HCMV exploits STING signaling and counteracts IFN and ISG induction to facilitate dendritic cell infection

Human cytomegalovirus (HCMV) is a widespread obligatory human pathogen causing life-threatening disease in immunocompromised hosts. Myeloid cells such as monocyte-derived dendritic cells (moDCs) are targets of HCMV. Here, we performed single-cell RNA sequencing, which revealed infection of most moDCs upon in vitro HCMV exposure, whereas only a fraction of them initiated viral gene expression. We identified three moDC subsets, of which CD1a−/CD86− cells showed the highest susceptibility. Upon HCMV entry, STING activation not only induced IFN-β, but also promoted viral gene expression. Upon progression of infection, IFN-β but not IFN-λ1 expression was inhibited. Similarly, ISG expression was initially induced and then shut off and thus allowed productive infection. Increased viral gene expression was associated with the induction of several pro- (RHOB, HSP1A1, DNAJB1) and anti-viral (RNF213, TNFSF10, IFI16) genes. Thus, moDC permissiveness to HCMV depends on complex interactions between virus sensing, regulation of IFNs/ISGs and viral gene expression.

Introduction to Special Issue: Study of Microbiological Safety in the Food Chain

Ensuring microbiological safety in the food (of animal origin) chain is a challenging task due to the complex interactions among animals, humans and the environment [...]

Genetic and QTL Analysis for Hilum-Eye Types in Cowpea (Vigna Unguiculata L. Walp)

Cowpea is an important food legume widely grown in the semi-arid tropics and serves as a main source of dietary protein, minerals, and vitamins. However, varieties differ from region to region based on the consumer’s preference for seed types determined by seed size, seed coat texture, seed color, and hilum-eye types. The genetics of seed size, seed color, and seed coat texture have been well documented, but the hilum-eye types have not been studied well because they represent seven different types with complex interactions. We studied the genetic segregation for hilum-eye types and determined the number of genes involved in a recombinant inbred line (RIL) population derived from a cross between a small eye parent ‘GEC’ and a Watson eye parent ‘IT98K-476-8’. The results demonstrated a three-gene model, W (Watson), S (small), and R (large), for cowpea seed hilum-eye type pattern and the interaction of these three genes, W, S, and R, resulted in five phenotypes, viz. self, Watson, small, large, and ring hilum-eye types. Moreover, we also mapped the RILs for hilum-eye types, identified three quantitative trait loci (QTLs), and aligned to the cowpea reference genome as QTL qHilum7.1, qHilum9.1, and qHilum10.1, corresponding to these three genes, Ring type (R), Watson type (W), and Small type (S) hilum-eye type patterns, respectively. Therefore, there was a complete agreement between the genetic analysis and QTL mapping for the number of genes controlling the hilum types in cowpea.

Phenology is the dominant control of methane emissions in a tropical non-forested wetland

Tropical wetlands are a significant source of atmospheric methane (CH4), but their importance to the global CH4 budget is uncertain due to a paucity of direct observations. Net wetland emissions result from complex interactions and co-variation between microbial production and oxidation in the soil, and transport to the atmosphere. Here we show that phenology is the overarching control of net CH4 emissions to the atmosphere from a permanent, vegetated tropical swamp in the Okavango Delta, Botswana, and we find that vegetative processes modulate net CH4 emissions at sub-daily to inter-annual timescales. Without considering the role played by papyrus on regulating the efflux of CH4 to the atmosphere, the annual budget for the entire Okavango Delta, would be under- or over-estimated by a factor of two. Our measurements demonstrate the importance of including vegetative processes such as phenological cycles into wetlands emission budgets of CH4.

Mapping Cell Phenomics with Multiparametric Flow Cytometry Assays

Phenomics explores the complex interactions among genes, epigenetics, symbiotic microorganisms, diet, and environmental exposure based on the physical, chemical, and biological characteristics of individuals and groups. Increasingly efficient and comprehensive phenotyping techniques have been integrated into modern phenomics-related research. Multicolor flow cytometry technology provides more measurement parameters than conventional flow cytometry. Based on detailed descriptions of cell phenotypes, rare cell populations and cell subsets can be distinguished, new cell phenotypes can be discovered, and cell apoptosis characteristics can be detected, which will expand the potential of cell phenomics research. Based on the enhancements in multicolor flow cytometry hardware, software, reagents, and method design, the present review summarizes the recent advances and applications of multicolor flow cytometry in cell phenomics, illuminating the potential of applying phenomics in future studies.

GABAA/Benzodiazepine Receptor Complex in the Dorsal Hippocampus Mediates the Effects of Chrysin on Anxiety-Like Behaviour in Female Rats

Systemic injections of the flavonoid chrysin (5,7-dihydroxyflavone) exert anxiolytic-like effects in ovariectomised and cycling female rats through actions on gamma-aminobutyric acid-A (GABAA) receptors; however, it is unknown if chrysin directly acts on brain structures that are involved in regulating emotional processes, such as the hippocampus. The present study evaluated the effects of intrahippocampal microinjections of 0.25, 0.5, and 1 μg of chrysin on anxiety-like behaviour in the elevated plus maze (EPM) and locomotor activity test (LAT) in female rats in proestrus and dioestrus. Similar doses of the neurosteroid allopregnanolone were used as a reference GABAergic anxiolytic drug. The participation of the GABAA/benzodiazepine receptor complex was evaluated by administering the antagonists picrotoxin, bicuculline and flumazenil. In proestrus, 0.5 and 1 μg of chrysin and allopregnanolone induced anxiogenic-like behaviour. In dioestrus, chrysin, and allopregnanolone (0.5 μg) induced anxiolytic-like effects. Picrotoxin, bicuculline and flumazenil prevented the effects of chrysin and allopregnanolone in both proestrus and dioestrus. None of the treatments significantly affected locomotor activity. These results indicate that the GABAA/benzodiazepine receptor complex in the dorsal hippocampus regulates the effects of chrysin on anxiety-like behaviour, similar to the actions of allopregnanolone. The divergent effects of treatments across the oestrous cycle phases suggest complex interactions between GABAA receptors and compounds with an anxiolytic potential.

Guanxin V Acts as an Antioxidant in Ventricular Remodeling

Background: Our previous studies have shown that Guanxin V (GXV) is safe and effective in the treatment of ventricular remodeling (VR), but its mechanism related to oxidative stress has not been studied deeply.Methods: We applied integrating virtual screening and network pharmacology strategy to obtain the GXV-, VR-, and oxidative stress-related targets at first, and then highlighted the shared targets. We built the networks and conducted enrichment analysis. Finally, the main results were validated by molecular docking and solid experiments.Results: We obtained 251, 11,425, and 9,727 GXV-, VR-, and oxidative stress-related targets, respectively. GXV-component-target-VR and protein–protein interaction networks showed the potential mechanism of GXV in the treatment of VR. The following enrichment analysis results gathered many biological processes and “two GXV pathways” of oxidative stress-related to VR. All our main results were validated by molecular docking and solid experiments.Conclusion: GXV could be prescribed for VR through the mechanism, including complex interactions between related components and targets, as predicted by virtual screening and network pharmacology and validated by molecular docking and solid experiments. Our study promotes the explanation of the biological mechanism of GXV for VR.

Multilocus Inherited Neoplasia Allele Syndrome (MINAS): an update

Multi-locus Inherited Neoplasia Allele Syndrome (MINAS) refers to individuals with germline pathogenic variants in two or more cancer susceptibility genes(CSGs). With increased use of exome/genome sequencing it would be predicted that detection of MINAS would become more frequent. Here we review recent progress in knowledge of MINAS. A systematic literature search for reports of individuals with germline pathogenic variants in 2 or more of 94 CSGs was performed. In addition, participants with multiple primary tumours who underwent genome sequencing as part of the Rare Disease arm of the UK 100,000 Genomes Project were interrogated to detect additional cases. We identified 385 MINAS cases (211 reported in the last 5 years, 6 from 100,000 genomes participants). Most (287/385) cases contained at least one pathogenic variant in either BRCA1 or BRCA2. 108/385 MINAS cases had multiple primary tumours at presentation and a subset of cases presented unusual multiple tumour phenotypes. We conclude that, as predicted, increasing numbers of individuals with MINAS are being have been reported but, except for individuals with BRCA1/BRCA2 MINAS, individual CSG combinations are generally rare. In many cases it appears that the clinical phenotype is that which would be expected from the effects of the constituent CSG variants acting independently. However, in some instances the presence of unusual tumour phenotypes and/or multiple primary tumours suggests that there may be complex interactions between the relevant MINAS CSGs. Systematic reporting of MINAS cases in a MINAS database (e.g. https://databases.lovd.nl/shared/diseases/04296) will facilitate more accurate prognostic predictions for specific CSG combinations.

Immunometabolism in bladder cancer microenvironment

The initiation and progression of bladder cancer (BC), is dependent on its tumor microenvironment (TME). On the other hand, cancer cells shape and train TME to support their development, respond to treatment and migration in an organism. Immune cells exert key roles in the BC microenvironment and have complex interactions with BC cells. These complicated interplays result in metabolic competition in the TME leading to nutrient deprivation, acidosis, hypoxia and metabolite accumulation, which impair immune cell function. Recent studies have demonstrated that immune cells functions are closely correlated with their metabolism. Immunometabolism describes the functional metabolic alterations that take place within immune cells and the role of these cells in directing metabolism and immune response in tissues or diseases such as cancer. Some molecules and their metabolites in the TME including glucose, fatty acids and amino acids can regulate the phenotype, function and metabolism of immune cells. Hence, here we describe some recent advances in immunometabolism and relate them to BC progression. A profound understanding of the metabolic reprogramming of BC cells and immune cells in the TME will offer novel opportunities for targeted therapies in future.

Employment status at transplant influences ethnic disparities in outcomes after deceased donor kidney transplantation

Background African American (AA) recipients of deceased-donor (DD) kidney transplants (KT) have shorter allograft survival than recipients of other ethnic groups. Reasons for this disparity encompass complex interactions between donors and recipients characteristics. Methods Outcomes from 3872 AA and 19,719 European American (EA) DDs who had one kidney transplanted in an AA recipient and one in an EA recipient were analyzed. Four donor/recipient pair groups (DRP) were studied, AA/AA, AA/EA, EA/AA, and EA/EA. Survival random forests and Cox proportional hazard models were fitted to rank and evaluate modifying effects of DRP on variables associated with allograft survival. These analyses sought to identify factors contributing to the observed disparities in transplant outcomes among AA and EA DDKT recipients. Results Transplant era, discharge serum creatinine, delayed graft function, and DRP were among the top predictors of allograft survival and mortality among DDKT recipients. Interaction effects between DRP with the kidney donor risk index and transplant era showed significant improvement in allograft survival over time in EA recipients. However, AA recipients appeared to have similar or poorer outcomes for DDKT performed after 2010 versus before 2001; allograft survival hazard ratios (95% CI) were 1.15 (0.74, 1.76) and 1.07 (0.8, 1.45) for AA/AA and EA/AA, compared to 0.62 (0.54, 0.71) and 0.5 (0.41, 0.62) for EA/EA and AA/EA DRP, respectively. Recipient mortality improved over time among all DRP, except unemployed AA/AAs. Relative to DDKT performed pre-2001, employed AA/AAs had HR = 0.37 (0.2, 0.69) versus 0.59 (0.31, 1.11) for unemployed AA/AA after 2010. Conclusion Relative to DDKT performed before 2001, similar or worse overall DCAS was observed among AA/AAs, while EA/EAs experienced considerable improvement regardless of employment status, KDRI, and EPTS. AA recipients of an AA DDKT, especially if unemployed, had worse allograft survival and mortality and did not appear to benefit from advances in care over the past 20 years.