bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integration of genetic colocalizations with physiological and pharmacological perturbations identifies cardiometabolic disease genes
Authors: Gloudemans Michael J. , Balliu Brunilda , Nachun Daniel , Durrant Matthew G. , Ingelsson Erik , Wabitsch Martin , Quertermous Thomas , Montgomery Stephen B. , Knowles Joshua W. , Carcamo-Orive Ivan 
Published: September 2021

AbstractBackgroundIdentification of causal genes for polygenic human diseases has been extremely challenging, and our understanding of how physiological and pharmacological stimuli modulate genetic risk at disease-associated loci is limited. Specifically, insulin resistance (IR), a common feature of cardiometabolic disease, including type 2 diabetes, obesity, and dyslipidemia, lacks well-powered GWAS, and therefore few associated loci and causal genes have been identified.ResultsHere, we perform and integrate LD-adjusted colocalization analyses across nine cardiometabolic traits combined with eQTLs and sQTLs from five metabolically relevant human tissues (subcutaneous and visceral adipose, skeletal muscle, liver, and pancreas). We identify 470 colocalized loci and prioritize 207 loci with a single colocalized gene. To elucidate upstream regulators and functional mechanisms for these genes, we integrate their transcriptional responses to 21 physiological and pharmacological cardiometabolic regulators in human adipocytes, hepatocytes, and skeletal muscle cells, and map their protein-protein interactions.ConclusionsOur use of transcriptional responses under metabolic perturbations to contextualize genetic associations from our state-of-the-art colocalization approach provides a list of likely causal genes and their upstream regulators in the context of IR-associated cardiometabolic risk.
Comparative transcriptomic analysis of maize ear heterosis during the inflorescence meristem differentiation stage
Authors: Shi Xia , li Weihua , Guo Zhanyong , Wu Mingbo , Zhang Xiangge , Yuan Liang , Qiu Xiaoqian , Xing Ye , Sun Xiaojing , Xie Huiling , Tang Jihua 
Published: September 2021

AbstractHeterosis is widely used in many crops; however, its genetic mechanisms are only partly understood. Here, we sampled inflorescence meristem (IM) ears from the single-segment substitution maize (Zea mays) line lx9801hlEW2b, containing a heterotic locus hlEW2b associated with ear width, the receptor parent lx9801, the test parent Zheng58, and their corresponding hybrids. After transcriptomic analysis, 1638 genes were identified in at least one hybrid with nonadditively expressed patterns and different expression levels between the two hybrids. In particular, 2263 (12.89%) and 2352 (14.65%) genes showed allele-specific expression (ASE) in Zheng58 × lx9801 and Zheng58 × lx9801hlEW2b, respectively. A functional analysis showed that these genes were enriched in development-related processes and biosynthesis and catabolism processes, which are potentially associated with heterosis. Additionally, nonadditive expression and ASE may fine-tune the expression levels of crucial genes (such as WUS and KNOX that control IM development) controlling auxin metabolism and ear development to optimal states, and transcriptional variation may play important roles in maize ear heterosis. The results provide new information that increases our understanding of the relationship between transcriptional variation and heterosis formation during maize ear development, which may be helpful in clarifying the genetic and molecular mechanisms of heterosis.
Streptococcus pneumoniaerapidly translocates from the nasopharynx through the cribriform plate to invade and inflame the dura
Authors: Audshasai Teerawit , Coles Jonathan A. , Panagiotou Stavros , Khandaker Shadia , Scales Hannah E. , Kjos Morten , Baltazar Murielle , Vignau Julie , Brewer James M. , Kadioglu Aras , Yang Marie 
Published: September 2021

AbstractThe entry routes and translocation mechanisms of bacterial pathogens into the central nervous system remain obscure. We report here thatStreptococcus pneumoniae(Sp) or polystyrene microspheres, applied to the nose of a mouse, appeared in the meninges of the dorsal cortex within minutes. Recovery of viable bacteria from dissected tissue and fluorescence microscopy showed that up to at least 72h, Sp and microspheres were predominantly in the outer of the two meninges, the pachymeninx. No Sp were found in blood or cerebrospinal fluid. Evidence that this was not an artifact of the method of administration is that in mice infected by horizontal transmission, Sp were also predominantly in the meninges and absent from blood. Intravital imaging through the skull, and flow cytometry showed recruitment and activation of LysM+cells in the dorsal pachymeninx at 5h and 10h following intranasal infection. Imaging of the cribriform plate suggested that both Sp and microspheres entered through its foramina via an inward flow of fluid connecting the nose to the pachymeninx. Our findings bring further insight into the invasion mechanisms of bacterial pathogens such as Sp into the central nervous system, but are also pertinent to the delivery of drugs to the brain, and the entry of air-borne particles into the cranium.
Associations between SARS-CoV-2 variants and risk of COVID-19 hospitalization among confirmed cases in Washington State: a retrospective cohort study
Authors: Paredes Miguel I. , Lunn Stephanie M. , Famulare Michael , Frisbie Lauren A. , Painter Ian , Burstein Roy , Roychoudhury Pavitra , Xie Hong , Bakhash Shah A. Mohamed , Perez Ricardo , Lukes Maria , Ellis Sean , Sathees Saraswathi , Mathias Patrick C. , Greninger Alexander , Starita Lea M. , Frazar Chris D. , Ryke Erica , Zhong Weizhi , Gamboa Luis , Threlkeld Machiko , Lee Jover , McDermot Evan , Truong Melissa , Nickerson Deborah A. , Bates Daniel L. , Hartman Matthew E. , Haugen Eric , Nguyen Truong N. , Richards Joshua D. , Rodriguez Jacob L. , Stamatoyannopoulos John A. , Thorland Eric , Melly Geoff , Dykema Philip E. , MacKellar Drew C. , Gray Hannah K. , Singh Avi , Peterson JohnAric M. , Russell Denny , Torres Laura Marcela , Lindquist Scott , Bedford Trevor , Allen Krisandra J. , Oltean Hanna N. 
Published: September 2021

AbstractBackgroundThe COVID-19 pandemic is dominated by variant viruses; the resulting impact on disease severity remains unclear. Using a retrospective cohort study, we assessed the hospitalization risk following infection with seven SARS-CoV-2 variants.MethodsOur study includes individuals with positive SARS-CoV-2 RT-PCR in the Washington Disease Reporting System with available viral genome data, from December 1, 2020 to January 14, 2022. The analysis was restricted to cases with specimens collected through sentinel surveillance. Using a Cox proportional hazards model with mixed effects, we estimated hazard ratios (HR) for hospitalization risk following infection with a variant, adjusting for age, sex, calendar week, and vaccination.Findings58,848 cases were sequenced through sentinel surveillance, of which 1705 (2.9%) were hospitalized due to COVID-19. Higher hospitalization risk was found for infections with Gamma (HR 3.20, 95%CI 2.40-4.26), Beta (HR 2.85, 95%CI 1.56-5.23), Delta (HR 2.28 95%CI 1.56-3.34) or Alpha (HR 1.64, 95%CI 1.29-2.07) compared to infections with ancestral lineages; Omicron (HR 0.92, 95%CI 0.56-1.52) showed no significant difference in risk. Following Alpha, Gamma, or Delta infection, unvaccinated patients show higher hospitalization risk, while vaccinated patients show no significant difference in risk, both compared to unvaccinated, ancestral lineage cases. Hospitalization risk following Omicron infection is lower with vaccination.ConclusionInfection with Alpha, Gamma, or Delta results in a higher hospitalization risk, with vaccination attenuating that risk. Our findings support hospital preparedness, vaccination, and genomic surveillance.SummaryHospitalization risk following infection with SARS-CoV-2 variant remains unclear. We find a higher hospitalization risk in cases infected with Alpha, Beta, Gamma, and Delta, but not Omicron, with vaccination lowering risk. Our findings support hospital preparedness, vaccination, and genomic surveillance.
Determinants of sleep quality in adults during the COVID-19 pandemic: COVID-Inconfidentes, a population-based study
Authors: de Menezes Júnior Luiz Antônio Alves , Lourenção Luciano Garcia , Andrade Amanda Cristina de Souza , Carraro Júlia Cristina Cardoso , Machado-Coelho George Luiz Lins , Meireles Adriana Lúcia 
Published: September 2021

ABSTRACTBackgroundThe coronavirus disease 2019 (COVID-19) pandemic has had a negative effect on the health and behavior of the world’s population.ObjectivesTo evaluate sleep quality and its associated factors in adults during the COVID-19 pandemic in Brazil.MethodsThis is a population-based serological survey of 1762 adults collected from October to December 2020 in the Iron Quadrangle region, Brazil. To measure sleep quality, we used the Pittsburgh Sleep Quality Index questionnaire and socio-demographic, health, health related behaviors, anxiety, vitamin D, weight gain/loss, and pandemic characteristics were assessed using a structured questionnaire. Univariate and multivariate analyses were performed to identify the factors associated with sleep quality.ResultsMore than half of the individuals evaluated had poor sleep quality (52.5%). In multivariate analysis, factors related to sleep quality included living alone (OR=2.36; 95%CI: 1.11-5.00), anxiety disorder (OR=2.22; 95%CI: 1.20-4.14), 5.0% weight loss during the pandemic (OR=1.66; 95%CI: 1.01-2.76), weight gain of 5.0% (OR=1.90; 95%CI: 1.08-3.34), insufficient vitamin D scenario (OR=1.47; 95%CI: 1.01-2.12), and symptoms of COVID-19 (OR=1.94; 95%CI: 1.25-3.01).ConclusionsOur study revealed that more than half of the participants had poor sleep quality during the COVID-19 outbreak, and the factors associated with poor sleep quality were related to the pandemic, such as insufficient vitamin D scenario and weight change.
De novo biosynthesis of para-nitro-L-phenylalanine in Escherichia coli
Authors: Butler Neil D. , Sen Sabyasachi , Lin Minwei , Kunjapur Aditya M. 
Published: September 2021

AbstractNitroaromatic functional groups can impart valuable properties to chemicals and to biological macromolecules including polypeptides. Para-nitro-L-phenylalanine (pN-Phe) is a nitroaromatic amino acid with uses including immune stimulation and fluorescence quenching. As the chemical synthesis of pN-Phe does not follow green chemistry principles and impedes provision of pN-Phe to engineered bacterial cells in some contexts, we sought to design a de novo biosynthetic pathway for pN-Phe in Escherichia coli. To generate the nitro chemical functional group, we identified natural diiron monooxygenases with measurable in vitro and in vivo activity on envisioned amine-containing precursors of para-amino-L-phenylalanine (pA-Phe) and para-aminophenylpyruvate. By expressing one of these N-oxygenase genes together with previously characterized genes for the biosynthesis of pA-Phe, we achieved the synthesis of pN-Phe from glucose. Through further optimization of the chassis, plasmid constructs, and media conditions, we were able to improve the selectivity of pN-Phe biosynthesis, resulting in a maximum titer of 819 µM in rich defined media under shake-flask conditions. These results provide a foundation for the biosynthesis of related nitroaromatic chemicals and for downstream biological applications that could utilize pN-Phe as a building block.HighlightsPara-nitro-L-phenylalanine (pN-Phe) is a valuable small molecule for its applications in genetic code expansion.We establish de novo biosynthesis of pN-Phe from glucose in E. coli, which is also the first example of a de novo pathway design for an unnatural but commonly used non-standard amino acid.We show the first use of an N-oxygenase enzyme in the de novo synthesis of a nitroaromatic product.Screening of natural N-oxygenases and strain engineering resulted in final pN-Phe titers of 820 ± 130 µM in shake flask experiments with rich defined media.
Kinetoplastid-specific X2-family kinesins interact with a kinesin-like pleckstrin homology domain protein that localizes to the trypanosomal microtubule quartet
Authors: Benz Corinna , Müller Nora , Kaltenbrunner Sabine , Váchová Hana , Vancová Marie , Lukeš Julius , Varga Vladimír , Hashimi Hassan 
Published: September 2021

ABSTRACTKinesins are motor proteins found in all eukaryotic lineages that move along microtubules to mediate cellular processes such as mitosis and intracellular transport. In trypanosomatids, the kinesin superfamily has undergone a prominent expansion, resulting in one of the most diverse kinesin repertoires that includes the two kinetoplastid-restricted families X1 and X2. Here, we characterize in Trypanosoma brucei TbKifX2A, an orphaned X2 kinesin. TbKifX2A tightly interacts with TbPH1, a kinesin-like protein with a likely inactive motor domain, a rarely reported occurrence. Both TbKifX2A and TbPH1 localize to the microtubule quartet (MtQ), a characteristic but poorly understood cytoskeletal structure that wraps around the flagellar pocket as it extends to the cell body anterior. The proximal proteome of TbPH1 revealed two other interacting proteins, the flagellar pocket protein FP45 and intriguingly another X2 kinesin, TbKifX2C. Simultaneous ablation of TbKifX2A/TbPH1 results in the depletion of FP45 and TbKifX2C and also an expansion of the flagellar pocket, among other morphological defects. TbKifX2A is the first motor protein to be localized to the MtQ. The observation that TbKifX2C also associates with the MtQ suggests that the X2 kinesin family may have co-evolved with the MtQ, both kinetoplastid-specific traits.
The exchange of vitamin B1 and its biosynthesis intermediates in synthetic microbial communities shapes the community composition and reveals complexities of nutrient sharing
Authors: Sathe Rupali R. M. , Paerl Ryan W. , Hazra Amrita B. 
Published: September 2021

AbstractMicrobial communities occupy diverse niches in nature, and exchanges of metabolites such as carbon sources, amino acids, and vitamins occur routinely among the community members. While large-scale metagenomic and metabolomic studies shed some light on these exchanges, the contribution of individual species and the molecular details of specific interactions are difficult to track. Here, we explore the molecular picture of vitamin B1 (thiamin) metabolism occurring in synthetic communities of Escherichia coli thiamin auxotrophs which engage in the exchange of thiamin and its biosynthesis intermediates. In E. coli, the two parts of thiamin – the 4-amino-5-hydroxymethyl-2-methylpyrimidine and the 4-methyl-5-(2-hydroxyethyl)thiazole – are synthesized by separate pathways using enzymes ThiC and ThiG, respectively, and are then joined by ThiE to form thiamin. We observed that even though E. coli ΔthiC, ΔthiE, and ΔthiG mutants are thiamin auxotrophs, co-cultures of ΔthiC-ΔthiE and ΔthiC-ΔthiG grow in a thiamin-deficient minimal medium, whereas the ΔthiE-ΔthiG co-culture does not. Analysis of the exchange of thiamin and its intermediates in Vibrio anguillarum co-cultures, and in mixed co-cultures of V. anguillarum and E. coli revealed that the general pattern of thiamin metabolism and exchange among microbes is conserved across species. Specifically, the microorganisms exchange HMP and thiamin easily among themselves but not THZ. Furthermore, we observe that the availability of exogenous thiamin in the media affects whether these strains interact with each other or grow independently. This underscores the importance of the exchange of essential metabolites as a defining factor in building and modulating synthetic or natural microbial communities.
Structure and function of one unclassified-class glutathioneS-transferase inLeptinotarsa decemlineata
Authors: Liu Yanjun , Moural Timothy , Koirala BK Sonu , Hernandez Jonathan , Shen Zhongjian , Alyokhin Andrei , Zhu Fang 
Published: September 2021

AbstractArthropod Glutathione S-transferases (GSTs) constitute a large family of multifunctional enzymes that are mainly associated with xenobiotic or stress adaptation. GST-mediated xenobiotic adaptation is through direct metabolism or sequestration of xenobiotics, and/or indirectly by providing protection against oxidative stress induced by xenobiotic exposure. To date, the roles of GSTs in xenobiotic adaptation in the Colorado potato beetle (CPB), a notorious agriculture pest of plants within Solanaceae have not been well studied. Here, we functionally expressed and characterized an unclassified-class GST, LdGSTu1. The three-dimensional structure of the LdGSTu1 was solved with a resolution up to 1.8 Å by x-ray crystallography. Recombinant LdGSTu1 was used to determine enzyme activity and kinetic parameters using 1-chloro-2,4-dinitrobenzene (CDNB), GSH, p-nitrophenyl acetate (PNA) as substrates. The enzyme kinetic parameters and enzyme-substrate interaction studies demonstrated that LdGSTu1 could catalyze the conjugation of GSH to both CDNB and PNA, with a higher turnover number for CDNB than PNA. The LdGSTu1 enzyme inhibition assays demonstrated that the enzymatic conjugation of GSH to CDNB could be inhibited by multiple pesticides, suggesting a potential function of LdGSTu1 in xenobiotic adaptation.
Addressing the agricultural financing gap in Malaysia via Manihah Agricultural Financing Model: will Islamic banks go the extra mile?
Authors: Abd Rahman Nur Hasnida , Md Zabri Mohd Zaidi , Ali Mohammad Mahbubi 
Published: September 2021

PurposeThis paper introduces the concept of manihah and develops a conceptual framework to address Malaysia's abandoned lands and food security issues.Design/methodology/approachThis is a conceptual paper based on insights from the existing literature and secondary data on food security, abandoned lands and manihah. Based on the prevailing gaps, the study proposes a conceptual framework of the Manihah Agricultural Financing Model to address Malaysia's abandoned land and food security issues.FindingsThe proposed model can address abandoned lands and food security issues due to the new incorporation of manihah within Malaysia's agricultural and Islamic financial industries' milieu.Research limitations/implicationsThis is a conceptual paper mainly intended to spark a discussion on the potentiality of manihah.Practical implicationsThe paper contends that Islamic banks have a crucial role in furthering the socio-economic development agenda under the value-based intermediation (VBI). The paper will also be an excellent introduction to Islamic bank practitioners in understanding manihah's relevance to their daily operation.Originality/valueThis paper introduces manihah as the potential solution to food security issues by utilizing abandoned lands.
“We don’t have any answers within the current framework”: tensions within cannabis policy change in Ireland
Authors: Ó. Rálaigh Chris , Morton Sarah 
Published: September 2021

Purpose
International policy approaches to cannabis production and use are changing rapidly, and within the Irish context, alternatives to prohibition are being considered. This study aims to explore policymaker’s attitudes towards the decriminalisation and legal regulation of cannabis for recreational use in the midst of an unfolding policy process, examining the degree which a “policy window” might be open for the implementation of cannabis policy change.

Design/methodology/approach
Semi-structured interviews were held with eight key informants within the policy field in Dublin, Ireland. Kingdon’s (2014) Multiple Streams framework was used to consider whether the problems, policy and political streams were aligning to support progressive policy change.

Findings
Irish policymakers indicated broad support for the decriminalisation of cannabis. The legal regulation of cannabis received more qualified support. Existing policy was heavily criticised with criminalisation identified as a clear failure. Of particular interest was the willingness of policymakers to offer opinions which contrasted with the policy positions of their organisations. While a policy window did open – and close – subsequent governmental commitments to examine the issue of drugs policy in a more deliberative process in the near future highlight the incremental nature of policy change.

Originality/value
This study provides unique insight into the opinions of policymakers in the midst of a prolonged period of policy evolution. A latent aspiration for historical policy change was situated within the realpolitik of more traditional approaches to policy development, demonstrating that the alignment of Kingdon’s (2014) problem, policy and political streams are essential for change in cannabis policy.
Dissecting the ecosystems’ determinants of entrepreneurial re-entry after a business failure
Authors: Espinoza-Benavides Jorge , Guerrero Maribel , Díaz David 
Published: September 2021

Purpose
This study aims to evaluate the role of entrepreneurial ecosystems conditions (formal, informal and social capital) on different types of entrepreneurial re-entry at a global scale.

Design/methodology/approach
Given this phenomenon’s nature, this study builds a panel of data of 54 economies covering different (advanced and emerging) countries across the globe during the period 2004–2017 by mixing multiples sources of information (e.g. Global Entrepreneurship Monitor, the World Economic Forum, the World Bank and the International Monetary Fund). The statistical analysis consisted of the fixed-effect dynamic generalized method of moments (GMM) estimation for panel data.

Findings
Three empirical insights emerge from the study. First, the entrepreneurial ecosystem’s formal conditions are mainly configured to support high-growth entrepreneurship ignoring re-entrepreneurs. Consequently, the formal conditions’ contribution is very limited in emerging economies. Second, the analysis of informal conditions revealed social media’s critical contribution for legitimizing entrepreneurship and supporting those entrepreneurs who want to re-enter the domestic or international market after a business failure. Third, social networks built during previous business angels or entrepreneurial experiences or with other entrepreneurs also play a crucial role for re-entrepreneurs to overcome the weaknesses in the entrepreneurial ecosystems’ conditions.

Originality/value
The study contributes to two ongoing academic debates among entrepreneurship scholars. The first is related to how the entrepreneurial ecosystem supports entrepreneurial activity in different economic contexts. The second is related to the study of the contextual determinants of entrepreneurial re-entry after a business failure.