bluuebunny/crossref_metadata_2025_split huggingface dataset:
A partially shared joint clustering framework for detecting protein complexes from multiple state-specific signed interaction networks
Authors: Zhan Youlin , Liu Jiahan , Wu Min , Heng Tan Chris Soon , Li Xiaoli , Ou-Yang Le 
Published: January 2023

ABSTRACTDetecting protein complexes is critical for studying cellular organizations and functions. The accumulation of protein-protein interaction (PPI) data enables the identification of protein complexes computationally. Although various computational approaches have been proposed to detect protein complexes from PPI networks, most of them ignore the signs of PPIs that reflect the ways proteins interact (activation or inhibition). As not all PPIs imply cocomplex relationships, taking into account the signs of PPIs can benefit the detection of protein complexes. Moreover, PPI networks are not static, but vary with the change of cell states or environments. However, existing protein complex identification algorithms are primarily designed for single-network clustering, and rarely consider joint clustering of multiple PPI networks. In this study, we propose a novel partially shared signed network clustering model (PS-SNC) for detecting protein complexes from multiple state-specific signed PPI networks jointly. PS-SNC can not only consider the signs of PPIs, but also identify the common and unique protein complexes in different states. Experimental results on synthetic and real datasets show that PS-SNC outperforms other state-of-the-art protein complex detection methods. Extensive analysis on real datasets demonstrate the effectiveness of PS-SNC in revealing novel insights about the underlying patterns of different cell lines.
COL7A1 expression improves prognosis prediction for patients with clear cell renal cell carcinoma atop of stage
Authors: Koca Dzenis , Séraudie Irinka , Jardiller Rémy , Cochet Claude , Filhol Odile , Guyon Laurent 
Published: January 2023

AbstractClear cell renal cell carcinoma (ccRCC) accounts for 75% of kidney cancers. Due to the high recurrence rate, and treatment options that come with high costs and potential side effects correct prognosis of patient survival is essential for the successful and effective treatment of patients. Novel biomarkers could play an important role in the assessment of the overall survival of patients. COL7A1 encodes for collagen type VII, a constituent of the basal membrane. COL7A1 is associated with survival in many cancers; however, the prognostic value of COL7A1 expression as a standalone biomarker in ccRCC has not been investigated. We used Kaplan-Meier curves and Cox proportional hazards model to investigate the prognostic value of COL7A1, as well as Gene Set Enrichment Analysis to investigate genes that are co-expressed with COL7A1. COL7A1 expression was used to stratify patients into four groups of expression, where the 5-year survival probability of each group was 72.4%, 59.1%, 34.15%, and 8.6% in order of increasing expression. Additionally, COL7A1 expression was successfully used to further divide patients of each stage and histological grade into groups of high and low risk. Similar results were obtained in independent cohorts.In-vitroknockdown of COL7A1 expression significantly impacted ccRCC cells’ ability to migrate and proliferate. To conclude, we identified COL7A1 as a new prognosis marker that can stratify ccRCC patients.
Osteoblast-intrinsic defect in glucose metabolism impairs bone formation in type II diabetic mice
Authors: Song Fangfang , Lee Won Dong , Marmo Tyler , Ji Xing , Song Chao , Liao Xueyang , Seeley Rebbeca , Yao Lutian , Liu Haoran , Long Fanxin 
Published: January 2023

AbstractSkeletal fragility is associated with type 2 diabetes mellitus (T2D), but the underlying mechanism is not well understood. Here, in a mouse model for youth-onset T2D, we show that both trabecular and cortical bone mass are reduced due to diminished osteoblast activity. Stable isotope tracing in vivo with13C-glucose demonstrates that both glycolysis and glucose fueling of the TCA cycle are impaired in diabetic bones. Similarly, Seahorse assays show suppression of both glycolysis and oxidative phosphorylation by diabetes in bone marrow mesenchymal cells as a whole, whereas single-cell RNA sequencing reveals distinct modes of metabolic dysregulation among the subpopulations. Metformin not only promotes glycolysis and osteoblast differentiation in vitro, but also improves bone mass in diabetic mice. Finally, targeted overexpression of Hif1a or Pfkfb3 in osteoblasts of T2D mice averts bone loss. The study identifies osteoblast-intrinsic defects in glucose metabolism as an underlying cause of diabetic osteopenia, which may be targeted therapeutically.
A single amino acid polymorphism in natural Metchnikowin alleles ofDrosophilaresults in systemic immunity and life history tradeoffs
Authors: Perlmutter Jessamyn I. , Chapman Joanne R. , Wilkinson Mason C. , Nevarez-Saenz Isaac , Unckless Robert L. 
Published: January 2023

AbstractAntimicrobial peptides (AMPs) are at the interface of interactions between hosts and microbes and are therefore expected to be fast evolving in a coevolutionary arms race with pathogens. In contrast, previous work demonstrated that one AMP, Metchikowin (Mtk), has a single residue that segregates as either proline (P) or arginine (R) in populations of four differentDrosophilaspecies, some of which diverged more than 10 million years ago. The recurrent finding of this polymorphism regardless of geography or host species, coupled with evidence of balancing selection inDrosophilaAMPs, suggest there is a distinct functional importance to each allele. The most likely hypotheses involve alleles having specificity to different pathogens or the more potent allele conferring a cost on the host. To assess their functional differences, we createdD. melanogasterlines with the P allele, R allele, orMtknull mutation using CRISPR/Cas9 genome editing. Here, we report results from experiments assessing the two hypotheses using these lines. In males, testing of systemic immune responses to a repertoire of bacteria and fungi demonstrated that the R allele performs as well or better than the P and null alleles with most infections. With some pathogens, however, females show results in contrast with males whereMtkalleles either do not contribute to survival or where the P allele outperforms the R allele. In addition, measurements of life history traits demonstrate that the R allele is more costly in the absence of infection for both sexes. These results provide strongin vivoevidence that differential fitness with or without infection and sex-based functional differences in alleles may be adaptive mechanisms of maintaining immune gene polymorphisms in contrast with expectations of rapid evolution. Therefore, a complex interplay of forces including pathogen species and host sex may lead to balancing selection for immune genotypes. Strikingly, this selection may act on even a single amino acid polymorphism in an AMP.
CD9 co-operation with syndecan-1 is required for a major staphylococcal adhesion pathway
Authors: Green Luke R. , Issa Rahaf , Albaldi Fawzyah , Urwin Lucy , Khalid Henna , Turner Claire E. , Ciani Barbara , Partridge Lynda J. , Monk Peter N. 
Published: January 2023

AbstractObjectivesEpithelial colonisation is a critical first step in bacterial pathogenesis.Staphylococcus aureuscan utilise several host factors to associate with cells, including α5βl integrin and heparan sulphate proteoglycans, such as the syndecans. Here, we demonstrate that a partner protein of both integrins and syndecans, the host membrane adapter protein tetraspanin CD9, is essential for syndecan-mediated staphylococcal adhesion. Fibronectin is also essential in this process while integrins are only critical for post-adhesion entry into human epithelial cells.Methods and ResultsTreatment of epithelial cells with CD9-derived peptide or heparin caused significant reductions in staphylococcal adherence, dependent on both CD9 and syndecan-1. Exogenous fibronectin caused a CD9-dependent increase in staphylococcal adhesion whereas blockade of β1 integrins did not affect adhesion but did reduce the subsequent internalisation of adhered bacteria. CD9 disruption or deletion increased β1 integrin-mediated internalisation, suggesting that CD9 coordinates sequential staphylococcal adhesion and internalisation.ConclusionsCD9 controls staphylococcal adhesion through syndecan-1, using a mechanism that likely requires CD9-mediated syndecan organisation to correctly display fibronectin at the host cell surface. We propose that CD9-derived peptides or heparin analogues could be developed as anti-adhesion treatments to inhibit the initial stages of staphylococcal pathogenesis.
Proline catabolism is key to facilitatingCandida albicanspathogenicity
Authors: Silao Fitz Gerald S. , Jiang Tong , Bereczky-Veress Biborka , Kühbacher Andreas , Ryman Kicki , Uwamohoro Nathalie , Jenull Sabrina , Nogueira Filomena , Ward Meliza , Lion Thomas , Urban Constantin F. , Rupp Steffen , Kuchler Karl , Chen Changbin , Peuckert Christiane , Ljungdahl Per O. 
Published: January 2023

AbstractCandida albicans, the primary etiology of human mycoses, is well-adapted to catabolize proline to obtain energy to initiate morphological switching (yeast to hyphal) and for growth. We report thatput1-/-andput2-/- strains, carrying defectiveProlineUTilization genes, display remarkable proline sensitivity withput2-/- mutants being hypersensitive due to the accumulation of the toxic intermediate P5C, which inhibits mitochondrial respiration. Theput1-/- andput2-/-mutations attenuate virulence inDrosophilaand murine candidemia models. Using intravital 2-photon microscopy and label-free non-linear imaging, we visualized the initial stages ofC. albicanscells colonizing a kidney in real-time, directly deep in the tissue of a living mouse, and observed morphological switching of wildtype but not ofput2-/-cells. Multiple members of theCandidaspecies complex, includingC. auris, are capable of using proline as a sole energy source. Our results indicate that a tailored proline metabolic network tuned to the mammalian host environment is a key feature of opportunistic fungal pathogens.
Obesity Modifies Clinical Outcomes of Right Ventricular Dysfunction
Authors: Ma Janet I. , Zern Emily , Jiang Nona , Wang Dongyu , Rambarat Paula , Pomerantsev Eugene , Picard Michael H. , Ho Jennifer E. 
Published: January 2023

AbstractIntroductionRight ventricular (RV) dysfunction is associated with increased mortality across a spectrum of cardiovascular diseases. The role of obesity in RV dysfunction and adverse outcomes is unclear.MethodsWe examined patients undergoing right heart catheterization between 2005-2016 in a hospital-based cohort. Linear regression was used to examine the association of obesity with hemodynamic indices of RV dysfunction [pulmonary artery pulsatility index (PAPi), right atrial pressure: pulmonary capillary wedge pressure ratio (RAP:PCWP), RV stroke work index (RVSWI)]. Cox models were used to examine the association of RV function measures with clinical outcomes.ResultsAmong 8285 patients (mean age 63 years, 40% women), higher BMI was associated with worse indices of RV dysfunction, including lower PAPi (β -0.26, SE 0.01, p <0.001), higher RA:PCWP ratio (β 0.25, SE 0.01, p-value <0.001), and lower RVSWI (β -0.05, SE 0.01, p-value <0.001). Over 7.3 years of follow-up, we observed 3006 mortality and 2004 heart failure (HF) hospitalization events. RV dysfunction was associated with greater risk of mortality (eg PAPi: HR 1.11 per 1-SD increase, 95% CI 1.04-1.18), with similar associations with risk of HF hospitalization. BMI modified the effect of RV dysfunction on outcomes (P-interaction <=0.005 for both), such that the effect of RV dysfunction was more pronounced at higher BMI.ConclusionsPatients with obesity had worse hemodynamic measured indices of RV function across a broad hospital-based sample. While RV dysfunction was associated with worse clinical outcomes including mortality and HF hospitalization, this association was especially pronounced among individuals with higher BMI.
Alternative splicing induced by bacterial pore-forming toxins sharpens CIRBP-mediated cell response toListeriainfection
Authors: Corre Morgane , Boehm Volker , Besic Vinko , Kurowska Anna , Viry Anouk , Mohammad Ammara , Sénamaud-Beaufort Catherine , Thomas-Chollier Morgane , Lebreton Alice 
Published: January 2023

AbstractCell autonomous responses to intracellular bacteria largely depend on gene expression reorganization. To gain isoform-level resolution into these regulations, we combined long- and short-read transcriptomic analyses of the response of intestinal epithelial cells to infection by the foodborne pathogenListeria monocytogenes. Among the most striking isoform-based regulations, expression of the cellular stress response regulator CIRBP (cold-inducible RNA-binding protein) and of several SRSFs (serine/arginine-rich splicing factors) switched from canonical transcripts to nonsense-mediated decay-sensitive isoforms by inclusion of “poison exons”. We showed that damage to host cell membranes caused by bacterial pore-forming toxins (listeriolysin O, perfringolysin, streptolysin, or aerolysin) led to the dephosphorylation of SRSF proteinsviathe inhibition of the kinase activity of CLK1, thereby driving CIRBP alternative splicing. CIRBP isoform usage was found to have consequences on infection, since selective repression of canonical CIRBP reduced intracellular bacterial load while that of the poison exon-containing isoform exacerbated it. Consistently, CIRBP-bound mRNAs were shifted towards stress-relevant transcripts in infected cells, with increased mRNA levels or reduced translation efficiency for some targets. Our results thus generalize the alternative splicing of CIRBP and SRSFs as a common response to biotic or abiotic stresses by extending its relevance to the context of bacterial infection.
Multiomics study ofCHCHD10S59L-related disease reveals energy metabolism downregulation: OXPHOS and β-oxidation deficiencies associated with lipids alterations
Authors: Hounoum Blandine Madji , Bellon Rachel , Genin Emmanuelle C , Bannwarth Sylvie , Lefevre Antoine , Fleuriol Lucile , Debayle Delphine , Gay Anne-Sophie , Petit-Paitel Agnès , Lacas-Gervais Sandra , Blasco Hélène , Emond Patrick , Paquis-Flucklinger Veronique , Ricci Jean-Ehrland 
Published: January 2023

AbstractMutations in the coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) gene have been associated with a large clinical spectrum including myopathy, cardiomyopathy and amyotrophic lateral sclerosis (ALS). Herein, we analyzed the metabolic changes induced by the p.S59LCHCHD10mutation to identify new therapeutic opportunities. Using metabolomic, lipidomic and proteomic analysis we observed a strong alteration of metabolism in plasma and heart ofChchd10S59L/+mice compared to their wild type littermates at pre-symptomatic and symptomatic stages. In plasma, levels of phospholipids were decreased while those of carnitine derivatives and most of amino acids were increased. The cardiac tissue fromChchd10S59L/+mice showed a decreased Oxidative Phosphorylation (OXPHOS) and β-oxidation proteins levels as well as tricarboxylic acid cycle (TCA) intermediates and carnitine pathway metabolism. In parallel, lipidomics analysis reveals a drastic change in the lipidome, including triglycerides, cardiolipin and phospholipids. Consistent with this energetic deficiency in cardiac tissue, we show that L-acetylcarnitine supplementation improves the mitochondrial network length in IPS-derived cardiomyocytes from a patient carrying theCHCHD10S59L/+mutation. These data indicate that a bioenergetic intermediate such as L-acetylcarnitine may restore mitochondrial function inCHCHD10-related disease, due to the reduction in energy deficit that could be compensated by carnitine metabolic pathways.
Remittances, institutional quality and investment in Sub-Saharan Africa
Authors: Mohammed Umar , Karagöl Erdal Tanas 
Published: January 2023

PurposeThis paper investigates the relationship between remittances, institutional quality and investment in Sub-Saharan African (SSA) countries using data from 2004 to 2018.Design/methodology/approachThe two-stage least squares (2SLS) estimator is the main methodology used, while the system generalized method of moments (Sys-GMM) technique is employed to test the robustness of the results.FindingsThe results show a positive and significant impact of remittances on investment in SSA. The findings further reveal a substitutional linkage between remittances and institutions in promoting investment. In essence, remittances serve as investment capital in countries with poor institutions. The results also show that the marginal significance of remittances as a source of funds for investment decreases in countries with well-developed institutions.Research limitations/implicationsThe sample excludes some of the SSA countries due to the unavailability of data.Practical implicationsIn the face of current institutional weaknesses, there is a need for SSA countries to prioritize policies that encourage the effective use of remittances for business activities. Furthermore, SSA countries must improve their economic freedom and democratic practices by reducing government size, protecting property rights, and promoting respect for political and civil rights.Originality/valueThis is the first study to analyze the relationship between remittances, institutional quality and investment in SSA. It also provides a novel framework for future research on the remittance–investment nexus.
Expatriate bubbles in Dubai: expatriates from West and East cohabitating with locals
Authors: Primecz Henriett 
Published: January 2023

PurposeFocussing on the stratification of expatriates and the boundaries between different types of expatriates and locals, this study investigates the lived experiences and testimonies of Eastern European expatriates and their relationships in Dubai. The purpose of this article to develop the current knowledge on expatriates cohabiting in a cosmopolitan city by providing empirical evidence on expatriate bubbles in Dubai.Design/methodology/approachExplorative qualitative research was conducted using online and face-to-face interviews, along with a week-long intensive ethnography with observations, interviews and informal discussions.FindingsThree distinct groups of people live in Dubai, namely, Westerners, expatriates from the East and Emiratis. They hardly mingle with each other on equal terms, but they do work in a complementary fashion. In Dubai, the status of East European experts, a subgroup of Westerners, is similar to their Western counterparts and in that they are considered European. Consequently, they experience a slight status development in comparison to when they work in the West. The research provides evidence on social stratification of expatriate bubbles.Research limitations/implicationsThis very short ethnography with a relatively small number of qualitative interviews could be complemented by a further in-depth study.Originality/valueExpatriate bubbles have not previously been empirically investigated from an Eastern European perspective, nor has the unique case of Dubai been analysed extensively. Distinct expatriate bubbles with their stratified hierarchies have been identified in this study.
Similarities and differences in motivation in cross-disciplinary biomedical, policy, and education health science teams: a mixed methods comparative case study using the MATRICx
Authors: Lotrecchiano Gaetano Romano , Balog Emily , Brundage Shelley , Deyo Patricia , Conlon Leocadia , Bugin Kevin , Sheffey Landria , Cook Ellen , Gentry Melissa 
Published: January 2023

Purpose
This study aims to investigate individual motivations for participating in collaborative health knowledge producing teams (KPTs), as well as satisfaction gained by participation in science teams. The authors focus on understanding motivators across team types, levels of engagement and alignment within and across teams and need satisfaction in a total of six science teams. Areas of strong congruence and divergence of motivating factors can be aligned across (i) learning and professional growth satisfaction, (ii) respect, collegiality and enjoyment satisfaction and (iii) accomplishment and discovery satisfaction. Levels of satisfaction are hierarchically mapped showing their relation to more external and communal foci to motivations that seek satisfaction of individual needs.

Design/methodology/approach
This mixed method comparative study uses data from the motivation assessment for team readiness integration and collaboration (MATRICx) tool and themes generated from semi-structured interviews. This methodology provided a means to compare a hierarchy of motivations against levels of collaborative engagement, as well as individual needs satisfaction and ultimately the identification of higher and lower-level motivations related to self and external foci.

Findings
The findings indicate that there are both similarities and differences in motivations in different health science teams when one compares biomedical, education and policy teams. A comparison of MATRICx data from across team types and teams suggests areas of strong congruence as well as areas of divergence in motivation factors.

Originality/value
The paper and its findings use a novel tool along with qualitative research techniques to identify motivation in KPTs and uses these data to understand what type of needs satisfaction are important across three areas of health science teaming. Our research informs team leaders, facilitators and consultants about the important motivations team members have entering teams and has the potential to provide a blueprint to ensure peak performance as individual team members seek to address their ever-growing professional needs.
All together now: Geographically coordinated miticide treatment benefits honey bee health
Authors: Woodford Luke , Sharpe Graeme , Highet Fiona , Evans David J. 
Published: January 2023

Abstract

Deformed wing virus (DWV) is a pathogenic virus of honey bees transmitted by the ectoparasitic mite Varroa destructor. Annual overwintering colony losses, accounting for ~25% of all colonies, are associated with high levels of Varroa‐DWV infestation. Effective miticide treatments are available to control Varroa. However, the absence of coordinated treatment means environmental transmission of mites continues unchecked. We aimed to determine whether rational, coordinated treatment is beneficial, and characterized the DWV population as an indicator of colony health.

This study uses coordinated treatment of Varroa in a geographically isolated environment (Isle of Arran, Scotland) over 3 years. The study area contained 50–84 colonies managed by ~20 amateur beekeepers. Sampling and virus analysis to assess strain diversity and viral loads were conducted before and after treatments, and changes in population diversity were quantified by sequence analysis.

Over the 3 years analysis of the virus population revealed that the dominant DWV variant shifted from Type A to Type B in all apiaries, regardless of mite levels or proximity to other colonies. During this period the number of managed colonies increased by 47% (57–84 colonies), but despite this, we estimate total mite numbers decreased by 58%.

Synthesis and applications. In this study, the beekeepers in Arran significantly improved the number of colonies they managed, without importing any bees onto the island, indicating that an improved focus on management techniques, through the combination of a coordinated miticide programme and an improved understanding of bee diseases, could yield positive results for bee health and sustainability.