able to discriminate advanced OA from earlier stages, predominantly driven by H9GZQ9, F6ZR63 and alanine. Combining biobank and HKJC datasets, discriminant analysis of principal components modelling prediction was good for mild OA (90%). This study has stratified equine OA using both metabolomic and proteomic SF profiles and identified a panel of markers of interest which may be applicable to grading OA severity. This is also the first study to undertake computational integration of NMR metabolomic and LC-MS/MS proteomic datasets of any biological system.
Planarian stem cells sense the identity of missing tissues to launch targeted regeneration
Authors: Bohr Tisha E. , Shiroor Divya A. , Adler Carolyn E.
Published: May 2020

In order to regenerate tissues successfully, stem cells must first detect injuries and then produce missing cell types through largely unknown mechanisms. Planarian flatworms have an extensive stem cell population responsible for regenerating any organ after amputation. Here, we compare stem cell responses to different injuries by amputation of a single organ, the pharynx, or removal of tissues from other organs by decapitation. We find that planarian stem cells adopt distinct behaviors depending on what tissue is missing: loss of non-pharyngeal tissues increases numbers of non-pharyngeal progenitors, while removal of the pharynx specifically triggers proliferation and expansion of pharynx progenitors. By pharmacologically inhibiting either proliferation or activation of the MAP kinase ERK, we identify a narrow window of time during which proliferation, followed by ERK signaling, produces pharynx progenitors necessary for regeneration. Further, unlike pharynx regeneration, eye regeneration does not depend on proliferation or ERK activation. These results indicate that stem cells tailor their proliferation and expansion to match the regenerative needs of the animal.
SARS-CoV-2 codon usage bias downregulates host expressed genes with similar codon usage
Authors: Alonso Andres Mariano , Diambra Luis
Published: May 2020

Severe acute respiratory syndrome is quickly spreading throughout the world and was declared as a pandemic by the World Health Organisation (WHO). The pathogenic agent is a new coronavirus (SARS-CoV-2) that infects pulmonary cells with great effectiveness. In this study we focus on the codon composition for the viral proteins synthesis and its relationship with the proteins synthesis of the host. Our analysis reveals that SARS-CoV-2 preferred codons have poor representation of G or C nucleotides in the third position, a characteristic which could conduct to an unbalance in the tRNAs pools of the infected cells with serious implications in host protein synthesis. By integrating this observation with proteomic data from infected cells, we observe a reduced translation rate of host proteins associated with highly expressed genes, and that they share the codon usage bias of the virus. The functional analysis of these genes suggests that this mechanism of epistasis contributes to understand some deleterious collateral effect as result of the viral replication. In this manner, our finding contribute to the understanding of the SARS-CoV-2 pathogeny and could be useful for the design of a vaccine based on the live attenuated strategy.
Neutralization of SARS-CoV-2 by destruction of the prefusion Spike
Authors: Huo Jiandong , Zhao Yuguang , Ren Jingshan , Zhou Daming , Duyvesteyn Helen ME , Ginn Helen M , Carrique Loic , Malinauskas Tomas , Ruza Reinis R , Shah Pranav NM , Tan Tiong Kit , Rijal Pramila , Coombes Naomi , Bewley Kevin , Radecke Julika , Paterson Neil G , Supasa Piyasa , Mongkolsapaya Juthathip , Screaton Gavin R , Carroll Miles , Townsend Alain , Fry Elizabeth E , Owens Raymond J , Stuart David I
Published: May 2020

There are as yet no licenced therapeutics for the COVID-19 pandemic. The causal coronavirus (SARS-CoV-2) binds host cells via a trimeric Spike whose receptor binding domain (RBD) recognizes angiotensin-converting enzyme 2 (ACE2), initiating conformational changes that drive membrane fusion. We find that monoclonal antibody CR3022 binds the RBD tightly, neutralising SARS-CoV-2 and report the crystal structure at 2.4 Å of the Fab/RBD complex. Some crystals are suitable for screening for entry-blocking inhibitors. The highly conserved, structure-stabilising, CR3022 epitope is inaccessible in the prefusion Spike, suggesting that CR3022 binding would facilitate conversion to the fusion-incompetent post-fusion state. Cryo-EM analysis confirms that incubation of Spike with CR3022 Fab leads to destruction of the prefusion trimer. Presentation of this cryptic epitope in an RBD-based vaccine might advantageously focus immune responses. Binders at this epitope may be useful therapeutically, possibly in synergy with an antibody blocking receptor attachment.

Highlights

CR3022 neutralises SARS-CoV-2

Neutralisation is by destroying the prefusion SPIKE conformation

This antibody may have therapeutic potential alone or with one blocking receptor attachment
Development and simulation of fully glycosylated molecular models of ACE2-Fc fusion proteins and their interaction with the SARS-CoV-2 spike protein binding domain
Authors: Bernardi Austen , Huang Yihan , Harris Bradley , Xiong Yongao , Nandi Somen , McDonald Karen A. , Faller Roland
Published: May 2020

We develop fully glycosylated computational models of ACE2-Fc fusion proteins which are promising targets for a COVID-19 therapeutic. These models are tested in their interaction with a fragment of the receptor-binding domain (RBD) of the Spike Protein S of the SARS-CoV-2 virus, via atomistic molecular dynamics simulations. We see that some ACE2 glycans interact with the S fragments, and glycans are influencing the conformation of the ACE2 receptor. Additionally, we optimize algorithms for protein glycosylation modelling in order to expedite future model development. All models and algorithms are openly available.
Identification of novel mutations in RNA-dependent RNA polymerases of SARS-CoV-2 and their implications on its protein structure
Authors: Chand Gyanendra Bahadur , Banerjee Atanu , Azad Gajendra Kumar
Published: May 2020

The rapid development of SARS-CoV-2 mediated COVID-19 pandemic has been the cause of significant health concern, highlighting the immediate need for the effective antivirals. SARS-CoV-2 is an RNA virus that has an inherent high mutation rate. These mutations drive viral evolution and genome variability, thereby, facilitating viruses to have rapid antigenic shifting to evade host immunity and to develop drug resistance. Viral RNA-dependent RNA polymerases (RdRp) perform viral genome duplication and RNA synthesis. Therefore, we compared the available RdRp sequences of SARS-CoV-2 from Indian isolates and ‘Wuhan wet sea food market virus’ sequence to identify, if any, variation between them. We report seven mutations observed in Indian SARS-CoV-2 isolates and three unique mutations that showed changes in the secondary structure of the RdRp protein at region of mutation. We also studied molecular dynamics using normal mode analyses and found that these mutations alter the stability of RdRp protein. Therefore, we propose that RdRp mutations in Indian SARS-CoV-2 isolates might have functional consequences that can interfere with RdRp targeting pharmacological agents.
Effects of regulatory network organization and environment on PmrD connector activity and polymyxin resistance inKlebsiella pneumoniaeandEscherichia coli
Authors: Chen Annie I. , Zhu Jun , Goulian Mark
Published: May 2020

Polymyxins are a class of cyclic peptides with antimicrobial activity against Gram-negative bacteria. Resistance to these compounds is often mediated by pathways that also confer resistance to host antimicrobial peptides. InEnterobacteriaceae, the PhoQ/PhoP and PmrB/PmrA two-component systems regulate many of the genes associated with these resistance mechanisms. InK. pneumoniae, spontaneous polymyxin resistance is frequently acquired through inactivation of the genemgrB, which encodes a negative regulator of PhoQ. However, this resistance mechanism has not been reported in other genera ofEnterobacteriaceae, despite the presence ofmgrBamong many members of this family. In addition, the frequency of developing spontaneous resistance to the antimicrobial peptide polymyxin through chromosomal mutations is much higher inKlebsiellacompared toSalmonellaorE. coli. Here we show that inK. pneumoniae, PmrD is not required for polymyxin resistance arising from inactivation ofmgrB. In addition, we show that inE. coli, the protein PmrD can activate PmrA under certain conditions. Our results suggest that the importance of PmrD connector activity in polymyxin resistance depends on both the network organization and on the environmental conditions associated with PmrB stimulation.
Co-evolution of Eukaryotic-like Vps4 and ESCRT-III Subunits in the Asgard Archaea
Authors: Lu Zhongyi , Fu Ting , Li Tianyi , Liu Yang , Zhang Siyu , Li Jinquan , Dai Junbiao , Koonin Eugene V , Li Guohui , Chu Huiying , Li Meng
Published: May 2020

The emergence of the endomembrane system is a key step in the evolution of cellular complexity during eukaryogenesis. The Endosomal Sorting Complex Required for Transport (ESCRT) machinery is essential and required for the endomembrane system functions in eukaryotic cells. Recently, genes encoding eukaryote-like ESCRT protein components have been identified in the genomes of Asgard archaea, a newly proposed archaeal superphylum that is thought to include the closest extant prokaryotic relatives of eukaryotes. However, structural and functional features of Asgard ESCRT remain uncharacterized. Here we show that Vps4, Vps2/24/46, and Vps20/32/60, the core functional components of the Asgard ESCRT, co-evolved eukaryote-like structural and functional features. Phylogenetic analysis shows that Asgard Vps4, Vps2/24/46, and Vps20/32/60 are closely related to their eukaryotic counterparts. Molecular dynamic simulation and biochemical assays indicate that Asgard Vps4 contains a eukaryote-like Microtubule Interacting and Transport (MIT) domain that binds the distinct type-1 MIT Interacting Motif and type-2 MIT Interacting Motif in Vps2/24/46, and Vps20/32/60, respectively. The Asgard Vps4 partly, but much more efficiently than homologs from other archaea, complements thevps4null mutant ofSaccharomyces cerevisiae, further supporting the functional similarity between the membrane remodeling machineries of Asgard archaea and eukaryotes. Thus, this work provides evidence that the ESCRT complexes from Asgard archaea and eukaryotes are evolutionarily related and functionally similar. Thus, despite the apparent absence of endomembranes in Asgard archaea, the eukaryotic ESCRT seems to have been directly inherited from an Asgard ancestor, to become a key component of the emerging endomembrane system.

IMPORTANCE

The discovery of Asgard archaea has changed the exiting ideas on the origins of Eukaryotes. Researchers propose that eukaryotic cells evolve from Asgard archaea. This hypothesis partly stems from the presence of multiple eukaryotic signature proteins in Asgard archaea, including homologues of ESCRT proteins that are essential components of the endomembrane system in eukaryotes. However, structural and functional features of Asgard ESCRT remain unknown. Our study provides evidence that Asgard ESCRT is functionally comparable to the eukaryotic counterparts suggesting that, despite the apparent absence of endomembranes in archaea, eukaryotic ESCRT was inherited from an Asgard archaeal ancestor, alongside the emergence of endomembrane system during eukaryogenesis.
Applying Lexical Link Analysis to Discover Insights from Public Information on COVID-19
Authors: Zhao Ying , Zhou Charles C.
Published: May 2020

SARS-Cov-2, the deadly and novel virus, which has caused a worldwide pandemic and drastic loss of human lives and economic activities. An open data set called the COVID-19 Open Research Dataset or CORD-19 contains large set full text scientific literature on SARS-CoV-2. The Next Strain consists of a database of SARS-CoV-2 viral genomes from since 12/3/2019. We applied an unique information mining method named lexical link analysis (LLA) to answer the call to action and help the science community answer high-priority scientific questions related to SARS-CoV-2. We first text-mined the CORD-19. We also data-mined the next strain database. Finally, we linked two databases. The linked databases and information can be used to discover the insights and help the research community to address high-priority questions related to the SARS-CoV-2’s genetics, tests, and prevention.

Significance Statement

In this paper, we show how to apply an unique information mining method lexical link analysis (LLA) to link unstructured (CORD-19) and structured (Next Strain) data sets to relevant publications, integrate text and data mining into a single platform to discover the insights that can be visualized, and validated to answer the high-priority questions of genetics, incubation, treatment, symptoms, and prevention of COVID-19.
Synthetic Zippers as an Enabling Tool for Engineering of Non-Ribosomal Peptide Synthetases
Authors: Bozhueyuek Kenan A. J. , Watzel Jonas , Abbood Nadya , Bode Helge B.
Published: May 2020

Non-ribosomal peptide synthetases (NRPSs) are the origin of a wide range of natural products, including many clinically used drugs. Engineering of these often giant biosynthetic machineries to produce novel non-ribosomal peptides (NRPs) at high titre is an ongoing challenge. Here we describe a strategy to functionally combine NRPS fragments of Gram-negative and -positive origin, synthesising novel peptides at titres up to 290 mg l-1. Extending from the recently introduced definition of eXchangeUnits (XUs), we inserted synthetic zippers (SZs) to split single protein NRPSs into up to three independently expressed and translated polypeptide chains. These synthetic type of NRPS (type S) enables easier access to engineering, overcomes cloning limitations, and provides a simple and rapid approach to building peptide libraries via the combination of different NRPS subunits.

One Sentence Summary

Divide and Conquer: A molecular tool kit to reprogram the biosynthesis of non-ribosomal peptides.
Roles of developmentally regulated KIF2A alternative isoforms in cortical neuron migration and differentiation
Authors: Akkaya Cansu , Atak Dila , Kamacioglu Altug , Akarlar Busra Aytul , Guner Gokhan , Bayam Efil , Taskin Ali Cihan , Ozlu Nurhan , Ince-Dunn Gulayse
Published: May 2020

KIF2A is a microtubule-depolymerizing kinesin motor protein with essential roles in neural progenitor division and axonal pruning during brain development. KIF2A is alternatively spliced in nervous tissue by specific RNA-binding proteins. However, how different KIF2A isoforms function during development of the cerebral cortex is not known. Here, we focus on threeKif2aisoforms expressed in mouse embryonic and postnatal cerebral cortex. We show that KIF2A is essential for dendritic pruning of primary cortical neurons in mice and that the functions of all three isoforms are sufficient for this process. Interestingly, only two of the isoforms can sustain radial migration of cortical neurons while a third isoform, lacking a key stretch of twenty amino acids, is ineffective. By proximity-labeling-based interactome mapping for individual KIF2A isoforms, we provide novel insight into how isoform specific interactions can confer changes to KIF2A protein function. Our interactome mapping identifies previously known KIF2A interactors, proteins localized to the mitotic spindle poles, and unexpectedly, also translation factors, ribonucleoproteins and proteins that are targeted to the mitochondria and ER, suggesting a novel transport function for KIF2A.
Optimization of crankpin bearing lubrication under dynamic loading considering effect of micro asperity contact
Authors: Nguyen Vanliem , Wu Zhenpeng , Le Vanquynh
Published: May 2020

Purpose

To improve the lubrication and tribology performance (LTP) of the crankpin bearing, this paper aims to propose the optimization of the crankpin bearing parameters considering effect of the high-speed dynamic load and micro asperity contact.

Design/methodology/approach

A numerical simulation method combined by the slider-crank-mechanism dynamic and lubrication models is applied to solve the dynamic and lubrication equations of crankpin bearing. These equations are then computed via an algorithm program written in Matlab software. The contact force (Wac) in the asperity contact region, friction force (Ff) and friction coefficient (μ) of crankpin bearing are chosen as objective functions. The original parameters and experimental data of the engine are used for the simulation to enhance the reliability of the research results. The parameters are then optimized to obtain the minimum values of Wac, Ff and μ.

Findings

The research results show that the LTP is significantly improved with optimized parameters. Particularly, the maximum values of Wac and Ff are greatly decreased by 27 and 32%, respectively.

Originality/value

Reducing the width, radius and surface roughness and increasing the radial clearance of crankpin bearing can improve better the LTP.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-02-2020-0072/
An integrated framework for prioritizing the outsourcing performance outcomes
Authors: Prajapati Himanshu , Kant Ravi , Tripathi Sandeep Mani
Published: May 2020

Purpose

Outsourcing is a crucial tool for an organization to focus on its core business operations. The purpose of this study is to find critical success factors (CSFs) of outsourcing and to prioritize the performance outcomes of outsourcing because of the adoption of its CSFs.

Design/methodology/approach

This research proposes the hybrid framework of fuzzy Delphi, fuzzy analytic hierarchy process (F-AHP) and fuzzy additive ratio assessment (F-ARAS) to fulfill the research objectives. Fuzzy Delphi is used to finalize the CSFs of outsourcing and F-AHP provides the relative weights to it. F-ARAS is used to prioritize the outsourcing performance indicators with respect to CSFs. The empirical case investigation of three Indian large-scale public sector process industries is conducted to demonstrate the applicability of the proposed framework.

Findings

The result shows that increased dominance in core activity, ability to increase or decrease capacity, improved financial performance, optimized resource utilization and increased market share are the top five performance outcomes because of the adoption of outsourcing CSFs.

Research limitations/implications

Factors such as cultural, political, environmental and size of the organization may have a significant implication on the research results.

Originality/value

This is a novel approach towards the prioritization of performance outcomes of outsourcing. Moreover, the present research is a helpful tool to manage outsourcing and choosing which performance outcome of outsourcing ought to be used to measure implementation. This will help to recognize potential opportunities and preparing strategic planning for both short-term and long-term goals.