-
Weeks Rutledge posted an update 7 hours, 43 minutes ago
Human papillomavirus type 16 (HPV16) is the most common HPV genotype found in invasive cervical cancer (ICC). Recent comprehensive genomics studies of HPV16 have revealed that a large number of minor nucleotide variations in the viral genome are present in each infected woman; however, it remains unclear whether such within-host variations of HPV16 are linked to cervical carcinogenesis. Here, by employing next-generation sequencing approaches, we explored the mutational profiles of the HPV16 genome within individual clinical specimens from ICC (n = 31) and normal cervix (n = 21) in greater detail. A total of 367 minor nucleotide variations (167 from ICC and 200 from the normal cervix) were detected throughout the viral genome in both groups, while nucleotide variations at high frequencies (>10% abundance in relative read counts in a single sample) were more prevalent in ICC (10 in ICC versus 1 in normal). Among the high-level variations found in ICC, six were located in the E1/E2 genes, and all of them were non-synonymous substitutions (Q142K, M207I, and L262V for E1; D153Y, R302T, and T357A for E2). In vitro functional analyses of these E1/E2 variants revealed that E1/M207I, E2/D153Y, and E2/R302T had reduced abilities to support viral replication, and that E2/D153Y and E2/R302T failed to suppress the viral early promoter. These results imply that some within-host variations of E1/E2 present at high levels in ICC may be positively selected for and contribute to cervical cancer development through dysfunction or de-stabilization of viral replication/transcription proteins.Baijiu is a traditional distilled beverage in China with a rich variety of aroma substances. 2,3,5,6-tetramethylpyrazine (TTMP) is an important component in Baijiu and has the function of promoting cardiovascular and cerebrovascular health. During the brewing of Baijiu, the microorganisms in jiuqu produce acetoin and then synthesize TTMP, but the yield of TTMP is very low. In this work, 2,3-butanediol dehydrogenase (BDH) coding gene BDH1 and another BDH2 gene were deleted or overexpressed to evaluate the effect on the content of acetoin and TTMP in Saccharomyces cerevisiae. The results showed that the acetoin synthesis of strain α5-D1B2 was significantly enhanced by disrupting BDH1 and overexpressing BDH2, leading to a 2.6-fold increase of TTMP production up to 10.55 mg/L. To further improve the production level of TTMP, the α-acetolactate synthase (ALS) of the pyruvate decomposition pathway was overexpressed to enhance the synthesis of diacetyl. However, replacing the promoter of the ILV2 gene with a strong promoter (PGK1p) to increase the expression level of the ILV2 gene did not result in further increased diacetyl, acetoin and TTMP production. Based on these evidences, we constructed the diploid strains AY-SB1 (ΔBDH1loxP/ΔBDH1loxP) and AY-SD1B2 (ΔBDH1loxP-PGK1p-BDH2-PGK1t/ΔBDH1loxP-PGK1p-BDH2-PGK1t) to ensure the fermentation performance of the strain is more stable in Baijiu brewing. The concentration of TTMP in AY-SB1 and AY-SD1B2 was 7.58 and 9.47 mg/L, respectively, which represented a 2.3- and 2.87-fold increase compared to the parental strain. This work provides an example for increasing TTMP production in S. ARS-1620 mw cerevisiae by genetic engineering, and highlight a novel method to improve the quality and beneficial health attributes of Baijiu.[This corrects the article DOI 10.3389/fmicb.2015.00075.].Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a widespread outbreak of highly pathogenic coronavirus disease 2019 (COVID-19). It is therefore important and timely to characterize interactions between the virus and host cell at the molecular level to understand its disease pathogenesis. To gain insights, we performed high-throughput sequencing that generated time-series data simultaneously for bioinformatics analysis of virus genomes and host transcriptomes implicated in SARS-CoV-2 infection. Our analysis results showed that the rapid growth of the virus was accompanied by an early intensive response of host genes. We also systematically compared the molecular footprints of the host cells in response to SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV). Upon infection, SARS-CoV-2 induced hundreds of up-regulated host genes hallmarked by a significant cytokine production, followed by virus-specific host antiviral responses. While the cytokine and antiviral responses triggered by SARS-CoV and MERS-CoV were only observed during the late stage of infection, the host antiviral responses during the SARS-CoV-2 infection were gradually enhanced lagging behind the production of cytokine. The early rapid host responses were potentially attributed to the high efficiency of SARS-CoV-2 entry into host cells, underscored by evidence of a remarkably up-regulated gene expression of TPRMSS2 soon after infection. Taken together, our findings provide novel molecular insights into the mechanisms underlying the infectivity and pathogenicity of SARS-CoV-2.Wine killer yeasts such as killer strains of Torulaspora delbrueckii and Saccharomyces cerevisiae contain helper large-size (4.6 kb) dsRNA viruses (V-LA) required for the stable maintenance and replication of killer medium-size dsRNA viruses (V-M) which bear the genes that encode for the killer toxin. The genome of the new V-LA dsRNA from the T. delbrueckii Kbarr1 killer yeast (TdV-LAbarr1) was characterized by high-throughput sequencing (HTS). The canonical genome of TdV-LAbarr1 shares a high sequence identity and similar genome organization with its Saccharomyces counterparts. It contains all the known conserved motifs predicted to be necessary for virus translation, packaging, and replication. Similarly, the Gag-Pol amino-acid sequence of this virus contains all the features required for cap-snatching and RNA polymerase activity, as well as the expected regional variables previously found in other LA viruses. Sequence comparison showed that two main clusters (99.2-100% and 96.3-98.8% identity) include mostd.The study investigated the impact of dietary montmorillonite on the growth performance, intestinal mucosal barrier, and microbial community in weaned piglets with control group (CON) and dietary supplementation of 0.2% montmorillonite (0.2% M). Compared with the CON group, 0.2% M feed in the diet increased the average daily gain (ADG) on days 15-35 and day 1-35 and the average daily feed intake on days 1-35 (ADFI) (0.05 less then P less then 0.1). Besides, higher villus height of the duodenum and jejunum and lower crypt depth of duodenum and colon were revealed in the 0.2% M group than in the CON group (P less then 0.05). Moreover, the V/C (ratio of the villus height and crypt depth) in the 0.2% M group was increased compared to that in the CON group both from the duodenum and ileum (P less then 0.05). The relative mRNA expression of mucin-1, ITGB1 (β1-integrins), and PKC (protein kinase C) of ileum in the 0.2% M group were upregulated (P less then 0.05) compared to that in the CON group. The digesta sample of ileum from piglets in the 0.