bluuebunny/crossref_metadata_2025_split huggingface dataset:
APELIN-13 AMELIORATES LPS-INDUCED ENDOTHELIAL-TO-MESENCHYMAL TRANSITION AND POST–ACUTE LUNG INJURY PULMONARY FIBROSIS BY SUPPRESSING TRANSFORMING GROWTH FACTOR-Β1 SIGNALING
Authors: Liu Huang , Shi Qingqiang , Tang Ling , Wang Hanghang , Wang Daoxin 
Published: November 2022

ABSTRACT
The pathophysiology of acute respiratory distress syndrome (ARDS) involves cytokine storms, alveolar-capillary barrier destruction, and fibrotic progression. Pulmonary interstitial fibrosis is an important factor affecting the prognosis of ARDS patients. Endothelial-to-mesenchymal transition (EndMT) plays an important role in the development of fibrotic diseases, and the occurrence of EndMT has been observed in experimental models of LPS-induced acute lung injury (ALI). Apelin is an endogenous active polypeptide that plays an important role in maintaining endothelial cell homeostasis and inhibiting fibrotic progression in various diseases. However, whether apelin attenuates EndMT in ALI and post-ALI pulmonary fibrosis remains unclear. We analyzed the serum levels of apelin-13 in patients with sepsis-associated ARDS to examine its possible clinical value. A murine model of LPS-induced pulmonary fibrosis and an LPS-challenged endothelial cell injury model were used to analyze the protective effect and underlying mechanism of apelin-13. Mice were treated with apelin-13 by i.p. injection, and human pulmonary microvascular endothelial cells were incubated with apelin-13 in vitro. We found that the circulating apelin-13 levels were significantly elevated in sepsis-associated ARDS patients compared with healthy controls. Our study also confirmed that LPS induced EndMT progression and pulmonary fibrosis, which were characterized by decreased CD31 expression and increased α-smooth muscle actin expression and collagen deposition. LPS also stimulated the production of transforming growth factor β1 and activated the Smad signaling pathway. However, apelin-13 treatment significantly attenuated these changes. Our findings suggest that apelin-13 may be a novel biomarker in patients with sepsis-associated ARDS. These results demonstrate that apelin-13 ameliorates LPS-induced EndMT and post-ALI pulmonary fibrosis by suppressing transforming growth factor β1 signaling.
LEUKOCYTE PHENOTYPING IN SEPSIS USING OMICS, FUNCTIONAL ANALYSIS, AND IN SILICO MODELING
Authors: Langston Jordan C. , Yang Qingliang , Kiani Mohammad F. , Kilpatrick Laurie E. 
Published: November 2022

ABSTRACT
Sepsis is a major health issue and a leading cause of death in hospitals globally. The treatment of sepsis is largely supportive, and there are no therapeutics available that target the underlying pathophysiology of the disease. The development of therapeutics for the treatment of sepsis is hindered by the heterogeneous nature of the disease. The presence of multiple, distinct immune phenotypes ranging from hyperimmune to immunosuppressed can significantly impact the host response to infection. Recently, omics, biomarkers, cell surface protein expression, and immune cell profiles have been used to classify immune status of sepsis patients. However, there has been limited studies of immune cell function during sepsis and even fewer correlating omics and biomarker alterations to functional consequences. In this review, we will discuss how the heterogeneity of sepsis and associated immune cell phenotypes result from changes in the omic makeup of cells and its correlation with leukocyte dysfunction. We will also discuss how emerging techniques such as in silico modeling and machine learning can help in phenotyping sepsis patients leading to precision medicine.
THE IMMUNOPATHOGENESIS OF POLYMICROBIAL SEPSIS
Authors: Zetoune Firas S. , Ward Peter A. 
Published: November 2022

ABSTRACT
This report deals with the advances made in the areas of complement and its role in sepsis, both in mice and in humans. The study relates to work over the past 25 years (late 1990s to October 2022). During this period, there has been very rapid progress in understanding the activation pathways of complement and the activation products of complement, especially the anaphylatoxin C5a and its receptors, C5aR1 and C5aR2. Much has also been learned about these pathways of activation that trigger activation of the innate immune system and the array of strong proinflammatory cytokines that can cause cell and organ dysfunction, as well as complement products that cause immunosuppression. The work in septic humans and mice, along with patients who develop lung dysfunction caused by COVID-19, has taught us that there are many strategies for treatment of humans who are septic or develop COVID-19–related lung dysfunction. To date, treatments in humans with these disorders suggest that we are in the midst of a new and exciting area related to the complement system.
A Threshold Criteria for Seasonal Amplification and Outbreaks of Mosquito-Borne Disease (MBD) Cases in Kerala using Climate Parameters
Authors: Chattopadhyay Rajib , Surendran Divya , Lekshmi S , Guhathakurta Pulak , Hosaliker K.S. , Pai D.S. , Manu M. S , Mohapatra M. 
Published: November 2022

AbstractModelling the dynamics of mosquito borne disease (MBD) cases is a challenging task. The current study first proposes a generic dynamical model to qualitatively understand the seasonality as well as outbreaks of malaria and dengue over the state of Kerala based on a climate forced oscillator model, which is then supplemented by a data driven model for quantitative evaluation. The proposed forced oscillator model is parametric and general in nature which can be qualitatively used to understand the seasonality and outbreaks. However, since parametric model-based estimation require estimation of multiple parameters and several closure assumptions, we used the K-means clustering which is a data driven clustering approach to understand the relationship between Malaria and Dengue cases and climate forcing. The results showed a clear relationship of the MBD cases with the first order and second order moments (i.e. mean and standard deviation) of the climate forcing parameters. Based on this, we came up with an objective threshold criterion which relates the climate parameters to the number of cases of malaria and dengue cases over Kerala.
The PBL teaching method in Neurology Education in the Traditional Chinese Medicine undergraduate students: An Observational Study
Authors: Kim Yun Jin 
Published: November 2022

AbstractObjectiveTo study the effect of the Problem Based Learning method in Neurology education for Traditional Chinese Medicine (TCM) undergraduate students.MethodsIn this observational study was conducted 2020/02 and 2020/04 intake the year three TCM undergraduate students of the School of Traditional Chinese Medicine, Xiamen University Malaysia. A total of 86 were enrolled in this study. They were randomly divided into conventional learning groups and PBL groups. Students who missed more than one session of the course and those who did not complete the questionnaires in the evaluation periods were excluded from the study (n=0). An independent sample t-test was used to compare the results between the two groups. A p-value <0.05 was considered significant.ResultsThe PBL group was significantly effective for the students’ theoretical and clinical practical examination scores, the satisfaction of teaching level, students’ perspectives, and self-learning skills, as well as significantly higher DREEM scores than students who participated with the conventional group (p<0.05).ConclusionThe PBL teaching method in Neurology education for TCM undergraduate students can involve an interesting learning method, significantly improve their learning performance, and the ability to analyze the problem-solving skills in the neurology disease and its management knowledge.
Genome-wide association study highlights escape from aphids by delayed growth inArabidopsis thaliana
Authors: Xu Chongmeng , Sato Yasuhiro , Yamazaki Misako , Brasser Marcel , Barbour Matthew A. , Bascompte Jordi , Shimizu Kentaro K. 
Published: November 2022

AbstractField studies have shown that plant phenological and architectural traits often explain substantial variation in herbivory. Although plant genes involved in physical and chemical defense are well studied, less is known about the genetic basis underlying effects of plant growth traits on herbivory. Here, we conducted a genome-wide association study (GWAS) of aphid abundance in a field population ofArabidopsis thaliana. This field GWAS detected a significant peak on the third chromosome ofA. thaliana. Out of candidate genes near this significant genomic region, a mutant of a ribosomal gene (AT3G13882) exhibited slower growth and later flowering than a wild type under laboratory conditions. A no-choice assay with the turnip aphid,Lipaphis erysimi, found that aphids were unable to successfully establish on the mutant. These findings suggest the potential role of growth-related genes in altering herbivore abundance.
DrFARM: Identification and inference for pleiotropic gene in GWAS
Authors: Chan Lap Sum , Li Gen , Fauman Eric B. , Laakso Markku , Boehnke Michael , Song Peter X.K. 
Published: November 2022

AbstractIn a standard analysis, pleiotropic variants are identified by running separate genome-wide association studies (GWAS) and combining results across traits. But such two-stage statistical approach may lead to spurious results. We propose a new statistical approach,Debiased-regularizedFactorAnalysisRegressionModel (DrFARM), through a joint regression model for simultaneous analysis of high-dimensional genetic variants and multilevel dependencies. This joint modeling strategy controls overall error to permit universal false discovery rate (FDR) control. DrFARM uses the strengths of the debiasing technique and the Cauchy combination test, both being theoretically justified, to establish a valid post selection inference on pleiotropic variants. Through extensive simulations, we show that DrFARM appropriately controls overall FDR. Applying DrFARM to data on 1,031 metabolites measured on 6,135 men from the Metabolic Syndrome in Men (METSIM) study, we identify 288 new metabolite associations at loci that did not reach statistical significance in prior METSIM metabolite GWAS.
Molecular evolution of non-visual opsin genes across environmental, developmental, and morphological adaptations in frogs
Authors: Boyette John L , Bell Rayna C , Fujita Matthew K , Thomas Kate N , Streicher Jeffrey W , Gower David J , Schott Ryan K 
Published: November 2022

AbstractNon-visual opsins are transmembrane proteins expressed in the eyes, skin, and brain of many animals. When paired with a light-sensitive chromophore, non-visual opsins form photopigment systems involved in various non-visual, light-detection functions, including circadian rhythm regulation, light-seeking behavior, and detection of seasonality. Previous research has primarily explored the diversity and function of non-visual opsins in model organisms, with few studies investigating their molecular evolution in non-model species. Here we explored molecular evolution of non-visual opsin genes in anuran amphibians (frogs and toads). With diverse lifestyles ranging from fossorial to aquatic, anurans inhabit a diverse array of light environments, which makes them a compelling system for studying the evolution of light detection mechanisms. Using whole-eye transcriptomes from 79 anuran species, as well as genomes and multi-tissue transcriptomes from an additional 15 species, we 1) identify which non-visual opsin genes are expressed in the eyes of anurans; 2) compare selective constraint (ω, or dN/dS) among non-visual opsin genes; and 3) test for potential adaptive evolution by comparing selection between discrete ecological classes in anurans (e.g. diurnal versus non-diurnal). We consistently recovered 14 non-visual opsin genes from anuran eye transcriptomes, compared to 18 genes that we recovered genome wide, and detected positive selection in a subset of these genes. We also found variation in selective constraint between discrete ecological and life-history classes, which may reflect functional adaptation in non-visual opsin genes. Although non-visual opsins remain poorly understood, these findings provide insight into their molecular evolution and set the stage for future research on their potential function across taxa with diverse environmental, developmental, and morphological adaptations.
A consensus score to combine inferences from multiple centres
Authors: Haselimashhadi Hamed , Babalola Kolawole , Wilson Robert , Groza Tudor , Muñoz-Fuentes Violeta 
Published: November 2022

AbstractExperiments in which data are collected by multiple independent resources, including multicentre data, different laboratories within the same centre or with different operators, are challenging in design, data collection and interpretation. Indeed, inconsistent results across the resources are possible. In this paper, we propose a statistical solution for the problem of multi-resource consensus inferences when statistical results from different resources show variation in magnitude, directionality, and significance. Our proposed method allows combining the corrected p-values, effect sizes and the total number of centres into a global consensus score. We apply this method to obtain a consensus score for data collected by the International Mouse Phenotyping Consortium (IMPC) across 11 centres. We show the application of this method to detect sexual dimorphism in haematological data and discuss the suitability of the methodology.
A Bioinformatic Study of the Distribution of Mn Oxidation Proteins in Sequenced Bacterial Genomes
Authors: Kurdi M. Zakaria , Olichney Jacob , Geszvain Kati 
Published: November 2022

1.AbstractBackgroundWhile many species of bacteria have been identified that can convert soluble, reduced manganese (Mn+2) into insoluble, oxidized Mn+4oxides, the mechanisms these bacteria employ and their distribution throughout the bacterial domain are less well understood. One of the best characterized MnOB is the gamma-proteobacteriumPseudomonas putidaGB-1, which uses three distinct proteins (PpMnxG, McoA and MopA) to oxidize Mn+2. The best characterized Mn oxidase enzyme is the MnxG homolog ofBacillussp. PL-12 (BaMnxG), which appears to be the only Mn oxidase in this species. MofA, found inLeptothrix discophorasp SS-1 is an additional putative Mn oxidase.ResultsBy querying publicly available databases of bacterial genome sequences for homologs to these Mn oxidase proteins, it was possible to determine the distribution of the proteins within bacteria. The overwhelming majority of homologs were found in just three phyla: proteobacteria, actinobacteria and firmicutes. These data do not preclude the possibility of novel Mn oxidase mechanisms in other as yet uncharacterized groups of bacteria. Each of the homologs had a statistically significant probability of being present as the solo Mn oxidase in a genome. When genomes did have more than one oxidase, they were present in the same combinations as inP. putidaGB-1.ConclusionsThese results do not support the initial hypothesis that multiple enzymes are required to complete the two-electron oxidation of Mn+2to Mn+4. Alternatively, the various Mn oxidase enzymes may be optimized to function under different environmental conditions; organisms likeP. putidaGB-1 may need to oxidize Mn at different temperatures, nutritional states or oxygen conditions.
Accuracy of a markerless motion capture system for balance related quantities
Authors: Chaumeil Anaïs , Lahkar Bhrigu Kumar , Dumas Raphaël , Muller Antoine , Robert Thomas 
Published: November 2022

AbstractBackgroundBalance studies usually focus on quantities describing the global body motion, such as the position of the whole-body centre of mass (CoM), its associated extrapolated centre of mass (XCoM) and the whole-body angular momentum (WBAM). Assessing such quantities using classical marker-based approach can be tedious and modify the participant’s behaviour. The recent development of markerless motion capture methods could bypass the issues related to the use of markers.Research questionCan we use markerless motion capture systems to study quantities that are relevant for balance studies?MethodsSixteen young healthy participants performed four different motor tasks: walking at self-selected speed, balance loss, walking on a narrow beam and countermovement jumps. Their movements were recorded simultaneously by marker-based and markerless motion capture systems. Videos were processed using a commercial markerless pose estimation software, Theia3D. The position of their CoM was computed, and the associated XCoM and WBAM were derived. Bland-Altman analysis was performed and root mean square error and coefficient of determination were computed to compare the results obtained with marker-based and markerless methods across all participants and tasks.ResultsBias remained of the magnitude of a few mm for CoM and XCoM position, and RMSE of CoM and XCoM was around 1 cm. Confidence interval for CoM and XCoM was under 2 cm except for one task in one direction. RMSE of the WBAM was less than 8% of the total amplitude in any direction, and bias was less than 1%.SignificanceResults suggest that the markerless motion capture system can be used in balance studies as the measured errors are in the range of the differences found between different models or populations in the literature. Nevertheless, one should be careful when assessing dynamic movements such as jumping, as they displayed the biggest errors.HighlightsMarkerless motion capture could bypass issues from classical marker-based approachesWe compared balance related quantities computed from both approachesMean differences were about 1cm on the position of the whole-body center of massObtained differences are acceptable for most applications
Environmental stress during larval development induces head methylome profile shifts in the migratory painted lady butterfly (Vanessa cardui)
Authors: Boman Jesper , Zhu Yishu , Höök Lars , Vila Roger , Talavera Gerard , Backström Niclas 
Published: November 2022

AbstractSeasonal environmental fluctuations provide formidable challenges for living organisms, especially small ectotherms such as butterflies. A common strategy to cope with harsh environments is to enter diapause, but some species avoid the unsuitable conditions by migrating. Despite a growing understanding of migration in the life cycles of some butterfly species, it is unknown how individuals register and store environmental cues to determine whether and where to migrate. Here, we explored how competition and host plant availability during larval development affect patterns of DNA methylation in the migratory painted lady (Vanessa cardui) butterfly. We identify a set of potentially functional methylome shifts associated with differences in the environment, indicating that DNA methylation is involved in the response to different conditions during larval development. By analysing the transcriptome for the same samples used for methylation profiling, we also uncovered a non-linear relationship between gene body methylation and gene expression. Our results provide a starting point for understanding the interplay between DNA methylation and gene expression in butterflies in general and how differences in environmental conditions during development can trigger unique epigenetic marks that might be important for behavioural decisions in the adult stage.
Reconciliation and evolution ofPenicillium rubensGenome-Scale Metabolic Networks – What about specialised metabolism?
Authors: Nègre Delphine , Larhlimi Abdelhalim , Bertrand Samuel 
Published: November 2022

AbstractIn recent years, genome sequencing of filamentous fungi has revealed a high proportion of specialised metabolites with growing pharmaceutical interest. However, detecting such metabolites throughin silicogenome analysis does not necessarily guarantee their expression under laboratory conditions. However, one plausible strategy for enabling their production lies in modifying the growth conditions. Devising a comprehensive experimental design testing in different culture environments is time-consuming and expensive. Therefore, usingin silicomodelling as a preliminary step, such as Genome-Scale Metabolic Network (GSMN), represents a promising approach to predicting and understanding the observed specialised metabolite production in a given organism. To address these questions, we reconstructed a new high-quality GSMN for thePenicillium rubensWisconsin 54-1255 strain, a commonly used model organism. Our reconstruction,iPrub22, adheres to current convention standards and quality criteria, incorporating updated functional annotations, orthology searches with different GSMN templates, data from previous reconstructions, and manual curation steps targeting primary and specialised metabolites. With a MEMOTE score of 74% and a metabolic coverage of 45%,iPrub22 includes 5,192 unique metabolites interconnected by 5,919 reactions, of which 5,033 are supported by at least one genomic sequence. Of the metabolites present iniPrub22, 13% are categorised as belonging to specialised metabolism. While our high-quality GSMN provides a valuable resource for investigating known phenotypes expressed inP. rubens, our analysis identifies bottlenecks related, in particular, to the definition of what is a specialised metabolite, which requires consensus within the scientific community. It also points out the necessity of accessible, standardised and exhaustive databases of specialised metabolites. These questions must be addressed to fully unlock the potential of natural product production inP. rubensand other filamentous fungi. Our work represents a foundational step towards the objective of rationalising the production of natural products through GSMN modelling.