bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Rate of Epigenetic Aging in Men Living With HIV Prior to Treatment
Authors: Sehl Mary E. , Breen Elizabeth Crabb , Shih Roger , Chen Larry , Wang Ruibin , Horvath Steve , Bream Jay H. , Duggal Priya , Martinson Jeremy , Wolinsky Steven M. , Martinez-Maza Otoniel , Ramirez Christina M. , Jamieson Beth D.
Published: February 2022

Background: Epigenetic aging is accelerated in tissues of persons living with HIV (PLWH) and may underlie the early onset of age-related illnesses. This study examines the rate-of-change in epigenetic age in PLWH following HIV infection but before HAART, using archived longitudinal samples from the Multicenter AIDS Cohort Study.

Methods: DNA was isolated from cryopreserved peripheral blood mononuclear cells from 101 men living with HIV, with baseline visit <2.5 years after HIV seroconversion (Visit 1) and follow-up visit <1.5 years before the initiation of HAART (Visit 2), and 100 HIV-uninfected men matched on age and visits with comparable time intervals. DNA methylation (DNAm) age was estimated for five clocks (Pan-tissue, Extrinsic, Phenotypic, Grim, and Skin & Blood age), and a DNAm-based estimate of telomere length (DNAmTL). Multivariate linear regression models were used to examine baseline factors associated with rate-of-aging, defined as (DNAm age visit 2–DNAm age visit 1)/(age visit 2–age visit 1).

Results: Epigenetic age increased approximately twice as fast in PLWH as uninfected controls (Pan-tissue, Extrinsic, and Phenotypic clocks). Shortening of DNAmTL was nearly 3-fold faster in PLWH than controls. Faster rate-of-aging was associated with HIV status (Pan-Tissue, Extrinsic, Phenotypic, and DNAmTL), white race (Extrinsic, DNAmTL), higher cumulative HIV viral load (Grim), and lower baseline DNAm age (Phenotypic, Skin & Blood).

Conclusion: Epigenetic rates-of-aging were significantly faster for untreated PLWH. Our findings expand on the important impact of HIV infection on biologic aging, both in elevating epigenetic age and increasing the rate-of-aging in the years following infection.
SSAM-lite: A Light-Weight Web App for Rapid Analysis of Spatially Resolved Transcriptomics Data
Authors: Tiesmeyer Sebastian , Sahay Shashwat , Müller-Bötticher Niklas , Eils Roland , Mackowiak Sebastian D. , Ishaque Naveed
Published: February 2022

The combination of a cell’s transcriptional profile and location defines its function in a spatial context. Spatially resolved transcriptomics (SRT) has emerged as the assay of choice for characterizing cells in situ. SRT methods can resolve gene expression up to single-molecule resolution. A particular computational problem with single-molecule SRT methods is the correct aggregation of mRNA molecules into cells. Traditionally, aggregating mRNA molecules into cell-based features begins with the identification of cells via segmentation of the nucleus or the cell membrane. However, recently a number of cell-segmentation-free approaches have emerged. While these methods have been demonstrated to be more performant than segmentation-based approaches, they are still not easily accessible since they require specialized knowledge of programming languages and access to large computational resources. Here we present SSAM-lite, a tool that provides an easy-to-use graphical interface to perform rapid and segmentation-free cell-typing of SRT data in a web browser. SSAM-lite runs locally and does not require computational experts or specialized hardware. Analysis of a tissue slice of the mouse somatosensory cortex took less than a minute on a laptop with modest hardware. Parameters can interactively be optimized on small portions of the data before the entire tissue image is analyzed. A server version of SSAM-lite can be run completely offline using local infrastructure. Overall, SSAM-lite is portable, lightweight, and easy to use, thus enabling a broad audience to investigate and analyze single-molecule SRT data.
Genome-Wide Characterization and Anthocyanin-Related Expression Analysis of the B-BOX Gene Family in Capsicum annuum L.
Authors: Wang Jin , Yang Guangbin , Chen Ying , Dai Yao , Yuan Qiaoling , Shan Qingyun , Pan Luzhao , Dai Li , Zou Xuexiao , Liu Feng , Xiong Cheng
Published: February 2022

The transcription factors, B-box (BBX), belong to a subfamily of the zinc finger family of proteins and exhibit multiple biological functions in plant growth, development, and abiotic stress response pathways. In this study, a total of 23 CaBBX members were identified using the pepper reference genome database. According to the gene structure, conserved domains, and the phylogenetic tree, 23 CaBBX genes were divided into four groups, wherein the analysis of the promoter region indicated the presence of cis-acting elements related to plant development, hormones, and stress response. Interspecies collinearity analysis showed that the CaBBXs had three duplicated gene pairs, and the highest gene density was found on chromosomes 2 and 7. Transcriptome RNA-seq data and quantitative polymerase chain reaction (qRT-PCR) analysis of pepper plants spanning the entire period showed that more than half of the CaBBX genes were widely expressed in diversity tissues of pepper. Co-expression network analysis indicated that the CaBBXs and the anthocyanin structural genes had a close co-expression relationship. Thus, it was reasonably speculated that the CaBBX genes may be involved in the regulation of anthocyanin biosynthesis. Overall, this study involved the genome-wide characterization of the CaBBX family and may serve as a solid foundation for further investigations on CaBBX genes involved in the anthocyanin synthesis mechanisms and development in pepper.
A Specific CD44lo CD25lo Subpopulation of Regulatory T Cells Inhibits Anti-Leukemic Immune Response and Promotes the Progression in a Mouse Model of Chronic Lymphocytic Leukemia
Authors: Goral Agnieszka , Firczuk Malgorzata , Fidyt Klaudyna , Sledz Marta , Simoncello Francesca , Siudakowska Karolina , Pagano Giulia , Moussay Etienne , Paggetti Jérôme , Nowakowska Patrycja , Gobessi Stefania , Barankiewicz Joanna , Salomon-Perzynski Aleksander , Benvenuti Federica , Efremov Dimitar G. , Juszczynski Przemyslaw , Lech-Maranda Ewa , Muchowicz Angelika
Published: February 2022

Regulatory T cells (Tregs) are capable of inhibiting the proliferation, activation and function of T cells and play an important role in impeding the immune response to cancer. In chronic lymphocytic leukemia (CLL) a dysfunctional immune response and elevated percentage of effector-like phenotype Tregs have been described. In this study, using the Eµ-TCL1 mouse model of CLL, we evaluated the changes in the Tregs phenotype and their expansion at different stages of leukemia progression. Importantly, we show that Tregs depletion in DEREG mice triggered the expansion of new anti-leukemic cytotoxic T cell clones leading to leukemia eradication. In TCL1 leukemia-bearing mice we identified and characterized a specific Tregs subpopulation, the phenotype of which suggests its role in the formation of an immunosuppressive microenvironment, supportive for leukemia survival and proliferation. This observation was also confirmed by the gene expression profile analysis of these TCL1-specific Tregs. The obtained data on Tregs are consistent with those described so far, however, above all show that the changes in the Tregs phenotype described in CLL result from the formation of a specific, described in this study Tregs subpopulation. In addition, functional tests revealed the ability of Tregs to inhibit T cells that recognize model antigens expressed by leukemic cells. Moreover, inhibition of Tregs with a MALT1 inhibitor provided a therapeutic benefit, both as monotherapy and also when combined with an immune checkpoint inhibitor. Altogether, activation of Tregs appears to be crucial for CLL progression.
Insufficient Iron Improves Pristane-Induced Lupus by Promoting Treg Cell Expansion
Authors: Gao Xiaofei , Song Yang , Lu Shuang , Hu Longyuan , Zheng Meiling , Jia Sujie , Zhao Ming
Published: February 2022

Trace element iron affects T cell biology, but the knowledge about the role of iron in regulating Treg cell expansion is limited. Treg cells play an important role in keeping peripheral T cell tolerance, increasing Treg cell expansion is a promising therapeutic method for SLE. Here we showed that iron deficiency promotes Treg cell expansion by reducing ROS accumulation, improving the disease progression of pristane-induced lupus. Increased oxidative stress inhibits Treg cell differentiation by inducing cell apoptosis. Our data suggest that altering iron metabolism promotes Treg cell expansion by preventing oxidation-induced cell death, which may provide a potential therapeutic strategy for SLE.
Age-Related Differences in Structure and Function of Nasal Epithelial Cultures From Healthy Children and Elderly People
Authors: Balázs Anita , Millar-Büchner Pamela , Mülleder Michael , Farztdinov Vadim , Szyrwiel Lukasz , Addante Annalisa , Kuppe Aditi , Rubil Tihomir , Drescher Marika , Seidel Kathrin , Stricker Sebastian , Eils Roland , Lehmann Irina , Sawitzki Birgit , Röhmel Jobst , Ralser Markus , Mall Marcus A.
Published: February 2022

The nasal epithelium represents the first line of defense against inhaled pathogens, allergens, and irritants and plays a key role in the pathogenesis of a spectrum of acute and chronic airways diseases. Despite age-dependent clinical phenotypes triggered by these noxious stimuli, little is known about how aging affects the structure and function of the airway epithelium that is crucial for lung homeostasis and host defense. The aim of this study was therefore to determine age-related differences in structural and functional properties of primary nasal epithelial cultures from healthy children and non-smoking elderly people. To achieve this goal, highly differentiated nasal epithelial cultures were established from nasal brushes at air–liquid interface and used to study epithelial cell type composition, mucin (MUC5AC and MUC5B) expression, and ion transport properties. Furthermore, we determined age-dependent molecular signatures using global proteomic analysis. We found lower numeric densities of ciliated cells and higher levels of MUC5AC expression in cultures from children vs. elderly people. Bioelectric studies showed no differences in basal ion transport properties, ENaC-mediated sodium absorption, or CFTR-mediated chloride transport, but detected decreased calcium-activated TMEM16A-mediated chloride secretory responses in cultures from children vs. elderly people. Proteome analysis identified distinct age-dependent molecular signatures associated with ciliation and mucin biosynthesis, as well as other pathways implicated in aging. Our data identified intrinsic, age-related differences in structure and function of the nasal epithelium and provide a basis for further studies on the role of these findings in age-dependent airways disease phenotypes observed with a spectrum of respiratory infections and other noxious stimuli.
Regulatory T Cells in Autoimmune Vasculitis
Authors: Jin Ke , Parreau Simon , Warrington Kenneth J. , Koster Matthew J. , Berry Gerald J. , Goronzy Jörg J. , Weyand Cornelia M.
Published: February 2022

Blood vessels are indispensable for host survival and are protected from inappropriate inflammation by immune privilege. This protection is lost in patients with autoimmune vasculitides, a heterogeneous group of diseases causing damage to arteries, arterioles, and capillaries. Vasculitis leads to vascular wall destruction and/or luminal occlusion, resulting in hemorrhage and tissue ischemia. Failure in the quantity and quality of immunosuppressive regulatory T cells (Treg) has been implicated in the breakdown of the vascular immune privilege. Emerging data suggest that Treg deficiencies are disease-specific, affecting distinct pathways in distinct vasculitides. Mechanistic studies have identified faulty CD8+Tregs in Giant Cell Arteritis (GCA), a vasculitis of the aorta and the large aortic branch vessels. Specifically, aberrant signaling through the NOTCH4 receptor expressed on CD8+Treg cells leads to rerouting of intracellular vesicle trafficking and failure in the release of immunosuppressive exosomes, ultimately boosting inflammatory attack to medium and large arteries. In Kawasaki’s disease, a medium vessel vasculitis targeting the coronary arteries, aberrant expression of miR-155 and dysregulated STAT5 signaling have been implicated in undermining CD4+Treg function. Explorations of mechanisms leading to insufficient immunosuppression and uncontrolled vascular inflammation hold the promise to discover novel therapeutic interventions that could potentially restore the immune privilege of blood vessels and pave the way for urgently needed innovations in vasculitis management.
Sero-Prevalence of West Nile Virus in Urban and Peri-Urban Poultry Farms of Guwahati, India
Authors: Talukdar Archana , Hazarika Razibuddin A. , Bora Durlav P. , Pegu Seema R. , Talukdar Phunu , Kader Nur A. , Mohakud Sidharth S. , Deka Naba Jyoti , Lindahl Johanna F.
Published: February 2022

West Nile virus (WNV) is a zoonotic, emerging mosquito-borne virus which can cause severe disease in the form of encephalitis and acute flaccid paralysis in humans. In Assam, northeast India, arboviruses seem to be re-emerging, however, WNV has been little studied. The present investigation was carried out from April, 2018 to March, 2019 to study sero-positivity of WNV in chicken in urban and peri-urban areas of Guwahati, the capital city of Assam. Four urban and four peri-urban areas of Guwahati were selected. A total of 864 chicken serum samples (72 samples per month) were screened by ELISA and further confirmed by haemagglutination inhibition (HI), which revealed that 3.13% of the chickens had been exposed to WNV, with 0.69% sero-positivity in urban areas compared to 5.56% in peri-urban. Peak sero-prevalence of WNV were reported during the month of July and August with 8.33% each with lowest sero-prevalence being recorded in November (1.39%) and no sero-positive birds from December to April. These results indicate that WNV is one of the actively circulating flaviviruses in Assam, and human febrile and encephalitic cases should be screened for the disease.
Antagonistic Activity of Lactic Acid Bacteria Against Pathogenic Vibrios and Their Potential Use as Probiotics in Shrimp (Penaeus vannamei) Culture
Authors: Thompson John , Weaver Mark A. , Lupatsch Ingrid , Shields Robin J. , Plummer Sue , Coates Christopher J. , Rowley Andrew F.
Published: February 2022

Probiotic use in aquaculture settings can be an approach for disease control and dietary supplementation. We assessed the antagonistic effect of culture supernatants of lactic acid bacteria on the growth of known shrimp pathogens,Vibrio(Listonella)anguillarum,Vibrio alginolyticus, andV. harveyi, using a quantitative microplate bioassay. Supernatants fromLactobacillus curvatussubsp.curvatus, L. plantarum, andPediococcus acidolacticisignificantly inhibited the growth of these vibrios. The active component(s) were heat stable (> 100°C) and resistant to freeze-thawing. Most of this inhibitory activity was brought about by the production of an acid pH; however, there was evidence for other factors playing a role. In the search for novel probiotic bacteria, an organism was isolated from the gastrointestinal tract of healthy whiteleg shrimp (Penaeus vannamei)—identified tentatively asCarnobacterium maltaromaticum. This isolate, however, had less potent vibriocidal activity than the lactic acid bacteria and reduced shrimp survival at a dose of 1 × 107bacteria/shrimp. During a 28-day feeding trial, juvenileP. vannameifed withL. plantarumsupplemented diets showed no gross changes in growth parameters compared with the control. We suggest that lactic acid bacteria could be incorporated into biofloc formulations to purge the growth of pathogenic vibrios in pond settings, rather than being fed directly to shrimp.
Design and Performance of Ultraviolet 368-nm AlGaN-Based Flip-Chip High-Voltage LEDs with Epitaxial Indium Tin Oxide/Al Reflective Mirror and Symmetry Electrode Arrangement
Authors: Ma Chuanzhe , Wang Xinchang , Lao Yuqin , Yang Jiachen , Chen Guojie , Wang Gang , Fan Bingfeng
Published: February 2022

In this letter, we describe the design and fabrication of high-power AlGaN-based ultraviolet (UV) flip-chip high-voltage light-emitting diodes (LEDs) operating at 368 nm with an epitaxial indium tin oxide (ITO)/Al reflecting mirror and symmetry electrode layout. Metal-organic chemical vapor deposition (MOCVD) was used to grow an ITO thin film as a transparent electrode on the LED surface. At 365 nm, epitaxial ITO thin films exhibited a transmittance of up to 93.6%. Additionally, the epitaxial ITO/Al reflective mirror has a reflectance of 81.2% at 365-nm. To investigate the electrical characteristics, four types of HV-LED micro-cells were constructed with varying n-type mesa structures and p-type interconnect electrodes. We demonstrated a forward voltage (Vf) of 7.86 V at 350 mA with a 2 × 2 mico-cells high-voltage ultraviolet 368-nm flip-chip LED after optimising electrode structure and device process.
Identification of Signature Genes and Characterizations of Tumor Immune Microenvironment and Tumor Purity in Lung Adenocarcinoma Based on Machine Learning
Authors: Feng Haiming , Zhao Ye , Yan Weijian , Wei Xiaoping , Lin Junping , Jiang Peng , Wang Cheng , Li Bin
Published: February 2022

The implication of the Estimation of Stromal and Immune cells in Malignant tumor tissues using expression data (ESTIMATE) method to determine the tumor microenvironment (TME) and tumor immune score including tumor purity represents an efficient method to identify and assess biomarkers for immunotherapy response in precision medicine. In this study we utilized a machine learning algorithm to analyze the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO) lung adenocarcinoma (LUAD) transcriptome data to evaluate the association between TME and tumor purity. Furthermore, we investigated whether fewer TME components or a few dominant genes can infer tumor purity. The results indicated that the 29 immune infiltrating components determined by the ssGSEA method could screen the 5 TME components [chemokine C-C-Motif receptor (CCR), T-helper-cells, Check-point, Treg, and tumor-infiltrating lymphocytes (TIL)] that significantly contributed the most to tumor purity prediction through regression tree and random forest regression methods. The findings revealed that higher activity of these five immune infiltrating components significantly lowered the tumor purity. Moreover, 5 TME components contributed significantly to the improvement of Mean Square Error (MES); therefore, we selected these five sets' genes and analyzed survival data to establish a prognostic model. We screened out 11 prognostic-related genes and constructed a risk model comprising 11 genes with good predictive value for patients' prognosis. Furthermore, we obtained four genes (GIMAP6, CD80, IL16, and CCR2) that had predictive advantages for tumor purity using random forest classification and random forest regression. The comprehensive score of genes for tumor purity prediction (CSGTPP) was obtained by least absolute shrinkage and selection operator (LASSO) regression indicated that four genes could be successfully used to classify high and low CSGTPP samples and that tumor purity was negatively correlated with CSGTPP. Survival analysis revealed that the higher the CSGTPP, the better the prognosis of patients. The association between a cluster of differentiation 274 (CD274) and CSGTPP revealed a higher expression of CD274 in the high CSGTPP group. Collectively, we speculated that CSGTPP could serve as a predictor of the response to immunotherapy and a promising indicator of immunotherapy effect.
Discovery of Potential Therapeutic Drugs for COVID-19 Through Logistic Matrix Factorization With Kernel Diffusion
Authors: Tian Xiongfei , Shen Ling , Gao Pengfei , Huang Li , Liu Guangyi , Zhou Liqian , Peng Lihong
Published: February 2022

Coronavirus disease 2019 (COVID-19) is rapidly spreading. Researchers around the world are dedicated to finding the treatment clues for COVID-19. Drug repositioning, as a rapid and cost-effective way for finding therapeutic options from available FDA-approved drugs, has been applied to drug discovery for COVID-19. In this study, we develop a novel drug repositioning method (VDA-KLMF) to prioritize possible anti-SARS-CoV-2 drugs integrating virus sequences, drug chemical structures, known Virus-Drug Associations, and Logistic Matrix Factorization with Kernel diffusion. First, Gaussian kernels of viruses and drugs are built based on known VDAs and nearest neighbors. Second, sequence similarity kernel of viruses and chemical structure similarity kernel of drugs are constructed based on biological features and an identity matrix. Third, Gaussian kernel and similarity kernel are diffused. Forth, a logistic matrix factorization model with kernel diffusion is proposed to identify potential anti-SARS-CoV-2 drugs. Finally, molecular dockings between the inferred antiviral drugs and the junction of SARS-CoV-2 spike protein-ACE2 interface are implemented to investigate the binding abilities between them. VDA-KLMF is compared with two state-of-the-art VDA prediction models (VDA-KATZ and VDA-RWR) and three classical association prediction methods (NGRHMDA, LRLSHMDA, and NRLMF) based on 5-fold cross validations on viruses, drugs, and VDAs on three datasets. It obtains the best recalls, AUCs, and AUPRs, significantly outperforming other five methods under the three different cross validations. We observe that four chemical agents coming together on any two datasets, that is, remdesivir, ribavirin, nitazoxanide, and emetine, may be the clues of treatment for COVID-19. The docking results suggest that the key residues K353 and G496 may affect the binding energies and dynamics between the inferred anti-SARS-CoV-2 chemical agents and the junction of the spike protein-ACE2 interface. Integrating various biological data, Gaussian kernel, similarity kernel, and logistic matrix factorization with kernel diffusion, this work demonstrates that a few chemical agents may assist in drug discovery for COVID-19.
Liquid Chromatography-Tandem Mass Spectrometry Analysis Demonstrates a Decrease in Porins and Increase in CMY-2 β-Lactamases in Escherichia coli Exposed to Increasing Concentrations of Meropenem
Authors: Foudraine Dimard E. , Aarents Camiel N. M. , Wattel Agnes A. , van Boxtel Ria , Strepis Nikolaos , ten Kate Marian T. , Verbon Annelies , Luider Theo M. , Klaassen Corné H. W. , Hays John , Dekker Lennard J. M. , Tommassen Jan , Goessens Wil H. F.
Published: February 2022

While Extended-Spectrum β-Lactamases (ESBL) and AmpC β-lactamases barely degrade carbapenem antibiotics, they are able to bind carbapenems and prevent them from interacting with penicillin-binding proteins, thereby inhibiting their activity. Further, it has been shown that Enterobacterales can become resistant to carbapenems when high concentrations of ESBL and AmpC β-lactamases are present in the bacterial cell in combination with a decreased influx of antibiotics (due to a decrease in porins and outer-membrane permeability). In this study, a targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was developed for the detection of the Escherichia coli porins OmpC and OmpF, its chromosomal AmpC β-lactamase, and the plasmid-mediated CMY-2 β-lactamase. BlaCMY–2–like positive E. coli isolates were cultured in the presence of increasing concentrations of meropenem, and resistant mutants were analyzed using the developed LC-MS/MS assay, Western blotting, and whole genome sequencing. In five strains that became meropenem resistant, a decrease in OmpC and/or OmpF (caused by premature stop codons or gene interruptions) was the first event toward meropenem resistance. In four of these strains, an additional increase in MICs was caused by an increase in CMY-2 production, and in one strain this was most likely caused by an increase in CTX-M-15 production. The LC-MS/MS assay developed proved to be suitable for the (semi-)quantitative analysis of CMY-2-like β-lactamases and porins within 4 h. Targeted LC-MS/MS could have additional clinical value in the early detection of non-carbapenemase-producing carbapenem-resistant E. coli.
Molecular Basis of Wrinkled Variants Isolated From Pseudoalteromonas lipolytica Biofilms
Authors: Zeng Zhenshun , Lin Shituan , Li Qian , Wang Weiquan , Wang Yuqi , Xiao Tangfu , Guo Yuexue
Published: February 2022

Many Pseudoalteromonas species are dominant biofilm-forming Gammaproteobacteria in the ocean. The formation of Pseudoalteromonas biofilms is often accompanied by the occurrence of variants with different colony morphologies that may exhibit increased marine antifouling or anticorrosion activities. However, the genetic basis of the occurrence of these variants remains largely unexplored. In this study, we identified that wrinkled variants of P. lipolytica mainly arose due to mutations in the AT00_08765, a wspF-like gene, that are associated with decreased swimming motility and increased cellulose production. Moreover, we found that the spontaneous mutation in flhA, encoding a flagellar biosynthesis protein, also caused a wrinkled colony morphology that is associated with cellulose overproduction, indicating that flhA plays a dual role in controlling flagellar assembly and polysaccharide production in P. lipolytica. Investigation of wrinkled variants harboring spontaneous mutation in dgcB, encoding a GGDEF domain protein, also demonstrated dgcB plays an important role in regulating cellulose production and swimming motility. In addition, by screening the suppressor of the AT00_08765 variant strain, we also identified that the spontaneous mutation in cheR and bcsC directly abolished the wrinkled phenotype of the AT00_08765 variant strain, suggesting that the chemosensory signaling transduction and cellulose production are crucial for the determination of the wrinkled phenotype in P. lipolytica. Taken together, this study provides insights into the genetic variation within biofilms of P. lipolytica.
Genetic Characteristics of Multiple Copies of Tn1546-Like Elements in ermB-Positive Methicillin-Resistant Staphylococcus aureus From Mainland China
Authors: Wang Haiping , Wu Dandan , Di Lingfang , Zhu Feiteng , Wang Zhengan , Sun Lu , Chen Yiyi , Jiang Shengnan , Zhuang Hemu , Chen Mengzhen , Ji Shujuan , Chen Yan
Published: February 2022

Objective

To determine the genetic structure of ermB-positive Tn1546-like mobile elements in methicillin-resistant Staphylococcus aureus (MRSA) from mainland China.

Methods

A total of 271 erythromycin-resistant MRSA isolates were isolated from Sir Run Run Shaw Hospital (SRRSH) from 2013 to 2015. Whole-genome sequencing was performed for the ermB-positive strains, and the genetic environment of the ermB genes was analyzed. Southern hybridization analysis and transformation tests were performed to confirm the location of the ermB gene.

Results

A total of 64 isolates (64/271, 23.6%) were ermB-positive strains, with 62 strains (62/64, 96.9%) belonging to the CC59 clone. The other two strains, SR130 and SR231, belonging to CC5-ST965, both harbored 14,567 bp ermB-positive Tn1546-like elements and displayed multidrug-resistant profiles. PFGE followed by Southern blot demonstrated that the ermB genes were located on the plasmids of both SR130 and SR231, while two copies of ermB were located on the chromosome of SR231. Further sequencing demonstrated that SR231 carried one Tn1546-ermB elements in the plasmid and two identical copies integrated on the chromosome, which had 99.99% identity to the element in the plasmid of SR130. The Tn1546-ermB elements were highly similar (100% coverage, >99.9% identity) to the element Tn6636 reported in a previous study from Taiwan. The plasmids (pSR130 and pSR231) harboring ermB-positive Tn1546-like elements were also identical to the mosaic plasmid pNTUH_5066148. However, conjugation of ermB-carrying plasmids of SR130 and SR231 were failed after triple repeats.

Conclusion

Multiple copies of ermB-positive Tn1546-like mobile elements were found in CC5-ST965 MRSA from mainland China, showing the wide dissemination of these Enterococcus faecium-originated ermB-positive Tn1546-like elements. Molecular epidemiological study of Tn1546-like elements is essential to avoid the spreading of resistant determinants.
Determination of Community Structure and Diversity of Seed-Vectored Endophytic Fungi in Alpinia zerumbet
Authors: Yan Kuan , Pei Zihao , Meng Lina , Zheng Yu , Wang Lian , Feng Ruizhang , Li Quanzi , Liu Yang , Zhao Xianming , Wei Qin , El-Sappah Ahmed H. , Abbas Manzar
Published: February 2022

Endophytic fungi act as seed endosymbiont, thereby playing a very crucial role in the growth and development of seeds. Seed-vectored endophytic fungi establish an everlasting association with seeds and travel from generation to generation. To explore the composition and diversity of endophytic fungi in Alpinia zerumbet seeds, high-throughput Illumina MiSeq sequencing was employed for the following stages: fruit formation period (YSJ1), young fruit period (YSJ2), early mature period (YSJ3), middle mature period (YSJ4), and late mature period (YSJ5). A total of 906,694 sequence reads and 745 operational taxonomic units (OTUs) were obtained and further classified into 8 phyla, 30 classes, 73 orders, 163 families, 302 genera, and 449 species. The highest endophytic fungal diversity was observed at YSJ5. The genera with the highest abundance were Cladosporium, Kodamaea, Hannaella, Mycothermus, Gibberella, Sarocladium, and Neopestalotiopsis. Functional Guild (FUNGuild) analysis revealed that endophytic fungi were undefined saprotroph, plant pathogens, animal pathogen–endophyte–lichen parasite–plant pathogen–wood saprotroph, and soil saprotrophs. Alternaria, Fusarium, Cladosporium, and Sarocladium, which are potential probiotics and can be used as biocontrol agents, were also abundant. This study is part of the Sustainable Development Goals of United Nations Organization (UNO) to “Establish Good Health and Well-Being.”
Light Triggered Enhancement of Antibiotic Efficacy in Biofilm Elimination Mediated by Gold-Silver Alloy Nanoparticles
Authors: Alves-Barroco Cinthia , Rivas-García Lorenzo , Fernandes Alexandra R. , Baptista Pedro Viana
Published: February 2022

Bacterial biofilm is a tri-dimensional complex community of cells at different metabolic stages involved in a matrix of self-produced extracellular polymeric substances. Biofilm formation is part of a defense mechanism that allows the bacteria to survive in hostile environments, such as increasing resistance or tolerance to antimicrobial agents, causing persistent infections hard to treat and impair disease eradication. One such example is bovine mastitis associated with Streptococcus dysgalactiae subsp. dysgalactiae (SDSD), whose worldwide health and economic impact is on the surge. As such, non-conventional nanobased approaches have been proposed as an alternative to tackle biofilm formation and to which pathogenic bacteria fail to adapt. Among these, metallic nanoparticles have gained significant attention, particularly gold and silver nanoparticles, due to their ease of synthesis and impact against microorganism growth. This study provides a proof-of-concept investigation into the use of gold-silver alloy nanoparticles (AuAgNPs) toward eradication of bacterial biofilms. Upon visible light irradiation of AuAgNPs there was considerable disturbance of the biofilms’ matrix. The hindering of structural integrity of the biofilm matrix resulted in an increased permeability for entry of antibiotics, which then cause the eradication of biofilm and inhibit subsequent biofilm formation. Additionally, our results that AuAgNPs inhibited the formation of SDSD biofilms via distinct stress pathways that lead to the downregulation of two genes critical for biofilm production, namely, brpA-like encoding biofilm regulatory protein and fbpA fibronectin-binding protein A. This study provides useful information to assist the development of nanoparticle-based strategies for the active treatment of biofilm-related infections triggered by photoirradiation in the visible.
Vaccine Candidate Against COVID-19 Based on Structurally Modified Plant Virus as an Adjuvant
Authors: Kovalenko Angelina O. , Ryabchevskaya Ekaterina M. , Evtushenko Ekaterina A. , Manukhova Tatiana I. , Kondakova Olga A. , Ivanov Peter A. , Arkhipenko Marina V. , Gushchin Vladimir A. , Nikitin Nikolai A. , Karpova Olga V.
Published: February 2022

A recombinant vaccine candidate has been developed based on the major coronaviruses’ antigen (S protein) fragments and a novel adjuvant—spherical particles (SPs) formed during tobacco mosaic virus thermal remodeling. The receptor-binding domain and the highly conserved antigenic fragments of the S2 protein subunit were chosen for the design of recombinant coronavirus antigens. The set of three antigens (Co1, CoF, and PE) was developed and used to create a vaccine candidate composed of antigens and SPs (SPs + 3AG). Recognition of SPs + 3AG compositions by commercially available antibodies against spike proteins of SARS-CoV and SARS-CoV-2 was confirmed. The immunogenicity testing of these compositions in a mouse model showed that SPs improved immune response to the CoF and PE antigens. Total IgG titers against both proteins were 9–16 times higher than those to SPs. Neutralizing activity against SARS-CoV-2 in serum samples collected from hamsters immunized with the SPs + 3AG was demonstrated.
Regulation of Reactive Oxygen Species Promotes Growth and Carotenoid Production Under Autotrophic Conditions in Rhodobacter sphaeroides
Authors: Lee Yu Rim , Lee Won-Heong , Lee Soo Youn , Lee Jiye , Kim Min-Sik , Moon Myounghoon , Park Gwon Woo , Kim Hui Su , Kim Jeong-Il , Lee Jin-Suk , Lee Sangmin
Published: February 2022

Industrial demand for capture and utilization using microorganisms to reduce CO2, a major cause of global warming, is significantly increasing. Rhodobacter sphaeroides is a suitable strain for the process of converting CO2 into high-value materials because it can accept CO2 and has various metabolic pathways. However, it has been mainly studied for heterotrophic growth that uses sugars and organic acids as carbon sources, not autotrophic growth. Here, we report that the regulation of reactive oxygen species is critical for growth when using CO2 as a sole carbon source in R. sphaeroides. In general, the growth rate is much slower under autotrophic conditions compared to heterotrophic conditions. To improve this, we performed random mutagenesis using N-methyl-N’-nitro-N-nitrosoguanidine (NTG). As a result, we selected the YR-1 strain with a maximum specific growth rate (μ) 1.44 day–1 in the early growth phase, which has a 110% faster growth rate compared to the wild-type. Based on the transcriptome analysis, it was confirmed that the growth was more sensitive to reactive oxygen species under autotrophic conditions. In the YR-1 mutant, the endogenous contents of H2O2 levels and oxidative damage were reduced by 33.3 and 42.7% in the cells, respectively. Furthermore, we measured that concentrations of carotenoids, which are important antioxidants. The total carotenoid is produced 9.63 g/L in the YR-1 mutant, suggesting that the production is 1.7-fold higher than wild-type. Taken together, our observations indicate that controlling ROS promotes cell growth and carotenoid production under autotrophic conditions.
Distinct Expansion of Group II Introns During Evolution of Prokaryotes and Possible Factors Involved in Its Regulation
Authors: Miura Masahiro C. , Nagata Shohei , Tamaki Satoshi , Tomita Masaru , Kanai Akio
Published: February 2022

Group II introns (G2Is) are ribozymes that have retroelement characteristics in prokaryotes. Although G2Is are suggested to have been an important evolutionary factor in the prokaryote-to-eukaryote transition, comprehensive analyses of these introns among the tens of thousands of prokaryotic genomes currently available are still limited. Here, we developed a bioinformatic pipeline that systematically collects G2Is and applied it to prokaryotic genomes. We found that in bacteria, 25% (447 of 1,790) of the total representative genomes had an average of 5.3 G2Is, and in archaea, 9% (28 of 296) of the total representative genomes had an average of 3.0 G2Is. The greatest number of G2Is per genome was 101 in Arthrospira platensis (phylum Cyanobacteriota). A comprehensive sequence analysis of the intron-encoded protein (IEP) in each G2I sequence was conducted and resulted in the addition of three new IEP classes (U1–U3) to the previous classification. This analysis suggested that about 30% of all IEPs are non-canonical IEPs. The number of G2Is per genome was defined almost at the phylum level, and at least in the following two phyla, Firmicutes, and Cyanobacteriota, the type of IEP was largely associated as a factor in the G2I increase, i.e., there was an explosive increase in G2Is with bacterial C-type IEPs, mainly in the phylum Firmicutes, and in G2Is with CL-type IEPs, mainly in the phylum Cyanobacteriota. We also systematically analyzed the relationship between genomic signatures and the mechanism of these increases in G2Is. This is the first study to systematically characterize G2Is in the prokaryotic phylogenies.
Isolation and Genetic Characterization of Parvoviruses From Dogs, Cats, Minks, and Raccoon Dogs in the Eastern Region of Shandong Province, China
Authors: Zhao Jiakai , Zhang Hao , Zhang Lu , Zhang Qiang , Zhou Ning , Du Taofeng , Zhao Qin , Zhou En-Min , Du Yongkun , Sun Yani
Published: February 2022

The eastern region of Shandong province, China, is an intensive economic mink and raccoon dog breeding area. To investigate the molecular variations of parvovirus in cats, dogs, minks, and raccoon dogs from this region, feline panleukopenia virus (FPV), canine parvovirus 2 (CPV-2), mink enteritis virus (MEV), and raccoon dog parvovirus (RDPV) were separately isolated and characterized from the respective animals with gastroenteritis. PCR amplification showed that there were 15/18 (83.3%), 9/13 (69.2%), 8/11 (72.7%), and 3/7 (42.9%) samples from the diseased animals separately positive for FPV, CPV-2, MEV, and RDPV. Of these, a total of six FPV, six MEV, four CPV-2, and three RDPV strains were successfully isolated using F81 cells. Next, the near-complete genomes of 19 parvovirus isolates were amplified and analyzed. The viral particle 2 (VP2) sequence alignment showed that they shared 97.2–100% nucleotide similarity. Phylogenetic analysis showed that the five FPV isolates were in the same branch, and an FPV isolate was closely related with MEV and RDPV isolates obtained in this study. These suggested that cross-species infection occurred in the Shandong region between the FPV, MEV, and RDPV. For the four CPV-2 isolates, three were antigenic variant strains CPV-2a, and the other was antigenic variant strain CPV-2c. Additionally, the mutations that had emerged in the VP2 amino acids of CPV-2 also occurred in the VP2 from the FPV, MEV, and RDPV isolates. This study suggested that the continuous evolution of the parvovirus may be accelerated in areas with a high density of economic animal trading/breeding, and controlling parvovirus infection in these animals remains a challenge.
Automatic Classification and Severity Estimation of Ataxia From Finger Tapping Videos
Authors: Nunes Adonay S. , Kozhemiako Nataliia , Stephen Christopher D. , Schmahmann Jeremy D. , Khan Sheraz , Gupta Anoopum S.
Published: February 2022

Digital assessments enable objective measurements of ataxia severity and provide informative features that expand upon the information obtained during a clinical examination. In this study, we demonstrate the feasibility of using finger tapping videos to distinguish participants with Ataxia (N = 169) from participants with parkinsonism (N = 78) and from controls (N = 58), and predict their upper extremity and overall disease severity. Features were extracted from the time series representing the distance between the index and thumb and its derivatives. Classification models in ataxia archived areas under the receiver-operating curve of around 0.91, and regression models estimating disease severity obtained correlation coefficients around r = 0.64. Classification and prediction model coefficients were examined and they not only were in accordance, but were in line with clinical observations of ataxia phenotypes where rate and rhythm are altered during upper extremity motor movement.
Proton Magnetic Resonance Spectroscopy for Diagnosis of Non-Motor Symptoms in Parkinson's Disease
Authors: Guan Ji-tian , Zheng Xin , Lai Lingfeng , Sun Shuyi , Geng Yiqun , Zhang Xiaolei , Zhou Teng , Wu Huan-ze , Chen Jia-qing , Yang Zhong-xian , zheng Xiao-hong , Wang Jia-xu , Chen Wei , Zhang You-qiao
Published: February 2022

Background

The current diagnosis of Parkinson's disease (PD) is mainly based on the typical clinical manifestations. However, 60% dopaminergic neurons have died when the typical clinical manifestations occur. Predictive neurobiomarkers may help identify those PD patients having non-motor disorders or in different stage and achieving the aim of early diagnosis. Up to date, few if any neuroimaging techniques have been described useful for non-movement disorders diagnosis in PD patients. Here, we investigated the alteration of metabolites in PD patients in different stage of PD and non-motor symptoms including sleep, gastrointestinal and cognitive dysfunction, by using the 1H-MRS.

Methods

A total of 48 subjects were included between 2017 and 2019: 37 PD (15 men, age 47–82 years) and 11 healthy people (8 men, age 49–74 years). All participants underwent MRI and multi-voxel 1H-MRS examination within 3 days in admission. Six kinds of metabolites, such as creatine (Cr), N-acetyl aspartate/creatine (NAA/Cr), N-acetyl aspartate/choline (NAA/Cho), choline/creatine (Cho/Cr), lipid/creatine (LL/Cr), and myo-Inositol/creatine ratio (mI/Cr) were tested among the PD group and the control groups. Statistical analyses and correlation analyses were performed by using SPSS. The p < 0.05 was considered statistically significant.

Results

Compared late PD group with a control group or early group, higher Cr ratio and lower NAA/Cr ratio were observed in the late PD group (p < 0.05). The mI/Cr in the late PD group was also lower than that in the early PD group (p < 0.05). Regarding the relationship between metabolites and NMS, Cho/Cr was higher in the sleep disorder group, whereas mI/Cr was lower in the gastrointestinal dysfunction group in comparison with the non-symptom groups. Moreover, Cr, Cho/Cr, mI/Cr, and LL/Cr were identified to have higher concentrations in the cognitive group in thalamus.

Conclusions

Proton magnetic resonance spectroscopy is an advanced tool to quantify the metabolic changes in PD. Three biomarkers (Cr, NAA/Cr, and mI/Cr) were detected in the late stage of PD, suggesting that these markers might be potential to imply the progression of PD. In addition, subgroups analysis showed that MRS of thalamus is a sensitive region for the detection of cognitive decline in PD, and the alteration of neurochemicals (involving Cr, Cho, mI, and LL) may be promising biomarkers to predict cognitive decline in PD.
Investigation of the Association Between History of Learning Disabilities and Primary Progressive Aphasia in Brazilian Portuguese Speakers
Authors: dos Reis Talita Gallas , Machado Thais Helena , Caramelli Paulo , Scornavacca Francisco , Fernandez Liana Lisboa , Beber Bárbara Costa
Published: February 2022

Primary Progressive Aphasia (PPA) is a neurological syndrome characterized by impaired language due to neurodegeneration. It is subdivided into three variants: semantic, agrammatic or nonfluent, and logopenic. Pieces of evidence have suggested that learning disabilities in childhood, such as dyslexia, might be susceptibility factors in the occurrence of PPA in adulthood. The objective of this study was to verify the existence of the relationship between PPA and the history of learning disabilities of patients and their children, compared to a control group of individuals with Alzheimer's disease (AD). A questionnaire was applied to investigate the presence of indicators of learning disabilities and difficulties in individuals with PPA and AD and their children. Twenty subjects with PPA and 16 with AD participated in the study. Our findings are presented and discussed in light of the current scientific evidence and the social, educational, and economic Brazilian scenario. Despite the challenges of doing research with individuals with PPA in Brazil, we present the first evidence about the investigation of association between the history of learning disabilities and difficulties and PPA in native Brazilian Portuguese speakers.
Regulatory B Cells Are Decreased and Functionally Impaired in Myasthenia Gravis Patients
Authors: Lin Ye , Chang Ting , Lin Jiaji , Sun Chenjing , Wei Chao , Zhao Jiao , Liu Rui , Yang Kun , Li Zhuyi
Published: February 2022

Myasthenia gravis (MG) is an autoimmune disease mediated by B cells secreting autoantibodies. Regulatory B (Breg) cells confirmed to have an immunosuppressive function play an important role in many autoimmune diseases. However, what about the changes in Breg cells in the thymus and peripheral blood of MG patients? The changes in the proportion of Breg cells in the peripheral blood of 41 MG patients without any drug treatment and 30 healthy controls were detected by flow cytometry. We found that the proportions of CD19+IL-10+cells and CD19+CD24hiCD38hicell subsets in MG patients were significantly lower than those in healthy controls. Then, we detected the proportion of CD19+IL-10+cells in thymus tissues of 10 healthy children, 4 healthy adults, and 12 MG patients by flow cytometry. However, the percentage of CD19+IL-10+cells was highest in healthy children (~8%), followed by healthy adults (~3%), and was lowest in MG patients (~0.5%). CD19+CD24hiCD38hiB cells exerted immunosuppressive functions in healthy people but were refractory in MG patients. Moreover, p-STAT3 downstream of CD40 may be impaired in CD24hiCD38hiB cells from the peripheral blood of MG patients.