bluuebunny/crossref_metadata_2025 huggingface dataset:
Association mapping and candidate genes for physiological non-destructive traits: Chlorophyll content, canopy temperature, and specific leaf area under normal and saline conditions in wheat
Authors: Said Alaa A. , Moursi Yasser S. , Sallam Ahmed
Published: September 2022

Wheat plants experience substantial physiological adaptation when exposed to salt stress. Identifying such physiological mechanisms and their genetic control is especially important to improve its salt tolerance. In this study, leaf chlorophyll content (CC), leaf canopy temperature (CT), and specific leaf area (SLA) were scored in a set of 153 (103 having the best genotypic data were used for GWAS analysis) highly diverse wheat genotypes under control and salt stress. On average, CC and SLA decreased under salt stress, while the CT average was higher under salt stress compared to the control. CT was negatively and significantly correlated with CC under both conditions, while no correlation was found between SLA and CC and CT together. High genetic variation and broad-sense-heritability estimates were found among genotypes for all traits. The genome wide association study revealed important QTLs for CC under both conditions (10) and SLA under salt stress (four). These QTLs were located on chromosomes 1B, 2B, 2D, 3A, 3B, 5A, 5B, and 7B. All QTLs detected in this study had major effects with R2 extending from 20.20% to 30.90%. The analysis of gene annotation revealed three important candidate genes (TraesCS5A02G355900, TraesCS1B02G479100, and TraesCS2D02G509500). These genes are found to be involved in the response to salt stress in wheat with high expression levels under salt stress compared to control based on mining in data bases.
The role of CDPKs in plant development, nutrient and stress signaling
Authors: Dekomah Simon Dontoro , Bi Zhenzhen , Dormatey Richard , Wang Yihao , Haider Fasih Ullah , Sun Chao , Yao Panfeng , Bai Jiangping
Published: September 2022

The second messenger calcium (Ca2+) is a ubiquitous intracellular signaling molecule found in eukaryotic cells. In plants, the multigene family of calcium-dependent protein kinases (CDPKs) plays an important role in regulating plant growth, development, and stress tolerance. CDPKs sense changes in intracellular Ca2+ concentration and translate them into phosphorylation events that initiate downstream signaling processes. Several functional and expression studies on different CDPKs and their encoding genes have confirmed their multifunctional role in stress. Here, we provide an overview of the signal transduction mechanisms and functional roles of CDPKs. This review includes details on the regulation of secondary metabolites, nutrient uptake, regulation of flower development, hormonal regulation, and biotic and abiotic stress responses.
Genetic susceptibility loci for Chlamydia trachomatis endometrial infection influence expression of genes involved in T cell function, tryptophan metabolism and epithelial integrity
Authors: Zhong Wujuan , Kollipara Avinash , Liu Yutong , Wang Yuhan , O’Connell Catherine M. , Poston Taylor B. , Yount Kacy , Wiesenfeld Harold C. , Hillier Sharon L. , Li Yun , Darville Toni , Zheng Xiaojing
Published: September 2022

Objectives

Identify genetic loci of enhanced susceptibility to Chlamydial trachomatis (Ct) upper genital tract infection in women.

Methods

We performed an integrated analysis of DNA genotypes and blood-derived mRNA profiles from 200 Ct-exposed women to identify expression quantitative trait loci (eQTL) and determine their association with endometrial chlamydial infection using a mediation test. We further evaluated the effect of a lead eQTL on the expression of CD151 by immune cells from women with genotypes associated with low and high whole blood expression of CD151, respectively.

Results

We identified cis-eQTLs modulating mRNA expression of 81 genes (eGenes) associated with altered risk of ascending infection. In women with endometrial infection, eGenes involved in proinflammatory signaling were upregulated. Downregulated eGenes included genes involved in T cell functions pivotal for chlamydial control. eGenes encoding molecules linked to metabolism of tryptophan, an essential chlamydial nutrient, and formation of epithelial tight junctions were also downregulated in women with endometrial infection. A lead eSNP rs10902226 was identified regulating CD151, a tetrospanin molecule important for immune cell adhesion and migration and T cell proliferation. Further in vitro experiments showed that women with a CC genotype at rs10902226 had reduced rates of endometrial infection with increased CD151 expression in whole blood and T cells when compared to women with a GG genotype.

Conclusions

We discovered genetic variants associated with altered risk for Ct ascension. A lead eSNP for CD151 is a candidate genetic marker for enhanced CD4 T cell function and reduced susceptibility.
Dysfunctional purinergic signaling correlates with disease severity in COVID-19 patients
Authors: Pietrobon Anna Julia , Andrejew Roberta , Custódio Ricardo Wesley Alberca , Oliveira Luana de Mendonça , Scholl Juliete Nathali , Teixeira Franciane Mouradian Emidio , de Brito Cyro Alves , Glaser Talita , Kazmierski Julia , Goffinet Christine , Turdo Anna Claudia , Yendo Tatiana , Aoki Valeria , Figueiró Fabricio , Battastini Ana Maria , Ulrich Henning , Benard Gill , Duarte Alberto Jose da Silva , Sato Maria Notomi
Published: September 2022

Ectonucleotidases modulate inflammatory responses by balancing extracellular ATP and adenosine (ADO) and might be involved in COVID-19 immunopathogenesis. Here, we explored the contribution of extracellular nucleotide metabolism to COVID-19 severity in mild and severe cases of the disease. We verified that the gene expression of ectonucleotidases is reduced in the whole blood of patients with COVID-19 and is negatively correlated to levels of CRP, an inflammatory marker of disease severity. In line with these findings, COVID-19 patients present higher ATP levels in plasma and reduced levels of ADO when compared to healthy controls. Cell type-specific analysis revealed higher frequencies of CD39+ T cells in severely ill patients, while CD4+ and CD8+ expressing CD73 are reduced in this same group. The frequency of B cells CD39+CD73+ is also decreased during acute COVID-19. Interestingly, B cells from COVID-19 patients showed a reduced capacity to hydrolyze ATP into ADP and ADO. Furthermore, impaired expression of ADO receptors and a compromised activation of its signaling pathway is observed in COVID-19 patients. The presence of ADO in vitro, however, suppressed inflammatory responses triggered in patients’ cells. In summary, our findings support the idea that alterations in the metabolism of extracellular purines contribute to immune dysregulation during COVID-19, possibly favoring disease severity, and suggest that ADO may be a therapeutic approach for the disease.
SARS-CoV-2 variants Alpha, Beta, Delta and Omicron show a slower host cell interferon response compared to an early pandemic variant
Authors: Laine Larissa , Skön Marika , Väisänen Elina , Julkunen Ilkka , Österlund Pamela
Published: September 2022

Since the start of the pandemic at the end of 2019, arising mutations in SARS-CoV-2 have improved its transmission and ability to circumvent the immunity induced by vaccination and previous COVID-19 infection. Studies on the effects of SARS-CoV-2 genomic mutations on replication and innate immunity will give us valuable insight into the evolution of the virus which can aid in further development of vaccines and new treatment modalities. Here we systematically analyzed the kinetics of virus replication, innate immune activation, and host cell antiviral response patterns in Alpha, Beta, Delta, Kappa, Omicron and two early pandemic SARS-CoV-2 variant-infected human lung epithelial Calu-3 cells. We observed overall comparable replication patterns for these variants with modest variations. Particularly, the sublineages of Omicron BA.1, BA.2 and a recombinant sublineage, XJ, all showed attenuated replication in Calu-3 cells compared to Alpha and Delta. Furthermore, there was relatively weak activation of primary innate immune signaling pathways, however, all variants produced enough interferons to induce the activation of STAT2 and production of interferon stimulated genes (ISGs). While interferon mRNA expression and STAT2 activation correlated with cellular viral RNA levels, ISG production did not. Although clear cut effects of specific SARS-CoV-2 genomic mutations could not be concluded, the variants of concern, including Omicron, showed a lower replication efficiency and a slower interferon response compared to an early pandemic variant in the study.
The role of complement in nonalcoholic fatty liver disease
Authors: Guo Zhenya , Fan Xiude , Yao Jianni , Tomlinson Stephen , Yuan Guandou , He Songqing
Published: September 2022

Nonalcoholic fatty liver disease (NAFLD) has become a leading cause of chronic liver diseases globally. NAFLD includes a range of hepatic manifestations, starting with liver steatosis and potentially evolving towards nonalcoholic steatohepatitis, cirrhosis or even hepatocellular carcinoma. Although the pathogenesis of NAFLD is incompletely understood, insulin resistance and lipid metabolism disorder are implicated. The complement system is an essential part of the immune system, but it is also involved in lipid metabolism. In particular, activation of the alternative complement pathway and the production of complement activation products such as C3a, C3adesArg (acylation stimulating protein or ASP) and C5a, are strongly associated with insulin resistance, lipid metabolism disorder, and hepatic inflammation. In this review, we briefly summarize research on the role of the complement system in NAFLD, aiming to provide a basis for the development of novel therapeutic strategies for NAFLD.
Crosstalk of necroptosis and pyroptosis defines tumor microenvironment characterization and predicts prognosis in clear cell renal carcinoma
Authors: Fu Liangmin , Bao Jiahao , Li Jinhui , Li Qiuyang , Lin Hansen , Zhou Yayun , Li Jiangbo , Yan Yixuan , Langston Marvin E. , Sun Tianhao , Guo Songliang , Zhou Xinwei , Chen Yuhang , Liu Yujun , Zhao Yiqi , Lu Jun , Huang Yong , Chen Wei , Chung Benjamin I. , Luo Junhang
Published: September 2022

Pyroptosis and necroptosis are two recently identified forms of immunogenic cell death in the tumor microenvironment (TME), indicating a crucial involvement in tumor metastasis. However, the characteristics of necroptosis and pyroptosis that define tumor microenvironment and prognosis in ccRCC patients remain unknown. We systematically investigated the transcriptional variation and expression patterns of Necroptosis and Pyroptosis related genes (NPRGs). After screening the necroptosis-pyroptosis clusters, the potential functional annotation for clusters was explored by GSVA enrichment analysis. The Necroptosis-Pyroptosis Genes (NPG) scores were used for the prognosis model construction and validation. Then, the correlations of NPG score with clinical features, cancer stem cell (CSC) index, tumor mutation burden (TMB), TME, and Immune Checkpoint Genes (ICGs) were also individually explored to evaluate the prognosis predictive values in ccRCC. Microarray screenings identified 27 upregulated and 1 downregulated NPRGs. Ten overall survival associated NPRGs were filtered to construct the NPG prognostic model indicating a better prognostic signature for ccRCC patients with lower NPG scores (P< 0.001), which was verified using the external cohort. Univariate and multivariate analyses along with Kaplan-Meier survival analysis demonstrated that NPG score prognostic model could be applied as an independent prognostic factor, and AUC values of nomogram from 1- to 5- year overall survival with good agreement in calibration plots suggested that the proposed prognostic signature possessed good predictive capabilities in ccRCC. A high-/sNPG score is proven to be connected with tumor growth and immune-related biological processes, according to enriched GO, KEGG, and GSEA analyses. Comparing patients with a high-NPG score to those with a low-NPG score revealed significant differences in clinical characteristics, growth and recurrence of malignancies (CSC index), TME cell infiltration, and immunotherapeutic response (P< 0.005), potentially making the NPG score multifunctional in the clinical therapeutic setting. Furthermore, AIM2, CASP4, GSDMB, NOD2, and RBCK1 were also found to be highly expressed in ccRCC cell lines and tumor tissues, and GASP4 and GSDMB promote ccRCC cells’ proliferation, migration, and invasion. This study firstly suggests that targeting the NPG score feature for TME characterization may lend novel insights into its clinical applications in the prognostic prediction of ccRCC.
Microbial dysbiosis and childhood asthma development: Integrated role of the airway and gut microbiome, environmental exposures, and host metabolic and immune response
Authors: Liu Conglin , Makrinioti Heidi , Saglani Sejal , Bowman Michael , Lin Lih-Ling , Camargo Carlos A. , Hasegawa Kohei , Zhu Zhaozhong
Published: September 2022

Asthma is a chronic and heterogeneous respiratory disease with many risk factors that typically originate during early childhood. A complex interplay between environmental factors and genetic predisposition is considered to shape the lung and gut microbiome in early life. The growing literature has identified that changes in the relative abundance of microbes (microbial dysbiosis) and reduced microbial diversity, as triggers of the airway-gut axis crosstalk dysregulation, are associated with asthma development. There are several mechanisms underlying microbial dysbiosis to childhood asthma development pathways. For example, a bacterial infection in the airway of infants can lead to the activation and/or dysregulation of inflammatory pathways that contribute to bronchoconstriction and bronchial hyperresponsiveness. In addition, gut microbial dysbiosis in infancy can affect immune development and differentiation, resulting in a suboptimal balance between innate and adaptive immunity. This evolving dysregulation of secretion of pro-inflammatory mediators has been associated with persistent airway inflammation and subsequent asthma development. In this review, we examine current evidence around associations between the airway and gut microbial dysbiosis with childhood asthma development. More specifically, this review focuses on discussing the integrated roles of environmental exposures, host metabolic and immune responses, airway and gut microbial dysbiosis in driving childhood asthma development.
Vitamin C deficiency reveals developmental differences between neonatal and adult hematopoiesis
Authors: Phadke Ira , Pouzolles Marie , Machado Alice , Moraly Josquin , Gonzalez-Menendez Pedro , Zimmermann Valérie S. , Kinet Sandrina , Levine Mark , Violet Pierre-Christian , Taylor Naomi
Published: September 2022

Hematopoiesis, a process that results in the differentiation of all blood lineages, is essential throughout life. The production of 1x1012 blood cells per day, including 200x109 erythrocytes, is highly dependent on nutrient consumption. Notably though, the relative requirements for micronutrients during the perinatal period, a critical developmental window for immune cell and erythrocyte differentiation, have not been extensively studied. More specifically, the impact of the vitamin C/ascorbate micronutrient on perinatal as compared to adult hematopoiesis has been difficult to assess in animal models. Even though humans cannot synthesize ascorbate, due to a pseudogenization of the L-gulono-γ-lactone oxidase (GULO) gene, its generation from glucose is an ancestral mammalian trait. Taking advantage of a Gulo-/- mouse model, we show that ascorbic acid deficiency profoundly impacts perinatal hematopoiesis, resulting in a hypocellular bone marrow (BM) with a significant reduction in hematopoietic stem cells, multipotent progenitors, and hematopoietic progenitors. Furthermore, myeloid progenitors exhibited differential sensitivity to vitamin C levels; common myeloid progenitors and megakaryocyte-erythrocyte progenitors were markedly reduced in Gulo-/- pups following vitamin C depletion in the dams, whereas granulocyte-myeloid progenitors were spared, and their frequency was even augmented. Notably, hematopoietic cell subsets were rescued by vitamin C repletion. Consistent with these data, peripheral myeloid cells were maintained in ascorbate-deficient Gulo-/- pups while other lineage-committed hematopoietic cells were decreased. A reduction in B cell numbers was associated with a significantly reduced humoral immune response in ascorbate-depleted Gulo-/- pups but not adult mice. Erythropoiesis was particularly sensitive to vitamin C deprivation during both the perinatal and adult periods, with ascorbate-deficient Gulo-/- pups as well as adult mice exhibiting compensatory splenic differentiation. Furthermore, in the pathological context of hemolytic anemia, vitamin C-deficient adult Gulo-/- mice were not able to sufficiently increase their erythropoietic activity, resulting in a sustained anemia. Thus, vitamin C plays a pivotal role in the maintenance and differentiation of hematopoietic progenitors during the neonatal period and is required throughout life to sustain erythroid differentiation under stress conditions.
Genetic factors underlying tacrolimus intolerance after liver transplantation
Authors: Liu Yuan , Wang Rui , Wen Peizhen , An Wenbin , Zheng Jinxin , Zhang Tao , Zhang Pengshan , Wang Haoyu , Zou Fan , Pan Hui , Fan Junwei , Peng Zhihai
Published: September 2022

Background

Tacrolimus (FK506) is the cornerstone of immunosuppression after liver transplantation (LT), however, clinically, switching from FK506 to cyclosporine (SFTC) is common in LT patients with tacrolimus intolerance. The aim of this study was to investigate the genetic risk of patients with tacrolimus intolerance.

Methods

A total of 114 LT patients were enrolled in this retrospective study. SNPs were genotyped using Infinium Human Exome-12 v1.2 BeadChip, and genome-wide gene expression levels were profiled using Agilent G4112F array.

Results

SFTC was a potential risk factor of dyslipidemia (OR=4.774[1.122-20.311], p = 0.034) and insulin resistance (IR) (OR=6.25[1.451-26.916], p = 0.014), but did not affect the survival of LT patients. Differential expression analysis showed donor CYP3A5, CYP2C9, CFTR, and GSTP1, four important pharmacogenetic genes were significantly up-regulated in the tacrolimus intolerance group. Twelve SNPs of these four genes were screened to investigate the effects on tacrolimus intolerance. Regression analysis showed donor rs4646450 (OR=3.23 [1.22-8.60] per each A allele, p = 0.01), donor rs6977165 (OR=6.44 [1.09-37.87] per each C allele, p = 0.02), and donor rs776746 (OR=3.31 [1.25-8.81] per each A allele, p = 0.01) were independent risk factors of tacrolimus intolerance.

Conclusions

These results suggested that SFTC was a potential risk factor for dyslipidemia and IR after LT. Besides, rs4646450, rs6977165, and rs776746 of CYP3A5 might be the underlying genetic risks of tacrolimus intolerance. This might help transplant surgeons make earlier clinical decisions about the use of immunosuppression.
SARS-CoV-2 antibody responses before and after a third dose of the BNT162b2 vaccine in Italian healthcare workers aged ≤60 years: One year of surveillance
Authors: Franzese Monica , Coppola Luigi , Silva Romina , Santini Stefano Angelo , Cinquanta Luigi , Ottomano Cosimo , Salvatore Marco , Incoronato Mariarosaria
Published: September 2022

This study monitored the anti-spike-receptor-binding domain (RBD) and neutralizing antibodies induced by the Pfizer/BioNTech mRNA BNT162b2 vaccine in a cohort of 163 healthcare workers aged ≤60 years. We have taken advantage of two study groups, both of whom received the first two doses in the same time window, but Group 1 (54 HCWs) received the third dose 2 months before Group 2 (68 HCWs) did. The cohorts were monitored from the 12th day after the first vaccine dose up to 1 month after the third vaccine dose for a total of eight time points and about 1 year of surveillance (T1 = 12 days after the first dose; T2 = 10 days after the second dose; T3 = 1 month after the second dose; T4 = 3 months after the second dose; T5 = 4 months after the second dose; T6 = 5 months after the second dose; T7 = 7 months after the second dose; T8 = 1 month after the third dose for Group 1; T8* = 9 months after the second dose for Group 2; T9 = 1 month after the third dose for Group 2). The mean value of anti-spike antibodies decreased faster over time, but at T7, its decline was significantly slowed (T7 vs. T8*). After the third dose, the anti-spike titer rose about 34-fold (T7 vs. T8 and T8* vs. T9) and the booster improved the anti-spike titer by about three times compared with that of the second dose (T3 vs. T8 and T3 vs. T9), and no difference was noted between the two groups. The neutralizing titer was evaluated at T3, T7, T8, and T9. Anti-spike and neutralizing antibodies were found to be strongly correlated (r2 = 0.980; p < 0.001). At T3, 70% of the participants had a neutralizing antibody titer >91% of total anti-spike antibodies that increased to 90% after the third dose (T8 and T9). However, when the anti-spike titer reached its lowest value (T7), the neutralizing antibody levels decreased even further, representing only 44% of total anti-spike antibodies (p < 0.0001). Our findings show that the third vaccine dose improves the humoral response, but the wane of the anti-spike and neutralizing antibody titers over time is more marked in the neutralizing antibodies.
Elevated serum C1q is an independent predictor of high residual platelet reactivity in CAD patients receiving clopidogrel therapy
Authors: Zhao Zehao , Ma Meishi , Huang Xin , Sun Tienan , Han Kangning , Yang Shiwei , Zhou Yujie
Published: September 2022

Background

Inflammation increases the risk of thrombosis in coronary artery disease (CAD) patients and affects the antiplatelet efficacy of clopidogrel. C1q interacts with platelets to activate platelets and induce thrombosis by participating in and regulating the inflammatory response. Whether C1q affects adenosine diphosphate (ADP)-induced platelet reactivity during clopidogrel therapy was unclear and our study aimed to explore the issue.

Method

We enrolled 1,334 CAD patients receiving clopidogrel therapy and evaluated the association between C1q level and high residual platelet reactivity (HRPR) using logistic regression and restricted cubic spline (RCS). HRPR was defined as ADP-induced maximum amplitude (MAADP) > 47 mm plus ADP-induced platelet aggregation (ADPi) < 50%.

Results

A total of 516 patients (38.7%) performed HRPR. The frequency of HRPR increases with the increase in C1q level (26.3%, 38.4%, 43.2%, and 46.7% for the 1st to 4th quartile of C1q). The result of multivariate logistic regression demonstrated elevated C1q as an independent predictor for HRPR (2ndquartile: OR = 1.722, 95% CI 1.215–2.440; 3rdquartile: OR = 2.015, 95% CI 1.413–2.874; 4thquartile: OR = 2.362, 95% CI 1.631–3.421, compared to the 1st quartile). RCS depicted the nonlinear relationship between C1q and HRPR risk (pfor non-linear < 0.05).

Conclusion

The current research is the first to explore the association of C1q and ADP-induced platelet reactivity and to demonstrate elevated C1q as an independent risk factor for HRPR in CAD patients during clopidogrel therapy.
The human myocardium harbors a population of naive B-cells with a distinctive gene expression signature conserved across species
Authors: Bermea Kevin C. , Kostelecky Nicolas , Rousseau Sylvie T. , Lin Chieh-Yu , Adamo Luigi
Published: September 2022

Introduction

Cardiac immunology studies in murine models have identified a sizeable population of myocardial B-cells and have shown that its modulation represents a promising strategy to develop novel therapies for heart failure. However, scarce data on B-cells in the human heart leaves unclear whether findings in rodents are relevant to human biology.

Methods

We performed immunohistochemical stains to characterize the amount and distribution of B-cells in human hearts, analyzing both fresh and post-mortem tissue. To gain insight into the biology of human myocardial B-cells we analyzed publicly-available spatial transcriptomics and single-cell sequencing datasets of myocardial and peripheral blood mononuclear cells (PBMCs). We validated these findings on primary B-cells sorted from the heart and peripheral blood of left ventricular assistive device recipients. To identify biological pathways upregulated in myocardial B-cells across species, we compared differential gene expression in myocardial vs peripheral blood B-cells across the studied human datasets and published rodent datasets.

Results

In healthy human heart samples, we found B-cells at a ratio of 1:8 compared to T-cells (2.41 ± 0.45 vs 19.36 ± 4.43, p-value <0.001). Myocardial B-cells were more abundant in the interstitium compared with the intravascular space (p-value=0.011), and also more abundant in the myocardium vs. epicardium (p-value=0.048). Single-cell gene expression analysis showed that the human myocardium harbored mostly naive B-cells with a gene expression profile distinct from that of PBMC B-cells. Cross-comparison of differentially-expressed genes in myocardial vs. PBMC B-cells across human and rodent datasets identified 703 genes with consistent differential gene expression across species (binomial p-value=2.9e-48). KEGG pathway analysis highlighted “B-cell receptor signaling pathway,” “Antigen processing and presentation,” and “Cytokine-cytokine receptor interaction” among the top pathways upregulated in cardiac B-cells (FDR <0.001) conserved between species.

Conclusions

Like the murine heart, the human heart harbors naive B-cells that are both intravascular and extravascular. Human myocardial B-cells are fewer and more evenly distributed between these two compartments than rodent myocardial B-cells. However, analysis of single-gene expression data indicates that the biological function of myocardial B-cells is conserved across species.
Gastrointestinal Talaromyces marneffei infection in a patient with AIDS: A case report and systematic review
Authors: Ling Fangmei , Guo Tao , Li Junrong , Chen Yidong , Xu Mingyang , Li Shuang , Zhu Liangru
Published: September 2022

Talaromyces marneffei is a thermally dimorphic fungus that affects multiple organs and frequently invades immunocompromised individuals. However, only a few studies have reported the presence of intestinal infection associated with T. marneffei. Herein, we reported a case of intestinal T. marneffei infection in a man who complained of a 1-month history of intermittent fever, abdominal pain, and diarrhea. The result of the human immunodeficiency virus antibody test was positive. Periodic acid-Schiff and Gomorrah’s methylamine silver staining of the intestinal biopsy tissue revealed T. marneffei infection. Fortunately, the patient’s symptoms rapidly resolved with prompt antifungal treatment. In addition, we summarized and described the clinical characteristics, management, and outcomes of patients with intestinal T. marneffei infection. A total of 29 patients were identified, the majority of whom (65.52%) were comorbid with acquired immunodeficiency syndrome. The main clinical features included anemia, fever, abdominal pain, diarrhea, weight loss, and lymphadenopathy. The transverse and descending colon, ileocecum, and ascending colon were the most common sites of lesions. A considerable number of patients (31.03%) developed intestinal obstruction, intestinal perforation, and gastrointestinal bleeding. Of the 29 patients, six underwent surgery, 23 survived successfully with antifungal treatment, five died of T. marneffei infection, and one died of unknown causes. T. marneffei intestinal infection should be considered when immunodeficient patients in endemic areas present with non-specific symptoms, such as fever, abdominal pain, and diarrhea. Appropriate and timely endoscopy avoids delays in diagnosis. Early aggressive antifungal therapy improves the clinical outcomes of patients.
Pathogenic variant c.1052T>A (p.Leu351Gln) in adenosine deaminase 2 impairs secretion and elevates type I IFN responsive gene expression
Authors: Bowers Sarah M. , Sundqvist Martina , Dancey Paul , Cabral David A. , Brown Kelly L.
Published: September 2022

Background

Adenosine deaminase 2 (ADA2) is a homodimeric, extracellular enzyme and putative growth factor that is produced by cells of the myeloid lineage and, catalytically, deaminates extracellular adenosine to inosine. Loss-of-(catalytic)-function variants in the ADA2 gene are associated with Deficiency of ADA2 (DADA2), an autosomal recessive disease associated with an unusually broad range of inflammatory manifestations including vasculitis, hematological defects and cytopenia. Previous work by our group led to the identification of ADA2 variants of novel association with DADA2, among which was a unique c.1052T>A (p.Leu351Gln; herein referred to as L351Q) variant located in the catalytic domain of the protein.

Methods

Mammalian (Flp-IN CHO) cells were engineered to stably express wild-type ADA2 and ADA2 protein variants, including the pathogenic L351Q variant identified in DADA2 patients. An enzyme assay and immunoblotting were used to assess ADA2 catalytic activity and secretion, respectively, and the outcome of experimentally induced inhibition of protein processing (Golgi transport and N-linked glycosylation) was assessed. Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to determine the relative expression of Type I Interferon stimulated genes (ISGs), IFIT3 and IRF7.

Results

In addition to abrogating catalytic activity, the L351Q variant impaired secretion of L351Q ADA2 resulting in an intracellular accumulation of L351Q ADA2 protein that was not observed in cells expressing wild-type ADA2 or other ADA2 protein variants. Retention of L351Q ADA2 was not attributable to impaired glycosylation on neighboring asparagine residues and did not impact cell growth or integrity. Constitutive expression of Type I ISGs IFIT3 and IRF7 was observed in cells expressing L351Q ADA2.

Conclusions

The impaired secretion of L351Q ADA2 may be an important factor leading to the severe phenotype observed in patients with this variant further emphasizing the importance of assessing impacts beyond catalytic activity when evaluating genotype-phenotype relationships in DADA2.
Prediction of extreme cargo ship panel stresses by using deconvolution
Authors: Gaidai Oleg , Yan Ping , Xing Yihan
Published: September 2022

Extreme value predictions typically originate from certain functional classes of statistical distributions to fit the data and are subsequently extrapolated. This paper describes an alternative method for extrapolation that is based on the intrinsic properties of the data set itself and that does not pre-assume any extrapolation functional class. The proposed novel extrapolation method can be utilized in engineering design. To illustrate this, this study uses two examples to showcase the advantages of the proposed method. The first example used synthetic data from a non-linear Duffing oscillator to illustrate the new method. The second example was an actual container ship sailing between Europe and America and experiencing large deck panel stresses in severe weather. In this example, actual onboard measured data were used in the present study. This example represents a real and physical case that is challenging to model due to the non-stationary and highly non-linear natures of the wave-ship load responses. This is especially so in the case of extreme responses, where the roles of second and higher-order responses tend to be more prominent and have higher contributions. The prediction accuracy of the proposed method was also validated versus the Naess–Gaidai extrapolation method. Finally, this study discusses new methods for generic smoothing of distribution tail irregularities due to underlying scarcity in the data set.
Impact of key parameters involved with plant-microbe interaction in context to global climate change
Authors: Shree Bharti , Jayakrishnan Unnikrishnan , Bhushan Shashi
Published: September 2022

Anthropogenic activities have a critical influence on climate change that directly or indirectly impacts plant and microbial diversity on our planet. Due to climate change, there is an increase in the intensity and frequency of extreme environmental events such as temperature rise, drought, and precipitation. The increase in greenhouse gas emissions such as CO2, CH4, NOx, water vapor, increase in global temperature, and change in rainfall patterns have impacted soil–plant-microbe interactions, which poses a serious threat to food security. Microbes in the soil play an essential role in plants’ resilience to abiotic and biotic stressors. The soil microbial communities are sensitive and responsive to these stressors. Therefore, a systemic approach to climate adaptation will be needed which acknowledges the multidimensional nature of plant-microbe-environment interactions. In the last two scores of years, there has been an enhancement in the understanding of plant’s response to microbes at physiological, biochemical, and molecular levels due to the availability of techniques and tools. This review highlights some of the critical factors influencing plant-microbe interactions under stress. The association and response of microbe and plants as a result of several stresses such as temperature, salinity, metal toxicity, and greenhouse gases are also depicted. New tools to study the molecular complexity of these interactions, such as genomic and sequencing approaches, which provide researchers greater accuracy, reproducibility, and flexibility for exploring plant-microbe–environment interactions under a changing climate, are also discussed in the review, which will be helpful in the development of resistant crops/plants in present and future.
Oropharyngeal microbiome profiled at admission is predictive of the need for respiratory support among COVID-19 patients
Authors: Bradley Evan S. , Zeamer Abigail L. , Bucci Vanni , Cincotta Lindsey , Salive Marie-Claire , Dutta Protiva , Mutaawe Shafik , Anya Otuwe , Tocci Christopher , Moormann Ann , Ward Doyle V. , McCormick Beth A. , Haran John P.
Published: September 2022

The oropharyngeal microbiome, the collective genomes of the community of microorganisms that colonizes the upper respiratory tract, is thought to influence the clinical course of infection by respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Infectious Disease 2019 (COVID-19). In this study, we examined the oropharyngeal microbiome of suspected COVID-19 patients presenting to the Emergency Department and an inpatient COVID-19 unit with symptoms of acute COVID-19. Of 115 initially enrolled patients, 50 had positive molecular testing for COVID-19+ and had symptom duration of 14 days or less. These patients were analyzed further as progression of disease could most likely be attributed to acute COVID-19 and less likely a secondary process. Of these, 38 (76%) went on to require some form of supplemental oxygen support. To identify functional patterns associated with respiratory illness requiring respiratory support, we applied an interpretable random forest classification machine learning pipeline to shotgun metagenomic sequencing data and select clinical covariates. When combined with clinical factors, both species and metabolic pathways abundance-based models were found to be highly predictive of the need for respiratory support (F1-score 0.857 for microbes and 0.821 for functional pathways). To determine biologically meaningful and highly predictive signals in the microbiome, we applied the Stable and Interpretable RUle Set to the output of the models. This analysis revealed that low abundance of two commensal organisms, Prevotella salivae or Veillonella infantium (< 4.2 and 1.7% respectively), and a low abundance of a pathway associated with LPS biosynthesis (< 0.1%) were highly predictive of developing the need for acute respiratory support (82 and 91.4% respectively). These findings suggest that the composition of the oropharyngeal microbiome in COVID-19 patients may play a role in determining who will suffer from severe disease manifestations.
Giant pandas’ staple food bamboo phyllosphere fungal community and its influencing factors
Authors: Kang Liwen , Luo Wei , Dai Qinglong , Zhou Hong , Wei Wei , Tang Junfeng , Han Han , Yuan Yuan , Long Juejie , Zhang Zejun , Hong Mingsheng
Published: September 2022

Giant pandas have developed a series of foraging strategies to adapt to their special bamboo diets. Although bamboo is an important food resource for giant pandas in Liziping National Nature Reserve (Liziping NR), China, there are relatively few studies on their phyllosphere fungal community and its influencing factors. Herein, we used ITS1 amplification and metagenomic sequencing to analyze the phyllosphere fungi diversity and functions (KEGG, CAZyme, and antibiotic resistance gene) and explore the influencing factors for the three giant pandas foraging bamboo species (Arundinaria spanostachya, AS; Yushania lineolate, YL; and Fargesia ferax, FF) over different seasons (spring vs. autumn) in Liziping NR, China. We found that Ascomycota and Basidiomycota were the most dominant phyla in the bamboo phyllosphere. The alpha diversity (e.g., the Sobs index and Shannon index) was relatively higher in autumn samples than in spring samples, and the community structure differed significantly between the three bamboo species in spring and autumn. Some biotic and abiotic variables (e.g., the elevation and mean base diameter of bamboo) significantly influenced the abundance, diversity, and community structure of the bamboo phyllosphere fungal community. Moreover, the functional analysis showed the differences in the glycoside hydrolase community and antibiotic resistance gene (ARG) profile between spring and autumn samples. Co–occurrence network modeling suggested that AS phyllosphere fungal communities in autumn employed a much more complex network than that in spring, and the abundance of multidrug, tetracycline, and glycopeptide resistance genes was high and closely correlated with other ARGs. These results indicate that fungal community’s abundance, diversity, and community structure are mainly affected by the season, host species, and elevation. The season and host species are major factors affecting the biological functions (KEGG and CAZyme), ARGs, and interactions between sympatric bacterial and fungal communities in bamboo phyllosphere. This integrated study can provide a reference basis for the seasonal management of bamboo resources foraged by wild giant pandas, and predict the risk of antibiotic resistance in bamboo phyllosphere fungal flora in Liziping NR (Xiaoxiangling mountains), China.
Prospects for the application of infectious virus detection technology based on propidium monoazide in African swine fever management
Authors: Zeng Dexin , Qian Bingxu , Li Yunfei , Zong Kai , Peng Wanqing , Liao Kai , Yu Xiaofeng , Sun Juanjuan , Lv Xiaying , Ding Liu , Wang Manman , Zhou Tingting , Jiang Yuan , Li Jinming , Xue Feng , Wu Xiaodong , Dai Jianjun
Published: September 2022

African swine fever (ASF) is a hemorrhagic and often fatal disease occurring in domestic pigs and wild boars. ASF can potentially greatly impact the global trade of pigs and pork products and threaten global food security. Outbreaks of ASF must be notified to the World Organization for Animal Health. In this study, we analyzed the feasibility of applying propidium monoazide (PMA) pretreatment-based infectious virus detection technology to ASF prevention and control and investigated the prospects of applying this technology for epidemic monitoring, disinfection effect evaluation, and drug development. PMA as a nucleic acid dye can enter damaged cells and undergo irreversible covalent crosslinking with nucleic acid under halogen light to prevent its amplification. Although this technology has been widely used for the rapid detection of viable bacteria, its application in viruses is rare. Therefore, we analyzed the theoretical feasibility of applying this technology to the African swine fever virus (ASFV) in terms of gene and cell composition. Rapid infectious ASFV detection technology based on PMA pretreatment would greatly enhance all aspects of ASF prevention and control, such as epidemic monitoring, disinfection treatment, and drug development. The introduction of this technology will also greatly improve the ability to prevent and control ASF.
Semi-rational engineering membrane binding domain of L-amino acid deaminase from Proteus vulgaris for enhanced α-ketoisocaproate
Authors: Song Yang , Wang Rui , Zhang Zixuan , Liu Xinran , Qi Lulu , Shentu Xuping , Yu Xiaoping
Published: September 2022

α-Keto acids are important raw materials for pharmaceuticals and functional foods, which could be produced from cheap feed stock by whole cell biocatalysts containing L-amino acid deaminases (L-AADs). However, the production capacity is limited by the low activity of L-AADs. The L-AAD mediated redox reaction employs the electron transport chain to transfer electrons from the reduced FADH2 to O2, implying that the interaction between L-AAD and the cell membrane affects its catalytic activity. To improve the catalytic activity of L-AAD from Proteus vulgaris, we redesigned the membrane-bound hydrophobic insertion sequences (INS, residues 325–375) by saturation mutagenesis and high-throughput screening. Mutants D340N and L363N exhibited higher affinity and catalytic efficiency for L-leucine, with half-life 1.62-fold and 1.28-fold longer than that of wild-type L-AAD. D340N catalyzed L-leucine to produce 81.21 g⋅L–1 α-ketoisocaproate, with a bioconversion rate of 89.06%, which was 17.57% higher than that of the wild-type. It is predicted that the mutations enhanced the interaction between the protein and the cell membrane.
The Contribution of Proton-Donor pKa on Reactivity Profiles of [FeFe]-hydrogenases
Authors: Kisgeropoulos Effie C. , Bharadwaj Vivek S. , Mulder David W. , King Paul W.
Published: September 2022

The [FeFe]-hydrogenases are enzymes that catalyze the reversible activation of H2 coupled to the reduction–oxidation of electron carriers. Members of the different taxonomic groups of [FeFe]-hydrogenases display a wide range of preference, or bias, for H2 oxidation or H2 production reactions, despite sharing a common catalytic cofactor, or H-cluster. Identifying the properties that control reactivity remains an active area of investigation, and models have emerged that include diversity in the catalytic site coordination environments and compositions of electron transfer chains. The kinetics of proton-coupled electron transfer at the H-cluster might be expected to be a point of control of reactivity. To test this hypothesis, systematic changes were made to the conserved cysteine residue that functions in proton exchange with the H-cluster in the three model enzymes: CaI, CpII, and CrHydA1. CaI and CpII both employ electron transfer accessory clusters but differ in bias, whereas CrHydA1 lacks accessory clusters having only the H-cluster. Changing from cysteine to either serine (more basic) or aspartate (more acidic) modifies the sidechain pKa and thus the barrier for the proton exchange step. The reaction rates for H2 oxidation or H2 evolution were surveyed and measured for model [FeFe]-hydrogenases, and the results show that the initial proton-transfer step in [FeFe]-hydrogenase is tightly coupled to the control of reactivity; a change from cysteine to more basic serine favored H2 oxidation in all enzymes, whereas a change to more acidic aspartate caused a shift in preference toward H2 evolution. Overall, the changes in reactivity profiles were profound, spanning 105 in ratio of the H2 oxidation-to-H2 evolution rates. The fact that the change in reactivity follows a common trend implies that the effect of changing the proton-transfer residue pKa may also be framed as an effect on the scaling relationship between the H-cluster di(thiolmethyl)amine (DTMA) ligand pKa and Em values of the H-cluster. Experimental observations that support this relationship, and how it relates to catalytic function in [FeFe]-hydrogenases, are discussed.
Network analysis reveals microbe-mediated impacts of aeration on deep sediment layer microbial communities
Authors: Wang Zhenyu , Liu Feifei , Li Enze , Yuan Yongqiang , Yang Yonggang , Xu Meiying , Qiu Rongliang
Published: September 2022

Over-aeration is a common remediation strategy for black and odorous water bodies, in which oxygen is introduced to impact aquatic microbial communities as an electron acceptor of high redox potential. In this study, black-odorous freshwater sediments were cultured for 9 weeks under aeration to investigate microbial covariations at different depths and time points. Based on community 16S rRNA gene sequencing, the microbial covariations were visualized using phylogenetic microbial ecological networks (pMENs). In the spatial scale, we identified smaller and more compact pMENs across all layers compared with the anaerobic control sediments, in terms of network size, average node connectivity, and modularity. The aerated middle layer had the most connectors, the least module hubs, a network hub, shorter average path length, and predominantly positive covariations. In addition, a significant sulfate accumulation in the aerated middle layer indicated the most intense sulfide oxidation, possibly because aeration prompted sediment surface Desulfobulbaceae, known as cable bacteria, to reach the middle layer. In the time scale, similarly, aeration led to smaller pMEN sizes and higher portions of positive covariations. Therefore, we conclude that elevated dissolved oxygen at the water-sediment interface may impact not only the surface sediment but also the subsurface and/or deep sediment microbial communities mediated by microorganisms, particularly by Desulfobulbaceae.
RNase III coding genes modulate the cross-kingdom biofilm of Streptococcus mutans and Candida albicans
Authors: Lu Yangyu , Lei Lei , Deng Yalan , Zhang Hongyu , Xia Mengying , Wei Xi , Yang Yingming , Hu Tao
Published: September 2022

Streptococcus mutans constantly coexists with Candida albicans in plaque biofilms of early childhood caries (ECC). The progression of ECC can be influenced by the interactions between S. mutans and C. albicans through exopolysaccharides (EPS). Our previous studies have shown that rnc, the gene encoding ribonuclease III (RNase III), is implicated in the cariogenicity of S. mutans by regulating EPS metabolism. The DCR1 gene in C. albicans encodes the sole functional RNase III and is capable of producing non-coding RNAs. However, whether rnc or DCR1 can regulate the structure or cariogenic virulence of the cross-kingdom biofilm of S. mutans and C. albicans is not yet well understood. By using gene disruption or overexpression assays, this study aims to investigate the roles of rnc and DCR1 in modulating the biological characteristics of dual-species biofilms of S. mutans and C. albicans and to reveal the molecular mechanism of regulation. The morphology, biomass, EPS content, and lactic acid production of the dual-species biofilm were assessed. Quantitative real-time polymerase chain reaction (qRT-PCR) and transcriptomic profiling were performed to unravel the alteration of C. albicans virulence. We found that both rnc and DCR1 could regulate the biological traits of cross-kingdom biofilms. The rnc gene prominently contributed to the formation of dual-species biofilms by positively modulating the extracellular polysaccharide synthesis, leading to increased biomass, biofilm roughness, and acid production. Changes in the microecological system probably impacted the virulence as well as polysaccharide or pyruvate metabolism pathways of C. albicans, which facilitated the assembly of a cariogenic cross-kingdom biofilm and the generation of an augmented acidic milieu. These results may provide an avenue for exploring new targets for the effective prevention and treatment of ECC.