Notes

Endomembrane targeting involving individual OAS1 p46 augments antiviral action.
udy provides a mechanistic process-based understanding of the early seedling establishment of B. planiculmis populations in response to increased soil saline-alkalization in natural wetlands.Potassium (K+) is one of essential mineral elements for plant growth and development. selleck chemical K+ channels, especially AKT1-like channels, play crucial roles in K+ uptake in plant roots. Maize is one of important crops; however, the K+ uptake mechanism in maize is little known. Here, we report the physiological functions of K+ channel ZMK1 in K+ uptake and homeostasis in maize. ZMK1 is a homolog of Arabidopsis AKT1 channel in maize, and mainly expressed in maize root. Yeast complementation experiments and electrophysiological characterization in Xenopus oocytes indicated that ZMK1 could mediate K+ uptake. ZMK1 rescued the low-K+-sensitive phenotype of akt1 mutant and enhanced K+ uptake in Arabidopsis. Overexpression of ZMK1 also significantly increased K+ uptake activity in maize, but led to an oversensitive phenotype. Similar to AKT1 regulation, the protein kinase ZmCIPK23 interacted with ZMK1 and phosphorylated the cytosolic region of ZMK1, activating ZMK1-mediated K+ uptake. ZmCIPK23 could also complement the low-K+-sensitive phenotype of Arabidopsis cipk23/lks1 mutant. These findings demonstrate that ZMK1 together with ZmCIPK23 plays important roles in K+ uptake and homeostasis in maize.Carotenoids are essential in human diet, so that the development of programs toward carotenoid enhancement has been promoted in several crops. The cereal tritordeum, the amphiploid derived from the cross between Hordeum chilense Roem. et Schulz. and durum wheat has a remarkable carotenoid content in the endosperm. Besides, a high proportion of these carotenoids are esterified with fatty acids. The identification of the gene(s) responsible for xanthophyll esterification would be useful for breeding as esterified carotenoids show an increased ability to accumulate within plant cells and have a higher stability during post-harvest storage. In this work, we analyzed five genes identified as candidates for coding the xanthophyll acyltransferase (XAT) enzyme responsible for lutein esterification in H. chilense genome. link2 All these genes were expressed during grain development in tritordeum, but only HORCH7HG021460 was highly upregulated. Sequence analysis of HORCH7HG021460 revealed a G-to-T transversion, causing a Glycine to Cysteine substitution in the protein of H290 (the only accession not producing quantifiable amounts of lutein esters, hereinafter referred as zero-ester) of H. chilense compared to the esterifying genotypes. An allele-specific marker was designed for the SNP detection in the H. chilense diversity panel. From the 93 accessions, only H290 showed the T allele and the zero-ester phenotype. Furthermore, HORCH7HG021460 is the orthologue of XAT-7D, which encodes a XAT enzyme responsible for carotenoid esterification in wheat. Thus, HORCH7HG021460 (XAT-7Hch) is a strong candidate for lutein esterification in H. chilense and tritordeum, suggesting a common mechanism of carotenoid esterification in Triticeae species. The transference of XAT-7Hch to wheat may be useful for the enhancement of lutein esters in biofortification programs.Immune checkpoint inhibitors (ICIs) are currently a first-line treatment option for clear cell renal cell carcinoma (ccRCC). However, recent clinical studies have shown that a large number of patients do not respond to ICIs. Moreover, only a few patients achieve a stable and durable response even with combination therapy based on ICIs. Available studies have concluded that the response to immunotherapy and targeted therapy in patients with ccRCC is affected by the tumor immune microenvironment (TIME), which can be manipulated by targeted therapy and tumor genomic characteristics. Therefore, an in-depth understanding of the dynamic nature of the TIME is important for improving the efficacy of immunotherapy or combination therapy in patients with advanced ccRCC. Here, we explore the possible mechanisms by which the TIME affects the efficacy of immunotherapy and targeted therapy, as well as the factors that drive dynamic changes in the TIME in ccRCC, including the immunomodulatory effect of targeted therapy and genomic changes. We also describe the progress on novel therapeutic modalities for advanced ccRCC based on the TIME. Overall, this review provides valuable information on the optimization of combination therapy and development of individualized therapy for advanced ccRCC.Dysregulated neutrophil activation contributes to the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Neutrophil-derived reactive oxygen species (ROS) and granule proteases are implicated in damage to and destruction of host tissues in both conditions (cartilage in RA, vascular tissue in SLE) and also in the pathogenic post-translational modification of DNA and proteins. Neutrophil-derived cytokines and chemokines regulate both the innate and adaptive immune responses in RA and SLE, and neutrophil extracellular traps (NETs) expose nuclear neoepitopes (citrullinated proteins in RA, double-stranded DNA and nuclear proteins in SLE) to the immune system, initiating the production of auto-antibodies (ACPA in RA, anti-dsDNA and anti-acetylated/methylated histones in SLE). Neutrophil apoptosis is dysregulated in both conditions in RA, delayed apoptosis within synovial joints contributes to chronic inflammation, immune cell recruitment and prolonged relemune disease.Antiretroviral treatment (ART) reduces the risk of developing active tuberculosis (TB) in HIV-1 co-infected persons. In order to understand host immune responses during ART in the context of Mycobacterium tuberculosis (Mtb) sensitization, we performed RNAseq analysis of whole blood-derived RNA from individuals with latent TB infection coinfected with HIV-1, during the first 6 months of ART. A significant fall in RNA sequence abundance of the Hallmark IFN-alpha, IFN-gamma, IL-6/JAK/STAT3 signaling, and inflammatory response pathway genes indicated reduced immune activation and inflammation at 6 months of ART compared to day 0. Further exploratory evaluation of 65 soluble analytes in plasma confirmed the significant decrease of inflammatory markers after 6 months of ART. Next, we evaluated 30 soluble analytes in QuantiFERON Gold in-tube (QFT) samples from the Ag stimulated and Nil tubes, during the first 6 months of ART in 30 patients. There was a significant decrease in IL-1alpha and IL-1beta (Ag-Nil) concentrations as well as MCP-1 (Nil), supporting decreased immune activation and inflammation. At the same time, IP-10 (Ag-nil) concentrations significantly increased, together with chemokine receptor-expressing CD4 T cell numbers. Our data indicate that ART-induced decrease in immune activation combined with improved antigen responsiveness may contribute to reduced susceptibility to tuberculosis in HIV-1/Mtb co-infected persons.Aging is associated with a decline in many components of the immune system (immunosenescence). link3 Probiotics may improve the immune response in older people. The objective was to determine the effect of the combination of two probiotic organisms [Lacticaseibacillus (previously known as Lactobacillus) rhamnosus GG (LGG) and Bifidobacterium animalis subsp. lactis, BB-12 (BB-12)] on a range of immune biomarkers measured in the blood of older people resident in care homes in the UK. In a randomized controlled trial, older people [aged 67-97 (mean 86) years] resident in care homes received the combination of LGG+BB-12 (1.3-1.6 × 109 CFU per day) or placebo for up to 12 months. Full blood count, blood immune cell phenotypes, plasma immune mediator concentrations, phagocytosis, and blood culture responses to immune stimulation were all measured. Response to seasonal influenza vaccination was measured in a subset of participants. Paired samples (i.e., before and after intervention) were available for 30 participants per group. LGG and BB-12 were more likely to be present in feces in the probiotic group and were present at higher numbers. There was no significant effect of the probiotics on components of the full blood count, blood immune cell phenotypes, plasma immune mediator concentrations, phagocytosis by neutrophils and monocytes, and blood culture responses to immune stimulation. There was an indication that the probiotics improved the response to seasonal influenza vaccination with significantly (p = 0.04) higher seroconversion to the A/Michigan/2015 vaccine strain in the probiotic group than in the placebo group (47 vs. 15%).Background The overall performance of a multiple component vaccine assessed by the vaccine-elicited immune responses across various strains in a repeated vaccination setting has not been well-studied, and the comparison between adults and teenagers is yet to be made. Methods A human cohort study was conducted at the University of Georgia, with 140 subjects (86 adults and 54 teenagers) repeatedly vaccinated in the 2017/2018 and 2018/2019 influenza seasons. Host information was prospectively collected, and serum samples were collected before and after vaccination in each season. The association between host factors and repeated measures of hemagglutination inhibition (HAI) composite scores was assessed by generalized linear models with generalized estimating equations. Results The mean HAI composite scores for the entire sample (t = 4.26, df = 139, p less then 0.001) and the teenager group (t = 6.44, df = 53, p less then 0.001) declined in the second season, while the changes in the adults were not statistically significant (t = -1.14, df = 85, p = 0.26). A mixture pattern of changes in both directions was observed in the adults when stratified by prior vaccination. In addition, the regression analysis suggested an interactive effect of age and BMI on the HAI composite scores in the overall population (beta = 0.005; 95% CI, 0.0008-0.01) and the adults (beta = 0.005; 95% CI, 0.0005-0.01). Conclusions Our study found distinct vaccine-elicited immune responses between adults and teenagers when both were repeatedly vaccinated in consecutive years. An interactive effect of age and BMI on the HAI composite scores were identified in the overall population and the adults.Regardless of the eventual site of disease, the point of entry for Mycobacterium tuberculosis (M.tb) is via the respiratory tract and tuberculosis (TB) remains primarily a disease of the lungs. Immunological biomarkers detected from the respiratory compartment may be of particular interest in understanding the complex immune response to M.tb infection and may more accurately reflect disease activity than those seen in peripheral samples. Studies in humans and a variety of animal models have shown that biomarkers detected in response to mycobacterial challenge are highly localized, with signals seen in respiratory samples that are absent from the peripheral blood. Increased understanding of the role of pulmonary specific biomarkers may prove particularly valuable in the field of TB vaccines. Here, development of vaccine candidates is hampered by the lack of defined correlates of protection (COPs). Assessing vaccine immunogenicity in humans has primarily focussed on detecting these potential markers of protection in peripheral blood.
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