bluuebunny/crossref_metadata_2025_split huggingface dataset:
Corporately Owned Plants need Space: An Analysis on Plant Biodiversity in Toronto’s Privately-owned Publicly Accessible Spaces
Authors: Ho Matthew R 
Published: February 2023

AbstractUrban plant biodiversity is a growing ecological concern for city planners and ecologists. While parks are serviced by the public sector, and yards are pruned by the private citizen, a growing proportion of urban green space is managed by corporations. Despite biodiversity targets set by city councils and public committees, actual plant surveys have not been performed. Employing coordinate data of Privately-Owned Publicly-accessible Spaces (POPS) from the City of Toronto, we sampled plant species richness in nine corporately-managed green spaces. Using linear mixed-effect models, we compared richness with various green space characteristics and found that site area is an important predictor. Our results concur with prior studies showing that habitat area may cause significant impacts to urbanized plant biodiversity.
TERT accelerates BRAF mutant-induced thyroid cancer dedifferentiation and progression by regulating ribosome biogenesis
Authors: Yu Pengcheng , Qu Ning , Zhu Rui , Hu Jiaqian , Han Peizhen , Tan Licheng , Gan Hualei , He Cong , Fang Chuantao , Lei Yubin , Li Jian , He Chenxi , Lan Fei , Shi Xiao , Wei Wenjun , Wang Yu , Ji Qinghai , Yu Fa-Xing , Wang Yu-Long 
Published: February 2023

AbstractTERT reactivation occurs frequently in human malignancies. While BRAF activating mutation widely existed in cancers at various stages, TERT reactivation mainly occurs in advanced tumors. However,in vivoevidence for TERT role in cancer progression and the underlying mechanism is currently lacking. In this study, we induced TERT and/or BRAF V600E expression in mouse thyroid epithelium. TERT overexpression alone had no evident effect on tumor initiation. BRAFVEexpression itself induced mediocre papillary thyroid cancer (PTC). Notably, the co-expression of BRAFVEand TERT resulted in aggressive poorly differentiated thyroid carcinoma (PDTC). Spatial transcriptome revealed that tumors from co-mutant mice were highly heterogeneous and dedifferentiation process significantly correlated with ribosomal pathways. Mechanistically, TERT boosted ribosomal RNA expression and protein synthesis. CX-5461, a rRNA transcription inhibitor, effectively blocked proliferation and induced redifferentiation. Thus, TERT promotes thyroid cancer progression by inducing dedifferentiation, and ribosome biogenesis inhibition represents a potential treatment strategy for TERT-reactivated cancers.Highlights➢TERT accelerated thyroid cancer dedifferentiation and metastasisin vivo➢TERT regulated rRNA metabolism and MTORC1/ S6K/RPS6 activities➢CX-5461 inhibited the progression of TERT-reactivated melanoma and thyroid cancer➢Inhibition of rRNA induced redifferentiation of advanced thyroid cancer with TERT activation
Ryanodine receptor 2 inhibition reduces dispersion of cardiac repolarization, improves contractile function and prevents sudden arrhythmic death in failing hearts
Authors: Joshi Pooja , Estes Shanea , DeMazumder Deeptankar , Knollmann Bjorn C. , Dey Swati 
Published: February 2023

AbstractIntroductionSudden cardiac death (SCD) from ventricular tachycardia/fibrillation (VT/VF) are a leading cause of death, but current therapies are limited. Despite extensive research on drugs targeting sarcolemmal ion channels, none have proven sufficiently effective for preventing SCD. Sarcoplasmic ryanodine receptor 2 (RyR2) Ca2+release channels, the downstream effectors of sarcolemmal ion channels, are underexplored in this context. Recent evidence implicates reactive oxygen species (ROS)- mediated oxidation and hyperactivity of RyR2s in the pathophysiology of SCD.ObjectiveTo test the hypothesis that RyR2 inhibition of failing arrhythmogenic hearts reduces sarcoplasmic Ca2+leak and repolarization lability, mitigates VT/VF/SCD and improves contractile function.MethodsWe used a guinea pig model that replicates key clinical aspects of human nonischemic HF, such as a prolonged QT interval, a high prevalence of spontaneous arrhythmic SCD, and profound Ca2+leak via a hyperactive RyR2. HF animals were randomized to receive dantrolene (DS) or placebo in early or chronic HF. We assessed the incidence of VT/VF and SCD (primary outcome), ECG heart rate and QT variability, echocardiographic left ventricular (LV) structure and function, immunohistochemical LV fibrosis, and sarcoplasmic RyR2 oxidation.ResultsDS treatment prevented VT/VF and SCD by decreasing dispersion of repolarization and ventricular arrhythmias. Compared to placebo, DS lowered resting heart rate, preserved chronotropic competency during transient β-adrenergic challenge, and improved heart rate variability and cardiac function.ConclusionInhibition of RyR2 hyperactivity with dantrolene mitigates the vicious cycle of sarcoplasmic Ca2+leak-induced increases in diastolic Ca2+and ROS-mediated RyR2 oxidation, thereby increasing repolarization lability and protecting against VT/VF/SCD. Moreover, the consequent increase in sarcoplasmic Ca2+load improves contractile function. These potentially life-saving effects of RyR2 inhibition warrant further investigation, such as clinical studies of repurposing dantrolene as a potential new therapy for heart failure and/or SCD.
Study Protocol for the Pilot Evaluation for SMartphone-adaptable Artificial Intelligence for PRediction and DeTection of Left Ventricular Systolic Dysfunction (The SMART-LV Pilot Study Protocol)
Authors: Dhingra Lovedeep Singh , Aminorroaya Arya , Sangha Veer , Khunte Akshay , Oikonomou Evangelos K , Mortazavi Bobak J , McNamara Robert , Herrin Jeph , Wilson Francis P , Krumholz Harlan M , Khera Rohan 
Published: February 2023

ABSTRACTIntroductionDespite a prevalence of 3-5% among adults, asymptomatic left ventricular systolic dysfunction (LVSD) remains underdiagnosed. There is a critical need for an accurate and widely accessible screening strategy for LVSD, given its association with preventable morbidity and premature mortality. A novel deep learning approach has demonstrated the ability to detect LVSD directly from ECG images, with retrospective validation across multiple institutions. There is a lack of prospective validation. In this pilot study, we evaluate the feasibility of screening and recruiting individuals for prospective echocardiography based on an image-based artificial intelligence (AI)-ECG algorithm applied to the ECG repository at a large academic medical center.Research Methods and AnalysisThis is the protocol for a prospective cohort study in outpatient primary care clinics of the Yale New Haven Hospital (YNHH). Adult patients who have undergone a 12-lead ECG without subsequent echocardiogram as a part of routine clinical care within 90 days of the ECG will be identified in the electronic health record (EHR). The AI-ECG model for LVSD will be deployed to YNHH ECG repository to define the probability of LVSD, identifying 5 patients each with high and low probability of LVSD. After discussion with primary care physicians, and subsequent contact by the study team, screened participants will be invited for and undergo an echocardiogram. The study participants and the cardiologists conducting the echocardiograms will be blinded to the results of the AI-ECG screen. The analysis will focus on feasibility metrics: the proportion (i) of all patients undergoing ECGs who have high probability of LVSD without subsequent echocardiogram, (ii) of patients who agree to participate in the study, and (iii) that undergo an echocardiogram. A descriptive exploration of the comparison of the AI-ECG and echocardiogram results will also be reported.Ethics and DisseminationAll patient EHR data required for assessing eligibility and conducting the AI-ECG screening will be accessed through secure servers approved for protected health information. Potential participants will only be contacted after they have discussed the study information with their primary care physician. All participants will be required to provide written informed consent before participation and data will be deidentified prior to analysis. This study protocol has been approved by the Yale Institutional Review Board (Protocol Number: 2000034006) and has been registered atClinicalTrials.gov(Identifier:NCT05630170). The results of the future validation study will be published in peer-reviewed journals and summaries will be provided to the study participants.
Biochemical and Genetic Evidence Supports Fyv6 as a Second-Step Splicing Factor inSaccharomyces cerevisiae
Authors: Lipinski Karli A. , Senn Katherine A. , Zeps Natalie J. , Hoskins Aaron A. 
Published: February 2023

ABSTRACTPrecursor mRNA (pre-mRNA) splicing is an essential process for gene expression in eukaryotes catalyzed by the spliceosome in two transesterification steps. The spliceosome is a large, highly dynamic complex composed of 5 small nuclear RNAs and dozens of proteins, some of which are needed throughout the splicing reaction while others only act during specific stages. The human protein FAM192A was recently proposed to be a splicing factor that functions during the second transesterification step, exon ligation, based on analysis of cryo-electron microscopy (cryo-EM) density. It was also proposed that Fyv6 might be the functionalS. cerevisiaehomolog of FAM192A; however, no biochemical or genetic data has been reported to support this hypothesis. Herein, we show that Fyv6 is a splicing factor and acts during exon ligation. Deletion ofFYV6results in genetic interactions with the essential splicing factors Prp8, Prp16, and Prp22; decreases splicingin vivoof reporter genes harboring intron substitutions that limit the rate of exon ligation; and changes 3’ splice site (SS) selection. Together, these data suggest that Fyv6 is a component of the spliceosome and the potential functional and structural homolog of human FAM192A.
Antibiotic hyper-resistance in a class I aminoacyl-tRNA synthetase with altered active site signature motif
Authors: Brkic A. , Leibundgut M. , Jablonska J. , Zanki V. , Car Z. , Petrovic-Perokovic V. , Maršavelski A. , Ban N. , Gruic-Sovulj I. 
Published: February 2023

AbstractAntibiotics target key biological processes that include protein synthesis. Bacteria respond by developing resistance, which increases rapidly due to antibiotics overuse. Mupirocin, a clinically used natural antibiotic, inhibits isoleucyl-tRNA synthetase (IleRS), an enzyme that links isoleucine to its tRNAIlefor protein synthesis. Two IleRSs, mupirocin-sensitive IleRS1 and resistant IleRS2, coexist in bacteria. The latter may also be found in resistantStaphylococcus aureusclinical isolates. Here, we describe the structural basis of mupirocin resistance and unravel a mechanism of hyper-resistance evolved by some IleRS2 proteins. We surprisingly find that an up to 103-fold increase in resistance originates from alteration of the HIGH motif, a signature motif of the class I aminoacyl-tRNA synthetases to which IleRSs belong. The structural analysis demonstrates how an altered HIGH motif could be adopted in IleRS2 but not IleRS1, providing insight into an elegant mechanism for coevolution of the key catalytic motif and associated antibiotic resistance.
Identification of two β-cell subtypes by 7 independent criteria
Authors: Dror Erez , Fagnocchi Luca , Wegert Vanessa , Apostle Stefanos , Grimaldi Brooke , Gruber Tim , Panzeri Ilaria , Heyne Steffen , Höffler Kira Daniela , Kreiner Victor , Ching Reagan , Lu Tess Tsai-Hsiu , Semwal Ayush , Johnson Ben , Senapati Parijat , Lempradl Adelheid M. , Schones Dustin , Imhof Axel , Shen Hui , Pospisilik John Andrew 
Published: February 2023

SummaryDespite the recent explosion in surveys of cell-type heterogeneity, the mechanisms that specify and stabilize highly related cell subtypes remain poorly understood. Here, focusing initially on exploring quantitative histone mark heterogeneity, we identify two major sub-types of pancreatic β-cells (βHIand βLO). βHIand βLOcells differ in their size, morphology, cytosolic and nuclear ultrastructure, transcriptional output, epigenomes, cell surface marker, and function. Importantly, βHIand βLOcells can be FACS separated live into CD24+(βHI) and CD24-(βLO) fractions. From an epigenetic viewpoint, βHI-cells exhibit ∼4-fold higher levels of H3K27me3, more compacted chromatin, and distinct chromatin organization that associates with a specific pattern of transcriptional output. Functionally, βHIcells have increased mitochondrial mass, activity, and insulin secretion bothin vivoandex vivo. Critically,EedandJmjd3loss-of-function studies demonstrate that H3K27me3 dosage is a significant regulator of βHI/ βLOcell ratioin vivo,yielding some of the first-ever specific models of β-cell sub-type distortion. βHIand βLOsub-types are conserved in humans with βHI-cells enriched in human Type-2 diabetes. These data identify two novel and fundamentally distinct β-cell subtypes and identify epigenetic dosage as a novel regulator of β-cell subtype specification and heterogeneity.HighlightsQuantitative H3K27me3 heterogeneity reveals 2 common β-cell subtypesβHIand βLOcells are stably distinct by 7 independent sets of parametersH3K27me3 dosage controls βHI/ βLOratio in vivoβHIand βLOcells are conserved in humans and enriched in Type-2 diabetes
The ALS/FTD-related C9orf72 hexanucleotide repeat expansion forms RNA condensates through multimolecular G-quadruplexes
Authors: Raguseo Federica , Huyghebaert Anouk , Li Jessica , Balendra Rubika , Howe Marija Petrić , Wang Yiran , Vadukul Devkee M. , Tanase Diana A. , Maher Thomas E. , Malouf Layla , Rubio-Sánchez Roger , Aprile Francesco A. , Elani Yuval , Patani Rickie , Michele Lorenzo Di , Antonio Marco Di 
Published: February 2023

AbstractAmyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases that exist on a clinico-pathogenetic spectrum, designated ALS/FTD. The most common genetic cause of ALS/FTD is the expansion of the intronic hexanucleotide repeat (GGGGCC)ninC9orf72. Here, we investigated the formation of nucleic-acid secondary structures in these expansion repeats, and their role in generating condensates characteristic of the diseases. We observed significant aggregation of the hexanucleotide sequence (GGGGCC)n, which we associated to the formation of multimolecular G-quadruplexes (mG4s), using a range of biophysical techniques. Exposing the condensates to G4-unfolding conditions led to prompt disassembly, highlighting the key role of mG4-formation in the condensation process. We further validated the biological relevance of our findings by demonstrating the ability of a G4-selective fluorescent probe to penetrateC9orf72mutant human motor neurons derived from ALS patients, which revealed clear fluorescent signal in putative condensates. Our findings strongly suggest that RNA G- rich repetitive sequences can form protein-free condensates sustained by multimolecular G- quadruplexes, highlighting their potential relevance as therapeutic targets forC9orf72mutation related ALS and FTD.
Pseudouridine prevalence in Kaposi’s sarcoma-associated herpesvirus transcriptome reveals an essential mechanism for viral replication
Authors: Mottram Timothy J. , Harper Katherine L. , Vasconcelos Elton J. R. , Anene Chinedu A. , Whitehouse Adrian 
Published: February 2023

AbstractPseudouridylation is a prevalent RNA modification shown to occur in tRNAs, rRNAs, snoRNAs and most recently mRNAs and lncRNAs. Emerging evidence suggests that this dynamic RNA modification is implicated in altering gene expression by regulating RNA stability, modulating translation elongation and modifying amino acid substitution rates. However, the role of pseudouridylation in infection is poorly understood. Here we demonstrate that Kaposi’s sarcoma-associated herpesvirus (KSHV) manipulates the pseudouridylation pathway to enhance replication. We show the pseudouridine synthases (PUS), PUS1 and PUS7 are essential for efficient KSHV lytic replication, supported by the redistribution of both PUS1 and PUS7 to viral replication and transcription complexes. We present a comprehensive analysis of KSHV RNA pseudouridylation, revealing hundreds of modified RNAs at single-nucleotide resolution. Notably, we further demonstrate that pseudouridylation of the KSHV-encoded polyadenylated nuclear RNA (PAN) plays a significant role in the stability of PAN RNA and in the association of the KSHV ORF57 protein. Our findings reveal a novel and essential role of pseudouridine modification in the KSHV replication cycle.
Vibrio choleraephage ICP3 requires O1 antigen for infection
Authors: Beckman Drew A. , Waters Christopher M. 
Published: February 2023

SUMMARYIn its natural aquatic environment, the bacterial pathogenVibrio cholerae, the causative agent of the enteric disease cholera, is in constant competition with bacterial viruses known as phages. Following ICP3 infection,V. choleraecultures that exhibited phage killing always recovered overnight, and clones isolated from these regrowth populations exhibited complete resistance to subsequent infections. Whole genome sequencing of these resistant mutants revealed seven distinct mutations in genes encoding for enzymes involved in O1 antigen biosynthesis, demonstrating that the O1 antigen is a previously uncharacterized putative receptor of ICP3. To further elucidate the specificity of the resistance conferred by these mutations, they were challenged with theV. cholerae-specific phages ICP1 and ICP2. All seven O1 antigen mutants demonstrated pan-resistance to ICP1 but not ICP2, which utilizes the OmpU outer membrane protein as a receptor. We show that resistant mutations to ICP1 and ICP3 evolve at a significantly higher frequency than ICP2, but these mutations have a significant fitness tradeoff toV. choleraeand are unable to evolve in the presence of an antimicrobial that mimics host cell defensins.
Influence of curvature distribution smoothing on the reduction of aerofoil self-noise
Authors: Shen Xiang , Avital Eldad , Ikram Zaheer , Yang Liming , Korakianitis Theodosios , Dala Laurent 
Published: February 2023

Purpose
This paper aims to investigate the influence of smooth curvature distributions on the self-noise of a low Reynolds number aerofoil and to unveil the flow mechanisms in the phenomenon.

Design/methodology/approach
In this paper, large Eddy simulation (LES) approach was performed to investigate the unsteady aerodynamic performance of both the original aerofoil E387 and the redesigned aerofoil A7 in a time-dependent study of boundary layer characteristics at Reynolds number 100,000 and angle of attack (AoA) 4-degree. The aerofoil A7 is redesigned from E387 by removing the irregularities in the surface curvature distributions and keeping a nearly identical geometry. Flow vorticity magnitude of both aerofoils, along with the spectra of the vertical fluctuating velocity component and noise level, are analysed to demonstrate the bubble flapping process near the trailing edge (TE) and the vortex shedding phenomenon.

Findings
This paper provides quantitative insights about how the flapping process of the laminar separation bubble (LSB) within the boundary layer near the TE affects the aerofoil self-noise. It is found that the aerofoil A7 with smooth curvature distributions presents a 10% smaller LSB compared to the aerofoil E387 at Reynolds number 100,000 and AoA 4-degree. The LES results also suggest that curvature distribution smoothing leads to a 6.5% reduction in overall broadband noise level.

Originality/value
This paper fulfils an identified need to reveal the unknown flow structure and the boundary layer characteristics that resulted in the self-noise reduction phenomenon yielded by curvature distribution smoothing.
Going green: an application of personal value theory to understand consumers visiting intention toward green hotels in Pakistan
Authors: Raza Ali , Farrukh Muhammad 
Published: February 2023

Purpose
Personal values, ascribed responsibility and green self-identity (GSI) have been analyzed separately for a long time, but a more in-depth investigation is required on the relationships between these variables and their combined effects on consumers' visiting intention toward green hotels. Thus, this study aims to draw on Schwartz's (1992) personal values framework and ascribed responsibility. It expands the Schwartz personal values framework by incorporating GSI as a moderator to understanding consumers' visiting intention toward green hotels.

Design/methodology/approach
Partial least squares-structural equation modeling was used to analyze 387 responses collected through a self-administered structured questionnaire from hotel consumers in Pakistan.

Findings
The findings revealed that ascribed responsibility and self-transcendence values were significant factors in predicting consumers' intention toward green hotels. Moreover, GSI significantly moderated between self-conservation values, self-transcendence values and attitude. However, the association between self-conservation values and attitude was found insignificant.

Practical implications
This study can assist hotel management in planning and implementing efficient hotel marketing strategies. Hospitality marketers should heed attention to self-transcendence values, ascribed responsibility and stress on using these aspects to sustain green hotels' adoption.

Originality/value
The study contributes to the literature on the antecedents of consumers' visiting intention toward green hotels by expanding the Schwartz personal values framework by adding ascribed responsibility. Further, the authors incorporated GSI as a moderator to understand consumers' visiting intentions toward green hotels in Pakistan.