bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brooklyn plots to identify co-expression dysregulation in single cell sequencing
Authors: Patil Arun H. , Halushka Marc K 
Published: June 2023

ABSTRACTAltered open chromatin regions, impacting gene expression, is a feature of some human disorders. We discovered it is possible to detect global changes in genomically-related gene co-expression within single cell RNA sequencing (scRNA-seq) data. We built a software package to generate and test non-randomness using ‘Brooklyn plots’ to identify the percent of genes significantly co-expressed from the same chromosome in ∼10MB intervals across the genome. These plots establish an expected low baseline of co-expression in scRNA-seq from most cell types, but, as seen in dilated cardiomyopathy cardiomyocytes, altered patterns of open chromatin appear. These may relate to larger regions of transcriptional bursting, observable in single cell, but not bulk datasets.
Exploring the Interactome of PML nuclear subdomains during fatty acid stress using APEX2-mediated proximity labeling
Authors: Thompson Jordan , Boisvert François-Michel , Salsman Jayme , Dellaire Graham , Ridgway Neale D. 
Published: June 2023

ABSTRACTWhen exposed to excess fatty acids, specific cell types produce nuclear lipid droplets (nLDs) that associate with promyelocytic leukemia (PML) protein to formLipidAssociatedPMLStructures (LAPS) that are enriched in lipid biosynthetic enzymes but deficient in canonical proteins associated with PML nuclear bodies (PML NBs). To identify the PML interactome during lipid stress, we employed proximity-dependent biotin identification (BioID) in U2OS cells expressing PMLI and PMLII fused to the ascorbate peroxidase APEX2 and cultured in the absence or presence of oleate to enhance lipid droplet formation. The resulting interactome included proteins enriched under oleate-treated conditions, such mitogen activated protein kinase-activated protein kinase 2 (MK2), ESCRT proteins and the COPII vesicle transport proteins Sec23B, Sec24A and USO1. COPII proteins co-localized with both PML-NBs and LAPS but were selectively enriched in PML-NBs following oleate treatment. The nuclear localization of USO1 was uniquely dependent on PML expression. Thus, the APEX2-PML proximity interactome implicates PML domains in the nuclear function of a non-canonical network of COPII vesicle trafficking proteins.SUMMARY STATEMENTThis is the first study to utilize APEX2 proximity labelling to identify the protein interactome of PML nuclear substructures and how interactions are modified under conditions of fatty acid-induced stress.
Stability of Alternative Bacteriorhodopsin Folds
Authors: Mackin Kristine A. , Theobald Douglas L. 
Published: June 2023

AbstractBacteriorhodopsin is a light-activated proton pump found in archaea and some single-celled eukaryotes (Findlay and Pappin, 1986; Sharma et al., 2006; Spudich et al., 2000). This protein adopts the 7TM fold found used by all type I and type II rhodopsins. In previous work, we used bacteriorhodopsin fromHaloterrigena turkmenicato demonstrate that substantially altered protein folds exhibit light-activated proton pumping (Kamo et al., 2006; Mackin et al., 2014). In this work, we further characterized these novel folds by assessing the stability of our mutants. We used SDS denaturation to calculate the change in unfolding free energy relative to the wild-type (Cao et al., 2012). We also determine the extinction coefficient for each mutant. These results demonstrate that even dramatic structural rearrangements do not critically destabilize the protein, although the extinction coefficient does vary independently of the stability and the proton-pumping activity. Interestingly, the position of the A helix in the protein sequence has the largest effect on the stability of the mutant; those mutants where A is not located at a terminus are destabilized compared to the wild-type.
Leucine alleviates cytokine storm syndrome by regulating macrophage polarization via the mTORC1/LXRα signaling pathway
Authors: Yan Hui , Liu Yao , Li Xipeng , Yu Bing , He Jun , Mao Xiangbing , Yu Jie , Huang Zhiqing , Luo Yuheng , Luo Junqiu , Wu Aimin , Chen Daiwen 
Published: June 2023

AbstractCytokine storms are associated with severe pathological damage and death in some diseases. Excessive activation of M1 macrophages and the subsequent secretion of pro-inflammatory cytokines are a major cause of cytokine storms. Therefore, promoting the polarization of M2 macrophages to restore immune balance is a promising therapeutic strategy for treating cytokine storm syndrome (CSS). This study was aimed at investigating the potential protective effects of leucine on lipopolysaccharide (LPS)-induced CSS in mice and exploring the underlying mechanisms. CSS was induced by LPS administration in mice, which were concurrently administered leucine orally. In vitro, BMDMs were polarized to M1 and M2 phenotypes with LPS and IL-4, respectively, and treated with leucine. Leucine decreased mortality in mice treated with lethal doses of LPS. Specifically, leucine decreased M1 polarization and promoted M2 polarization, thus diminishing pro-inflammatory cytokine levels and ameliorating CSS in mice. Further studies revealed that leucine induced macrophage polarization through the mechanistic target of rapamycin complex 1 (mTORC1)/liver X receptor α (LXRα) pathway, which synergistically enhanced the expression of the IL-4-induced M2 marker Arg1 and subsequent M2 polarization. In summary, this study revealed that leucine ameliorates CSS in LPS mice by promoting M2 polarization through the mTORC1/LXRα/Arg1 signaling pathway. Our findings indicate that a fundamental link between metabolism and immunity contributes to the resolution of inflammation and the repair of damaged tissues.
DNAJC12 in monoamine metabolism, neurodevelopment and neurodegeneration
Authors: Deng Isaac Bul , Follett Jordan , Bu Mengfei , Farrer Matthew J. 
Published: June 2023

AbstractRecent studies show that mutations inDNAJC12, a co-chaperone for monoamine synthesis may cause mild hyperphenylalaninemia with infantile dystonia, young-onset parkinsonism, developmental delay and cognitive deficits. To this end,DNAJC12gene has been included in newborn screening, most revealingly in Spain, and those results are a testament to the importance of early diagnosis and treatment in combating human diseases. However, practitioners may be unaware of these advances and it is probable that many patients, especially adults, have yet to receive molecular testing forDNAJC12. Therefore, this review summarizes genotype-phenotype relationships and treatment paradigms for patients withDNAJC12mutations. It provides an overview of the structure of DNAJC12 protein, known mutations, domains and binding partners, and elaborates on its role in monoamine synthesis, disease etiology and pathogenesis.
Single-session measures of quadriceps neuromuscular function are reliable in healthy females and unaffected by age
Authors: O’Bryan Steven J. , Hiam Danielle , Lamon Séverine 
Published: June 2023

AbstractObjectiveThe inter-session reliability of a wide range of measures used to characterize the aging neuromuscular system is unknown, particularly in females. The aim of this study was to determine the inter-session reliability of quadriceps neuromuscular function assessed via maximal voluntary and evoked force and electromyography responses in healthy young and older females.MethodsTwenty-six females aged 19 – 74 years completed two identical testing sessions 9 ± 7 days apart. Quadriceps neuromuscular function measurements included isometric maximal voluntary force (MVC), high and low frequency twitch force, voluntary and evoked electromyography (EMG) in superficial quadriceps (RMS, M-wave and H-reflex), and maximal torque (T0), velocity (V0) and power (PMAX) derived from torque-velocity and power-velocity relationships. Intra-class correlation coefficients (ICC), coefficients of variation (CoV) and Bland-Altman plots were used to assess inter-session reliability. The effect of participant age on inter-session reliability was assessed by linear regression.ResultsExcellent reliability (ICC > 0.8) was shown for all voluntary and evoked mechanical outcomes and systematic bias was essentially absent. Similarly, allvastus lateralisEMG outcomes showed excellent reliability (ICC > 0.8) with CoVs < 12%, which were better thanvastus medialisandrectus femorisoutcomes. Participant age was not associated with inter-session reliability (P > 0.05).ConclusionExcellent reliability of voluntary and evoked force andvastus lateralisEMG outcomes measured in healthy females can be attained in one testing session, irrespective of age, increasing feasibility for future research. The random error should however be considered when quantifying age-related differences and/or adaptation to exercise in female neuromuscular function.New and NoteworthyThe test-retest reliability of a diverse range of measures used to quantify neuromuscular function were assessed in younger and older females for the first time. We show that reliable measures of maximal voluntary and evoked quadriceps force and electromyography outcomes can be obtained in one testing session, irrespective of participant age. Thus, neuromuscular function can be accurately assessed across the female lifespan with minimal inconvenience imposed on participants, increasing feasibility for future research.
Paeniclostridium sordellii NanS works synergistically with TcsL to increase cytotoxicity and the severity of pathogenesis in the murine uterus
Authors: Bernard Sarah C. , Kroh Heather K. , Washington M. Kay , Lacy D. Borden 
Published: June 2023

AbstractPaeniclostridium sordellii, a pathogen capable of causing lethal uterine infections post-partum or post-abortion, produces a variety of potential virulence factors. Lethal toxin (TcsL) has been found to be essential for lethalP. sordelliiinfections, but the physiological role of NanS, a sialidase, remains elusive. Here, we purify enzymatically activeP. sordelliiNanS and report the crystal structure. We show that NanS works in a synergistic manner with TcsL to increase cytotoxicity and cell rounding of tissue culture cells. Using a mouse model of hormone-dependent uterine intoxication, we show that NanS augments TcsL-induced lethality in diestrus mice. In estrus mice, the combination of NanS and TcsL significantly increases uterine histologic damage compared to challenge with TcsL alone. This suggests that NanS enhancement of TcsL-induced uterine epithelial injury may potentiate TcsL access to the tissue when mucus is present.Author SummaryP. sordelliiproduces several proteins predicted to contribute to lethal uterine infections following childbirth, stillbirth, or abortion. The role of lethal toxin (TcsL) in causing lethal outcomes, has been well documented, but little is known of how NanS, a sialidase, contributes to disease development. Previous reports have suggested a role for NanS in increasing the tissue culture cell toxicity fromP. sordelliisupernatants. In this study, we show in cell culture and using a uterine mouse model that TcsL and NanS work together to increase cell cytotoxicity and to worsen disease outcome. This finding suggests an accessory role for NanS to enhanceP. sordelliipathogenesis when host environmental conditions reduce the influence of TcsL.
A Common Pathway for Detergent-Assisted Oligomerization of Aβ42
Authors: Kunnath Muhammedkutty Fidha Nazreen , Prasad Ramesh , Gao Yuan , Rao Sudarshan Tarunya , Robang Alicia S. , Watzlawik Jens O. , Rosenberry Terrone L. , Paravastu Anant K. , Zhou Huan-Xiang 
Published: June 2023

AbstractAmyloid beta (Aβ) aggregation is a slow process without seeding or assisted nucleation. Sodium dodecyl sulfate (SDS) micelles stabilize Aβ42 small oligomers (in the dimer-tetramer range); subsequent SDS removal leads to a 150-kD Aβ42 oligomer. Dodecylphosphorylcholine (DPC) micelles also stabilize an Aβ42 tetramer. Here we characterize the detergent-assisted oligomerization pathway by solid-state NMR spectroscopy and molecular dynamics simulations. SDS and DPC-induced oligomers have the same structure, implying a common oligomerization pathway. An antiparallel β-sheet formed by the C-terminal region, the only stable structure in SDS and DPC micelles, is directly incorporated into the 150-kD oligomer. Three Gly residues (at positions 33, 37, and 38) create holes that are filled by the SDS and DPC hydrocarbon tails, thereby turning a potentially destabilizing feature into a stabilizing factor. These observations have implications for endogenous Aβ aggregation at cellular interfaces.
Integrated genomic and functional analyses of human skin-associatedStaphylococcusreveals extensive inter- and intra-species diversity
Authors: Joglekar Payal , Conlan Sean , Lee-Lin Shih-Queen , Deming Clay , Kashaf Sara Saheb ,   NISC Comparative Sequencing Program, Kong Heidi H. , Segre Julia A. 
Published: June 2023

ABSTRACTHuman skin is stably colonized by a distinct microbiota that functions together with epidermal cells to maintain a protective physical barrier.Staphylococcus, a prominent genus of the skin microbiota, participates in colonization resistance, tissue repair, and host immune regulation in strain specific manners. To unlock the potential of engineering skin microbial communities, we aim to fully characterize the functional diversity of this genus within the context of the skin environment. We conducted metagenome and pan-genome analyses of isolates obtained from distinct body sites of healthy volunteers, providing a detailed biogeographic depiction of staphylococcal species that colonize our skin.S. epidermidis,S. capitis,andS. hominiswere the most abundant species present in all volunteers and were detected at all body sites. Pan-genome analysis of these three species revealed that the genus-core was dominated by central metabolism genes. Species-specific core genes were enriched in host colonization functions. The majority (∼68%) of genes were detected only in a fraction of isolate genomes, underscoring the immense strain-specific gene diversity. Conspecific genomes grouped into phylogenetic clades, exhibiting body site preference. Each clade was enriched for distinct gene-sets that are potentially involved in site tropism. Finally, we conducted gene expression studies of select isolates showing variable growth phenotypes in skin-like medium.In vitroexpression revealed extensive intra- and inter-species gene expression variation, substantially expanding the functional diversification within each species. Our study provides an important resource for future ecological and translational studies to examine the role of shared and strain-specific staphylococcal genes within the skin environment.SIGNIFICANCEThe bacterial genusStaphylococcusis a prominent member of the human skin microbiome, performing important and diverse functions such as tuning immunity, driving tissue repair, and preventing pathogen colonization. Each of these functions is carried out by a subset of staphylococcal strains, displaying differences in gene content and regulation. Delineating the genomic and functional diversity ofStaphylococcuswill enable researchers to unlock the potential of engineering skin communities to promote health. Here, we present a comprehensive multi-omics analysis to characterize the inter- and intra-species diversity present in human skin-associated staphylococci. Our study is the first to conduct a detailed pan-genome comparison between prominent skin staphylococcal species giving a valuable insight into gene sharing and provides an important resource.
Structural properties of the HNF-1A transactivation domain
Authors: Kind Laura , Driver Mark , Raasakka Arne , Onck Patrick R. , Njølstad Pål Rasmus , Arnesen Thomas , Kursula Petri 
Published: June 2023

AbstractHepatocyte nuclear factor 1α (HNF-1A) is a transcription factor with important gene regulatory roles in pancreatic β-cells.HNF1Agene variants are associated with a monogenic form of diabetes (HNF1A-MODY) or an increased risk for type 2 diabetes. While several pancreatic target genes of HNF-1A have been described, a lack of knowledge regarding the structure-function relationships in HNF-1A prohibits a detailed understanding of HNF-1A-mediated gene transcription, which is important for precision medicine and improved patient care. Therefore, we aimed to characterize the understudied transactivation domain (TAD) of HNF-1Ain vitro. We present a bioinformatic approach to dissect the TAD sequence, analyzing protein structure, sequence composition, sequence conservation, and the existence of protein interaction motifs. Moreover, we developed the first protocol for the recombinant expression and purification of the HNF-1A TAD. Small-angle X-ray scattering and synchrotron radiation circular dichroism suggested a disordered conformation for the TAD. Furthermore, we present functional data on HNF-1A undergoing liquid-liquid phase separation, which is in line within silicopredictions and may be of biological relevance for gene transcriptional processes in pancreatic β-cells.
Assessment of building retrofit scenarios using embodied energy and life cycle impact assessment
Authors: Tokede Olubukola , Boggavarapu Mani Kumar , Wamuziri Sam 
Published: June 2023

PurposeCrucial transition of the Indian residential building sector into a low-emission economy require an in-depth understanding of the potentials for retrofitting the existing building stock. There are, however, limited studies that have recognised the interdependencies and trade-offs in the embodied energy and life cycle impact assessment of retrofit interventions. This research appraises the life cycle assessment and embodied energy output of a residential building in India to assess the environmental implications of selected retrofit scenarios.Design/methodology/approachThis study utilises a single case study building project in South India to assess the effectiveness and impact of three retrofit scenarios based on life cycle assessment (LCA) and embodied energy (EE) estimates. The LCA was conducted using SimaPro version 9.3 and with background data from Ecoinvent database version 3.81. The EE estimates were calculated using material coefficients from relevant databases in the published literature. Monte Carlo Simulation is then used to allow for uncertainties in the estimates for the scenarios.FindingsThe three key findings that materialized from the study are as follows: (1) the retrofitting of Indian residential buildings could achieve up to 20% reduction in the life cycle energy emissions, (2) the modification of the building envelope and upgrading of the building service systems could suffice in providing optimum operational energy savings, if the electricity from the grid is sourced from renewable plants, and (3) the production of LEDs and other building services systems has the highest environmental impacts across a suite of LCA indicators.Originality/valueThe retrofitting of residential buildings in India will lead to better and improved opportunities to meet the commitments in the Paris Climate Change Agreement and will lead to enhanced savings for building owners.
Human resource management, quality of patient care and burnout during the pandemic: a job demands-resources approach
Authors: Salas-Vallina Andrés , Herrera Justo , Rofcanin Yasin 
Published: June 2023

PurposeBased on the job-demands resources model, this study examines the potential of human resource management practices to simultaneously improve physicians' burnout and quality of patient care during the COVID-19 pandemic.Design/methodology/approachDrawing on a sample of 499 physicians working in specialised medical units, structural equation models through PLS-SEM was used to check the proposed hypotheses.FindingsThe results show that human resource management can reduce physicians' burnout and increase quality of patient care by considering job demands and job resources as mediators. In addition, this study suggests that burnout and quality of patient care can be improved simultaneously.Research limitations/implicationsThis research is focused on healthcare, which opens important opportunities to extend the proposed model in other public and private industries.Practical implicationsManagers need to understand that fostering well-being among employees is crucial for human resource management and impacts positively on employee performance.Originality/valueThis study offers a double mediation process whereby job demands and job resources are key underlying mechanisms through which human resource management practices reduce burnout and improve performance in a compatible way.
Digital technologies, social entrepreneurship and resilience during crisis in developing countries: evidence from Nigeria
Authors: Nakpodia Franklin , Ashiru Folajimi , You Jacqueline Jing , Oni Oluwasola 
Published: June 2023

PurposeSocial entrepreneurship (SE) is a complex phenomenon designed to resolve numerous societal challenges while remaining economically viable. However, how social entrepreneurs in developing countries have deployed digital technologies to address communal challenges during the Covid-19 crisis is largely undocumented. This research examines social entrepreneurs' adoption of digital technologies, the multi-level organisational conditions, and associated innovative outcomes of engaging digital technologies.Design/methodology/approachBased on the organisational resilience theoretical framework, this research employs a qualitative methodology, comprising 38 semi-structured interviews with Nigerian SE firms, to investigate social entrepreneurs' engagement with digital technologies.FindingsThe study’s findings reveal 19 pathways through which digital technologies enabled organisational resilience outcomes by Nigerian SE firms during the Covid-19 pandemic. This allows the authors to show, via a 3 × 3 matrix, how social entrepreneurs deploy digital technologies to build proximate, dynamic, and continuous resilience in a weak institutional context.Originality/valueThe study’s findings enables the authors to advance the SE – digital technologies – resilience scholarship in a developing economy.
A bibliometric analysis on innovation in philanthropy research: a study based on Scopus database
Authors: Medias Fahmi , Rosari Reni , Susamto Akhmad Akbar , Ab Rahman Asmak Binti 
Published: June 2023

Purpose
Intellectual curiosity about innovation in philanthropic organizations has grown recently. This study aims to provide a thorough bibliometric analysis of the patterns and trends in the scientific literature on innovation in philanthropy.

Design/methodology/approach
Based on the Scopus database, a descriptive bibliometric analysis with a visualization tool (RStudio®) was used to assess the creation of 159 articles on innovation in philanthropic organizations.

Findings
This research finds a large number of papers on innovation in philanthropic organizations. According to this study, the USA has published more research than any other country. The Icahn School of Medicine has the most popular publications, followed by the Bill & Melinda Gates Foundation. According to the number of citations, the Journal of Business Ethics is the most prolific journal. However, according to the h-index, Corporate Reputation Review is the most important publication. Halme M is regarded as a prominent scholar. With 244 citations, the work of Kramer MR and Porter ME is the most referenced. “Philanthropy” is the most often used keywords category, followed by “innovation” and “social innovation”.

Practical implications
This study can serve as a useful reference for researchers conducting bibliometric research by offering information on the field’s famous authors. Furthermore, the outcomes of this study make it straightforward for researchers to seek extensive academic collaboration in this field.

Originality/value
To the best of the authors’ knowledge, this study is the first to present a pattern in research on innovation in philanthropic organizations.