bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUMO interacting motif (SIM) of S100A1 is critical for S100A1 post-translational protein stability
Authors: Jebessa Zegeye H. , Glaser Manuel , Zhao Jemmy , Schneider Andrea , Seenivasan Ramkumar , Busch Martin , Ritterhoff Julia , Wade Rebecca C. , Most Patrick 
Published: January 2023

AbstractS100A1 is a small EF-type Ca2+sensor protein that belongs to the multigenic S100 protein family. It is abundantly expressed in cardiomyocytes (CMs) and has been described as a key regulator of CM performance due to its unique ability to interact with structural contractile proteins, regulators of cardiac Ca2+cycling, and mitochondrial proteins. However, our understanding of the molecular mechanisms regulating S100A1 protein levels is limited. We used the bioinformatics tool GPS-SUMO2.0 to identify a putative SUMO interacting motif (SIM) on S100A1. Consistently, a S100A1:SUMO interaction assay showed a Ca2+-dependent interaction of S100A1 with SUMO proteins. In neonatal rat ventricular myocytes (NRVM) and COS1 cells, S100A1 protein abundance increased in the presence of overexpressed SUMO1 without affecting the S100A1 mRNA transcript. We then generated S100A1 truncation mutants, where the SIM motif was removed by truncation or in which the core residues of the SIM motif (residues 77-79) were deleted or replaced by alanine. In COS1 cells and NRVM, overexpression of these S100A1 mutants led to elevated S100A1 mutant mRNA levels but failed to produce respective protein levels. Protein expression of these mutants could be rescued from degradation by addition of the proteasome inhibitor MG-132. By using an information-driven approach to dock the three-dimensional structures of S100A1 and SUMO, we predict a novel interaction mode between the SIM in S100A1 and SUMO. This study shows an important role of SUMO:SIM-mediated protein:protein interaction in the regulation of post-translational protein stability, and provides mechanistic insights into the indispensability of the core SIM for S100A1 post-translational stability.
Migratory patterns of two major influenza virus host species on tropical islands
Authors: Lebarbenchon Camille , Boucher Solenn , Feare Chris , Dietrich Muriel , Larose Christine , Humeau Laurence , Corre Matthieu Le , Jaeger Audrey 
Published: January 2023

AbstractAnimal migration is a major driver of infectious agent dispersal. Duck and seabirds migrations, for instance, play a key role in the spatial transmission dynamics and gene flows of avian influenza viruses (AIV), worldwide. On tropical islands, brown and lesser noddies (Anous stolidusandA. tenuirostris) may be important AIV hosts, but the lack of knowledge on their migratory behaviour limits our understanding of virus circulation in island networks. Here we show that high connectivity between islands generated by post-breeding behaviours could be a major driver in the spread and the maintenance of AIV among tropical islands. Tracking data highlight two types of behaviours during the non-breeding season: birds either staying in the vicinity of their breeding ground (on Bird Island, Seychelles), or moving to and roosting on other islands in the Indian Ocean. Differences in roosting places are detected between migrant birds, ranging from the Tanzanian coast to the Maldives archipelago and Tromelin Island. Epidemiological data further support that brown and lesser noddies are major hosts for AIV, although significant variation of seroprevalence between species suggest that other drivers are involved in virus infection and transmission dynamics.
Viral capsid, antibody, and receptor interactions: experimental analysis of the antibody escape evolution of canine parvovirus
Authors: López-Astacio Robert A. , Adu Oluwafemi F. , Goetschius Daniel J. , Lee Hyunwook , Weichert Wendy S. , Wasik Brian R. , Frueh Simon P. , Alford Brynn K. , Voorhees Ian E.H. , Flint Joseph F. , Saddoris Sarah , Goodman Laura B. , Holmes Edward C. , Hafenstein Susan L. , Parrish Colin R. 
Published: January 2023

ABSTRACTCanine parvovirus (CPV) is a small non-enveloped single-stranded DNA virus that causes serious diseases in dogs worldwide. The original strain of the virus (CPV-2) emerged in dogs during the late-1970s due to a host range switch of a virus similar to the feline panleukopenia virus (FPV) that infected another host. The virus that emerged in dogs had altered capsid receptor- and antibody-binding sites, with some changes affecting both functions. Further receptor and antibody binding changes arose when the virus became better adapted to dogs or to other hosts. Here, we usein vitroselection and deep sequencing to reveal how two antibodies with known interactions select for escape mutations in CPV. The antibodies bind two distinct epitopes, and one largely overlaps the host receptor binding site. We also engineered antibody variants with altered binding structures. Viruses were passaged with the wild type or mutated antibodies, and their genomes deep sequenced during the selective process. A small number of mutations were detected only within the capsid protein gene during the first few passages of selection, and most sites remained polymorphic or were slow to go to fixation. Mutations arose both within and outside the antibody binding footprints on the capsids, and all avoided the TfR-binding footprint. Many selected mutations matched those that have arisen in the natural evolution of the virus. The patterns observed reveal the mechanisms by which these variants have been selected in nature and provide a better understanding of the interactions between antibody and receptor selections.IMPORTANCEAntibodies protect animals against infection by many different viruses and other pathogens, and we are gaining new information about the epitopes that induce antibody responses against viruses and the structures of the bound antibodies. However, less is known about the processes of antibody selection and antigenic escape and the constraints that apply in this system. Here, we use anin vitromodel system and deep genome sequencing to reveal the mutations that arise in the virus genome during selection by each of two monoclonal antibodies or their engineered variants. High-resolution structures of each of the Fab: capsid complexes revealed their binding interactions. The engineered forms of the wild-type antibodies or mutant forms allowed us to examine how changes in antibody structure influence the mutational selection patterns seen in the virus. The results shed light on the processes of antibody binding, neutralization escape, and receptor binding, and likely have parallels for many other viruses.
Aids to Improve Statistical Risk Communication in Patients Consenting for Surgery and Interventional Procedures: a Systematic Review
Authors: Jalal Arif HB , Chatzopoulou Despoina , Marcus Hani J , Pandit Anand S 
Published: January 2023

ABSTRACTObjectiveEvaluate the effect of risk communication tools on the understanding of statistical risk of complications occurring in patients undergoing a surgical or interventional procedure.Summary Background DataInformed consent is an essential process in clinical decision-making, through which healthcare providers educate patients about the benefits, risks and alternatives of a procedure. Numerical risk information is by nature probabilistic and difficult to communicate. Aids which support statistical risk communication and studies assessing their effectiveness are needed.MethodsA systematic search was performed across Medline, Embase, PsycINFO, Scopus and Web of Science until July 2021 with a repeated search in September 2022. Studies examining risk communication tools (e.g. informative leaflets, audio-video) in adults (age>16) patients undergoing a surgical or interventional procedure were included. Studies only assessing understanding of non-statistical aspects of the procedure were excluded. Both randomised control trials (RCTs) and observational studies were included. Cochrane risk-of-bias and the Newcastle-Ottawa Scale were used to assess the quality of studies. Due to heterogeneity of the studies, a narrative synthesis was performed (PROSPERO ID: CRD42022285789).ResultsA total of 4348 articles were identified and following abstract and full-text screening a total of 11 articles were included. 8 studies were RCTs and 3 were cross-sectional. The total number of adult patients was 1030. The most common risk communication tool used was additional written information (n=7). Of the 8 RCTs, 5 showed statistically significant improvements in the intervention group in outcomes relating to recall of statistical risk. Quality assessment of RCTs found some concerns with all studies.ConclusionsRisk communication tools appear to improve recall of statistical risk. Additional prospective trials are warranted which can compare various aids and determine the most effective method of improving patient understanding.
A Moving Target: Impacts of Lowering Viral Load Suppression Cutpoints on Progress Towards HIV Epidemic Control Goals
Authors: Rosen Joseph G. , Reynolds Steven J. , Galiwango Ronald M. , Kigozi Godfrey , Quinn Thomas C. , Ratmann Oliver , Ndyanabo Anthony , Nelson Lisa J. , Nakigozi Gertrude , Nalugemwa Margaret , Rucinski Katherine B. , Kennedy Caitlin E. , Chang Larry W. , Kagaayi Joseph , Serwadda David , Grabowski M. Kate 
Published: January 2023

SummaryRedefining viral load suppression (VLS) using lower cutpoints could impact progress towards the UNAIDS 95-95-95 targets. We assessed impacts of lowering the VLS cutpoint on achieving the 95-95-95 VLS target in the Rakai Community Cohort Study. Population VLS fell from 86% to 84% and 76%, respectively, after lowering VLS cutpoints from <1,000 to <200 and <50 copies/mL. The fraction of viremic persons increased by 17% after lowering the VLS cutpoint from <1,000 to <200 copies/mL.
circRNA-sponging: a pipeline for extensive analysis of circRNA expression and their role in miRNA sponging
Authors: Hoffmann Markus , Schwartz Leon , Ciora Octavia-Andreea , Trummer Nico , Willruth Lina-Liv , Jankowski Jakub , Lee Hye Kyung , Baumbach Jan , Furth Priscilla , Hennighausen Lothar , List Markus 
Published: January 2023

ABSTRACTMotivationCircular RNAs (circRNAs) are long non-coding RNAs (lncRNAs) often associated with diseases and considered potential biomarkers for diagnosis and treatment. Among other functions, circRNAs have been shown to act as microRNA (miRNA) sponges, preventing the role of miRNAs that repress their targets. However, there is no pipeline to systematically assess the sponging potential of circRNAs.ResultsWe developed circRNA-sponging, a nextflow pipeline that (1) identifies circRNAs via backsplicing junctions detected in RNA-seq data, (2) quantifies their expression values in relation to their linear counterparts spliced from the same gene, (3) performs differential expression analysis, (4) identifies and quantifies miRNA expression from miRNA-sequencing (miRNA-seq) data, (5) predicts miRNA binding sites on circRNAs, (6) systematically investigates potential circRNA-miRNA sponging events, (7) creates a network of competing endogenous RNAs, and (8) identifies potential circRNA biomarkers. We showed the functionality of the circRNA-sponging pipeline using RNA sequencing data from brain tissues, where we identified two distinct types of circRNAs characterized by a specific ratio of the number of the binding site to the length of the transcript. The circRNA-sponging pipeline is the first end-to-end pipeline to identify circRNAs and their sponging systematically with raw total RNA-seq and miRNA-seq files, allowing us to better indicate the functional impact of circRNAs as a routine aspect in transcriptomic research.Availabilityhttps://github.com/biomedbigdata/circRNA-spongingContactmarkus.daniel.hoffmann@tum.de;markus.list@tum.deSupplementary MaterialSupplementary data are available at Bioinformatic Advances online.
Functional characterization of the language network of polyglots and hyperpolyglots with precision fMRI
Authors: Malik-Moraleda Saima , Jouravlev Olessia , Taliaferro Maya , Mineroff Zachary , Cucu Theodore , Mahowald Kyle , Blank Idan A. , Fedorenko Evelina 
Published: January 2023

AbstractHow do polyglots—individuals who speak five or more languages—process their languages, and what can this population tell us about the language system? Using fMRI, we identified the language network in each of 34 polyglots (including 16 hyperpolyglots with knowledge of 10+ languages) and examined its response to the native language, non-native languages of varying proficiency, and unfamiliar languages. All language conditions engaged all areas of the language network relative to a control condition. Languages that participants rated as higher-proficiency elicited stronger responses, except for the native language, which elicited a similar or lower response than a non-native language of similar proficiency. Furthermore, unfamiliar languages that were typologically related to the participants’ high-to-moderate-proficiency languages elicited a stronger response than unfamiliar unrelated languages. The results suggest that the language network’s response magnitude scales with the degree of engagement of linguistic computations (e.g., related to lexical access and syntactic-structure building). We also replicated a prior finding of weaker responses to native language in polyglots than non-polyglot bilinguals. These results contribute to our understanding of how multiple languages co-exist within a single brain and provide new evidence that the language network responds more strongly to stimuli that more fully engage linguistic computations.
Evolution of protease activation and specificity via alpha-2-macroglobulin-mediated covalent capture
Authors: Knyphausen Philipp , Rangel-Pereira Mariana , Brear Paul , Hyvönen Marko , Jermutus Lutz , Hollfelder Florian 
Published: January 2023

AbstractTailoring of the activity and specificity of proteases is critical for their utility across industrial, medical and research purposes. However, engineering or evolving protease catalysts is challenging and often labour intensive. Here, we describe a generic method to accelerate this process based on yeast display. We introduce the protease selection system A2Mcapthat covalently captures protease catalysts by repurposed alpha-2-macroglobulin (A2Ms). To demonstrate the utility of A2Mcapfor protease engineering we exemplify the directed activity and specificity evolution of six serine proteases. This resulted in a variant ofStaphylococcus aureusserin-protease-like (Spl) protease SplB, an enzyme used for recombinant protein processing that no longer requires activation by N-terminal signal peptide removal. SCHEMA-based domain shuffling was used to map the specificity determining regions of Spl proteases leading to a chimeric scaffold that supports specificity switching via subdomain exchange. The ability of A2Mcapto overcome key challengesen routeto tailor-made proteases suggests easier access to such reagents in the future.
Cas9-induced nonhomologous recombination inC. elegans
Authors: Zdraljevic Stefan , Walter-McNeill Laura , Marquez Heriberto , Kruglyak Leonid 
Published: January 2023

AbstractIdentification of the genetic basis of phenotypic variation within species remains challenging. In species with low recombination rates, such asCaenorhabditis elegans, genomic regions linked to a phenotype of interest by genetic mapping studies are often large, making it difficult to identify the specific genes and DNA sequence variants that underlie phenotypic differences. Here, we introduce a method that enables researchers to induce targeted recombination inC. eleganswith Cas9. We demonstrate that high rates of targeted recombination can be induced by Cas9 in a genomic region in which naturally occurring recombination events are exceedingly rare. We anticipate that Cas9-induced nonhomologous recombination (CINR) will greatly facilitate high-resolution genetic mapping in this species.
Glutathione transferase photoaffinity labeling demonstrates GST activation by safeners and NPR1-independent activation by BTH
Authors: Farre Maria Font , Brown Daniel , König Maurice , Killinger Brian J. , Kaschani Farnusch , Kaiser Markus , Wright Aaron T. , Burton Jonathan , van der Hoorn Renier A. L. 
Published: January 2023

ABSTRACTGlutathione transferases (GSTs) represent a large and diverse enzyme family involved in detoxification of small molecules by glutathione conjugation in crops, weeds and model plants. Here, we introduce an easy and quick assay for photoaffinity labeling of GSTs to study global GST activation in various plant species. The small molecule probe contains glutathione, a photoreactive group, and a minitag for coupling to reporter tags via click chemistry. Under UV irradiation, this probe quickly and robustly labels GSTs in crude protein extracts. Enrichment and MS analysis of labeled proteins from Arabidopsis identified ten GSTs from the Phi(F) and Tau(U) classes. Photoaffinity labeling of GSTs demonstrated GST activation in wheat seedlings upon treatment with safeners, and in Arabidopsis leaves upon infection with avirulent bacteria. Photoaffinity labeling and proteomics identified six Phi- and Tau-class GSTs that are induced upon treatment with salicylic acid (SA) analog benzothiadiazole (BTH) and these were tested for enhancing immunity in disease assays. Our data confirm that BTH-induced GST activation is independent of NPR1, the master regulator of SA signaling.
Towards personalised early prediction of Intra-Operative Hypotension following anesthesia using Deep Learning and phenotypic heterogeneity
Authors: Garmendia Anna Tselioudis , Gkouzionis Ioannis , Triantafyllidis Charalampos P. , Dimakopoulos Vasileios , Liliopoulos Sotirios , Vuckovic Dragana , Paseiro-Garcia Lucas , Chadeau-Hyam Marc 
Published: January 2023

AbstractIntra-Operative Hypotension (IOH) is a haemodynamic abnormality that is commonly observed in operating theatres following general anesthesia and associates with life-threatening post-operative complications. Using Long Short Term Memory (LSTM) models applied to Electronic Health Records (EHR) and time-series intra-operative data in 604 patients that underwent colorectal surgery we predicted the instant risk of IOH events within the next five minutes. K-means clustering was used to group patients based on pre-clinical data. As part of a sensitivity analysis, the model was also trained on patients clustered according to Mean artelial Blood Pressure (MBP) time-series trends at the start of the operation using K-means with Dynamic Time Warping. The baseline LSTM model trained on all patients yielded a test set Area Under the Curve (AUC) value of 0.83. In contrast, training the model on smaller sized clusters (grouped by EHR) improved the AUC value (0.85). Similarly, the AUC was increased by 4.8% (0.87) when training the model on clusters grouped by MBP. The encouraging results of the baseline model demonstrate the applicability of the approach in a clinical setting. Furthermore, the increased predictive performance of the model after being trained using a clustering approach first, paves the way for a more personalised patient stratification approach to IOH prediction using clinical data.
An integrated model for international market and entry mode selections for Chinese contractors
Authors: Li Liping , Chen Chuan , Martek Igor , Li Guanghua 
Published: January 2023

PurposeGiven their interrelationship, international market selection (IMS) and entry mode selection (EMS) must be considered jointly if an optimal entry strategy is to be realized. However, researchers in the field of international construction have the tendency to consider IMS and EMS independently or sequentially. Therefore, this paper aims to explore a holistic framework that can accommodate IMS and EMS concurrently and test it using empirical data.Design/methodology/approachhis study includes theoretical and empirical research. In theoretical part, an integrated decision model of IMS and EMS is proposed adopting literature review and theoretical derivation, then hypotheses are developed for the impact of decision-making factors. In the latter part, the IMS and EMS of 54 Chinese contractors in 67 countries were investigated, empirical data are collected according to hypotheses, an ordinal logistic regression model is established for statistics analysis. Finally, findings are drawn by comparing literature-based hypotheses with data-based analysis results.FindingsResults show that empirical data fit theoretical model well. Findings are: IMS and EMS can be integrated into a holistic decision-making framework when be properly sequenced. When IMS and EMS are determined simultaneously, the decision can benefit from a sharing of common information. And the roles of at least 13 common factors are empirically demonstrated in this study.Research limitations/implicationsThe integrated decision sequence proposed in this study is applicable for a specific market, and cannot compare multiple alternative markets directly. The decision-making factors identified in this paper do not cover the enterprise strategic objectives and some other factors. Empirical data and some theoretical assumptions are based on the international market entry strategy of Chinese contractors. Therefore, the conclusions may not be completely applicable to global contractors though have certain reference value.Originality/valueBased on the idea of holistic decision-making of IMS and EMS, this study proposes an international market entry strategy (IMES) sequence and an explicit model for determinants, then tests them with empirical data. This paper provides a new idea to manage IMS and EMS concurrently, which can improve the efficiency of IMES decision-making and avoid missing optimal alternatives. This study paves the way for a practical model and provides reference for contractors' international market entry strategy.
Comparison of flow structures for vane and rod type vortex generators on a wind turbine airfoil
Authors: Tiwari Nishchay , Flaszynski Pawel , Suresh Thanushree , Szulc Oskar 
Published: January 2023

Purpose
The purpose of this paper is to investigate and compare the effects of rod and vane-type vortex generators for wind turbine applications. In large wind turbine rotors, an attached flow at all sections along the span direction is difficult to achieve which leads to an increase in aerodynamic losses, noise generation, and fatigue stress. Therefore, flow control strategies such as vortex generators (VGs) are beneficial to improve performance.

Design/methodology/approach
The benefits of the application of rod-type vortex generators (RVGs) to control flow separation on a wind turbine airfoil are assessed numerically using computational fluid dynamics (CFD). The validation of the computational model is conducted against the experimental data available for the DU96-W-180 wind turbine airfoil equipped with 44 RVGs. In addition, a revised wind tunnel angle of attack (AoA) calibration procedure (based on CFD) is proposed that is applicable for separated flows. A comparison of the RVGs to the conventional vane-type vortex generators (VVGs) is presented for inflow velocity of 30 m/s and AoA leading to significant flow separation. A parametric evaluation of the geometric characteristics of both types of VGs is conducted to quantify the generated streamwise vortices.

Findings
The comparison of the induced flow structures and aerodynamic efficiency enhancements proves that RVGs may be used as an alternative to the more conventional VVGs applied on wind turbine blades for boundary layer separation control.

Originality/value
A new type of VG (rod) has been investigated and compared against conventional VG (vanes) for wind turbine applications.