bluuebunny/crossref_metadata_2025_split huggingface dataset:
Presence of sodium taurocholate co-transporting polypeptide and Hepatitis B replication marker on placenta: Another home for the virus
Authors: Garg Garima , MN Meenu , Patel Kajal , Purwar Shashank , Mukhopadhyay Sramana , Mishra Nitu , Gupta Sudheer , Rawat Sumit Kumar , Khosla Ritu , Singh Jitendra , Nema Shashwati , Biswas Debasis , Singh Anirudh K , Vyas Ashish Kumar 
Published: January 2022

AbstractBackgroundThe role of sodium taurocholate co-transporting polypeptide (NTCP), in facilitating the binding of Hepatitis B virus (HBV) on surface of hepatocytes is well documented. Expression of NTCP in extra hepatic cells may make these cells susceptible to HBV infection and support cellular proliferation akin to hepatocytes. Placental replication of HBV is not well explored. In this study we have assessed the expression of NTCP and HBV replication markers (HBeAg, HBcAg, and HBV DNA) in placental cells, to investigate if these cells act as host for HBV.MethodsFourty one HBsAg+ve pregnant women along with 10 healthy controls were enrolled after obtaining informed consent. The HBV DNA in placenta was detected by qPCR using primers for X and core ORF. Expression of NTCP in placenta was analyzed by qRT-PCR and further investigated by immunohistochemistry (IHC) along with HBV replication biomarkers, HBeAg, and HBcAg.ResultsHBsAg positive subjects were divided in two groups on the basis of viral load [High Viral Load (HVL) Group; viral load ≥ 2000IU/ml, Low Viral Load (LVL) Group; viral load <2000IU/ml] according to INASL guidelines 2018. HBV infected females showed increased expression of NTCP in trophoblasts of placenta compared to control group (HVL 3.69±0.13 Vs Control 1.74±0.15, p=0.0117). Furthermore, significant difference in NTCP expression was also observed between HVL and LVL group (HVL 3.69±0.13 Vs LVL 1.98±0.17, p=0.022) and positively correlated with the maternal HBV DNA load. Membranous and/or cytoplasmic immunostaining of NTCP, and cytoplasmic staining of HBeAg and HBcAg in trophoblasts along with presence of HBV DNA indicated that trophoblasts are not only susceptible to HBV infection but may also be a site for viral replication.ConclusionsThis is the pioneer study, which demonstrates expression of NTCP on placenta which may facilitate the entry of HBV. Furthermore, the study establishes the presence of HBeAg in placenta of patients without circulating HBeAg, indicating these cells may act as replication host/reservoir. This pioneering finding hints at the possibility of exploring the potential of NTCP blocking strategies in preventing vertical transmission of HBV.
Structural basis of peptidomimetic agonism revealed by small molecule GLP-1R agonists Boc5 and WB4-24
Authors: Cong Zhaotong , Zhou Qingtong , Li Yang , Chen Li-Nan , Zhang Zi-Chen , Liang Anyi , Liu Qing , Wu Xiaoyan , Dai Antao , Xia Tian , Wu Wei , Zhang Yan , Yang Dehua , Wang Ming-Wei 
Published: January 2022

AbstractGlucagon-like peptide-1 receptor (GLP-1R) agonists are effective in treating type 2 diabetes and obesity with proven cardiovascular benefits. However, most of them are peptides and require subcutaneous injection except for orally available semaglutide. Boc5 was identified as the first orthosteric non-peptidic agonist of GLP-1R that mimics a broad spectrum of bioactivities of GLP-1 in vitro and in vivo. Here, we report the cryo-electron microscopy structures of Boc5 and its analog WB4-24 in complex with the human GLP-1R and Gs protein. Bound to the extracellular domain, extracellular loop 2, and transmembrane (TM) helices 1, 2, 3 and 7, one arm of both compounds inserted deeply into the bottom of the orthosteric binding pocket that is usually accessible by peptidic agonists, thereby partially overlapping with the residues A8-D15 in GLP-1. The other three arms, meanwhile, extended to the TM1-TM7, TM1-TM2, and TM2-TM3 clefts showing an interaction feature substantially similar to a previously known small molecule agonist LY3502970. Such a unique binding mode creates a distinct conformation that confers both peptidomimetic agonism and biased signaling induced by non-peptidic modulators at GLP-1R. Further, the conformational difference between Boc5 and WB4-24, two closed related compounds, provides a structural framework for fine tuning of pharmacological efficacy in the development of future small molecule therapeutics targeting GLP-1R.SignificanceGLP-1R agonists are efficacious in the treatment of type 2 diabetes and obesity. While most clinically used agents require subcutaneous injection, Boc5, as the first orthosteric non-peptidic agonist of GLP-1R, suffers from poor oral bioavailability that hinders its therapeutic development. The cryo-electron microscopy structures of Boc5 and its closely related analog WB4-24 presented here reveal a previously unknown binding pocket located deeper in the transmembrane domain for non-peptidic GLP-1R agonists. Molecular interaction with this site may facilitate a broad spectrum of in vivo agonistic activities, in addition to that with the upper helical bundles presumably responsible for biased signaling. These findings deepen our understanding of peptidomimetic agonism at GLP-1R and may help design better drug leads against this important target.
Nucleoplasmic Lamin C Rapidly Accumulates at Sites of Nuclear Envelope Rupture with BAF and cGAS
Authors: Kono Yohei , Adam Stephen A. , Reddy Karen L. , Zheng Yixian , Medalia Ohad , Goldman Robert D. , Kimura Hiroshi , Shimi Takeshi 
Published: January 2022

AbstractIn mammalian cell nuclei, the nuclear lamina (NL) underlies the nuclear envelope (NE) to maintain nuclear structure. The nuclear lamins, the major structural components of the NL, are involved in the protection against NE rupture induced by mechanical stress. However, the specific role of the lamins in repair of NE ruptures has not been fully determined. Our analyses using immunofluorescence and live-cell imaging revealed that lamin C but not the other lamin isoforms rapidly accumulated at sites of NE rupture induced by laser microirradiation in mouse embryonic fibroblasts. The immunoglobulin-like fold domain and the NLS were required for the recruitment from the nucleoplasm to the rupture sites with the Barrier-to-autointegration factor (BAF). The accumulation of nuclear BAF and cytoplasmic cyclic GMP-AMP synthase (cGAS) at the rupture sites was in part dependent on lamin A/C. These results suggest that nucleoplasmic lamin C, BAF and cGAS concertedly accumulate at sites of NE rupture for repair.SummaryKono et al. show the rapid recruitment of nucleoplasmic lamin C to sites of nuclear envelope rupture with Barrier-to-autointegration factor. Lamin A/C is also involved in nuclear DNA sensing with cytoplasmic cGAS at the ruptured sites.
Identification and molecular characterization of novel viruses in Ugandan cattle
Authors: Balinandi Stephen , Hayer Juliette , Cholleti Harindranath , Wille Michelle , Lutwama Julius J. , Malmberg Maja , Mugisha Lawrence 
Published: January 2022

AbstractThe risk for the emergence of novel viral zoonotic diseases in animals and humans in Uganda is high given its geographical location with high biodiversity. We aimed to identify and characterize viruses in 175 blood samples from cattle selected in Uganda using molecular approaches. We identified 8 viral species belonging to 4 families (Flaviviridae, Peribunyaviridae, Reoviridae and Rhabdoviridae) and 6 genera (Hepacivirus, Pestivirus, Orthobunyavirus, Coltivirus, Dinovernavirus and Ephemerovirus). Four viruses were novel and tetantively named as Zikole virus (Family: Flaviviridae), Zeboroti virus (Family: Reoviridae), Zebtine virus (Family: Rhabdoviridae) and Kokolu virus (Family: Rhabdoviridae). In addition, Bovine hepacivirus, Obodhiang virus, Aedes pseudoscutellaris reovirus and Schmallenberg virus were identified for the first time in Ugandan cattle. We report a broad range of viruses including novel ones in the blood of cattle likely as reservoir hosts for emergence of novel viruses with serious public health implications.HighlightsPan PCR and High Throughput Sequencing Approaches reveal novel viruses in the blood of cattle.Identified 8 viral species belonging to 4 families: Flaviviridae, Peribunyaviridae, Reoviridae and Rhabdoviridae60% of the identified viruses were found in the Ankole cattle breed
GJA1-20k, an internally translated isoform of Connexin 43, is an actin capping protein
Authors: Baum Rachel , Palatinus Joseph A. , Waghalter Miriam , Shimura Daisuke , Jin Qianru , Kuzmanovich Lucas , Xiao Shaohua , Kléber André G. , Grintsevich Elena E. , Hong TingTing , Shaw Robin M. 
Published: January 2022

AbstractPreviously, we identified that GJA1-20k, an internally translated isoform of Connexin 43, mediates an actin-dependent protective form of mitochondrial fission (Shimura, Nuebel et al. 2021). We found that when GJA1-20k is present, bands of actin surround mitochondria at locations enriched with GJA1-20k, inducing mitochondrial fission which generates less oxygen free radicals, protecting hearts subjected to ischemia-reperfusion injury. Here, we report that GJA1-20k is a direct actin binding protein and thereby identify the mechanism by which GJA1-20k is able to recruit and stabilize actin filaments around the mitochondria. Surprisingly, GJA1-20k functions as a canonical actin capping protein, producing both truncated actin puncta and stabilized actin filaments. GJA1-20k contains an RPEL-like actin binding motif, and we confirm with both computational modeling and biochemistry, that this domain is crucial for actin capping. The actin capping functionality of GJA1-20k adds GJA1-20k to the family of proteins that regulate actin dynamics. As a stress responsive protein, GJA1-20k can help explain cytoskeletal dependent responses to cellular stress, from delivery of channels to affecting mitochondrial size and function.
Light-driven biological actuators to probe the rheology of 3D microtissues
Authors: Méry Adrien , Ruppel Artur , Revilloud Jean , Balland Martial , Cappello Giovanni , Boudou Thomas 
Published: January 2022

AbstractThe mechanical properties of biological tissues are key to the regulation of their physical integrity and function. Although the application of external loading or biochemical treatments allows to estimate these properties globally, it remains problematic to assess how such external stimuli compare with internal, cell-generated contractions. Here we engineered 3D microtissues composed of optogenetically-modified fibroblasts encapsulated within collagen. Using light to control the activity of RhoA, a major regulator of cellular contractility, we induced local mechanical perturbation within 3D fibrous microtissues, while tracking in real time microtissue stress and strain. We thus investigated the dynamic regulation of light-induced, local contractions and their spatio-temporal propagation in microtissues. By comparing the evolution of stresses and strains upon stimulation, we demonstrated the potential of our technique for quantifying tissue elasticity and strain propagation, before examining the possibility of using light to create and map local anisotropies in mechanically heterogeneous microtissues. Altogether, our results open an avenue to guide the formation of 3D tissues while non-destructively charting their rheology of 3D tissues in real time, using their own constituting cells as internal actuators.
Reliable cell retention of mammalian suspension cells in microfluidic cultivation chambers
Authors: Schmitz Julian , Stute Birgit , Täuber Sarah , Kohlheyer Dietrich , von Lieres Eric , Grünberger Alexander 
Published: January 2022

AbstractWe present a new microfluidic trapping concept to retain randomly moving suspension cells inside a cultivation chamber. In comparison to previously published complex multilayer structures, we achieve cell retention by a thin PDMS barrier, which can be easily integrated into various PDMS-based cultivation devices. Cell loss during cultivation is effectively prevented while diffusive media supply is still ensured.
Recurrent emergence of carbapenem resistance in Klebsiella pneumoniae mediated by an inhibitory ompK36 mRNA secondary structure
Authors: Wong Joshua L. C. , David Sophia , Sanchez-Garrido Julia , Woo Jia Z. , Low Wen Wen , Morecchiato Fabio , Giani Tommaso , Rossolini Gian Maria , Brett Stephen J. , Clements Abigail , Aanensen David M , Rouskin Silvi , Frankel Gad 
Published: January 2022

AbstractOuter membrane porins in Gram-negative bacteria facilitate antibiotic influx. In Klebsiella pneumoniae (KP), modifications in the porin OmpK36 are implicated in increasing resistance to carbapenems. Analysis of large KP genome collections, encompassing major healthcare-associated clones, revealed the recurrent emergence of a synonymous cytosine to thymine transition at position 25 (25c>t) in ompK36. We show that the 25c>t transition increases carbapenem resistance through depletion of OmpK36 from the outer membrane. The mutation attenuates KP in a murine pneumonia model, which accounts for its limited clonal expansion observed by phylogenetic analysis. However, in the context of carbapenem treatment, the 25c>t transition tips the balance towards treatment failure, thus accounting for its recurrent emergence. Mechanistically, the 25c>t transition mediates an intramolecular mRNA interaction between a uracil encoded by 25t and the first adenine within the Shine-Dalgarno sequence. This specific interaction leads to the formation of an RNA stem structure, which obscures the ribosomal binding site thus disrupting translation. While mutations reducing OmpK36 expression via transcriptional silencing are known, we uniquely demonstrate the repeated selection of a synonymous ompK36 mutation mediating translational suppression in response to antibiotic pressure.
Applied phenomics and genomics for improving barley yellow dwarf resistance in winter wheat
Authors: Silva Paula , Evers Byron , Kieffaber Alexandria , Wang Xu , Brown Richard , Gao Liangliang , Fritz Allan , Crain Jared , Poland Jesse 
Published: January 2022

AbstractBarley yellow dwarf (BYD) is one of the major viral diseases of cereals. Phenotyping BYD in wheat is extremely challenging due to similarities to other biotic and abiotic stresses. Breeding for resistance is additionally challenging as the wheat primary germplasm pool lacks genetic resistance, with most of the few resistance genes named to date originating from a wild relative species. The objectives of this study were to, i) evaluate the use of high-throughput phenotyping (HTP) from unmanned aerial systems to improve BYD assessment and selection, ii) identify genomic regions associated with BYD resistance, and iii) evaluate genomic prediction models ability to predict BYD resistance. Up to 107 wheat lines were phenotyped during each of five field seasons under both insecticide treated and untreated plots. Across all seasons, BYD severity was lower with the insecticide treatment and plant height (PTHTM) and grain yield (GY) showed increased values relative to untreated entries. Only 9.2% of the lines were positive for the presence of the translocated segment carrying resistance gene Bdv2 on chromosome 7DL. Despite the low frequency, this region was identified through association mapping. Furthermore, we mapped a potentially novel genomic region for resistance on chromosome 5AS. Given the variable heritability of the trait (0.211 – 0.806), we obtained relatively good predictive ability for BYD severity ranging between 0.06 – 0.26. Including Bdv2 on the predictive model had a large effect for predicting BYD but almost no effect for PTHTM and GY. This study was the first attempt to characterize BYD using field-HTP and apply GS to predict the disease severity. These methods have the potential to improve BYD characterization and identifying new sources of resistance will be crucial for delivering BYD resistant germplasm.
Generation of rat lungs by blastocyst complementation in Fgfr2b-deficient mouse model
Authors: Yuri Shunsuke , Murase Yuki , Isotani Ayako 
Published: January 2022

AbstractRegenerative medicine is a tool to compensate for the shortage of lungs for transplantation, but it remains difficult to construct a lung in vitro due to the complex three-dimensional structures and multiple cell types required. A blastocyst complementation method using interspecies chimeric animals has been attracting attention as a way to create complex organs in animals, but successful lung formation has not yet been achieved. Here, we applied a “reverse-blastocyst complementation method” to clarify the conditions required to form lungs in an Fgfr2b-deficient mouse model. We then successfully formed a rat-derived lung in the mouse model without generating a mouse line by applying a tetraploid-based organ-complementation method. Importantly, rat lung epithelial cells retained their developmental timing even in the mouse body. This result provides useful insights regarding the need to overcome the barrier of species-specific developmental timing in order to generate functional lungs in interspecies chimeras.
Opposite roles of Rad5 in DNA damage tolerance: playing in both error-free and mutagenic lesion bypass
Authors: Masłowska Katarzyna H. , Pagès Vincent 
Published: January 2022

ABSTRACTDNA Damage Tolerance (DDT) functions to bypass replication-blocking lesions and is divided into two distinct pathways: error-prone Translesion Synthesis (TLS) and error-free Damage Avoidance (DA).Rad5 is a a multifunctional protein that is involved in these DDT processes. Rad5 contains three well defined domains: a RING domain that promotes PCNA polyubiquitination, a ssDNA-dependent ATPase/helicase domain, and a Rev1-binding domain. Both the RING domain and the ATPase/helicase domain are conserved in human Rad5 ortholog HLTF.In this study we used domain-specific mutants to address the contribution of each of Saccharomyces cerevisiae Rad5 functions to lesion tolerance. Using an assay based on the insertion of a single lesion into a defined locus in the genome of a living yeast cell, we demonstrate that Rad5 plays two opposite roles in lesion tolerance: i) Rad5 favors error-free lesion bypass by activating template switching through polyubiquitination of PCNA; ii) Rad5 is required for TLS by recruiting the TLS polymerase Rev1. We also show that the helicase activity does not play any role in lesion tolerance.
Investigation into the adoption of open government data among students: the behavioural intention-based comparative analysis of three countries
Authors: Lněnička Martin , Nikiforova Anastasija , Saxena Stuti , Singh Purnima 
Published: January 2022

PurposeOpen government data (OGD) are considered as a technology capable of promoting transparency openness, and accountability, which in turn has a positive impact on innovation activities and creates responsive government, collaboration, cooperation, co-creation and participation. The purpose of this paper is to explore the adoption of OGD and open data portals among students, in an attempt to discover how governments can improve their actions in this respect.Design/methodology/approachThis study develops a behavioural intention-based analysis using constructs from the Unified Theory of Acceptance and Use of Technology, which is supplemented with additional constructs that meet the purpose of the study. In total, ten constructs divided into 33 items constituted the input for our study. Input data for the developed model have been collected through a structured questionnaire distributed between bachelor's and master's level students in three countries – the Czech Republic, India and Latvia. A structural equation modelling technique was used to analyse the relationships between variables of the model and test the nine hypothesis defined.FindingsSix constructs have been identified to facilitate significant relationships with behavioural intention. The analysis of the results of the three countries allows us to draw more objective conclusions in respect to the aim of the study and to reveal country-specific aspects that need to be addressed in the future.Originality/valueThis study adds to the existing literature few theoretical and practical aspects. It highlights the role of open data portals as a central point of OGD infrastructures. It enables governments to understand the relationships among the related constructs, improving their actions and modifying their data infrastructures accordingly.
Do connoisseur consumers care about sustainability? Exploring coffee consumption practices through netnography
Authors: Bartoloni Sara , Ietto Beatrice , Pascucci Federica 
Published: January 2022

PurposeThe coffee industry has experienced two major trends: the development of connoisseur consumption of specialty coffee and the importance of sustainability. Despite the increasing concomitant relevance of both trends, literature on how sustainability has been interlacing with connoisseur consumption is rather limited. Therefore, this paper aims to analyse how connoisseur consumers (CC) integrate sustainability into their coffee consumption practices.Design/methodology/approachThe paper adopts a qualitative netnographic approach through an interpretive cultural analysis of specialty coffee bloggers narratives, conceived as a specific sub-group of CC that tend to be particularly active on social media.FindingsThrough the lens of social practice theories, the study reveals that CC are likely to implement and perceive sustainability very differently from the dominant mass market as subject to the influence of their shared rituals, values, norms and symbolic meanings. Such findings are relevant under a managerial perspective as they also generate insights on how to foster environmentally friendly practices in coffee consumers as well as on how to create more sustainable marketing strategies.Originality/valueThe study contributes to the literature on coffee consumption behaviour and sustainability. First, by analysing actual behaviours rather than intended, the study offers an alternative approach to the dominant paradigm of linear decisions models in the study of sustainable consumption. Second, because CC possess a unique consumption style, different from the mainstream market, the analysis has led towards the identification of alternative sustainable consumption patterns and enablers.
Application of blockchain technology for agrifood supply chain management: a systematic literature review on benefits and challenges
Authors: Srivastava Ayushi , Dashora Kavya 
Published: January 2022

PurposeThis study aims to explore and analyze the application of blockchain technology (BKCT) in agrifood supply chain management (AFSM).Design/methodology/approachA systematic literature review (SLR) using Scopus, Emerald and Web of Science covering publications from 2016 to 2021 (till June). Out of 429 papers, 89 papers were shortlisted from journals based on citation analysis. The citation analysis was followed by a content analysis was for an in-depth analysis.FindingsRegarding the application of BKCT in the agrifood supply chain, the study highlights the issue of food safety, traceability, transparency, eliminating intermediaries and integrating Internet of things (IoT) with BKCT as prominent applications in the agrifood sector. The study also uses the case of honey supply chain to use the explored applications in the agrifood sector and provides a traceability solution based on blockchain integrated with IoT. The challenges of BKCT as identified in the study are scalability, privacy, security, lack of regulations and lack of skills and training.Research limitations/implicationsThe review considers only academic papers obtained from specific databases with their relevance based on number of citations.Originality/valueThe study contributes to filling the existing research gap through this SLR on the application of BKCT in AFSCM. The content analysis further assists in exploring the benefits and challenges of BKCT in the agrifood sector. Thus, the academic articles selected aid in this process.