bluuebunny/crossref_metadata_2025 huggingface dataset:
Insight parameter drug design for human beta-tryptase inhibition integrated molecular docking, QSAR, molecular dynamics simulation, and pharmacophore modelling studies of alpha-keto-[1,2,4]-oxadiazoles
Authors: Yu Chai Xin , Tan Jian Wei , Imran Syahrul , Rullah Kamal , Tham Chau Ling
Published: July 2022

Dengue hemorrhagic fever (DHF) is life-threatening severe dengue with a hallmark of vascular leakage. A mast cell protease, beta-tryptase, has been found to promote vascular leakage in DHF patients, which could be a potential target for the treatment of DHF. This study aims to develop a theoretical background for the design and selection of beta-tryptase inhibitors through these approaches: two-dimensional quantitative structure-activity relationships (2D-QSAR) study, molecular docking analysis, molecular dynamics (MD) simulation, and structure-based pharmacophore modelling (PM). A total of 34 beta-keto-[1,2,3]-oxadiazoles scaffold-based compounds, obtained from a past study, were used to generate 2D-QSAR models by Genetic Function Approximation (GFA). The generated 2D-QSAR models were used to investigate the relationships between the molecular structure and the potency of beta-tryptase inhibition. Molecular docking explores the binding affinities and binding interactions of the beta-keto-[1,2,3]-oxadiazoles scaffold-based compounds with beta-tryptase (PDB Code 4A6L) by the CDOCKER tool in Discovery Studio. In addition, MD simulation was performed using GROMACS on the docked complex of the reported most active compound, compound 11e, to study the binding mechanism of the compound towards beta-tryptase. Finally, a structure-based pharmacophore model was generated from the same docked complex to identify the important features that contribute positively to the inhibitory activity of the compound towards beta-tryptase. The best 2D-QSAR model has demonstrated statistically significant results through its r2, q2, and r2 (pred) values of 0.9077, 0.733, and 0.8104, respectively. The docking results of compound 11e showed lower CDOCKER energy than the 4A6L co-crystallised ligand, indicating good binding affinity. Furthermore, compound 11e has a similar binding pattern as the 4A6L co-crystallised ligand, which involves the binding of active residues such as Asp207, SER208, and GLY237. The MD simulation shows that the 4A6L-compound 11e complex has RMSD below 2 angstrom throughout the 100ns of simulation, indicating that the docked complex is stable. Besides, MD simulation showed that the inhibitory potency of compound 11e is contributed by hydrogen bonding with 4A6L active site residues, which are ASP207, SER208, and GLY237. The best pharmacophore model identified features that contribute to the inhibitory potency of a compound, which included hydrogen bond acceptor, ionic interaction, hydrophobic interaction, and aromatic ring. This study has fundamentally supplied valuable insight and knowledge for developing novel chemical compounds with improved inhibitory ability against human beta-tryptase.
Ab-AMR: A Comprehensive Repository of Acinetobacter baumannii to Understand the Molecular Landscape of Antimicrobial Resistance
Authors: Sharma Tina , Kumar Rakesh , Bhardwaj Anshu
Published: July 2022

Ab-AMR is a comprehensive repository of drug resistance mechanisms in Acinetobacter baumannii. The current version of Ab-AMR provides a drug resistance profile of 788 genomes. In order to ensure that the datasets in Ab-AMR have relevance both to the research and clinical community, standards of defining MIC breakpoints, whole genome sequence quality metrics as defined by EUCAST/CLSI and classification of isolates into susceptible, MDR, XDR and PDR as defined by CDC/ECDC are implemented. As of now, 364 DR determinants associated with antibiotic inactivation (β-lactamases, aminoglycoside modification, chloramphenicol acetyltransferase), efflux, protein modulating permeability and alteration of target site are comprehensively annotated. In addition, data from pangenome analysis across 788 genomes is also provided for identification of core and accessory DR determinants. AB ATCC 17978 (Accession-CP000521.1), the reference strain, was annotated on January 1, 2014 but subsequently the same strain was re-annotated on March 21, 2017 (NZ_CP018664.1) due to incorrect assembly. Therefore, the genome comparison of both, 2014 and 2017 versions were performed for maintaining the correct annotations as most of the literature data referred to the earlier version of the reference genome. In Ab-AMR, the reference coordinates of the revised reference genome are used to represent manually curated and comprehensively annotated data on 614 essential genes, 1334 genes mapped to pathways, 221 PDB structures, 81 reported drug targets, 364 genes with reported resistance mechanism, 118 transcription factors, 4 sigma factors and 14 two component systems. Ab-AMR is made using the standard php-mysql framework and offers various search tools including a query builder that facilitates query on over 60 different features for addressing complex questions like core genes which are also essential and have a role to play in drug resistance with no known human homolog, etc. Ab-AMR offers a centralized data resource for systematic mapping of DR determinants, both plasmid and chromosomal mediated, along with deep annotation of clinical isolates.

Database URL: https://datascience.imtech.res.in/anshu/ab-amr/
Is the interaction of technology useful in laboratory haematology diagnostics?
Authors: Falda Alessandra , Falda Marco , Pacioni Aurelio , Borgo Giada , Russelli Rosolino , Antico Antonio
Published: July 2022

Background

Monoclonal B lymphocytosis (MBL) increases with age and individuals with high count MBL progress to chronic lymphocytic leukaemia requiring therapy at a rate of ∼1%-5% per year. These cases usually have atypical lymphocytes at the microscope, abnormal representation in the scattergram, and positivity of flags. Using XN9000 (Sysmex), we noticed cases of MBL without this correlation. We studied customized gates for discovering MBL cases of our interest.

Methods

We considered 212 peripheral blood samples with known phenotypes: 76.7% negative and 23.3% positive for B, T, or NK lymphocytes clones. We created gates studying the XN9000 FCS files in Diva software to identify new areas for better delimiting subpopulations of our interest and calculating sensitivity and specificity.

Results

We found significant differences between negative and positive groups for Q-flag “Blasts/Abn Lympho?” (B/AL) and LY-X (p <0.05) with lymphocyte counts below 5×109/L.

A new gate P1 normalized by P2 (P1n) differentiated between phenotypes much better than Q-flag B/AL with lymphocyte counts ≤ 5 ×109/L. Moreover, cases with MBL CD5 positive had higher medians (p <0.05).

Conclusion

We propose a gate P1n as a new Q-flag for lymphocytes count ≤ 5 ×109/L, in order to hypothesize the presence of MBL CD5 positives.
Protein as evolvable functionally-constrained amorphous matter
Authors: Tripathy Madhusmita , Srivastava Anand , Sastry Srikanth , Rao Madan
Published: July 2022

We explore current ideas around the representation of a protein as an amorphous material, in turn represented by an abstract graph 𝒢 with edges weighted by elastic stiffnesses. By embedding this graph in physical space, we can map every graph to a spectrum of conformational fluctuations and responses (as a result of say, ligand-binding). This sets up a “genotype-phenotype” map, which we use to evolve the amorphous material to select for fitness. Using this, we study the emergence of allosteric interaction, hinge joint, crack formation and a slide bolt in functional proteins such as Adenylate kinase, HSP90, Calmodulin and GPCR proteins. We find that these emergent features are associated with specific geometries and mode spectra of floppy or liquid-like regions. Our analysis provides insight into understanding the architectural demands on a protein that enable a prescribed function and its stability to mutations.
Three-dimensional humanized gingival tissue model to study oral microbiome
Authors: Adelfio Miryam , Martin-Moldes Zaira , Erndt-Marino Joshua , Tozzi Lorenzo , Duncan Margaret J. , Hasturk Hatice , Kaplan David L. , Ghezzi Chiara E.
Published: July 2022

The oral cavity contains different microenvironments, as the non-shedding surface of the teeth and the epithelial mucosa, where oral barriers and microbial communities coexist. The interactions and balances between these two communities are responsible for oral tissue homeostasis or dysbiosis, that ultimately dictate health or disease. Disruption of this equilibrium is the first necessary step towards chronic inflammation and permanent tissue damage in the case of chronic periodontitis. There are currently no experimental models able to mimic the structural, physical, and metabolic conditions present in the oral gingival tissue to support the long-term investigation of host-pathogens unbalances. Herein, we report a 3D anatomical gingival in vitro model based on human primary culture that recapitulates the native tissue organization, and a native oxygen gradient within the gingival pocket to support human microbiome persistence with a physiologically relevant level of microbial diversity as well as native spatial organization. The modulation of inflammatory markers in the presence of oral microbiome suggested the humanized functional response of this model. The model will be used in future studies to investigate host-pathogen unbalances in gingivitis and periodontal disease.
Hippocampal and Medial Prefrontal Cortical Maps Represent Episodes and Rules in a Common Task Space
Authors: Srinivasan Aditya , Riceberg Justin S. , Goodman Michael R. , Srinivasan Arvind , Guise Kevin G. , Shapiro Matthew L.
Published: July 2022

Memory helps us adapt to changing circumstances but needs guidance to retrieve relevant episodes. Episodic memory requires the hippocampus, the prefrontal cortex (PFC) guides memory retrieval, but how their representations interact is unclear. Using state-space analysis of neuronal spiking, we found CA1 and PFC activity within and between rats formed similar, low-dimensional, region-specific “shapes” representing different tasks tested in the same maze. Task shapes were organized by behaviorally salient variables including time and maze start and goal locations. PFC predicted CA1 representations when both regions were needed to solve a spatial memory task, but not in a cue approach task that required neither region. Task demands imposed common dimensions on CA1 and PFC maps whose topologies distinguished episodic and rule-related computations.
Osteocytes regulate organismal senescence of bone and bone marrow
Authors: Ding Peng , Gao Chuan , Gao Youshui , Liu Delin , Li Hao , Xu Jun , Chen Xiaoyi , Huang Yigang , Zhang Changqing , Zheng Minghao , Gao Junjie
Published: July 2022

The skeletal system contains a series of sophisticated cellular lineages arisen from the mesenchymal stem cells (MSC) and hematopoietic stem cells (HSC), that determine the homeostasis of bone and bone marrow. Here we reasoned that osteocyte may exert a function in regulation of these lineage cell specifications and tissue homeostasis. Using a mouse model of conditional deletion of osteocytes by the expression of diphtheria toxin subunitα(DTA) in dentin matrix protein 1 (DMP-1) positive osteocytes, we demonstrated that partial ablation of DMP-1positive osteocytes caused severe sarcopenia, osteoporosis and degenerative kyphosis, leading to shorter lifespan in these animals. Osteocyte reduction altered mesenchymal lineage commitment resulting in impairment of osteogenesis and induction of osteoclastogensis. Single cell RNA sequencing further revealed that hematopoietic lineage was mobilized towards myeloid lineage differentiation with expanded myeloid progenitors, neutrophils and monocytes, while the lymphopoiesis was impaired with reduced B cells in the osteocyte ablation mice. The acquisition of a senescence-associated secretory phenotype (SASP) in both osteoprogenic and myeloid lineage cells was the underlying cause. Together, we showed that osteocytes play critical roles in regulating of lineage cell specifications in bone and bone marrow through mediation of organismal senescence.
Scaling up submerged fermentation process of Aspergillus fumigatus mga for an efficient metabolite production (xylanase)
Authors: Gares Maroua , Hiligsmann Serge , Kacem Chaouche Noreddine
Published: July 2022

Fungal metabolites production at an industrial scale requires a sufficient yield at relatively low cost. Indeed, the scaling-up process is one of the main bottlenecks in the fermentation procedure; the reproduction of the best conditions achieved in small bio-reactors when transferring them to a much larger fermentation scale is near impossible.

The present study seeks to study the fermentation profile of Aspergillus fumigatus fungi, in order to spot it logarithmic phase using xylose as substrate in different volumes; 250 mL flasks, 2 L and 20 L bioreactors, before conducting further experiments for an efficient secondary metabolite production (xylanase). The agitation speed impact on the morphological changing of this fungi was also studied.
Network analysis reveals the molecular bases of statin pleiotropy that vary with genetic background
Authors: del Rio Hernandez Cintya E. , Campbell Lani J. , Atkinson Paul H. , Munkacsi Andrew B.
Published: July 2022

Many approved drugs are pleiotropic, for example statins, whose main cholesterol lowering activity is complemented by anticancer and pro-diabetogenic mechanisms involving poorly characterized genetic interaction networks. We investigated these using theSaccharomyces cerevisiaegenetic model where most genetic interactions known are limited to the statin-sensitive S288C genetic background. We therefore broadened our approach by investigating gene interactions to include two statin-resistant UWOPS87-2421 and Y55 genetic backgrounds. Networks were functionally focused by selection ofHMG1andBTS1mevalonate pathway genes for detecting genetic interactions. Networks, multi-layered by genetic background, were analysed for modifying key genes using network centrality (degree, betweenness, closeness), pathway enrichment, functional community modules and gene ontology. Statin treatment induces the unfolded protein response and we found modifying genes related to dysregulated endocytosis and autophagic cell death. To translate results to human cells, human orthologues were searched for other drugs targets, thus identifying candidates for synergistic anticancer bioactivity.
SOCS2 regulation of growth hormone signaling requires a canonical interaction with phosphotyrosine
Authors: Li Kunlun , Meza-Guzman Lizeth , Whitehead Lachlan , Leong Evelyn , Kueh Andrew , Alexander Warren S. , Kershaw Nadia J. , Babon Jeffrey J. , Doggett Karen , Nicholson Sandra E.
Published: July 2022

Suppressor Of Cytokine Signaling (SOCS) 2 is the critical negative regulator of growth hormone (GH) and prolactin signaling. Mice lacking SOCS2 display gigantism with increased body weight and length, and an enhanced response to GH treatment. Here we characterized mice carrying a germ-line R96C mutation within the SOCS2-SH2 domain, which disrupts the ability of SOCS2 to interact with tyrosine phosphorylated targets.Socs2R96C/R96Cmice displayed a similar increase in growth as previously observed in SOCS2 null (Socs2-/-) mice, with a proportional increase in body and organ weight, and bone length. Embryonic fibroblasts isolated fromSocs2R96C/R96CandSocs2-/-mice also showed a comparable increase in phosphorylation of STAT5 following GH stimulation, indicating the critical role of phosphotyrosine binding in SOCS2 function.
The evolution of cooperation in the unidirectional linear division of labour of finite roles
Authors: Afif Nirjhor Md Sams , Nakamaru Mayuko
Published: July 2022

Evolution of cooperation is a puzzle in evolutionary biology and social sciences. Previous studies assumed that players are equal and have symmetric relationships. In our society, players are in different roles, have an asymmetric relationship, and cooperate together. We focused on the linear division of labour in a unidirectional chain that has finite roles, each of which is assigned to one group with cooperators and defectors. A cooperator in an upstream group produces and modifies a product, paying a cost of cooperation, and hands it to a player in a downstream group who obtains the benefit from the product. If players in all roles cooperate, a final product can be completed. However, if a player in a group chooses defection, the division of labour stops, the final product cannot be completed, and all players in all roles suffer damage. By using the replicator equations of the asymmetric game, we investigate which sanction system promotes the evolution of cooperation in the division of labour. We find that not the benefit of the product but the cost of cooperation matters to the evolutionary dynamics and that the probability of finding a defector determines which sanction system promotes the evolution of cooperation.
Drivers and prevalence of COVID-19 vaccine uptake among homeless and precariously housed people in France: a cross-sectional population-based study
Authors: Roederer Thomas , Mollo Bastien , Vincent Charline , Leduc Ghislain , Sayyad Jessica , Mosnier Marine , Vandentorren Stéphanie
Published: July 2022

Background

Few global data exist regarding COVID-19 vaccine coverage in people experiencing homelessness (PEH) or precariously housed (PH) who are at high risk for COVID-19 infection, hospitalization, and death. Given the absence of documented French data, we aimed to determine COVID-19 vaccine coverage in PEH/PH in France, and its drivers.

Methods

We carried out a cross-sectional study following a two-stage cluster-sampling design in Ile-de-France and Marseille, France, in late 2021. Participants aged over 18 years were recruited where they slept the previous night, and then stratified for analysis into three housing groups (“Streets”, “Accommodated”, and “Housed”). Interviews were conducted face-to-face in the participant’s preferred language. Multilevel univariate and multivariable logistic regression models were built.

Findings

3,690 individuals were surveyed: 855 in the “Housed” stratum, 2,321 in the “Accommodated” stratum and 514 in the “Streets” stratum. 76·2% (95%CI 74·3-78·1) reported receiving at least one COVID-19 vaccine dose. Vaccine uptake varied by stratum, with uptake highest (85.6%; reference) in “Housed”, followed by “Accommodated” (75·4%; AOR=0·79 ; 95%CI 0·51-1·09 vs Housed) and lowest in “Streets” (42·0%; AOR=0·38 ; 95%CI 0·25-0·57 vs Housed). Use for vaccine certificate, socioeconomic drivers and vaccine hesitancy explained vaccine coverage.

Interpretation

In France, PEH/PH are less likely than the general population likely to receive COVID-19 vaccines; with the most excluded being the least likely. The influence of both structural drivers and vaccine beliefs in PEH/PH reinforces the importance of targeted outreach, on-site vaccination and sensitisation activities to further vaccine uptake.

Funding

Santé Publique France, Agence Nationale de Recherches sur le Sida/Capnet, Agence Régionale de Santé – Ile de France, Médecins Sans Frontières, and Société de Pathologie Infectieuse de Langue Française.
A pilot surveillance report of SARS-CoV-2 rapid antigen test results among volunteers in Germany, 1st week of July 2022
Authors: Stemler Jannik , Salmanton-García Jon , Weise Ben , Többen Christina , Joisten Carolin , Fleig Julian , Cornely Oliver A.
Published: July 2022

We hypothesized that reported SARS-CoV-2 infection numbers are underestimated and piloted a point prevalence by rapid antigen testing in the VACCELERATE volunteer registry.

Between July-1 and July-7, 2022, 7/419 (1.67%) tests were positive. Compared to reports of the German Federal Government, our results suggest a 2.39-fold higher prevalence.

Our findings imply that the actual prevalence of SARS-CoV-2 may be higher than detected by current surveillance systems, so that current pandemic surveillance and testing strategies need to be adapted.
COVID-19 Vaccine Booster Dose Willingness Among Patients with Inflammatory Bowel Disease on Infliximab and Vedolizumab: A Cross-Sectional Study
Authors: Shehab Mohammad , Alrashed Fatema , Alfadhli Ahmad
Published: July 2022

Background

Vaccination has been effective in preventing COVID-19 infections and related mortality. However, waning immunity after the two-dose vaccination prompted health authorities to recommend a third dose of COVID-19 vaccine to boost immunity. The aim of our study was to assess willingness to receive a third (booster) dose among patients with IBD.

Methods

A cross-sectional study was performed at a tertiary care inflammatory bowel disease center. Patients were recruited at the infusion room from January 1st, 2022, until March 31st, 2022. The primary outcome was the prevalence of BNT162b2 third (booster) dose in infliximab- or vedolizumab-treated patients with IBD. The secondary outcome evaluated whether the prevalence of BNT162b2 third (booster) dose differed based on type of COVID-19 vaccine, gender, age, type of biologic therapy and citizenship.

Results

In total, 499 patients with IBD were included in this study. The median age was 34.5 years, and 60% had ulcerative colitis (UC). Among the study participants, 302 (60.5%) patients were vaccinated with BNT162b2, and 197 (39.5%) were vaccinated with ChAdOx1 nCoV-19. Of the total number of participants, 400 (80.2%) were receiving infliximab, and 99 (19.8%) were receiving vedolizumab. Overall, 290 (58.1%) of the included patients were willing to receive the third (booster) dose. Patients vaccinated with BNT162b2 were more likely to receive booster dose compared to patients vaccinated with ChAdOx1 nCoV-19 [201 (66.5%) vs 101 (33.5%), p = 0.014]. Infliximab-treated patients were more likely to receive booster dose compared to patients receiving vedolizumab [310 (77.5%) vs 62 (62.6%), p = 0.002]. There was no statistical difference in willingness to receive booster dose in terms of age, nationality, or gender.

Conclusion

The percentage of patients with IBD willing or have received a third (booster) dose of BNT162b2 vaccine was lower compared to general population. In addition, patients who received two doses of BNT162b2 vaccines were more likely to receive a third (booster) dose compared to patients who received ChAdOx1 nCoV-19. Patients treated with infliximab were more likely to receive a third (booster) dose of COVID-19 vaccine.
Phenome-wide association network demonstrates close connection with individual disease trajectories from the HUNT study
Authors: Hall Martina , Skinderhaug Marit K. , Almaas Eivind
Published: July 2022

Background

Disease networks offer a potential road map of connections between diseases. Several studies have created disease networks where diseases are connected either based on shared genes or Single Nucleotide Polymorphisms (SNP) associations. However, it is still unclear to which degree SNP-based networks map to empirical co-observed diseases within a different, general, adult study population spanning over a long time period.

Methods

We create a SNP-based disease network (PheNet) from a large population using the UK biobank phenome-wide association studies. Importantly, the SNP-associations are adjusted for linkage disequilibrium, case/control imbalances, as well as relatedness. We map the PheNet on to significantly co-occurring diseases in the Norwegian HUNT study population, and further, identify consecutively occurring diseases with significant occurrence in the PheNet.

Results

We find that the overlap between the networks are far larger than expected, where most diseases tend to link to diseases of the same category and some categories are more linked to each other than expected by chance. Considering the ordering of consecutively occurring diseases in the HUNT data, we find that many diabetic disorders and cardiovascular disorders are subsequent the diagnostication of obesity and overweight, and cardiovascular disorders that often tend to be observed subsequent to other diseases are associated with higher mortality rates.

Conclusions

The HUNT sub-PheNet showing both genetically and co-observed diseases offers an interesting framework to study groups of diseases and examine if they, in fact, are comorbidities and pinpoint exactly which mutation(s) that constitute shared cause of the diseases. This could be of great benefit to both researchers and clinicians studying relationships between diseases.
Spatially resolved host-bacteria-fungi interactomes via spatial metatranscriptomics
Authors: Saarenpää Sami , Shalev Or , Ashkenazy Haim , de Oliveira-Carlos Vanessa , Lundberg Derek Severi , Weigel Detlef , Giacomello Stefania
Published: July 2022

All multicellular organisms are closely associated with microbes, which have a major impact on the health of their host. The interactions of microbes among themselves and with the host take place at the microscale, forming complex networks and spatial patterns that are rarely well understood due to the lack of suitable analytical methods. The importance of high-resolution spatial molecular information has become widely appreciated with the recent advent of spatially resolved transcriptomics. Here, we present Spatial metaTranscriptomics (SmT), a sequencing-based approach that leverages 16S/18S/ITS/poly-d(T) multimodal arrays for simultaneous host transcriptome- and microbiome-wide characterization of tissues at 55-µm resolution. We showcase SmT in outdoor-grown Arabidopsis thaliana leaves as a model system, and found tissue-scale bacterial and fungal hotspots. By network analysis, we study inter- and intra-kingdom spatial interactions among microbes, as well as the host response to microbial hotspots. SmT is a powerful new strategy that will be pivotal to answering fundamental questions on host-microbiome interplay.
Sex-biased proteomic response to tomato spotted wilt virus infection of the salivary glands of Frankliniella occidentalis, the western flower thrips
Authors: Rajarapu Swapna Priya , Ben-Mahmoud Sulley , Benoit Joshua B. , Ullman Diane E. , Whitfield Anna E. , Rotenberg Dorith
Published: July 2022

Successful transmission of tomato spotted wilt virus (TSWV) by Frankliniella occidentalis requires robust infection of the salivary glands (SGs) and virus delivery to plants during salivation. Feeding behavior and transmission efficiency are sexually-dimorphic traits of this thrips vector species. Proteins secreted from male and female SG tissues, and the effect of TSWV infection on the thrips SG proteome are unknown. To begin to discern thrips factors that facilitate virus infection of SGs and transmission by F. occidentalis, we used gel- and label-free quantitative and qualitative proteomics to address two hypotheses: (i) TSWV infection modifies the composition and/or abundance of SG-expressed proteins in adults; and (ii) TSWV has a differential effect on the male and female SG proteome and secreted saliva. Our study revealed a sex-biased SG proteome for F. occidentalis, and TSWV infection modulated the SG proteome in a sex-dependent manner as evident by the number, differential abundance, identities and generalized roles of the proteins. Male SGs exhibited a larger proteomic response to the virus than female SGs. Intracellular processes modulated by TSWV in males indicated perturbation of SG cytoskeletal networks and cell-cell interactions (basement membrane, BM and extracellular matrix proteins, ECM), and subcellular processes consistent with a metabolic slow-down under infection. Several differentially-abundant proteins in infected male SGs play critical roles in viral life cycles of other host-virus pathosystems. In females, TSWV modulated processes consistent with tissue integrity and active translational and transcriptional regulation. A core set of proteins known for their roles in plant cell-wall degradation and protein metabolism were identified in saliva of both sexes, regardless of virus infection status. Saliva proteins secreted by TSWV- infected adults indicated energy generation, consumption and protein turnover, with an enrichment of cytoskeletal/BM/ECM proteins and tricarboxylic acid cycle proteins in male and female saliva, respectively. The nonstructural TSWV protein NSs - a multifunctional viral effector protein reported to target plant defenses against TSWV and thrips - was identified in female saliva. This study represents the first description of the SG proteome and secretome of a thysanopteran and provides many candidate proteins to further unravel the complex interplay between the virus, insect vector, and plant host.
TWISTED DWARF1 mediates myosin XI-associated vesicle trafficking required for auxin transport
Authors: Liu Jie , Zhu Jinsheng , Di Donato Martin , Hao Pengchao , Ren Haiyun , Geisler Markus
Published: July 2022

Defects in plant development caused by loss-of the FKBP42, TWISTED DWARF1 (TWD1), have so far been accounted to a dual function of TWD1 acting as an ABCB chaperone that positively regulates ABCB biogenesis and transport activity. On the other hand, TWD1 was characterized as a modulator of actin cytoskeleton bundling and dynamics by interaction with ACTIN7, however, currently it is unclear if both events are connected.

Here, we show that TWD1 positively regulates pollen tube germination and growth by controlling actin organization. We identify and verify myosin XI-K as TWD1 interacting protein, which is most likely linking the action of TWD1 on the actin cytoskeleton. We provide evidence that myosin XI-K is required for proper auxin exporter trafficking and auxin export. Further, we show that ER-localized TWD1 reshapes the ER network to overlay actin cables similar to mutations of myosin-XI and thus controls cytoplasmic streaming.

In summary, our data support a model in that TWD1 functions as an ER–actin adapter proteins involved in myosin-dependent ER motility and cargo trafficking. Our findings provide a molecular explanation for the defects in early ABCB biogenesis in twd1 that are caused by defects in the three-way interaction between the ER, cytosolic myosin-XI and F-actin.
Do socially responsible higher education institutions contribute to sustainable regional growth and innovation?
Authors: Pedro Eugénia de Matos , Leitão João , Alves Helena
Published: July 2022

Purpose

This study aims to analyse the efficiency of public higher education institutions (HEIs) through teaching and learning (T&L), research and technology (R&T) and social responsibility (SR) activities. It also aims to assess the external factors influencing the efficiency of T&L, R&T and SR, and influence of this efficiency on sustainable regional economic growth and innovation intensity.

Design/methodology/approach

The empirical approach is based on a two-step data envelopment analysis to compare the efficiency of 23 Portuguese public HEIs, using a Tobit regression, to assess the influence of the factors affecting HEI efficiency which in turn affects regional sustainability and innovation.

Findings

The results lead to the following conclusions: HEIs with better SR efficiency are situated in large urban centres; an insular location is positively associated with HEIs’ T&L and SR efficiency; HEIs’ T&L and SR efficiency positively influence regional gross domestic product (GDP); and HEIs’ R&T efficiency positively influences R&D in regional GDP.

Practical implications

This study offers implications in the domain of sustainable regional growth. The study recommends that the policies of HEIs should concentrate on developing activities that meet the needs of the region. It also emphasizes the need to invest in recruitment of qualified lecturers and researchers, and creation of relevant PhD positions. The study also emphasizes the need for government actions to consider the most disadvantaged regions and create infrastructure to attract new companies and people.

Originality/value

This study contributes to the existing literature on the efficiency of HEIs by considering the efficiency of not only T&L and R&T but also SR. It also analyses the influencers of both HEIs’ efficiency and regional development.
Design and locomotion analysis of a close-chain leg-wheel mobile platform
Authors: Fan Xiang-Ming , Ruan Qiang
Published: July 2022

Purpose

To take the advantages of terrain-adaptive capability of legged platform and fast-moving ability of wheeled platform, this paper aims to design a leg-wheel mobile platform for obstacle surmounting and analyze the feasibility and locomotivity of different moving modes.

Design/methodology/approach

The platform consists of six leg-wheel units. Each of the units has a close-chain mechanical leg and an actuated wheel at the end of the leg. The platform moves with two modes: legged mode and leg-wheel composite mode. The legged mode achieves high mobility driven by crank motors, while the leg-wheel composite mode achieves obstacle-surmounting ability actuated by crank motors and pitch link motors and obtains high efficiency with the hub motors. The gait planning in different modes has been carried out and the obstacle-surmounting capacity has been analyzed.

Findings

Based on the results of kinematic analysis and gait planning of the close-chain leg-wheel platform, the high mobility and efficiency obstacle-surmounting ability are demonstrated with the two movement modes. The feasibility of the design and the performance of the mobile platform is verified with the prototype experiment. The results of this paper show that the platform possesses good obstacle-surmounting capability.

Originality/value

The work presented in this paper is a novel exploration to design a close-chain leg mechanism and with an actuated wheel in series. The close-chain leg mechanism has the advantages of high leg lift and single degree of freedom characteristics, which makes the platform obtain the ability of obstacle-surmounting.
Examining firm self-regulation in the automobile industry: the role of situational factors, firm characteristics and association influence
Authors: Cavazos David E. , Heller Nathan
Published: July 2022

Purpose

The current study seeks to contribute to current self-regulation research by first exploring the association between the cost of self-regulation and firm self-regulation. The mediating role of association membership and firm slack is additionally explored.

Design/methodology/approach

Longitudinal analysis of firm-initiated product recalls for 15 manufacturers in the USA automobile industry from 1966 to 2012 has several important findings regarding the motivations for firm self-regulation.

Findings

The influence of industry associations and firm absorbed slack both contribute to firm self-regulation.

Originality/value

The current study begins to address the importance of firm characteristics in predicting self-regulation activities. The bulk of existing research has examined self-regulation at the industry level as an activity performed as a result of the adoption of formalized industry sanctioned standards of practice. This research contributes to such work by examining firm proactivity in the absence of such formal standards.
The role of trade unions in promoting CSR in Bangladesh’s ready-made garments sector: the post-pandemic scenario
Authors: Khan Md. Rahat , Rammal Hussain Gulzar
Published: July 2022

Purpose

This study investigates the effectiveness of trade unions in preserving and promoting the rights of the worker, and being their voice in ensuring safe working conditions as part of the firms’ CSR activities.

Design/methodology/approach

Data were collected from employees, managers, and owners of ready-made garments firms in Bangladesh. An open-ended survey instrument was used and distributed widely. Analysis of the 200 responses was undertaken using the qualitative narrative technique.

Findings

The findings show that, unlike traditional labor-management relations, in Bangladesh managers tend to have a more favorable attitude towards unions than employees do. The strong political links between the factory owners and the unions’ leadership raise questions about whose interest the unions represent.

Practical implications

The authors highlight how adopting a CSR agenda can help unions make better representations on behalf of their members. This, in turn, can enhance the workforce’s efficiency and help strengthen the sector to develop processes to help face disruptions like those experienced during the COVID-19 pandemic.

Originality/value

The study is unique in addressing the role of unions in promoting CSR activities in emerging economies, where the formal institutional application remains limited. The study’s findings can help explain some of the sector’s challenges.
Architectural design research through reflection: a sub-approach under “research by design”
Authors: Uzunkaya Aslı , Paker Kahvecioğlu Nurbin
Published: July 2022

Purpose

This study is based on a research approach proposal aiming to reveal tacit knowledge that shapes architectural design processes through subjective accumulations and tools. With the premise that design embodies tacit and personal knowledge, it proposes an alternative way to decipher this subjective medium.

Design/methodology/approach

The proposed research approach, “(architectural) design research through reflection”, basically belongs to “research by design” method and narrowed in the focus of reflection. It enables to study how tacit knowledge functions within processes of architectural design without being its very subject. The proposal and the product of the approach, revealing diagram, are developed through the “architect's” tools and the involvement of the “researchers” in the process. It is also supported by a conceptual basis created from literature on reflection.

Findings

By means of the proposal, the reflective accumulation of the subjects, that is, the tacit knowledge, is investigated in relation to practice. The revealing diagram is presented as a tool through which relations can be interpreted within the framework of subjects. It is a tool by which the subjects, tools and processes of the architectural design product can be analysed.

Originality/value

The study contributes to architectural research by shifting the perspective on reflective knowledge that shapes design processes.
Antibacterial activity and cytotoxicity of a novel bacteriocin isolated from Pseudomonas sp. strain 166
Authors: Wang Yu , Haqmal M. Aman , Liang Yue‐dong , Muhammad Inam , Zhao Xiao‐Ou , Elken Emad Mohammed , Gao Yun‐Hang , Jia Yu , He Cheng‐guang , Wang Yi‐Ming , Kong Ling‐Cong , Ma Hong‐Xia
Published: July 2022

Pseudomonas sp. strain 166 was isolated from soil samples from Changbai Mountains. A novel bacteriocin PA166 from Pseudomonas sp. 166 was purified using ammonium sulfate, dextran gel chromatography column and Q‐Sepharose column chromatography successively. The molecular mass of bacteriocin PA166 was found to be 49.38 kDa by SDS‐PAGE and liquid chromatography–mass spectrometry (MS)/MS. Bacteriocin PA166 showed stability at a wide range of pH (2–10), and thermal stability (40, 60, 80 and 100°C). The bacteriocin PA166 antimicrobial activity was slightly inhibited by Ca2+, K+ and Mg2+. The minimum bactericidal concentrations of bacteriocin PA166 against five Pasteurella multocida strains ranged from 2 to 8 μg ml−1. Bacteriocin PA166 showed low cytotoxicity and a higher treatment index (TI = 82.51). Fluorescence spectroscopy indicated that bacteriocin PA166 destroyed the cell membrane to exert antimicrobial activity. In summary, bacteriocin PA166 had strong antibacterial activity, high TI and low toxicity, and hence could serve as a potential clinical therapeutic drug.
Emotion regulation in substance use disorders: a systematic review and meta‐analysis
Authors: Stellern Jordan , Xiao Ke Bin , Grennell Erin , Sanches Marcos , Gowin Joshua L. , Sloan Matthew E.
Published: July 2022

Background and aims

The ability to regulate emotions effectively has been associated with resilience to psychopathology. Individuals with substance use disorders (SUDs) have been shown to have higher levels of negative emotionality, with some evidence suggesting impairment in emotion regulation compared with individuals without SUDs. However, no previous attempt has been made to systematically review the literature to assess the magnitude of this difference. We aimed to assess the association between SUD diagnosis and emotion regulation as measured by the Difficulties in Emotion Regulation Scale (DERS) and Emotion Regulation Questionnaire (ERQ) through a systematic review and meta‐analysis of existing findings.

Methods

The systematic review was conducted using PubMed, PsycINFO and Embase. We examined cross‐sectional studies that compared a SUD group with a control group and measured emotion regulation using the DERS or the ERQ. The primary analysis focused on papers using the DERS, as this was the predominant instrument in the literature.

Results

Twenty‐two studies met our primary analysis criteria, representing 1936 individuals with a SUD and 1567 controls. Individuals with SUDs relative to controls had significantly greater DERS scores, with a mean difference of 21.44 [95% confidence interval (CI) = 16.49–26.40, P < 0.001] and Hedges’ g = 1.05 (95% CI = 0.86–1.24, P < 0.001). The difference was robust, remaining significant after removing outliers and studies with high risk of bias. Individuals with SUDs demonstrated poorer emotion regulation on each subscale of the DERS, with the largest deficits in the Strategies and Impulse subscales. The ERQ analysis revealed greater use of expressive suppression in those with SUDs relative to controls (Hedges’ g = 0.76, 95% CI = 0.25–1.28, P = 0.004).

Conclusions

People with substance use disorders appear to have greater difficulties in emotion regulation than people without substance use disorders.
An optimized workflow for microCT imaging of formalin‐fixed and paraffin‐embedded (FFPE) early equine embryos
Authors: Handschuh Stephan , Okada Carolina T. C. , Walter Ingrid , Aurich Christine , Glösmann Martin
Published: July 2022

Here, we describe a workflow for high‐detail microCT imaging of formalin‐fixed and paraffin‐embedded (FFPE) equine embryos recovered on Day 34 of pregnancy (E34), a period just before placenta formation. The presented imaging methods are suitable for large animals' embryos with intention to study morphological and developmental aspects, but more generally can be adopted for all kinds of FFPE tissue specimens. Microscopic 3D imaging techniques such as microCT are important tools for detecting and studying normal embryogenesis and developmental disorders. To date, microCT imaging of vertebrate embryos was mostly done on embryos that have been stained with an X‐ray dense contrast agent. Here, we describe an alternative imaging procedure that allows to visualize embryo morphology and organ development in unstained FFPE embryos. Two aspects are critical for high‐quality data acquisition: (i) a proper sample mounting leaving as little as possible paraffin around the sample and (ii) an image filtering pipeline that improves signal‐to‐noise ratio in these inherently low‐contrast data sets. The presented workflow allows overview imaging of the whole embryo proper and can be used for determination of organ volumes and development. Furthermore, we show that high‐resolution interior tomographies can provide virtual histology information from selected regions of interest. In addition, we demonstrate that microCT scanned embryos remain intact during the scanning procedure allowing for a subsequent investigation by routine histology and/or immunohistochemistry. This makes the presented workflow applicable also to archival paraffin‐embedded material.
Patterns of curative treatment for non‐small cell lung cancer in New South Wales, Australia
Authors: Batumalai Vikneswary , Descallar Joseph , Gabriel Gabriel , Delaney Geoff P. , Oar Andrew , Barton Michael B. , Vinod Shalini K.
Published: July 2022

Introduction

There is a lack of large population‐based studies examining patterns of curative treatment for non‐small cell lung cancer (NSCLC) in Australia. This study aimed to evaluate the utilization of curative treatment for NCSLC at a population level and identify factors associated with its use in New South Wales (NSW), Australia.

Methods

Patients diagnosed with localized or locoregional NSCLC between 2009 and 2014 were identified from the NSW Central Cancer Registry. Curative treatment was defined as surgery or radiotherapy with a 45 Gy minimum dose. Univariate and multivariable analyses were performed to investigate factors associated with the receipt of curative treatment. A Cox proportional‐hazards regression model was used to analyze the factors associated with 2‐year overall survival (OS).

Results

Of the 5722 patients diagnosed with NSCLC in the study period, 3355 (59%) patients received curative treatment and 2367 (41%) patients did not receive curative treatment. The receipt of curative treatment was significantly associated with younger patients, female gender, localized disease, and Charlson Comorbidity Index (CCI) = 0. The use of curative treatment increased significantly over time from 2009 (55%) to 2014 (63%) and varied significantly from 24% to 70% between local health districts (LHDs) of residence. Younger age, female gender, localized disease, CCI = 0, and overseas country of birth were significantly associated with 2‐year OS. The 2‐year OS significantly improved from 70% in 2009 to 77% in 2014 for patients who received curative treatment.

Conclusion

The use of curative treatment for patients with potentially curable NSCLC was low at 59%. However, the use of curative treatment and survival have increased over time. Significant variation was noted in the use of curative treatment between LHDs.
Infection after ureteroscopy for ureteric stones: analysis of 71 305 cases in the Hospital Episode Statistics database
Authors: Veeratterapillay Rajan , Gravestock Paul , Harding Chris , Shaw Matthew , Fitzpatrick John , Keltie Kim , Cognigni Paola , Sims Andrew , Rogers Alistair
Published: July 2022

Objectives

To investigate the burden of infectious complications following ureteroscopy (URS) for ureteric stones on a national level in England using data from the Hospital Episodes Statistics (HES) data warehouse.

Materials and Methods

A retrospective cohort was identified and followed up in HES during the period April 2013 to March 2020 for all procedure codes relating to ureteroscopic stone treatment (M27.1, M27.2, M27.3). Treatment episodes relating to the first URS (‘index ureteroscopy’) for each patient were further analysed. All subsequent admissions within 30 days were also captured. The primary outcome was diagnosis of urinary tract infection (UTI; including all codes relating to a UTI/sepsis within the first 30 days of index URS). Secondary outcomes were critical care attendance, attendance at the accident and emergency department (A&E) within 30 days, and mortality.

Results

A total of 71 305 index ureteroscopies were eligible for analysis. The median age was 55 years, and 81% of procedures were elective and 45% were undertaken as day‐cases. At the time of index URS, 16% of patients had diabetes, 0.5% had coexisting neurological disease and 40% had an existing stent/nephrostomy. Overall, 6.8% of the cohort (n = 4822) had a diagnosis of UTI within 30 days of index URS (3.9% immediately after surgery). A total of 339 patients (0.5%) required an unplanned stay in critical care during their index URS admission; 8833 patients (12%) attended A&E within 30 days. Overall mortality was 0.18% (60 in‐hospital, 65 within 30 days); 40 deaths (0.056%) included infection as a contributing cause of death.

Conclusion

We present the largest series evaluating infectious complications after ureteroscopic stone treatment. The procedure is safe, with low inpatient infective complication and critical care admission rates.