bluuebunny/crossref_metadata_2025 huggingface dataset:
Different Purkinje cell pathologies cause specific patterns of progressive ataxia in mice
Authors: Jaarsma Dick , Birkisdóttir Maria B. , van Vossen Randy , Oomen Demi W.G.D. , Akhiyat Oussama , Vermeij Wilbert P. , Koekkoek Sebastiaan K.E. , De Zeeuw Chris I. , Bosman Laurens W.J.
Published: August 2023

Background

Gait ataxia is one of the most common and impactful consequences of cerebellar dysfunction. Purkinje cells, the sole output neurons of the cerebellar cortex, are often involved in the underlying pathology, but their specific functions during locomotor control in health and disease remain obfuscated.

Objectives

We aimed to describe the effect of gradual adult-onset Purkinje cell degeneration on gaiting patterns in mice and whether two different mechanisms that both lead to Purkinje cell degeneration caused different patterns in the development of gait ataxia.

Methods

Using the ErasmusLadder together with a newly developed limb detection algorithm and machine learning-based classification, we subjected mice to a physically challenging locomotor task with detailed analysis of single limb parameters, intralimb coordination and whole-body movement. We tested two Purkinje cell-specific mouse models, one involving stochastic cell death due to impaired DNA repair mechanisms (Pcp2-Ercc1-/-), the other carrying the mutation that causes spinocerebellar ataxia type 1 (Pcp2-ATXN1[82Q]).

Results

Both mouse models showed increasingly stronger gaiting deficits, but the sequence with which gaiting parameters deteriorated depended on the specific mutation.

Conclusions

Our longitudinal approach revealed that gradual loss of Purkinje cell function can lead to a complex pattern of loss of function over time, and this pattern depends on the specifics of the pathological mechanisms involved. We hypothesize that this variability will also be present in disease progression in patients, and our findings will facilitate the study of therapeutic interventions in mice, as very subtle changes in locomotor abilities can be quantified by our methods.
Zebrafishacta1bas a Candidate for Modeling Human Actin Cardiomyopathies
Authors: Prill Kendal , Ojehomon Matiyo , Sandhu Love , Young Sarah , Dawson John F.
Published: August 2023

Heart failure is the leading cause of mortality worldwide, primarily associated with cardiovascular disease. Many heart muscle diseases are caused by mutations in genes that encode contractile proteins, including cardiac actin mutations. Zebrafish are an advantageous system for modelling cardiac diseases due to their ability to develop without a functional heart throughout embryonic development. However, genome duplication in the teleost lineage poses a unique challenge by increasing the number of genes involved in heart development. Four actin genes are expressed in the zebrafish heart:acta1b, actc2, and duplicates ofactc1aon chromosomes 19 and 20. In this study, we characterize the actin genes involved in early zebrafish heart development usingin situhybridization and CRISPR targeting to determine the most suitable gene for modelling actin changes observed in human patients with heart disease. Theactc1aandacta1bgenes are predominantly expressed during embryonic heart development, resulting in severe cardiac phenotypes when targeted with CRISPR. Considering the duplication of theactc1agene, we recommendacta1bas the best gene for targeted cardiac actin research.
Antibody effector functions are required for broad and potent protection of neonates from herpes simplex virus infection
Authors: Slein Matthew D. , Backes Iara M. , Garland Callaghan R. , Kelkar Natasha S. , Leib David A. , Ackerman Margaret E.
Published: August 2023

The failure of multiple herpes simplex virus (HSV) vaccine candidates that induce neutralizing antibody responses raises the hypothesis that other activities, such as Fc domain-dependent effector functions, may be critical for protection. While neonatal HSV (nHSV) infection result in mortality and lifelong neurological morbidity in humans, it is uncommon among neonates with a seropositive birthing parent, suggesting the potential efficacy of antibody-based therapeutics to protect neonates. We therefore investigated the mechanisms of monoclonal antibody (mAb)-mediated protection in a mouse model of nHSV infection. Both neutralization and effector functions contributed to robust protection against nHSV-1. In contrast, effector functions alone were sufficient to protect against nHSV-2, exposing a functional dichotomy between virus types that is consistent with vaccine trial results. Together, these results emphasize that effector functions are crucial for optimal mAb-mediated protection, informing effective Ab and vaccine design, and demonstrating the potential of polyfunctional Abs as potent therapeutics for nHSV infections.Graphical abstract.

Mechanistic dissection of antibody-mediated protection from HSV.

Monoclonal antibodies (mAbs) with varying neutralizing potencies and Fc modifications that impact effector function were evaluated in wildtype (WT) and FcγR-/- mice to define mechanisms of antibody-mediated protection from HSV infection. To model human vulnerability to HSV disease during the neonatal period, neonatal mice were challenged with HSV, treated with mAb, and then assessed for morbidity and mortality. We observed that polyfunctional mAbs provide broader and more potent protection than antibodies with either low neutralization or low effector function. Moreover, while sufficient for protection against HSV-1, neutralization activity alone was unable to protect from HSV-2 infection.
Molecular Property Diagnostic Suite for COVID-19 (MPDSCOVID-19): An open access disease specific drug discovery portal
Authors: Priyadarsinee Lipsa , Jamir Esther , Nagamani Selvaraman , Mahanta Hridoy Jyoti , Kumar Nandan , John Lijo , Sarma Himakshi , Kumar Asheesh , Gaur Anamika Singh , Sahoo Rosaleen , Vaikundamani S. , Murugan N. Arul , Priyakumar U. Deva , Raghava G.P.S. , Bharatam Prasad V. , Parthasarathi Ramakrishnan , Subramanian V. , Sastry G. Madhavi , Sastry G. Narahari
Published: August 2023

Computational drug discovery is intrinsically interdisciplinary and has to deal with the multifarious factors which are often dependent on the type of disease. Molecular Property Diagnostic Suite (MPDS) is a Galaxy based web portal which was conceived and developed as a disease specific web portal, originally developed for tuberculosis (MPDSTB). As specific computational tools are often required for a given disease, developing a disease specific web portal is highly desirable. This paper emphasises on the development of the customised web portal for COVID-19 infection and is referred to as MPDSCOVID-19. Expectedly, the MPDS suites of programs have modules which are essentially independent of a given disease, whereas some modules are specific to a particular disease. In the MPDSCOVID-19portal, there are modules which are specific to COVID-19, and these are clubbed in SARS-COV-2 disease library. Further, the new additions and/or significant improvements were made to the disease independent modules, besides the addition of tools from galaxy toolshed. This manuscript provides a latest update on the disease independent modules of MPDS after almost 6 years, as well as provide the contemporary information and tool-shed necessary to engage in the drug discovery research of COVID-19. The disease independent modules include file format converter and descriptor calculation under the data processing module; QSAR, pharmacophore, scaffold analysis, active site analysis, docking, screening, drug repurposing tool, virtual screening, visualisation, sequence alignment, phylogenetic analysis under the data analysis module; and various machine learning packages, algorithms and in-house developed machine learning antiviral prediction model are available. The MPDS suite of programs are expected to bring a paradigm shift in computational drug discovery, especially in the academic community, guided through a transparent and open innovation approach. The MPDSCOVID-19can be accessed athttp://mpds.neist.res.in:8085.
Substrate-Specific Function of PNPLA3 Facilitates Hepatic VLDL-Triglyceride Secretion During Stimulated Lipogenesis
Authors: Johnson Scott , Bao Hanmei , McMahon Cailin , Chen Yongbin , Burr Stephanie , Anderson Aaron , Madeyski-Bengtson Katja , Lindén Daniel , Han Xianlin , Liu Jun
Published: August 2023

The I148M variant of PNPLA3 is strongly linked to hepatic steatosis. Evidence suggests a gain-of-function role for the I148M mutant as an ATGL inhibitor, leaving the physiological relevance of wild-type PNPLA3 undefined. Here we show that PNPLA3 selectively degrades triglycerides (TGs) enriched in polyunsaturated fatty acids (PUFAs) independently of ATGL in cultured cells and mice. Lipidomics and metabolite tracing analyses demonstrated that PNPLA3 mobilizes PUFAs from intracellular TGs for phospholipid desaturation, supporting hepatic secretion of TG-rich lipoproteins. Consequently, mice with liver-specific knockout or acute knockdown of PNPLA3 both exhibited aggravated liver steatosis and concomitant decreases in plasma VLDL-TG, phenotypes that manifest only under lipogenic conditions. I148M-knockin mice similarly displayed impaired hepatic TG secretion during lipogenic stimulation. Our results highlight a specific context whereby PNPLA3 facilitates the balance between hepatic TG storage and secretion and suggest the potential contributions of I148M variant loss-of-function to the development of hepatic steatosis in humans.

Summary Statement

We define the physiological role of wild type PNPLA3 in maintaining hepatic VLDL-TG secretion.
Strong genetic differentiation but limited niche partitioning in a sympatric species pair separated by an allochronic reproductive barrier
Authors: Irvine Mitchell , Stewart Zachary , Kumaran Nagalingam , Manawaduge Chapa G. , Ryan James , Balagawi Solomon , Missenden Brendan , Starkie Melissa , Clarke Anthony R. , Hurwood David , Prentis Peter
Published: August 2023

The combination of differential adaptation to ecological niches and the development of reproductive barriers are considered helpful for maintaining co-existing species. In the absence of one of these elements, species boundaries are expected to breakdown. The tephritid fruit fly species pair,Bactrocera tryoniandB. neohumeralis, have significant overlap in geographic range and host use, with time of day of male mating the only known difference in their mating systems. Using a combination of ecological (seasonal abundance, host use and habitat use) and genomic data, we tested the differing roles of competition and assortative mating on the maintenance of the species boundaries in this species pair. Genome-wide SNP analyses found strong genetic differentiation between the species with no evidence for hybridization in the field. Most outlier SNPs were restricted to narrow regions towards the centromeres and telomeres of chromosomes and high nucleotide diversity rates were observed throughout the chromosomes of both species. Enrichment of annotation terms indicated an overabundance of genes with the ‘abnormal neuroanatomy’ term. Terms of interest associated with sleep and circadian rhythm, potentially important to the allochronic reproductive barrier, were non-enriched. Ecological data found limited evidence for ecological differentiation between the two species based on significant positive correlations between species numbers trapped at different times of the year, trapped in different habitats within a region, or when reared from fruit.

Our study highlights the significance of assortative mating over ecological differentiation for sympatric maintenance of theB. tryoni/B. neohumeralissibling pair.
The early communication stages between serine proteases and enterovirus capsids in the race for viral disintegration
Authors: Corre Marie-Hélène , Rey Benjamin , David Shannon C. , Torii Shotaro , Chiappe Diego , Kohn Tamar
Published: August 2023

Enteroviruses are human pathogens known to challenge water safety1,2. Among the microbial stressors found in water, bacterial serine proteases contribute to the control of enterovirus persistence3. However, the structural interactions accounting for the susceptibility of enteroviruses to proteases remains unexplained. Here, we describe the molecular mechanisms involved in the recruitment of serine proteases to viral capsids. Among the virus types used, coxsackievirus A9 (CVA9), but not CVB5 and echovirus 11 (E11), was inactivated by Subtilisin A in a host-independent manner, while Bovine Pancreatic Trypsin (BPT) only reduced CVA9 infectivity in a host-dependent manner. Predictive interaction models of each protease with capsid protomers indicate the main targets as internal disordered protein (IDP) segments exposed either on the 5-fold vertex (DE loop VP1) or at the 5/2-fold intersection (C-terminal end VP1) of viral capsids. We further show that a functional binding protease/capsid depends on both the strength and the evolution over time of protease-VP1 complexes, and lastly on the local adaptation of proteases on surrounding viral regions. Finally, we identified three residues on CVA9 capsid that trigger cleavage by Subtilisin A, one of which acts as a sensor residue contributing to enzyme recognition on the DE loop. Overall, this study describes an important biological mechanism involved in enteroviruses biocontrol.
PQS and Pyochelin inPseudomonas aeruginosaShare Inner Membrane Transporters to Mediate Iron Uptake
Authors: Zhang Heng , Yang Jianshe , Cheng Juanli , Zeng Jing , Ma Xin , Lin Jinshui
Published: August 2023

Bacteria uptake different forms of iron through various channels to meet their needs. Our previous studies have shown that TseF, a type VI secretion system effector for Fe uptake, facilitates the delivery of outer membrane vesicle (OMV)-associated PQS-Fe3+to bacterial cells by involving the Fe(III) pyochelin receptor FptA and the porin OprF. However, the form in which the PQS-Fe3+complex enters the periplasm and how it is taken up into the cytoplasm remain unclear. Here, we first demonstrate that the PQS-Fe3+complex enters the cell directly through FptA or OprF. Next, we find that inner membrane transporters such as FptX, PchHI, and FepBCDG are not only necessary forP. aeruginosato uptake PQS-Fe3+and PCH-Fe3+, but also necessary for the virulence ofP. aeruginosatowardGalleria mellonellalarvae. Furthermore, we suggest that the function of PQS-Fe3+(but not PQS)-mediated quorum-sensing regulation is dependent on FptX, PchHI, and FepBCDG. Additionally, the findings indicate that, unlike FptX, both FepBCDG and PchHI play no role in the autoregulatory loop involving PchR, but further deletion offepBCDGandpchHIcan reverse the inactive PchR phenotype caused byfptXdeletion and reactivate the expression of the PCH pathway genes under iron-limited conditions. Finally, this work detected the interaction between FptX, PchHI, and FepBCDG, indicating that a larger complex could be formed to mediate uptake of PQS-Fe3+and PCH-Fe3+. These results pave the way for a better understanding of the PQS and PCH iron uptake pathway, and provide future directions to tackleP. aeruginosainfections.

IMPORTANCE

Iron is a key factor forP. aeruginosato break through the host’s defense system and successfully infect. To acquire the necessary iron from the host,P. aeruginosahas evolved a number of strategies, the most common being the synthesis, secretion, and uptake of siderophores such as pyoverdine, pyochelin, and the quorum-sensing signaling molecule PQS. However, despite intensive studies of the siderophore uptake pathways ofP. aeruginosa, our understanding of how siderophores transport iron across the inner membrane into the cytoplasm is still far from complete. Here, we reveal that PQS and pyochelin inP. aeruginosashare inner membrane transporters such as FptX, PchHI and FepBCDG to mediate iron uptake. Meanwhile, PQS and pyochelin-mediated signaling operates to a large extent via these inner membrane transporters. Our study revealed an interesting phenomenon of shared uptake pathways between PQS and pyochelin, which will lead us to reexamine the role of these two molecules in the iron uptake and virulence ofP. aeruginosa.
Copy number variation alters local and global mutational tolerance
Authors: Avecilla Grace , Spealman Pieter , Matthews Julia , Caudal Elodie , Schacherer Joseph , Gresham David
Published: August 2023

Copy number variants (CNVs), duplications and deletions of genomic sequences, contribute to evolutionary adaptation but can also confer deleterious effects and cause disease. Whereas the effects of amplifying individual genes or whole chromosomes (i.e., aneuploidy) have been studied extensively, much less is known about the genetic and functional effects of CNVs of differing sizes and structures. Here, we investigatedSaccharomyces cerevisiae(yeast) strains that acquired adaptive CNVs of variable structures and copy numbers following experimental evolution in glutamine-limited chemostats. Although beneficial in the selective environment, CNVs result in decreased fitness compared with the euploid ancestor in rich media. We used transposon mutagenesis to investigate mutational tolerance and genome-wide genetic interactions in CNV strains. We find that CNVs increase mutational target size, confer increased mutational tolerance in amplified essential genes, and result in novel genetic interactions with unlinked genes. We validated a novel genetic interaction between different CNVs andBMH1that was common to multiple strains. We also analyzed global gene expression and found that transcriptional dosage compensation does not affect most genes amplified by CNVs, although gene-specific transcriptional dosage compensation does occur for ∼12% of amplified genes. Furthermore, we find that CNV strains do not show previously described transcriptional signatures of aneuploidy. Our study reveals the extent to which local and global mutational tolerance is modified by CNVs with implications for genome evolution and CNV-associated diseases, such as cancer.
A novel energetic cocrystal of DATNBI/TNT with low sensitivity and an unexpected polymorphic transition
Authors: Wang Zhiqiang , Xu Jinjiang , Zhao Zhi , Zhang Zhenqi , Tong Yi
Published: August 2023

A novel type of 4,4′,5,5′-tetranitro-1H,1′H-(2,2′-biimidazole)-1,1′-diamine (DATNBI)/TNT energetic cocrystal (cocrystal-1) was prepared by the solvent evaporation method. The molar ratio of the cocrystal is 1:2 and the crystal density is 1.784 g cm−3 at 23°C. It belongs to the triclinic system with space group P
1. The thermal stability, mechanical sensitivity and detonation performance of cocrystal-1 were studied. Compared with DATNBI, the mechanical sensitivity (H
50 and FS, friction sensitivity) and thermal stability (T
d, detonation temperature) of cocrystal-1 were significantly improved (H
50, FS and T
d of DATNBI and cocrystal-1 are, respectively, 27.8 cm, 160 N, 240°C and 65.6 cm, >360 N, 253°C). Combining these results with other characterizations, it was found that cocrystal-1 exhibited a polymorphic transformation, phase separation and melting of the two single components in succession. The ability to control the properties and understand the structural stability of this explosive cocrystal is of great value.
Audit committees in public companies listed on the Warsaw Stock Exchange: compliance with hard law in practice
Authors: Gad Jacek
Published: August 2023

Purpose

The article aims to determine the implementation extent of the regulations around appointment and characteristics of audit committees and regulations concerning disclosure of information about the audit committee in Polish practice.

Design/methodology/approach

The author analyzed the informative content of management reports and corporate governance statements. The survey covered all domestic companies listed on the Warsaw Stock Exchange in the years from 2017 to 2021.

Findings

The new guidelines resulting from hard law had a significant impact on the corporate governance on the Polish capital market. According to the research results, over the analyzed years, the share of companies listed on the Warsaw Stock Exchange, which appointed an audit committee within the supervisory board, clearly increased. Moreover, the research found that in the period under study, not all companies fulfilled the obligation to disclose information about the audit committee resulting from hard law. In particular, this applies to disclosures on how the members of the audit committee acquired competencies in the area of accounting.

Practical implications

The article concerns the operation of the audit committee in public companies listed on the Polish capital market. The study can serve as a reference point for further research on corporate governance. The results of the research may be an indication for those who create legal solutions in the area of corporate governance.

Originality/value

This is the first such comprehensive study on the characteristics of the audit committee and disclosures about the audit committee resulting from the introduction of hard law in this area.
How ambidextrous leadership enhances employee creativity: a quantitative approach
Authors: Yasmeen Aiza , Ajmal Saran Khan
Published: August 2023

Purpose

Based on the leader-members exchange (LMX) theory, the purpose of this paper is to examine the impact of ambidextrous leadership on employee creativity through ambidextrous behavior. The study also investigates an organizational culture that amplifies the positive influence of ambidextrous leadership on employee creativity.

Design/methodology/approach

Primary data were collected form 300 permanent employees of the local government department of Azad Jammu and Kashmir (AJK). Hypotheses were tested by using Hayes PROCESS macro.

Findings

Results indicated that ambidextrous style of leadership and employee creativity is mediated by ambidextrous behavior of employees. The findings of the study also established the fact that the relationship of ambidextrous leadership and employee creativity is subject to the organizational culture.

Research limitations/implications

The current study was carried out in the local government department; researchers can conduct research by studying multiple government departments at once. In addition, the present study is cross-sectional; scholars in future can take a longitudinal approach to capture employee creativity at different points of time.

Practical implications

For establishing a welcoming innovation atmosphere and assist workers' creative behaviors, ambidextrous leadership should be practiced by leaders from day-to-day operations. Leaders must create flexible abilities to adapt internal resources (knowledge and values) in the public sector into new behavioral patterns that encourage employee creativity.

Originality/value

This is the first study that investigates the ambidextrous behavior as a vital intervening mechanism in the ambidextrous leadership–employee creativity linkage. Further, this study provides first empirical evidence by study the organizational culture as a moderator in determine the impact of ambidextrous leadership on employee creativity.
Assessing the impact of COVID-19 on architectural education: a case study of Jordanian Universities
Authors: Alhusban Ahmad A. , Alhusban Safa A. , Alhusban Mohammad-Ward A.
Published: August 2023

Purpose

This research aimed to define the factors that may impact the effectiveness of online architectural education during COVID-19 and to examine the degree of students' and instructors' satisfaction with these factors among Jordanian governmental universities. Further, the research examines the relationships/interrelationships between the degree of their satisfaction with these factors and the students' and instructors' age, gender, education level, home size, and family size.

Design/methodology/approach

Different research methods were used to achieve the research purposes, including semi-structured interviews, online questionnaires and reviewing recent literature. This research used descriptive statistics and Pearson product-moment correlation coefficient (Pearson r) to analyze the data.

Findings

This research found that online architectural education during COVID-19 was stressful. It was ineffective in teaching practical architectural courses like design and negatively affected the architectural learning process and outcomes. In contrast, the online teaching of architectural theoretical courses was reliable and convenient if the students and instructors had intentional, sufficient technological and appropriate resources. Online architectural education negatively affected the students' design ability and skills, peer review, intended learning outcomes (ILOs) achievements, the quality of feedback, workload, interaction mode, participation, collaboration, productivity and increased cheating on online exams. The home environment was unsuitable for online architectural education. Family interventions, privacy, home size and family size significantly influence online architectural education's effectiveness.

Originality/value

Students' and instructors' satisfaction determines the continuity of using online teaching mode, which depends on information quality, system quality, service quality, perceived ease of use, perceived usefulness, achieved intended learning outcomes, cognitive absorption, skills, motivation, engagement, implementing resources and strategies and positive emotions as hope and enjoyment. Students' and instructors' satisfaction reflects how they view their learning experience, which is crucial in assessing the effectiveness of online education quality that focuses on the context, input, process and product, which is still not clearly understood, particularly for developing countries.
Prediction of storey drift for reinforced concrete structures subjected to pulse-like ground motions using machine learning classification models
Authors: Wani Faisal Mehraj , Vemuri Jayaprakash , Chenna Rajaram
Published: August 2023

Purpose

Near-fault pulse-like ground motions have distinct and very severe effects on reinforced concrete (RC) structures. However, there is a paucity of recorded data from Near-Fault Ground Motions (NFGMs), and thus forecasting the dynamic seismic response of structures, using conventional techniques, under such intense ground motions has remained a challenge.

Design/methodology/approach

The present study utilizes a 2D finite element model of an RC structure subjected to near-fault pulse-like ground motions with a focus on the storey drift ratio (SDR) as the key demand parameter. Five machine learning classifiers (MLCs), namely decision tree, k-nearest neighbor, random forest, support vector machine and Naïve Bayes classifier , were evaluated to classify the damage states of the RC structure.

Findings

The results such as confusion matrix, accuracy and mean square error indicate that the Naïve Bayes classifier model outperforms other MLCs with 80.0% accuracy. Furthermore, three MLC models with accuracy greater than 75% were trained using a voting classifier to enhance the performance score of the models. Finally, a sensitivity analysis was performed to evaluate the model's resilience and dependability.

Originality/value

The objective of the current study is to predict the nonlinear storey drift demand for low-rise RC structures using machine learning techniques, instead of labor-intensive nonlinear dynamic analysis.
Investigating the conceptual link between appearance-related self-discrepancies and retail therapy shopping behavior through motivational routes
Authors: Lee Jonggeun , Sadachar Amrut
Published: August 2023

Purpose

The purpose of this study was to propose and examine a conceptual model delineating how two different types of appearance-related self-discrepancies (i.e. the ideal appearance self-discrepancy vs. the ought appearance self-discrepancy) influence retail therapy shopping behavior through motivational route (i.e. approach motivation vs. avoidance motivation).

Design/methodology/approach

This study utilized the online survey for data collection. Using a national sample of 532 US consumers who had retail therapy shopping experience, the conceptual model was tested through various statistical techniques, including confirmatory factor analysis, exploratory factor analysis and structural equation modeling.

Findings

Results revealed that the ought appearance self-discrepancy positively influenced retail therapy shopping behavior through avoidance motivation and emotion-focused coping strategy, whereas the ideal appearance self-discrepancy did not influence retail therapy shopping behavior. The results also suggested that the effect of two different types of appearance-related self-discrepancies on motivations in retail therapy shopping context varied depending on the gender (i.e. male vs. female).

Originality/value

Results suggest implications regarding potential target market strategies to retailers and provide a better understanding of retail therapy shoppers' characteristics and psychological mechanisms for consumer researchers.
ChlOR, a GMC family oxidoreductase that evolved independently from the actinomycete, confers resistance to amphenicol antibiotics
Authors: Qian Yingying , Cheng Minggen , Lai Lin , Zhou Jing , Zylstra Gerben J. , Huang Xing
Published: August 2023

Overuse of the amphenicol antibiotics chloramphenicol (CHL) and thiamphenicol (TAP) poses a great threat to ecosystem safety and human health. The strain, Nocardioides sp. LMS‐CY, Nocardioides sp. QY071 and Nocardioides sp. L‐11A, classified as a gram‐positive actinomycete, harbours a complete CHL metabolic pathway. However, the metabolic genes (clusters) involved in the entire pathway in gram‐positive actinomycetes are still limited. Here, chlORLMS, chlORQY071 and chlORL‐11A completely from the actinomycete Nocardioides spp. were found to act on the C1‐OH of the CHL/TAP side chain, directly converting CHL/TAP to 4‐nitrobenzaldehyde (PNBD)/4‐methylsulfonyl benzaldehyde (PMBD) and transforming PNBD/PMBD into 4‐nitrobenzyl alcohol (PNBM)/4‐methylsulfonyl phenyl methanol (PMBM). Furthermore, oxidoreductases can transform PNBM into 4‐nitrobenzoate (PNBA). The oxidoreductases ChlORLMS, ChlORQY071 and ChlORL‐11A were all classified as cellobiose dehydrogenases from the glucose methanol choline (GMC) family. Based on the Swiss‐Prot database, ChlORQY071 exhibited a lower identity (27.12%–35.10% similarity) with the reported oxidoreductases. Enzymatic and molecular docking analyses showed that ChlORQY071 and ChlORL‐11A from the two similar genomes were remarkably more effective in metabolizing CHL than ChlORLMS. Overall, the detailed resistance mechanism of CHL/TAP by actinomycete strains isolated from soil and livestock manure will provide insights into the occurrence of CHL/TAP resistance genes in the environment, resistance risk and bioremediation of CHL/TAP‐contaminated environments.
Living a ‘Digital Life’ and ready to cope with crises? Highlighting young adults' conceptions of crisis and emergency preparedness
Authors: Eriksson Mats
Published: August 2023

Increasing numbers of people are spending more and more time in digital landscapes, with many still unknown consequences for crisis and emergency management. This exploratory, in‐depth, qualitative interview study (N = 14) explores conceptions about local and individual crisis and emergency preparedness among a small group of young adults representing the most digitally savvy generation in Sweden. The results show that the respondents exhibit a complex and ambivalent attitude to crisis and emergency preparedness issues. Considering their digital habits and skills, the respondents emphasise their own responsibility, social ties, and expectations of help from the authorities and the local community when describing how they intend to face and manage a crisis in practice. This exploratory study contributes preliminary and tentative theoretical knowledge to a highly limited body of work specifically addressing citizens' crisis and emergency preparedness in a digitalized world.
Retrospective observational study of changes in serum cytokines and adiponectin with continuous plasma exchange with dialysis therapy for severe COVID‐19
Authors: Suzuki Yuya , Nakae Hajime , Satoh Kasumi , Hirasawa Nobuhisa , Kameyama Komei , Irie Yasuhito , Kitamura Toshiharu , Nara Tasuku , Maeno Kyohei , Yoshida Kenji , Okuyama Manabu
Published: August 2023

Introduction

Coronavirus disease 2019 (COVID‐19) is associated with a marked increase in the inflammatory cytokines, IL‐6 and IL‐18. Blood purification therapy aimed at controlling cytokines is one treatment option; however, evidence of its effectiveness is needed. Plasma exchange with dialysis (PED) is a blood purification method involving selective plasma exchange with dialysate flowing through the outer hollow fiber of the plasma separator. In this retrospective study, we investigated the efficacy of continuous PED (cPED) over 48 h in five patients with severe COVID‐19.

Methods

We assessed changes in IL‐6 and IL‐18, as well as adiponectin (APN).

Results

There were no significant differences in changes in IL‐6 and IL‐18, but there was a marked improvement in cases with abnormally high IL‐6 and IL‐18 levels at baseline. APN, which inhibits inflammatory cytokines, was significantly elevated post‐cPED.

Conclusion

Our results suggest that cPED therapy is an effective treatment for COVID‐19.
Mapping stream and floodplain geomorphometry with the Floodplain and Channel Evaluation Tool
Authors: Hopkins Kristina G. , Ahmed Labeeb , Claggett Peter R. , Lamont Samuel , Metes Marina J. , Noe Gregory B.
Published: August 2023

Broad‐scale mapping of stream channel and floodplain geomorphic metrics is critical to improve the understanding of geomorphic change, biogeochemical processes, riverine habitat quality, and opportunities for management intervention. The Floodplain and Channel Evaluation Tool (FACET) was developed to provide an open‐source tool for automated processing of digital elevation models (DEMs) to generate regional‐scale estimates of bank height, channel width, floodplain width, and a suite of other fluvial geomorphic dimensions that can be summarized at the stream reach‐ or catchment‐scale. FACET was tested on 3‐m DEMs covering the Delaware River watershed and 85% of the Chesapeake Bay watershed in the United States (U.S.) and on 1‐m DEMs for a subset of the study area. Accuracy was assessed from data collected at 67 field sites in the study area. FACET successfully measured geomorphometry for over 270,000 stream reaches (88% of streams attempted) in the study area. Factors that reduced the ability of FACET to accurately estimate geomorphic metrics included errors in DEM hydro‐conditioning, gradually sloping banks, incised stream channels, and the use of fixed input parameters to define buffer lengths. Even with these limitations, FACET was able to map regional patterns in stream and floodplain geomorphometry providing a robust dataset that can enhance modeling and management efforts throughout the mid‐Atlantic region, U.S.
The interplay of episodic power in enabling and coercive budgetary designs in universities: A case study
Authors: Seneviratne Chaturika , Hoque Zahirul
Published: August 2023

This paper explores how power exercised at the individual level within existing power relations in a university influences its enabling and coercive budgeting forms. A qualitative case study in a Sri Lankan university involved interviews and document analysis. Findings demonstrate the dominance of coercive controls over enabling controls in the university due to the power and influence of dominant individuals stemming from ongoing struggles among those pursuing diverse interests and strategic actions. We contribute to the literature by demonstrating how power is mobilised by actors and its impact on the variations of the enabling and coercive budgetary forms and practice.
Abdominal aortic branches of red‐rumped agouti (Dasyprocta leporina Linnaeus, 1758)
Authors: Tertulino Moisés Dantas , de Sousa Ana Caroline Freitas Caetano , Gurgel João Vitor de Oliveira , Lopes Igor Renno Guimarães , Diniz João Augusto Rodrigues Alves , de Paula Valéria Veras , de Paula Antunes João Marcelo Azevedo , de Oliveira Radan Elvis Matias , de Oliveira Moacir Franco
Published: August 2023

Understanding the cardiovascular system is fundamental in diagnosing pathologies and interpreting exams, such as contrast radiographs. In this context, the present study describes the collateral abdominal aorta artery branches of red‐rumped agouti. Ten red‐rumped agoutis, six males and four females, were assessed. The vascular system was perfused with Neoprene 450 latex coloured with a yellow pigment, dissected and analysed. Three euthanized animals were perfused with a barium sulfate solution (1 g mL−1) associated with latex Neoprene 450 at a 1:3 ratio to obtain contrast‐enhanced radiographs. The abdominal aorta emitted the celiac artery, which in turn originated the left gastric, hepatic and splenic arteries. The second collateral branch comprised the cranial mesenteric artery, followed by the renal arteries, which emitted the adrenal arteries, with the caudal emergence of the gonadal arteries. The caudal mesenteric artery appeared in a caudal direction. The abdominal aorta divided after reaching the pelvic cavity entrance, originating the right and left common iliac arteries. Before its bifurcation, the abdominal aorta dorsocaudally emitted its last collateral branch, the median sacral artery. The collateral branches of the aorta, therefore, resemble previously described rodent patterns, with few variations.
Australian rural medical students' perceived readiness for work as a junior doctor: A cross‐sectional national survey
Authors: Graham Patrick , Padley James , Williams Susan , Gonzalez‐Chica David , Isaac Vivian , Walters Lucie
Published: August 2023

Objective

To report self‐perceived readiness for work as a junior doctor in a national cohort of rural clinical school students.

Design

Cross‐sectional study using a self‐report questionnaire. Independent variables included 14 individual readiness items related to clinical and professional tasks, sociodemographic data and reported experience of rural clinical school (RCS) training. Participants were 668 medical students (55.3% females) completing a full academic year in rural Australia. Multivariable analysis explored factors associated with overall readiness for work as a junior doctor.

Findings

86% agreed that RCS experience prepared them to undertake the roles and responsibilities of a junior doctor. Self‐ratings for specific clinical and professional tasks varied from a mean score of 5.9–8.0 out of 10, and 13 of the 14 items were associated with the outcome (p‐value <0.001, except for performing spirometry). Lowest readiness scores were seen for some aspects including raising concerns about a colleague (mean score 6.1) or responding to workplace bullying (mean score 6.0). Aspects of the RCS experience that were strongly associated with overall readiness included: feeling a valued team‐member (OR 9.28, 95%CI 2.43–35.39), feeling well‐supported academically (OR 6.64, 95%CI 3.39–13.00), having opportunity for unsupervised but supported clinical practice (OR 4.67, 95%CI 1.45–15.00), having a rural mentor (OR 3.38, 95%CI 1.89–6.06) and having a previous health professional qualification (OR 2.7, 95%CI 1.32–5.54).

Discussion

Most RCS students felt ready for work as a junior doctor. Important aspects of RCS experience are likely to include students feeling integrated within the clinical team and having opportunities for authentic clinical roles. There remains a significant challenge for medical school curricula to address professional areas where graduates felt less prepared.
Realms unseen
Authors: Saffitz Jane L.
Published: August 2023

Since 2006, albinism has emerged as both a subject and an object of contestation in Tanzania and beyond. An abiding global narrative purports that, as a recessively inherited condition, albinism is fetishized by Africans who falsely attribute otherworldly potentials to albino body parts and commodify them in a grisly market run by “traditional” healers and their patrons. In response, translocal albinism rights stakeholders have formed to cement a singular notion of albinism and, with “it,” a notion of unseen power that cancels the agency of particular nonhumans. Their work diverges from those who insist on multiple other instantiations of albinism and worlds unseen, some of which offer compelling explanations of recent violence rooted in entanglement and complicity, rather than an Indigenous cosmology. In this context, I argue for a conceptual and methodological approach to social movements and minority groups rooted in decolonizing unseen realms and embracing epistemic and ontological openness.
Do I care for you more when you really need help? An experimental test of the effect of clinical urgency on compassion in health care
Authors: Pavlova Alina , Paine Sarah‐Jane , Cavadino Alana , O'Callaghan Anne , Consedine Nathan S.
Published: August 2023

Objectives

To experimentally investigate whether more urgent patient presentations elicit greater compassion from health care professionals than less urgent, facilitating future research and thinking to address systemic barriers to compassion in health care.

Design

This is a pre‐registered online study with an experimental, within‐subjects repeated‐measure study design. Two clinical vignettes that systematically varied the urgency of patient presentation were utilized. Both vignettes depicted a patient with difficult behaviours typically associated with lower compassion.

Methods

Health care professionals (doctors, nurses and allied health practitioners) recruited from all 20 District Health Boards across Aotearoa/New Zealand completed two vignettes in a counterbalanced order. Paired‐samplet‐tests were used to test the effect of the presentation urgency on indices of compassion.

Results

A total of 939 participants completed the vignettes (20% doctors, 47%, nurses and 33% allied health professionals). As expected, participants reported greater care and motivation to help the more urgent patient. However, the more urgent patient was also perceived as less difficult, and exploratory analyses showed that perceived patient difficulty was associated with lower caring and motivation to help, particularly in the less urgent patient.

Conclusions

This is the first work to experimentally test the relationship between the urgency of patient presentation and compassion in health care. Although the association between urgency and difficulty is complex, our findings are consonant with evolutionary views in which urgent distress elicits greater compassion. A system‐wide orientation towards efficiency and urgency may exacerbate this ‘bias’ which must be addressed to ensure more equitable compassion in health care.
Experience matters: The mediating role of gameful experience in the relationship between gamified competition and perceived innovation culture
Authors: Schmidt Corinna Vera Hedwig , Manske Jonas , Flatten Tessa Christina
Published: August 2023

Employees perceiving their organizational culture as innovative increase their output and enhance company performance. A potential approach to improving employees' perception of an innovation culture involves implementing gamified competition in the workplace. Despite the numerous studies on gamified competition, its relationship with employees' perceived innovation culture and the role of their gameful experience remains unclear. On the basis of affordance theory, we explain how gamified competition increases employees' perceived innovation culture (inter‐perception) through the mechanism of gameful experiences (intra‐perception). We survey a sample of 382 sales employees from German credit institutions who work with a gamified sales application. With the use of structural equation modelling, we find that gamified competition is positively related to perceived innovation culture. However, when including the mediator, results show that employees' gameful experience fully mediates the relationship between gamified competition and perceived innovation culture. Our study underlines the need for research to shift to an experience‐oriented employee perspective that will enable a better understanding of the impact a gamified competition has on employees' perceptions. Our findings can help managers to design, predict, and adapt gamified competition in the workplace.
Organisational climate and change‐orientated behaviour: The mediating effects of employee learning culture and perceptions of performance appraisal
Authors: Gil Alfonso J. , Mataveli Mara , Garcia‐Alcaraz Jorge L. , Ibanez‐Somovilla Laura
Published: August 2023

The characteristics of the working environment, particularly organisational climates, serve as fundamental tools for interpreting change‐orientated behaviour. However, examining employees' norms and attitudes would help clarify the guidelines for supporting organisational change. The present study has two objectives: first, to analyse the effect of organisational climate on change‐orientated behaviour, and secondly, to analyse the multiple mediation effect of both employee learning culture and perceptions of performance appraisal between the organisational climate and change‐orientated behaviour. A questionnaire was distributed to a sample of 359 employees in Spain. The research model was tested using partial least squares structural equation modelling. Organisational climate was found to have a positive effect on change‐orientated behaviour. Employee learning culture and perceptions of performance appraisal also partly mediated organisational climate and change behaviour. This work shows the importance of organisational climates in the development of employees' behaviour towards change.
Genetic lineage tracing in skin reveals predominant expression of HEY2 in dermal papilla during telogen and that HEY2+ cells contribute to the regeneration of dermal cells during wound healing
Authors: Wang Yan‐Ge , Yuan Vicky Lan , Liao Xin‐Hua
Published: August 2023

Dermal papilla (DP) cells are specialized mesenchymal cells that play a crucial role in regulating hair morphology, colour and growth through the secretion of specific factors. It is still unclear what the source of progenitor cells is for dermal cell regeneration during wound healing, and whether DP cells are involved in this process. We analyzed the gene expression profile of various skin cell populations using existing datasets and found that the Hey2 gene was predominantly expressed in DP cells. We introduced Hey2‐CreERT2 knockin mice and crossed them with Rosa26‐ZsGreen reporter mice. After induction in the double transgenic mice by administration of tamoxifen, the reporter ZsGreen was found to be predominantly expressed in DP cells both at anagen and telogen phases, and broadly expressed in some other dermal cells at anagen. We also created a wound after tamoxifen induction, and found there were abundant ZsGreen+ cells in the regenerated dermis. We conclude that the HEY2+ DP cells and dermal cells exhibit some stemness properties and can contribute to the dermal cell regeneration during wound healing.