bluuebunny/crossref_metadata_2025 huggingface dataset:
PM2.5 induces inflammatory responses via oxidative stress-mediated mitophagy in human bronchial epithelial cells
Authors: Zhai Xuedi , Wang Jianshu , Sun Jiaojiao , Xin Lili
Published: January 2022

Background

Fine particulate matter (PM2.5) is a ubiquitous air pollutant, and it has been reported to be closely associated with lung inflammatory injury. In this study, the potential molecular mechanisms underlying PM2.5-induced cellular inflammation in human bronchial epithelial (BEAS-2B) cells were investigated.

Materials and methods

Ambient PM2.5 particulates from Suzhou, China, were collected and re-suspended in ultrapure water. Cellular damages, characterized by oxidative stress, mitochondrial injury, and inflammatory cytokine production, were determined in 24 h PM2.5-treated BEAS-2B cells with or without 3-methyladenine (3-MA; autophagy inhibitor) pretreatment. Biomarkers related to oxidative damage, inflammatory injury and autophagy signaling pathways were also measured.

Results

Uptake of PM2.5 in BEAS-2B cells induced cellular oxidative damage, mitochondrial injury, and inflammatory responses as indicated by a significant decrease in GSH/GSSG ratio, increased MDA content, dilated mitochondria with loss and rupture of crista, and production of inflammatory cytokines. Activation of Nrf-2/TXNIP-mediated NF-κB and Bnip3L/NIX-dependent mitophagy signaling pathways, as well as accumulation of autophagosomes and autolysosomes, were also observed. A 6 h pretreatment of 3-MA increased PM2.5-induced oxidative damage and cellular inflammation as indicated by increasing protein levels of HO-1, TXNIP, Bnip3L/NIX and IL-8 gene expression.

Conclusions

PM2.5 induced cellular inflammatory injury by oxidative stress, mitochondrial dysfunction, and mitophagy initiation. Although induction of Bnip3L/NIX-mediated mitophagy in BEAS-2B cells appeared to confer protection in response to PM2.5, dysfunction of autophagic flux may be a critical contributor to defective mitophagy and cellular inflammatory response.
Genome-wide DNA N6-adenine methylation in sea buckthorn (Hippophae rhamnoides L.) fruit development
Authors: Zhang Guoyun , Diao Songfeng , Song Yating , He Caiyun , Zhang Jianguo
Published: January 2022

As a new epigenetic mark, DNA N6-adenine (6mA) methylation plays an important role in various biological processes and has been reported in many prokaryotic organisms in recent years. However, the distribution patterns and functions of DNA 6mA modification have been poorly studied in non-model crops. In this study, we observed that the methylation ratio of 6mA was about 0.016% in the sea buckthorn (Hippophae rhamnoides L.) genome using mass spectrometry. We first constructed a comprehensive 6mA landscape in sea buckthorn genome using nanopore sequencing at single-base resolution. Distribution analysis suggested that 6mA methylated sites were widely distributed in the sea buckthorn chromosomes, which were similar to those in Arabidopsis and rice. Furthermore, reduced 6mA DNA methylation is associated with different expression of genes related to the fruit-ripening process in sea buckthorn. Our results revealed that 6mA DNA modification could be considered an important epigenomic mark and contributes to the fruit ripening process in plants.
Oncology Residency and the Evolution of Specialty Practice
Authors: Wilson Christopher M. , Tran Rachel Tabak , Tally Zachary S.
Published: January 2022

Over the past few decades, oncology rehabilitation has transformed from a niche clinical area to an established specialty practice with a defined scope of knowledge and skills. Since the passage of board certification in the APTA House of Delegates in 2016, the Description of Specialty Practice has defined the scope and parameters of this specialization and has set benchmarks for practitioner knowledge, skills, and behaviors. Concurrently, several institutions have established oncology residencies for physical therapists, with many others in the developing stages. Residencies are extensive postgraduate, on-the-job training opportunities whereby a resident is closely mentored by a team of clinical experts. Accreditation standards for oncology residencies are established by the American Board of Physical Therapy Residency and Fellowship Education. This article provides perspectives on the current role of and future opportunities for oncology physical therapy residency programs. The infrastructure, institutional support, and development of residents and faculty mentors show great potential to further the specialty area, enhance patient access, and elevate the quality of services available to persons living with and beyond cancer.
Residency Education as a Catalyst for Quality Amidst the Shifting Climate of Health Care
Authors: Bertram Jessica , Manvi Sruti
Published: January 2022

Physical therapists continue to take on increased levels of autonomy within the medical field, often serving as points of entry into the health care system. The increased responsibility for diagnosis, referral, and supervision of patients requires that clinicians possess a depth of knowledge to effectively manage the patient. The expansion of specialty practice is necessary to meet the needs of a health care system that is increasingly focused on the value of delivered services. Residency programs are uniquely positioned to meet the demands of quality by providing intensive training for clinicians in a specialty area. The structure and learning environment of a residency program is conducive to the development and practice of advanced clinical reasoning skills and the organization of knowledge across the spectrum of patient complexity. By executing the delivery of care efficiently and effectively, residency graduates bring value not only to the patient but also to their organization, the specialty, and the health care system as whole. The purposes of this perspective article are (1) to examine the role of residency education within the context of the health care system, (2) to explore the relationship between value and residency pedagogy, and (3) to identify key components that drive quality in residency education.
Developmental Care Practice and Documentation Variability in the Cardiac ICU
Authors: Miller Thomas A. , Elhoff Justin J. , Alexander Nneka M. , Butler Samantha C. , Uzark Karen C. , Glotzbach Kristi L. , Mahle William T. , Lisanti Amy J.
Published: January 2022

OBJECTIVES:

Describe variability in developmental care practices, as documented in the electronic health record, for infants undergoing congenital heart surgery.

DESIGN:

Multicenter, retrospective, cohort study.

SETTING:

Six pediatric cardiac centers.

PATIENTS:

One hundred eighty-two infants undergoing one of three index operations: Norwood palliation, aortic arch reconstruction with ventricular septal defect closure, or arterial switch.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Core domains of developmental care encompassing pain assessment, feeding, infant holding, caregiver involvement, therapy, and psychosocial services were reviewed. Practices varied across individuals, institutions, and the hospital stay. At five of six sites, greater than 90% of individuals had physical or occupational therapy services as part of their care, but the day of first evaluation ranged from day of admission to postoperative day 28. Similar patterns were seen in feeding team and social work involvement. Consistent documentation of developmental care was dependent on the domain and site. Of the total days reviewed (n = 1,192), pain scores were documented in 95%. In those same days, documentation of whether or not a patient was out of the crib to be held varied by site from 11% to 93%. Type of oral feeding, breast versus bottle, was documented on the day prior to discharge 48% of the time.

CONCLUSIONS:

There are significant, quantifiable variations in documented developmental care practices at both the individual and site level. More reliable documentation of developmental care practices is required to associate these variables with later outcomes and investigate disparities in individualized developmental care practices.
Sexual History Documentation and Sexually Transmitted Infection Screening for Mental Health Patients in a Pediatric Emergency Department
Authors: Ekstrom Joanna , Alfath Zineb , Schneider Kari
Published: January 2022

Objectives

Adolescents with psychiatric conditions more commonly engage in high-risk sexual behaviors and are at increased risk of sexually transmitted infections (STIs) and when presenting to pediatric emergency departments (PEDs) may be an important population in which to target screening efforts. This study aimed to determine frequency of physician-documented sexual history and STI screening in adolescents presenting to a PED with mental health-related complaints.

Methods

Retrospective study of patients aged 14 to 18 years presenting to a PED February 2015 to September 2016. Electronic records were reviewed for demographics, chief complaint, sexual history documentation, STI screening, resident involvement in patient care, and disposition. Proportions were calculated for frequencies, whereas χ2and Fisher exact tests evaluated factors associated with documentation of sexual history and STI screening.

Results

Two hundred eighty-five patient encounters were identified. Age range was 15 to 18 years with an average of 16 years, and 58% were girls. The most common chief complaint was “intentional ingestion/overdose” (169 encounters, 59%) followed by “suicidal/attempted suicide” (59, 21%). Seventy-seven patients (27%) had sexual history documented. Girls were more likely to have sexual history documented (75% vs 52%,P= 0.0004). Forty-five (59%) patients were noted to be sexually active, and 17 (38%) of these were screened for STI. There was no relationship between screening and race, sex, or involvement of a resident in patient care.

Conclusions

In a high-risk PED population, physicians documented sexual history only 27% of the time. Female patients were more likely to have a sexual history documented. In patients with sexual history indicating risk for STI, less than half were screened.
The Pocket Flap: A Pericranial Galeal-Frontalis Flap for Lining and Graft Coverage in Nasal Reconstruction
Authors: Pfaff Miles J. , Muetterties Corbin , Nahabet Edward , Roostaeian Jason
Published: January 2022

Complex nasal defects can necessitate nasal lining, bone and cartilage, and skin reconstruction. Defects requiring lining and structural support without the need for skin resurfacing are relatively uncommon. The following case report describes in detail a pericranial galeal-frontalis flap that is used to both reconstruct the nasal lining and provide adequate cartilage graft coverage. The pericranial galeal-frontalis flap provides yet another option for the reconstructive surgeon faced with complex defects of the nasal dorsum.
Mediation analysis to inform policy on coronary revascularization by expected time to treatment: Analytical framework
Authors: Sobolev Boris , Kuramoto Lisa
Published: January 2022

Objectives

Clinical guidelines favour coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI) for patients with stable complex coronary disease. Yet the benefit of CABG as established in trials may not be generalizable to populations in which treatment method determines time to treatment, typically being longer for CABG. For cases in which the cardiac anatomy is suitable for either treatment, it is unclear whether it is appropriate to recommend CABG, which is likely to be delayed, if PCI can be performed sooner. This paper outlines an analytical framework for a policy analysis of the timing of coronary revascularization.

Methods

We constructed a thought experiment to examine whether time to treatment will influence the advantage of CABG. We substantiated the use of mediation analysis to estimate the extent to which differences in outcomes between CABG and PCI would change if times to CABG were the same as times to PCI.

Results

We designed a study that uses data from a population-based patient registry to obtain effect measures of mediation analysis: the total effect, the natural indirect effect, and the natural direct effect. The partitioning of the total effect will allow us to estimate the proportional reduction in the risk of an outcome if the time to CABG was similar to that of PCI.

Interpretation

Treatment recommendation, resource allocation and scheduling benchmarks will be guided by understanding the extent to which the time to treatment mediates the relation between revascularization method and outcome.
Statistical Inference Using GLEaM Model with Spatial Heterogeneity and Correlation between Regions
Authors: Tan Yixuan , Zhang Yuan , Cheng Xiuyuan , Zhou Xiao-Hua
Published: January 2022

A better understanding of the various patterns in the coronavirus disease 2019 (COVID-19) spread in different parts of the world is crucial to its prevention and control. Motivated by the celebrated GLEaM model (Balcan et al., 2010[1]), this paper proposes a pioneering stochastic dynamic model to depict the evolution of COVID-19. The model allows spatial and temporal heterogeneity of transmission parameters and involves transportation between regions. Based on the proposed model, this paper also designs a two-step procedure for parameter inference, which utilizes the correlation between regions through a prior distribution that imposes graph Laplacian regularization on transmission parameters. Experiments on simulated data and real-world data in China and Europe indicate that the proposed model achieves higher accuracy in predicting the newly confirmed cases than baseline models.
An in vitro and in vivo approach for the isolation of Omicron variant from human clinical specimens
Authors: Yadav Pragya D. , Gupta Nivedita , Potdar Varsha , Mohandas Sreelekshmy , Sahay Rima R. , Sarkale Prasad , Shete Anita M. , Razdan Alpana , Patil Deepak Y. , Nyayanit Dimpal A. , Joshi Yash , Patil Savita , Majumdar Triparna , Dighe Hitesh , Malhotra Bharti , Shastri Jayanthi , Abraham Priya
Published: January 2022

Due to failure of virus isolation of Omicron variant in Vero CCL-81 from the clinical specimen’s of COVID-19 cases, we infected Syrian hamsters and then passage into Vero CCL-81 cells. The Omicron sequences were studied to assess if hamster could incorporate any mutation to changes its susceptibility. L212C mutation, Tyrosine 69 deletion, and C25000T nucleotide change in spike gene and absence of V17I mutation in E gene was observed in sequences of hamster passage unlike human clinical specimen and Vero CCL-81 passages. No change was observed in the furin cleavage site in any of the specimen sequence which suggests usefulness of these isolates in future studies.
The hyper-transmissible SARS-CoV-2 Omicron variant exhibits significant antigenic change, vaccine escape and a switch in cell entry mechanism
Authors: Willett Brian J. , Grove Joe , MacLean Oscar A. , Wilkie Craig , Logan Nicola , Lorenzo Giuditta De , Furnon Wilhelm , Scott Sam , Manali Maria , Szemiel Agnieszka , Ashraf Shirin , Vink Elen , Harvey William T. , Davis Chris , Orton Richard , Hughes Joseph , Holland Poppy , Silva Vanessa , Pascall David , Puxty Kathryn , da Silva Filipe Ana , Yebra Gonzalo , Shaaban Sharif , Holden Matthew T. G. , Pinto Rute Maria , Gunson Rory , Templeton Kate , Murcia Pablo R. , Patel Arvind H. ,   The COVID-19 Genomics UK (COG-UK) Consortium, Haughney John , Robertson David L. , Palmarini Massimo , Ray Surajit , Thomson Emma C.
Published: January 2022

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron, the fifth VOC to be described, harbours 30 amino acid mutations in spike including 15 in the receptor-binding domain. Here, we demonstrate substantial evasion of neutralisation by Omicronin vitrousing sera from vaccinated individuals. Importantly, these data are mirrored by a substantial reduction in real-world vaccine effectiveness that is partially restored by booster vaccination. We also demonstrate that Omicron does not induce cell syncytia and favours a TMPRSS2-independent endosomal entry pathway. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant.
The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources
Authors: DiStefano Marina T. , Goehringer Scott , Babb Lawrence , Alkuraya Fowzan S. , Amberger Joanna , Amin Mutaz , Austin-Tse Christina , Balzotti Marie , Berg Jonathan S. , Birney Ewan , Bocchini Carol , Bruford Elspeth A. , Coffey Alison J. , Collins Heather , Cunningham Fiona , Daugherty Louise C. , Einhorn Yaron , Firth Helen V. , Fitzpatrick David R. , Foulger Rebecca E. , Goldstein Jennifer , Hamosh Ada , Hurles Matthew R. , Leigh Sarah E. , Leong Ivone US. , Maddirevula Sateesh , Martin Christa L. , McDonagh Ellen M. , Olry Annie , Puzriakova Arina , Radtke Kelly , Ramos Erin M. , Rath Ana , Riggs Erin Rooney , Roberts Angharad M. , Rodwell Charlotte , Snow Catherine , Stark Zornitza , Tahiliani Jackie , Tweedie Susan , Ware James S. , Weller Phillip , Williams Eleanor , Wright Caroline F. , Yates T Michael. , Rehm Heidi L.
Published: January 2022

PURPOSE

Several groups and resources provide information that pertains to the validity of gene-disease relationships used in genomic medicine and research; however, universal standards and terminologies to define the evidence base for the role of a gene in disease, and a single harmonized resource were lacking. To tackle this issue, the Gene Curation Coalition (GenCC) was formed.

METHODS

The GenCC drafted harmonized definitions for differing levels of gene-disease validity based on existing resources, and performed a modified Delphi survey with three rounds to narrow the list of terms. The GenCC also developed a unified database to display curated gene-disease validity assertions from its members.

RESULTS

Based on 241 survey responses from the genetics community, a consensus term set was chosen for grading gene-disease validity and database submissions. As of December 2021, the database contains 15,241 gene-disease assertions on 4,569 unique genes from 12 submitters. When comparing submissions to the database from distinct sources, conflicts in assertions of gene-disease validity ranged from 5.3% to 13.4%.

CONCLUSION

Terminology standardization, sharing of gene-disease validity classifications, and resolution of curation conflicts will facilitate collaborations across international curation efforts and in turn, improve consistency in genetic testing and variant interpretation.
Rare schizophrenia risk variant burden is conserved in diverse human populations
Authors: Liu Dongjing , Meyer Dara , Fennessy Brian , Feng Claudia , Cheng Esther , Johnson Jessica S. , Park You Jeong , Rieder Marysia-Kolbe , Ascolillo Steven , de Pins Agathe , Dobbyn Amanda , Lebovitch Dannielle , Moya Emily , Nguyen Tan-Hoang , Wilkins Lillian , Hassan Arsalan ,   Psychiatric Genomics Consortium Phase 3 Targeted Sequencing of Schizophrenia Study Team,   Schizophrenia Exome Meta-analysis Consortium, Burdick Katherine E. , Buxbaum Joseph D. , Domenici Enrico , Frangou Sophia , Hartmann Annette M. , Malhotra Dheeraj , Pato Carlos N. , Pato Michele T. , Ressler Kerry , Roussos Panos , Rujescu Dan , Arango Celso , Bertolino Alessandro , Blasi Giuseppe , Bocchio-Chiavetto Luisella , Campion Dominique , Carr Vaughan , Fullerton Janice M. , Gennarelli Massimo , González-Peñas Javier , Levinson Douglas F. , Mowry Bryan , Nimgaokar Vishwajit L. , Pergola Giulio , Rampino Antonio , Rivera-Sanchez Margarita , Schwab Sibylle G. , Wildenauer Dieter B. , Daly Mark , Neale Benjamin , Singh Tarjinder , O’Donovan Michael C. , Owen Michael J. , Walters James T. , Ayub Muhammad , Malhotra Anil K. , Lencz Todd , Sullivan Patrick F. , Sklar Pamela , Stahl Eli A. , Huckins Laura M. , Charney Alexander W.
Published: January 2022

Schizophrenia is a chronic mental illness that is amongst the most debilitating conditions encountered in medical practice. A recent landmark schizophrenia study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This study -- and most other large-scale human genetic studies -- was mainly composed of individuals of European ancestry, and the generalizability of the findings in non-European populations is unclear. To address this gap in knowledge, we designed a custom sequencing panel based on current knowledge of the genetic architecture of schizophrenia and applied it to a new cohort of 22,135 individuals of diverse ancestries. Replicating earlier work, cases carried a significantly higher burden of rare protein-truncating variants among constrained genes (OR=1.48, p-value = 5.4 × 10−6). In meta-analyses with existing schizophrenia datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five continental populations. Two genes (SRRM2andAKAP11) were newly implicated as schizophrenia risk genes, and one gene (PCLO) was identified as a shared risk gene for schizophrenia and autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of schizophrenia being conserved across diverse human populations.
Immunological Cross-Reactivity to Dengue Virus among Persons with Neuroinvasive West Nile Virus Infection
Authors: Raabe Vanessa , Natrajan Muktha S. , Huerta Chris , Xu Yongxian , Lai Lilin , Mulligan Mark J.
Published: January 2022

Antibody dependent enhancement has been well described between Zika and dengue viruses, but is poorly characterized between West Nile and dengue viruses. We demonstrate that neuroinvasive West Nile virus infection leads to the development of non-neutralizing, cross-reactive IgG antibodies to dengue and Zika viruses capable of causing antibody dependent enhancement in vitro of dengue virus and leads to the formation of flavivirus cross-reactive memory B cells in some patients.
Macrocycle-stabilization of its interaction with 14-3-3 increases plasma membrane localization and activity of CFTR
Authors: Stevers Loes M. , Wolter Madita , Carlile Graeme W. , Macdonald Dwight , Richard Luc , Gielkens Frank , Thomas David Y. , Chakka Sai Kumar , Peterson Mark L. , Thomas Helmut , Brunsveld Luc , Ottmann Christian
Published: January 2022

Impaired activity of the chloride channel CFTR is the cause of cystic fibrosis. 14-3-3 proteins have been shown to stabilize CFTR and increase its biogenesis and activity. Here, we report the identification and mechanism of action of a macrocycle stabilizing the 14-3-3/CFTR complex, a first-in-class molecular glue. This molecule rescues plasma membrane localization and chloride transport of F508del-CFTR and works additively with the CFTR pharmacological chaperone corrector lumacaftor (VX-809).
Explaining the microbial diversity conundrum: can microbiome composition be crucial for host fitness, while highly divergent among healthy individuals?
Authors: Daybog Itay , Kolodny Oren
Published: January 2022

Recent empirical studies offer conflicting findings regarding the relation between host fitness and the composition of its microbiome, a conflict which we term themicrobial β - diversity conundrum: it has been shown that the microbiome is crucial for host wellbeing and survival. At the same time, different healthy individuals’ microbiome compositions, even in the same population, often differ dramatically, contrary to the notion that a vital trait should be highly conserved. Moreover, gnotobiotic individuals exhibit highly deleterious phenotypes, supporting the notion that the microbiome is paramount to host fitness. However, the introduction of almost arbitrarily selected microbiota into the system often achieves a significant rescue effect of the deleterious phenotypes, even microbiota from soil or phylogenetically distant host species, highlighting an apparent paradox. Here we suggest several solutions to the paradox using a computational framework, simulating the population dynamics of hosts and their microbiomes over multiple generations. The answers, relating to factors such as host population size, the specific mode of contribution of the microbes to host fitness, and the typical microbiome richness, offer solutions to the conundrum by creating scenarios where even when a host’s fitness is determined in full by its microbiome composition, this composition has little or no effect on the natural selection dynamics of the population.
Omicron variant escapes therapeutic mAbs contrary to eight prior main VOC
Authors: Boschi Céline , Colson Philippe , Bancod Audrey , Moal Valérie , Scola Bernard La
Published: January 2022

Monocolonal antibodies (mAbs) are currently used for active immunization of COVID-19 in immunocompromised patients. We herein show that in spite there are variations in susceptibility to available mAbs that are authorized for clinical use in France tested on the original B.1.1 virus and 9 variants of concern or of interest, the cocktail casirivimab/imdevimab (REGN-CoV-2) showed a major synergistic effect. However, none of the four mAbs either alone or in combination neutralized the new Omicron variant. Our data strongly warrant a reinforcement of protective measures against infection for immunocompromised patients.
Phylogeographic analysis reveals an ancient East African origin of the human herpes simplexvirus 2 dispersal out-of-Africa
Authors: Havens Jennifer L. , Calvignac-Spencer Sébastien , Merkel Kevin , Burrel Sonia , Boutolleau David , Wertheim Joel O.
Published: January 2022

Human herpes simplex virus 2 (HSV-2) is a globally ubiquitous, slow evolving DNA virus. HSV-2 genomic diversity can be divided into two main groups: an African lineage and worldwide lineage. Competing hypotheses have been put forth to explain the history of HSV-2. HSV-2 may have originated in Africa and then followed the first wave of human migration out of Africa between 50-100 kya. Alternatively, HSV-2 may have migrated out of Africa via the trans-Atlantic slave trade within the last 150-500 years. The lack of HSV-2 genomes from West and Central Africa, combined with a lack of molecular clock signal in HSV-2 has precluded robust testing of these competing hypotheses. Here, we expand the geographic sampling of HSV-2 genomes in order to resolve the geography and timing of divergence events within HSV-2. We analyze 65 newly sequenced HSV-2 genomes collected from primarily West and Central Africa along with 330 previously published genomes sampled over a 47-year period. Evolutionary simulations confirm that the molecular clock in HSV-2 is too slow to be detected using available data. However, phylogeographic analysis indicates that all biologically plausible evolutionary rates would place the ancestor of the worldwide lineage in East Africa, arguing against the trans-Atlantic slave trade as the source of worldwide diversity. The best supported evolutionary rates between 4.2×10−8 and 5.6×10−8 substitutions/site/year suggest a most recent common ancestor for HSV-2 around 90-120 kya and initial dispersal around 21.9-29.3 kya. These dates suggest HSV-2 left Africa during subsequent waves of human migration out of East Africa.
Volatile anesthetics inhibit presynaptic cGMP signaling to depress presynaptic excitability in rat hippocampal neurons
Authors: Speigel Iris , Osman Vanessa , Hemmings Hugh C
Published: January 2022

Volatile anesthetics alter presynaptic function including effects on Ca2+ influx and neurotransmitter release. These actions are proposed to play important roles in their pleiotropic neurophysiological effects including unconsciousness and amnesia. The nitric oxide and cyclic guanosine monophosphate (NO/cGMP) signaling pathway has been implicated in presynaptic mechanisms, and disruption of NO/cGMP signaling has been shown to alter sensitivity to volatile anesthetics in vivo. We investigated NO/cGMP signaling in relation to volatile anesthetic actions in cultured rat hippocampal neurons using pharmacological tools and genetically encoded biosensors of cGMP levels. Using the fluorescent biosensor cGull we found that electrical stmulation-evoked NMDA-type glutamate receptor-independent presynaptic cGMP transients were inhibited −33.2% by isoflurane (0.51 mM) and −23.8% by sevoflurane (0.57 mM) (p<0.0001) compared to a stimulation without anesthetic. Isoflurane and sevoflurane inhibition of stimulation-evoked increases in presynaptic Ca2+ concentration, measured with synaptophysin-GCaMP6f, and synaptic vesicle exocytosis, measured with synaptophysin-pHlourin, were reduced by in neurons expressing the cGMP scavenger sponGee. This reduction in anesthetic effect was recapitulated by inhibiting HCN channels, a cGMP-modulated effector that can facilitate glutamate release. We propose that volatile anesthetics depress presynaptic cGMP signaling and downstream effectors like HCN channels that are essential to presynaptic function and excitability. These findings identify a novel mechanism by which volatile anesthetics depress synaptic transmission via second messenger signaling involving the NO/cGMP pathway.
A global Anopheles gambiae gene co-expression network constructed from hundreds of experimental conditions with missing values
Authors: Kuang Junyao , Buchon Nicolas , Michel Kristin , Scoglio Caterina
Published: January 2022

Gene co-expression networks can be used to determine gene regulation and attribute gene function to biological processes. Different high throughput technologies, including one and two-channel microarrays and RNA-sequencing, allow evaluating thousands of gene expression data simultaneously, but these methodologies provide results that cannot be directly compared. Thus, it is complex to analyze coexpression relations between genes, especially when there are missing values arising for experimental reasons. Networks are a helpful tool for studying gene co-expression, where nodes represent genes and edges represent co-expression of pairs of genes. In this paper, we propose a method for constructing a gene co-expression network for the Anopheles gambiae transcriptome from 257 unique studies obtained with different methodologies and experimental designs. We introduce the sliding threshold approach to select node pairs with high Pearson correlation coefficients. The robustness of the method was verified by comparing edge weight distributions under random removal of conditions. The properties of the constructed network are studied in this paper, including node degree distribution, coreness, and community structure. The network core is largely comprised of genes that encode components of the mitochondrial respiratory chain and the ribosome, while different communities are enriched for genes involved in distinct biological processes. This suggests that the overall network structure is driven to maximize the integration of essential cellular functions, possibly allowing the flexibility to add novel functions.
E.PAGE: A curated database and enrichment tool to predict gene modules associated with gene-environment interactions
Authors: Muralidharan Sachin , Ali Sarah , Yang Lilin , Badshah Joshua , Zahir Farah , Ali Rubbiya , Chandra Janin , Frazer Ian , Thomas Ranjeny , Mehdi Ahmed M.
Published: January 2022

Background

The purpose of this study was to manually and semi-automatically curate a database and develop an R package that will provide a comprehensive resource to uncover associations between biological processes and environmental factors in health and disease.

We followed a two-step process to achieve the objectives of this study. First, we conducted a systematic review of existing gene expression datasets to identify those with integrated genomic and environmental factors. This enabled us to curate a comprehensive genomic-environmental database for four key environmental factors (smoking, diet, infections and toxic chemicals) associated with various autoimmune and chronic conditions. Second, we developed a statistical analysis package that allows users to interrogate the relationships between differentially expressed genes and environmental factors under different disease conditions.

Results

The initial database search run on the Gene Expression Omnibus (GEO) and the Molecular Signature Database (MSigDB) retrieved a total of 90,018 articles. After title and abstract screening against pre-set criteria, a total of 186 studies were selected. From those, 243 individual sets of genes, or “gene modules”, were obtained. We then curated a database containing four environmental factors, namely cigarette smoking, diet, infections and toxic chemicals, along with a total of 25789 genes that had an association with one or more of these gene modules. In six case studies, the database and statistical analysis package were then tested with lists of differentially expressed genes obtained from the published literature related to type 1 diabetes, rheumatoid arthritis, small cell lung cancer, COVID-19, cobalt exposure and smoking. On testing, we uncovered statistically enriched biological processes, which revealed pathways associated with environmental factors and the genes.

Conclusions

A novel curated database and software tool is provided as an R Package. Users can enter a list of genes to discover associated environmental factors under various disease conditions.
BDSF is a degradation-prone quorum-sensing signal detected by the histidine kinase RpfC of Xanthomonas campestris pv. campestris
Authors: Tian Xiu-Qi , Wu Yao , Cai Zhen , Qian Wei
Published: January 2022

Diffusible signal factors (DSFs) are medium-chain fatty acids that induce bacterial quorum sensing. Among these compounds, BDSF is a structural analog of DSF that is commonly detected in bacterial species (e.g., Xanthomonas, Pseudomonas, and Burkholderia). Additionally, BDSF contributes to the interkingdom communication regulating fungal life stage transitions. How BDSF is sensed in Xanthomonas spp. and the functional diversity between BDSF and DSF remain unclear. In this study, we generated genetic and biochemical evidence that BDSF is a low-active regulator of X. campestris pv. campestris quorum sensing, whereas trans-BDSF seems not a signaling compound. BDSF is detected by the sensor histidine kinase RpfC. Although BDSF has relatively low physiological activities, it binds to the RpfC sensor with a high affinity and activates RpfC autophosphorylation to a level that is similar to that induced by DSF in vitro. The inconsistency in the physiological and biochemical activities of BDSF is not due to RpfC– RpfG phosphorylation or RpfG hydrolase. Neither BDSF nor DSF controls the phosphotransferase and phosphatase activities of RpfC or the ability of RpfG hydrolase to degrade the bacterial second messenger cyclic di-GMP. We demonstrated that BDSF is prone to degradation by RpfB, a critical fatty acyl-CoA ligase involved in the turnover of DSF-family signals. rpfB mutations lead to substantial increases in BDSF-induced quorum sensing. Although DSF and BDSF are similarly detected by RpfC, our data suggest that their differential degradation in cells is the major factor responsible for the diversity in their physiological effects.

IMPORTANCE

Diffusible signal factor (DSF) family are quorum-sensing signals employed by gram-negative bacteria. These signals are a group of cis-2-unsaturated fatty acids, such as DSF, BDSF, IDSF, CDSF, and SDSF. However, the functional divergence of various DSF signals remains unclear. The present study demonstrates that though BDSF is a low active quorum-sensing signal than that of DSF, it binds histidine kinase RpfC with a higher affinity and activates RpfC autophosphorylation to the similar level as DSF. Rather than regulation of enzymatic activities of RpfC and its cognate response regulator RpfG encoding a c-di-GMP hydrolase, BDSF is prone to degradation in bacterial cells by RpfB, which effectively avoided the inhibition of bacterial growth by accumulating high concentration of BDSF. Therefore, our study shed new light on the functional difference of quorum-sensing signals and revealed that bacteria balance quorum-sensing and growth by fine-turning concentration of signaling chemical.
Hybridization of Oligonucleotide Probes in Aqueous Solutions: Washing in Buffers Containing Quaternary Ammonium Salts
Authors: Green Michael R. , Sambrook Joseph
Published: January 2022

In this protocol, hybridization is first performed in conventional aqueous solvents at a temperature well below the melting temperature, and the hybrids are then washed at higher stringency in buffers containing quaternary alkylammonium salts. TMACl is used with probes that are 14–50 nt in length, whereas TEACl is used with oligonucleotides that are 50–200 nt in length.
Simulation of iron losses in induction machines using an iron loss model for rotating magnetization loci in no electrical steel
Authors: Nell Martin Marco , Schauerte Benedikt , Brimmers Tim , Hameyer Kay
Published: January 2022

Purpose

Various iron loss models can be used for the simulation of electrical machines. In particular, the effect of rotating magnetic flux density at certain geometric locations in a machine is often neglected by conventional iron loss models. The purpose of this paper is to compare the adapted IEM loss model for rotational magnetization that is developed within the context of this work with other existing models in the framework of a finite element simulation of an exemplary induction machine.

Design/methodology/approach

In this paper, an adapted IEM loss model for rotational magnetization, developed within the context of the paper, is implemented in a finite element method simulation and used to calculate the iron losses of an exemplary induction machine. The resulting iron losses are compared with the iron losses simulated using three other already existing iron loss models that do not consider the effects of rotational flux densities. The used iron loss models are the modified Bertotti model, the IEM-5 parameter model and a dynamic core loss model. For the analysis, different operating points and different locations within the machine are examined, leading to the analysis of different shapes and amplitudes of the flux density curves.

Findings

The modified Bertotti model, the IEM-5 parameter model and the dynamic core loss model underestimate the hysteresis and excess losses in locations of rotational magnetizations and low-flux densities, while they overestimate the losses for rotational magnetization and high-flux densities. The error is reduced by the adapted IEM loss model for rotational magnetization. Furthermore, it is shown that the dynamic core loss model results in significant higher hysteresis losses for magnetizations with a high amount of harmonics.

Originality/value

The simulation results show that the adapted IEM loss model for rotational magnetization provides very similar results to existing iron loss models in the case of unidirectional magnetization. Furthermore, it is able to reproduce the effects of rotational flux densities on iron losses within a machine simulation.
Integrating inspection management (IM) in piping system of petroleum industry in Iran
Authors: Amani Nima
Published: January 2022

Purpose

This paper aims to report on the findings from a research project, incorporated by Iran’s Ministry of Petroleum, investigating the integration of inspection management with analysis of document information.

Design/methodology/approach

A combination of group and individual interviews were undertaken with qualitative methods of analysis to develop an integrated process model. The model developed uses integrity management factors, which allows flexibility and the early integration of inspection management systems at a strategic level, although detailed planning is still required through the use of integrated management tools. The model combines information on responsibilities, tasks and policies, of personnel in the inspection management of the piping system with the oil and gas industry.

Findings

The six inspection activities recognized for the main practical model are, namely, identify pipeline situation; inspect and measure defects; inspection assessment; design inspection; implement inspection activities and measure and report inspection.

Originality/value

This research presented not only a process but also the framework and techniques to manage and improve management effectiveness and inspection efficiency in pipelines of the oil and gas industry. This study will be useful to researchers maintenance professionals and others concerned with inspection and maintenance management of facilities and equipment in the oil and gas industry.
The effect of the financial crisis on audit quality: European evidence
Authors: Kyriakou Maria I.
Published: January 2022

Purpose

This paper aims to examine the impact of the recent financial crisis on audit quality by analysing discretionary accruals.

Design/methodology/approach

This study considers a sample of German, French, Italian and Spanish non-financial firms from 2005 to 2013 to investigate the auditor’s independence. It uses a cross-sectional and time-series ordinary least squares regression model to control for other predictors of the auditor’s independence when the financial crisis produces a decrease in audit quality.

Findings

The proportion of the non-financial firms having lower audit quality was higher during the financial crisis. In addition, during the crisis auditors were less likely to provide a higher audit quality for these non-financial firms. The level of audit quality returned to normal levels during the post-crisis years when the crisis had ceased.

Originality/value

These findings contribute to the literature on the impact of economic and financial changes on audit quality. In addition, this research finds that the Big Four accounting firms provide a higher audit quality in different circumstances from non-Big Four accounting firms, and that audit quality decreased during the crisis and returned to normal in the post-crisis period.
Probabilistic assessment of complex system consisting three subsystems, multi-failure threats and copula repair approach
Authors: Jibril Abbas Bin , Singh V.V. , Rawal Dilip Kumar
Published: January 2022

Purpose

The purpose of this paper is to deliberate the system reliability of a system in combination of three subsystems in a series configuration in which all three subsystems function under a k-out-of-n: G operational scheme. Based on computed results, it has been demonstrated that copula repair is better than general repair for system better performance. The supplementary variable approach with implications of copula distribution has been employed for assessing the system performance.

Design/methodology/approach

Probabilistic assessment of complex system consisting three subsystems, multi-failure threats and copula repair approach is used in this study. Abbas Jubrin Bin, V.V. Singh, D.K. Rawal, in this research paper, have analyzed a system consisting of three subsystems in a series configuration in which all three subsystems function under a k-out-of-n: G operational scheme. The supplementary variable approach with implications of copula distribution has been employed for assessing the system performance. Based on computed results, it has been demonstrated that copula repair is better than general repair for system better performance.

Findings

In this analysis, four different cases of availability are analysed for Gumbel–Hougaard family copula and also four cases for general repair with similar failure rates are studied. The authors found that when failure rates increase, the system availability decreases, and when the system follows copula repair distribution, the system availability is better than general repair.

Research limitations/implications

This research may be implemented in various industrial systems where the subsystems are configured under k-out-of-n: G working policy. It is also advisable that copula repair is highly recommended for best performances from the system. On the basis of mean time to system failure (MTSF) computations, the failure rate which affects system failure more needs to be controlled by monitoring, servicing and replacing stratagem.

Practical implications

This research work has great implications in various industrial systems like power plant systems, nuclear power plant, electricity distributions system, etc. where the k-out-of-n-type of system operation scheme is validated for system operations with the multi-repair.

Originality/value

This work is a new work by authors. In the previously available technical analysis of the system, the researchers have analyzed the repairable system either supplementary variable approach, supplementary variable and system which have two subsystems in a series configuration. This research work analyzed a system with three subsystems with a multi-repair approach and supplementary variables.
Strategic crisis response: managerial implications and direction for recovery and survival
Authors: Thakur Ramendra , Hale Dena
Published: January 2022

Purpose

The purpose of this paper is to provide managers with insights to help survive a crisis, create advantage during slow-growth recoveries and thrive when the crisis is over. Given the environment at the time of this paper, this paper focuses on widespread crises, such as a public health crisis like COVID-19.

Design/methodology/approach

The authors offer a conceptual framework, grounded in the attribution theory and situation crisis communication theory (SCCT), for managers to use when determining which crisis response strategy is most appropriate to use during a crisis. Propositions based on this framework are provided. This paper focuses on widespread crises, such as a public health crisis, particularly on the COVID-19 pandemic. Based on the framework proposed for organizational crisis response strategy and recovery, several insights for managers across a variety of industries emerge. Consideration of the best strategic approach to a crisis is essential, and time is critical. This framework provides a starting point for creating a proper response strategy when a crisis arises that is not within the organization’s crisis management planning. Managerial implications for several industries, such as restaurant, hotel, airline, education, retail, medical and other professional services, and theoretical implications to further the advancement of understanding are provided.

Findings

The findings of this paper demonstrate that organizations that apply an accommodative strategy during unintentional crises will survive, while during intentional crises, they will thrive in the marketplace. Similarly, organizations that apply an offensive strategy during unintentional crises will thrive, while during intentional crises, they will survive in the marketplace.

Practical implications

This paper provides a framework highlighting strategies that best protect an organization during both internally and externally caused crises. The response strategy and crisis framework are based on the attribution theory and SCCT. Building on this framework, six propositions are postulated. In keeping with this strategy and crisis framework, this study provides several crisis response insights for managers across a variety of industries. These suggestions act as a guide for managers when assessing how to respond in the early days of a crisis and what to do to recover from it.

Originality/value

This paper provides a crisis-strategy matrix, grounded in the attribution theory and SCCT, to provide decision-making guidance to help managers survive a crisis, create advantage during slow-growth recoveries and thrive when the crisis is over. The authors provide multiple industry insights related to the “how to” and the “what to” in the recovery from and survival through internally and externally caused crises.