Robertsgammelgaard6441

Transient promoter activation assay in Arabidopsis protoplasts verified that BrMYBL2.1-G, but not BrMYBL2.1-P, can repress transcriptional activation of BrCHS and BrDFR, which was activated by co-expression with BrPAP1 and BrTT8. We determined that BrMYBL2.1-P may be more prone to degradation than BrMYBL2.1-G via ubiquitination. Taken together, these results demonstrate that BrMYBL2.1-G blocks the activity of the MBW complex and thus represses anthocyanin biosynthesis, whereas the variant BrMYBL2.1-P from purple Chinese cabbage cannot, thus leading to higher anthocyanin accumulation.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disease. To date, more than 1000 genes have been shown to be associated with ASD, and only a few of these genes account for more than 1% of autism cases. Klf7 is an important transcription factor of cell proliferation and differentiation in the nervous system, but whether klf7 is involved in autism is unclear.

We first performed ChIP-seq analysis of klf7 in N2A cells, then performed behavioral tests and RNA-seq in klf7

mice, and finally restored mice with adeno-associated virus (AAV)-mediated overexpression of klf7 in klf7

mice.

Klf7 targeted genes are enriched with ASD genes, and 631 ASD risk genes are also differentially expressed in klf7

mice which exhibited the core symptoms of ASD. When klf7 levels were increased in the central nervous system (CNS) in klf7

adult mice, deficits in social interaction, repetitive behavior and majority of dysregulated ASD genes were rescued in the adults, suggesting transcriptional regulation. Moreover, knockdown of klf7 in human brain organoids caused dysregulation of 517 ASD risk genes, 344 of which were shared with klf7

mice, including some high-confidence ASD genes.

Our findings highlight a klf7 regulation of ASD genes and provide new insights into the pathogenesis of ASD and promising targets for further research on mechanisms and treatments.

Our findings highlight a klf7 regulation of ASD genes and provide new insights into the pathogenesis of ASD and promising targets for further research on mechanisms and treatments.Cold stress is one of the abiotic stress conditions that severely limit plant growth and development and productivity. Triacylglycerol lipases are important metabolic enzymes for the catabolism of triacylglycerols and, therefore, play important roles in cellular activities including seed germination and early seedling establishment. However, whether they play a role in cold stress responses remains unknown. In this study, we characterized two Arabidopsis triacylglycerol lipases, MPL1 and LIP1 and defined their role in cold stress. The expression of MPL1 and LIP1 is reduced by cold stress, suggesting that they may be negative factors related to cold stress. Indeed, we found that loss-of-function of MPL1 and LIP1 resulted in increased cold tolerance and that the mpl1lip1 double mutant displayed an additive effect on cold tolerance. We performed RNA-seq analysis to reveal the global effect of the mpl1 and lip1 mutations on gene expression under cold stress. The mpl1 mutation had a small effect on gene expression under both under control and cold stress conditions whereas the lip1 mutation caused a much stronger effect on gene expression under control and cold stress conditions. The mpl1lip1 double mutant had a moderate effect on gene expression under control and cold stress conditions. Together, our results indicate that MPL1 and LIP1 triacylglycerol lipases are negative regulators of cold tolerance without any side effects on growth in Arabidopsis and that they might be ideal candidates for breeding cold-tolerant crops through genome editing technology.Anther indehiscence and pollen sterility caused by high temperature (HT) stress have become a major problem that decreases the yield of cotton. Pollen- and anther-specific genes play a critical role in the process of male reproduction and the response to HT stress. In order to identify pollen-specific genes that respond to HT stress, a comparative transcriptome profiling analysis was performed in the pollen and anthers of Gossypium hirsutum HT-sensitive Line H05 against other tissue types under normal temperature (NT) conditions, and the analysis of a differentially expressed gene was conducted in the pollen of H05 under NT and HT conditions. In total, we identified 1111 pollen-specific genes (PSGs), 1066 anther-specific genes (ASGs), and 833 pollen differentially expressed genes (DEGs). Moreover, we found that the late stage of anther included more anther- and pollen-specific genes (APSGs). Stress-related cis-regulatory elements (CREs) and hormone-responsive CREs are enriched in the promoters of APSGs, suggesting that APSGs may respond to HT stress. SKF-34288 molecular weight However, 833 pollen DEGs had only 10 common genes with 1111 PSGs, indicating that PSGs are mainly involved in the processes of pollen development and do not respond to HT stress. Promoters of these 10 common genes are enriched for stress-related CREs and MeJA-responsive CREs, suggesting that these 10 common genes are involved in the process of pollen development while responding to HT stress. This study provides a pathway for rapidly identifying cotton pollen-specific genes that respond to HT stress.The sharp eyespot, mainly caused by the soil-borne fungus Rhizoctonia cerealis, is a devastating disease endangering production of wheat (Triticum aestivum). Multi-Antimicrobial Extrusion (MATE) family genes are widely distributed in plant species, but little is known about MATE functions in wheat disease resistance. In this study, we identified TaPIMA1, a pathogen-induced MATE gene in wheat, from RNA-seq data. TaPIMA1 expression was induced by Rhizoctonia cerealis and was higher in sharp eyespot-resistant wheat genotypes than in susceptible wheat genotypes. Molecular biology assays showed that TaPIMA1 belonged to the MATE family, and the expressed protein could distribute in the cytoplasm and plasma membrane. Virus-Induced Gene Silencing plus disease assessment indicated that knock-down of TaPIMA1 impaired resistance of wheat to sharp eyespot and down-regulated the expression of defense genes (Defensin, PR10, PR1.2, and Chitinase3). Furthermore, TaPIMA1 was rapidly induced by exogenous H2O2 and jasmonate (JA) treatments, which also promoted the expression of pathogenesis-related genes. These results suggested that TaPIMA1 might positively regulate the defense against R. cerealis by up-regulating the expression of defense-associated genes in H2O2 and JA signal pathways. This study sheds light on the role of MATE transporter in wheat defense to Rhizoctonia cerealis and provides a potential gene for improving wheat resistance against sharp eyespot.CD8+ T lymphocytes are a heterogeneous class of cells that play a crucial role in the adaptive immune response against pathogens and cancer. During their lifetime, they acquire cytotoxic functions to ensure the clearance of infected or transformed cells and, in addition, they turn into memory lymphocytes, thus providing a long-term protection. During ageing, the thymic involution causes a reduction of circulating T cells and an enrichment of memory cells, partially explaining the lowering of the response towards novel antigens with implications in vaccine efficacy. Moreover, the persistent stimulation by several antigens throughout life favors the switching of CD8+ T cells towards a senescent phenotype contributing to a low-grade inflammation that is a major component of several ageing-related diseases. In genetically predisposed young people, an immunological stress caused by viral infections (e.g., HIV, CMV, SARS-CoV-2), autoimmune disorders or tumor microenvironment (TME) could mimic the ageing status with the consequent acceleration of T cell senescence. This, in turn, exacerbates the inflamed conditions with dramatic effects on the clinical progression of the disease. A better characterization of the phenotype as well as the functions of senescent CD8+ T cells can be pivotal to prevent age-related diseases, to improve vaccine strategies and, possibly, immunotherapies in autoimmune diseases and cancer.Colorectal cancer (CRC) is the second most common cause of cancer death in the world. Both modifiable and nonmodifiable risk factors play a significant role in the pathogenesis of this tumor. The diagnosis is usually made late due to limitations of screening tests; therefore, the scientists are looking for new diagnostic tools such as gene or miRNA expression or different proteins' concentrations, e.g., vascular endothelial growth factor (VEGF) family members. The VEGF family (VEGF-A, VEGF-B, VEGF-C, VEGF-D and PlGF) plays a key role in the processes of blood vessel formation in embryonic development as well as in pathological angiogenesis and lymphangiogenesis, which allow the tumor to grow exponentially. Blockage of VEGF-related pathways seems to be a valid therapeutic target. It was suggested in recent studies, that besides already used drugs, e.g., bevacizumab, there are other agents with potential usefulness in anticancer activity such as miRNAs, TMEA, granzyme K, baicalein and arginine. Moreover, VEGF proteins were assessed to induce the expression of anti-apoptotic proteins such as BCL-2 and BAX. Therefore, investigations concerning the usefulness of VEGF family members, not only in the development but also in the therapy of CRC, in order to fully elucidate their role in carcinogenesis, are extremely important.Monocytes expressing the inflammation suppressing active CD11b, a beta2 integrin, may regulate neuroinflammation and modify clinical outcomes in amyotrophic lateral sclerosis (ALS). In this single site, retrospective study, peripheral blood mononuclear cells from 38 individuals living with ALS and 20 non-neurological controls (NNC) were investigated using flow cytometry to study active CD11b integrin classical (CM), intermediate (IM) and non-classical (NCM) monocytes during ALS progression. Seventeen ALS participants were sampled at the baseline (V1) and at two additional time points (V2 and V3) for longitudinal analysis. Active CD11b+ CM frequencies increased steeply between the baseline and V3 (ANOVA repeated measurement, p < 0.001), and the V2/V1 ratio negatively correlated with the disease progression rate, similar to higher frequencies of active CD11b+ NCM at the baseline (R = -0.6567; p = 0.0031 and R = 0.3862; p = 0.0168, respectively). CD11b NCM, clinical covariates and neurofilament light-chain plasma concentration at the baseline predicted shorter survival in a multivariable and univariate analysis (CD11b NCM-HR 1.05, CI 1.01-1.11, p = 0.013. Log rank above median 43 months and below median 21.22 months; p = 0.0022). Blood samples with the highest frequencies of active CD11b+ IM and NCM contained the lowest concentrations of soluble CD11b. Our preliminary data suggest that the levels of active CD11b+ monocytes and NCM in the blood predict different clinical outcomes in ALS.Inflammation in the context of Human Immunodeficiency Virus (HIV) establishes early and persists beyond antiretroviral therapy (ART). As such, we have shown excess B-cell activating factor (BAFF) in the blood of HIV-infected progressors, as soon as in the acute phase, and despite successful ART. Excess BAFF was associated with deregulation of the B-cell compartment; notably, with increased frequencies of a population sharing features of both transitional immature (TI) and marginal zone (MZ) B-cells, we termed Marginal Zone precursor-like (MZp). We have reported similar observations with HIV-transgenic mice, Simian Immunodeficiency Virus (SIV)-infected macaques, and more recently, with HIV-infected Beninese commercial sex workers, which suggests that excess BAFF and increased frequencies of MZp B-cells are reliable markers of inflammation in the context of HIV. Importantly, we have recently shown that in healthy individuals, MZps present an important regulatory B-cell (Breg) profile and function. Herein, we wish to review our current knowledge on MZ B-cell populations, especially their Breg status, and that of other B-cell populations sharing similar features.