bluuebunny/crossref_metadata_2025_split huggingface dataset:
Susceptibility of wild canids to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Authors: Porter Stephanie M. , Hartwig Airn E. , Bielefeldt-Ohmann Helle , Bosco-Lauth Angela M. , Root J. Jeffrey 
Published: February 2022

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has proven to be a promiscuous virus, capable of infecting a variety of different animal species, but much work remains in determining the susceptibility of common wildlife species to the virus. Here, we demonstrate that following experimental inoculation with SARS-CoV-2, red fox (Vulpes vulpes) become infected and can shed virus in oral and respiratory secretions. Conversely, experimentally challenged coyotes (Canis latrans) did not become infected or shed virus. Our results add red fox to the animal species known to be susceptible to SARS-CoV-2 and suggest that they may contribute to continued maintenance and transmission of the virus.Article Summary LineExperimental infection of red fox (Vulpes vulpes) and coyotes (Canis latrans) with SARS-CoV-2 revealed that red fox are susceptible to infection and can shed virus, while coyotes do not become infected.
Impact of APOE ε3 and ε4 genotypes on plasma proteome signatures in Alzheimer’s disease
Authors: Kaur Gurjeet , Poljak Anne , Masters Colin L , Fowler Christopher , Sachdev Perminder 
Published: February 2022

AbstractThe ε4 allele of the apolipoprotein E (APOE) gene is a high-risk factor for Alzheimer’s disease (AD). However, approximately 25%–40% of patients with AD do not carry the APOEε4 allele, and the pathophysiological mechanisms underlying AD are less evident in these individuals. The main objective of this study was to understand better the changes in plasma that may contribute to disease pathogenesis in AD and how APOEε3 and APOEε4 contribute to biomarker profiles in AD. We conducted an in-depth plasma proteomics analysis using intensive depletion of high-abundant plasma proteins using the Agilent multiple affinity removal liquid chromatography (LC) column-Human 14 (Hu14) followed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS PAGE) technique. In this study, we identified a high number of protein expression alterations in plasma which were found uniquely in APOEε3 and APOEε4 carriers. These differentially expressed proteins (DEPs) were associated with several molecular functions, including complement cascade, glycolysis, metabolism, plasma lipoprotein assembly, remodelling, and clearance. In addition to unique changes in both APOE genotypes, many proteins were also dysregulated in the presence of both APOEε3 and APOEε4 genotypes depicting the involvement of these proteins in the pathogenesis of AD regardless of the APOE genotypes. We also compared the plasma proteomes of ε4 and ε3 carriers in normal controls, which provided insight into factors that may provide protection from progression to AD despite the presence of the ε4 allele. Furthermore, our findings also identified some proteins previously discovered in AD CSF and brain proteomics signatures that could provide clinically meaningful information.
Using Unassigned NMR Chemical Shifts to Model RNA Secondary Structure
Authors: Moudgal Neel , Arhin Grace , Frank Aaron T. 
Published: February 2022

AbstractNMR-derived chemical shifts are sensitive probes of RNA structure. However, the need to assign NMR spectra hampers their utility as a direct source of structural information. In this report, we describe a simple method that uses unassigned 2D NMR spectra to model the secondary structure of RNAs. Similar to assigned chemical shifts, we could use unassigned chemical shift data to reweight conformational libraries such that the highest weighted structure closely resembles their reference NMR structure. Furthermore, the application of our approach to the 3’- and 5’-UTR of the SARS-CoV-2 genome yields structures that are, for the most part, consistent with the secondary structure models derived from chemical probing data. Therefore, we expect the framework we describe here will be useful as a general strategy for rapidly generating preliminary structural RNA models directly from unassigned 2D NMR spectra. As we demonstrated for the 337-nt and 472-nt UTRs of SARS-CoV-2, our approach could be especially valuable for modeling the secondary structures of large RNA.
A cross taxonomic comparison of bird and butterfly communities of Tamhini Wildlife Sanctuary across two decades
Authors: Dsouza Shawn , Padhye Anand 
Published: February 2022

AbstractHuman disturbance can alter the structure and function of ecological communities. We studied bird and butterfly communities of Tamhini wildlife sanctuary to understand the effects two decades of changing land use and management. We replicated a previous study conducted between 1998 and 2001, sampling 7 line transects every fortnight between April 2016 and April 2017. We analyzed the diversity and structure of functional groups and compared our findings to previous surveys. Species diversity increased for both taxa, however, community composition was significantly different across studies. Changing land may affect multiple trophic levels and alter community assembly and ecosystem function.
Good work in the COVID-19 recovery: priorities and changes for the future
Authors: Griffiths Melda Lois , Gray Benjamin J , Kyle Richard G , Davies Alisha R 
Published: February 2022

AbstractEmployment is a wider determinant of health, and the COVID-19 pandemic has disrupted working lives, with individuals having to adapt to new ways of working. These new experiences may shape what kind of work people want in future. This research used a sample of working adults in Wales to identify the workforce’s priorities for future work, and the employment changes that they have considered making since the start of the COVID-19 pandemic. Data was collected at two time-points (May-June 2020; December 2020-January 2021) in a nationally-representative longitudinal household survey across Wales.Work priorities remained largely stable throughout the pandemic, however the desire to work close to home increased as the pandemic progressed. Those in poorer health prioritised flexibility, and were more likely to consider retiring than their healthier counterparts. Becoming self-employed was more likely to be considered by those with limiting pre-existing conditions or low mental well-being. Over 20% of the total sample had considered retraining, with those with low mental well-being, younger individuals and those experiencing financial insecurity being more likely to consider doing so. Furloughed individuals were more likely to consider retraining, becoming self-employed, securing permanent employment and compressing their working hours.Those prone to facing insecurity within their working lives (those that were furloughed, those experiencing financial insecurity, and those in ill-health) were all more likely to consider changing their employment conditions – these groups may require additional support in accessing secure and flexible work. Action is needed to ensure that good work, that is good for health, is equally accessible for all.
Secretin receptor as a target in gastrointestinal cancer: expression analysis and ligand development
Authors: Klussmeier Anja , Aurich Stefan , Niederstadt Lars , Wiedenmann Bertram , Grötzinger Carsten 
Published: February 2022

AbstractSecretin was originally discovered as a gastrointestinal peptide that stimulates fluid secretion from pancreas and liver and delays gastric emptying. In disease, secretin receptor (SCTR) was found to occur as a splice variant in gastrinoma and pancreatic adenocarcinoma. Overexpression of SCTR has been described for gastrinomas, carcinoid tumors of the lung and cholangiocarcinoma. SCTR therefore remains a candidate target for molecular tumor imaging as well as for peptide receptor radioligand therapy (PRRT) in a number of oncological indications. The aim of this study was to characterize SCTR expression in esophageal and pancreatic cancer. 65 of 70 PDAC tissues stained strongly positive for SCTR in immunohistochemistry, as were most of 151 esophageal cancer samples, with minor influence of grading in both entities. In addition, the aim of this study was to further delineate residues in human secretin that are critical for binding to and activation of the human SCTR. For a potential development of short and metabolically stable analogs for clinical use, it was intended to probe the peptide for its capacity to incorporate deletions and substitutions without losing its affinity to SCTR. A library of 146 secretin variants containing single amino acid substitutions as well as truncations on either end was tested using β-arrestin2-GFP translocation and fluorescent ligand internalization high-content analysis and cAMP assays run in agonist and antagonist mode as well as a radioligand binding. The main structural determinants of SCTR binding and activation were localized to the N-terminus, with His1, Asp3 being among the most sensitive positions, followed by Phe6, Thr7 and Leu10. Aminoterminal truncation caused a rapid decline in receptor activity and most of these variants proved to be partial agonists showing antagonistic properties. In this study, the most potent antagonist showed an IC50 of 309 ± 74 nM in the β-arrestin2-GFP translocation assay on human SCTR while remaining a weak partial agonist. Future studies will have to demonstrate the utility of further enhanced secretin analogues as tracers for in vivo imaging and therapy.
A Genetically encoded BRET-based SARS-CoV-2 Mpro protease activity sensor
Authors: Geethakumari Anupriya M , Ahmed Wesam S , Rasool Saad , Fatima Asma , Uddin S.M. Nasir , Aouida Mustapha , Biswas Kabir H 
Published: February 2022

AbstractThe SARS-CoV-2 main protease, Mpro, is critical for its replication and is an appealing target for designing anti-SARS-CoV-2 agents. In this regard, a number of assays have been developed based on its cleavage sequence preferences to monitor its activity. These include the usage of Fluorescence Resonance Energy Transfer (FRET)-based substrates in vitro and a FlipGFP reporter, one which fluoresces after Mpro-mediated cleavage, in live cells. Here, we have engineered a pair of genetically encoded, Bioluminescence Resonance Energy Transfer (BRET)-based sensors for detecting SARS-CoV-2 Mpro proteolytic activity in living host cells as well as in vitro assays. The sensors were generated by sandwiching Mpro N-terminal autocleavage sites, either AVLQSGFR (short) or KTSAVLQSGFRKME (long), in between the mNeonGreen and nanoLuc proteins. Co-expression of the sensor with the Mpro in live cells resulted in its cleavage in a dose- and time-dependent manner while mutation of the critical C145 residue (C145A) in Mpro completely abrogated the sensor cleavage. Importantly, the BRET-based sensors displayed increased sensitivities and specificities as compared to the recently developed FlipGFP-based Mpro sensor. Additionally, the sensors recapitulated the inhibition of Mpro by the well-characterized pharmacological agent GC376. Further, in vitro assays with the BRET-based Mpro sensors revealed a molecular crowding-mediated increase in the rate of Mpro activity and a decrease in the inhibitory potential of GC376. The sensor developed here will find direct utility in studies related to drug discovery targeting the SARS-CoV-2 Mpro and functional genomics application to determine the effect of sequence variation in Mpro.
Quantifying changes in individual-specific template-based representations of center-of-mass dynamics during walking with ankle exoskeletons using Hybrid-SINDy
Authors: Rosenberg Michael C. , Proctor Joshua L. , Steele Katherine M. 
Published: February 2022

AbstractAnkle exoskeletons alter whole-body walking mechanics, energetics, and stability by altering center-of-mass (CoM) motion. Controlling the dynamics governing CoM motion is, therefore, critical for maintaining efficient and stable gait. However, how CoM dynamics change with ankle exoskeletons is unknown, and how to optimally model individual-specific CoM dynamics, especially in individuals with neurological injuries, remains a challenge. Here, we evaluated individual-specific changes in CoM dynamics in unimpaired adults and one individual with post-stroke hemiparesis while walking in shoes-only and with zero-stiffness and high-stiffness passive ankle exoskeletons. To identify optimal sets of physically interpretable mechanisms describing CoM dynamics, termedtemplate signatures, we leveraged hybrid sparse identification of nonlinear dynamics (Hybrid-SINDy), an equation-free data-driven method for inferring sparse hybrid dynamics from a library of candidate functional forms. In unimpaired adults, Hybrid-SINDy automatically identified spring-loaded inverted pendulum-like template signatures, which did not change with exoskeletons (p>0.16), except for small changes in leg resting length (p<0.001). Conversely, post-stroke paretic-leg rotary stiffness mechanisms increased by 37-50% with zero-stiffness exoskeletons. While unimpaired CoM dynamics appear robust to passive ankle exoskeletons, how neurological injuries alter exoskeleton impacts on CoM dynamics merits further investigation. Our findings support Hybrid-SINDy’s potential to discover mechanisms describing individual-specific CoM dynamics with assistive devices.
HOXD13 is a direct EWS-FLI1 target and moderates fusion-dependent transcriptional states
Authors: Apfelbaum April A. , Wu Feinan , Magnuson Brian , Hawkins Allegra G. , Jiménez Jennifer A. , Taylor Sean D. , Pfaltzgraff Elise R. , Song Jane Y. , Hall Cody , Wellik Deneen M. , Ljungman Mats , Furlan Scott , Ryan Russell J.H. , Sarthy Jay F. , Lawlor Elizabeth R. 
Published: February 2022

AbstractOncogenic fusion proteins display exquisite tissue specificity, revealing that malignant transformation requires cooperation with cell-autonomous factors. Recent studies have also demonstrated that tumorigenicity of Ewing sarcoma requires precise regulation of the transcriptional activity of the EWS-FLI1 oncogenic driver. Here we show that the developmentally and anatomically restricted transcription factor HOXD13 is a direct target of EWS-FLI1. Transcriptomic and CUT&RUN studies revealed that HOXD13 binds active, fusion-bound enhancers, resulting in altered expression of EWS-FLI1-induced targets. More strikingly, HOXD13 was found to bind and activate cis-regulatory regions of genes that are normally repressed by EWS-FLI1. Single-cell sequencing demonstrated marked intra-tumoral heterogeneity of HOXD13 transcriptional activity and revealed that antagonism between HOXD13-mediated gene activation and EWS-FLI1-dependent gene repression confers a spectrum of transcriptional cell states along a mesenchymal axis. Thus, HOXD13 serves as an internal rheostat for EWS-FLI1 activity, providing a paradigm for tissue-specific transcription factors as critical partners in fusion-driven cancers.
Variation of the Rdr1 gene insertion in wild populations of Nicotiana benthamiana (Solanaceae) and insights into recent species divergence
Authors: Cauz-Santos Luiz A. , Dodsworth Steven , Samuel Rosabelle , Christenhusz Maarten J.M. , Patel Denise , Shittu Taiwo , Jakob Aljaž , Paun Ovidiu , Chase Mark W. 
Published: February 2022

SummaryOne of the most commonly encountered and frequently cited laboratory organisms worldwide is classified taxonomically as Nicotiana benthamiana (Solanaceae), an accession of which, typically referred to as LAB, is renowned for its unique susceptibility to a wide range of plant viruses and hence capacity to be transformed using a variety of methods. However, the origin and age of LAB and the evolution of N. benthamiana across its wide distribution in Australia remains relatively underexplored.Here, we have used multispecies coalescent methods on genome-wide single nuclear polymorphisms (SNPs) to assess species limits, phylogenetic relationships and divergence times within N. benthamiana.Our results show that the previous taxonomic concept of this species in fact comprises five geographically, morphologically and genetically distinct species, one of which includes LAB.Remarkably, we provide clear evidence that LAB is closely related to accessions collected further north in the Northern Territory; this species split much earlier from their common ancestor than the other four in this clade and is morphologically the most distinctive. Furthermore, this long-isolated species typically grows in sheltered sites in subtropical/tropical monsoon areas of northern Australia, contradicting the previously advanced hypothesis that this species is an extremophile that has traded viral resistance for precocious development.
Genome-wide CRISPR Screens Identify Ferroptosis as a Novel Therapeutic Vulnerability in Acute Lymphoblastic Leukemia
Authors: Lalonde Marie-Eve , Sasseville Marc , Gélinas Anne-Marie , Milanese Jean-Sébastien , Béland Kathie , Drouin Simon , Haddad Elie , Marcotte Richard 
Published: February 2022

AbstractAcute lymphoblastic leukemia (ALL) is the most frequent cancer diagnosed in children. Despite the great progress achieved over the last 40 years, with cure rates now exceeding 85%, refractory or relapsed ALL still exhibit a dismal prognosis. This poor outcome reflects the lack of treatment options specifically targeting relapsed or refractory ALL. To address this gap, we have performed whole-genome CRISPR/Cas drop-out screens on a panel of seven B-ALL cell lines. Our results demonstrate that while there was a significant overlap in gene essentiality between ALL cell lines and other cancer types survival of ALL cell lines was dependent on several unique metabolic pathways, including an exquisite sensitivity to GPX4 depletion and ferroptosis induction and GPX4 KO. Detailed molecular analysis of B-ALL cells suggest that they are primed to undergo ferroptosis as they exhibit high steady-state oxidative stress potential, a low buffering capacity, and a disabled GPX-independent secondary lipid peroxidation detoxification pathway. Finally, we validated the sensitivity of B-ALL to ferroptosis induction using patient-derived B-ALL samples.
Bank competition, interest rate pass-through and the impact of the global financial crisis: evidence from Hong Kong and Macao
Authors: Li Jingya , Li Zongyuan , Liu Ming-Hua 
Published: February 2022

PurposeThe authors examine the interest rate pass-through in Hong Kong (HK) and Macao both in the long term and short term.Design/methodology/approachThe authors use time series methodology, i.e. unit root, cointegration and error correction models.FindingsThe results show that in the post-global financial crisis (GFC) period, both the long-run and short-run interest rate pass-through from policy rates to prime rates have disappeared in Macao and are weakened significantly in Hong Kong. The long-term relationship between deposit rates and policy rates no longer exists in either market while the short-term relationship has been reduced significantly.Research limitations/implicationsThe results indicate that the effectiveness of monetary policy in HK and Macao has been seriously undermined in the post-GFC period. New tools are needed in both regions.Practical implicationsMonetary policy transmission via bank interest rates in both HK and Macao are no longer effective after the outbreak of the GFC.Social implicationsEffort to stimulate the economy and/or control inflation will be hampered.Originality/valueTo the best of the authors’ knowledge, this is the first study to examine the impact of the GFC on the effectiveness of monetary policy transmission in HK and Macao.
A multiproject scheduling and resource management model in projects construction
Authors: Cheraghi Esmail , Zohrehvandi Shakib , Vanhoucke Mario , Mohamadpour Tosarkani Babak 
Published: February 2022

PurposeThis research presents a multiproject scheduling and resource management (MPSRM) model that includes an M/M/c/n queue system, a p-hub median model, a parallel machine scheduling and a hub location problem solution method. This research aims to design a project network and then sequence raw materials delivery to hub factories.Design/methodology/approachThis research is implemented as a case study in construction and industrial company. It considers several mines to supply raw materials for production in hub factories. In the sequencing phase, a parallel mine scheduling problem specifies the delivery of raw materials to hub factories. Furthermore, a multisource project scheduling model is studied and designed for building project-oriented companies.FindingsThe results suggest that the proposed MPSRM model in this study significantly reduces project transportation costs. Therefore, creating accurate planning in projects, especially in construction projects where transportation plays an important role, can help reduce time and costs. Researchers, project managers and those dealing with projects can use this model to exploit their projects.Research limitations/implicationsWhen the number of construction projects in a construction company increases in a region, choosing an appropriate strategy to supply resources and raw materials becomes very important in terms of profit and loss and project completion as scheduled. An increase in transportation demands alongside the economic development on the one hand and providing competitive transportation services, on the other hand, have increasingly spotlighted the significance of hub networks in transportation systems. In addition, in this research, there is no suitable access road from the mines to the project sites, and considering the workload, if any of the projects become a hub, a proper road should be built.Originality/valueTo the best of the knowledge, there is no outstanding research in which a p-hub median location problem by considering queuing model and different transportation modes and a parallel machine scheduling problem are studied simultaneously.
Can a connection with the indigenous cultural values encourage sustainable apparel consumption?
Authors: Chakraborty Swagata , Sadachar Amrut 
Published: February 2022

PurposeThe authors investigated the role of cultural (i.e. traditional and religious) values in predicting the relationships between the attitudes toward the environment and slow fashion and the purchase intention for sustainable apparel.Design/methodology/approachAn online survey was conducted in Amazon Mechanical Turk with the millennials of the US (n = 317). The data were analyzed through structural equation modeling (SEM).FindingsThe connection with indigenous cultural values in terms of the (1) traditional values positively influenced attitudes toward the environment and slow fashion; (2) religious values positively influenced attitude toward slow fashion but did not influence attitude toward the environment. (3) Both attitudes towards environment and slow fashion positively influenced purchase intention for sustainable apparel. (4) The connection with cultural values did not influence purchase intention toward sustainable apparel directly; however, (5) attitude toward slow fashion mediated the relationship between connection with cultural values and purchase intention for sustainable apparel both in terms of traditional and religious values, and (6) attitude toward the environment mediated the relationship between connection with traditional values and purchase intention for sustainable apparel.Practical implicationsInstead of focusing only on pro-environmental messages, marketers should use culture-specific cues to evoke favorable attitudinal and behavioral responses toward sustainable apparel.Social implicationsAdvertisement cues of sustainable apparel imbuing the target market's cultural values could help in protecting culturally significant elements of nature in the long-term by evoking positive attitudes toward the environment and slow fashion and encouraging purchase intention for sustainable apparel in the short-term.Originality/valueThe authors indicated the importance of indigenous cultural values in shaping favorable attitudes toward the environment and slow fashion and purchase intention for sustainable apparel.