bluuebunny/crossref_metadata_2025 huggingface dataset:
PAD4 Immunization Triggers Anti-Citrullinated Peptide Antibodies in Normal Mice: Analysis With Peptide Arrays
Authors: Hemon Marie F. , Lambert Nathalie C. , Arnoux Fanny , Roudier Jean , Auger Isabelle
Published: March 2022

The critical immunological event in rheumatoid arthritis (RA) is the production of antibodies to citrullinated proteins (ACPAs), ie proteins on which arginines have been transformed into citrullines by peptidyl arginine deiminases (PAD). In C3H mice, immunization with PAD4 triggers the production of ACPAs. Here, we developed a peptide array to analyze the fine specificity of anti-citrullinated peptide antibodies and used it to characterize the ACPA response after hPAD4 immunization in mice expressing different H-2 haplotypes. Sera from C3H, DBA/2, BALB/c and C57BL/6 mice immunized with human PAD4 (hPAD4) or control-matched mice immunized with phosphate buffered saline (PBS) were used to screen peptide arrays containing 169 peptides from collagen, filaggrin, EBNA, proteoglycan, enolase, alpha and beta fibrinogen, histon and vimentin. Human PAD4 immunization induced antibodies directed against numerous citrullinated peptides from fibrinogen, histon 4 and vimentin. Most peptides were recognized under their arginine and citrullinated forms. DBA/2 and BALB/c mice (H-2d) had the lowest anti-citrullinated peptide IgG responses. C3H (H-2k) and BL6 mice (H-2b) had the highest anti-citrullinated peptide IgG responses. The newly developed peptide array allows us to characterize the ACPA production after hPAD4 immunization in mice on the H-2d, H-2k or H-2b backgrounds. This sensitive tool will be useful for further studies on mice for prevention of ACPA production by PAD tolerization.
Visual Analysis of Colorectal Cancer Immunotherapy: A Bibliometric Analysis From 2012 to 2021
Authors: Ma Long , Ma Jixiang , Teng Muzhou , Li Yumin
Published: March 2022

An increasing number of studies have shown that immunotherapy serves a significant role in treating colorectal cancer (CRC) and has become a hotspot. However, few studies used the bibliometric method to analyze this field comprehensively. This study collected 1,899 records of CRC immunotherapy from 2012 to October 31, 2021, and used CiteSpace to analyze regions, institutions, journals, authors, and keywords to predict the latest trends in CRC immunotherapy research. The United States and China, contributing more than 60% of publications, were the main drivers in this field. Sun Yat-sen University was the most active institution, while the National Cancer Institute had the highest frequency of citations. Most publications were published in the Journal for Immunotherapy of Cancer. Adam E Snook was the most prolific writer, while Dung T. Le was the most commonly co-cited author. “T cell”, “MMI” and “PD-1blocked” were the most widely studied aspects of CRC immunotherapy. “Immune checkpoint inhibitor”, “combination therapy”, “drug therapy” and “liver metastases” were current research hotspots. “Tumor microenvironment”, “neutrophils”, “tumor-associated macrophages”, and “suppressor cell” have emerged as research hotspots in recent years. “Gut microbiota”, “nanoparticle” and “tumor mutational burden” as recently emerged frontiers of research that should be closely monitored.
Enhanced Immune Responses in Mice Induced by the c-di-GMP Adjuvanted Inactivated Vaccine for Pseudorabies Virus
Authors: Hou Liting , Yu Xiaoming , Zhang Yuanyuan , Du Luping , Zhang Yuanpeng , Cheng Haiwei , Zheng Qisheng , Chen Jin , Hou Jibo
Published: March 2022

Cyclic dimeric guanosine monophosphate (c-di-GMP) is a bacterial second messenger with immunomodulatory activities in mice, suggesting potential applications as a vaccine immunopotentiator or therapeutic agent. In this study, we evaluated the efficacy of c-di-GMP as an immunopotentiator for pseudorabies virus (PRV) inactivated vaccine in a murine model. We found that c-di-GMP improved the humoral and cellular immune responses induced by PRV inactivated vaccine and its effects on immunity reached the level comparable to that of a live attenuated vaccine. Furthermore, c-di-GMP enhanced the murine antibody response against the viral glycoprotein gB up to 120 days after immunization. The c-di-GMP–adjuvanted PRV inactivated vaccine induced long-term humoral immunity by promoting a potent T follicular helper cell response, which is known to directly control the magnitude of the germinal center B cell response. Furthermore, the c-di-GMP enhanced the response of bone marrow plasma cells and upregulated the expression of Bcl-2 and Mcl-1, which have been identified as anti-apoptotic regulatory genes of germinal center and memory B cells. Our findings open a new avenue for improving the immune efficacy of PRV inactivated vaccines.
Humoral and Cellular Immunogenicity and Safety of Five Different SARS-CoV-2 Vaccines in Patients With Autoimmune Rheumatic and Musculoskeletal Diseases in Remission or With Low Disease Activity and in Healthy Controls: A Single Center Study
Authors: Szebeni Gábor J. , Gémes Nikolett , Honfi Dániel , Szabó Enikő , Neuperger Patrícia , Balog József Á. , Nagy Lajos I. , Szekanecz Zoltán , Puskás László G. , Toldi Gergely , Balog Attila
Published: March 2022

Background

Vaccine-induced immunity is essential for controlling the COVID-19 pandemic. Data on humoral and cellular immunogenicity and safety of different SARS-CoV-2 vaccines in patients with autoimmune rheumatic and musculoskeletal diseases (RMDs) are limited.

Methods

A single center observational study evaluated the immunogenicity and safety of the two-dose regimen of the BBIBP-CorV inactivated, Gam-COVID-Vac and AZD1222 adenovirus-based, and BNT162b2 and mRNA-1273 mRNA-based vaccines in patients with RMDs (n = 89) compared with healthy controls (n = 74). Neutralizing anti-RBD (receptor binding domain) specific antibodies and SARS-CoV-2 specific T-cell response were measured one and four months after the second vaccine dose in parallel with vaccination efficacy and safety.

Results

Disease-specific comparison showed that antibody response at four months was higher in spondylarthropathies compared to rheumatoid arthritis and autoimmune RMDs. Risk factors for reduced immunogenicity included longer disease duration, positive immunoserological profile and anti-CD20 therapy of patients. The rate of positive anti-RBD antibody response for healthy controls versus patients after 4 months post vaccination was 69% vs. 55% for the inactivated viral vaccine BBIBP-CorV, 97% vs. 53% for the pooled data of adenovirus vector-based vaccines Gam-COVID-Vac and AZD1222, or 100% vs. 81% for the pooled data of mRNA vaccines BNT162b2 and mRNA-1273, respectively. Patients who received the Gam-COVID-Vac or mRNA-1273 vaccines had a higher proportion of TNF-α producing CD4+ T-cells upon SARS-CoV-2 antigen stimulation compared to the inactivated viral vaccine.

Conclusion

All five investigated vaccines were immunogenic in the majority of patients and healthy controls with variable antibody and T-cell response and an acceptable safety profile.
Early-Life Antibiotic Exposure Associated With Varicella Occurrence and Breakthrough Infections: Evidence From Nationwide Pre-Vaccination and Post-Vaccination Cohorts
Authors: Lin Teng-Li , Fan Yi-Hsuan , Chang Yi-Ling , Ho Hsiu J. , Liang Li-Lin , Chen Yi-Ju , Wu Chun-Ying
Published: March 2022

Background

Antibiotic-driven dysbiosis may impair immune function and reduce vaccine-induced antibody titers.

Objectives

This study aims to investigate the impacts of early-life antibiotic exposure on subsequent varicella and breakthrough infections.

Methods

This is a nationwide matched cohort study. From Taiwan’s National Health Insurance Research Database, we initially enrolled 187,921 children born from 1997 to 2010. Since 2003, the Taiwan government has implemented a one-dose universal varicella vaccination program for children aged 1 year. We identified 82,716 children born during the period 1997 to 2003 (pre-vaccination era) and 48,254 children born from July 1, 2004, to 2009 (vaccination era). In the pre-vaccination era, 4,246 children exposed to antibiotics for at least 7 days within the first 2 years of life (Unvaccinated A-cohort) were compared with reference children not exposed to antibiotics (Unvaccinated R-cohort), with 1:1 matching for gender, propensity score, and non-antibiotic microbiota-altering medications. Using the same process, 9,531 children in the Vaccinated A-cohort and Vaccinated R-cohort were enrolled from the vaccination era and compared. The primary outcome was varicella. In each era, demographic characteristics were compared, and cumulative incidences of varicella were calculated. Cox proportional hazards model was used to examine associations.

Results

In the pre-vaccination era, the 5-year cumulative incidence of varicella in the Unvaccinated A-cohort (23.45%, 95% CI 22.20% to 24.70%) was significantly higher than in the Unvaccinated R-cohort (16.72%, 95% CI 15.62% to 17.82%) (p<.001). In the vaccination era, a significantly higher 5-year cumulative incidence of varicella was observed in the Vaccinated A-cohort (1.63%, 95% 1.32% to 1.93%) than in the Vaccinated R-cohort (1.19%, 95% CI 0.90% to 0.45%) (p=0.006). On multivariate analyses, early-life antibiotic exposure was an independent risk factor for varicella occurrence in the pre-vaccination (adjusted hazard ratio [aHR] 1.92, 95% CI 1.74 to 2.12) and vaccination eras (aHR 1.66, 95% CI 1.24 to 2.23). The use of penicillins, cephalosporins, macrolides, or sulfonamides in infancy was all positively associated with childhood varicella regardless of vaccine administration.

Conclusions

Antibiotic exposure in early life is associated with varicella occurrence and breakthrough infections.
Similar CD4/CD8 Ratio Recovery After Initiation of Dolutegravir Plus Lamivudine Versus Dolutegravir or Bictegravir-Based Three-Drug Regimens in Naive Adults With HIV
Authors: Martínez-Sanz Javier , Ron Raquel , Moreno Elena , Sánchez-Conde Matilde , Muriel Alfonso , López Cortés Luis Fernando , Blanco José Ramón , Pineda Juan Antonio , Mena Álvaro , Calzado Isbert Sonia , Moreno Santiago , Serrano-Villar Sergio
Published: March 2022

Background

The initiation of antiretroviral treatment based on a 2-drug regimen (2DR) with dolutegravir plus lamivudine has demonstrated non-inferior efficacy than dolutegravir-based three-drug regimens (3DR). We aimed to assess whether the treatment initiation with this 2DR has a different impact on the CD4/CD8 ratio recovery than INSTI-based 3DR.

Methods

We emulated a target trial using observational data from the Spanish HIV Research Network cohort (CoRIS). The outcomes of interest were the normalization of the CD4/CD8 ratio at 48 weeks using three different cutoffs: 0.5, 1.0, and 1.5. We matched each participant who started 2DR with up to four participants who received 3DR. Subsequently, we fitted generalized estimating equation (GEE) models and used the Kaplan–Meier method for survival curves.

Results

We included 485, 805, and 924 participants for cutoffs of 0.5, 1.0, and 1.5, respectively. At 48 weeks, 45% of participants achieved a CD4/CD8 ratio >0.5, 15% achieved a ratio >1.0, and 6% achieved a ratio >1.5. GEE models yielded a similar risk of reaching a CD4/CD8 ratio >0.5 (OR 1.00, 95% CI 0.67 - 1.50), CD4/CD8 >1.0 (OR 1.03, 95% CI 0.68 - 1.58), and CD4/CD8 >1.5 (OR 0.86, 95% CI 0.48 - 1.54) between both treatment strategies. There were no differences between 2DR and 3DR in the incidence ratio of CD4/CD8 ratio normalization at 0.5, 1.0 and 1.5 cut-offs.

Conclusions

In this large cohort study in people with HIV, ART initiation with dolutegravir plus lamivudine vs. dolutegravir or bictegravir-based triple antiretroviral therapy showed no difference in the rates of CD4/CD8 normalization at 48 weeks.
Neuromyelitis Optica Spectrum Disorder With Anti-Aquaporin-4 Antibody: Outcome Prediction Models
Authors: Wang Liang , Du Lei , Li Qinying , Li Fang , Wang Bei , Zhao Yuanqi , Meng Qiang , Li Wenyu , Pan Juyuan , Xia Junhui , Wu Shitao , Yang Jie , Li Heng , Ma Jianhua , ZhangBao Jingzi , Huang Wenjuan , Chang Xuechun , Tan Hongmei , Yu Jian , Zhou Lei , Lu Chuanzhen , Wang Min , Dong Qiang , Lu Jiahong , Zhao Chongbo , Quan Chao
Published: March 2022

Background

Recognizing the predictors of disease relapses in patients with anti-aquaporin-4 antibody (AQP4-ab)-positive neuromyelitis optica spectrum disorder (NMOSD) is essential for individualized treatment strategy. We aimed to identify the factors that predicted relapses among patients with AQP4-ab-positive NMOSD, develop outcome prediction models, and validate them in a multicenter validation cohort.

Methods

Between January 2015 and December 2020, 820 patients with NMOSD were registered at Huashan Hospital. We retrospectively reviewed their medical records, and included 358 AQP4-ab-positive patients with 1135 treatment episodes. Univariate and multivariate analyses were used to explore the predictors of relapse, severe visual or motor disability during follow-up. A model predicting the 1- and 2-year relapse-free probability was developed and validated in an external validation cohort of 92 patients with 213 treatment episodes.

Results

Lower serum AQP4-ab titer (< 1:100), higher Expanded Disability Status Scale (EDSS) score at onset (≥ 2.5), and use of intravenous methylprednisolone (IVMP) at the first attack predicted an overall lower annualized relapse rate. Older age (> 48 years), optic neuritis at onset, and higher onset EDSS score (≥ 2.5) significantly increased the risk for blindness, while IVMP at the first attack and maintenance therapy reduced the risk for blindness. Myelitis at onset increased the possibility of motor disability (EDSS ≥ 6.0), severe motor disability or death (EDSS ≥ 8.0), while maintenance therapy reduced these possibilities. Anderson and Gill model identified that the risk factors predicting recurrent relapses under certain treatment status were female gender, high AQP4-ab titer (≥ 1:100), previous attack under same therapy, lower EDSS score at treatment initiation (< 2.5), and no maintenance therapy or oral prednisone lasting less than 6 months. A nomogram using the above factors showed good discrimination and calibration abilities. The concordance indexes in the primary and validation cohort were 0.66 and 0.65, respectively.

Conclusion

This study reports the demographic, clinical and therapeutic predictors of relapse, and severe visual or motor disability in NMOSD. Early identification of patients at risk of unfavorable outcomes is of paramount importance to inform treatment decisions.
Bioaccumulation of Per and Polyfluoroalkyl Substances in Antarctic Breeding South Polar Skuas (Catharacta maccormicki) and Their Prey
Authors: Alfaro Garcia Laura Andrea , Descamps Sébastien , Herzke Dorte , Chastel Olivier , Carravieri Alice , Cherel Yves , Labadie Pierre , Budzinski Hélène , Munoz Gabriel , Bustamante Paco , Polder Anuschka , Gabrielsen Geir Wing , Bustnes Jan Ove , Borgå Katrine
Published: March 2022

Per and polyfluoroalkyl substances (PFASs) are found in Antarctic wildlife, with high levels in the avian top predator south polar skua (Catharacta maccormicki). As increasing PFAS concentrations were found in the south polar skua during the breeding season in Antarctica, we hypothesised that available prey during the breeding period contributes significantly to the PFAS contamination in skuas. To test this, we compared PFAS in south polar skuas and their main prey from two breeding sites on opposite sides of the Antarctic continent: Antarctic petrel (Thalassoica antarctica) stomach content, eggs, chicks, and adults from Svarthamaren in Dronning Maud Land and Adélie penguin chicks (Pygoscelis adeliae) from Dumont d’Urville in Adélie Land. Of the 22 PFAS analysed, seven were present in the majority of samples, except petrel stomach content [only perfluoroundecanoate (PFUnA) present] and Adélie penguins (only four compounds present), with increasing concentrations from the prey to the skuas. The biomagnification factors (BMFs) were higher at Dumont d’Urville than Svarthamaren. When adjusted to reflect one trophic level difference, the BMFs at Svarthamaren remained the same, whereas the ones at Dumont d’Urville doubled. At both the colonies, the skua PFAS pattern was dominated by perfluorooctanesulfonic acid (PFOS), followed by PFUnA, but differed with the presence of branched PFOS and perfluorotetradecanoate (PFTeA) and lack of perfluorononanoate (PFNA) and perfluorodecanoate (PFDA) at Dumont d’Urville. At Svarthamaren, the pattern in the prey was comparable to the skuas, but with a higher relative contribution of PFTeA in prey. At Dumont d’Urville, the pattern in the prey differed from the skuas, with the domination of PFUnA and the general lack of PFOS in prey. Even though the PFAS levels are low in Antarctic year-round resident prey, the three lines of evidence (pattern, BMF difference, and BMF adjusted to one trophic level) suggest that the Antarctic petrel are the significant source of PFAS in the Svarthamaren skuas, whereas the skuas in Dumont d’Urville have other important sources to PFAS than Adélie penguin, either in the continent or external on the inter-breeding foraging grounds far from Antarctica.
Aged Plastic Leaching of Dissolved Organic Matter Is Two Orders of Magnitude Higher Than Virgin Plastic Leading to a Strong Uplift in Marine Microbial Activity
Authors: Romera-Castillo Cristina , Birnstiel Stéphanie , Álvarez-Salgado Xosé Antón , Sebastián Marta
Published: March 2022

Plastic debris reaching the ocean is exponentially increasing in parallel with plastic production. Once into seawater, plastic starts to leach organic compounds that are presumably additives and plastic oligomers, and that process is enhanced by solar radiation. From previous studies with virgin plastic, it has been estimated that up to 23,600 metric tons of dissolved organic carbon (DOC) can be released into seawater every year from all the plastic entering the ocean. However, most plastic found in the ocean has been aged through weathering and sunlight radiation, which could result in enhanced leaching. Despite this, dissolved organic matter (DOM) leaching from aged plastic and the effect on microbial communities and their activity has never been explored. Here we studied DOM leaching by aged plastic collected from a sand beach and how it compares with that from virgin plastic. After characterizing the DOM leached from plastic through fluorescence techniques, we also explored the bioavailability of the DOM leached and its fluorescent fraction through biodegradation experiments. Finally, we determined single cell activities of the prokaryotic community growing on the plastic leachates. We found that the release of DOC by aged plastic was two order of magnitude higher than that leached by virgin new plastic. Extrapolating that into the ocean and assuming that most of the plastic arriving there is not new, we estimated that up to 57,000 metric tons of DOC can be released by plastic debris every year. A fraction of the DOM released by plastic was fluorescent (FDOM), especially in the protein-like region, and bioavailable to microbial uptake, as it is also shown by the increase in the single cell activities of the bacteria growing on the leachates. Since most plastics in the ocean have been exposed to sunlight radiation provoking aging, our results unveil that the amount of carbon released by plastics is much higher than hitherto recognized, and thus will have a stronger impact in the oceanic carbon cycle and in marine ecosystems.
Conductive, Anti-Corrosion, Self-Healing Smart Coating Technology Incorporating Graphene-Based Nanocomposite Matrix
Authors: Benavides-Guerrero Jaime , Banerjee Debika , Gedamu Dawit , Gerlein Luis Felipe , Cloutier Sylvain G.
Published: March 2022

Chromate conversion coatings have been in service for decades providing robust corrosion protection to a wide variety of aluminum alloys. However, it is also known that anti-corrosive coatings containing Cr6+ contributes to DNA damage, cause cancer and are not environmentally friendly. Consequently, regulatory restrictions over the use Cr6+ were established to mitigate the environmental damage and health problems. To answer to this hurdle and to meet the emergent need for environmentally friendly anti-corrosive coatings, we have successfully developed an innovative coating that combines anti-corrosive, low electrical resistance, and self-healing properties. First, we present two different coatings, that aim to display low electrical resistance properties: one containing only graphene and the other containing Zn nanoparticles and graphene. Confocal laser imaging and SEM microscopy was used to observe the morphology of the coatings. The electrical resistance was measured using the 4-wire connection Kelvin method. We compare the anticorrosive response for both coatings under neutral salt spray test (NSSt). Raman spectroscopy was performed before and after to understand the effect of NSSt corrosive species on the coatings. Then, we select the coating with lower electrical resistance, and we program on it a self-healing mechanism to boost its life service. Finally cyclic voltammetry is performed to confirm the excellent blocking properties of the tested coatings. All the coatings presented in this work are applied on aluminum AA 2024T351 and the optimal spray parameters for nanofillers dispersion are obtained. Our findings show great potential for preventing corrosion and compatibility with fully automated large-scale applications in different fields such as aerospace, automotive, construction, submarines and many more.
Investigation of Serum and Macular Carotenoids in Central Serous Chorioretinopathy
Authors: Ji Yuying , Gan Yuhong , Su Yongyue , Zhang Yining , Li Miaoling , Mi Lan , Zuo Chengguo , Wen Feng
Published: April 2022

Purpose

This study aimed to evaluate serum lutein and zeaxanthin levels and macular pigment optical density (MPOD) in central serous chorioretinopathy (CSC).

Methods

Fifty-four patients with acute CSC (28–56 years old; 44 men and 10 women) and 62 matched controls were enrolled. Serum lutein and zeaxanthin were measured using the high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method. MPOD was measured at 7° of eccentricity and reported in parameters as “max” and “mean” optical density (OD) (Visucam 200; Carl Zeiss Meditec). MPOD was re-measured in 9 patients whose subretinal fluid was absorbed.

Results

The average max OD and the mean OD in CSC were 0.275 ± 0.047 d.u. and 0.098 ± 0.018 d.u., respectively, which were significantly lower than the control (p < 0.001). The average MPOD value in the unaffected eyes of patients with CSC was 0.298 ± 0.045 for max OD, 0.106 ± 0.017 for mean OD, and both were significantly lower compared with the affected eyes (p < 0.001 for max OD, p = 0.01 for mean OD). In the 9 follow-up patients, the decrease in MPOD was partially recovered. The mean serum level was 409.80 ± 182.52 ng/ml for lutein and 22.97 ± 12.23 ng/ml for zeaxanthin in patients with CSC. In controls, the mean serum level was 393.38 ± 202.44 ng/ml for lutein and 22.16 ± 10.12 ng/ml for zeaxanthin. The difference was not statistically significant (p = 0.649, p = 0.698, respectively).

Conclusion

MPOD decreased within 7° of eccentricity in CSC without serum lutein and zeaxanthin changes. The decrease may be due to the subretinal fluid. Whether local oxidative stress is involved in CSC and the supplementation with lutein and zeaxanthin is helpful for CSC requires further investigation.
Measures of Clonal Hematopoiesis: Are We Missing Something?
Authors: Bystrykh Leonid V. , Belderbos Mirjam E.
Published: March 2022

Clonal Hematopoiesis (CH) is a common, age-related phenomenon of growing scientific interest, due to its association with hematologic malignancy, cardiovascular disease and decreased overall survival. CH is commonly attributed to the preferential outgrowth of a mutant hematopoietic stem cell (HSC) with enhanced fitness, resulting in clonal imbalance. In-depth understanding of the relation between HSC clonal dynamics, CH and hematologic malignancy requires integration of fundamental lineage tracing studies with clinical data. However, this is hampered by lack of a uniform definition of CH and by inconsistency in the analytical methods used for its quantification. Here, we propose a conceptual and analytical framework for the definition and measurement of CH. First, we transformed the conceptual definition of CH into the CH index, which provides a quantitative measure of clone numbers and sizes. Next, we generated a set of synthetic data, based on the beta-distribution, to simulate clonal populations with different degrees of imbalance. Using these clonal distributions and the CH index as a reference, we tested several established indices of clonal diversity and (in-)equality for their ability to detect and quantify CH. We found that the CH index was distinct from any of the other tested indices. Nonetheless, the diversity indices (Shannon, Simpson) more closely resembled the CH index than the inequality indices (Gini, Pielou). Notably, whereas the inequality indices mainly responded to changes in clone sizes, the CH index and the tested diversity indices also responded to changes in the number of clones in a sample. Accordingly, these simulations indicate that CH can result not only by skewing clonal abundancies, but also by variation in their overall numbers. Altogether, our model-based approach illustrates how a formalized definition and quantification of CH can provide insights into its pathogenesis. In the future, use of the CH index or Shannon index to quantify clonal diversity in fundamental as well as clinical clone-tracing studies will promote cross-disciplinary discussion and progress in the field.
High-Frequency Variability of Bacterioplankton in Response to Environmental Drivers in Red Sea Coastal Waters
Authors: Ansari Mohd Ikram , Calleja Maria LI. , Silva Luis , Viegas Miguel , Ngugi David Kamanda , Huete-Stauffer Tamara Megan , Morán Xosé Anxelu G.
Published: March 2022

Autotrophic and heterotrophic bacterioplankton are essential to the biogeochemistry of tropical ecosystems. However, the processes that govern their dynamics are not well known. We provide here a high-frequency assessment of bacterial community dynamics and concurrent environmental factors in Red Sea coastal waters. Weekly sampling of surface samples during a full annual cycle at an enclosed station revealed high variability in ecological conditions, which reflected in changes of major bacterioplankton communities. Temperature varied between 23 and 34°C during the sampling period. Autotrophic (Synechococcus, 1.7–16.2 × 104 cells mL−1) and heterotrophic bacteria (1.6–4.3 × 105 cells mL−1) showed two maxima in abundance in spring and summer, while minima were found in winter and autumn. Heterotrophic cells with high nucleic acid content (HNA) peaked in July, but their contribution to the total cell counts (35–60%) did not show a clear seasonal pattern. Actively respiring cells (CTC+) contributed between 4 and 51% of the total number of heterotrophic bacteria, while live cells (with intact membrane) consistently accounted for over 90%. Sequenced 16S rRNA amplicons revealed a predominance of Proteobacteria in summer and autumn (>40%) and a smaller contribution in winter (21–24%), with members of the Alphaproteobacteria class dominating throughout the year. The contribution of the Flavobacteriaceae family was highest in winter (21%), while the Rhodobacteraceae contribution was lowest (6%). Temperature, chlorophyll-a, and dissolved organic carbon concentration were the environmental variables with the greatest effects on bacterial abundance and diversity patterns.
Skin Microbiota Variation Among Bat Species in China and Their Potential Defense Against Pathogens
Authors: Li Zhongle , Li Aoqiang , Dai Wentao , Leng Haixia , Liu Sen , Jin Longru , Sun Keping , Feng Jiang
Published: March 2022

Host-associated skin bacteria are essential for resisting pathogen infections and maintaining health. However, we have little understanding of how chiropteran skin microbiota are distributed among bat species and their habitats, or of their putative roles in defending against Pseudogymnoascus destructans in China. In this study, we characterized the skin microbiomes of four bat species at five localities using 16S rRNA gene amplicon sequencing to understand their skin microbial composition, structure, and putative relationship with disease. The alpha- and beta-diversities of skin microbiota differed significantly among the bat species, and the differences were affected by environmental temperature, sampling sites, and host body condition. The chiropteran skin microbial communities were enriched in bacterial taxa that had low relative abundances in the environment. Most of the potential functions of skin microbiota in bat species were associated with metabolism. Focusing on their functions of defense against pathogens, we found that skin microbiota could metabolize a variety of active substances that could be potentially used to fight P. destructans. The skin microbial communities of bats in China are related to the environment and the bat host, and may be involved in the host’s defense against pathogens.
Integrated Trinity Test With RPA-CRISPR/Cas12a-Fluorescence for Real-Time Detection of Respiratory Syncytial Virus A or B
Authors: Gong Ling , Wang Xiaowen , Li Zhu , Huang Guichuan , Zhang Wei , Nie Jin , Wu Chunyan , Liu Daishun
Published: March 2022

Respiratory syncytial virus (RSV) is a common virus that causes respiratory infection, especially severe respiratory infection in infants and young children, the elderly people over 65 years old, and people with weak immunity. Currently, RSV infection has no effective vaccine and antiviral treatment. The number of deaths due to RSV infection increases every year. Moreover, RSV A infection occurs in a large number and has severe clinical symptoms and complications than RSV B infection. Therefore, the development of a simple, rapid, and inexpensive detection method with high amplification efficiency, high sensitivity, and specificity is very important for the diagnosis of RSV A or RSV B infection, which can help in the early clinical medication and prevent the progress of the disease. Therefore, we developed an integrated trinity test with an RPA-CRISPR/Cas12a-fluorescence (termed IT-RAISE) assay system to detect RSV A or RSV B. The characteristic of the IT-RAISE system is that after target recognition, the reporter single-stranded DNA (ssDNA) is cleaved by Cas12a that is activated by different crRNAs to detect the generated fluorescent signal. This method is simple and helps in adding all reagents rapidly. It is a high-sensitive method that can detect 1.38 × 101 copies/μl of the target sequences, and it can distinguish RSV A or RSV B infection within 37 min. In addition, clinical specimens were detected for IT-RAISE system. It was found that the sensitivity and specificity of RSV A were 73.08 and 90%, respectively, and those of RSV B were 42.86 and 93.33%, respectively. The cost of ONE specimen for IT-RAISE system was approximately $ 2.6 (excluding rapid RNA extraction and reverse transcription costs). IT-RAISE system has good clinical application prospects for detecting RSV A or RSV B infection; it is a simple, rapid, and inexpensive method with high amplification efficiency, high sensitivity, and high specificity. The IT-RAISE system might also detect other viral or bacterial infections.
Metagenomic Insights Into the Changes of Antibiotic Resistance and Pathogenicity Factor Pools Upon Thermophilic Composting of Human Excreta
Authors: Werner Katharina A. , Schneider Dominik , Poehlein Anja , Diederich Nina , Feyen Lara , Axtmann Katharina , Hübner Tobias , Brüggemann Nicolas , Prost Katharina , Daniel Rolf , Grohmann Elisabeth
Published: March 2022

In times of climate change, practicing a form of sustainable, climate-resilient and productive agriculture is of primordial importance. Compost could be one form of sustainable fertilizer, which is increasing humus, water holding capacity, and nutrient contents of soils. It could thereby strengthen agriculture toward the adverse effects of climate change, especially when additionally combined with biochar. To get access to sufficient amounts of suitable materials for composting, resources, which are currently treated as waste, such as human excreta, could be a promising option. However, the safety of the produced compost regarding human pathogens, pharmaceuticals (like antibiotics) and related resistance genes must be considered. In this context, we have investigated the effect of 140- and 154-days of thermophilic composting on the hygienization of human excreta and saw dust from dry toilets together with straw and green cuttings with and without addition of biochar. Compost samples were taken at the beginning and end of the composting process and metagenomic analysis was conducted to assess the fate of antibiotic resistance genes (ARGs) and pathogenicity factors of the microbial community over composting. Potential ARGs conferring resistance to major classes of antibiotics, such as beta-lactam antibiotics, vancomycin, the MLSB group, aminoglycosides, tetracyclines and quinolones were detected in all samples. However, relative abundance of ARGs decreased from the beginning to the end of composting. This trend was also found for genes encoding type III, type IV, and type VI secretion systems, that are involved in pathogenicity, protein effector transport into eukaryotic cells and horizontal gene transfer between bacteria, respectively. The results suggest that the occurrence of potentially pathogenic microorganisms harboring ARGs declines during thermophilic composting. Nevertheless, ARG levels did not decline below the detection limit of quantitative PCR (qPCR). Thresholds for the usage of compost regarding acceptable resistance gene levels are yet to be evaluated and defined.
PPARγ Ameliorates Mycobacterium tuberculosis H37Ra-Induced Foamy Macrophage Formation via the ABCG1-Dependent Cholesterol Efflux Pathway in THP-1 Macrophages
Authors: Ye Yutao , Liu Jun , Guo Yang , Gao Yujie , Rao Jiayue , Su Rigu , Zhang Lu , Huang Zikun , Luo Qing , Li Junming
Published: March 2022

Foamy macrophages are present during the course of Mycobacterium tuberculosis (Mtb) infection and seems to be nutrient-rich reservoir and secure reservoir for the bacilli, which leads to bacterial persistence and infection transmission. Peroxisome proliferator activated receptor γ (PPARγ) is a key transcription factor for cholesterol metabolism in macrophages and its role in regulating atherosclerosis related foamy macrophages (FMs) formation has been well-studied. However, knowledge about the mechanism of PPARγ regulating Mtb infection induced FM formation remains very limited. In this study, we investigate the functional role of PPARγ in Mtb H37Ra infection-induced foamy macrophages formation. H37Ra infection induced a time-dependent decreased expression of PPARγ that paralleled the augmented lipid body formation in THP1-derived macrophages. PPARγ antagonist GW9662 significantly potentiate H37Ra induced lipid body formation and inhibit ABCG1 expression, overexpression of ABCG1 by transduced macrophages with lentivirus significantly reversed the promotion effect of GW9662 on FM formation. Moreover, Treatment with a TLR2 neutralizing antibody ameliorated the activation of ABCG1 by Mtb H37Ra without significantly effecting the suppression of PPARγ, suggesting a greater role for TLR2 to regulate ABCG1 compared to PPARγ. Overall, this study showed that PPARγ is involved in ameliorating FM formation by regulating ABCG1 expression, these observations expose a novel role of PPARγ in the Mtb infection induced FM formation.
A Transcriptomic Study Reveals That Fish Vibriosis Due to the Zoonotic Pathogen Vibrio vulnificus Is an Acute Inflammatory Disease in Which Erythrocytes May Play an Important Role
Authors: Hernández-Cabanyero Carla , Sanjuán Eva , Reyes-López Felipe E. , Vallejos-Vidal Eva , Tort Lluis , Amaro Carmen
Published: April 2022

Vibrio vulnificus is a marine zoonotic pathogen associated with fish farms that is considered a biomarker of climate change. Zoonotic strains trigger a rapid death of their susceptible hosts (fish or humans) by septicemia that has been linked to a cytokine storm in mice. Therefore, we hypothesize that V. vulnificus also causes fish death by triggering a cytokine storm in which red blood cells (RBCs), as nucleated cells in fish, could play an active role. To do it, we used the eel immersion infection model and then analyzed the transcriptome in RBCs, white BCs, and whole blood using an eel-specific microarray platform. Our results demonstrate that V. vulnificus triggers an acute but atypical inflammatory response that occurs in two main phases. The early phase (3 h post-infection [hpi]) is characterized by the upregulation of several genes for proinflammatory cytokines related to the mucosal immune response (il17a/f1 and il20) along with genes for antiviral cytokines (il12β) and antiviral factors (ifna and ifnc). In contrast, the late phase (12 hpi) is based on the upregulation of genes for typical inflammatory cytokines (il1β), endothelial destruction (mmp9 and hyal2), and, interestingly, genes related to an RNA-based immune response (sidt1). Functional assays revealed significant proteolytic and hemolytic activity in serum at 12 hpi that would explain the hemorrhages characteristic of this septicemia in fish. As expected, we found evidence that RBCs are transcriptionally active and contribute to this atypical immune response, especially in the short term. Based on a selected set of marker genes, we propose here an in vivo RT-qPCR assay that allows detection of early sepsis caused by V. vulnificus. Finally, we develop a model of sepsis that could serve as a basis for understanding sepsis caused by V. vulnificus not only in fish but also in humans.
AwAreA Regulates Morphological Development, Ochratoxin A Production, and Fungal Pathogenicity of Food Spoilage Fungus Aspergillus westerdijkiae Revealed by an Efficient Gene Targeting System
Authors: Wang Gang , Li Yujie , Yang Bolei , Li Erfeng , Wu Wenqing , Si Peidong , Xing Fuguo
Published: March 2022

Aspergillus westerdijkiae, the producer of ochratoxin A (OTA), which is of worldwide concern, is an import fungal species in agriculture, food, and industry. Here, we got the uridine auxotrophic mutant of A. westerdijkiae by deleting AwpyrG. The ΔAwpyrG could be used for bio-transformation with exogenous AfpyrG expression cassette as a selection marker. In order to enhance the efficiency of gene targeting, Awku70 and Awlig4 were homologously deleted from ΔAwpyrG. The efficiencies of homologous replacement for ΔAwku70 and ΔAwlig4 were 95.7 and 87.0% in the deletion of AwAreA, respectively, demonstrating a drastic increase from 4.3% of the wild type (WT) strain. Furthermore, the function of AwAreA was identified with AwAreA deletion mutant and the control strain ΔAwku70. AwAreA regulated the growth and conidiation of A. westerdijkiae in response to nitrogen sources. The concentration of OTA for ΔAwku70 was in the range of 19.4 to 186.9 ng/cm2 on all kinds of nitrogen sources. The OTA production influenced by the deletion of AwAreA was different based on nitrogen sources. Pathogenicity assays on pears, grapes, salted meat, and cheese showed that AwAreA acted as a negative regulator in the infection of food substrates. Therefore, the genetic methods and engineered strains enable us to substantially expand the use of A. westerdijkiae, one of more than twenty OTA-producing fungi, in the study of mycotoxin biosynthesis and regulation, and consequently to aim at providing new ways for controlling this pathogen.
Hepatitis B Virus Genotype G: The Odd Cousin of the Family
Authors: Araujo Natalia M. , Osiowy Carla
Published: March 2022

With a widespread distribution but low prevalence worldwide, the hepatitis B virus (HBV) genotype G (HBV/G) is a recently described genotype for which the origin and biology are poorly understood. Some unique features make HBV/G the most peculiar of all genotypes. In this review, we reflect on the major milestones in HBV/G research, highlighting the main aspects of its discovery, molecular epidemiology, and virological and clinical characteristics. We also illustrate common pitfalls in the routine detection, which may lead to underestimated rates of HBV/G infection. Large-scale analysis of data from dozens of articles was further performed, with the aim of gaining comprehensive insights into the epidemiological aspects of HBV/G. Finally, we point out recent findings on HBV/G origins and discuss new perspectives regarding the evolutionary history of HBV/G and the plausibility of an African geographic re-emergence of this genotype.
Network Pharmacology and Experimental Validation to Reveal the Pharmacological Mechanisms of Chongcaoyishen Decoction Against Chronic Kidney Disease
Authors: Fan Zhenliang , Chen Jingjing , Yang Qiaorui , He Jiabei
Published: March 2022

Objective: To explore the pharmacological mechanisms of Chongcaoyishen decoction (CCYSD) against chronic kidney disease (CKD) via network pharmacology analysis combined with experimental validation.

Methods: The bioactive components and potential regulatory targets of CCYSD were extracted from the TCMSP database, and the putative CKD-related target proteins were collected from the GeneCards and OMIM database. We matched the active ingredients with gene targets and conducted regulatory networks through Perl5 and R 3.6.1. The network visualization analysis was performed by Cytoscape 3.7.1, which contains ClueGO plug-in for GO and KEGG analysis. In vivo experiments were performed on 40 male SD rats, which were randomly divided into the control group (n = 10), sham group (n = 10), UUO group (n = 10), and CCYSD group (n = 10). A tubulointerstitial fibrosis model was constructed by unilateral ureteral obstruction through surgery and treated for seven consecutive days with CCYSD (0.00657 g/g/d). At the end of treatment, the rats were euthanized and the serum and kidney were collected for further detection.

Results: In total, 53 chemical compounds from CCYSD were identified and 12,348 CKD-related targets were collected from the OMIM and GeneCards. A total of 130 shared targets of CCYSD and CKD were acquired by Venn diagram analysis. Functional enrichment analysis suggested that CCYSD might exert its pharmacological effects in multiple biological processes, including oxidative stress, apoptosis, inflammatory response, autophagy, and fiber synthesis, and the potential targets might be associated with JAK-STAT and PI3K-AKT, as well as other signaling pathways. The results of the experiments revealed that the oxidative stress in the UUO group was significantly higher than that in normal state and was accompanied by severe tubulointerstitial fibrosis (TIF), which could be effectively reversed by CCYSD (p < 0.05). Meanwhile, aggravated mitochondrial injury and autophagy was observed in the epithelial cells of the renal tubule in the UUO group, compared to the normal ones (p < 0.05), while the intervention of CCYSD could further activate the autophagy and reduce the mitochondrial injury (p < 0.05).

Conclusion: We provide an integrative network pharmacology approach combined with in vivo experiments to explore the underlying mechanisms governing the CCYSD treatment of CKD, which indicates that the relationship between CCYSD and CKD is related to its activation of autophagy, promotion of mitochondrial degradation, and reduction of tissue oxidative stress injury, promoting the explanation and understanding of the biological mechanism of CCYSD in the treatment of CKD.
Trace Amine-Associated Receptor 2 Is Expressed in the Limbic Brain Areas and Is Involved in Dopamine Regulation and Adult Neurogenesis
Authors: Efimova Evgeniya V. , Kuvarzin Saveliy R. , Mor Mikael S. , Katolikova Nataliia V. , Shemiakova Taisiia S. , Razenkova Valeria , Ptukha Maria , Kozlova Alena A. , Murtazina Ramilya Z. , Smirnova Daria , Veshchitskii Aleksandr A. , Merkulyeva Natalia S. , Volnova Anna B. , Musienko Pavel E. , Korzhevskii Dmitrii E. , Budygin Evgeny A. , Gainetdinov Raul R.
Published: April 2022

Trace amines are a group of biogenic amines that are structurally and functionally close to classical monoamine neurotransmitters. Trace amine-associated receptors (TAARs) are emerging as promising targets for treating neuropsychiatric disorders. It has been documented that all TAARs, apart from TAAR1, function as olfactory receptors involved in sensing innate odors encoded by volatile amines. However, recently, brain expression and function of TAAR5 were also demonstrated. In this study, we assessed the behavior, brain neurochemistry, and electrophysiology changes in knock-out mice lacking Trace amine-associated receptor 2 (TAAR2) but expressing beta-Galactosidase mapping expression of TAAR2 receptors. As expected, we detected beta-Galactosidase staining in the glomerular layer of the olfactory bulb. However, we also found staining in the deeper layers of the olfactory bulb and several brain regions, including the hippocampus, cerebellum, cortex, raphe nuclei, hypothalamus, and habenula, indicating that TAAR2 receptors are not only expressed in the olfactory system but are also present in the limbic brain areas that receive olfactory input. In behavioral experiments, TAAR2 knock-out (TAAR2-KO) mice showed increased locomotor activity and less immobility in the forced swim test, with no changes in anxiety level. Furthermore, TAAR2-KO mice showed alterations in brain electrophysiological activity—particularly, decreased spectral power of the cortex and striatum in the 0, 9–20 Hz range. TAAR2-KO mice also had elevated tissue dopamine levels in the striatum and an increased dopaminergic neuron number in the Substantia Nigra. In addition, an increased brain-derived neurotrophic factor (BDNF) mRNA level in the striatum and Monoamine Oxidase B (MAO-B) mRNA level in the striatum and midbrain was found in TAAR2-KO mice. Importantly, TAAR2-KO mice demonstrated an increased neuroblast-like and proliferating cell number in the subventricular and subgranular zone, indicating increased adult neurogenesis. These data indicate that in addition to its role in the innate olfaction of volatile amines, TAAR2 is expressed in limbic brain areas and regulates the brain dopamine system, neuronal electrophysiological activity, and adult neurogenesis. These findings further corroborated observations in TAAR1-KO and TAAR5-KO mice, indicating common for TAAR family pattern of expression in limbic brain areas and role in regulating monoamine levels and adult neurogenesis, but with variable involvement of each subtype of TAAR receptors in these functions.