bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep assessment of human disease-associated ribosomal RNA modifications using Nanopore direct RNA sequencing
Authors: Naarmann-de Vries Isabel S. , Zorbas Christiane , Lemsara Amina , Bencun Maja , Schudy Sarah , Meder Benjamin , Eschenbach Jessica , Lafontaine Denis L.J. , Dieterich Christoph 
Published: November 2021

AbstractThe catalytically active component of ribosomes, rRNA, is long studied and heavily modified. However, little is known about functional and pathological consequences of changes in human rRNA modification status. Direct RNA sequencing on the Nanopore platform enables the direct assessment of rRNA modifications. We established a targeted Nanopore direct rRNA sequencing approach and applied it to CRISPR-Cas9 engineered HCT116 cells, lacking specific enzymatic activities required to establish defined rRNA base modifications. We analyzed these sequencing data along with wild type samples andin vitrotranscribed reference sequences to specifically detect changes in modification status. We show for the first time that direct RNA-sequencing is feasible on smaller, i.e. Flongle, flow cells. Our targeted approach reduces RNA input requirements, making it accessible to the analysis of limited samples such as patient derived material. The analysis of rRNA modifications during cardiomyocyte differentiation of human induced pluripotent stem cells, and of heart biopsies from cardiomyopathy patients revealed altered modifications of specific sites, among them pseudouridines, 2’-O-methylation of riboses and acetylation of cytidines. Targeted direct rRNA-seq analysis with JACUSA2 opens up the possibility to analyze dynamic changes in rRNA modifications in a wide range of biological and clinical samples.
Intrasexual cuticular hydrocarbon dimorphism in a wasp sheds light on hydrocarbon biosynthesis genes in Hymenoptera
Authors: Moris Victoria C. , Podsiadlowski Lars , Martin Sebastian , Oeyen Jan Philip , Donath Alexander , Petersen Malte , Wilbrandt Jeanne , Misof Bernhard , Liedtke Daniel , Thamm Markus , Scheiner Ricarda , Schmitt Thomas , Niehuis Oliver 
Published: November 2021

AbstractCuticular hydrocarbons (CHCs) cover the cuticle of insects and serve as desiccation barrier and for chemical communication. While the main enzymatic steps of CHC biosynthesis are well understood, few of the underlying genes have been identified. Here we show how exploitation of intrasexual CHC dimorphism in a mason wasp, Odynerus spinipes, in combination with whole-genome sequencing and comparative transcriptomics facilitated identification of such genes. RNAi-mediated knockdown of twelve candidate gene orthologs in honey bees, Apis mellifera, confirmed nine genes impacting CHC profile composition. Most of them have predicted functions consistent with current knowledge of CHC metabolism. However, we found first-time evidence for a fatty acid amide hydrolase also influencing CHC profile composition. In situ hybridization experiments furthermore suggest trophocytes participating in CHC biosynthesis. Our results set the base for experimental CHC profile manipulation in Hymenoptera and imply that the evolutionary origin of CHC biosynthesis predates the arthropods’ colonization of land.
Vaccinia virus D10 has broad decapping activity that is regulated by mRNA splicing
Authors: Ly Michael , Burgess Hannah M. , Mohr Ian , Glaunsinger Britt A. 
Published: November 2021

AbstractThe mRNA 5’ cap structure serves both to protect transcripts from degradation and promote their translation. Cap removal is thus an integral component of mRNA turnover that is carried out by cellular decapping enzymes, whose activity is tightly regulated and coupled to other stages of the mRNA decay pathway. The poxvirus vaccinia virus (VACV) encodes its own decapping enzymes, D9 and D10, that act on cellular and viral mRNA, but may be regulated differently than their cellular counterparts. Here, we evaluated the targeting potential of these viral enzymes using RNA sequencing from cells infected with wild-type and decapping mutant versions of VACV as well as in uninfected cells expressing D10. We found that D9 and D10 target an overlapping subset of viral transcripts but that D10 plays a dominant role in depleting the vast majority of human transcripts, although not in an indiscriminate manner. Unexpectedly, the splicing architecture of a gene influences how robustly its corresponding transcript is targeted by D10, as transcripts derived from intronless genes are less susceptible to enzymatic decapping by D10. As all VACV genes are intronless, preferential decapping of transcripts from intron-encoding genes provides an unanticipated mechanism for the virus to disproportionately deplete host transcripts and remodel the infected cell transcriptome.
Pluripotency-Independent Induction of Human Trophoblast Stem Cells from Fibroblasts
Authors: Naama Moriyah , Radwan Ahmed , Zayat Valery , Sebban Shulamit , Rahamim Moran , Lasry Rachel , Jaber Mohammad , Sabag Ofra , Yassen Hazar , Orzech Dana , Khatib Areej , Epsztejn-Litman Silvina , Novoselsky-Persky Michal , Makedonski Kirill , Deri Noy , Goldman-Wohl Debra , Cedar Howard , Yagel Simcha , Eiges Rachel , Buganim Yosef 
Published: November 2021

SUMMARYRecent studies demonstrated that human trophoblast stem-like cells (hTS-like cells) can be derived from naïve embryonic stem cells or be induced from somatic cells by the pluripotency factors, OSKM. This raises two main questions; (i) whether human induced TSCs (hiTSCs) can be generated independently to pluripotent state or factors and (ii) what are the mechanisms by which hTSC state is established during reprogramming. Here, we identify GATA3, OCT4, KLF4 and MYC (GOKM) as a pluripotency-independent combination of factors that can generate stable and functional hiTSCs, from both male and female fibroblasts. By using single and double knockout (KO) fibroblasts for major pluripotency genes (i.e. SOX2 or NANOG/PRDM14) we show that GOKM not only is capable of generating hiTSCs from the KO cells, but rather that the efficiency of the process is increased. Through H3K4me2 and chromatin accessibility profiling we demonstrate that GOKM target different loci and genes than OSKM, and that a significant fraction of them is related to placenta and trophoblast function. Moreover, we show that GOKM exert a greater pioneer activity compared to OSKM. While GOKM target many specific hTSC loci, OSKM mainly target hTSC loci that are shared with hESCs. Finally, we reveal a gene signature of trophoblast-related genes, consisting of 172 genes which are highly expressed in blastocyst-derived TSCs and GOKM-hiTSCs but absent or mildly expressed in OSKM-hiTSCs.Taken together, these results imply that not only is the pluripotent state, and SOX2 specifically, not required to produce functional hiTSCs, but that pluripotency-specific factors actually interfere with the acquisition of the hTSC state during reprogramming.
YAP1 Activation by Human Papillomavirus E7 Promotes Basal Cell Identity in Squamous Epithelia
Authors: Hatterschide Joshua , Castagnino Paola , Kim Hee Won , Sperry Steven M. , Montone Kathleen T. , Basu Devraj , White Elizabeth A. 
Published: November 2021

AbstractPersistent human papillomavirus (HPV) infection of stratified squamous epithelial cells causes nearly five percent of cancer cases worldwide. HPV-positive oropharyngeal cancers harbor few mutations in the Hippo signaling pathway compared to HPV-negative cancers at the same anatomical site, prompting the hypothesis that an HPV-encoded protein inactivates the Hippo pathway and activates the Hippo effector YAP1. The HPV E7 oncoprotein is required for HPV infection and for HPV-mediated oncogenic transformation. We investigated the effects of HPV oncoproteins on YAP1 and found that E7 activates YAP1, promoting YAP1 nuclear localization in basal epithelial cells. YAP1 activation by HPV E7 required that E7 bind and degrade the tumor suppressor PTPN14. E7 required YAP1 transcriptional activity to extend the lifespan of primary keratinocytes, indicating that YAP1 activation contributes to E7 carcinogenic activity. Maintaining infection in basal cells is critical for HPV persistence, and here we demonstrate that YAP1 activation causes HPV E7 expressing cells to be retained in the basal compartment of stratified epithelia. We propose that YAP1 activation resulting from PTPN14 inactivation is an essential, targetable activity of the HPV E7 oncoprotein relevant to HPV infection and carcinogenesis.
Calcium current modulation by the γ1 subunit depends on alternative splicing of CaV1.1
Authors: El Ghaleb Yousra , Ortner Nadine J. , Posch Wilfried , Fernández-Quintero Monica L. , Tuinte Wietske E. , Monteleone Stefania , Draheim Henning J. , Liedl Klaus R. , Wilflingseder Doris , Striessnig Jörg , Tuluc Petronel , Flucher Bernhard E. , Campiglio Marta 
Published: November 2021

AbstractThe skeletal muscle voltage-gated calcium channel (CaV1.1) primarily functions as voltage sensor for excitation-contraction coupling. Conversely, its ion-conducting function is modulated by multiple mechanisms within the pore-forming α1S subunit and the auxiliary α2δ-1 and γ1 subunits. Particularly, developmentally regulated alternative splicing of exon 29, which inserts 19 amino acids in the extracellular IVS3-S4 loop of CaV1.1a, greatly reduces the current density and shifts the voltage-dependence of activation to positive potentials outside the physiological range. We generated a new HEK293-cell line stably expressing α2δ-1, β3, and STAC3. When the adult (CaV1.1a) and the embryonic (CaV1.1e) splice variants were expressed in these cells, the difference in the voltage-dependence of activation observed in muscle cells was reproduced, but not the reduced current density of CaV1.1a. Only when we further co-expressed the γ1 subunit, the current density of CaV1.1a, but not of CaV1.1e, was reduced by >50 %. In addition, γ1 caused a shift of the voltage-dependence of inactivation to negative voltages in both variants. Thus, the current-reducing effect of γ1, but not its effect on inactivation, is specifically dependent on the inclusion of exon 29 in CaV1.1a. Molecular structure modeling revealed several direct ionic interactions between oppositely charged residues in the IVS3-S4 loop and the γ1 subunit. However, substitution of these residues by alanine, individually or in combination, did not abolish the γ1-dependent reduction of current density, suggesting that structural rearrangements of CaV1.1a induced by inclusion of exon 29 allosterically empower the γ1 subunit to exert its inhibitory action on CaV1.1 calcium currents.SummaryEl Ghaleb et al. analyzed the effects of the γ1 subunit on current properties and expression of the adult (CaV1.1a) and embryonic (CaV1.1e) calcium channel splice variants, demonstrating that γ1 reduces the current amplitude in a splicing-dependent manner.
Three year experience of Upper Gastrointestinal Endoscopic procedures at a tertiary care hospital of South Punjab
Authors: Din Chaudhary Farooq Mohyud , Gul Muhammad Asif , Hameed Rizwan , Ilyas Muhammad , Zubair Muhammad , Umar Qasim , Altaf Syeda Manal , Tameez-ud-din Ahsan 
Published: November 2021

ABSTRACTIntroductionEndoscopy has become a necessity in diagnosing gastrointestinal (GI) disorders. The objective of our study was to evaluate the different indications and findings of upper GI endoscopy.MethodsThis retrospective analysis was undertaken at department of Gastroenterology, Nishtar Hospital Multan. Records of all upper GI endoscopic procedures from 1st January 2018 till 31st December 2020 were evaluated.ResultsA total 3299 upper GI endoscopic procedures were perfumed during the three-year time period. Mean age was 47 years. Majority of patients were males. Almost 48% of patients belonged to the middle-aged group. The most common indication was upper GI bleeding (57%), followed by dyspepsia (15%). The most common finding was esophageal varices (43%), followed by portal gastropathy (26%) and gastritis (16%).ConclusionThis study concludes that the majority of endoscopies are being undertaken as a result of complications of cirrhosis and portal hypertension.
Effectiveness of non-pharmaceutical measures (NPIs) on COVID-19 in Europe: A systematic literature review
Authors: Vardavas Constantine I. , Nikitara Katerina , Aslanoglou Katerina , Hilton-Boon Michele , Phalkey Revati , Leonardi-Bee Jo , Magiorkinis Gkikas , Katsaounou Paraskevi , Pharris Anastasia , Severi Ettore , Suk Jonathan E. 
Published: November 2021

AbstractBackgroundThe study objective was to conduct a systematic review to assess the effectiveness of non-pharmaceutical interventions (NPIs) to reduce the transmission of SARS-CoV-2 in Europe during the first wave of the pandemic.MethodsWe searched OVID Medline, EMBASE, and the Cochrane and Campbell Databases for Systematic Reviews published up to April 15th 2021. Focusing on community (meso-level) and society (macro-level) level NPIs, we included all study designs, while a geographic restriction was limited to the EU, UK and European Economic Area (EEA) countries. Using the PICO framework, two reviewers independently extracted data and assessed quality using appropriate quality appraisal tools. A qualitative synthesis was performed, with NPIs grouped initially by a) Physical Distancing measures, b) Case detection and management measures, and c) hygiene measures and subsequently by country.ResultsOf 17,692 studies initially assessed, 45 met all inclusion criteria. Most studies (n=30) had a modelling study design, while 13 were observational, one quasi-experimental and one experimental. Evidence from across the European continent, presented by country, indicates that the implementations of physical distancing measures (i.e., lockdowns/quarantines), preferably earlier in the pandemic, reduce the number of cases and hospitalisation across settings and for which the timing and duration are essential parameters. Case detection and management measures were also identified as effective measures at certain levels of testing and incidence, while hygiene and safety measures complemented the implementation of physical distancing measures.ConclusionsThis literature review represents a comprehensive assessment of the effectiveness of NPIs in Europe up to April 2021. Despite heterogeneity across studies, NPIs, as assessed within the context of this systematic review at the macro and meso level, are effective in reducing SARS-CoV-2 transmission rates and COVID-19 hospitalisation rates and deaths in the European Region and may be applied as response strategies to reduce the burden of COVID-19 in forthcoming waves.
The β-NGF/TrkA signalling pathway is associated with the production of anti- nucleoprotein IgG in convalescent COVID-19
Authors: Usai Carla , Gibbons Joseph M. , Pade Corinna , Li Wenhao , Jacobs Sabina R.M. , McKnight Áine , Kennedy Patrick T. F. , Gill Upkar S. 
Published: November 2021

AbstractBackgroundThe presentation of SARS-CoV-2 infection varies from asymptomatic to severe COVID. Similarly, high variability in the presence, titre and duration of specific antibodies has been reported. While some host factors determining these differences, such as age and ethnicity have been identified, the underlying molecular mechanisms underpinning these differences remain poorly defined.MethodsWe analysed serum and PBMC from 17 subjects with a previous PCR confirmed SARS-CoV-2 infection and 10 unexposed volunteers following the first wave of the pandemic, in the UK. Anti-NP IgG and neutralising antibodies were measured, as well as a panel of infection and inflammation related cytokines. The virus-specific T cell response was determined by IFN-γ ELISPOT and flow cytometry after over-night incubation of PBMCs with pools of selected SARS-CoV-2 specific peptides.ResultsSeven of 17 convalescent subjects had undetectable levels of anti-NP IgG, and a positive correlation was shown between anti-NP IgG levels and the titre of neutralising antibodies (IC50). In contrast, a discrepancy was noted between antibody levels and T cell IFN-γ production by ELISpot following stimulation with specific peptides. Among the analysed cytokines, β-NGF and IL-1α levels were significantly different between anti-NP positive and negative subjects, and only β-NGF significantly correlated with anti-NP positivity. Interestingly, CD4+ T cells of anti-NP negative subjects expressed lower amounts of the β-NGF-specific receptor TrkA.ConclusionsOur results suggest that the β-NGF/TrkA signalling pathway is associated with the production of anti-NP specific antibody in mild SARS-CoV-2 infection and the mechanistic regulation of this pathway in COVID-19 requires further investigation.
Two Modulatory Inputs Exert Reciprocal Reinforcing Effects on Synaptic Input of Premotor Interneurons for Withdrawal in Terrestrial Snails
Authors: Maksimova Olga A. , Bravarenko Natalia I. , Balaban Pavel M. 
Published: November 2021

A cluster of serotonergic cells in the rostral part of pedal ganglia of the terrestrial snail Helix lucorum was shown previously to participate in modulation of withdrawal behavior, and to be necessary for elaboration of aversive withdrawal conditioning in intact snails. In the present experiments local extracellular stimulation of the serotonergic cells elicited a pairing-specific increase (difference between paired and explicitly unpaired sessions was significant, P < 0.01) of synaptic responses in the premotor interneurons involved in withdrawal to paired nerve stimulation. Intracellular stimulation of only one Pd4 cell from the pedal group of serotonergic neurons increased (P < 0.05) synaptic responses to contingent test nerve stimulation significantly in the same premotor interneurons for 2–3 hr.Mesocerebral cells are known to participate in male sexual behavior, and their extracellular stimulation was shown previously to suppress the amplitude of synaptic responses in withdrawal interneurons. Local extracellular stimulation of the mesocerebral cells elicited a pairing-specific decrease (P < 0.01) of synaptic responses to contingent test nerve stimulation in the premotor interneurons involved in withdrawal for 2–3 hr. Paired application of met-enkephaline (10−6m, some mesocerebral cells are enkephaline-like immunoreactive) also selectively decreased synaptic responses to contingent nerve stimulation in the premotor interneurons for hours. Thus, two modulatory inputs exert pairing-specific effects that influence the same synaptic connection in opposite directions, which may underlie the long-term up- and down-regulation of behavioral responses.
Thermal elastohydrodynamic lubrication characteristics and optimisation of the ball-type tripod universal joint
Authors: Yang Fuqin , Han Xiaojie , Si Mingqing 
Published: November 2021

Purpose
This paper aims to study the influence of three-column groove shell radius, ball radius, lubricating oil viscosity and elastic modulus on the thermal elastohydrodynamic lubrication (TEHL) characteristics and optimisation of the ball-type tripod universal joint.

Design/methodology/approach
The point contact TEHL model of the joint was developed, and the multi-grid method was used to solve it. The influence of three-column groove shell radius, ball radius, lubricating oil viscosity and elastic modulus on the lubrication characteristics was analysed. Further, the optimisation of the joint TEHL performance was carried out by the Kriging approximation model combined with the multi-objective particle swarm optimisation (MOPSO) algorithm.

Findings
The research results show that increasing groove shell radius and ball radius can effectively increase the oil film thickness, and decrease the oil film pressure, as well as the temperature rise. Decreasing elastic modulus can reduce the oil film temperature rise and pressure, and increasing viscosity can effectively increase the oil film thickness. The optimised minimum oil film thickness increases by 33.23% and the optimised maximum oil film pressure and maximum temperature rise decrease by 11.92% and 28.87%, respectively. Furthermore, the relative error of each response output is less than 10%.

Originality/value
This study applies TEHL theory to the tribological research of the ball-type tripod universal joint, and the joint’s lubrication performance is improved greatly by the Kriging model and MOPSO algorithm, which provides an effective measure to raise the joint’s working efficiency.
When workers matter most: a study of worker cooperatives and the prioritization of workers through COVID-19
Authors: Prushinskaya Olga , Pockrandt Jamie , McKinley Julian , Hoover Melissa 
Published: November 2021

PurposeAs a part of the authors’ continued efforts to understand the experience and trends related to small business cooperatives, the US Federation of Worker Cooperatives (USFWC) and the Democracy at Work Institute (DAWI) explored themes around the impact of the COVID-19 pandemic on worker cooperatives and democratic workplaces.Design/methodology/approachThe USFWC and DAWI conduct a biannual Economic Census of worker cooperatives and democratic workplaces. Survey themes this year included questions around the impact of the COVID-19 pandemic on individual firms.FindingsGeneral findings indicate that worker cooperatives experienced financial losses similar to conventional small businesses, but that this varied widely by industry. Although it has been found that BIPOC-owned conventional small businesses have been some of the hardest hit during the pandemic, the authors find that there may be some mitigating protective effects of the worker cooperative form when the authors explore the impacts on worker cooperatives with a majority BIPOC workforce. Additionally, the authors find that worker cooperatives and democratic workplaces strive to ensure the safety and wellbeing of their workers even when facing significant financial challenges throughout the pandemic.Research limitations/implicationsThis research utilizes non-random convenience sampling in data collection. The outreach for our biannual Economic Census is concentrated on a highly connected worker cooperative and democratic workplace network, the experiences of which may not generalize to the larger worker cooperative and democratic workplace landscape. Additionally, outreach efforts were hindered by challenges presented by the pandemic that were not present in prior census years, as was firm bandwidth to respond, which likely affected the sample composition in comparison to prior years.Originality/valueWorker cooperatives have been proven to be a resilient crisis response form of business, but little is known about how the worker cooperative ecosystem in the United States is faring in the face of the continuing COVID-19 crisis.