bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioinformatics Analysis of Expression Profiles and Prognostic Values of the Signal Transducer and Activator of Transcription Family Genes in Glioma
Authors: Ji Wei , Liu Yuankun , Xu Bin , Mei Jie , Cheng Chao , Xiao Yong , Yang Kun , Huang Weiyi , Jiao Jiantong , Liu Hongyi , Shao Junfei
Published: July 2021

Signal transducer and activator of transcription (STAT) family genes—of which there are seven members: STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, and STAT6—have been associated with the progression of multiple cancers. However, their prognostic values in glioma remain unclear. In this study, we systematically investigated the expression, the prognostic value, and the potential mechanism of the STAT family genes in glioma. The expression of STAT1/2/3/5A/6 members were significantly higher and positively correlated with IDH mutations, while the expression of STAT5B was lower and negatively correlated with IDH mutations in glioma. Survival analysis indicated that the upregulation of STAT1/2/3/5A/6 and downregulation of STAT5B expression was associated with poorer overall survival in glioma. Joint effects analysis of STAT1/2/3/5A/5B/6 expression suggested that the prognostic value of the group was more significant than that of each individual gene. Thus, we constructed a risk score model to predict the prognosis of glioma. The receiver operating characteristic curve and calibration curves showed good performance as prognostic indicators in both TCGA (The Cancer Genome Atlas) and the CGGA (Chinese Glioma Genome Atlas) databases. Furthermore, we analyzed the correlation between STAT expression with immune infiltration in glioma. The Protein–protein interaction network and enrichment analysis showed that STAT members and co-expressed genes mainly participated in signal transduction activity, Hepatitis B, the Jak-STAT signaling pathway, transcription factor activity, sequence-specific DNA binding, and the cytokine-mediated signaling pathway in glioma. In summary, our study analyzed the expression, prognostic values, and biological roles of the STAT gene family members in glioma, based on which we developed a new risk score model to predict the prognosis of glioma more precisely.
A Single-Step Genome Wide Association Study on Body Size Traits Using Imputation-Based Whole-Genome Sequence Data in Yorkshire Pigs
Authors: Liu Huatao , Song Hailiang , Jiang Yifan , Jiang Yao , Zhang Fengxia , Liu Yibing , Shi Yong , Ding Xiangdong , Wang Chuduan
Published: July 2021

The body shape of a pig is the most direct production index, which can fully reflect the pig’s growth status and is closely related to important economic traits. In this study, a genome-wide association study on seven body size traits, the body length (BL), height (BH), chest circumference (CC), abdominal circumference (AC), cannon bone circumference (CBC), rump width (RW), and chest width (CW), were conducted in Yorkshire pigs. Illumina Porcine 80K SNP chips were used to genotype 589 of 5,572 Yorkshire pigs with body size records, and then the chip data was imputed to sequencing data. After quality control of imputed sequencing data, 784,267 SNPs were obtained, and the averaged linkage disequilibrium (r2) was 0.191. We used the single-trait model and the two-trait model to conduct single-step genome wide association study (ssGWAS) on seven body size traits; a total of 198 significant SNPS were finally identified according to the P-value and the contribution to the genetic variance of individual SNP. 11 candidate genes (CDH13, SIL1, CDC14A, TMRPSS15, TRAPPC9, CTNND2, KDM6B, CHD3, MUC13, MAPK4, and HMGA1) were found to be associated with body size traits in pigs; KDM6B and CHD3 jointly affect AC and CC, and MUC13 jointly affect RW and CW. These genes are involved in the regulation of bone growth and development as well as the absorption of nutrients and are associated with obesity. HMGA1 is proposed as a strong candidate gene for body size traits because of its important function and high consistency with other studies regarding the regulation of body size traits. Our results could provide valuable information for pig breeding based on molecular breeding.
Hypothesis Testing With Rank Conditions in Phylogenetics
Authors: Long Colby , Kubatko Laura
Published: July 2021

A phylogenetic model of sequence evolution for a set ofntaxa is a collection of probability distributions on the 4npossible site patterns that may be observed in their aligned DNA sequences. For a four-taxon model, one can arrange the entries of these probability distributions into three flattening matrices that correspond to the three different unrooted leaf-labeled four-leaf trees, or quartet trees. The flattening matrix corresponding to the tree parameter of the model is known to satisfy certain rank conditions. Methods such as ErikSVD and SVDQuartets take advantage of this observation by applying singular value decomposition to flattening matrices consisting of empirical data. Each possible quartet is assigned an “SVD score” based on how close the flattening is to the set of matrices of the predicted rank. When choosing among possible quartets, the one with the lowest score is inferred to be the phylogeny of the four taxa under consideration. Since ann-leaf phylogenetic tree is determined by its quartets, this approach can be generalized to infer larger phylogenies. In this article, we explore using the SVD score as a test statistic to test whether phylogenetic data were generated by a particular quartet tree. To do so, we use several results to approximate the distribution of the SVD score and to give upper bounds on thep-value of the associated hypothesis tests. We also apply these hypothesis tests to simulated phylogenetic data and discuss the implications for interpreting SVD scores in rank-based inference methods.
Bioinformatic Analysis of Temporal and Spatial Proteome Alternations During Infections
Authors: Rahmatbakhsh Matineh , Gagarinova Alla , Babu Mohan
Published: July 2021

Microbial pathogens have evolved numerous mechanisms to hijack host’s systems, thus causing disease. This is mediated by alterations in the combined host-pathogen proteome in time and space. Mass spectrometry-based proteomics approaches have been developed and tailored to map disease progression. The result is complex multidimensional data that pose numerous analytic challenges for downstream interpretation. However, a systematic review of approaches for the downstream analysis of such data has been lacking in the field. In this review, we detail the steps of a typical temporal and spatial analysis, including data pre-processing steps (i.e., quality control, data normalization, the imputation of missing values, and dimensionality reduction), different statistical and machine learning approaches, validation, interpretation, and the extraction of biological information from mass spectrometry data. We also discuss current best practices for these steps based on a collection of independent studies to guide users in selecting the most suitable strategies for their dataset and analysis objectives. Moreover, we also compiled the list of commonly used R software packages for each step of the analysis. These could be easily integrated into one’s analysis pipeline. Furthermore, we guide readers through various analysis steps by applying these workflows to mock and host-pathogen interaction data from public datasets. The workflows presented in this review will serve as an introduction for data analysis novices, while also helping established users update their data analysis pipelines. We conclude the review by discussing future directions and developments in temporal and spatial proteomics and data analysis approaches. Data analysis codes, prepared for this review are available fromhttps://github.com/BabuLab-UofR/TempSpac, where guidelines and sample datasets are also offered for testing purposes.
Expression Profiling and Functional Analysis of Candidate Col10a1 Regulators Identified by the TRAP Program
Authors: Bian Huiqin , Zhu Ting , Liang Yuting , Hei Ruoxuan , Zhang Xiaojing , Li Xiaochen , Chen Jinnan , Lu Yaojuan , Gu Junxia , Qiao Longwei , Zheng Qiping
Published: July 2021

Hypertrophic chondrocytes and their specific marker, the type X collagen gene (Col10a1), are critical components of endochondral bone formation during skeletal development. We previously found that Runx2 is an indispensable mouse Col10a1 gene regulator and identified many other transcription factors (TFs) that potentially interact with the 150-bp Col10a1 cis-enhancer. However, the roles of these candidate TFs in Col10a1 expression and chondrocyte hypertrophy have not been elucidated. Here, we focus on 32 candidate TFs recently identified by analyzing the 150-bp Col10a1 enhancer using the transcription factor affinity prediction (TRAP) program. We found that 12 TFs (Hoxa3, Lsx, Evx2, Dlx5, S8, Pax2, Egr2, Mef2a, Barhl2, GKlf, Sox17, and Crx) were significantly upregulated and four TFs (Lhx4, Tbx5, Mef2c, and Hb9) were significantly downregulated in hypertrophic MCT cells, which show upregulation of Col10a1 expression. Most of the differential expression pattern of these TFs conformed with the results obtained from ATDC5 cell model and primary mouse chondrocytes. Notably, Tbx5 was downregulated upon Col10a1 upregulation, overexpression of Tbx5 decreased Col10a1 expression, and knock-down of Tbx5 increased Col10a1 expression in hypertrophic chondrocytes, suggesting that Tbx5 is a negative regulator of Col10a1. We further generated a stable Tbx5-overexpressing ATDC5 cell line and ColX-Tbx5 transgenic mice driven by Col10a1-specific enhancers and promoters. Tbx5 overexpression decreased Col10a1 expression in ATDC5 cells cultured as early as day 7 and in limb tissue on post-natal day 1. Slightly weaker alkaline phosphatase staining was also observed in cell culture on day 7 and in limb digits on embryonic day 17.5, indicating mildly delayed ossification. Further characterization of these candidate Col10a1 transcriptional regulators could help identify novel therapeutic targets for skeletal diseases associated with abnormal chondrocyte hypertrophy.
Bronchopulmonary Dysplasia Predicted by Developing a Machine Learning Model of Genetic and Clinical Information
Authors: Dai Dan , Chen Huiyao , Dong Xinran , Chen Jinglong , Mei Mei , Lu Yulan , Yang Lin , Wu Bingbing , Cao Yun , Wang Jin , Zhou Wenhao , Qian Liling
Published: July 2021

Background

An early and accurate evaluation of the risk of bronchopulmonary dysplasia (BPD) in premature infants is pivotal in implementing preventive strategies. The risk prediction models nowadays for BPD risk that included only clinical factors but without genetic factors are either too complex without practicability or provide poor-to-moderate discrimination. We aim to identify the role of genetic factors in BPD risk prediction early and accurately.

Methods

Exome sequencing was performed in a cohort of 245 premature infants (gestational age <32 weeks), with 131 BPD infants and 114 infants without BPD as controls. A gene burden test was performed to find risk genes with loss-of-function mutations or missense mutations over-represented in BPD and severe BPD (sBPD) patients, with risk gene sets (RGS) defined as BPD–RGS and sBPD–RGS, respectively. We then developed two predictive models for the risk of BPD and sBPD by integrating patient clinical and genetic features. The performance of the models was evaluated using the area under the receiver operating characteristic curve (AUROC).

Results

Thirty and 21 genes were included in BPD–RGS and sBPD–RGS, respectively. The predictive model for BPD, which combined the BPD–RGS and basic clinical risk factors, showed better discrimination than the model that was only based on basic clinical features (AUROC, 0.915 vs. AUROC, 0.814, P = 0.013, respectively) in the independent testing dataset. The same was observed in the predictive model for sBPD (AUROC, 0.907 vs. AUROC, 0.826; P = 0.016).

Conclusion

This study suggests that genetic information contributes to susceptibility to BPD. The predictive model in this study, which combined BPD–RGS with basic clinical risk factors, can thus accurately stratify BPD risk in premature infants.
Pre-Treatment Neutrophil Count as a Predictor of Antituberculosis Therapy Outcomes: A Multicenter Prospective Cohort Study
Authors: Carvalho Anna Cristina C. , Amorim Gustavo , Melo Mayla G. M. , Silveira Ana Karla A. , Vargas Pedro H. L. , Moreira Adriana S. R. , Rocha Michael S. , Souza Alexandra B. , Arriaga María B. , Araújo-Pereira Mariana , Figueiredo Marina C. , Durovni Betina , Lapa-e-Silva José R. , Cavalcante Solange , Rolla Valeria C. , Sterling Timothy R. , Cordeiro-Santos Marcelo , Andrade Bruno B. , Silva Elisangela C. , Kritski Afrânio L. ,   the RePORT Brazil consortium
Published: July 2021

Background

Neutrophils have been associated with lung tissue damage in many diseases, including tuberculosis (TB). Whether neutrophil count can serve as a predictor of adverse treatment outcomes is unknown.

Methods

We prospectively assessed 936 patients (172 HIV-seropositive) with culture-confirmed pulmonary TB, enrolled in a multicenter prospective cohort study from different regions in Brazil, from June 2015 to June 2019, and were followed up to two years. TB patients had a baseline visit before treatment (month 0) and visits at month 2 and 6 (or at the end of TB treatment). Smear microscopy, and culture for Mycobacterium tuberculosis (MTB) were performed at TB diagnosis and during follow-up. Complete blood counts were measured at baseline. Treatment outcome was defined as either unfavorable (death, treatment failure or TB recurrence) or favorable (cure or treatment completion). We performed multivariable logistic regression, with propensity score regression adjustment, to estimate the association between neutrophil count with MTB culture result at month 2 and unfavorable treatment outcome. We used a propensity score adjustment instead of a fully adjusted regression model due to the relatively low number of outcomes.

Results

Among 682 patients who had MTB culture results at month 2, 40 (5.9%) had a positive result. After regression with propensity score adjustment, no significant association between baseline neutrophil count (103/mm3) and positive MTB culture at month 2 was found among either HIV-seronegative (OR = 1.06, 95% CI = [0.95;1.19] or HIV-seropositive patients (OR = 0.77, 95% CI = [0.51; 1.20]). Of 691 TB patients followed up for at least 18 months and up to 24 months, 635 (91.9%) were either cured or completed treatment, and 56 (8.1%) had an unfavorable treatment outcome. A multivariable regression with propensity score adjustment found an association between higher neutrophil count (103/mm3) at baseline and unfavorable outcome among HIV-seronegative patients [OR= 1.17 (95% CI= [1.06;1.30]). In addition, adjusted Cox regression found that higher baseline neutrophil count (103/mm3) was associated with unfavorable treatment outcomes overall and among HIV-seronegative patients (HR= 1.16 (95% CI = [1.05;1.27]).

Conclusion

Increased neutrophil count prior to anti-TB treatment initiation was associated with unfavorable treatment outcomes, particularly among HIV-seronegative patients. Further prospective studies evaluating neutrophil count in response to drug treatment and association with TB treatment outcomes are warranted.
Low-Density Neutrophils in Healthy Individuals Display a Mature Primed Phenotype
Authors: Blanco-Camarillo Carlos , Alemán Omar Rafael , Rosales Carlos
Published: July 2021

Neutrophils are the most abundant leukocytes in human peripheral blood, comprising about 70% of all leukocytes. They are regarded as the first line of defense of the innate immune system, but neutrophils have also the ability of regulating the adaptive immune response. Recently, However, multiple phenotypes and functional states of neutrophils have been reported, particularly in inflammation, autoimmunity, and cancer. One possible subtype of neutrophils, the so-called low-density neutrophils (LDN) is found among mononuclear cells (MNC), monocytes and lymphocytes, after separating the leukocytes from blood by density gradient centrifugation. LDN increase in numbers during several pathological conditions. However, LDN present in healthy conditions have not been investigated further. Therefore, in order to confirm the presence of LDN in blood of healthy individuals and to explore some of their cellular functions, neutrophils and MNC were isolated by density gradient centrifugation. Purified neutrophils were further characterized by multicolor flow cytometry (FACS) and then, using the same FACS parameters cells in the MNC fraction were analyzed. Within the MNC, LDN were consistently found. These LDN had a normal mature neutrophil morphology and displayed a CD10+, CD11b+, CD14low, CD15high, CD16bhigh, CD62L+, CD66b+, and CXCR4+ phenotype. These LDN had an enhanced reactive oxygen species (ROS) production and increased phagocytic capacity and were able to produce neutrophil extracellular traps (NET) similarly to neutrophils. These data confirm the presence of a small number of LDN is blood of healthy individuals and suggest that these LDN represent mature cells with a primed phenotype.
PPE38-Secretion-Dependent Proteins of M. tuberculosis Alter NF-kB Signalling and Inflammatory Responses in Macrophages
Authors: Gallant James , Heunis Tiaan , Beltran Caroline , Schildermans Karin , Bruijns Sven , Mertens Inge , Bitter Wilbert , Sampson Samantha L.
Published: July 2021

It was previously shown that secretion of PE-PGRS and PPE-MPTR proteins is abolished in clinicalM. tuberculosisisolates with a deletion in theppe38-71operon, which is associated with increased virulence. Here we investigate the proteins dependent on PPE38 for their secretion and their role in the innate immune response using temporal proteomics and protein turnover analysis in a macrophage infection model. A decreased pro-inflammatory response was observed in macrophages infected with PPE38-deficientM. tuberculosisCDC1551 as compared to wild type bacteria. We could show that dampening of the pro-inflammatory response is associated with activation of a RelB/p50 pathway, while the canonical inflammatory pathway is active during infection with wild typeM. tuberculosisCDC1551. These results indicate a molecular mechanism by whichM. tuberculosisPE/PPE proteins controlled by PPE38 have an effect on modulating macrophage responses through NF-kB signalling.
Fish Spawning Aggregations in the Southeast Florida Coral Reef Ecosystem Conservation Area: A Case Study Synthesis of User Reports, Literature, and Field Validation Efforts
Authors: Binder Benjamin M. , Taylor J. Christopher , Gregg Kurtis , Boswell Kevin M.
Published: July 2021

The formation of fish spawning aggregations (FSAs) is an essential part of the life history of many economically important fish species; however, their status are often poorly described in the literature either due to their occurrence in remote locations, during seasons with unsafe ocean conditions, or because they move on space and time scales that are difficult to predict and validate. Even in areas that are relatively accessible and heavily fished, such as southeast Florida, regionally relevant information describing FSA dynamics is generally absent from the literature and unaccounted for in existing management plans. We propose that this can be attributed to the fact that information is often held by stakeholders or found in unpublished manuscripts and reports. These sources are not widely disseminated and are therefore difficult to locate and integrate into fisheries management decisions. In this paper, we present a case study demonstrating the value of regional data syntheses as a tool to improve management activities in southeast Florida. Specifically, we engaged with local stakeholders to collect reports of FSA occurrence, and used Web of Science queries to collate information describing the reproductive dynamics of locally occurring snapper and grouper species. Reports were combined with regional FSA literature and provided to managers as a support tool to anticipate FSA occurrence, and to guide policy development and future FSA research. Resource users identified 13 potential aggregations from five species, but Web of Science queries revealed a paucity of information. Echosounder, camera, and fisheries dependent surveys were then used to corroborate reportedly active cubera snapper (Lutjanus cyanopterus), hogfish (Lachnolaimus maximus), and gag grouper (Mycteroperca microlepis) aggregations. Variability in the spatiotemporal aspects of FSA occurrence make them difficult to study, but this may also explain how certain species have avoided detrimental impacts from aggregation fishing. These data represent a first step toward describing FSAs that have historically occurred in the Southeast Florida Coral Reef Ecosystem Conservation Area and can be used by managers to prioritize future research efforts focused on species or hotspots of multispecies activity along the northern extent of the Florida Reef Tract.
Plastic Responses of Gilthead Seabream Sparus aurata to Wild and Aquaculture Pressured Environments
Authors: Talijančić Igor , Žužul Iva , Kiridžija Viktorija , Šiljić Jasna , Pleadin Jelka , Grubišić Leon , Šegvić-Bubić Tanja
Published: July 2021

Fish farms, as artificial marine structures with a constant food supply, have a high capacity to attract surrounding wild fish. Different phenotypes of abundant gilthead seabream have been recorded in natural and aquaculture pressured environments in the eastern Adriatic Sea, where the influence of tuna farming on plastic traits associated with habitat use and foraging behaviour remains largely unknown. Several traits, such as body and otolith shape, external colouration, diet preference, and proximate tissue content, were analysed to examine habitat selection of the tuna farm-associated phenotype in comparison to wild and farmed phenotypes. Foraging behavioural shifts in prey selectivity, from hard-shelled bivalves towards soft textured baitfish feed, and local hydrodynamic conditions have initiated plastic responses in farm-associated seabream. Consequently, morphological traits connected with feeding and swimming performance and paler vs. vivid body colouration patterns differed between wild and farm-associated fish, highlighting the existence of resource polymorphism in gilthead seabream. While otolith shape proved to be a reliable phenotypic tracer in distinguishing farmed from wild and farm-associated fish, reduced sensitivity was found between individuals residing in the vicinity of tuna farms and wild ones. To fully understand the impact of fish farms on associated gilthead seabream and its plastic response with a distinctive morph outcome, the underlying molecular mechanisms involved in the regulation of alternative phenotypes needs to be investigated.
Comparison of the Filtration Efficiency of Different Face Masks Against Aerosols
Authors: Stahl Connor , Frederick Kevin , Chaudhary Sachin , Morton Christopher J. , Loy Douglas , Muralidharan Krishna , Sorooshian Armin , Parthasarathy Sairam
Published: July 2021

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic can spread through virus-containing aerosols ( ≤ 5 μm) and larger airborne droplets. Quantifying filtration efficiency of different kinds of masks and linings for aerosols that fall within the most penetrating particle size (80-400 nm) is critical to limiting viral transmission. The objective of our experiment was to compare the “real-world” filtering efficiency of different face masks for fine aerosols (350 nm) in laboratory simulations.

Methods: We performed a simulated bench test that measured the filtering efficiency of N95 vs. N99 masks with elastomeric lining in relation to baseline (“background”) aerosol generation. A mannequin head was placed within a chamber and was attached to an artificial lung simulator. Particles of known size (350 ± 6 nm aerodynamic diameter) were aerosolized into the chamber while simulating breathing at physiological settings of tidal volume, respiratory rate, and airflow. Particle counts were measured between the mannequin head and the lung simulator at the tracheal airway location.

Results: Baseline particle counts without a filter (background) were 2,935 ± 555 (SD) cm−3, while the N95 (1348 ± 92 cm−3) and N99 mask with elastomeric lining (279 ± 164 cm−3; p <0.0001) exhibit lower counts due to filtration.

Conclusion: The filtration efficiency of the N95 (54.1%) and N99 (90.5%) masks were lower than the filtration efficiency rating. N99 masks with elastomeric lining exhibit greater filtration efficiency than N95 masks without elastomeric lining and may be preferred to contain the spread of SARS-CoV-2 infection.
A Little Experience Goes a Long Way: Chlormethine/Mechlorethamine Treatment Duration as a Function of Clinician-Level Patient Volume for Mycosis Fungoides Cutaneous T-Cell Lymphoma (MF-CTCL)—A Retrospective Cohort Study
Authors: Querfeld Christiane , Pacheco Theresa , Haverkos Bradley , Binder Gary , Angello James , Poligone Brian
Published: July 2021

Topical chlormethine yields high response rates in mycosis fungoides cutaneous T-cell lymphoma with early discontinuation often attributed to skin reactions. We evaluated over 4,000 patients and found an association of clinician case volume with treatment duration and early discontinuation of chlormethine gel. The minority of clinicians with high patient volume markedly outperformed clinicians with only few patients on both outcome parameters, yet case volume as low as five patients seemed to mark a threshold for avoiding early discontinuation of treatment regimen.
Exposure to Plasma From Non-alcoholic Fatty Liver Disease Patients Affects Hepatocyte Viability, Generates Mitochondrial Dysfunction, and Modulates Pathways Involved in Fat Accumulation and Inflammation
Authors: Grossini Elena , Garhwal Divya Praveen , Calamita Giuseppe , Romito Raffaele , Rigamonti Cristina , Minisini Rosalba , Smirne Carlo , Surico Daniela , Bellan Mattia , Pirisi Mario
Published: July 2021

Changes of lipidic storage, oxidative stress and mitochondrial dysfunction may be involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Although the knowledge of intracellular pathways has vastly expanded in recent years, the role and mechanisms of circulating triggering factor(s) are debated. Thus, we tested the hypothesis that factors circulating in the blood of NAFLD patients may influence processes underlying the disease. Huh7.5 cells/primary human hepatocytes were exposed to plasma from 12 NAFLD patients and 12 healthy subjects and specific assays were performed to examine viability, H2O2 and mitochondrial reactive oxygen species (ROS) release, mitochondrial membrane potential and triglycerides content. The involvement of NLRP3 inflammasome and of signaling related to peroxisome-proliferator-activating-ligand-receptor-γ (PPARγ), sterol-regulatory-element-binding-protein-1c (SREBP-1c), nuclear-factor-kappa-light-chain-enhancer of activated B cells (NF-kB), and NADPH oxidase 2 (NOX2) was evaluated by repeating the experiments in the presence of NLRP3 inflammasome blocker, MCC950, and through Western blot. The results obtained shown that plasma of NAFLD patients was able to reduce cell viability and mitochondrial membrane potential by about 48 and 24% (p < 0.05), and to increase H2O2, mitochondrial ROS, and triglycerides content by about 42, 19, and 16% (p < 0.05), respectively. An increased expression of SREBP-1c, PPARγ, NF-kB and NOX2 of about 51, 121, 63, and 46%, respectively, was observed (p < 0.05), as well. Those effects were reduced by the use of MCC950. Thus, in hepatocytes, exposure to plasma from NAFLD patients induces a NAFLD-like phenotype by interference with NLRP3-inflammasome pathways and the activation of intracellular signaling related to SREBP-1c, PPARγ, NF-kB and NOX2.
Lower Funneling Pathways in Scedosporium Species
Authors: Poirier Wilfried , Ravenel Kevin , Bouchara Jean-Philippe , Giraud Sandrine
Published: July 2021

Lignin, a natural polyaromatic macromolecule, represents an essential component of the lignocellulose biomass. Due to its complexity, the natural degradation of this molecule by microorganisms still remains largely misunderstood. Extracellular oxidative degradation is followed by intracellular metabolic degradation of conserved aromatic intermediate compounds (protocatechuate, catechol, hydroxyquinol, and gentisic acid) that are used as carbon and energy sources. The lower funneling pathways are characterized by the opening of the aromatic ring of these molecules through dioxygenases, leading to degradation products that finally enter into the tricarboxylic acid (TCA) cycle. In order to better understand the adaptation mechanisms ofScedosporiumspecies to their environment, these specific catabolism pathways were studied. Genes encoding ring-cleaving dioxygenases were identified inScedosporiumgenomes by sequence homology, and a bioinformatic analysis of the organization of the corresponding gene clusters was performed. In addition, these predictions were confirmed by evaluation of the expression level of the genes of the gentisic acid cluster. When the fungus was cultivated in the presence of lignin or gentisic acid as sole carbon source, experiments revealed that the genes of the gentisic acid cluster were markedly overexpressed in the twoScedosporiumspecies analyzed (Scedosporium apiospermumandScedosporium aurantiacum). Only the gene encoding a membrane transporter was not overexpressed in the gentisic acid-containing medium. Together, these data suggest the involvement of the lower funneling pathways inScedosporiumadaptation to their environment.
Multi-Omics Analysis Reveals Disturbance of Nanosecond Pulsed Electric Field in the Serum Metabolic Spectrum and Gut Microbiota
Authors: Dong Yeping , Lu Jiahua , Wang Ting , Huang Zhiliang , Chen Xinhua , Ren Zhigang , Hong Liangjie , Wang Haiyu , Yang Dezhi , Xie Haiyang , Zhang Wu
Published: July 2021

Nanosecond pulsed electric field (nsPEF) is a novel ablation technique that is based on high-intensity electric voltage to achieve tumour-killing effect in the target region, and increasingly considered for treating tumours of the liver, kidneys and other organs with rich blood supply. This study aims to observe effect of nsPFE treatment on serum metabolites and gut microbiota. The serum and faecal specimens of the pigs were collected pre- and post-treatment. The gut microbiota of pigs was sequenced by Illumina Miseq platform for analysing the diversity and alterations of gut microbiota. Liquid chromatography-mass spectrometry (LC-MS)-based metabonomic analysis and Pearson coefficient method were also used to construct the interaction system of different metabolites, metabolic pathways and flora. A total of 1,477 differential metabolites from the serum were identified by four cross-comparisons of different post-operative groups with the control group. In addition, an average of 636 OTUs per sample was detected. Correlation analysis also revealed the strong correlation between intestinal bacteria and differential metabolites. The nsPEF ablation of the liver results in a degree of liver damage that affects various metabolic pathways, mainly lipid metabolism, as well as gut microbiota. In conclusion, our study provided a good point for the safety and feasibility of applying nsPEF on liver through the integrated analysis of metabolomics and microbiomes, which is beneficial for the improvement of nsPEF in clinical use.
Using Whole Genome Sequences to Investigate Adenovirus Outbreaks in a Hematopoietic Stem Cell Transplant Unit
Authors: Myers Chloe E. , Houldcroft Charlotte J. , Roy Sunando , Margetts Ben K. , Best Timothy , Venturini Cristina , Guerra-Assunção Jose A. , Williams Charlotte A. , Williams Rachel , Dunn Helen , Hartley John C. , Rao Kanchan , Rolfe Kathryn J. , Breuer Judith
Published: July 2021

A recent surge in human mastadenovirus (HAdV) cases, including five deaths, amongst a haematopoietic stem cell transplant population led us to use whole genome sequencing (WGS) to investigate. We compared sequences from 37 patients collected over a 20-month period with sequences from GenBank and our own database of HAdVs. Maximum likelihood trees and pairwise differences were used to evaluate genotypic relationships, paired with the epidemiological data from routine infection prevention and control (IPC) records and hospital activity data. During this time period, two formal outbreaks had been declared by IPC, while WGS detected nine monophyletic clusters, seven were corroborated by epidemiological evidence and by comparison of single-nucleotide polymorphisms. One of the formal outbreaks was confirmed, and the other was not. Of the five HAdV-associated deaths, three were unlinked and the remaining two considered the source of transmission. Mixed infection was frequent (10%), providing a sentinel source of recombination and superinfection. Immunosuppressed patients harboring a high rate of HAdV positivity require comprehensive surveillance. As a consequence of these findings, HAdV WGS is being incorporated routinely into clinical practice to influence IPC policy contemporaneously.
Analysis of the Taxonomy and Pathogenic Factors of Pectobacterium aroidearum L6 Using Whole-Genome Sequencing and Comparative Genomics
Authors: Xu Peidong , Wang Huanwei , Qin Chunxiu , Li Zengping , Lin Chunhua , Liu Wenbo , Miao Weiguo
Published: July 2021

Soft rot pectobacteria are devastating plant pathogens with a global distribution and a broad host range. Pectobacterium aroidearum L6, previously isolated from leaves of Syngonium podophyllum, is a pectolytic bacterial pathogen that causes typical soft rot on S. podophyllum. There is a shortage for genome data of P. aroidearum, which seriously hinders research on classification and pathogenesis of Pectobacterium. We present here the complete genome sequence of P. aroidearum L6. The L6 strain carries a single 4,995,896-bp chromosome with 53.10% G + C content and harbors 4,306 predicted protein-coding genes. We estimated in silico DNA–DNA hybridization and average nucleotide identity values in combination with the whole-genome-based phylogeny from 19 Pectobacterium strains including P. aroidearum L6. The results showed that L6 and PC1 formed a population distinct from other populations of the Pectobacterium genus. Phylogenetic analysis based on 16S rRNA and genome sequences showed a close evolutionary relationship among Pectobacterium species. Overall, evolutionary analysis showed that L6 was in the same branch with PC1. In comparison with 18 Pectobacterium spp. reference pathogens, strain L6 had 2,712 gene families, among which 1,632 gene families were identified as orthologous to those strains, as well as 1 putative unique gene family. We discovered 478 genes, 10.4% of the total of predicted genes, that were potentially related to pathogenesis using the Virulence Factors of Pathogenic Bacteria database. A total of 25 genes were related to toxins, 35 encoded plant cell-wall degrading enzymes, and 122 were involved in secretion systems. This study provides a foundation for a better understanding of the genomic structure of P. aroidearum and particularly offers information for the discovery of potential pathogenic factors and the development of more effective strategies against this pathogen.
Development of a Direct and Rapid Detection Method for Viable but Non-culturable State of Pediococcus acidilactici
Authors: Guan Yu , Wang Kan , Zeng Yang , Ye Yanrui , Chen Ling , Huang Tengyi
Published: July 2021

Pediococcus acidilactici may significantly reduce the pH-value, and thus has different influence, including serving as a probiotic in human microbiota but a spoilage in human food as it could change the flavor. Pediococcus acidilactici is also capable of entering into the viable but non-culturable (VBNC) state causing false negative results of standard culture-based detection method. Thus, development of detection method for VBNC state P. acidilactici is of great significance. In this study, propidium monoazide (PMA) combined with cross priming amplification (CPA) was developed to detect the VBNC cells of P. acidilactici and applied on the detection in different systems. With detection limit of 104 cells/ml, high sensitivity, and 100% specificity, PMA-CPA can successfully detect VBNC cells of P. acidilactici and be applied in with high robustness.
Inhibitory Effect of Puroindoline Peptides on Campylobacter jejuni Growth and Biofilm Formation
Authors: Talukdar Prabhat K. , Turner Kyrah L. , Crockett Torin M. , Lu Xiaonan , Morris Craig F. , Konkel Michael E.
Published: July 2021

Puroindolines are small, amphipathic, wheat proteins that determine the hardness of the wheat kernel and protect crops from different pathogens. Puroindoline A (PinA) and puroindoline B (PinB) are two major isoforms of puroindolines. These proteins have antibacterial and antifungal properties mainly attributed to their characteristic tryptophan-rich domains (TRDs). In this in vitro study, we investigated the antimicrobial effect of PinA and PinB synthetic peptides against the growth and biofilm formation of Campylobacter jejuni. C. jejuni is an important microaerobic, foodborne pathogen that causes gastrointestinal and neurological diseases in humans. Our results showed that: (1) PinA, but not PinB, has strong antimicrobial activity against C. jejuni clinical strains 81-176 and F38011, Escherichia coli O157:H7, methicillin-resistant Staphylococcus aureus, Salmonella enterica serovar Typhimurium, and Listeria monocytogenes; (2) The substitution of two tryptophan residues to glycine (W→G) in the TRD of PinA abolishes its antimicrobial activity against these microorganisms; (3) PinA functions additively with two common antibiotics (ciprofloxacin and erythromycin) to inhibit or inactivate C. jejuni strains; (4) PinA damages the C. jejuni cellular membrane, (5) PinA is cytotoxic to human INT 407 cells at high concentrations; and (6) PinA inhibits C. jejuni biofilm formation. In summary, this study demonstrates the antimicrobial activity of PinA against C. jejuni growth and biofilm formation and further confirms the potential use of PinA as a therapeutic agent in health care or as preservatives in the agri-food industry.
Indian Ethnomedicinal Phytochemicals as Promising Inhibitors of RNA-Binding Domain of SARS-CoV-2 Nucleocapsid Phosphoprotein: An In Silico Study
Authors: Muthumanickam Sankar , Kamaladevi Arumugam , Boomi Pandi , Gowrishankar Shanmugaraj , Pandian Shunmugiah Karutha
Published: July 2021

SARS-CoV-2, an etiological agent of COVID-19, has been the reason for the unexpected global pandemic, causing severe mortality and imposing devastative effects on public health. Despite extensive research work put forward by scientist around globe, so far, no suitable drug or vaccine (safe, affordable, and efficacious) has been identified to treat SARS-CoV-2. As an alternative way of improvising the COVID-19 treatment strategy, that is, strengthening of host immune system, a great deal of attention has been given to phytocompounds from medicinal herbs worldwide. In a similar fashion, the present study deliberately focuses on the phytochemicals of three Indian herbal medicinal plantsviz.,Mentha arvensis,Coriandrum sativum, andOcimum sanctumfor their efficacy to target well-recognized viral receptor protein through molecular docking and dynamic analyses. Nucleocapsid phosphoprotein (N) of SARS-CoV-2, being a pivotal player in replication, transcription, and viral genome assembly, has been recognized as one of the most attractive viral receptor protein targets for controlling the viral multiplication in the host. Out of 127 phytochemicals screened, nine (linarin, eudesmol, cadinene, geranyl acetate, alpha-thujene, germacrene A, kaempferol-3-O-glucuronide, kaempferide, and baicalin) were found to be phenomenal in terms of exhibiting high binding affinity toward the catalytic pocket of target N-protein. Further, the ADMET prediction analysis unveiled the non-tumorigenic, noncarcinogenic, nontoxic, non-mutagenic, and nonreproductive nature of the identified bioactive molecules. Furthermore, the data of molecular dynamic simulation validated the conformational and dynamic stability of the docked complexes. Concomitantly, the data of the present study validated the anti-COVID efficacy of the bioactives from selected medicinal plants of Indian origin.
HOXC13-AS Induced Extracellular Matrix Loss via Targeting miR-497-5p/ADAMTS5 in Intervertebral Disc
Authors: Jing Wanli , Liu Wei
Published: July 2021

Background/Aims: LncRNAs are a new modulator in the development of intervertebral disc degeneration. However, the functional role and mechanism of HOXC13-AS in intervertebral disc degeneration remain unclear.

Methods: qRT-PCR analysis was performed to measure the relative expression levels of HOXC13-AS and miR-497-5p, and the levels of IL-1β, IL-6, and TNF-α in the medium supernatant were analyzed by ELISA. The related mechanism between HOXC13-AS and miR-497-5p was detected by luciferase assays.

Results: The results revealed that TNF-α and IL-1β induced HOXC13-AS expression in NP cells. HOXC13-AS was overexpressed in IDD specimens compared to control specimens, and higher expression of HOXC13-AS was correlated with high Pfirrmann scores. Ectopic expression of HOXC13-AS promoted MMP-3 and ADAMTS4 and inhibited aggrecan and collagen II expression in NP cells. Furthermore, overexpression of HOXC13-AS increased the expression of inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Our results demonstrated that TNF-α and IL-1β induced ADAMTS5 expression and suppressed miR-497-5p expression. miR-497-5p was downregulated in IDD specimens compared to control specimens, and the lower expression of miR-497-5p was correlated with high Pfirrmann scores. The miR-497-5p level was negatively proportional to HOXC13-AS expression in IDD specimens. Luciferase analysis data indicated that ADAMTS5 was a direct target gene of miR-497-5p. HOXC13-AS induced inflammatory cytokine expression and ECM degradation by modulating miR-497-5p/ADAMTS5.

Conclusion: HOXC13-AS may be a treatment target for IDD.
Carbon Nanotubes Induce Metabolomic Profile Disturbances in Zebrafish: NMR-Based Metabolomics Platform
Authors: Ganesan Raja , Vasantha-Srinivasan Prabhakaran , Sadhasivam Deepa Rani , Subramanian Raghunandhakumar , Vimalraj Selvaraj , Suk Ki Tae
Published: July 2021

The present study aims to investigate the metabolic effects of single-walled carbon nanotubes (SWCNT) on zebrafish (Danio rerio) using 1H nuclear magnetic resonance (1H-NMR) spectroscopy. However, there is no significant information available regarding the characterization of organic molecules, and metabolites with SWCNT exposure. Noninvasive biofluid methods have improved our understanding of SWCNT metabolism in zebrafish in recent years. Here, we used targeted metabolomics to quantify a set of metabolites within biological systems. SWCNT at various concentrations was given to zebrafish, and the metabolites were extracted using two immiscible solvent systems, methanol and chloroform. Metabolomics profiling was used in association with univariate and multivariate data analysis to determine metabolomic phenotyping. The metabolites, malate, oxalacetate, phenylaniline, taurine, sn-glycero-3-phosphate, glycine, N-acetyl mate, lactate, ATP, AMP, valine, pyruvate, ADP, serine, niacinamide are significantly impacted. The metabolism of amino acids, energy and nucleotides are influenced by SWCNT which might indicate a disturbance in metabolic reaction networks. In conclusion, using high-throughput analytical methods, we provide a perspective of metabolic impacts and the underlying associated metabolic pathways.
The Central Role of Redox-Regulated Switch Proteins in Bacteria
Authors: Fassler Rosi , Zuily Lisa , Lahrach Nora , Ilbert Marianne , Reichmann Dana
Published: July 2021

Bacteria possess the ability to adapt to changing environments. To enable this, cells use reversible post-translational modifications on key proteins to modulate their behavior, metabolism, defense mechanisms and adaptation of bacteria to stress. In this review, we focus on bacterial protein switches that are activated during exposure to oxidative stress. Such protein switches are triggered by either exogenous reactive oxygen species (ROS) or endogenous ROS generated as by-products of the aerobic lifestyle. Both thiol switches and metal centers have been shown to be the primary targets of ROS. Cells take advantage of such reactivity to use these reactive sites as redox sensors to detect and combat oxidative stress conditions. This in turn may induce expression of genes involved in antioxidant strategies and thus protect the proteome against stress conditions. We further describe the well-characterized mechanism of selected proteins that are regulated by redox switches. We highlight the diversity of mechanisms and functions (as well as common features) across different switches, while also presenting integrative methodologies used in discovering new members of this family. Finally, we point to future challenges in this field, both in uncovering new types of switches, as well as defining novel additional functions.
Metabolic Brain Network Analysis With 18F-FDG PET in a Rat Model of Neuropathic Pain
Authors: Huo Bei-Bei , Zheng Mou-Xiong , Hua Xu-Yun , Shen Jun , Wu Jia-Jia , Xu Jian-Guang
Published: July 2021

Neuropathic pain has been found to be related to profound reorganization in the function and structure of the brain. We previously demonstrated changes in local brain activity and functional/metabolic connectivity among selected brain regions by using neuroimaging methods. The present study further investigated large-scale metabolic brain network changes in 32 Sprague–Dawley rats with right brachial plexus avulsion injury (BPAI). Graph theory was applied in the analysis of 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) PET images. Inter-subject metabolic networks were constructed by calculating correlation coefficients. Global and nodal network properties were calculated and comparisons between pre- and post-BPAI (7 days) status were conducted. The global network properties (including global efficiency, local efficiency and small-world index) and nodal betweenness centrality did not significantly change for all selected sparsity thresholds following BPAI (p > 0.05). As for nodal network properties, both nodal degree and nodal efficiency measures significantly increased in the left caudate putamen, left medial prefrontal cortex, and right caudate putamen (p < 0.001). The right entorhinal cortex showed a different nodal degree (p < 0.05) but not nodal efficiency. These four regions were selected for seed-based metabolic connectivity analysis. Strengthened connectivity was found among these seeds and distributed brain regions including sensorimotor area, cognitive area, and limbic system, etc. (p < 0.05). Our results indicated that the brain had the resilience to compensate for BPAI-induced neuropathic pain. However, the importance of bilateral caudate putamen, left medial prefrontal cortex, and right entorhinal cortex in the network was strengthened, as well as most of their connections with distributed brain regions.