Structural insights into the negative regulation of BRI1 signaling by BRI1-interacting protein BKI1

Brassinosteroids (BRs) are essential steroid hormones that have crucial roles in plant growth and development. BRs are perceived by the cell-surface receptor-like kinase brassinosteroid insensitive 1 (BRI1). In the absence of BRs, the cytosolic kinase domain (KD) of BRI1 is inhibited by its auto-inhibitory carboxyl terminus, as well as by interacting with an inhibitor protein, BRI1 kinase inhibitor 1 (BKI1). How BR binding to the extracellular domain of BRI1 leads to activation of the KD and dissociation of BKI1 into the cytosol remains unclear. Here we report the crystal structure of BRI1 KD in complex with the interacting peptide derived from BKI1. We also provide biochemical evidence that BRI1-associated kinase 1 (BAK1) plays an essential role in initiating BR signaling. Steroid-dependent heterodimerization of BRI1 and BAK1 ectodomains brings their cytoplasmic KDs in the right orientation for competing with BKI1 and transphosphorylation.     

G protein-coupled receptors in energy homeostasis

G-protein coupled receptors (GPCRs) compromise the largest membrane protein superfamily which play vital roles in physiological and pathophysiological processes including energy homeostasis. Moreover, they also represent the up-to-date most successful drug target. The gut hormone GPCRs, such as glucagon receptor and GLP-1 receptor, have been intensively studied for their roles in metabolism and respective drugs have developed for the treatment of metabolic diseases such as type 2 diabetes (T2D). Along with the advances of biomedical research, more GPCRs have been found to play important roles in the regulation of energy homeostasis from nutrient sensing, appetite control to glucose and fatty acid metabolism with various mechanisms. The investigation of their biological functions will not only improve our understanding of how our body keeps the balance of energy intake and expenditure, but also highlight the possible drug targets for the treatment of metabolic diseases. The present review summarizes GPCRs involved in the energy control with special emphasis on their pathophysiological roles in metabolic diseases and hopefully triggers more intensive and systematic investigations in the field so that a comprehensive network control of energy homeostasis will be revealed, and better drugs will be developed in the foreseeable future.     

C-MYC Aberrations as Prognostic Factors in Diffuse Large B-cell Lymphoma: A Meta-Analysis of Epidemiological Studies

Objectives

Various studies have investigated the prognostic value of C-MYC aberrations in diffuse large B-cell lymphoma (DLBCL). However, the role of C-MYC as an independent prognostic factor in clinical practice remains controversial. A systematic review and meta-analysis were performed to clarify the clinical significance of C-MYC aberrations in DLBCL patients.

Methods

The pooled hazard ratios (HRs) for overall survival (OS) and event-free survival (EFS) were calculated as the main effect size estimates. The procedure was conducted according to the Cochrane handbook and PRISMA guidelines, including the use of a heterogeneity test, publication bias assessment, and meta-regression, as well as subgroup analyses.

Results

Twenty-four eligible studies enrolling 4662 patients were included in this meta-analysis. According to the nature of C-MYC aberrations (gene, protein, and mRNA), studies were divided into several subgroups. For DLBCL patients with C-MYC gene abnormalities, the combined HR was 2.22 (95% confidence interval, 1.89 to 2.61) for OS and 2.29 (95% confidence interval, 1.81 to 2.90) for EFS, compared to patients without C-MYC gene abnormalities. For DLBCL patients with overexpression of C-MYC protein and C-MYC mRNA, pooled HRs for OS were 2.13 and 1.62, respectively. C-MYC aberrations appeared to play an independent role among other well-known prognostic factors in DLBCL. Addition of rituximab could not overcome the inferior prognosis conferred by C-MYC.

Conclusion

The present systematic review and meta-analysis confirm the prognostic value of C-MYC aberrations. Screening of C-MYC should have definite prognostic meaning for DLBCL stratification, thus guaranteeing a more tailored therapy.     

Isolation,Identification, Biocontrol Activity,and Plant Growth Promoting Capability of a Superior Streptomyces tricolor Strain HM10

Streptomyces is a genus with known biocontrol activity, producing a broad range of biologically active substances. Our goal was to isolate local Streptomyces species, evaluate their capacity to biocontrol the selected phytopathogens, and promote the plant growth via siderophore and indole acetic acid (IAA) production and phosphate solubilization. Eleven isolates were obtained from local soil samples in Saudi Arabia via the standard serial dilution method and identified morphologically by scanning electron microscope (SEM) and 16S rRNA amplicon sequencing. The biocontrol of phytopathogens was screened against known soil-borne fungi and bacteria. Plant growth promotion capacity was evaluated based on siderophore and IAA production and phosphate solubilization capacity. From eleven isolates obtained, one showed 99.77% homology with the type strain Streptomyces tricolor AS 4.1867, and was designated S. tricolor strain HM10. It showed aerial hyphae in SEM, growth inhibition of ten known phytopathogens in in vitro experiments, and the production of plant growth promoting compounds such as siderophores, IAA, and phosphate solubilization capacity. S. tricolor strain HM10 exhibited high antagonism against the fungi tested (i.e., Colletotrichum gloeosporides with an inhibition zone exceeding 18 mm), whereas the lowest antagonistic effect was against Alternaria solani (an inhibition zone equal to 8 mm). Furthermore, the most efficient siderophore production was recorded to strain HM8, followed by strain HM10 with 64 and 22.56 h/c (halo zone area/colony area), respectively. Concerning IAA production, Streptomyces strain HM10 was the most effective producer with a value of 273.02 μg/ml. An autochthonous strain S. tricolor HM10 should be an important biological agent to control phytopathogens and promote plant growth.