The influenza virus PB1 protein functions as a catalytic subunit of the viral RNA-dependent RNA polymerase and contains the highly conserved motifs of RNA-dependent RNA polymerases together with putative nucleotide-binding sites. PB1 also binds to viral genomic RNAs and its replicative intermediates through the promoter regions. The detail function and interplay between functional domains are not clarified although a part of structures and functions of PB1 have been clarified. In this study, we analyzed the function of PB1 subunit in the sense of nucleotide recognition using ribavirin, which is a nucleoside analog and inhibits viral RNA synthesis of many RNA viruses including influenza virus. We screened ribavirin-resistant PB1 mutants from randomly mutated PB1 cDNA library using a mini-replicon assay, and we identified a single mutation at the amino acid position 27 of PB1 as an important residue for the nucleotide recognition.
The influenza virus genome forms viral ribonucleoprotein (vRNP) complexes with nucleoprotein and viral RNA-dependent RNA polymerases (RdRp), PB1, PB2, and PA subunits. The vRNP complex catalyzes both genome replication and transcription reactions. PB1 contains the motifs highly conserved among RdRps and functions as a catalytic subunit of RdRp. The N-terminal region of PB1 between amino acid (a.a.) positions 1–83 contains both putative vRNA and cRNA promoter binding sites and a PA binding site. However, except for the PA binding site, the crystal structure and the function of the N-terminal region of PB1 are poorly understood. Here, we have examined the functional structure of the N-terminal region of PB1. The regions between a.a. positions 1–50 are highly conserved between influenza A and B viruses, but amino acids at positions 16, 27, and 44 are different between two viruses. To elucidate the functional importance of these amino acids in replication and transcription of the viral genome, we generated viruses containing mutations at these positions by reverse genetics and examined replication and transcription activities of these mutants. We found that a.a. positions 27 and 44 are responsible for the viral replication activity but not transcription activity.
Selenium nanoparticles (SeNPs) with diameters from 64.8 to 110.1 nm were successfully synthesized by γ-irradiation of solutions containing Se4+ and water-soluble yeast β-glucan. The size and size distribution of SeNPs were analyzed by dynamic light scattering (DLS). Analytical X-ray diffraction (XRD) pattern results confirmed the crystal structure of the Se nanoparticles and Fourier transform infrared (FTIR) spectroscopy revealed that β-glucan could interact with SeNPs through steric (Se…O) linkages leading to a homogeneous and translucent solution state for 60 days without any precipitates. In vivo tests in cytoxan-induced immunosuppressed mice revealed that the daily supplementation of SeNPs/β-glucan at concentrations of 6 mg per kg body weight of tested mice significantly stimulated the generation of cellular immune factors (white blood cells, neutrophil, lymphocyte, B cells, CD4+ cells, CD34+ cells and natural killer cells) and humoral immune indexes (IgM, IgG, TNF-α, IFN-γ and IL-2) in peripheral blood, bone marrow and spleen of the immunosuppressed mice. The obtained results indicated that radiation-synthesized SeNPs/β-glucan may be a candidate for further evaluation as an agent for the prevention of immunosuppression in chemotherapy.
Anti-aging is one of the top goals in the field of health care and aesthetics. Anti-aging cosmetics derived from nature are oriented to long-term development, bringing safety to users and being environmentally friendly. The aim of this study was to develop an anti-aging cosmetic formulation process based on coconut oil in combination with deer antler stem cell extract. The results show that the presence of deer antler stem cell extract added to the foundation made the serum product highly stable and helped improve skin aging significantly after 2 weeks of use. The skin site where the serum product was applied showed a smooth and elastic skin surface, with very few fine lines and shallow wrinkles. Serum reduced the number of wrinkles (48.09% compared to commercial serum (ME) and 60.31% compared to positive control (PC)), reduced skin recovery time (39.31% compared to ME and 67.1% of PC) after two weeks of use. After 2 weeks of use, collagen density increased 10.18% compared to ME and 63.76% compared to control. Epidermal thickness increased by 106.1% compared to PC and 121.7% compared to ME.
Background: Identification of germline and somatic BRCA1/2 mutations in ovarian cancer is important for genetic counseling and treatment decision making with poly ADP ribose polymerase inhibitors. Unfortunately, data on the frequency of BRCA1/2 mutations in Vietnamese patients are scare. Methods: We aim to explore the occurrence of BRCA1/2 mutations in 101 Vietnamese patients with ovarian cancer including serous (n = 58), endometrioid (n = 14), mucinous (n = 24), and clear cell (n = 5) carcinomas. BRCA1/2 mutations were detected from formalin-fixed parafinembedded tumor samples using the Oncomine TM BRCA Research Assay on Personal Genome Machine Platform with Ion Reporter Software for sequencing data analysis. The presence of pathogenic mutations was confirmed by Sanger sequencing. Results: We found no BRCA2 mutation in the entire cohort. Four types of pathogenic mutations in BRCA1 (Ser454Ter, Gln541Ter, Arg1751Ter, and Gln1779AsnfsTer14) were detected in 8 unrelated patients (7.9%) belonging to serous and endometrioid carcinoma groups. Except for the c.1360_1361delAG (Ser454Ter) mutation in BRCA1 exon 11 that was somatic, the other mutations in exons 11, 20, and 22 were germline. Interestingly, the recurrent Arg1751Ter mutation in BRCA1 exon 20 appeared in 4 patients, suggesting that this is a founder mutation in Vietnamese patients. Conclusion: Mutational analysis of tumor tissue using next generation sequencing allowed the detection of both germline and somatic BRCA1/2 mutations.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.