bluuebunny/crossref_metadata_2025_split huggingface dataset:
Examining Health Service Rates Among Residents of Retirement Homes and Other Older Adult Populations in Ontario, Canada: A Population-Based Cohort Study
Authors: Manis Derek R. , Poss Jeffrey W. , Jones Aaron , Rochon Paula A. , Bronskill Susan E. , Campitelli Michael A. , Perez Richard , Stall Nathan M. , Rahim Ahmad , Babe Glenda , Tarride Jean-Éric , Abelson Julia , Costa Andrew P. 
Published: September 2021

ABSTRACTBackgroundThere are no standardized reporting systems or assessments specific to residents of retirement homes in North America. As such, little is known about these older adults as a distinct population. We created a new population-level cohort of residents of retirement homes and examined their health service rates relative to other older adult populations.MethodsWe conducted a population-based retrospective cohort study in Ontario, Canada in 2018. The postal codes of all licensed retirement homes (n= 757) were classified and linked to individual-level health system administrative data to derive a cohort of residents of retirement homes. A generalized linear model with a gamma distribution and log link function was used to model rates of emergency department visits, hospitalizations, alternate levels of care (ALC) days, primary care visits, and specialist physician visits.ResultsResidents of retirement homes comprised two percent of the older adult population in Ontario (n= 54,773; 2.3%). After adjustment for relevant characteristics, residents of retirement homes had 10 times the rate of emergency department visits (Relative Rate [RR] 10.02, 95% Confidence Interval [CI] 9.83 to 10.21), 20 times the rate of hospitalizations (RR 20.43, 95% CI 20.08 to 20.78), and 44 times the rate ALC days (RR 43.91, 95% CI 43.28 to 44.54) compared to community-dwelling older adults.InterpretationResidents of retirement homes are a distinct older adult population with high rates of hospital-based care. Our findings contribute to policy debates about the provision of health care in privately operated congregate care settings for older adults.
A BioID-derived proximity interactome for SARS-CoV-2 proteins
Authors: May Danielle G. , Martin-Sancho Laura , Anschau Valesca , Liu Sophie , Chrisopulos Rachel J. , Scott Kelsey L. , Halfmann Charles T. , Peña Ramon Díaz , Pratt Dexter , Campos Alexandre R. , Roux Kyle J. 
Published: September 2021

AbstractThe novel coronavirus SARS-CoV-2 is responsible for the ongoing COVID-19 pandemic and has caused a major health and economic burden worldwide. Understanding how SARS-CoV-2 viral proteins behave in host cells can reveal underlying mechanisms of pathogenesis and assist in development of antiviral therapies. Here we use BioID to map the SARS-CoV-2 virus-host interactome using human lung cancer derived A549 cells expressing individual SARS-CoV-2 viral proteins. Functional enrichment analyses revealed previously reported and unreported cellular pathways that are in association with SARS-CoV-2 proteins. We have also established a website to host the proteomic data to allow for public access and continued analysis of host-viral protein associations and whole-cell proteomes of cells expressing the viral-BioID fusion proteins. Collectively, these studies provide a valuable resource to potentially uncover novel SARS-CoV-2 biology and inform development of antivirals.
Basal Gp78-dependent mitophagy promotes mitochondrial health and limits mitochondrial ROS
Authors: Alan Parsa , Vandevoorde Kurt R. , Joshi Bharat , Cardoen Ben , Gao Guang , Mohammadzadeh Yahya , Hamarneh Ghassan , Nabi Ivan R. 
Published: September 2021

ABSTRACTMitochondria are major sources of cytotoxic reactive oxygen species (ROS) that contribute to cancer progression. Mitophagy, the selective elimination of mitochondria by autophagy, monitors and maintains mitochondrial health and integrity, eliminating ROS-producing mitochondria. However, mechanisms underlying mitophagic control of mitochondrial homeostasis under basal conditions remain poorly understood. Gp78 E3 ubiquitin ligase is an endoplasmic reticulum membrane protein that induces mitochondrial fission and mitophagy of depolarized mitochondria. Here, we report that CRISPR/Cas9 knockout of Gp78 in HT-1080 fibrosarcoma cells increased mitochondrial volume and rendered cells resistant to carbonyl cyanide m-chlorophenyl hydrazone (CCCP)-induced mitophagy. These effects were phenocopied by knockdown of the essential autophagy protein ATG5 in wild-type HT-1080 cells. Use of the mito-Keima mitophagy probe confirmed that Gp78 promoted both basal and damage-induced mitophagy. Application of a spot detection algorithm (SPECHT) to GFP-mRFP tandem fluorescent-tagged LC3 (tfLC3)-positive autophagosomes reported elevated autophagosomal maturation in wild-type HT-1080 cells relative to Gp78 knockout cells, predominantly in proximity to mitochondria. Mitophagy inhibition by either Gp78 knockout or ATG5 knockdown reduced mitochondrial potential and increased mitochondrial ROS. Live cell analysis of tfLC3 in HT-1080 cells showed the preferential association of autophagosomes with mitochondria of reduced potential. Basal Gp78-dependent mitophagic flux is therefore selectively associated with reduced potential mitochondria promoting maintenance of a healthy mitochondrial population and limiting ROS production.
Development of novel potent ligands for GPR85, an orphan G protein-coupled receptor expressed in the brain
Authors: Sakai Aya , Yasui Takeshi , Watanave Masashi , Tatsumi Rine , Yamamoto Yoshihiko , Takano Wataru , Tani Yuki , Okamura Izumi , Hirai Hirokazu , Takeda Shigeki 
Published: September 2021

AbstractGPR85 is a member of the G protein-coupled receptor and is a super-conserved receptor expressed in the brain sub-family (SREB) with GPR27 and GPR173. These three receptors are “orphan receptors”; however, their endogenous ligands have not been identified. SREB has garnered the interest of many scientists because it is expressed in the central nervous system and is evolutionarily conserved. In particular, brain mass is reported to be increased and learning and memory are improved in GPR85 knockout mice (Matsumoto et al., 2008). In this study, we characterized newly synthesized compounds using a GPR85-Gsα fusion protein and the [35S]GTPγS binding assay and identified novel GPR85 inverse-agonists with IC50 values of approximately 1 µM. To analyze the neurochemical character of the compounds and investigate the physiological significance of GPR85, we used cerebellar Purkinje cells expressing GPR85 and an electrophysiological technique. Based on the results, the inverse-agonist compound for GPR85 modulated potassium channel opening. Together with the results of previous gene analysis of GPR85, we expect that the development of the GPR85 ligand will provide new insights into a few types of neurological disorders.
Copeptin response to acute physical stress during hypohydration: An exploratory secondary analysis
Authors: Carroll Harriet A. , Melander Olle 
Published: September 2021

AbstractPurposePlasma copeptin (a surrogate marker of arginine vasopressin) is increasingly being used as a marker of stress in several research and clinical contexts. However, the response to an acute physical stressor in healthy adults has not yet been tested meaning it is unclear whether copeptin reflects dynamic changes in stress or whether this is moderated by different basal copeptin concentrations and how this relates to other stress hormones.MethodsSecondary data analysis in a subsample of participants (n = 7; n = 1 woman) who opted-in for muscle biopsies in a randomised crossover study investigating the effects of acute hypohydration (HYPO) versus rehydration (RE) on metabolism.ResultsPlasma copeptin responded to the muscle biopsy stress stimulus, with a similar magnitude of difference according to basal concentrations during HYPO and RE; however, the peak was higher and concentrations typically took longer to return to baseline during HYPO. Despite large differences in copeptin concentrations, adrenocorticotropin hormone (ACTH) and cortisol showed a similar trends in response to the biopsies, regardless of hydration status.ConclusionCopeptin responded dynamically to an acute physical stressor (muscle biopsy). HYPO induced higher basal copeptin concentrations compared to RE, and resulted in a higher and prolonged copeptin response. Further research should investigate the mechanisms underlying the lack of differences in ACTH and cortisol according to hydration status.
On the origin and evolution of Drosophila new genes during spermatogenesis
Authors: Su Qianwei , He Huangyi , Zhou Qi 
Published: September 2021

AbstractOrigin of functional new genes is a basic biological process that has significant contribution to organismal diversity. Previous studies in both Drosophila and mammals showed that new genes tend to be expressed in testis, and avoid the X chromosome presumably because meiotic sex chromosome inactivation (MSCI). Here we analyze the published single-cell transcriptome data of Drosophila adult testis and find an enrichment of male germline mitotic genes, but an underrepresentation of meiotic genes on the X chromosome. This can be attributed to an excess of autosomal meiotic genes that were derived from their X-linked mitotic progenitors, which provides direct cell-level evidence for MSCI in Drosophila. We reveal that new genes, particularly those produced by retrotransposition, tend to exhibit an expression shift toward late spermatogenesis compared to their parental copies, probably due to the more intensive sperm competition or sexual conflict. Our results dissect the complex factors including the age, the origination mechanisms and the chromosomal locations that influence the new gene origination and evolution in testis, and identify new gene cases that show divergent cell-level expression pattern from their progenitors for future functional studies.
Influenza A (N1-N9) and Influenza B (B/Vic and B/Yam) Neuraminidase Pseudotypes as Tools for Pandemic Preparedness and Improved Influenza Vaccine design
Authors: da Costa Kelly A.S. , Del Rosario Joanne Marie M. , Ferrari Matteo , Vishwanath Sneha , Asbach Benedikt , Kinsley Rebecca , Wagner Ralf , Heeney Jonathan L. , Carnell George W. , Temperton Nigel J. 
Published: September 2021

AbstractTo better understand how inhibition of the influenza neuraminidase (NA) protein contributes to protection against influenza, and to investigate its breadth and cross-neutralizing activity, we have produced lentiviral vectors pseudotyped with an avian H11 hemagglutinin (HA) and the NA (N1-N9) of all influenza A and (B/Victoria and B/Yamagata) influenza B subtypes. These NA viral pseudotypes (PV) possess stable NA activity and can be utilized as target antigens in in vitro assays to assess vaccine immunogenicity. Employing these NA PV, we have developed an enzyme-linked lectin assay (pELLA) for routine serology to measure neuraminidase inhibition (NI) titers of reference antisera, monoclonal antibodies, and post-vaccination sera with various influenza antigens. We have also shown that pELLA is more sensitive than the commercially available NA-Fluor™ in detecting NA inhibition in these samples. Our studies may lead to establishing the protective NA titer that contributes to NA-based immunity. This will aid in the design of superior, longer lasting, and more broadly protective vaccines that can be employed together with HA-targeted vaccines in a pre-pandemic approach.
Single-Round Remodeling of the Active Site of an Artificial Metalloenzyme using an Ultrahigh-Throughput Double Emulsion Screening Assay
Authors: Vallapurackal Jaicy , Stucki Ariane , Liang Alexandria Deliz , Klehr Juliane , Dittrich Petra S. , Ward Thomas R. 
Published: September 2021

AbstractThe potential of high-throughput compartmentalization renders droplet microfluidics an attractive tool for directed evolution of enzymes as it permits maintenance of the phenotype-genotype linkage throughout the entire optimization procedure. In particular, water-in-oil-in-water double emulsions droplets (DEs) produced by microfluidics enable the analysis of reaction compartments at ultra-high-throughput using commercially available fluorescence-activated cell sorting (FACS) devices. Here we report a streamlined method applicable for the ultrahigh-throughput screening of an artificial metalloenzyme (ArM), an artificial deallylase (ADAse), in double emulsions. The DE-protocol was validated by screening a four hundred member, double-mutant streptavidin library for the CpRu-catalyzed uncaging of aminocoumarin. The most active variants, identified by next generation sequencing of the sorted DE droplets with highest fluorescent intensity, are in good agreement with 96-well plate screening hits. These findings, thus, pave the way towards the systematic implementation of commercially available FACS for the directed evolution of metalloenzymes making ultrahigh-throughput screening more broadly accessible. The use of microfluidics for the formation of uniform compartments with precise control over reagents and cell encapsulation further facilitates the establishment of highly reliable quantitative assays.
Large-scale two-photon calcium imaging in freely moving mice
Authors: Zong Weijian , Obenhaus Horst A. , Skytøen Emilie R. , Eneqvist Hanna , de Jong Nienke L. , Jorge Marina R. , Moser May-Britt , Moser Edvard I. 
Published: September 2021

SummaryWe developed a miniaturized two-photon microscope (MINI2P) for fast, high-resolution, multiplane calcium imaging of over 1,000 neurons at a time in freely moving mice. With a microscope weight below 3g and a highly flexible connection cable, MINI2P allowed imaging to proceed with no impediment of behavior in half-hour free-foraging trials compared to untethered, unimplanted animals. The improved cell yield was achieved through a new optical system design featuring an enlarged field of view (FOV) and a new micro-tunable lens with increased z-scanning range and speed that allowed for fast and stable imaging of multiple, interleaved planes as well as 3D functional imaging. A novel technique for successive imaging across multiple, adjacent FOVs enabled recordings from more than 10,000 neurons in the same animal. Large-scale proof-of-principle data were obtained from cell populations in visual cortex, medial entorhinal cortex, and hippocampus, revealing spatial tuning of cells in all areas, including visual cortex.HighlightsWe developed a lightweight 2-photon miniscope for imaging in freely-foraging miceActivity can be monitored in volumes of over 1,000 visual or entorhinal-cortex cellsA new z-scanning module allows fast imaging across multiple interleaved planesSuccessive imaging from adjacent regions enables imaging from more than 10,000 cells
Progenitor-intrinsic Metabolic Sensing Promotes Hematopoietic Homeostasis
Authors: Pizzato Hannah A. , Wang Yahui , Wolfgang Michael J. , Finck Brian N. , Patti Gary J. , Bhattacharya Deepta 
Published: September 2021

SummaryHematopoietic homeostasis is maintained by stem and progenitor cells in part by extrinsic feedback cues triggered by mature cell loss. We demonstrate a different mechanism by which hematopoietic progenitors intrinsically anticipate and prevent the loss of mature progeny through metabolic switches. We examined hematopoiesis in mice conditionally deficient in long-chain fatty acid oxidation (carnitine palmitoyltransferase 2,Cpt2), glutaminolysis (glutaminase,Gls), or mitochondrial pyruvate import (mitochondrial pyruvate carrier 2,Mpc2). While genetic ablation ofCpt2orGlsminimally impacted most blood lineages, deletion ofMpc2led to a sharp decline in mature myeloid cells. However, MPC2-deficient myeloid cells rapidly recovered due to a transient increase in myeloid progenitor proliferation. Competitive bone marrow chimera and stable isotope tracing experiments demonstrated that this proliferative burst was intrinsic to MPC2-deficient progenitors and accompanied by a metabolic switch to glutaminolysis. Thus, hematopoietic progenitors intrinsically adjust to metabolic perturbations independently of feedback from downstream mature cells to maintain homeostasis.
Methodological considerations in analyzing synchronization of resting-state brain networks with the intrinsic electrical rhythm of the stomach: Advantages of weighted phase-locking
Authors: Choe Ann S. , Tang Bohao , Smith Kimberly R. , Honari Hamed , Lindquist Martin A. , Caffo Brian S. , Pekar James J. 
Published: September 2021

ABSTRACTPurposeTo evaluate the amplitude-weighted phase-locking value (awPLV) as a measure of synchronization of brain resting-state networks (RSNs) with the gastric basal electrical rhythm (BER).MethodsA recent study combined rsfMRI with concurrent cutaneous electrogastrography (EGG), in a highly-sampled individual who underwent 22 scanning sessions (two 15-minute runs per session) at 3.0 Tesla. After excluding three sessions due to weak EGG signals, 9.5 hours of data remained, from which 18 RSNs were estimated using spatial independent component analysis. Previously, using the phase-locking value (PLV), three of the 18 RSNs were determined to be synchronized with the BER. However, RSN power fluctuations in the gastric frequency band could reduce sensitivity of PLV. Accordingly, the current reanalysis used awPLV to unweight contributions from low power epochs. Mismatched EGG and rsfMRI data (from different days) served as surrogate data; for each RSN, empirical awPLV was compared with chance-level awPLV using a Wilcoxon rank test. P-values were adjusted using with a false discovery rate of 0.05. Additionally, simulations were performed to compare PLV and awPLV error rates under settings with a known ground truth.ResultsSimulations show high false-negative rates when using PLV, but not awPLV. Reanalysis of the highly-sampled individual data using awPLV indicates that 11 of the 18 RSNs were synchronized with the BER.ConclusionSimulations indicate that awPLV is a more sensitive measure of stomach/brain synchronization than PLV. Reanalysis results imply communication between the enteric nervous system and brain circuits not typically considered responsive to gastric state or function.
Semi-automated analysis of an optical ATP indicator in neurons
Authors: Dehkharghanian Taher , Hashemiaghdam Arsalan , Ashrafi Ghazaleh 
Published: September 2021

AbstractSignificanceThe firefly enzyme luciferase has been used in a wide range of biological assays, including bioluminescence imaging of ATP. The biosensor Syn-ATP utilizes subcellular targeting of luciferase to nerve terminals for optical measurement of ATP in this compartment. Manual analysis of Syn-ATP signals is challenging due to signal heterogeneity and cellular motion in long imaging sessions. Here, we have leveraged machine learning tools to develop a method for analysis of bioluminescence images.AimOur goal was to create a semi-automated pipeline for analysis of bioluminescence imaging to improve measurements of ATP content in nerve terminals.ApproachWe developed an image analysis pipeline that applies machine learning toolkits to distinguish neurons from background signals, and excludes neural cell bodies, while also incorporating user input.ResultsSide-by-side comparison of manual and semi-automated image analysis demonstrated that the latter improves precision and accuracy of ATP measurements.ConclusionsOur method streamlines data analysis and reduces user-introduced bias, thus enhancing the reproducibility and reliability of quantitative ATP imaging in nerve terminals.
Crystal structure of the complex of DNA with the C-terminal domain of TYE7 from Saccharomyces cerevisiae
Authors: Gui Wei , Xue Lu , Yue Jian , Kuang Zhiling , Jin Yuping , Niu Liwen 
Published: September 2021

TYE7, a bHLH (basic helix–loop–helix) transcription factor from Saccharomyces cerevisiae, is involved in the regulation of many genes, including glycolytic genes. Meanwhile, accumulating evidence indicates that TYE7 also functions as a cyclin and is linked to sulfur metabolism. Here, the structure of TYE7 (residues 165–291) complexed with its specific DNA was determined by X-ray crystallography. Structural analysis and comparison revealed that His185 and Glu189 are conserved in base recognition. However, Arg193 is also involved in base recognition in the structures that were compared. In the structure in this study, Arg193 in chain A has two conformations and makes a salt bridge with the phosphate backbone structure. In addition, a series of corresponding electrophoretic mobility shift assays were performed to better understand the DNA-binding mechanism of the bHLH domain of TYE7.
Internal branding, employees' brand commitment and moderation role of transformational leadership: an empirical study in Indian telecommunication context
Authors: Binu Raj Asha 
Published: September 2021

PurposeThe purpose of this paper is to examine the relationship between internal branding (IB) and employees' brand commitment and analyze how transformational leadership (TFL) moderates this relationship.Design/methodology/approachData were collected through structured questionnaires from 394 employees in Indian telecommunication sector. The hypotheses and conceptual model were tested by structural equation modeling (SEM), using Statistical Package for Social Sciences (SPSS) and Analysis of Moment Structures (AMOS).FindingsThe results suggest that employees' brand commitment is higher when organizations implement IB supported by transformational leaders. Results also indicate that impact of IB on affective commitment (AC) and normative commitment (NC) is greater than its impact on continuance commitment (CC).Research limitations/implicationsConsistent with the brand commitment dimensions, the findings present an empirically tested comprehensive and integrative model of IB moderated by TFL. This study provides scholars a deeper understanding of relationship among IB, employee's commitment and TFL. Though multicollinearity is addressed, presence of cross-sectional data is a limitation in the study.Practical implicationsThe study would help practicing managers to gain a new perspective to manage their internal brand mechanisms through TFL style by stimulating change among employees and create emotionally committed brand advocates.Originality/valueThis paper suggests an empirically validated framework of IB tested for moderation effect by TFL. It adds value to literature by reinforcing the effect of IB employees' AC and NC, especially among customer contact employees who represent brand during customer service delivery in telecommunication sector.