bluuebunny/crossref_metadata_2025 huggingface dataset:
Experiences and needs of parents whose child has attempted suicide
Authors: Raney Kayla , Popa Kim , Gallegos Cara
Published: October 2022

Purpose:

To explore the stress, experience, and unmet needs of parents whose child has attempted suicide.

Methods:

A 23-question survey and a 53-item Family Management Measurement questionnaire were distributed to the parents of children admitted to an acute care facility for a suicide attempt (SA). Quantitative data were analyzed using Statistical Analysis System. Responses to the open-ended questions were sorted, synthesized, and clustered into tentative categories.

Results:

Eleven parents enrolled, but only 10 completed the qualitative questions. Three themes emerged: feelings of helplessness, uncertainty, and life management difficulty. Parents rated their stress as moderate (6.6 out of 10). Internal consistency (Cronbach's alpha) was questionable (0.69); however, three of six subscales were good to excellent (0.81-0.95).

Conclusion:

Families experience stress, feelings of hopelessness, and uncertainty after an SA. More research is needed to better understand and quantify parental experiences.
Effect of the Premature Infant Oral Motor Intervention on Sucking Capacity in Preterm Infants in Turkey
Authors: Guler Selver , Cigdem Zerrin , Lessen Knoll Brenda S. , Ortabag Tulay , Yakut Yavuz
Published: October 2022

Background:

Preterm infants have oral feeding difficulty that often delays discharge, indicating a need for evidence-based interventions for oral–motor development.

Purpose:

To test the Premature Infant Oral Motor Intervention (PIOMI) on the development of oral–motor function, feeding, and anthropometric outcomes using sucking manometry.

Methods:

A single-blind randomized experimental design was conducted with a sample of 60 preterm infants from 2 neonatal intensive care units between May 2019 and March 2020. The experimental group received PIOMI for 5 min/d for 14 consecutive days. Sucking capacity, anthropometrics (weight and head circumference), bottle feeding, breast/chest feeding initiation, and length of hospital stay were measured. The Yakut Sucking Manometer (PCT/TR2019/050678) was developed specifically for this study and tested for the first time.

Results:

The experimental group had a statistically significant percent increase over controls in sucking power (69%), continuous sucking before releasing the bottle (16%), sucking time (13%), and sucking amount (12%) with partial η2 values of interaction between the groups of 0.692, 0.164, 0.136, and 0.121, respectively. The experimental group had a higher increase in weight (89%) and head circumference (81%) over controls (F = 485.130, P < .001; F = 254.754, P < .001, respectively). The experimental group transitioned to oral feeding 9.9 days earlier than controls (t = −2.822; P = .007), started breast/chest feeding 10.8 days earlier (t = 3.016; P = .004), and were discharged 3.0 days earlier.

Implications for Research/Practice:

The PIOMI had a significant positive effect on anthropometrics, sucking capacity, readiness to initiate bottle and breast/chest feeding, and a 3-day reduction in length of hospital stay.
The cultural transmission of tacit knowledge
Authors: Miton Helena , DeDeo Simon
Published: October 2022

A wide variety of cultural practices have a ‘tacit’ dimension, whose principles are neither obvious to an observer, nor known explicitly by experts. This poses a problem for cultural evolution: if beginners cannot spot the principles to imitate, and experts cannot say what they are doing, how can tacit knowledge pass from generation to generation? We present a domain-general model of ‘tacit teaching’, drawn from statistical physics, that shows how high-accuracy transmission of tacit knowledge is possible. It applies when the practice’s underlying features are subject to interacting and competing constraints. Our model makes predictions for key features of the teaching process. It predicts a tell-tale distribution of teaching outcomes, with some students near-perfect performers while others receiving the same instruction are disastrously bad. This differs from standard cultural evolution models that rely on direct, high-fidelity copying, which lead to a much narrower distribution of mostly mediocre outcomes. The model also predicts generic features of the cultural evolution of tacit knowledge. The evolution of tacit knowledge is expected to be bursty, with long periods of stability interspersed with brief periods of dramatic change, and where tacit knowledge, once lost, becomes essentially impossible to recover.
Rheology of marine sponges reveals anisotropic mechanics and tuned dynamics
Authors: Kraus Emile A. , Mellenthin Lauren E. , Siwiecki Sara A. , Song Dawei , Yan Jing , Janmey Paul A. , Sweeney Alison M.
Published: October 2022

Sponges are animals that inhabit many aquatic environments while filtering small particles and ejecting metabolic wastes. They are composed of cells in a bulk extracellular matrix, often with an embedded scaffolding of stiff, siliceous spicules. We hypothesize that the mechanical response of this heterogeneous tissue to hydrodynamic flow influences cell proliferation in a manner that generates the body of a sponge. Towards a more complete picture of the emergence of sponge morphology, we dissected a set of species and subjected discs of living tissue to physiological shear and uniaxial deformations on a rheometer. Various species exhibited rheological properties such as anisotropic elasticity, shear softening and compression stiffening, negative normal stress, and non-monotonic dissipation as a function of both shear strain and frequency. Erect sponges possessed aligned, spicule-reinforced fibres which endowed three times greater stiffness axially compared with orthogonally. By contrast, tissue taken from shorter sponges was more isotropic but time-dependent, suggesting higher flow sensitivity in these compared with erect forms. We explore ecological and physiological implications of our results and speculate about flow-induced mechanical signalling in sponge cells.
How the epidemiology of disease-resistant and disease-tolerant varieties affects grower behaviour
Authors: Murray-Watson Rachel E. , Cunniffe Nik J.
Published: October 2022

Population-scale effects of resistant or tolerant crop varieties have received little consideration from epidemiologists. When growers deploy tolerant crop, population-scale disease pressures are often unaffected. This only benefits growers using tolerant varieties, selfishly decreasing yields for others. However, resistant crop can reduce disease pressure for all. We coupled an epidemiological model with game theory to understand how this affects uptake of control. Each time a grower plants a new crop, they must decide whether to use an improved (i.e. tolerant/resistant) or unimproved variety. This decision is based on strategic-adaptive expectations in our model, with growers comparing last season’s profit with an estimate of what is expected from the alternative crop. Despite the positive feedback loop promoting use of a tolerant variety whenever it is available, a mixed unimproved- and tolerant-crop equilibrium can persist. Tolerant crop can also induce bistability between a scenario in which all growers use tolerant crop and the disease-free equilibrium, where no growers do. However, due to ‘free-riding’ by growers of unimproved crop, resistant crop nearly always exists in a mixed equilibrium. This work highlights how growers respond to contrasting incentives caused by tolerant and resistant varieties, and the distinct effects on yields and population-scale deployment.
Leptospira sanjuanensis sp. nov., a pathogenic species of the genus Leptospira isolated from soil in Puerto Rico
Authors: Fernandes Luis G. V. , Stone Nathan E. , Roe Chandler C. , Goris Marga G. A. , van der Linden Hans , Sahl Jason W. , Wagner David M. , Nally Jarlath E.
Published: October 2022

Two spirochetes (designated strains LGVF01 and LGVF02T) were isolated from soil samples in San Juan, Puerto Rico in HAN media after selection using a combination of ELISA, agar plating, and colony screening by Fluorescent Antibody Testing (FAT) and PCR for lipL32 and secY. Isolates were helix-shaped, aerobic, fast-growing, and highly motile. Genome sequence analysis indicated that both strains should be classified as members of a novel species within the pathogenic (P1) clade of the genus

Leptospira

. The average nucleotide identity between the two strains was 99.2 %, but below 93.2 % when compared to any previously described leptospiral species. Serotyping of strain LGVF02T indicates that it does not belong within any serogroup of

Leptospira

suggesting it also represents a new serovar. Collectively, strains LGVF01 and LGVF02T represent a new species of pathogenic leptospires for which the name Leptospira sanjuanensis sp. nov. is proposed. The type strain is LGVF02T (=NVSL-LGVF02T=KIT0302T).
Development of a Mobile Application to Represent Food Intake in Inpatients: Dietary Data Systematization
Authors: Molter ARJO , Brazil PE , Fonseca CF , Bacelo AC
Published: October 2022

Background

Nutritional risk situations related to decreased food intake in the hospital environment hinder nutritional care and increase malnutrition in hospitalized patients and are often associated with increased morbidity and mortality.

Objective

To develop and test the reliability of a mobile application as a virtual instrument to assess the acceptability and quality of hospital diets for inpatients.

Methods

This intra- and interobserver development and reliability study investigated an in-hospital food intake monitoring application based on a validated instrument for patients with infectious diseases who were treated at the Evandro Chagas National Institute of Infectious Diseases (INI/FIOCRUZ). The instrument was sequentially administered to patients 48 h after admission to INI hospital units using the printed instrument (paper) and the tested digital application (ARIETI) simultaneously. The tested reliability factor was the consistency of the method in the digital platform, checking whether the application provided equivalent data to the paper instrument, and finally a statistical analysis plan was performed in the R platform version 4.2.0. This project was authorized by the FIOCRUZ/INI Research Ethics Committee under CAAE 35379820.4.0000.5262.

Results

The ARIETI was developed and tested for reliability in 70 participants, showing similar ability to show caloric intake in Kcal (p = 1.72 E-03), protein intake (g) (p = 0.006362), the proportion of caloric intake (p = 1.54 E-05), and the protein intake (p = 0.003501) relative to the prescribed goal. The application was superior to the paper-based instrument, accelerating the diagnosis of nutritional risk based on food intake by up to 250 s (50–350 min).

Conclusions

The ARIETI optimized the time between diagnosis of nutritional risk related to dietary intake and the nutritionist’s decision making, showing an improved ability to maintain information quality compared to the paper-based instrument.
CORRELATION BETWEEN MEASURED PARAMETERS OF RISK AND PROGNOSIS IN SUBJECTS WITH CHRONIC PERIODONTITIS
Authors: Chandra Rampalli Viswa , Shravan Tulasi
Published: October 2022

Aims

In most ofcases, clinical parameters associated with poor prognosis are the same as the factors associated with increased risk, but the relationship between risk and prognosis remains unclear.The objective of this study was to evaluate the correlation between measured parameters of predictive risk and prognosisin subjects with chronic periodontitis.

Methods

300 subjects participated in the study. Modified periodontal risk assessment model (MPRA) was used to assess the risk and prognosis was evaluated by using McGuire and Nunn prognostic criteria.

Results

Among the subjects, 57.3%, 38% and 4.7% were categorized as having high, low and medium risk respectively. Assessment of prognosis among study subjects showed that 38.0%, 24.0%, 17.7%, 17.0%, 2.0%and1.3% had good, fair, excellent, poor, hopeless and questionable prognosis respectively. Though majority of the subjects had good prognosis (114 subjects;38%), there was a substantial variability in the distribution of the measured parameters as per the risk scores within this cohort. A strong positive correlation was seen between prognosis and probing depth (PD)≥5mm. There was a weak, but statistically significant correlation between predictive risk from MPRA and various types of prognosis(rs=0.507;p<0.001).

Conclusion

The measures used to assess risk and prognosis are almost similar;butthe weak correlation between risk and prognosisseems to suggest that an increased risk of developing periodontal disease need notnecessarily indicate a bad prognosis.
Clinical antiviral efficacy of remdesivir and casirivimab/imdevimab against the SARS-CoV-2 Delta and Omicron variants
Authors: Jittamala Podjanee , Schilling William HK , Watson James A , Luvira Viravarn , Siripoon Tanaya , Ngamprasertchai Thundon , Almeida Pedro J , Ekkapongpisit Maneerat , Cruz Cintia , Callery James J , Boyd Simon , Anunsittichai Orawan , Hongsuwan Maliwan , Singhaboot Yutatirat , Pagornrat Watcharee , Tuntipaiboontana Runch , Kruabkontho Varaporn , Ngernseng Thatsanun , Tubprasert Jaruwan , Abdad Mohammad Yazid , Keayarsa Srisuda , Madmanee Wanassanan , Aguiar Renato S , Santos Franciele M , Batty Elizabeth M , Hanboonkunupakarn Pongtorn , Hanboonkunupakarn Borimas , Sookprome Sakol , Poovorawan Kittiyod , Imwong Mallika , Taylor Walter RJ , Chotivanich Vasin , Sangketchon Chunlanee , Ruksakul Wiroj , Chotivanich Kesinee , Pukrittayakamee Sasithon , Dondorp Arjen M , Day Nicholas PJ , Teixeira Mauro M , Piyaphanee Watcharapong , Phumratanaprapin Weerapong , White Nicholas J
Published: October 2022

Background

Uncertainty over the therapeutic benefit provided by parenteral remdesivir in COVID-19 has resulted in varying treatment guidelines. Early in the pandemic the monoclonal antibody cocktail, casirivimab/imdevimab, proved highly effective in clinical trials but because of weak or absentin vitroactivity against the SARS-CoV-2 Omicron BA.1 subvariant, it is no longer recommended.

Methods

In a multicenter open label, randomized, controlled adaptive platform trial, low-risk adult patients with early symptomatic COVID-19 were randomized to one of eight treatment arms including intravenous remdesivir (200mg followed by 100mg daily for five days), casirivimab/imdevimab (600mg/600mg), and no study drug. The primary outcome was the viral clearance rate in the modified intention-to-treat population derived from daily log10viral densities (days 0-7) in standardized duplicate oropharyngeal swab eluates. This ongoing adaptive trial is registered atClinicalTrials.gov(NCT05041907).

Results

Acceleration in mean estimated SARS-CoV-2 viral clearance, compared with the contemporaneous no study drug arm (n=64), was 42% (95%CI 18 to 73%) for remdesivir (n=67). Acceleration with casirivimab/imdevimab was 58% (95%CI: 10 to 120) in Delta (n=13), and 20% (95%CI: 3 to 43) in Omicron variant (n=61) infections compared with contemporaneous no study drug arm (n=84). In apost hocsubgroup analysis viral clearance was accelerated by 8% in BA.1 (95%CI: −21 to 59) and 23% (95%CI: 3 to 49) in BA.2 and BA.5 Omicron subvariants.

Conclusions

Parenteral remdesivir accelerates viral clearance in early symptomatic COVID-19. Despite substantially reducedin vitroactivities, casirivimab/imdevimab retainsin vivoantiviral activity against COVID-19 infections caused by currently prevalent Omicron subvariants.

Brief summary

In early symptomatic COVID-19 remdesivir accelerated viral clearance by 42% while the monoclonal antibody cocktail casirivimab/imdevimab accelerated clearance by approximately 60% in SARS-CoV-2 Delta variant infections, and by approximately 25% in infections with Omicron subvariants BA.2 and BA.5.
Single-cell molecular profiling using ex vivo functional readouts fuels precision oncology in glioblastoma
Authors: Panovska Dena , Nazari Pouya , Cole Basiel , Creemers Pieter-Jan , Derweduwe Marleen , Solie Lien , Gassen Sofie Van , Claeys Annelies , Verbeke Tatjana , Saeys Yvan , Van Der Plancken David , Bosisio Francesca M. , Put Eric , Bamps Sven , Clement Paul M. , Verfaillie Michiel , Sciot Raf , Ligon Keith L. , Vleeschouwer Steven De , Antoranz Asier , Smet Frederik De
Published: October 2022

Background

Functional profiling of freshly isolated glioblastoma cells is being evaluated as a next-generation method for precision oncology. While promising, its success largely depends on the method to evaluate treatment activity which requires sufficient resolution and specificity.

Methods

Here, we describe the ‘precisiononcology bysingle-cellprofiling usingex vivoreadouts of functionality’ (PROSPERO) assay to evaluate the intrinsic susceptibility of high- grade brain tumor cells to respond to therapy. Different from other assays, PROSPERO extends beyond life/death screening by rapidly evaluating acute molecular drug responses at single-cell resolution.

Results

The PROSPERO assay was developed by correlating short-term single-cell molecular signatures using CyTOF to long-term cytotoxicity readouts in representative patient- derived glioblastoma cell cultures (n=14) that were exposed to radiotherapy and the small- molecule p53/MDM2 inhibitor AMG232. The predictive model was subsequently projected to evaluate drug activity in freshly resected GBM samples from patients (n=34).Here,PROSPERO revealed an overall limited capacity of tumor cells to respond to therapy, as reflected by the inability to induce key molecular markers uponex vivotreatment exposure, while retaining proliferative capacity, insights that were validated in PDX models. This approach also allowed the investigation of cellular plasticity, which in PDCLs highlighted therapy-induced proneural-to-mesenchymal transitions, while in patients’ samples this was more heterogeneous.

Conclusion

PROSPERO provides a precise way to evaluate therapy efficacy by measuring molecular drug responses using specific biomarker changes in freshly resected brain tumor samples, in addition to providing key functional insights in cellular behavior, which may ultimately complement standard, clinical biomarker evaluations.
In vitromodelling of oral microbial invasion in the human colon
Authors: Etienne-Mesmin Lucie , Meslier Victoria , Uriot Ophélie , Fournier Elora , Deschamps Charlotte , Denis Sylvain , David Aymeric , Jegou Sarah , Morabito Christian , Quinquis Benoit , Thirion Florence , Oñate Florian Plaza , Le Chatelier Emmanuelle , Ehrlich S. Dusko , Blanquet-Diot Stéphanie , Almeida Mathieu
Published: October 2022

Recent advances in the human microbiome characterization have revealed significant oral microbial detection in stools of dysbiotic patients. However, little is known about the potential interactions of these invasive oral microorganisms with commensal intestinal microbiota and host. In this proof of concept study, we propose a new model of oral to gut invasion by the combined use of anin vitromodel simulating both the physicochemical and microbial (lumen and mucus-associated microbes) parameters of the human colon (M-ARCOL), a salivary enrichment protocol and whole metagenome shotgun sequencing. Oral invasion of the intestinal microbiota was simulated by injection of enriched saliva in thein vitrocolon model inoculated with faecal sample from the same healthy adult donor. The mucosal compartment of M-ARCOL was able to retain the highest species richness levels over time, whilst it decreased in the luminal compartment. This study also showed that oral microorganisms preferably colonized the mucosal microenvironment, suggesting potential oral-to-intestinal mucosal competitions. This new model of oral-to-gut invasion can provide useful mechanistic insights into the role of oral microbiome in various disease processes.
Suramin action in African trypanosomes involves a RuvB-like DNA helicase
Authors: Albisetti Anna , Hälg Silvan , Zoltner Martin , Mäser Pascal , Wiedemar Natalie
Published: October 2022

Suramin is one of the oldest drugs in use today. It is still the treatment of choice for the hemolymphatic stage of African sleeping sickness caused byTrypanosoma brucei rhodesienseand it is also used for surra in camels, caused byTrypanosoma evansi. Yet despite one hundred years of use, suramin’s mode of action is not fully understood. Suramin is a polypharmacologic molecule that inhibits diverse proteins. Here we demonstrate that a DNA helicase of the pontin/ruvB-like 1 family, termedT. bruceiRuvBL1, is involved in suramin resistance in African trypanosomes. Bloodstream-formT. b. rhodesienseunder long-term selection for suramin resistance acquired a homozygous point mutation, isoleucin-312 to valine, close to the ATP binding site ofT. bruceiRuvBL1. The introduction of this missense mutation, by reverse genetics, into drug-sensitive trypanosomes significantly decreased their sensitivity to suramin. Intriguingly, the corresponding residue ofT. evansiRuvBL1 was found mutated in a suramin-resistant field isolate, in that case to a leucin. RuvBL1 (Tb927.4.1270) is predicted to build a heterohexameric complex with RuvBL2 (Tb927.4.2000). RNAi-mediated silencing of gene expression of eitherT. bruceiRuvBL1 or RuvBL2 caused cell death within 72 h. At 36 h after induction of RNAi, bloodstream-form trypanosomes exhibited a cytokinesis defect resulting in the accumulation of cells with two nuclei and two or more kinetoplasts. Taken together, these data indicate that RuvBL1 DNA helicase is among the primary targets of suramin in African trypanosomes.

Abstract Importance

African trypanosomes cause sleeping sickness in humans, nagana in cattle, and surra in camels – lethal diseases for which there is no vaccine and only few drugs. One of the drugs is suramin, developed by Bayer in 1916. Yet despite 100 years of use, suramin’s mode of action is not fully understood at the molecular level. Here we show that a DNA helicase is involved:Trypanosoma brucei rhodesiense(causative agent of sleeping sickness) selected for suramin resistance acquired a point mutation in the DNA helicase RuvBL1 that, when introduced to wild-type trypanosomes, reduced their sensitivity to suramin. Intriguingly, the same site in RuvBL1 was mutated also in a suramin-resistant field isolate ofT. evansi(causative agent of surra). We further demonstrate that RuvBL1 is essential for proper cell division ofT. brucei. Thus we conclude that inhibition of RuvBL1 contributes to the trypanocidal action of suramin.
Purine and carbohydrate availability driveEnterococcus faecalisfitness during wound infection
Authors: Tan Casandra Ai Zhu , Chong Kelvin Kian Long , Yeong Daryl Yu Xuan , Ng Celine Hui Min , Ismail Muhammad Hafiz , Tay Vanessa Shi Yun , Ali Yusuf , Kline Kimberly A.
Published: October 2022

Enterococcus faecalisis commonly isolated from a variety of wound types. Despite its prevalence, the pathogenic mechanisms ofE. faecalisduring wound infection are poorly understood. Using a mouse wound infection model, we performedin vivo E. faecalistransposon sequencing and RNA sequencing to identify fitness determinants that are crucial for replication and persistence ofE. faecalisduring wound infection. We found thatE. faecalispurine biosynthesis genes are important for bacterial replication during the early stages of wound infection, a time when purine metabolites are rapidly consumed byE. faecaliswithin wounds. We also found that theE. faecalisMptABCD phosphotransferase system (PTS), involved in the import of galactose and mannose, is crucial forE. faecalispersistence within wounds of both healthy and diabetic mice, especially when carbohydrate availability changes throughout the course of infection. Duringin vitrogrowth with mannose as the sole carbohydrate source, shikimate and purine biosynthesis genes were downregulated in the OG1RF ΔmptDmutant compared to the isogenic wild-type strain, suggesting a link between mannose transport, shikimate, and purine biosynthesis. Together, our results suggest that dynamic and temporal microenvironment changes at the wound site affects pathogenic requirements and mechanisms ofE. faecalisand raise the possibility of lowering exogenous purine availability and/or targeting galactose/mannose PTS to control wound infections.

IMPORTANCE

AlthoughE. faecalisis a common wound pathogen, its pathogenic mechanisms during wound infection are unexplored. Here, combining a mouse wound infection model within vivotransposon and RNA sequencing approaches, we identified theE. faecalispurine biosynthetic pathway and galactose/mannose MptABCD phosphotransferase system as essential forE. faecalisacute replication and persistence during wound infection, respectively. The essentiality of purine biosynthesis and the MptABCD PTS is driven by the rapid consumption of purine metabolites byE. faecalisduring acute replication and changing carbohydrate availability during the course of wound infection. Overall, our findings reveal the importance of the wound microenvironment inE. faecaliswound pathogenesis and how these metabolic pathways can be targeted to better control wound infections.
Interim Analysis of a Phase I Randomized Clinical Trial on the Safety and Immunogenicity of the mRNA-1283 SARS-CoV-2 Vaccine in Adults
Authors: Yassini Patrick , Hutchens Mark , Paila Yamuna D. , Schoch Lorraine , Aunins Anne , Siangphoe Uma , Paris Robert
Published: October 2022

Background

This interim analysis of an ongoing phase I randomized clinical trial evaluated the safety, reactogenicity, and immunogenicity of mRNA-1283, a next-generation SARS-CoV-2 messenger RNA (mRNA)-based vaccine encoding 2 segments of the spike protein (ie, receptor binding and N-terminal domains).

Methods

Healthy aged adults 18-55 years (n = 104) were randomized (1:1:1:1:1) to receive 2 doses of mRNA-1283 (10, 30, or 100 μg) or mRNA-1273 (100 μg) administered 28 days apart, or a single dose of mRNA-1283 (100 μg). Safety was assessed and immunogenicity was measured by serum neutralizing antibody (nAb) or binding antibody (bAb) responses.

Results

At the interim analysis, no safety concerns were identified and no serious adverse events, adverse events of special interest, or deaths were reported. Solicited systemic adverse reactions were more frequent with higher dose levels of mRNA-1283 than with mRNA-1273. At day 57, all dose levels of the 2-dose mRNA-1283 regimen (including the lowest dose level [10 μg]) induced robust nAb and bAb responses that were comparable to those of mRNA-1273 (100 μg).

Conclusions

mRNA-1283 was generally safe in adults, with all dose levels of the 2-dose regimen (10, 30, and 100 μg) eliciting similar immunogenicity as the 2-dose mRNA-1273 regimen (100 μg).

Clinical Trials Registration

Clinicaltrials.gov,NCT04813796
The epigenetic modifier DOT1L regulates gene regulatory networks necessary for cardiac patterning and cardiomyocyte cell cycle withdrawal
Authors: Cattaneo Paola , Hayes Michael G. B. , Baumgarten Nina , Hecker Dennis , Peruzzo Sofia , Kunderfranco Paolo , Larcher Veronica , Zhang Lunfeng , Contu Riccardo , Fonseca Gregory , Spinozzi Simone , Chen Ju , Condorelli Gianluigi , Schulz Marcel H , Heinz Sven , Guimarães-Camboa Nuno , Evans Sylvia M.
Published: October 2022

Mechanisms by which specific histone modifications regulate distinct gene regulatory networks remain little understood. We investigated how H3K79me2, a modification catalyzed by DOT1L and previously considered a general transcriptional activation mark, regulates gene expression in mammalian cardiogenesis. Early embryonic cardiomyocyte ablation ofDot1lrevealed that H3K79me2 does not act as a general transcriptional activator, but rather regulates highly specific gene regulatory networks at two critical cardiogenic junctures: left ventricle patterning and postnatal cardiomyocyte cell cycle withdrawal. Mechanistic analyses revealed that H3K79me2 in two distinct domains, gene bodies and regulatory elements, synergized to promote expression of genes activated by DOT1L. Surprisingly, these analyses also revealed that H3K79me2 in specific regulatory elements contributed to silencing genes usually not expressed in cardiomyocytes. As DOT1L mutants had increased numbers of postnatal mononuclear cardiomyocytes and prolonged cardiomyocyte cell cycle activity, controlled inhibition of DOT1L might be a strategy to promote cardiac regeneration post-injury.
Identification of RNA virus-derived RdRp sequences in publicly available transcriptomic datasets
Authors: Olendraite Ingrida , Brown Katherine , Firth Andrew E.
Published: October 2022

RNA viruses are abundant, highly diverse, and infect all or most eukaryotic organisms. However, only a tiny fraction of the number and diversity of RNA virus species have been catalogued. To cost effectively expand the diversity of known RNA virus sequences we mined publicly available transcriptomic datasets. We developed 77 family-level Hidden Markov Model profiles for the viral RNA dependent RNA polymerase – the only universal “hall-mark” gene of RNA viruses. By using these to search the NCBI Transcriptome Shotgun Assembly database, we identified 5,867 contigs encoding RNA virus RdRps or fragments thereof and analysed their diversity, taxonomic classification, phylogeny and host associations. Our study expands the known diversity of RNA viruses, and the 77 curated RdRp pHMMs provide a useful resource for the virus discovery community.
Metagenomic analyses reveal the influence of depth layers on marine biodiversity in tropical and subtropical regions
Authors: Santiago Bianca C. F. , de Souza Iara D. , Cavalcante João Vitor F. , Morais Diego A. A. , Dalmolin Rodrigo J. S.
Published: October 2022

The emergence of open ocean global-scale studies provided important information about the genomics of oceanic microbial communities. Metagenomic analyses shed a light on the structure of marine habitats, unraveling the biodiversity of different water masses. Many biological and environmental factors can contribute to marine organism composition, such as depth. However, much remains unknown about the taxonomic and functional features of microbial communities in different water layer depths. Here, we performed a metagenomic analysis of 76 samples from the Tara Ocean Project, distributed in 8 collection stations located in tropical or subtropical regions, and sampled from three layers of depth (surface water layer – SRF, deep chlorophyll maximum layer – DCM, and mesopelagic zone – MES). In total, we assigned genomic sequences to 669.713.333 organisms. The SRF and DCM depth layers are similar in abundance and diversity, while the MES layer presents greater diversity than the other layers. Diversity clustering analysis shows differences regarding the taxonomic content of samples. At the domain level, bacteria prevail in the majority of samples, and the MES layer presents the highest proportion of archaea among all samples. A core of essential biological functions was identified between the depth layers, such as DNA replication, translation, transmembrane transport, and DNA repair. However, some biological functions were found exclusively in each depth layer, suggesting different functional profiles for each of them. Taken together, our results indicate that the depth layer influences microbial sample composition and diversity.
Prevention of thrombocytopenia and thrombosis in heparin-induced thrombocytopenia (HIT) using deglycosylated KKO: A novel therapeutic?
Authors: Sarkar Amrita , Khandelwal Sanjay , Kim Hyunjun , Gruel Yves , Rollin Jerome , Wool Geoffrey D. , Arepally Gowthami M. , Cines Douglas B. , Rauova Lubica , Poncz Mortimer
Published: October 2022

Heparin-induced thrombocytopenia (HIT) is characterized by mild thrombocytopenia associated with a highly prothrombotic state due to the development of pathogenic antibodies that recognize human (h) platelet factor 4 (PF4) complexed with various polyanions. While non-heparin anticoagulants and intravenous immunoglobulin (IVIG) are the mainstay of care, bleeding may develop, and risk of new thromboembolic events remain. We had described a mouse IgGκ2b antibody KKO that mimics the sentinel features of pathogenic HIT antibodies, including binding to the same neoepitope on hPF4:polyanion complexes. KKO, like HIT IgGs, activates platelets through FcγRIIA and induces complement activation. We now asked whether Fc-modified KKO can be used as a novel therapeutic to prevent or treat HIT. Using the endoglycosidase EndoS, we created deglycosylated KKO (DGKKO). DGKKO bound to PF4-polyanion complexes, and blocked FcγRIIA-dependent activation of PF4 treated platelets by KKO, 5B9 (another HIT-like monoclonal antibody), and isolated IgGs from HIT patients. DGKKO also decreased complement activation and deposition of C3c on platelets. Injection of DGKKO into “HIT mice” lacking mouse PF4, but transgenic for hPF4 and FcγRIIA, prevented and reversed thrombocytopenia when injected before or after KKO, 5B9 or HIT IgG, respectively, in a microfluidic system. DGKKO reversed antibody-induced thrombus growth in HIT mice. In contrast, DGKKO was ineffective in preventing thrombosis by IgG from a patient with the HIT-related disorder, vaccine-induced immune thrombotic thrombocytopenia. Thus, DGKKO may represent a new class of therapeutics for targeted treatment of patients with HIT.

Key Points

Deglycosylated (DG) KKO can reverse thrombocytopenia in a HIT murine model.

DGKKO can prevent/reverse thrombosisin vitroand in a HIT murine model.
Centriolar subdistal appendages promote double strand break repair through homologous recombination
Authors: Rodríguez-Real Guillermo , Domínguez-Calvo Andrés , Prados-Carvajal Rosario , Bayona-Feliú Aleix , Gomes-Pereira Sónia , Balestra Fernando R. , Huertas Pablo
Published: October 2022

The centrosome is a cytoplasmic organelle with roles in microtubule organization which has also been proposed to act as a hub for cellular signaling. Some centrosomal components are required for full activation of the DNA Damage Response. However, if the centrosome regulates specific DNA repair pathways is not known. Here, we show that centrosomes presence is required to fully activate recombination, specifically to completely license its initial step, the so-called DNA end resection. Furthermore, we identify a centriolar structure, the subdistal appendages, and a specific factor, CEP170, as the critical centrosomal component involved in the regulation of recombination and resection, albeit it does not control end-joining repair. Cells lacking centrosomes or depleted for CEP170 are, consequently, hyper-sensitive to DNA damaging agents. Moreover, low levels of CEP170 in multiple cancer types correlate with an increase of the mutation burden associated with specific mutational signatures and a better prognosis, suggesting that changes in CEP170 can act as a mutation driver but also could be targeted to improve current oncological treatments.
Carbon-atom hybridization tunes the halogen-bond strength in the series of DABCO·C2H2n
I2 (n = 0–2) cocrystals
Authors: Torubaev Yury , Skabitskiy Ivan
Published: October 2022

Two new cocrystals of 1,4-diazabicyclo[2.2.2]octane (DABCO, C6H12N2) with 1,2-diiodoethene (1,2-C2H2I2) and 1,2-diiodoethane (1,2-C2H4I2) complete a series of halogen-bond-assisted cocrystals which started with DABCO·C2I2 [Perkins et al. (2012). CrystEngComm, 14, 3033–3038]. The structural and computational analysis of this series illustrate the correlation between the polarization of the I atom and the hybridization of the C atom bound to it. The formation of a rather stable halogen bond by the alkylic iodide of saturated 1,2-C2H4I2 was unusual and respective cocrystals are formed only in nonpolar solvents, while, in the polar medium of acetonitrile, a very intense reaction of DABCO quaternization takes place resulting in 1-(2-iodoethyl)-4-aza-1-azoniabicyclo[2.2.2]octane triiodide, C8H16IN2
+·I3
− or [N(CH2CH2)3N–CH2CH2I][I3].
Unravelling the regulation pathway of photosynthetic AB-GAPDH
Authors: Marotta Roberto , Del Giudice Alessandra , Gurrieri Libero , Fanti Silvia , Swuec Paolo , Galantini Luciano , Falini Giuseppe , Trost Paolo , Fermani Simona , Sparla Francesca
Published: October 2022

Oxygenic phototrophs perform carbon fixation through the Calvin–Benson cycle. Different mechanisms adjust the cycle and the light-harvesting reactions to rapid environmental changes. Photosynthetic glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is a key enzyme in the cycle. In land plants, different photosynthetic GAPDHs exist: the most abundant isoform is formed by A2B2 heterotetramers and the least abundant by A4 homotetramers. Regardless of the subunit composition, GAPDH is the major consumer of photosynthetic NADPH and its activity is strictly regulated. While A4-GAPDH is regulated by CP12, AB-GAPDH is autonomously regulated through the C-terminal extension (CTE) of its B subunits. Reversible inhibition of AB-GAPDH occurs via the oxidation of a cysteine pair located in the CTE and the substitution of NADP(H) with NAD(H) in the cofactor-binding site. These combined conditions lead to a change in the oligomerization state and enzyme inhibition. SEC–SAXS and single-particle cryo-EM analysis were applied to reveal the structural basis of this regulatory mechanism. Both approaches revealed that spinach (A2B2)
n
-GAPDH oligomers with n = 1, 2, 4 and 5 co-exist in a dynamic system. B subunits mediate the contacts between adjacent tetramers in A4B4 and A8B8 oligomers. The CTE of each B subunit penetrates into the active site of a B subunit of the adjacent tetramer, which in turn moves its CTE in the opposite direction, effectively preventing the binding of the substrate 1,3-bisphosphoglycerate in the B subunits. The whole mechanism is made possible, and eventually controlled, by pyridine nucleotides. In fact, NAD(H), by removing NADP(H) from A subunits, allows the entrance of the CTE into the active site of the B subunit, hence stabilizing inhibited oligomers.
The #MeToo legacy and “the Collective Us”: conceptualising accountability for sexual misconduct at work
Authors: Goncharenko Galina
Published: October 2022

Purpose

This study aims to analyse how the collective processing of the #MeToo legacy in the form of community discourses and activism conceptualises organisational accountability for sexual misconduct at work and enhances the development of new accountability instruments.

Design/methodology/approach

The study draws on social movement theory and the intellectual problematics of accountability, together with the empirical insights from two research engagement projects established and facilitated by the author.

Findings

The study reveals multiple dimensions of how post-#MeToo community activism impacted the conceptualisation of organisational accountability for sexual misconduct at work. The movement enhanced discourses prompting a new societal sense of accountability for sexual wrongdoings. This in turn facilitated public demands for accountability that pressured organisations to respond. The accountability crisis created an opportunity for community activists to influence understanding of organisational accountability for sexual misconduct at work and to propose new accountability instruments advancing harassment reporting technology, as well as an enhancing the behavioural consciousness and self-assessment of individuals.

Originality/value

The study addresses a topic of social importance in analysing how community activism arising from a social movement has transformed accountability demands and thus both advanced the conceptualisation of organisational accountability for sexual misconduct at work and established socially desirable practices for it. The study contributes to theory by revealing the emancipatory potential of community activism to influence organisational accountability practices and to propose new instruments at a moment of organisational hesitation and crisis of accountability.
When work and life boundaries are blurred: the effect of after-hours work communication through communication technology on employee outcomes
Authors: Kim Katie Haejung , Chon Myoung-Gi
Published: October 2022

Purpose

As new work environments have been created and accelerated due to technological advances, after-hours work communication has become one of the prominent features of the technology-enabled work environment. Grounded in the conservation of resources theory, this study aims to uncover the effects of after-hours work communication through communication technologies on employees' burnout and extra-role behaviors.

Design/methodology/approach

The study conducted an online survey of 315 US full-time employees from a wide range of industrial sectors.

Findings

The findings of the study show that after-hours work communication through communication technologies increases employees' negative extra-role behaviors, specifically counterproductive work behavior and negative word-of-mouth. Furthermore, emotional exhaustion partially mediated the relationship between after-hours work communication and negative extra-role behaviors.

Practical implications

The study provides practical implications for an organization's effective optimization of work-related communication to overcome adverse consequences for employees and organizations. Corporate leaders and communication professionals are encouraged to establish clear guidelines related to the use of communication technologies after hours and exercise leadership practices to prevent after-hours communication through communication technologies from contributing to employees' burnout.

Originality/value

The findings enhance the understanding of the role of after-hours work communication through communication technologies in the workplace by revealing how the effects of after-hours work communication enabled by communication technologies on employees' psychological well-being spills over to organizational effectiveness.
The SECURE STAIRS framework: preliminary evaluation of formulation developments in the Children and Young People’s Secure Estate
Authors: McKeown Annette , Martin Aisling , Farooq Romana , Wilson Amy , Addy Chelsea , Kennedy Patrick J.
Published: October 2022

Purpose

The purpose of this paper is to evaluate pre- and post-formulation findings with multi-disciplinary staff within two secure children’s homes (SCHs) in the North East of England.

Design/methodology/approach

Multi-disciplinary staff teams involved in formulation across two SCHs were administered pre- and post-formulation questionnaires. The pre- and post-formulation questionnaires focused on five domains: knowledge; confidence; motivation; understanding; and satisfaction with treatment plan.

Findings

A total of 338 pre- and post-formulation questionnaires were administered across 43 formulation meetings. The highest proportion of formulation attendees were: residential staff (44%); mental health staff (17%); case managers (12%); and education staff (9%). Paired samples t-tests showed significant post-formulation improvements across all domains including: knowledge [t(337) = 22.65, p < 0.001]; confidence [t(337) = 15.12, p < 0.001]; motivation [t(337) = 8.27, p < 0.001]; understanding [t(337) = 19.13, p < 0.001]; and satisfaction [t(337) = 18.81, p < 0.001].

Research limitations/implications

The SECURE STAIRS framework has supported formulation developments across the Children and Young People’s Secure Estate. Preliminary findings within two SCHs suggest multi-disciplinary staff teams find psychologically informed formulation beneficial. Future directions are considered including future evaluation of young person involvement in formulation meetings.

Originality/value

There is a notable lack of existing research within the child and young people secure estate evaluating the impact of SECURE STAIRS trauma-informed care developments including the impact of team formulation. This paper adds to the evidence base.
Impact of internal corporate social responsibility: a parallel mediation analysis
Authors: Ranjan Sushant , Dash Sanket
Published: October 2022

Purpose

Workplace deviant behaviors (WDBs) have a significant negative impact on firms. Present study explores the role of employees’ perception of firms’ internal corporate social responsibility (internal CSR) in reducing their intention to engage in WDB. Social exchange theory (SET) and job demand-resource (JD-R) model form the conceptual underpinning of the study.

Design/methodology/approach

Hypotheses were developed based on a comprehensive literature review and tested on employees working in various public and private sector organizations in India. AMOS and SPSS PROCESS macro were used to test the conceptual model.

Findings

Employees’ perception of firms’ internal CSR reduced their intention to engage in WDB. Occupational strain was confirmed as a mediator in the above mentioned relationship. Further, the study also establishes internal CSR as an antecedent to increased perceptions of procedural justice.

Practical implications

Managers may leverage internal CSR communication as a tool to minimize WDB at the workplace. Moreover, it may also be used to reduce occupational strain and strengthen the perceptions of fairness among employees.

Originality/value

Very limited research is available on internal CSR and WDB. Through this study authors contribute to the nascent literature by affirming the negative relationship between internal CSR and WDB using the SET and JD-R model.
Different degree of loss‐of‐function among four missense mutations in the EDAR gene responsible for autosomal recessive hypohidrotic ectodermal dysplasia may be associated with the phenotypic severity
Authors: Yagi Sasagu , Yasuno Shuichiro , Ansai Osamu , Hayashi Ryota , Shimomura Yutaka
Published: October 2022

Hypohidrotic ectodermal dysplasia is a rare condition characterized by hypohidrosis, hypodontia, and hypotrichosis. The disease can show X‐linked recessive, autosomal dominant or autosomal recessive inheritance trait. Of these, the autosomal forms are caused by mutations in either EDAR or EDARADD. To date, the underlying pathomechanisms or genotype–phenotype correlations for autosomal forms have not completely been disclosed. In this study, we performed a series of in vitro studies for four missense mutations in the death domain of EDAR protein: p.R358Q, p.G382S, p.I388T, and p.T403M. The results revealed that p.R358Q‐ and p.T403M‐mutant EDAR showed different expression patterns from wild‐type EDAR in both western blots and immunostainings. NF‐κB reporter assays demonstrated that all the mutant EDAR showed reduced activation of NF‐κB, but the reduction by p.G382S‐ and p.I388T‐mutant EDAR was moderate. Co‐immunoprecipitation assays showed that p.R358Q‐ and p.T403M‐mutant EDAR did not bind with EDARADD at all, whereas p.G382S‐ and p.I388T‐mutant EDAR maintained the affinity to some extent. Furthermore, we demonstrated that all the mutant EDAR proteins analyzed aberrantly bound with TRAF6. Sum of the data suggest that the degree of loss‐of‐function is different among the mutant EDAR proteins, which may be associated with the severity of the disease.