bluuebunny/crossref_metadata_2025 huggingface dataset:
DNA Methylation Analysis of Ribosomal DNA in Adults With Down Syndrome
Authors: Ravaioli Francesco , Zampieri Michele , Morandi Luca , Pirazzini Chiara , Pellegrini Camilla , De Fanti Sara , Gensous Noémie , Pirazzoli Gian Luca , Sambati Luisa , Ghezzo Alessandro , Ciccarone Fabio , Reale Anna , Monti Daniela , Salvioli Stefano , Caiafa Paola , Capri Miriam , Bürkle Alexander , Moreno-Villanueva Maria , Garagnani Paolo , Franceschi Claudio , Bacalini Maria Giulia
Published: April 2022

Control of ribosome biogenesis is a critical aspect of the regulation of cell metabolism. As ribosomal genes (rDNA) are organized in repeated clusters on chromosomes 13, 14, 15, 21, and 22, trisomy of chromosome 21 confers an excess of rDNA copies to persons with Down syndrome (DS). Previous studies showed an alteration of ribosome biogenesis in children with DS, but the epigenetic regulation of rDNA genes has not been investigated in adults with DS so far. In this study, we used a targeted deep-sequencing approach to measure DNA methylation (DNAm) of rDNA units in whole blood from 69 adults with DS and 95 euploid controls. We further evaluated the expression of the precursor of ribosomal RNAs (RNA45S) in peripheral blood mononuclear cells (PBMCs) from the same subjects. We found that the rDNA promoter tends to be hypermethylated in DS concerning the control group. The analysis of epihaplotypes (the combination of methylated and unmethylated CpG sites along the same DNA molecule) showed a significantly lower intra-individual diversity in the DS group, which at the same time was characterized by a higher interindividual variability. Finally, we showed that RNA45S expression is lower in adults with DS. Collectively, our results suggest a rearrangement of the epigenetic profile of rDNA in DS, possibly to compensate for the extranumerary rDNA copies. Future studies should assess whether the regulation of ribosome biogenesis can contribute to the pathogenesis of DS and explain the clinical heterogeneity characteristic of the syndrome.
HerbKG: Constructing a Herbal-Molecular Medicine Knowledge Graph Using a Two-Stage Framework Based on Deep Transfer Learning
Authors: Zhu Xian , Gu Yueming , Xiao Zhifeng
Published: April 2022

Recent advances have witnessed a growth of herbalism studies adopting a modern scientific approach in molecular medicine, offering valuable domain knowledge that can potentially boost the development of herbalism with evidence-supported efficacy and safety. However, these domain-specific scientific findings have not been systematically organized, affecting the efficiency of knowledge discovery and usage. Existing knowledge graphs in herbalism mainly focus on diagnosis and treatment with an absence of knowledge connection with molecular medicine. To fill this gap, we present HerbKG, a knowledge graph that bridges herbal and molecular medicine. The core bio-entities of HerbKG include herbs, chemicals extracted from the herbs, genes that are affected by the chemicals, and diseases treated by herbs due to the functions of genes. We have developed a learning framework to automate the process of HerbKG construction. The resulting HerbKG, after analyzing over 500K PubMed abstracts, is populated with 53K relations, providing extensive herbal-molecular domain knowledge in support of downstream applications. The code and an interactive tool are available athttps://github.com/FeiYee/HerbKG.
Association Between the TP53 Polymorphisms and Breast Cancer Risk: An Updated Meta-Analysis
Authors: Zhao Lin , Yin Xiang-Xiongyi , Qin Jun , Wang Wei , He Xiao-Feng
Published: April 2022

Background: The relationship of TP53 codons 72, IVS3 16 bp, and IVS6+62A > G polymorphisms with breast cancer (BC) risk has been analyzed in seventeen published meta-analyses. However, the credibility of statistically significant associations was ignored and many new studies have been reported on these themes.

Objectives: To explore whether TP53 codons 72, IVS3 16 bp, and IVS6+62A > G polymorphisms are associated with BC risk and the clinical phenomena.

Methods: To comprehensively search the data (through October 25, 2021), we provided a clear search strategy and reviewed the references of published meta-analyses. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were used.

Results: The current meta-analysis had a larger sample size than the previous ones: 99 studies with 43,951 BC and 48,479 controls for TP53 codon 72 polymorphism, 35 studies with 8,705 BC and 7,516 controls for IVS3 16 bp polymorphism, and 25 studies with 12,222 BC and 12,895 controls for IVS6+62A > G polymorphism. Five gene models were used to explore the association between the three polymorphisms and BC risk, and partial positive results were similar to published meta-analyses results. However, a large number of significant results were considered to be unreliable after correcting with Bayesian false-discovery probability (BFDP), except for the association between TP53 IVS3 16 bp polymorphism and BC risk in overall analysis (GG vs. CC: BFDP = 0.738), matched studies (GG vs. CC: BFDP = 0.173; GG vs. CC + CG: BFDP = 0.447), and tumor size below 2 cm (GG vs. CC: BFDP = 0.088; GG + CG vs. CC: BFDP = 0.730; GG vs. CC + CG: BFDP = 0.311). These unreliable results were confirmed again without new solid results emerging in further sensitivity analysis (only studies in compliance with the quality assessment standard).

Conclusion: After considering the quality of the included studies and the reliability of the results, the present meta-analysis suggested that TP53 codons 72, IVS3 16 bp, and IVS6+62A > G polymorphisms were not significantly associated with the BC risk. Those results which prove that these three polymorphisms increase BC risk are more likely to be false-positive results due to various confounding factors.
“Big Data” Approaches for Prevention of the Metabolic Syndrome
Authors: Jiang Xinping , Yang Zhang , Wang Shuai , Deng Shuanglin
Published: April 2022

Metabolic syndrome (MetS) is characterized by the concurrence of multiple metabolic disorders resulting in the increased risk of a variety of diseases related to disrupted metabolism homeostasis. The prevalence of MetS has reached a pandemic level worldwide. In recent years, extensive amount of data have been generated throughout the research targeted or related to the condition with techniques including high-throughput screening and artificial intelligence, and with these “big data”, the prevention of MetS could be pushed to an earlier stage with different data source, data mining tools and analytic tools at different levels. In this review we briefly summarize the recent advances in the study of “big data” applications in the three-level disease prevention for MetS, and illustrate how these technologies could contribute tobetter preventive strategies.
Differential Long Non-Coding RNA Expression Analysis in Chronic Non-Atrophic Gastritis, Gastric Mucosal Intraepithelial Neoplasia, and Gastric Cancer Tissues
Authors: Liu Xin-Yuan , Zhang Tian-Qi , Zhang Qi , Guo Jing , Zhang Peng , Mao Tao , Tian Zi-Bin , Zhang Cui-Ping , Li Xiao-Yu
Published: April 2022

Gastric cancer (GC) has a high incidence worldwide, and when detected, the majority of patients have already progressed to advanced stages. Long non-coding RNAs (lncRNAs) have a wide range of biological functions and affect tumor occurrence and development. However, the potential role of lncRNAs in GC diagnosis remains unclear. We selected five high-quality samples from each group of chronic non-atrophic gastritis, gastric mucosal intraepithelial neoplasia, and GC tissues for analysis. RNA-seq was used to screen the differentially expressed lncRNAs, and we identified 666 differentially expressed lncRNAs between the chronic non-atrophic gastritis and GC groups, 13 differentially expressed lncRNAs between the gastric mucosal intraepithelial neoplasia and GC groups, and 507 differentially expressed lncRNAs between the chronic non-atrophic gastritis and gastric mucosal intraepithelial neoplasia groups. We also identified six lncRNAs (lncRNA H19, LINC00895, lnc-SRGAP2C-16, lnc-HLA-C-2, lnc-APOC1-1, and lnc-B3GALT2-1) which not only differentially expressed between the chronic non-atrophic gastritis and GC groups, but also differentially expressed between the gastric mucosal intraepithelial neoplasia and GC groups. Furthermore, RT-qPCR was used to verify the differentially co-expressed lncRNAs. LncSEA was used to conduct a functional analysis of differentially expressed lncRNAs. We also predicted the target mRNAs of the differentially expressed lncRNAs through bioinformatics analysis and analyzed targeting correlations between three differentially co-expressed lncRNAs and mRNAs (lncRNA H19, LINC00895, and lnc-SRGAP2C-16). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were used to explore the functions of target mRNAs of differentially expressed lncRNAs. In conclusion, our study provides a novel perspective on the potential functions of differentially expressed lncRNAs in GC occurrence and development, indicating that the differentially expressed lncRNAs might be new biomarkers for early GC diagnosis.
CRISPR/Cas9 Based Site-Specific Modification of FAD2 cis-Regulatory Motifs in Peanut (Arachis hypogaea L)
Authors: Neelakandan Anjanasree K. , Wright David A. , Traore Sy M. , Chen Xiangyu , Spalding Martin H. , He Guohao
Published: April 2022

Peanut (Arachis hypogaeaL.) seed is a rich source of edible oil, comprised primarily of monounsaturated oleic acid and polyunsaturated linoleic acid, accounting for 80% of its fatty acid repertoire. The conversion of oleic acid to linoleic acid, catalyzed by Fatty Acid Desaturase 2 (FAD2) enzymes, is an important regulatory point linked to improved abiotic stress responses while the ratio of these components is a significant determinant of commercial oil quality. Specifically, oleic acid has better oxidative stability leading to longer shelf life and better taste qualities while also providing nutritional based health benefits. Naturally occurringFAD2gene knockouts that lead to high oleic acid levels improve oil quality at the potential expense of plant health though. We undertook a CRISPR/Cas9 based site-specific genome modification approach designed to downregulate the expression of two homeologousFAD2genes in seed while maintaining regulation in other plant tissues. Twocis-regulatory elements the RY repeat motif and 2S seed protein motif in the 5′UTR and associated intron ofFAD2genes are potentially important for regulating seed-specific gene expression. Using hairy root and stable germ line transformation, differential editing efficiencies were observed at both CREs when targeted by single gRNAs using two different gRNA scaffolds. The editing efficiencies also differed when two gRNAs were expressed simultaneously. Additionally, stably transformed seed exhibited an increase in oleic acid levels relative to wild type. Taken together, the results demonstrate the immense potential of CRISPR/Cas9 based approaches to achieve high frequency targeted edits in regulatory sequences for the generation of novel transcriptional alleles, which may lead to fine tuning of gene expression and functional genomic studies in peanut.
High Expression of DC-STAMP Gene Predicts Adverse Outcomes in AML
Authors: Liang Qian , Zhang Lele , Wang Wenjun , Zhao Jingyu , Li Qiaoli , Pan Hong , Gao Zhen , Fang Liwei , Shi Jun
Published: April 2022

Acute myeloid leukemia (AML) is a genetically heterogeneous hematological malignancy with poor prognosis. We explored the RNA sequence data and clinical information of AML patients from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database to search for the core molecule for prognosis. The DC-STAMP expression was significantly higher in AML patients, which was linked to old age, unfavorable cytogenetic risk, and death (all p < 0.05). Furthermore, it was revealed that high DC-STAMP expression was an independent unfavorable factor for overall survival (OS) by univariate analysis [hazard ratio (HR): 2.683; 95% confidence interval (CI): 1.723–4.178; p < 0.001] and multivariate analysis (HR: 1.733; 95% CI: 1.079–2.781; p = 0.023). The concordance index (C-index 0.734, 95% CI: 0.706–0.762), calibration curves, and decision curve analysis showed the certain predictive accuracy of a nomogram model based on multivariate analysis for OS. In addition, we found that the differentially expressed gene (DEG) enrichment pathways of high- and low-DC-STAMP expression group enrichment pathways were focused on channel activity and platelet alpha granule by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), while gene set enrichment analysis (GSEA) pathways were mainly involved in mTORC1 signaling and TNF-α signaling via the NF-kB pathway. Moreover, a protein–protein interaction (PPI) network demonstrated that DC-STAMP interacted with two hub genes (PPBP and PF4), which were highly regulated and associated with poor survival. Finally, high DC-STAMP expression showed a significantly positive correlation with four immune cell [NK CD56 (dim) cells, macrophages, cytotoxic cells, and CD8 (+) T cells] infiltration and high level of immune checkpoint genes (PDCD1, CD274, CTLA-4, and TIGIT). Therefore, our results suggest that high expression of DC-STAMP predicts adverse outcomes for AML patients.
Label-free Quantitative Proteomic Analysis of Cerebrospinal Fluid and Serum in Patients With Relapse-Remitting Multiple Sclerosis
Authors: Liu Haijie , Wang Ziwen , Li He , Li Meijie , Han Bo , Qi Yuan , Wang Huailu , Gao Juan
Published: April 2022

Background: The lack of effective serum and cerebrospinal fluid (CSF) biomarkers remains a barrier to early diagnosis and treatment of multiple sclerosis (MS). The study is to identify the diagnostic biomarkers of serum and CSF in patients who suffered MS.

Methods: At first, we performed differential analysis of CSF and serum proteomics on control and relapse-remitting multiple sclerosis (RRMS) patients. Secondly, CSF and serum’s differential proteins were compared, in order to identify the significative proteins. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis were performed on the differential proteins in serum and CSF respectively to clarify their common biological functions and pathways.

Results: At the first step, in CSF, 73 proteins were significantly differentially expressed in the RRMS set compared with the controls. In serum, 22 proteins were differentially expressed. Secondly, we found MMP2 C8G and CFH were the same high expression trend in CSF and serum. Finally, we found the differential proteins in serum and CSF are mostly participated in biological processes: immuno-inflammatory response, neuronal development, cell adhesion and signaling.

Conclusion: MMP2, C8G and CFH may participate in the pathogenesis of RRMS, which are the potential diagnostic biomarkers of the disease.
Isoforms of Neuropilin-2 Denote Unique Tumor-Associated Macrophages in Breast Cancer
Authors: Dhupar Rajeev , Jones Katherine E. , Powers Amy A. , Eisenberg Seth H. , Ding Kai , Chen Fangyuan , Nasarre Cecile , Cen Zhanpeng , Gong Yi-Nan , LaRue Amanda C. , Yeh Elizabeth S. , Luketich James D. , Lee Adrian V. , Oesterreich Steffi , Lotze Michael T. , Gemmill Robert M. , Soloff Adam C.
Published: April 2022

Tumor-associated macrophages (TAMs) exert profound influence over breast cancer progression, promoting immunosuppression, angiogenesis, and metastasis. Neuropilin-2 (NRP2), consisting of the NRP2a and NRP2b isoforms, is a co-receptor for heparin-binding growth factors including VEGF-C and Class 3 Semaphorins. Selective upregulation in response to environmental stimuli and independent signaling pathways endow the NRP2 isoforms with unique functionality, with NRP2b promoting increased Akt signaling via receptor tyrosine kinases including VEGFRs, MET, and PDGFR. Although NRP2 has been shown to regulate macrophage/TAM biology, the role of the individual NRP2a/NRP2b isoforms in TAMs has yet to be evaluated. Using transcriptional profiling and spectral flow cytometry, we show that NRP2 isoform expression was significantly higher in TAMs from murine mammary tumors. NRP2a/NRP2b levels in human breast cancer metastasis were dependent upon the anatomic location of the tumor and significantly correlated with TAM infiltration in both primary and metastatic breast cancers. We define distinct phenotypes of NRP2 isoform-expressing TAMs in mouse models of breast cancer and within malignant pleural effusions from breast cancer patients which were exclusive of neuropilin-1 expression. Genetic depletion of either NRP2 isoform in macrophages resulted in a dramatic reduction of LPS-induced IL-10 production, defects in phagosomal processing of apoptotic breast cancer cells, and increase in cancer cell migration following co-culture. By contrast, depletion of NRP2b, but not NRP2a, inhibited production of IL-6. These results suggest that NRP2 isoforms regulate both shared and unique functionality in macrophages and are associated with distinct TAM subsets in breast cancer.
Laboratory Biomarkers for Diagnosis and Prognosis in COVID-19
Authors: Battaglini Denise , Lopes-Pacheco Miquéias , Castro-Faria-Neto Hugo C. , Pelosi Paolo , Rocco Patricia R. M.
Published: April 2022

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) causes a wide spectrum of clinical manifestations, with progression to multiorgan failure in the most severe cases. Several biomarkers can be altered in coronavirus disease 2019 (COVID-19), and they can be associated with diagnosis, prognosis, and outcomes. The most used biomarkers in COVID-19 include several proinflammatory cytokines, neuron-specific enolase (NSE), lactate dehydrogenase (LDH), aspartate transaminase (AST), neutrophil count, neutrophils-to-lymphocytes ratio, troponins, creatine kinase (MB), myoglobin, D-dimer, brain natriuretic peptide (BNP), and its N-terminal pro-hormone (NT-proBNP). Some of these biomarkers can be readily used to predict disease severity, hospitalization, intensive care unit (ICU) admission, and mortality, while others, such as metabolomic and proteomic analysis, have not yet translated to clinical practice. This narrative review aims to identify laboratory biomarkers that have shown significant diagnostic and prognostic value for risk stratification in COVID-19 and discuss the possible clinical application of novel analytic strategies, like metabolomics and proteomics. Future research should focus on identifying a limited but essential number of laboratory biomarkers to easily predict prognosis and outcome in severe COVID-19.
Endoplasmic Reticulum Stress and Its Role in Homeostasis and Immunity of Central and Peripheral Neurons
Authors: Perner Caroline , Krüger Elke
Published: April 2022

Neuronal cells are specialists for rapid transfer and translation of information. Their electrical properties relay on a precise regulation of ion levels while their communicationvianeurotransmitters and neuropeptides depends on a high protein and lipid turnover. The endoplasmic Reticulum (ER) is fundamental to provide these necessary requirements for optimal neuronal function. Accumulation of misfolded proteins in the ER lumen, reactive oxygen species and exogenous stimulants like infections, chemical irritants and mechanical harm can induce ER stress, often followed by an ER stress response to reinstate cellular homeostasis. Imbedded between glial-, endothelial-, stromal-, and immune cells neurons are constantly in communication and influenced by their local environment. In this review, we discuss concepts of tissue homeostasis and innate immunity in the central and peripheral nervous system with a focus on its influence on ER stress, the unfolded protein response, and implications for health and disease.
Specialized Pro-Resolving Mediators Reduce Scarring After Cleft Lip Repair
Authors: Papathanasiou Evangelos , Scott Andrew R. , Trotman Carroll Ann , Beale Corinna , Price Lori Lyn , Huggins Gordon S. , Zhang Yang , Georgakoudi Irene , Van Dyke Thomas E.
Published: April 2022

Objective

Residual scarring after cleft lip repair surgery remains a challenge for both surgeons and patients and novel therapeutics are critically needed. The objective of this preclinical experimental study was to evaluate the impact of the methyl-ester of pro-resolving lipid mediator lipoxin A4 (LXA4-ME) on scarring in a novel rabbit model of cleft lip repair.

Methods

A defect of the lip was surgically created and repaired in eight six-week old New Zealand white rabbits to simulate human cleft lip scars. Rabbits were randomly assigned to topical application of PBS (control) or 1 ug of LXA4-ME (treatment). 42 days post surgery all animals were euthanized. Photographs of the cleft lip area defect and histologic specimens were evaluated. Multiple scar assessment scales were used to compare scarring.

Results

Animals treated with LXA4-ME exhibited lower Visual Scar Assessment scores compared to animals treated with PBS. Treatment with LXA4-ME resulted in a significant reduction of inflammatory cell infiltrate and density of collagen fibers. Control animals showed reduced 2D directional variance (orientation) of collagen fibers compared to animals treated with LXA4-ME demonstrating thicker and more parallel collagen fibers, consistent with scar tissue.

Conclusions

These data suggest that LXA4-ME limits scarring after cleft lip repair and improves wound healing outcomes in rabbits favoring the resolution of inflammation. Further studies are needed to explore the mechanisms that underlie the positive therapeutic impact of LXA4-ME on scarring to set the stage for future human clinical trials of LXA4-ME for scar prevention or treatment after cleft lip repair.
Production of Cytotoxic Antibodies After Intra-Articular Injection of Allogeneic Synovial Membrane Mesenchymal Stem Cells With and Without LPS Administration
Authors: Rosa Gustavo dos Santos , Krieck André Massahiro Teramoto , Padula Enrico Topan , Stievani Fernanda de Castro , Rossi Mariana Correa , Pfeifer João Pedro Hübbe , Basso Roberta Martins , Braz Aline Márcia Marques , Golim Márjorie de Assis , Alves Ana Liz Garcia
Published: April 2022

Allogeneic mesenchymal stem cells (MSC) are widely used in clinical routine due to the shorter expansion time and reliability of its quality. However, some recipients can produce alloantibodies that recognize MSCs and activate the immune system, resulting in cell death. Although antibody production was already described after MSC injection, no previous studies described the immune response after intra-articular MSC injection in acute synovitis. This study aimed to evaluate the influence of inflammation on immune response after single and repeated intra-articular injections of synovial membrane MSC (SMMSC). Horses were divided in three groups: control group (AUTO) received autologous synovial membrane MSCs; whereas group two (ALLO) received allogeneic SMMSCs and group three (ALLO LPS) was submitted to acute experimental synovitis 8 h before SMMSCs injection. The procedure was repeated for all groups for 28 days. Physical and lameness evaluations and synovial fluid analysis were performed. Sera from all animals were obtained before and every 7 days after each injection up to 4 weeks, to perform microcytotoxicity assays incubating donor SMMSCs with recipients’ sera. The first injection caused a mild and transient synovitis in all groups, becoming more evident and longer in ALLO and ALLO LPS groups after the second injection. Microcytotoxicity assays revealed significant antibody production as soon as 7 days after SMMSC injection in ALLO and ALLO LPS groups, and cytotoxicity scores of both groups showed no differences at any time point, being equally different from AUTO group. Although inflammation is capable of inducing MHC expression in MSCs, which enhances immune recognition, cytotoxicity scores were equally high in ALLO and ALLO LPS groups, making it difficult to determine the potentiation effect of inflammation on antibody production. Our findings suggest that inflammation does not display a pivotal role in immune recognition on first allogeneic MSC injection. In a translational way, since specific antibodies were produced against MSCs, patients that need more than one MSC injection may benefit from a first allogeneic injection followed by subsequent autologous injections.
Gut Microbial Antigenic Mimicry in Autoimmunity
Authors: Garabatos Nahir , Santamaria Pere
Published: April 2022

The gut microbiota plays a major role in the developmental biology and homeostasis of cells belonging to the adaptive and innate arms of the immune system. Alterations in its composition, which are known to be regulated by both genetic and environmental factors, can either promote or suppress the pathogenic processes underlying the development of various autoimmune diseases, including inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes and rheumatoid arthritis, to just name a few. Cross-recognition of gut microbial antigens by autoreactive T cells as well as gut microbe-driven alterations in the activation and homeostasis of effector and regulatory T cells have been implicated in this process. Here, we summarize our current understanding of the positive and negative associations between alterations in the composition of the gut microbiota and the development of various autoimmune disorders, with a special emphasis on antigenic mimicry.
Insights Into the Role of the Lung Virome During Respiratory Viral Infections
Authors: Porto Bárbara N.
Published: April 2022

The virome constitutes the viral component of the microbiome and it consists of the genomes of all the viruses that inhabit a particular region of the human body, including those that cause acute, persistent or latent infection, and retroviral elements integrated to host chromosomes. The human virome is composed by eukaryotic viruses, bacteriophages and archaeal viruses. The understanding of the virome composition and role on human health has been delayed by the absence of specific tools and techniques to accurately characterize viruses. However, more recently, advanced methods for viral diagnostics, such as deep sequencing and metagenomics, have allowed a better understanding of the diverse viral species present in the human body. Previous studies have shown that the respiratory virome modulates the host immunity and that, since childhood, the human lung is populated by viruses for whom there is no disease association. Whether these viruses are potentially pathogenic and the reason for their persistence remain elusive. Increased respiratory viral load can cause exacerbation of chronic pulmonary diseases, including COPD, cystic fibrosis, and asthma. Moreover, the presence of resident viral populations may contribute to the pathogenesis of community-acquired respiratory virus infections. In this mini review, I will discuss the recent progress on our understanding of the human lung virome and summarize the up-to-date knowledge on the relationships among community-acquired respiratory viruses, the lung virome and the immune response to better understand disease pathophysiology and the factors that may lead to viral persistence.
Ship Strike Risk for Fin Whales (Balaenoptera physalus) Off the Garraf coast, Northwest Mediterranean Sea
Authors: Tort Castro Beatriu , Prieto González Rocío , O’Callaghan Seán A. , Dominguez Rein-Loring Paula , Degollada Bastos Eduard
Published: April 2022

Ship strikes are a widespread conservation issue for many cetacean species globally. Population level impacts depend on the occurrence and severity of collisions, which may lead to life altering injuries or fatalities. Such impacts are a major concern for large, long-lived, and reproductively slow species like the fin whale. Since 2014, a seasonal feeding aggregation of fin whales has been monitored from February to June off the Catalan coast (Spain), in the northwest Mediterranean Sea. Oceanographical factors influence the occurrence and high density of krill within submarine canyons along the continental shelf, resulting in high whale abundance within a small spatial area. The study area extends 37 km offshore across a 1,944 km2marine strip situated between the towns of Torredembarra and Castelldefels. This fin whale feeding ground is exposed to high density marine vessel traffic, given its location between the northern Mediterranean shipping lane, which links Barcelona and Tarragona Ports to the Atlantic Ocean and wider Mediterranean Basin. Ship strikes represent the greatest conservation threat for fin whales in the Mediterranean Sea. At least four fin whales have been found dead in Barcelona Port since 1986 due to ship strikes and seven live whales have been documented with injuries in the study area since 2018. Fin whale distribution was mapped with known high-risk marine vessels’ (cargo, tanker and passenger vessels) shipping lanes. Vessel density and shipping lanes characterised by speed were considered. Collision risk was estimated monthly based on the predicted fin whale occurrence and traffic density. Several shipping lanes crossed the fin whale feeding habitat every month with an average speed of 15 kn. Cargo vessels displayed the highest ship-strike risk during April, overlapping with the peak of fin whale sightings in the critical feeding area. Slower vessel speeds (8 kn) in waters <200 m depth or along the continental shelf should be implemented along the Catalan coast, during the whale season. These suggestions should be applied into the Barcelona Port transport separation scheme. Ship strike risk for this species will persist unless active management plans are adapted in the region to mitigate its risk.
Cytomegalovirus-Immune Recovery Retinitis After Initiation of Highly Active Antiretroviral Therapy: A Case Series
Authors: Qian Yiwen , Wang Luoziyi , Jiang Jing , Suo Jinshan , Weng Huan , Che Xin , Lu Hongzhou , Wang Zhiliang
Published: April 2022

Purpose

To delineate the characteristics and treatment of cytomegalovirus-immune recovery retinitis (CMV-IRR) in human immunodeficiency virus (HIV) patients with immune recovery under effective highly active antiretroviral therapy (HAART) regimen.

Methods

We reported four patients with HIV who were diagnosed with CMV-IRR soon after effective HAART. Plasma levels of CD4 T cells, HAART regimen, and other clinical and laboratory characteristics of the four patients were described. Patients were monitored for ocular manifestations and clinical signs under effective ocular and systemic anti-cytomegalovirus (CMV) and corticosteroid treatment for 12 months.

Results

With HAART, plasma levels of CD4 T cell counts rose remarkably. The mean baseline CD4 count of the four patients was 14.5 (range from 7 to 33) cells/μl before HAART and 183.25 (range from 153 to 220) cells/μl when diagnosed with CMV-IRR. Ophthalmic examination demonstrated severe vitreous opacities and necrotizing retinitis, intraretinal hemorrhages, and vasculitis. A large number of CMV sequencing was detected by DNA sequencing of vitreous samples. All four patients were recovered from CMV-IRR with anti-CMV and corticosteroid treatment.

Conclusions

Cytomegalovirus-immune recovery retinitis is a new diagnosis of HIV-associated ocular complication under HAART. These findings suggest that the immunological effects of HAART may accelerate the CMV retinitis in patients with very low initial CD4 T cell counts. HIV patients are recommended to have a thorough fundus examination before HAART initiation and a close follow-up especially in those with low CD4 counts to avoid the progression of CMV retinitis.
Development of a New Genus-Specific Quantitative Real-Time PCR Assay for the Diagnosis of Scrub Typhus in South America
Authors: Jiang Ju , Martínez-Valdebenito Constanza , Weitzel Thomas , Farris Christina M. , Acosta-Jamett Gerardo , Abarca Katia , Richards Allen L.
Published: April 2022

Scrub typhus is a potentially severe rickettsiosis, caused by Orientia tsutsugamushi in the Asia-Pacific region. Recently, however, two distinct pathogens, “Candidatus Orientia chuto” and “Candidatus Orientia chiloensis”, have been discovered in the Middle East and South America, respectively. Since the novel pathogens differ significantly from O. tsutsugamushi, many established diagnostic methods are unreliable. This work describes the development and validation of a new quantitative real-time PCR (qPCR) assay (Orien16S) for the detection of all known Orientia species. Based on a 94 bp sequence of the 16S rRNA gene (rrs), Orien16S recognized DNA samples from O. tsutsugamushi (n = 41), Ca. O. chiloensis (n = 5), and Ca. O. chuto (n = 1), but was negative for DNA preparations from closely related rickettsiae and other members of the order Rickettsiales (n = 22) as well as unrelated bacterial species (n = 11). After its implementation in Chile, the assay was verified, correctly identifying all tested eschar and buffy coat samples (n = 28) of clinical suspected cases. Furthermore, Orien16S detected Orientia DNA in trombiculid mites collected in endemic regions in southern Chile. The presented novel qPCR assay provides a useful tool for detecting Orientia and diagnosing scrub typhus from all geographical regions.
SUMOylation Is Essential for Dengue Virus Replication and Transmission in the Mosquito Aedes aegypti
Authors: Weng Shih-Che , Shiao Shin-Hong
Published: April 2022

Small ubiquitin-like modifier (SUMO) is a reversible post-translational protein modifier. Protein SUMOylation regulates a wide variety of cellular processes and is important for controlling virus replication. Earlier studies suggest that dengue virus envelope protein interacts with Ubc9, the sole E2-conjugating enzyme required for protein SUMOylation in mammalian cells. However, little is known about the effect of protein SUMOylation on dengue virus replication in the major dengue vector, Aedes aegypti. Thus, in this study, we investigated the impact of protein SUMOylation on dengue virus replication in A. aegypti. The transcription of A. aegypti Ubc9 was significantly increased in the midgut after a normal blood meal. Silencing AaUbc9 resulted in significant inhibition of dengue virus NS1 protein production, viral genome transcription, and reduced viral titer in the mosquito saliva. In addition, we showed that dengue virus E proteins and prM proteins were SUMOylated post-infection. The amino acid residues K51 and K241 of dengue virus E protein were essential for protein SUMOylation. Taken together, our results reveal that protein SUMOylation contributes to dengue virus replication and transmission in the mosquito A. aegypti. This study introduces the possibility that protein SUMOylation is beneficial for virus replication and facilitates virus transmission from the mosquito.
Staphylococcus aureus ftnA 3’-Untranslated Region Modulates Ferritin Production Facilitating Growth Under Iron Starvation Conditions
Authors: Menendez-Gil Pilar , Catalan-Moreno Arancha , Caballero Carlos J. , Toledo-Arana Alejandro
Published: April 2022

Iron acquisition and modulation of its intracellular concentration are critical for the development of all living organisms. So far, several proteins have been described to be involved in iron homeostasis. Among them, ferritins act as the major iron storage proteins, sequestering internalized iron and modulating its concentration inside bacterial cells. We previously described that the deletion of the 3’-untranslated region (3’UTR) of the ftnA gene, which codes for ferritin in Staphylococcus aureus, increased the ftnA mRNA and ferritin levels. Here, we show that the ferritin levels are affected by RNase III and PNPase, which target the ftnA 3’UTR. Rifampicin mRNA stability experiments revealed that the half-life of the ftnA mRNA is affected by both RNase III and the ftnA 3’UTR. A transcriptional fusion of the ftnA 3’UTR to the gfp reporter gene decreased green fluorescent protein (GFP) expression, indicating that the ftnA 3’UTR could work as an independent module. Additionally, a chromosomal deletion of the ftnA 3’UTR impaired S. aureus growth under conditions of iron starvation. Overall, this work highlights the biological relevance of the ftnA 3’UTR for iron homeostasis in S. aureus.
Evaluation of the Effects of a Short Supplementation With Tannins on the Gut Microbiota of Healthy Subjects
Authors: Molino Silvia , Lerma-Aguilera Alberto , Jiménez-Hernández Nuria , Rufián Henares José Ángel , Francino M. Pilar
Published: April 2022

Western diet, high in fats and sugars and low in greens, contributes to dysbiosis of the gut microbiota, which can lead to a variety of chronic diseases related with inflammation. Supplementation with bioactive compounds can help to maintain a healthy eubiotic state. Thus, we performed a 4-weeks nutritional intervention on healthy volunteers to investigate whether a blend of natural tannin extracts could induce healthy changes in the microbial intestinal ecosystem. Changes in the composition and functionality of the microbiota could be observed from the first two weeks onward. 16S rRNA amplicon next-generation sequencing (NGS) revealed a significant increase in microbial diversity at the end of the intervention, as well as trends toward increases in the relative abundances of several beneficial taxa, such as Ruminococcus bicirculans, Faecalibacterium prausnitzii, Lachnospiraceae UCG 010, Lachnospiraceae NK4A136, Bacteroides thetaiotaomicron and B. uniformis. Remarkably, some of the identified taxa were also identified as responsible for an increase in the production of short-chain fatty acids (SCFAs), microbial metabolites that contribute to the modulation of the immune system and have various other anti-inflammatory functions in the gut. Taken together, these results suggest that the tannin supplementation could exert a prebiotic effect by selectively stimulating the growth and the activity of bacteria that are advantageous for the host.
Soil Environments Influence Gut Prokaryotic Communities in the Larvae of the Invasive Japanese Beetle Popillia japonica Newman
Authors: Avila-Arias Helena , Scharf Michael E. , Turco Ronald F. , Richmond Douglas S.
Published: April 2022

Invasive scarab beetles, like the Japanese beetle Popillia japonica Newman (JB), spend most of their lives as larvae feeding in the soil matrix. Despite the potential importance of the larval gut microbial community in driving the behavior, physiology, and nutritional ecology of this invasive insect, the role of soil biological and physicochemical characteristics in shaping this community are relatively unknown. Our objectives were to (1) characterize the degree to which larval gut microbial communities are environmentally acquired, (2) examine the combined effects of the gut region (i.e., midgut, hindgut) and local soil environments on gut microbial communities, and (3) search for soil physicochemical correlates that could be useful in future studies aimed at characterizing gut microbial community variation in soil-dwelling scarabs. Gut communities from neonates that were never in contact with the soil were different from gut communities of third instar larvae collected from the field, with neonate gut communities being significantly less rich and diverse. The influence of compartment (soil, midgut, or hindgut) on prokaryotic α- and β-diversity varied with location, suggesting that JB larval gut communities are at least partially shaped by the local environment even though the influence of compartment was more pronounced. Midgut microbiota contained transient communities that varied with the surrounding soil environment whereas hindgut microbiota was more conserved. Prokaryotic communities in the hindgut clustered separately from those of soil and midgut, which displayed greater interspersion in ordination space. Soil cation exchange capacity, organic matter, water holding capacity, and texture were moderately correlated (≥29%) with gut prokaryotic microbial composition, especially within the midgut. Findings suggest that microbial communities associated with the JB gut are partially a function of adaptation to local soil environments. However, conditions within each gut compartment appear to shape those communities in transit through the alimentary canal.
Epidemiological Impact of GII.17 Human Noroviruses Associated With Attachment to Enterocytes
Authors: Estienney Marie , Tarris Georges , Abou-Hamad Nicole , Rouleau Alain , Boireau Wilfrid , Chassagnon Rémi , Ayouni Siwar , Daval-Frerot Philippe , Martin Laurent , Bouyer Frédéric , Le Pendu Jacques , de Rougemont Alexis , Belliot Gael
Published: April 2022

For the last 30 years, molecular surveys have shown that human norovirus (HuNoV), predominantly the GII.4 genotype, is one of the main causative agents of gastroenteritis. However, epidemiological surveys have revealed the worldwide emergence of GII.17 HuNoVs. Genetic analysis confirmed that GII.17 strains are distributed into three variants (i.e., Kawasaki 308, Kawasaki 323, and CS-E1). Here, virus-like particles (VLPs) were baculovirus-expressed from these variants to study putative interactions with HBGA. Qualitative analysis of the HBGA binding profile of each variant showed that the most recent and predominant GII.17 variant, Kawasaki 308, possesses a larger binding spectrum. The retrospective study of GII.17 strains documented before the emergence of the dominant Kawasaki 308 variant showed that the emergence of a new GII.17 variant could be related to an increased binding capacity toward HBGA. The use of duodenal histological sections confirmed that recognition of enterocytes involved HBGA for the three GII.17 variants. Finally, we observed that the relative affinity of recent GII.17 VLPs for HBGA remains lower than that of the GII.4-2012 variant. These observations suggest a model whereby a combination of virological factors, such as polymerase fidelity and increased affinity for HBGA, and immunological factors was responsible for the incomplete and non-persistent replacement of GII.4 by new GII.17 variants.
The Periplasmic Domain of the Ion-Conducting Stator of Bacterial Flagella Regulates Force Generation
Authors: Homma Michio , Kojima Seiji
Published: April 2022

The bacterial flagellar stator is a unique ion-conducting membrane protein complex composed of two kinds of proteins, the A subunit and the B subunit. The stator couples the ion-motive force across the membrane into rotational force. The stator becomes active only when it is incorporated into the flagellar motor. The periplasmic region of the B subunit positions the stator by using the peptidoglycan-binding (PGB) motif in its periplasmic C-terminal domain to attach to the cell wall. Functional studies based on the crystal structures of the C-terminal domain of the B subunit (MotBC or PomBC) reveal that a dramatic conformational change in a characteristic α-helix allows the stator to conduct ions efficiently and bind to the PG layer. The plug and the following linker region between the transmembrane (TM) and PG-binding domains of the B subunit function in regulating the ion conductance. In Vibrio spp., the transmembrane protein FliL and the periplasmic MotX and MotY proteins also contribute to the motor function. In this review, we describe the functional and structural changes which the stator units undergo to regulate the activity of the stator to drive flagellar rotation.
Diversity of Microfungi in a High Radon Cave Ecosystem
Authors: Martin-Pozas Tamara , Nováková Alena , Jurado Valme , Fernandez-Cortes Angel , Cuezva Soledad , Saiz-Jimenez Cesareo , Sanchez-Moral Sergio
Published: April 2022

Castañar Cave is a clear example of an oligotrophic ecosystem with high hygrothermal stability both seasonal and interannual and the particularity of registering extraordinary levels of environmental radiation. These environmental conditions make the cave an ideal laboratory to evaluate both the responses of the subterranean environment to sudden changes in the matter and energy fluxes with the exterior and also any impact derived from its use as a tourist resource under a very restrictive access regime. In 2008, a fungal outbreak provoked by a vomit contaminated the sediments which were removed and subsequently treated with hydrogen peroxide. Fungal surveys were carried out in 2008 and 2009. The visits were resumed in 2014. Here, 12 years after the outbreak, we present an exhaustive study on the cave sediments in order to know the distribution of the different fungal taxa, as well as the prevalence and spatio-temporal evolution of the fungi caused by the vomit over the years under the conditions of relative isolation and high radiation that characterize this cave.
Not All Liver Abscesses Are Created Equal: The Impact of Tylosin and Antibiotic Alternatives on Bovine Liver Abscess Microbial Communities and a First Look at Bacteroidetes-Dominated Communities
Authors: Pinnell Lee J. , Whitlow Carla Weissend , Huebner Katherine L. , Bryant Tony C. , Martin Jennifer , Belk Keith E. , Morley Paul S.
Published: April 2022

Liver abscesses (LAs) are extremely prevalent in cattle and result in significant economic losses due to liver condemnation, decreased growth and production, and lower carcass quality. LAs are commonly attributed to the transition to diets high in rapidly fermentable starch which results in rumen epithelial inflammation that allows pathogenic bacteria to gain entry to liver through transportviathe hepatic portal vein. The most common intervention for LAs is the inclusion of antibiotics in feedlot diets, under the supervision of a veterinarian; this treatment is associated with reduced occurrence of LAs in this and other studies. Here, through the largest LA 16S rRNA gene sequencing study to date, we demonstrate that the inclusion of tylosin and antibiotic alternatives (the essential oil limonene andSaccharomyces cerevisiaefermentation product) had little impact on LA microbial community composition. Importantly, members of Bacteroidetes (Bacteroidesspp. andPorphyromonasspp.) were identified as the dominant taxa in conjunction with low proportions of Fusobacteria in nearly a quarter (61/259) of all LA communities analyzed in this study. The relative abundances of the phyla Fusobacteria and Bacteroidetes had a strongly negative correlation, and LA microbial communities rarely contained high abundances of both of these dominant phyla. Further, based on the presence of taxa discriminant of Bacteroidetes-dominated LAs within over 400 bovine gut communities, we provide evidence suggestive of Bacteroidetes-dominated abscess communities originating in more distal portions of the bovine gut. Together, these findings suggest that some LA microbial communities may originate from portions of the gut other than the rumen.
Microbial Adaptation to Enhance Stress Tolerance
Authors: Tan Yong-Shui , Zhang Ren-Kuan , Liu Zhi-Hua , Li Bing-Zhi , Yuan Ying-Jin
Published: April 2022

Microbial cell factories have been widely used in the production of various chemicals. Although synthetic biology is useful in improving the cell factories, adaptation is still widely applied to enhance its complex properties. Adaptation is an important strategy for enhancing stress tolerance in microbial cell factories. Adaptation involves gradual modifications of microorganisms in a stressful environment to enhance their tolerance. During adaptation, microorganisms use different mechanisms to enhance non-preferred substrate utilization and stress tolerance, thereby improving their ability to adapt for growth and survival. In this paper, the progress on the effects of adaptation on microbial substrate utilization capacity and environmental stress tolerance are reviewed, and the mechanisms involved in enhancing microbial adaptive capacity are discussed.