Identification and Validation of a Prognostic Model Based on Three MVI-Related Genes in Hepatocellular Carcinoma

MVI has significant clinical value for treatment selection and prognosis evaluation in hepatocellular carcinoma (HCC). We aimed to construct a model based on MVI-Related Genes (MVIRGs) for risk assessment and prognosis prediction in patients with HCC. This study utilized various statistical analysis methods for prognostic model construction and validation in the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) cohorts, respectively. In addition, immunohistochemistry and qRT-PCR were used to analyze and identify the value of the model in our cohort. After the analyses, 153 differentially expressed MVIRGs were identified, and three key genes were selected to construct a prognostic model. The high-risk group showed significantly lower overall survival (OS), and this trend was observed in all subgroups: different age groups, genders, stages, and grades. Risk score was a risk factor independent of age, gender, stage, and grade. Moreover, the ICGC cohort validated the prognostic value of the model corresponding to the TCGA. In our cohort, qRT-PCR and immunohistochemistry showed that all three genes had higher expression levels in HCC samples than in normal controls. High expression levels of genes and high-risk scores showed significantly lower recurrence-free survival (RFS) and OS, especially in MVI-positive HCC samples. Therefore, the prognostic model constructed by three MVIRGs can reliably predict the RFS and OS of patients with HCC and is valuable for guiding clinical treatment selection and prognostic assessment of HCC.     

cDNA cloning of an alternative splicing variant of protein kinase C delta (PKC deltaIII), a new truncated form of PKCdelta, in rats

Recently, an alternative splicing variant of mouse protein kinase C delta (PKC deltaII, GenBank Accession No. AB011812) has been reported which has a 78 bp (26 amino acid) insertion at the caspase-3 recognition sequence in the V3 region of PKC delta (PKC deltaI). We isolated a cDNA encoding a new variant of PKC delta (PKC deltaIII, AF219629), which has a 83 bp insertion at the same site in the V3 region, by RT-PCR using rat testis RNA as a template. In rats, the 83 bp insertion causes inframe termination, and rat PKC deltaIII protein is expressed as a truncated form, having only the regulatory domain without a catalytic domain. Genomic DNA analysis revealed that the difference between mouse PKC deltaII and rat PKC deltaIII is derived from the different sequence at the 5'-splicing donor sites. To investigate the potential functions of the truncated form of PKC delta, rat PKC deltaIII fused to green fluorescent protein (GFP) was expressed in CHO-K1 cells. PKC deltaIII-GFP was localized in the cytoplasm with dot-like accumulation and highly expressed on the plasma membrane, whereas PKC deltaI-GFP is localized homogeneously throughout the cytoplasm, including the nucleoplasm. Stimulation by phorbol ester caused weak translocation of deltaIII-GFP from the cytosol to the plasma membrane. These results suggest that PKC deltaIII may show a dominant negative effect against PKC deltaI, and that the modulation of signal transduction by alternative splicing variant may play a crucial role in the physiological and/or pathological conditions, and the pathogenesis of disease.     

The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway

Protein ubiquitination and deubiquitination are dynamic processes implicated in the regulation of numerous cellular pathways. Monoubiquitination of the Fanconi anemia (FA) protein FANCD2 appears to be critical in the repair of DNA damage because many of the proteins that are mutated in FA are required for FANCD2 ubiquitination. By screening a gene family RNAi library, we identify the deubiquitinating enzyme USP1 as a novel component of the Fanconi anemia pathway. Inhibition of USP1 leads to hyperaccumulation of monoubiquitinated FANCD2. Furthermore, USP1 physically associates with FANCD2, and the proteins colocalize in chromatin after DNA damage. Finally, analysis of crosslinker-induced chromosomal aberrations in USP1 knockdown cells suggests a role in DNA repair. We propose that USP1 deubiquitinates FANCD2 when cells exit S phase or recommence cycling after a DNA damage insult and may play a critical role in the FA pathway by recycling FANCD2.     

Potential Applications in Sewage Bioremediation of the Highly Efficient Pyridine-Transforming Paenochrobactrum sp.

Applied Biochemistry and Microbiology - A pyridine-transforming strain P2 was isolated from sewage collected from Guangzhou oil stain field(China).According to the system analysis, it was...     

Ecological and acoustic responses of bush crickets to anthropogenic and natural ecotones

Biodiversity and Conservation - Ecotones occur naturally throughout complex landscapes. Each ecotone has particular ecological conditions resulting in species-specific responses. Across...     

The importance of naturally attenuated SARS-CoV-2in the fight against COVID-19

The current SARS-CoV-2 pandemic is wreaking havoc throughout the world and has rapidly become a global health emergency. A central question concerning COVID-19 is why some individuals become sick and others not. Many have pointed already at variation in risk factors between individuals. However, the variable outcome of SARS-CoV-2 infections may, at least in part, be due also to differences between the viral subspecies with which individuals are infected. A more pertinent question is how we are to overcome the current pandemic. A vaccine against SARS-CoV-2 would offer significant relief, although vaccine developers have warned that design, testing and production of vaccines may take a year if not longer. Vaccines are based on a handful of different designs (i), but the earliest vaccines were based on the live, attenuated virus. As has been the case for other viruses during earlier pandemics, SARS-CoV-2 will mutate and may naturally attenuate over time (ii). What makes the current pandemic unique is that, thanks to state-of-the-art nucleic acid sequencing technologies, we can follow in detail how SARS-CoV-2 evolves while it spreads. We argue that knowledge of naturally emerging attenuated SARS-CoV-2 variants across the globe should be of key interest in our fight against the pandemic.