bluuebunny/crossref_metadata_2025_split huggingface dataset:
Xenogeneic silencing strategies in bacteria are dictated by RNA polymerase promiscuity
Authors: Forrest David , Warman Emily A. , Erkelens Amanda M. , Dame Remus T. , Grainger David C. 
Published: March 2022

AbstractHorizontal gene transfer facilitates dissemination of favourable traits among bacteria. However, foreign DNA can also reduce host fitness: incoming sequences with a higher AT content than the host genome can misdirect transcription. Xenogeneic silencing proteins counteract this by modulating RNA polymerase binding. In this work, we compare xenogeneic silencing strategies of two distantly related model organisms: Escherichia coli and Bacillus subtilis. In E. coli, silencing is mediated by the H-NS protein that binds extensively across horizontally acquired genes. This prevents spurious non-coding transcription, mostly intragenic in origin. By contrast, binding of the B. subtilis Rok protein is more targeted and mostly silences expression of functional mRNAs. The difference reflects contrasting transcriptional promiscuity in E. coli and B. subtilis, largely attributable to housekeeping RNA polymerase σ factors. Thus, whilst RNA polymerase specificity is key to the xenogeneic silencing strategy of B. subtilis, transcriptional promiscuity must be overcome to silence horizontally acquired DNA in E. coli.
Accelerating flash droughts induced by the joint influence of soil moisture depletion and atmospheric aridity
Authors: Qing Yamin , Wang Shuo , Ancell Brian C. , Yang Zong-Liang 
Published: March 2022

AbstractThe emergence of flash drought has attracted widespread attention due to its rapid onset. However, little is known about the recent evolution of flash droughts in terms of the speed of onset and the causes of such a rapid onset phase of flash droughts. Here, we present a comprehensive assessment of the onset development of flash droughts and the underlying mechanisms on a global scale. We find that 33.64−46.18% of flash droughts with 5-day onset of drying, and there is a significant increasing trend in the proportion of flash droughts with the 1-pentad onset time globally during the period 2000−2020. Flash droughts do not appear to be occurring more frequently in most global regions, just coming on faster. In addition, atmospheric aridity is likely to create a flash drought-prone environment, and the joint influence of soil moisture depletion and atmospheric aridity further accelerates the rapid onset of flash droughts.
Astrocytic phagocytosis contributes to demyelination after focal cortical ischemia in mice
Authors: Wan Ting , Zhu Wusheng , Zhao Ying , Zhang Xiaohao , Ye Ruidong , Zuo Meng , Xu Pengfei , Huang Zhenqian , Zhang Chunni , Xie Yi , Liu Xinfeng 
Published: March 2022

AbstractIschemic stroke can cause secondary myelin damage in the white matter distal to the primary injury site. The contribution of astrocytes during secondary demyelination and the underlying mechanisms are unclear. Here, using a mouse of distal middle cerebral artery occlusion, we show that lipocalin-2 (LCN2), enriched in reactive astrocytes, expression increases in nonischemic areas of the corpus callosum upon injury. LCN2-expressing astrocytes acquire a phagocytic phenotype and are able to uptake myelin. Myelin removal is impaired in Lcn2−/− astrocytes. Inducing re-expression of truncated LCN2(Δ2–20) in astrocytes restores phagocytosis and leads to progressive demyelination in Lcn2−/− mice. Co-immunoprecipitation experiments show that LCN2 binds to low-density lipoprotein receptor-related protein 1 (LRP1) in astrocytes. Knockdown of Lrp1 reduces LCN2-induced myelin engulfment by astrocytes and reduces demyelination. Altogether, our findings suggest that LCN2/LRP1 regulates astrocyte-mediated myelin phagocytosis in a mouse model of ischemic stroke.
Sex-linked deubiquitinase establishes uniparental transmission of chloroplast DNA
Authors: Joo Sunjoo , Kariyawasam Thamali , Kim Minjae , Jin EonSeon , Goodenough Ursula , Lee Jae-Hyeok 
Published: March 2022

AbstractMost sexual organisms inherit organelles from one parent, commonly by excluding organelles from the smaller gametes. However, post-mating elimination of organelles derived from one gamete ensures uniparental inheritance, where the underlying mechanisms to distinguish organelles by their origin remain obscure. Mating in Chlamydomonas reinhardtii combines isomorphic plus and minus gametes, but chloroplast DNA from minus gametes is selectively degraded in zygotes. Here, we identify OTU2p (otubain protein 2), encoded in the plus mating-type locus MT+, as the protector of plus chloroplast. Otu2p is an otubain-like deubiquitinase, which prevents proteasome-mediated degradation of the preprotein translocase of the outer chloroplast membrane (TOC) during gametogenesis. Using OTU2p-knockouts and proteasome inhibitor treatment, we successfully redirect selective DNA degradation in chloroplasts with reduced TOC levels regardless of mating type, demonstrating that plus-specific Otu2p establishes uniparental chloroplast DNA inheritance. Our work documents that a sex-linked organelle quality control mechanism drives the uniparental organelle inheritance without dimorphic gametes.
Role of mobile genetic elements in the global dissemination of the carbapenem resistance gene blaNDM
Authors: Acman Mislav , Wang Ruobing , van Dorp Lucy , Shaw Liam P. , Wang Qi , Luhmann Nina , Yin Yuyao , Sun Shijun , Chen Hongbin , Wang Hui , Balloux Francois 
Published: March 2022

AbstractThe mobile resistance gene blaNDM encodes the NDM enzyme which hydrolyses carbapenems, a class of antibiotics used to treat some of the most severe bacterial infections. The blaNDM gene is globally distributed across a variety of Gram-negative bacteria on multiple plasmids, typically located within highly recombining and transposon-rich genomic regions, which leads to the dynamics underlying the global dissemination of blaNDM to remain poorly resolved. Here, we compile a dataset of over 6000 bacterial genomes harbouring the blaNDM gene, including 104 newly generated PacBio hybrid assemblies from clinical and livestock-associated isolates across China. We develop a computational approach to track structural variants surrounding blaNDM, which allows us to identify prevalent genomic contexts, mobile genetic elements, and likely events in the gene’s global spread. We estimate that blaNDM emerged on a Tn125 transposon before 1985, but only reached global prevalence around a decade after its first recorded observation in 2005. The Tn125 transposon seems to have played an important role in early plasmid-mediated jumps of blaNDM, but was overtaken in recent years by other elements including IS26-flanked pseudo-composite transposons and Tn3000. We found a strong association between blaNDM-carrying plasmid backbones and the sampling location of isolates. This observation suggests that the global dissemination of the blaNDM gene was primarily driven by successive between-plasmid transposon jumps, with far more restricted subsequent plasmid exchange, possibly due to adaptation of plasmids to their specific bacterial hosts.
Structural basis of leukotriene B4 receptor 1 activation
Authors: Wang Na , He Xinheng , Zhao Jing , Jiang Hualiang , Cheng Xi , Xia Yu , Eric Xu H. , He Yuanzheng 
Published: March 2022

AbstractLeukotriene B4 receptor 1 (BLT1) plays crucial roles in the acute inflammatory responses and is a valuable target for anti-inflammation treatment, however, the mechanism by which leukotriene B4 (LTB4) activates receptor remains unclear. Here, we report the cryo-electron microscopy (cryo-EM) structure of the LTB4 -bound human BLT1 in complex with a Gi protein in an active conformation at resolution of 2.91 Å. In combination of molecule dynamics (MD) simulation, docking and site-directed mutagenesis, our structure reveals that a hydrogen-bond network of water molecules and key polar residues is the key molecular determinant for LTB4 binding. We also find that the displacement of residues M1013.36 and I2717.39 to the center of receptor, which unlock the ion lock of the lower part of pocket, is the key mechanism of receptor activation. In addition, we reveal a binding site of phosphatidylinositol (PI) and discover that the widely open ligand binding pocket may contribute the lack of specificity and efficacy for current BLT1-targeting drug design. Taken together, our structural analysis provides a scaffold for understanding BLT1 activation and a rational basis for designing anti-leukotriene drugs.
Exploratory study reveals far reaching systemic and cellular effects of verapamil treatment in subjects with type 1 diabetes
Authors: Xu Guanlan , Grimes Tiffany D. , Grayson Truman B. , Chen Junqin , Thielen Lance A. , Tse Hubert M. , Li Peng , Kanke Matt , Lin Tai-Tu , Schepmoes Athena A. , Swensen Adam C. , Petyuk Vladislav A. , Ovalle Fernando , Sethupathy Praveen , Qian Wei-Jun , Shalev Anath 
Published: March 2022

AbstractCurrently, no oral medications are available for type 1 diabetes (T1D). While our recent randomized placebo-controlled T1D trial revealed that oral verapamil had short-term beneficial effects, their duration and underlying mechanisms remained elusive. Now, our global T1D serum proteomics analysis identified chromogranin A (CHGA), a T1D-autoantigen, as the top protein altered by verapamil and as a potential therapeutic marker and revealed that verapamil normalizes serum CHGA levels and reverses T1D-induced elevations in circulating proinflammatory T-follicular-helper cell markers. RNA-sequencing further confirmed that verapamil regulates the thioredoxin system and promotes an anti-oxidative, anti-apoptotic and immunomodulatory gene expression profile in human islets. Moreover, continuous use of oral verapamil delayed T1D progression, promoted endogenous beta-cell function and lowered insulin requirements and serum CHGA levels for at least 2 years and these benefits were lost upon discontinuation. Thus, the current studies provide crucial mechanistic and clinical insight into the beneficial effects of verapamil in T1D.
Promoter/enhancer-based controllability of regulatory networks
Authors: Devkota Prajwal , Wuchty Stefan 
Published: March 2022

AbstractUnderstanding the mechanisms of tissue-specific transcriptional regulation is crucial as mis-regulation can cause a broad range of diseases. Here, we investigated transcription factors (TF) that are indispensable for the topological control of tissue specific and cell-type specific regulatory networks as a function of their binding to regulatory elements on promoters and enhancers of corresponding target genes. In particular, we found that promoter-binding TFs that were indispensable for regulatory network control regulate genes that are tissue-specifically expressed and overexpressed in corresponding cancer types. In turn, indispensable, enhancer-binding TFs were enriched with disease and signaling genes as they control an increasing number of cell-type specific regulatory networks. Their target genes were cell-type specific for blood and immune-related cell-types and over-expressed in blood-related cancers. Notably, target genes of indispensable enhancer-binding TFs in cell-type specific regulatory networks were enriched with cancer drug targets, while target genes of indispensable promoter-binding TFs were bona-fide targets of cancer drugs in corresponding tissues. Our results emphasize the significant role control analysis of regulatory networks plays in our understanding of transcriptional regulation, demonstrating potential therapeutic implications in tissue-specific drug discovery research.
Heterogeneous network flow and Petri nets characterize multilayer complex networks
Authors: Ademovic Tahirovic Alma , Angeli David , Strbac Goran 
Published: March 2022

AbstractInteracting subsystems are commonly described by networks, where multimodal behaviour found in most natural or engineered systems found recent extension in form of multilayer networks. Since multimodal interaction is often not dictated by network topology alone and may manifest in form of cross-layer information exchange, multilayer network flow becomes of relevant further interest. Rationale can be found in most interacting subsystems, where a form of multimodal flow across layers can be observed in e.g., chemical processes, energy networks, logistics, finance, or any other form of conversion process relying on the laws of conservation. To this end, the formal notion of heterogeneous network flow is proposed, as a multilayer flow function aligned with the theory of network flow. Furthermore, dynamic equivalence is established with the framework of Petri nets, as the baseline model of concurrent event systems. Application of the resulting multilayer Laplacian flow and flow centrality is presented, along with graph learning based inference of multilayer relationships over multimodal data. On synthetic data the proposed framework demonstrates benefits of multimodal flow derivation in critical component identification. It also displays applicability in relationship inference (learning based function approximation) on multimodal time series. On real-world data the proposed framework provides, among others, multimodal flow interpretation of U.S. economic activity, uncovering underlying empirical steady state probability distribution, as well as inherent network (economic) robustness.
Prognostic nomograms for predicting overall survival and cancer-specific survival in patients with angiosarcoma, a SEER population-based study
Authors: Jiang Ting , Ye Zixiang , Shao Tianyu , Luo Yiyang , Wang Binbin 
Published: March 2022

AbstractAngiosarcoma (AS) is a kind of highly aggressive cancer with high occurrence and mortality rates. This study aimed to establish a comprehensive and validated prognostic nomogram with various clinical indicators in non-metastatic AS patients after surgery. Data of non-metastatic AS patients diagnosed after surgery between 2010 and 2015 was retrieved from the surveillance epidemiology and end results database. Univariate and multivariate Cox proportional hazards regression analysis were performed to identify the independent prognostic factors associated with survival to construct the predictive nomogram of 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) rates. Concordance-index (C-index), calibration plots and receiver operating characteristic (ROC) curves were applied to evaluate the predictive ability of the nomograms. 251 patients in total were divided into the training group (N = 177) and the validation group (N = 74). After the multivariate Cox regression analysis, gender, AJCC stage group 7th ed, T, N stage 7th ed, histologic grade and primary site were statistically identified as independent factors with OS and CSS (P < 0.05). We incorporated the significant factors above and age into nomograms. The C-index of the nomograms for OS and CCS in the training cohort was 0.757 (95%CI 0.697–0.817) and 0.762 (95%CI 0.702–0.822), meanwhile, the C-index of those in the validation cohort was 0.749 (95%CI 0.668–0.830) and 0.756 (95%CI 0.676–0.836) respectively. The results of calibration plots and ROC curve showed the nomograms qualified to measure the risk and prognosis. Our study has developed novel and practical nomograms for predicting prognosis in patients with non-metastatic AS after surgery contributing to cancer management.
Examinations the optical, mechanical, and shielding properties of Ag2O doped B2O3–Bi2O3–SrF2–Na2O glasses for gamma ray shield applications
Authors: Abouhaswa A. S. , Almurayshid Mansour , Almasoud Fahad , Sayyed M. I. , Mahmoud K. A. 
Published: March 2022

AbstractA series of five glass samples have a chemical composition of (55-x) B2O3 + 5 Bi2O3 + 20SrF2 + 20Na2O + xAg2O with varied doping ratios x = 0, 1, 2, 3, and 4 mol% were fabricated using the melt quenching technique to study the effect of B2O3 replacement by Ag2O on the physical, mechanical, optical and gamma-ray shielding capacity of the fabricated glasses. The Cary 5000 UV–Vis–NIR measured the optical absorption in the wavelength range between 200 and 3000 nm. Based on the measured optical absorption, energy (direct/indirect) bandgap and Urbach energy were calculated. Moreover, the measured samples density, molar volume, packing density, dissociation energy, and mechanical properties for the fabricated glasses were calculated using the concepts of the Makishima-Mackenzie model. In this regard, the microhardness was decreased from 4.070 to 3.931 GPa with raising the Ag2O concentration. The effect of B2O3 replacement on the shielding capacity was also evaluated using the Monte Carlo simulation. The simulation results showed that the replacement of B2O3 causes a significant increase in the shielding parameters like linear attenuation coefficient and radiation shielding capacity. The best radiation shielding properties were achieved for a glass sample with 4 mol% Ag2O compound. Its linear attenuation coefficient varied between 8.091 and 0.134 cm−1, raising the gamma photon energy between 0.059 and 2.506 MeV.
The association between the non-HDL-cholesterol to HDL-cholesterol ratio and 28-day mortality in sepsis patients: a cohort study
Authors: Chang Le , Chen Xinglin , Lian Cheng 
Published: March 2022

AbstractThe focus of this study was to explore the association between the non-HDL-cholesterol to HDL-cholesterol (non-HDLc/HDLc) ratio and mortality in septic patients. This was a retrospective cohort study of patients with sepsis in the eICU Collaborative Research Database (eICU-CRD) from 208 distinct ICUs across the United States between 2014 and 2015 that explored. All-cause mortality within 28 days after ICU admission. A multivariable logistic regression model was used to estimate the risk of death. Of the 724 patients with a median age of 68 years, 43 (5.94%) died within 28 days after ICU admission. When the non-HDLc/HDLc ratio was < 3.3, the mortality rate decreased with an adjusted odds ratio (OR) of 0.60 (95% CI 0.37–0.99, P = 0.043) for every 1 increment in the non-HDLc/HDLc ratio. When the non-HDLc/HDLc ratio was ≥ 3.3, the mortality rate increased with an adjusted OR of 1.28 (95% CI 1.01–1.62, P = 0.039) for every one increment in the non-HDLc/HDLc ratio. For patients with sepsis, the association between the non-HDLc/HDLc ratio and the 28-day mortality risk was a U-shaped curve. A higher or lower non-HDLc/HDLc ratio was associated with an increased risk of 28-day mortality.
Emergency department utilization in patients with hypertrophic cardiomyopathy: a nationwide population-based study
Authors: Choi You-Jung , Kim Bongseong , Lee Hyun-Jung , Lee Heesun , Park Jun-Bean , Lee Seung-Pyo , Han Kyungdo , Kim Yong-Jin , Kim Hyung-Kwan 
Published: March 2022

AbstractDespite the increasing burden of hypertrophic cardiomyopathy (HCM) on healthcare resources, data on emergency department (ED) utilization in HCM are lacking. This nationwide population-based study extracted 14,542 HCM patients from the National Health Insurance Service database between 2015–2016, and investigated their ED utilization during a one-year period. The reason for ED utilization was defined as the primary diagnosis upon discharge from EDs. The clinical outcome was defined as hospitalization or all-cause mortality within 90 days after the ED visits. A total of 3209 (22.1%) HCM patients visited EDs within a one-year period (mean age, 66.8 ± 13.8 years; male, 57.4%). The majority (71.1%) of HCM patients who visited the EDs were aged ≥ 60 years. The ED utilization rate was higher in women than in men (26.3% versus 19.7%, P < 0.001). Cardiovascular diseases were the most common reason for ED visits (n = 1333, 41.5%). Among HCM patients who visited EDs, 1195 (37.2%) were hospitalized, and 231 (7.2%) died within 90 days. ED visits for cardiovascular disease was associated with a higher 90-day all-cause mortality (adjusted odds ratio, 2.72; 95% confidence interval 1.79–4.12). These findings would serve as a basis for future research to establish medical policies on ED utilization in HCM.
Gene-based association tests using GWAS summary statistics and incorporating eQTL
Authors: Cao Xuewei , Wang Xuexia , Zhang Shuanglin , Sha Qiuying 
Published: March 2022

AbstractAlthough genome-wide association studies (GWAS) have been successfully applied to a variety of complex diseases and identified many genetic variants underlying complex diseases via single marker tests, there is still a considerable heritability of complex diseases that could not be explained by GWAS. One alternative approach to overcome the missing heritability caused by genetic heterogeneity is gene-based analysis, which considers the aggregate effects of multiple genetic variants in a single test. Another alternative approach is transcriptome-wide association study (TWAS). TWAS aggregates genomic information into functionally relevant units that map to genes and their expression. TWAS is not only powerful, but can also increase the interpretability in biological mechanisms of identified trait associated genes. In this study, we propose a powerful and computationally efficient gene-based association test, called Overall. Using extended Simes procedure, Overall aggregates information from three types of traditional gene-based association tests and also incorporates expression quantitative trait locus (eQTL) information into a gene-based association test using GWAS summary statistics. We show that after a small number of replications to estimate the correlation among the integrated gene-based tests, the p values of Overall can be calculated analytically. Simulation studies show that Overall can control type I error rates very well and has higher power than the tests that we compared with. We also apply Overall to two schizophrenia GWAS summary datasets and two lipids GWAS summary datasets. The results show that this newly developed method can identify more significant genes than other methods we compared with.
A pavement distresses identification method optimized for YOLOv5s
Authors: Guo Keyou , He Chengbo , Yang Min , Wang Sudong 
Published: March 2022

AbstractAutomatic detection and recognition of pavement distresses is the key to timely repair of pavement. Repairing the pavement distresses in time can prevent the destruction of road structure and the occurrence of traffic accidents. However, some other factors, such as a single object category, shading and occlusion, make detection of pavement distresses very challenging. In order to solve these problems, we use the improved YOLOv5 model to detect various pavement distresses. We optimize the YOLOv5 model and introduce attention mechanism to enhance the robustness of the model. The improved model is more suitable for deployment in embedded devices. The optimized model is transplanted to the self-built intelligent mobile platform. Experimental results show that the improved network model proposed in this paper can effectively identify pavement distresses on the self-built intelligent mobile platform and datasets. The precision, recall and mAP are 95.5%, 94.3% and 95%. Compared with YOLOv5s and YOLOv4 models, the mAP of the improved YOLOv5s model is increased by 4.3% and 25.8%. This method can provide technical reference for pavement distresses detection robot.