A new design without control population for identification of gastric cancer-related allele combinations based on interaction of genes

Objective

The purpose of this study was to develop a novel approach without control population to examine the relationship between the presence of specific allele combinations at different loci with the onset of gastric cancer.

Methods

DNA samples were collected from patients with gastric cancer. Alleles from short tandem repeat loci were determined using the STR Profiler Plus PCR amplification kit (15 STR loci). The observed and expected frequencies of specific allele combinations were calculated; statistically significant allele combinations were identified by comparing the observed frequency with the expected frequency. The age at disease onset of patients carrying a specific allele combination was further analysed; allele combinations related to the gastric cancer were effectively identified from the large number of possible allele combinations by cross-validation of the 2 sets of analytical results.

Results

A total of 2209 pairwise combinations were obtained by computer counting, of which 11 pairs of genes showed significant differences between the observed and expected frequencies (p < 0.05). The p value for the cross-validation was also less than 0.05 for 2 pair of alleles (D8S1179-16 and D5S818-13; D2S1338-23 and D6S1043-11).

Conclusion

Gastric cancer onset may be associated with these allele combinations. The new methodology without control group will enable additional discoveries pertaining to the relationship between specific allele combinations at different loci and the onset of complex diseases.     

Molecular diversity of arbuscular mycorrhizal fungi associated with two co-occurring perennial plant species on a Tibetan altitudinal gradient

Plant communities on Mount Segrila on the Tibetan Plateau show distinct changes at different altitudes, but little information is available on belowground communities of arbuscular mycorrhizal fungi (AMF). Root samples of two co-occurring species, Pennisetum centrasiaticum and Kobresia sp., growing in open grasslands at eight altitudes (3,446–4,556 m) were analyzed for diversity of AMF by PCR, cloning, and sequencing. Dominant plants were well colonized by AMF even at higher altitudes where spore density in rhizospheres decreased dramatically. A total of 29 operational taxonomic units (OTUs) of AMF were detected, and some novel sequence types were found. Acaulosporaceae and Glomeraceae were the dominant families. There was no significant difference in OTU richness along elevational gradients in Kobresia sp., but OTU richness in P. centrasiaticum was higher at intermediate elevations. Elevation, host plant species, and soil variables (pH, soil organic matter, and available P and N) were found to have significant effects on the overall AMF community across all elevations. Fungal community composition differed significantly between the two plant species at each elevation, and the similarity was generally higher at the intermediate elevations. No significant difference in compositional similarity was observed for Kobresia sp. with increasing elevation, but the dissimilarity increased significantly for P. centrasiaticum. These results suggest that host identity is an important determinant for the structure of the AMF communities along the elevational gradients in high altitude environments.     

Pre-ribosomal RNA reorganizes DNA damage repair factors in nucleus during meiotic prophase and DNA damage response

In response to DNA double-strand breaks(DSBs),DNA damage repair factors are recruited to DNA lesions and form nuclear foci.However,the underlying molecular mech...     

Regulation of CK2 by phosphorylation and O-GlcNAcylation revealed by semisynthesis

Protein serine-threonine kinase casein kinase II (CK2) is involved in a myriad of cellular processes including cell growth and proliferation through its phosphorylation of hundreds of substrates, yet how CK2 function is regulated is poorly understood. Here we report that the CK2 catalytic subunit CK2α is modified by O-linked β-N-acetyl-glucosamine (O-GlcNAc) on Ser347, proximal to a cyclin-dependent kinase phosphorylation site (Thr344). We use protein semisynthesis to show that phosphorylation of Thr344 increases the cellular stability of CK2α by strengthening its interaction with Pin1, whereas glycosylation of Ser347 seems to be antagonistic to Thr344 phosphorylation and permissive to proteasomal degradation. By performing kinase assays with site-specifically phospho- and glyco-modified CK2α in combination with CK2β and Pin1 binding partners on human protein microarrays, we show that the kinase substrate selectivity of CK2 is modulated by these specific post-translational modifications. This study suggests how a promiscuous protein kinase can be regulated at multiple levels to achieve particular biological outputs.     

Baculovirus infection triggers a shift from amino acid starvation-induced autophagy to apoptosis

Autophagy plays a central role in regulating important cellular functions such as cell survival during starvation and control of infectious pathogens. On the other hand, many pathogens have evolved mechanisms of inhibition of autophagy such as blockage of the formation of autophagosomes or the fusion of autophagosomes with lysosomes. Baculoviruses are important insect pathogens for pest control, and autophagy activity increases significantly during insect metamorphosis. However, it is not clear whether baculovirus infection has effects on the increased autophagy. In the present study, we investigated the effects of the Autographa californica nucleopolyhedrovirus (AcMNPV) infection on autophagy in SL-HP cell line from Spodoptera litura induced under amino acid deprivation. The results revealed that AcMNPV infection did not inhibit autophagy but triggered apoptosis under starvation pressure. In the early stage of infection under starvation, mitochondrial dysfunction was detected, suggesting the organelles might be involved in cell apoptosis. The semi-quantitative PCR assay revealed that the expression of both p35 and ie-1 genes of AcMNPV had no significant difference between the starved and unstarved SL-HP cells. The western blot analysis showed that no cleavage of endogenous Atg6 occurred during the process of apoptosis in SL-HP cells. These data demonstrated that some permissive insect cells may defend baculovirus infection via apoptosis under starvation and apoptosis is independent of the cleavage of Atg6 in SL-HP cells.     

Curcumin modulates the self-assembly of the islet amyloid polypeptide by disassembling α-helix

Understanding how small molecules affect amyloid formation is of major biomedical and pharmaceutical importance due to the association of amyloid with incurable diseases including Alzheimer's, Parkinson's, and type II diabetes. Using solution state (1)H NMR, we demonstrate that curcumin, a planar biphenolic compound found in the Indian spice turmeric, delays the self-assembly of islet amyloid polypeptide to NMR-invisible assemblies. Accompanying circular dichroism studies show that curcumin disassembles α-helix in maturing assemblies of IAPP. The amount of α-helix disassembled correlates with predicted and experimentally determined helical content of IAPP obtained by others. Taken together, these results indicate that curcumin modulates IAPP self-assembly by unfolding α-helix on pathway to amyloid. The implications of this work in the elucidation of the mechanism for amyloid formation by IAPP in the presence of curcumin are discussed.     

Metastable region of phase diagram: optimum parameter range for processing ultrahigh molecular weight polyethylene blends

Numerous studies suggest that two-phase morphology and thick interface are separately beneficial to the viscosity reduction and mechanical property maintainence of the matrix when normal molecular weight polymer (NMWP) is used for modification of ultrahigh molecular weight polyethylene (UHMWPE). Nevertheless, it is very difficult to obtain a UHMWPE/NMWP blend which may demonstrate both two-phase morphology and thick interface. In this work, dissipative particle dynamics simulations and Flory-Huggins theory are applied in predicting the optimum NMWP and the corresponding conditions, wherein the melt flowability of UHMWPE can be improved while its mechanical properties can also be retained. As is indicated by dissipative particle dynamics simulations and phase diagram calculated from Flory-Huggins theory, too small Flory-Huggins interaction parameter (χ) and molecular chain length of NMWP (N(NMWP)) may lead to the formation of a homogeneous phase, whereas very large interfacial tension and thin interfaces might also appear when parameters N(NMWP) and χ are too large. When these parameters are located in the metastable region of the phase diagram, however, two-phase morphology occurs and interfaces of the blends are extremely thick. Therefore, metastable state is found to be advisable for both the viscosity reduction and mechanical property improvement of the UHMWPE/NMWP blends.