bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time spent in outdoor light is associated with increased blood pressure, higher hypertension risk, and lower hypotension risk
Authors: Li Sicheng , Lu Liyong , Xian Wenpan , Li Jiawei , Xu Shuaiming , Chen Jiajin , Wang Yan 
Published: April 2024

AbstractObjectiveLight exposure is considered to be associated with reduced blood pressure (BP). However, longitudinal epidemiological studies concerning the light‒BP association with large samples are still limited.MethodsThis cohort study enrolled over 300,000 participants from the UK Biobank. Information on time spent in outdoor light during typical summer or winter days was obtained through questionnaires. Cases of hypertension and hypotension were identified using the 10th edition of International Classification of Diseases codes. Cox proportional hazard regression models were employed to estimate the light‒BP associations, restricted cubic splines were utilized to detect potential nonlinear associations, subgroup analyses were conducted to identify effect modifiers, and causal mediation analyses were performed to explore potential mechanisms.ResultsUsing summer light exposure as an illustration, after a median follow-up of 13.4 years, each additional hour of summer light exposure was associated with an increased risk of hypertension (hazard ratio [HR] 1.011, 95% confidence interval [CI] 1.006‒1.017,P-nonlinear=0.803) and a decreased risk of hypotension (0.988, 0.977‒ 0.998,P-nonlinear=0.109). The light‒BP association is stronger in females (P=0.022), those with short sleep duration (P=0.049), and those with high genetic risk of hypertension (P<0.001). Potential mechanisms included increasing biological age (proportion mediated, 24.1%,P<0.001), neutrophil count (5.4%,P<0.001), BMI (32.0%,P<0.001), etc.ConclusionsContrary to previous findings, our study revealed a positive association between light exposure and BP. Potential mechanisms include inflammation, aging, and behavioral lifestyle changes. Further epidemiological and experimental investigations are warranted to validate these novel findings.
Socio-ecological context modulates significance of territorial contest competition inDrosophila prolongata
Authors: De Nardo Alessio N. , Biswas Broti , Perdigón Ferreira Jhoniel , Meena Abhishek , Lüpold Stefan 
Published: April 2024

AbstractThe intensity and direction of sexual selection is intricately linked to the social and ecological context. Both operational sex ratios (OSRs) and population densities can affect the ability of males to monopolize resources and mates, and thus the form and intensity of sexual selection on them. Here, we studied how the mating system of the promiscuous and strongly sexually dimorphic fruit flyDrosophila prolongataresponds to changes in the OSR and population density. We recorded groups of flies over five days and quantified territory occupancy, mating success, and competitive fertilization success. Although sexual selection was stronger under male-biased than even OSRs but unrelated to density, realized selection on morphological traits was higher under even OSRs and increased with density. Larger and more territorial males achieved both higher mating success and competitive fertilization success, but only under even OSRs. Our combined results also support a shift in the mating system from territorial contest competition to scramble competition under male-biased OSRs and potentially at low density, where there was no clear contribution of the measured traits to reproductive success. Our study emphasizes the limitations of traditional selection metrics and the role of the socio-ecological context in predicting adaptation to a changing environment.SignificanceMating systems are complex and dynamic, adapting to ongoing ecological change. Studies often assume that changes in the socio-ecological context alter the intensity of sexual selection on traits indicating individual fitness, but our work onDrosophila prolongatachallenges this view. By manipulating operational sex ratio and population density, and jointly investigating territorial behavior and both pre- and post-mating reproductive success over several days, we reveal the plastic mating strategies in this fly. This dynamism underscores the limitations of static classifications and the importance of studying selection across diverse socio-ecological contexts. This broader perspective advances our understanding of the tight connections between environmental change, population demographics, and the evolutionary process.
Syntenic lncRNAs exhibit DNA regulatory functions with sequence evolution
Authors: Ranjan Gyan , Scaria Vinod , Sivasubbu Sridhar 
Published: April 2024

AbstractSyntenic long non-coding RNAs (lncRNAs) often show limited sequence conservation across species, prompting concern in the field. This study delves into functional signatures of syntenic lncRNAs between humans and zebrafish. Syntenic lncRNAs have high expression in zebrafish and ∼90% near protein-coding genes in sense or antisense orientation. During early zebrafish development and human embryonic stem cells (H1-hESC), are enriched with cis-regulatory repressor signatures, influencing development-associated genes. In later zebrafish developmental stages and specific human cell lines, these lncRNAs serve as enhancers or transcription-start-sites(TSS) for protein-coding. Analysis of Transposable Elements (TEs) in syntenic lncRNA sequence divergence unveils intriguing patterns, human lncRNAs show enrichment in simple repeat elements, while zebrafish counterparts exhibit LTR element enrichment. This sequence evolution, possibly stemming from post-rearrangement mutations, enhances DNA elements or cis-regulatory functions. It may also contribute to vertebrate innovation by creating novel TF binding sites within the locus. This study sheds light on the conserved functionality of syntenic lncRNAs through DNA elements, emphasizing their role across species despite sequence divergence.
An image processing pipeline for electron cryo-tomography in RELION-5
Authors: Burt Alister , Toader Bogdan , Warshamanage Rangana , von Kügelgen Andriko , Pyle Euan , Zivanov Jasenko , Kimanius Dari , Bharat Tanmay A.M. , Scheres Sjors H.W. 
Published: April 2024

AbstractElectron tomography of frozen, hydrated samples allows structure determination of macromolecular complexes that are embedded in complex environments. Provided that the target complexes may be localised in noisy, three-dimensional tomographic reconstructions, averaging images of multiple instances of these molecules can lead to structures with sufficient resolution forde novoatomic modelling. Although many research groups have contributed image processing tools for these tasks, a lack of standardisation and inter-operability represents a barrier for newcomers to the field. Here, we present an image processing pipeline for electron tomography data in RELION-5, with functionality ranging from the import of unprocessed movies to the automated building of atomic models in the final maps. Our explicit definition of metadata items that describe the steps of our pipeline has been designed for inter-operability with other software tools and provides a framework for further standardisation.
PARP14 is pro- and anti-viral host factor that promotes IFN production and affects the replication of multiple viruses
Authors: Parthasarathy Srivatsan , Saenjamsai Pradtahna , Hao Hongping , Ferkul Anna , Pfannenstiel Jessica J. , Suder Ellen L. , Bejan Daniel S. , Chen Yating , Schwarting Nancy , Aikawa Masanori , Muhlberger Elke , Orozco Robin C. , Sullivan Christopher S. , Cohen Michael S. , Davido David J. , Hume Adam J. , Fehr Anthony R. 
Published: April 2024

ABSTRACTPARP14 is a 203 kDa multi-domain protein that is primarily known as an ADP-ribosyltransferase, and is involved in a variety of cellular functions including DNA damage, microglial activation, inflammation, and cancer progression. In addition, PARP14 is upregulated by interferon (IFN), indicating a role in the antiviral response. Furthermore, PARP14 has evolved under positive selection, again indicating that it is involved in host-pathogen conflict. We found that PARP14 is required for increased IFN-I production in response to coronavirus infection lacking ADP-ribosylhydrolase (ARH) activity and poly(I:C), however, whether it has direct antiviral function remains unclear. Here we demonstrate that the catalytic activity of PARP14 enhances IFN-I and IFN-III responses and restricts ARH-deficient murine hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication. To determine if PARP14’s antiviral functions extended beyond CoVs, we tested the ability of herpes simplex virus 1 (HSV-1) and several negative-sense RNA viruses, including vesicular stomatitis virus (VSV), Ebola virus (EBOV), and Nipah virus (NiV), to infect A549 PARP14 knockout (KO) cells. HSV-1 had increased replication in PARP14 KO cells, indicating that PARP14 restricts HSV-1 replication. In contrast, PARP14 was critical for the efficient infection of VSV, EBOV, and NiV, with EBOV infectivity at less than 1% of WT cells. A PARP14 active site inhibitor had no impact on HSV-1 or EBOV infection, indicating that its effect on these viruses was independent of its catalytic activity. These data demonstrate that PARP14 promotes IFN production and has both pro– and anti-viral functions targeting multiple viruses.IMPORTANCEThe antiviral response is largely regulated by post-translation modifications (PTM), including ADP-ribosylation. PARP14 is an ADP-ribosyltransferase that is upregulated by interferon and is under positive selection, indicating that it is involved in host-pathogen conflict. However, no anti-viral function has been described for PARP14. Here, we found that PARP14 represses both coronavirus and HSV-1 replication, demonstrating that PARP14 has anti-viral functions. Surprisingly, we also found that PARP14 also has pro-viral functions, as it was critical for the efficient infection of several RNA viruses, including Ebola and Nipah viruses, which have high mortality and are viruses with pandemic potential. These data indicate that PARP14 has both pro– and anti-viral functions and is a potential therapeutic target for highly pathogenic RNA viruses.
Loss of RNF2 delays tumour development in BAP1-deficient mesothelioma
Authors: Landman Nick , Hulsman Danielle , Badhai Jitendra , van Lohuizen Maarten 
Published: April 2024

AbstractThe tumour suppressor geneBAP1is mutated in more than half of the malignant mesothelioma patients. This catalytic subunit of Polycomb repressive deubiquitinating (PR-DUB) complex, plays an important role in maintaining gene expression levels by deubiquitinating the PRC1-mediated histone H2A lysine 119 mono-ubiquitination (H2AK119ub1). Published studies report varying degrees of importance of H2AK119ub1 in Polycomb-regulated gene expression in different cell types. Recently published data by our own lab suggests a global redistribution of the H2AK119ub1 mark from promoter to intergenic regions upon loss of BAP1. PRC1-mediated mono-ubiquitination is dependent on the E3 ubiquitin ligase function of RNF2 (RING1B). Here, by knocking-outRnf2, we show that loss of H2AK119ub1 levels leads to a decrease in clonogenic potential ofBap1-deficient mesothelioma cellsin vitroand a delay in tumour onsetin vivo.
Ultra-deep proteomics by Thin-diaPASEF with a 60-cm long column system
Authors: Konno Ryo , Ishikawa Masaki , Nakajima Daisuke , Hagiwara Sho , Inukai Kaori , Ohara Osamu , Kawashima Yusuke 
Published: April 2024

AbstractRecent advances have allowed for the detection of 10,000 proteins from cultured human cell samples, such as HeLa and HEK293T cells in a single-shot proteome analysis. However, deeper analysis remains challenging. Therefore, in this study, we aimed to perform a deep proteomic single-shot analysis using timsTOF HT. To achieve deep proteomics, we developed Thin-diaPASEF, a parallel accumulation-serial fragmentation (PASEF) technology featuring a thinly dividedm/zaxis only in regions of high ion density. Furthermore, using a 60-cm long C18 column with a particle size of 1.7 µm, an average of 11,698, 11,615 and 11,019 unique proteins were successfully detected from 500 ng of HEK293T, HeLa and K562 cell digests, respectively, with a 100 min active gradient. The same system was used to analyzeLycopersicon esculentumlectin (LEL) enriched plasma and serum. The LEL method identified an average of 8,613 and 4,078 unique proteins, in plasma and serum, respectively. Our ultra-deep proteomic analysis system will be helpful for the in-depth comparison of proteins in medical and biological research because it enables the analysis of highly proteome coverage in a single-shot.
In vitrotranscription-based biosensing of glycolate for prototyping of a complex enzyme cascade
Authors: Barthel Sebastian , Brenker Luca , Diehl Christoph , Bohra Nitin , Giaveri Simone , Paczia Nicole , Erb Tobias J 
Published: April 2024

AbstractIn vitrometabolic systems allow the reconstitution of natural and new-to-nature pathways outside of their cellular context and are of increasing interest in bottom-up synthetic biology, cell-free manufacturing and metabolic engineering. Yet, the prototyping of suchin vitronetworks is very often restricted by time- and cost-intensive analytical methods. To overcome these limitations, we sought to develop anin vitrotranscription (IVT)-based biosensing workflow that offers fast results at low-cost, minimal volumes and high-throughput. As a proof-of-concept, we present an IVT biosensor for the so-called CETCH cycle, a complexin vitrometabolic system that converts CO2into glycolate. To quantify glycolate production, we constructed a sensor module that is based on the glycolate repressor GlcR fromParacoccus denitrificans, and established an IVT biosensing off-line workflow that allows to measure glycolate from CETCH samples from the µM to mM range. We characterized the influence of different cofactors on IVT output and further optimized our IVT biosensor against varying sample conditions. We show that availability of free Mg2+is a critical factor in IVT biosensing and that IVT output is heavily influenced by ATP, NADPH and other phosphorylated metabolites frequently used inin vitrosystems. Our final biosensor is highly robust and shows an excellent correlation between IVT output and classical LC-MS quantification, but notably at ∼10-fold lowered cost and ∼10 times faster turnover time. Our results demonstrate the potential of IVT-based biosensor systems to break current limitations in biological design-build-test cycles for the prototyping of individual enzymes, complex reaction cascades andin vitrometabolic networks.
Rescue of lysosomal acid lipase deficiency in mice by rAAV8 liver gene transfer
Authors: Laurent Marine , Harb Rim , Jenny Christine , Oustelandt Julie , Jimenez Simon , Cosette Jeremie , Landini Francesca , Ferrante Aristide , Corre Guillaume , Vujic Nemanja , Piccoli Claudia , Brassier Anais , Van Wittenberghe Laetitia , Ronzitti Giuseppe , Kratky Dagmar , Pacelli Consiglia , Amendola Mario 
Published: April 2024

AbstractLysosomal acid lipase deficiency (LAL-D) is an autosomal recessive disorder caused by mutations in theLIPAgene, which results in lipid accumulation leading to multi-organ failure. If left untreated, the severe form of LAL-D results in premature death within the first year of life due to failure to thrive and hepatic insufficiency. Enzyme replacement therapy is the only available supportive treatment consisting in weekly systemic injections of recombinant LAL protein. Here, we characterized a novelLipa-/-mouse model and developed a curative gene therapy treatment based on thein vivoadministration of recombinant (r)AAV8 vector encoding the humanLIPAtransgene under the control of a hepatocyte-specific promoter. We defined the minimal rAAV8 dose required to rescue disease lethality and to correct cholesterol and triglyceride accumulation in multiple organs and blood. Finally, using liver transcriptomic and biochemical analysis, we showed mitochondrial impairment inLipa-/-mice and its recovery by gene therapy. Overall, ourin vivogene therapy strategy achieves a stable long-term LAL expression sufficient to correct the disease phenotype in theLipa-/-mouse model and offers a new therapeutic option for LAL-D patients.One Sentence SummaryWe’ve developed a liver-targeted gene therapy using recombinant AAV8 to effectively cure Lysosomal acid lipase deficiency by correcting lipid accumulation and by normalizing gene expression pattern and mitochondrial function inLipa-/-mouse model.
Targeting the sphingolipid rheostat in IDH1mutglioma alters cholesterol homeostasis and triggers apoptosis via membrane degradation
Authors: Dowdy Tyrone , Vilamu Helena Muley , Lita Adrian , Li Aiguo , Yamasaki Tomohiro , Zhang Lumin , Chari Raj , Song Hua , Zhang Meili , Zhang Wei , Briceno Nicole , Davis Dionne , Gilbert Mark R. , Larion Mioara 
Published: April 2024

AbstractThe cross-regulation of metabolism and trafficking is not well understood for the vital sphingolipids and cholesterol constituents of cellular compartments. While reports are starting to surface on how sphingolipids like sphingomyelin (SM) dysregulate cholesterol levels in different cellular compartments (Jiang et al., 2022), limited research is available on the mechanisms driving the relationship between sphingolipids and cholesterol homeostasis, or its biological implications. Previously, we have identified sphingolipid metabolism as a unique vulnerability for IDH1mutgliomas via a rational drug design. Herein, we show how modulating sphingolipid levels affects cholesterol homeostasis in brain tumors. However, we unexpectedly discovered for the first time that C17 sphingosine and NDMS addition to cancer cells alters cholesterol homeostasis by impacting its cellular synthesis, uptake, and efflux leading to a net decrease in cholesterol levels and inducing apoptosis. Our results reflect a reverse correlation between the levels of sphingosines, NDMS, and unesterified, free cholesterol in the cells. We show that increasing sphingosine and NDMS (a sphingosine analog) levels alter not only the trafficking of cholesterol between membranes but also the efflux and synthesis of cholesterol. We also demonstrate that despite the effort to remove free cholesterol by ABCA1-mediated efflux or by suppressing machinery for the influx (LDLR) and biosynthetic pathway (HMGCR), apoptosis is inevitable for IDH1mutglioma cells. This is the first study that shows how altering sphingosine levels directly affects cholesterol homeostasis in cancer cells and can be used to manipulate this relationship to induce apoptosis in IDH1mutgliomas.
CENP-C-targeted PLK-1 regulates kinetochore function inC. elegansembryos
Authors: Borja Laura Bel , Taylor Samuel J.P. , Soubigou Flavie , Pelisch Federico 
Published: April 2024

SUMMARYPolo-like kinase 1 (PLK1) is present in centrosomes, nuclear envelope, and kinetochores and plays a significant role in meiosis and mitosis. PLK-1 depletion or inhibition has severe consequences for spindle assembly, spindle assembly checkpoint (SAC) activation, chromosome segregation, and cytokinesis. BUB1 targets PLK1 to the outer kinetochore and, in mammals, the inner kinetochore PLK1 targeting is mediated by the constitutive centromere associated network (CCAN). BUB1-targeted PLK1 plays a key role in SAC activation and a SAC-independent role through targeting CDC-20. In contrast, whether there is a specific, non-redundant role for inner kinetochore targeted PLK1 is unknown. Here, we used theC. elegansembryo to study the role of inner kinetochore PLK1. We found that CENP-C, the sole CCAN component inC. elegansand other species, targets PLK1 to the inner kinetochore during prometaphase and metaphase. Disruption of the CENP-C/PLK1 interaction leads to an imbalance in kinetochore components and a defect in chromosome congression, without affecting CDC-20 recruitment. These findings indicate that PLK1 kinetochore recruitment by CENP-C has at least partially distinct functions than outer kinetochore PLK1, providing a platform for better understanding the different roles played by PLK1 during mitosis.
Potential use of blockchain technology in construction supply chain management of Brazil
Authors: Pinto Varela Alberte Elaine , de Oliveira Novelli Gabriel 
Published: April 2024

Purpose
This paper aims to analyze practices, processes and outcomes related to construction supply chain management (CSCM) in Brazil to identify opportunities and direct actions and strategies to improve the Brazilian sector through blockchain technology (BT).

Design/methodology/approach
The study collected empirical data through semi-structured interviews with consumers and distributors to identify how the CSCM functions today. The interviews were structured and analyzed around the following topics: processes, digitalization, quality and weakness of the activities performed. The opportunities for using BT in CSCM were identified by crossing these results with evidence in the bibliography.

Findings
The study identified deficiencies, gaps and good practices applied to information management in the sector. Also, it analyzed the features, drivers and barriers of BT from a practical perspective. The findings suggested that BT is feasible and promising, reducing costs and enhancing process transparency. The need to overcome cultural and economic barriers is a challenging task.

Originality/value
This study brings a new perspective on using BT in CSCM, relating it to the demands and particularities of the construction sector in Brazil. The study identifies a limited panorama of chronic CSCM concerns, given BT’s infinite opportunities. And it motivates a gradual transition toward installing a new technological culture based on BT that focuses on priority care for the sector’s chronic deficiencies. The results can guide practical actions for the successful insertion of BT in the CSCM, laying the foundations for significant future research.
What factors determine the intention to use and recommend public autonomous shuttles in a real-life setting?
Authors: Quinones Myriam , Romero Jaime , Schmitz Anne , Díaz-Martín Ana M. 
Published: April 2024

PurposeUser acceptance is a necessary precondition to implementing self-driving buses as a solution to public transport challenges. Focusing on potential users in a real-life setting, this paper aims to analyze the factors that affect their willingness to use public autonomous shuttles (PASs) as well as their word-of-mouth (WOM) intentions.Design/methodology/approachGrounded on Unified Theory of Acceptance and Use of Technology (UTAUT2), the study was carried out on a sample of 318 potential users in a real-life setting. The hypothesized relationships were tested using partial least squares structural equation modeling (PLS-SEM).FindingsThe study reveals that performance expectancy, facilitating conditions, hedonic motivation and trust are significant predictors of PAS usage intention, which is, in turn, related to WOM communication. Additionally, the factors that impact the intention to use a PAS are found to exert an indirect effect on WOM, mediated by usage intention.Practical implicationsThis study includes practical insights for transport decision-makers on PAS service design, marketing campaigns and WOM monitoring.Originality/valueWhile extant research focuses on passengers who have tried autonomous shuttles in experimental settings, this article adopts the perspective of potential users who have no previous experience with these vehicles and identifies the link between usage intention and WOM communication in a real-life traffic environment.