bluuebunny/crossref_metadata_2025 huggingface dataset:
Conserved satellite DNA motif and lack of interstitial telomeric sites in highly rearranged AfricanNothobranchiuskillifish karyotypes
Authors: Lukšíková Karolína , Pavlica Tomáš , Altmanová Marie , Štundlová Jana , Pelikánová Šárka , Simanovsky Sergey A. , Krysanov Eugene Yu. , Jankásek Marek , Hiřman Matyáš , Reichard Martin , Ráb Petr , Sember Alexandr
Published: March 2023

Repetitive DNA may have significant impact on genome evolution. African annual killifishes of the genusNothobranchius(Teleostei: Nothobranchiidae), which has adapted to temporary water pools in African savannahs, possess genomes with high repeat content. They are also characterized by rapid karyotype and sex chromosome evolution but the role of genome repeats in these processes remains largely unknown. Here, we analyzed the distribution of telomeric (TTAGGG)nrepeat and Nfu-SatC satellite DNA (isolated formerly fromN. furzeri) by fluorescencein situhybridization in representatives across theNothobranchiusphylogeny (15 species), and withFundulosoma thierryias an outgroup. All analyzed taxa shared the presence of Nfu-SatC repeat but with diverse organization and distribution on chromosomes (from small clusters scattered genome-wide, to large localized accumulations, or a combined pattern). Nfu-SatC landscape was similar in conspecific populations ofN. guentheriandN. melanospilusbut slightly-to-moderately differed between populations ofN. pienaari, and between closely relatedN. kuhntaeandN. orthonotus. Inter-individual variability in Nfu-SatC patterns was found inN. orthonotusandN. krysanovi, including distinct segments present often in heterozygous condition. We revealed mostly no sex-linked patterns of studied repeat’s distribution in any of the sampled species including those with known sex chromosomes. Only inN. brieni(having an X1X2Y multiple sex chromosome system), Nfu-SatC probe covered substantial portion of the Y chromosome, similarly as formerly found inN. furzeriandN. kadleci(XY sex chromosomes), sister species not closely related toN. brieni. All studied species further shared patterns of telomeric FISH, with expected signals at the ends of all chromosomes and no additional interstitial telomeric sites. In summary, we revealed i) the presence of conserved satDNA class inNothobranchiusclade (a rare pattern among ray-finned fishes), ii) independent trajectories ofNothobranchiussex chromosome diferentiation, with recurrent and convergent accumulation of Nfu-SatC on the Y chromosome in some species, and iii) genus-wide shared propensity to loss of telomeric repeats during the mechanism of interchromosomal rearrangements. Collectively, our findings advance our understanding of genome structure, mechanisms of karyotype reshuffling and sex chromosome differentiation inNothobranchiuskillifishes from the genus-wide perspective.
k-mer-based GWAS enhances the discovery of causal variants and candidate genes in soybean
Authors: Lemay Marc-André , de Ronne Maxime , Bélanger Richard , Belzile François
Published: March 2023

Genome-wide association studies (GWAS) are powerful statistical methods that detect associations between genotype and phenotype at genome scale. Despite their power, GWAS frequently fail to pinpoint the causal variant or the gene controlling a trait at a given locus in crop species. Assessing genetic variants beyond single-nucleotide polymorphisms (SNPs) could alleviate this problem, for example by including structural variants (SVs). In this study, we tested the potential of SV-andk-mer-based GWAS in soybean by applying these methods to 13 traits. We also performed conventional GWAS analysis based on SNPs and small indels for comparison. We assessed the performance of each GWAS approach based on results at loci for which the causal genes or variants were known from previous genetic studies. We found thatk-mer-based GWAS was the most versatile approach and the best at pinpointing causal variants or candidate genes based on the most significantly associatedk-mers. Moreover,k-mer-based analyses identified promising candidate genes for loci related to pod color, pubescence form, and resistance to the oomycetePhytophthora sojae. In our dataset, SV-based GWAS did not add value compared tok-mer-based GWAS and may not be worth the time and computational resources required to genotype SVs at population scale. Despite promising results, significant challenges remain regarding the downstream analysis ofk-mer-based GWAS. Notably, better methods are needed to associate significantk-mers with sequence variation. Together, our results suggest that couplingk-mer-and SNP/indel-based GWAS is a powerful approach for discovering candidate genes in crop species.
The amino acid composition of a protein influences its expression
Authors: Thompson Reece , Simon Pickard Benjamin
Published: March 2023

The quantity of each protein in a cell only is only partially correlated with its gene transcription rate. Independent influences on protein synthesis levels include mRNA sequence motifs, amino acyl-tRNA synthesis levels, elongation factor action, and protein susceptibility to degradation. Here we report two novel forms of interaction between the amino acid composition of a protein and its expression level.

In animals, the differing origins of amino acids define a nutritional classification system and indicate their potential for scarcity – essential amino acids (EAA) are solely obtained from dietary supply, non-essential amino acids (NEAA) from biosynthetic supply, and conditionally essential amino acids (CEAA) from both. Accessing public proteomic datasets, we demonstrate that CEAA sequence composition is inversely correlated with expression – a rule of supply that is further magnified by rapid cellular proliferation. Similarly, proteins with the most extreme compositions of EAA are reduced in abundance. Homeostatic responses to malnutrition may result from the reductions in expression of extreme composition proteins participating in biological systems such as taste and food-seeking behaviour, oxidative phosphorylation, and chemokine function. The rule can also influence general human phenotypes and disease susceptibility: stature proteins are enriched in CEAAs, and a curated dataset of over 700 cancer proteins is significantly under-represented in EAAs.

A second rule, whereby individual amino acids influence protein expression is also described. This rule is shared across all kingdoms of life and rooted in the immutable structural and encoding parameters of each amino acid. Species-specific environmental survival pathways are shown to be enriched in proteins with amino acid compositions favouring higher expression according to this rule.

These two rules of protein expression regulation promise new insights into systems biology, evolutionary studies, experimental research design, and public health intervention.
Integrative multi-omic sequencing reveals the MMTV-Myc mouse model mimics human breast cancer heterogeneity
Authors: Broeker Carson D. , Ortiz Mylena M. O. , Murillo Michael S. , Andrechek Eran R.
Published: March 2023

Background

Breast cancer is a complex and heterogeneous disease with distinct subtypes and molecular profiles corresponding to different clinical outcomes. Mouse models of breast cancer are widely used, but their relevance in capturing the heterogeneity of human disease is unclear. Previous studies have shown the heterogeneity at the gene expression level for the MMTV-Myc model, but have only speculated on the underlying genetics.

Results

Herein, we examine three common histological subtypes of the MMTV-Myc model through whole genome sequencing and have integrated these results with gene expression data. Significantly, key genomic alterations driving cell signaling pathways were well conserved within histological subtypes. Genomic changes included frequent, co-occurring mutations in KIT and RARA in the microacinar histological subtype as well as SCRIB mutations in the EMT subtype. EMT tumors additionally displayed strong KRAS activation signatures downstream of genetic activating events primarily ascribed to KRAS activating mutations, but also FGFR2 amplification. Analogous genetic events in human breast cancer showed stark decreases in overall survival. In further analyzing transcriptional heterogeneity of the MMTV-Myc model, we report a supervised machine learning model that classifies MMTV-Myc histological subtypes and other mouse models as being representative of different human intrinsic breast cancer subtypes.

Conclusions

We conclude the well-established MMTV-Myc mouse model presents further opportunities for investigation of human breast cancer heterogeneity.
A Universal Method for Crossing Molecular and Atlas Modalities using Simplex-Based Image Varifolds and Quadratic Programming
Authors: Stouffer Kaitlin M. , Trouvé Alain , Younes Laurent , Kunst Michael , Ng Lydia , Zeng Hongkui , Anant Manjari , Fan Jean , Kim Yongsoo , Miller Michael I.
Published: March 2023

This paper explicates a solution to the problem of building correspondences between molecular-scale transcriptomics and tissue-scale atlases. The central model represents spatial transcriptomics as generalized functions encoding molecular position and high-dimensional transcriptomic-based (gene, cell type) identity. We map onto low-dimensional atlas ontologies by modeling each atlas compartment as a homogeneous random field with unknown transcriptomic feature distribution. The algorithm presented solves simultaneously for the minimizing geodesic diffeomorphism of coordinates and latent atlas transcriptomic feature fractions by alternating LDDMM optimization for coordinate transformations and quadratic programming for the latent transcriptomic variables. We demonstrate the universality of the algorithm in mapping tissue atlases to gene-based and cell-based MERFISH datasets as well as to other tissue scale atlases. The joint estimation of diffeomorphisms and latent feature distributions allows integration of diverse molecular and cellular datasets into a single coordinate system and creates an avenue of comparison amongst atlas ontologies for continued future development.
Phylobone: A comprehensive database of bone extracellular matrix proteins in human and model organisms
Authors: Fontcuberta-Rigo Margalida , Nakamura Miho , Puigbò Pere
Published: March 2023

The bone extracellular matrix (ECM) contains minerals deposited on highly crosslinked collagen fibrils and hundreds of non-collagenous proteins. Some of these proteins are key to the regulation of bone formation and regenerationviasignaling pathways, and play important regulatory and structural roles. However, the complete list of bone extracellular matrix proteins, their roles, and the extent of individual and cross-species variations have not been fully captured in both humans and model organisms. Here, we introduce the most comprehensive resource of bone extracellular matrix (ECM) proteins that can be used in research fields such as bone regeneration, osteoporosis, and mechanobiology. The Phylobone database (available athttps://phylobone.com) includes 255 proteins potentially expressed in the bone extracellular matrix (ECM) of humans and 30 species of vertebrates. A bioinformatics pipeline was used to identify the evolutionary relationships of bone ECM proteins. The analysis facilitated the identification of potential model organisms to study the molecular mechanisms of bone regeneration. A network analysis showed high connectivity of bone ECM proteins. A total of 214 functional protein domains were identified, including collagen and the domains involved in bone formation and resorption. Information from public drug repositories was used to identify potential repurposing of existing drugs. The Phylobone database provides a platform to study bone regeneration and osteoporosis in light of (biological) evolution, and will substantially contribute to the identification of molecular mechanisms and drug targets.
De novodesign of stable proteins that efficaciously inhibit oncogenic G proteins
Authors: Cummins Matthew C. , Tripathy Ashutosh , Sondek John , Kuhlman Brian
Published: March 2023

Many protein therapeutics are competitive inhibitors that function by binding to endogenous proteins and preventing them from interacting with native partners. One effective strategy for engineering competitive inhibitors is to graft structural motifs from a native partner into a host protein. Here, we develop and experimentally test a computational protocol for embedding binding motifs in de novo designed proteins. The protocol uses an “inside-out” approach: Starting with a structural model of the binding motif docked against the target protein, the de novo protein is built by growing new structural elements off the termini of the binding motif. During backbone assembly, a score function favors backbones that introduce new tertiary contacts within the designed protein and do not introduce clashes with the target binding partner. Final sequences are designed and optimized using the molecular modeling program Rosetta. To test our protocol, we designed small helical proteins to inhibit the interaction between Gαqand its effector PLC-β isozymes. Several of the designed proteins remain folded above 90°C and bind to Gαqwith equilibrium dissociation constants tighter than 80 nM. In cellular assays with oncogenic variants of Gαq, the designed proteins inhibit activation of PLC-β isozymes and Dbl-family RhoGEFs. Our results demonstrate that computational protein design, in combination with motif grafting, can be used to directly generate potent inhibitors without further optimization via high throughput screening or selection.

statement for broader audience

Engineered proteins that bind to specific target proteins are useful as research reagents, diagnostics, and therapeutics. We used computational protein design to engineer de novo proteins that bind and competitively inhibit the G protein, Gαq, which is an oncogene for uveal melanomas. This computational method is a general approach that should be useful for designing competitive inhibitors against other proteins of interest.
Intraspecies genomic divergence of coral algal symbionts shaped by gene duplication
Authors: Shah Sarah , Dougan Katherine E. , Chen Yibi , Bhattacharya Debashish , Chan Cheong Xin
Published: March 2023

Dinoflagellates of Order Suessiales include the diverse Family Symbiodiniaceae known for their role as essential coral reef symbionts, and the cold-adaptedPolarella glacialis. These taxa inhabit a broad range of ecological niches and exhibit extensive genomic divergence, although their genomes are in the smaller size ranges (haploid size < 3 Gbp) compared to most other dinoflagellates. Different isolates of a species are known to form symbiosis with distinct hosts and exhibit different regimes of gene expression, but intraspecies whole-genome divergence remains little known. Focusing on three Symbiodiniaceae species (the free-livingEffrenium voratum, and the symbioticSymbiodinium microadriaticumandDurusdinium trenchii) and the free-living outgroupP. glacialis, all for which whole-genome data from multiple isolates are available, we assessed intraspecies genomic divergence at sequence and structural levels. Our analysis based on alignment and alignment-free methods revealed greater extent of intraspecies sequence divergence in symbiodiniacean species than inP. glacialis. Our results also reveal the implications of gene duplication in generating functional innovation and diversification of Symbiodiniaceae, particularly inD. trenchiifor which whole-genome duplication was involved. Interestingly, tandem duplication of single-exon genes was found to be more prevalent in genomes of free-living species than in those of symbiotic species. These results in combination demonstrate the remarkable intraspecies genomic divergence in dinoflagellates under the constraint of reduced genome sizes, shaped by genetic duplications and symbiogenesis events during diversification of Symbiodiniaceae.
PERK arm of UPR selectively regulates ferroptosis in colon cancer cells by modulating the expression of SLC7A11 (System Xc-)
Authors: Saini Krishan Kumar , Chaturvedi Priyank , Sinha Abhipsa , Singh Manish Pratap , Khan Muqtada Ali , Verma Ayushi , Nengroo Mushtaq Ahmad , Satrusal Saumya Ranjan , Meena Sanjeev , Singh Akhilesh , Srivastava Sameer , Sarkar Jayanta , Datta Dipak
Published: March 2023

Ferroptosis, a genetically and biochemically distinct form of programmed cell death, is characterised by an iron-dependent accumulation of lipid peroxides. Therapy-resistant tumor cells display vulnerability toward ferroptosis. Endoplasmic Reticulum (ER) stress and Unfolded Protein Response (UPR) play a critical role in cancer cells to become therapy resistant. Tweaking the balance of UPR to make cancer cells susceptible to ferroptotic cell death could be an attractive therapeutic strategy. To decipher the emerging contribution of ER-stress in the ferroptotic process, we observe that ferroptosis inducer RSL3 promotes UPR (PERK, ATF6, and IRE1α), along with overexpression of cystine-glutamate transporter SLC7A11 (System Xc-). Exploring the role of a particular UPR arm in modulating SLC7A11 expression and subsequent ferroptosis, we notice that PERK is selectively critical in inducing ferroptosis in colorectal carcinoma. PERK inhibition reduces ATF4 expression and recruitment to the promoter ofSLC7A11and results in its downregulation. Loss of PERK function not only primes cancer cells for increased lipid peroxidation but also limits in vivo colorectal tumor growth, demonstrating active signs of ferroptotic cell deathin situ. Further, by performing TCGA data mining and using colorectal cancer patient samples, we demonstrate that the expression ofPERKandSLC7A11is positively correlated. Overall, our experimental data indicate that PERK is a negative regulator of ferroptosis and loss of PERK function sensitizes colorectal cancer cells to ferroptosis. Therefore, small molecule PERK inhibitors hold huge promise as novel therapeutics and their potential can be harnessed against the apoptosis-resistant condition.
Self-organized BMP signaling dynamics underlie the development and evolution of tetrapod digit patterns
Authors: Grall Emmanuelle , Feregrino Christian , Fischer Sabrina , De Courten Aline , Hiscock Tom W. , Tschopp Patrick
Published: March 2023

Repeating patterns of synovial joints are a highly conserved feature of articulated digits, with variations in joint number and location giving rise to a diverse range of digit morphologies and limb functions across the tetrapod clade. During development, joints form iteratively within the growing digit ray, as a population of distal progenitors alternately specifies joint and phalanx cell fates to segment the digit into distinct elements. Whilst numerous molecular pathways have been implicated in this fate choice, it remains unclear how they give rise to a repeating pattern. Here, using single cell RNA-sequencing and spatial gene expression profiling, we investigate the transcriptional dynamics of interphalangeal joint specificationin vivo. Combined with mathematical modelling, we predict that interactions within the BMP signaling pathway – between the ligand GDF5, the inhibitor NOG, and the intracellular effector pSMAD – result in a self-organizing Turing system that forms periodic joint patterns. Our model is able to recapitulate the spatiotemporal gene expression dynamics observedin vivo, as well as phenocopy digit malformations caused by BMP pathway perturbations. By contrastingin silicosimulations within vivomorphometrics of two morphologically distinct digits, we show how changes in signaling parameters and growth dynamics can result in variations in the size and number of phalanges. Together, our results reveal a self-organizing mechanism that underpins tetrapod digit patterning and its evolvability, and, more broadly, illustrate how Turing systems based on a single molecular pathway may generate complex repetitive patterns in a wide variety of organisms.
Sex-dependent manifestations of intracranial aneurysms
Authors: Wälchli Thomas , Ndengera Martin , Constanthin Paul E. , Bisschop Jeroen , Morel Sandrine , Gautschi Oliver , Berhouma Moncef , Kalyvas Aristotelis , Monnier Philippe P. , Winkler Ethan A. , Kortman Hans , Bhatia Kartik , Dammann Philipp , Jägersberg Max , Gondar Renato , Schaller Karl , Kwak Brenda R. , Bijlenga Philippe
Published: March 2023

Background

Intracranial aneurysms (IAs) are more common in females than in males, however, there is still very limited knowledge on sex-dependent differences regarding aneurysm location, multiplicity, rupture risk, risk factors and histopathology.

Methods

This prospective, consecutive cohort study examined whether IAs differ in multiplicity, location, geometry, rupture risk, risk factors and histology between sexes.

Results

We included 982 patients (714 women, 268 men) totaling 1484 IAs (1056 unruptured, 397 ruptured). Three hundred sixty-three patients (36.97%) had multiple IAs, the proportion of which was significantly higher in females. In women, the ICA (40.79%) was the most frequent location for IAs, whereas in men most were found along the ACA territory (32.86%). Men were significantly more often diagnosed with ruptured aneurysms. Aneurysm geometry did not differ between sexes, however, ruptured aneurysms in men presented with a significantly larger neck diameter than unruptured ones. Regarding risk factors for aneurysm rupture, blood pressure control was more effective in women, whereas the effect of smoking status did not show clear sex-dependent differences. Histologically, wall-type classification analysis showed significantly more severe aneurysm wall types in men.

Conclusion

IA prevalence in women is significantly higher than in men. Women more often present with multiple IAs whereas men were more often diagnosed with ruptured IAs. Sex-specific differences in IA location were identified whereas geometry of IAs did not differ between sexes. IAs in men showed a more severe histological wall type. Further research is needed to unravel the molecular mechanisms underlying these important sex-dependent manifestations in IAs.
Coronavirus pathogenesis in mice explains the SARS-CoV-2 multi-organ spread by red blood cells hitch-hiking
Authors: Toro A , Arevalo AP , Pereira-Gómez M , Sabater A , Zizzi EA , Pascual G , Lage-Vickers S , Porfido JL , Achinelli I , Seniuk R , Bizzotto J , Moreno P , Costabile A , Fajardo A , Rodriguez F , Nin N , Sanchis P , Anselmino N , Labanca E , Cotignola J , Navone N , Alonso DF , Vazquez E , Gentile F , Cherkasov A , Moratorio G , Crispo M , Gueron G
Published: March 2023

SARS-CoV-2 infection causes a multisystemic disease that affects numerous organs beyond the respiratory system. Thus, it is well known that COVID-19 is associated with a wide range of hematological disorders; however, it remains unclear how the SARS-CoV-2 virus is able to navigate from tissue to tissue. In this work, we performed a comprehensive analysis of the pleiotropic effects of a prototypical coronavirus in its natural host, the validated preclinical model of murine hepatitis virus (MHV). Throughout this study we compared our results with the real-world data from COVID-19 patients (including autopsies). Thus, the presence of viral RNA was only detected in less than 25% of the human serum samples, whereas all had multiple positive nasal swabs for SARS-CoV-2. Notably, we found viral RNA not only in lungs, but also in heart and kidney of deceased COVID-19 patients. Subsequently, we investigated the association between viral organotropism and clinical manifestations employing the MHV murine model. Results from RT-qPCR and viral infectivity showcased the presence of viral RNA and infectious particles in multiple organs including liver, lung, brain, heart, kidney, spleen and pancreas, and even the blood of infected mice. Surprisingly, when comparing plasma and red blood cells (RBCs)-enriched fraction, higher viral load levels were detected in RBCs, with decreased RBC count, and hematocrit and hemoglobin levels in infected mice. Next, we treated infected mice with hemin triggering more aggressive symptoms. Strikingly, when combining hemin treatment with chloroquine (a compound that known to interact with the heme group and induces a conformational change in its structure) the infection and its clinical manifestations were distinctly attenuated. Computational docking suggested that heme is able to bind to MHV Spike protein in a similar way to the one, experimentally observed for SARS-CoV-2. Overall, our results lead to a global perspective of COVID-19 beyond the canonical focus on the respiratory system, and strongly support the multi-organ extent of coronavirus infection through specific interactions with RBC hemoproteins.
Sexual orientation and gender identity reporting in highly cited alcohol research
Authors: Connolly Dean J. , Coduri-Fulford Santino , Tugulu Connor , Yalew Meron , Moss Elizabeth , Yang Justin C.
Published: March 2023

Purpose

This study aimed to measure the frequency of high-quality and transparent sexual orientation and gender identity data collection and reporting in highly cited alcohol use research, using the extant literature to identify community-informed priorities for the measurement of these variables.

Methods

A single search to identify alcohol use literature was conducted on PubMed with results restricted to primary research articles published between 2015 and 2022. The 200 most highly cited studies from each year were identified and their titles and abstracts reviewed against inclusion criteria following deduplication. Following full-text review and data extraction, the fidelity of the results was verified with a random sample prior to analyses.

Results

The final sample comprised 580 records. Few studies reported gender identity (n=19; 33.4%) and, of these, 7.2% reported the associated gender identity measure. A two-stage approach to measuring gender was adopted in five studies and 13 studies recorded non-binary gender identities (reported by 0.9% of the whole sample). Nineteen (3.3%) studies reported sexual orientation and more than half of these provided the sexual orientation measure. Five studies adopted a two-step approach to measuring gender identity and open offered a free-text response option. Eight of 20 studies reporting gender identity and sexual orientation measures were classified as sexual and gender minority specialist research.

Conclusions

Transparent and culturally competent gender identity and sexual orientation reporting is lacking in highly cited alcohol research.
Usefulness of pystan and numpyro in Bayesian item response theory
Authors: Nishio Mizuho , Ota Eiji , Matsuo Hidetoshi , Matsunaga Takaaki , Miyazaki Aki , Murakami Takamichi
Published: March 2023

Purpose:

The purpose of this study is to compare two libraries dedicated to Markov chain Monte Carlo method: pystan and numpyro.

Materials and methods:

Bayesian item response theory (IRT), 1PL-IRT and 2PL-IRT, were implemented with pystan and numpyro. Then, the Bayesian 1PL-IRT and 2PL-IRT were applied to two types of medical data obtained from a published paper. The same prior distributions of latent parameters were used in both pystan and numpyro. Estimation results of latent parameters of 1PL-IRT and 2PL-IRT were compared between pystan and numpyro. Additionally, the computational cost of Markov chain Monte Carlo method was compared between the two libraries. To evaluate the computational cost of IRT models, simulation data were generated from the medical data and numpyro.

Results:

For all the combinations of IRT types (1PL-IRT or 2PL-IRT) and medical data types, the mean and standard deviation of the estimated latent parameters were in good agreement between pystan and numpyro. In most cases, the sampling time using Markov chain Monte Carlo method was shorter in numpyro than that in pystan. When the large-sized simulation data were used, numpyro with a graphics processing unit was useful for reducing the sampling time.

Conclusion:

Numpyro and pystan were useful for applying the Bayesian 1PL-IRT and 2PL-IRT.
Who is responsible for nurse wellbeing in a crisis? A single centre perspective
Authors: Hughes Luke , Petrella Anika , Fern Lorna A , Taylor Rachel M
Published: March 2023

Background

Leadership during the COVID-19 pandemic often manifested as a command- and-control style of leadership which had detrimental emotional impacts on staff particularly the nursing workforce. Organisational responsibility for staff wellbeing would be necessary in another pandemic and leadership emerged as a key indicator of the overall health of an organisation and its workforce. Leadership can have detrimental effects on staff wellbeing or it can greatly boost their ability to handle a crisis. We sought to explore the interrelationship between leadership and nurses’ wellbeing in an inner-city university hospital during the initial wave of the pandemic.

Methods

Secondary analysis of interview data collected during a hospital-wide evaluation of barriers and facilitators to changes implemented to support the surge of COVID-19 related admissions during wave 1. Data were collected through semi-structured video interviews between May and July 2020. Interviews were analysed using Framework analysis

Results

Thirty-one nurses participated including matrons (n=7), sisters (n=8) and specialist nursing roles (n=16). Three overarching themes were identified: impact on nurses, personal factors and organisational factors. The impact on nurses manifested as distress and fatigue. Coping and help-seeking behaviours were found to be the two personal factors which underpinned nurses’ wellbeing. The organisational factors that impacted nurses’ wellbeing included decision-making, duty and teamwork.

Conclusions

The wellbeing of the workforce is pivotal to the health service, and it is mutually beneficial for patients, staff, and leaders. Addressing how beliefs and misconceptions around wellbeing are communicated, and accessing psychological support is a key priority to support nurses during pandemics.
Development and Validation of a novelin vitrodiagnostic test for endometriosis
Authors: Herranz-Blanco Bárbara , Daoud Elza , Viganò Paola , García-Velasco Juan Antonio , Colli Enrico
Published: March 2023

STRUCTURED ABSTRACT

Objective

To develop a non-invasive diagnostic test for endometriosis.

Design

We conducted two studies: the development study (study 1) aimed at (i) evaluating the ability of CA125, brain-derived neurotrophic factor (BDNF) and clinical variables in segregating between cases and controls and (ii) developing a diagnostic algorithm based on those results. In the validation study (study 2), the clinical performance of the developedin vitrodiagnostic (IVD) test, in diagnosing endometriosis was validated.

Interventions

Serum samples and clinical variables extracted from psychometric questionnaires were collected from the Oxford Endometriosis CaRe Centre biobank (UK). Case/control classification was performed based on laparoscopy and histological verification of endometrial glands and/or stroma in the excised lesions.

Main outcome measures

Study 1 and 2 includedn=204 andn=79 patients, respectively. CA125 and BDNF concentrations were determined using the endometriosis IVD ELISA kit. In study 2, serum CA125 and BDNF concentrations and clinical variables were introduced into the IVD test software hosting the data treatment algorithm, which generates the qualitative diagnostic result (“positive” or “negative”).

Results

Results from study 1 showed that, for both biomarkers levels, a statistically significant difference was found between cases and controls. Among all clinical variables related to patients’ medical history considered, six were significantly different between cases and controls: record of a previous surgery to investigate endometriosis presence, painful periods leading to referral for endometriosis presence, severity of menstrual pain during last cycle, age at first experience of intercourse pain, age at first regular use of painkillers and age at first diagnosis of ovarian cyst. In study 2, the novel endometriosis IVD test demonstrated sensitivity and specificity values of 46.2% (25.5-66.8%) and 100% (86.7-100%), respectively.

Conclusion

BDNF and CA125, together with patient’s clinical variables allowed efficient segregation between controls and endometriosis cases. Due to its high specificity, the novel endometriosis IVD test is an accurate rule-in non-invasive method, potentially contributing to diagnose endometriosis.
Genetic structure and genome-wide association study of the traditional Kazakh horses
Authors: Pozharskiy A. , Abdrakhmanova A. , Beishova I. , Shamshidin A. , Nametov A. , Ulyanova T. , Bekova G. , Kikebayev N. , Kovalchuk A. , Ulyanov V. , Turabayev A. , Khusnitdinova M. , Zhambakin K. , Sapakhova Z. , Shamekova M. , Gritsenko D.
Published: March 2023

Horses are traditionally used in Kazakhstan as a source of food and as working and saddle animals as well. Here, for the first time, microarray-based medium-density SNP genotyping of six traditionally defined types and breeds of indigenous Kazakh horses was conducted to reveal their genetic structure and find markers associated with animal size and weight. The results showed that the pre-defined separation between breeds and sampled populations was not supported by the molecular data. The lack of genetic variation between breeds and populations was revealed by the principal component analysis (PCA), ADMIXTURE, and distance based analyses, as well as the general population parameters expected and observed heterozygosity (HeandHo)and between group fixation index (Fst). The comparison with previously published data on global horse breed diversity revealed the relatively high level of individual diversity of Kazakh horses in comparison with the wellknown foreign breeds. The Mongolian and Tuva breeds were identified as the closest horse landraces, demonstrating similar patterns of internal variability. The genome-wide association analysis was performed for animal size and weight as the traits directly related with meat productivity of horses. The analysis identified a set of 60 SNPs linked with horse genes involved in the regulation of processes of development of connective tissues and the bone system, neural system, immune system regulation, and other processes. The present study is novel and introduces Kazakh horses as a promising genetic source for horse breeding and selection.
Methylglyoxal is the main culprit to impairing neuronal function: mediated through tryptophan depletion
Authors: Samsuzzaman Md. , Lee Jae Hyuk , Hong Seong-Min , Park Hyun jun , Chang Keun-A , Kim Hyun-Bum , Park Myoung Gyu , Eo Hyeyoon , Oh Myung Sook , Kim Sun Yeou
Published: March 2023

Depression is a common and prevalent illness and the exact cause of major depressive disorder is not known. Here, we investigated how methylglyoxal (MGO) stress induces depression and unveiled the potential molecular mechanism. Ourin vivoresults suggested that MGO caused depression in mice, confirmed by several behavioral tests. Interestingly, it halted the mice’s brain’s tryptophan levels and its related neurotransmitters. In addition, MGO induced a reduction in the number of cells in different hippocampal regions. Moreover, it decreased tryptophan hydroxylase 1 (TPH1) and tryptophan hydroxylase 1 (TPH2) levels in the brain and large intestine. Surprisingly, MGO showed the highest affinity and trapping ability toward tryptophan. Most importantly, combined treatment with MGO-tryptophan displayed similar effects as those exhibited by the tryptophan-null treatment in neuronal cells, which included neuronal apoptosis, decrease TPH1 and TPH2 levels, and inhibition of neuronal outgrowth. However, tryptophan treatment improved MGO induced depression-like behavior of mice and recovered the loss of neuronal and hippocampal cells. Subsequently, it also induced MGO detoxifying factors, tryptophan levels, and reduces inflammation in the intestine. Collectively, our data revealed that MGO induced depression facilitated by neuronal and synaptic dysfunction is mediated through the disturbance of tryptophan metabolism in the brain and intestine.
Water-soluble 4-(dimethylaminomethyl)heliomycin exerts greater antitumor effects than parental heliomycin by targeting the tNOX-SIRT1 axis and apoptosis in oral cancer cells
Authors: Islam Atikul , Chang Yu-Chun , Chen Xiao-Chi , Weng Chia-Wei , Chen Chien-Yu , Wang Che-Wei , Chen Mu-Kuan , Tikhomirov Alexander S. , Shchekotikhin Andrey E. , Chueh Pin Ju
Published: March 2023

The antibiotic heliomycin (resistomycin), which is generated fromStreptomyces resistomycificus, has multiple activities, including anticancer effects. Heliomycin was first described in the 1960s, but its clinical applications have been hindered by extremely low solubility. A series of 4-aminomethyl derivatives of heliomycin were synthesized to increase water solubility; studies showed that they had anti-proliferative effects, but the drug targets remained unknown. In this study, we conducted cellular thermal shift assays (CETSA) and molecular docking simulations to identify and validate that heliomycin and its water-soluble derivative, 4-(dimethylaminomethyl)heliomycin (designated compound 4-dmH) engaged and targeted with sirtuin-1 (SIRT1) in p53-functional SAS and p53-mutated HSC-3 oral cancer cells. We further addressed the cellular outcome of SIRT1 inhibition by these compounds and found that, in addition to SIRT1, the water-soluble 4-dmH preferentially targeted a tumor-associated NADH oxidase (tNOX, ENOX2). The direct binding of 4-dmH to tNOX decreased the oxidation of NADH to NAD+which diminished NAD+-dependent SIRT1 deacetylase activity, ultimately inducing apoptosis and significant cytotoxicity in both cell types, as opposed to the parental heliomycin-induced autophagy. We also observed that tNOX and SIRT1 were both upregulated in tumor tissues of oral cancer patients compared to adjacent normal tissues, suggesting their clinical relevance. Finally, the better therapeutic efficacy of 4-dmH was confirmed in tumor-bearing mice, which showed greater tNOX and SIRT1 downregulation and tumor volume reduction when treated with 4-dmH compared to heliomycin. Taken together, ourin vitroandin vivofindings suggest that the multifaceted properties of water-soluble 4-dmH enable it to offer superior antitumor value compared to parental heliomycin, and indicated that it functions through targeting the tNOX-NAD+-SIRT1 axis to induce apoptosis in oral cancer cells.
Organizational citizenship behavior for the environment decoded: sustainable leaders, green organizational climate and person-organization fit
Authors: Iqbal Qaisar , Piwowar-Sulej Katarzyna
Published: March 2023

Purpose

This study examines how sustainable leadership influences organizational citizenship behavior toward the environment, directly and through a green organizational climate. This study also investigates the moderating effect of person-organization fit on the relationship between green organizational climate and employees' organizational citizenship behavior for the environment.

Design/methodology/approach

Data were collected from 241 employees of manufacturing firms in China with one month's lag. Statistical analyses were conducted with the use of PLS-SEM.

Findings

This study confirmed that sustainable leadership significantly influenced organizational citizenship behavior for the environment, both directly and indirectly through a green organizational climate. It also revealed that the relationship between green organizational climate and employees' organizational citizenship behavior for the environment was contingent on the person-organization fit.

Originality/value

To the best of the authors' knowledge, this study is the first to analyze how sustainable leadership reinforces employees' organizational citizenship behavior for the environment by providing insight into the mediating role of green organizational climate and person-organization fit as a moderator. Moreover, through a combination of three theoretical perspectives (social learning theory, social exchange theory and the theory of person-organization fit), this study advances the academic knowledge on how organizational citizenship behavior for the environment develops, thus providing a more complex explanation of the relationship between the examined variables.
Migration informal human capital of returnees to Central Europe: a new rescource for organisations
Authors: Grabowska Izabela , Jastrzebowska Agata
Published: March 2023

Purpose

This paper aims to investigate the interplay between international migration, soft skills and job and life satisfaction after returns.

Design/methodology/approach

The paper uses the dataset of Human Capital in Poland 2010–2014 representative surveys with 4040 return migrants, who worked temporarily abroad and returned to an origin in comparison with almost 70,000 stayers, who never worked abroad. In this study, Poland is treated as a strategic research site for the labor migration processes, which happened after the biggest European Union enlargement in 2004.

Findings

This study discovered that working abroad had a positive relation with cognitive, intrapersonal and interpersonal competencies, as well as job and life satisfaction. However, the relations differ depending on the key destination country.

Practical implications

This study discusses the implications for future research and practice, offering recommendations to organizations on how to embed employees with these resources in companies and how to support return migrants and their potential employers with the use of migratory informal human capital in personnel management and counseling.

Originality/value

This paper brings quantitative arguments about the hidden impacts of international migration on human capital by uniquely comparing the migrant population with the non-migrant population.
How and when does top management interaction with customers impact customer satisfaction?
Authors: Ifie Kemefasu
Published: March 2023

Purpose

This paper aims to investigate the effect of top management’s customer interactions (TMCI) on customer satisfaction. This study argues that TMCI’s overall relationship with customer satisfaction follows an inverted-U shape due to its positive and disruptive effects on the customer relationship efforts of frontline service/sales employees (FSEs). This paper further investigates the frontline competence of both FSEs and the top management team (TMT) as moderators of the impact of TMCI on customer satisfaction.

Design/methodology/approach

The conceptual model was tested empirically using data from managers, frontline employees and customers of microfinance firms. A multilevel structural equation modeling approach was used to test the hypothesized model.

Findings

The results show that TMCI has a curvilinear relationship with customer satisfaction. The results also show that frontline employees’ collective efficacy attenuates this relationship by shifting the turning point of the curvilinear effect to the right. Furthermore, TMT frontline competence amplifies both the positive and negative effects of TMCI on customer satisfaction.

Research limitations/implications

This study advances knowledge on the effects of TMCI on customer satisfaction and highlights the nuanced relationship between top management involvement and indicators of firm performance.

Practical implications

The findings show the importance of considering the frontline competence of both top management and frontline employees when encouraging TMCI in organizations.

Originality/value

To the best of the author’s knowledge, this study is one of the first to examine TMCI’s direct impact on customer satisfaction and propose the frontline competence of both top management and frontline employees as boundary conditions on this relationship.
“What else is new?” identifying emerging psychosocial risk factors in hospitality employment
Authors: Gjerald Olga , Furunes Trude , Mathisen Gro Ellen
Published: March 2023

Purpose

The purpose of this study is to identify new psychosocial risk factors in the assessment of job demands and job resources in hospitality employment and to initiate the development of a psychosocial hospitality risk indicator (PHRI). The argument is underpinned by the findings from an exploratory study of health and safety representatives (HSE) in the hospitality sector.

Design/methodology/approach

Using focus-group interviews with 15 HSE representatives from 13 hospitality companies in lodging, housekeeping, and food and beverage segments, this research explored perceived psychosocial risks in different hospitality jobs through the lens of the JD-R (job demands-job resources) model.

Findings

This study suggests that factors such as conditioned flexibility, technological requirements, multicultural workforce interactions, lack of support from customers and lack of emotion ventilation represent new risk factors in the psychosocial work environment if not properly managed. A list of items to assess these new psychosocial risks is provided, and a model of different knowledge sources for the further development of the PHRI is suggested.

Originality/value

This is the first paper to identify new psychosocial risks in hospitality employment through the lens of a health and safety work perspective. A key theoretical contribution of this research is the extension of the JD-R model with new variables representing service-specific job demands and resources and the development of items for future risk assessment in hospitality jobs.
Incentivizing knowledge institutions for entrepreneurship and society
Authors: Aparicio Sebastian , Hughes Mathew (Mat) , Audretsch David , Urbano David
Published: March 2023

Purpose

Going beyond the traditional approach of formal and informal institutions as antecedents of entrepreneurship (directly) and development (indirectly), this paper seeks to explore knowledge institutions as a necessary input for entrepreneurship and the development of societies.

Design/methodology/approach

Institutional economics lenses are utilized to observe other factors (e.g. the number of R&D staff and researchers from the public sector) that involve laws and socialization processes, which at the same time create knowledge useful for entrepreneurs and society. These ideas are tested through a sample of 281 observations from 17 autonomous communities and two autonomous cities in Spain. The information coming from the Global Entrepreneurship Monitor (GEM), Ministry of Economics, Industry, and Competitiveness, and INE (Instituto Nacional de Estadística), was analyzed through 3SLS, which is useful for a simultaneous equation strategy.

Findings

Knowledge institutions such as the number of R&D staff and researchers from the public sector are found positively associated with entrepreneurship, which is a factor directly and positively linked to economic development across Spanish regions.

Originality/value

The findings help the operationalization of other institutions considered in institutional economics theory and its application to entrepreneurship research. Moreover, the results bring new insights into the knowledge spillover theory of entrepreneurship in the public sector, in which the institutional analysis is implicit.