Kava Components Down-Regulate Expression of AR and AR Splice Variants and Reduce Growth in Patient-Derived Prostate Cancer Xenografts in Mice

Men living in Fiji and drinking kava have low incidence of prostate cancer (PCa). However, the PCa incidence among Fijian men who had migrated to Australia, increased by 5.1-fold. We therefore examined the potential effects of kava root extracts and its active components (kavalactones and flavokawains) on PCa growth and androgen receptor (AR) expression. PCa cell lines (LNCaP, LAPC-4, 22Rv1, C4-2B, DU145 and PC-3) with different AR expression, and a transformed prostate myofibroblast cell line (WPMY-1), were treated with a commercial kava extract, kavalactones (kawain, 5′6′-dehydrokawain, yangonin, methysticin) and flavokawain B. Expression of AR and its target genes (PSA and TMPRSS2) was examined. Two novel patient-derived PCa xenograft models from high grade PCa specimens were established by implanting the specimens into nude mice and passing tumor pieces through subcutaneous injection in nude mice, and then treated with kava extract and flavokawain B to examine their effects on tumor growth, AR expression and serum PSA levels. The kava extract and flavokawain B effectively down-regulated the expression of both the full-length AR and AR splice variants. The kava extract and kavalactones accelerated AR protein degradation, while flavokawain B inhibited AR mRNA transcription via decreasing Sp1 expression and the binding of Sp1 to the AR promoter. The kava root extract and flavokawain B reduce tumor growth, AR expression in tumor tissues and levels of serum PSA in the patient-derived PCa xenograft models. These results suggest a potential usefulness of a safe kava product or its active components for prevention and treatment of advanced PCa by targeting AR

On the Transport Properties of a Quark-Hadron Coulomb Lattice in the Cores of Neutron Stars

Already more that 40 years ago, it has been suggested that because of the enormous mass densities in the cores of neutron stars, the hadrons in the centers of neutron stars may undergo a phase transition to deconfined quark matter. In this picture, neutron stars could contain cores made of pure (up, down, strange) quark matter which are surrounded by a mixed phase of quarks and hadrons. More than that, because of the competition between the Coulomb and the surface energies associated with the positively charged regions of nuclear matter and negatively charged regions of quark matter, the mixed phase may develop geometrical structures, similarly to what is expected of the sub-nuclear liquid-gas phase transition. In this paper we restrict ourselves to considering the formation of rare phase blobs in the mixed quark-hadron phase. The influence of rare phase blobs on the thermal and transport properties of neutron star matter is investigated. The total specific heat, $c_V$, thermal conductivity, $\kappa$, and electron-blob Bremsstrahlung neutrino emissivities, $\epsilon_{\nu,\text{BR}}$, of quark-hybrid matter are computed and the results are compared with the associated thermal and transport properties of standard neutron star matter. Our results show that the contribution of rare phase blobs to the specific heat is negligibly small. This is different for the neutrino emissivity from electron-blob Bremsstrahlung scattering, which turns out to be of the same order of magnitude as the total contributions from other Bremsstrahlung processes for temperatures below about $10^8$ K.Comment: minor changes, accepted by Phys. Rev.

Modelling VARTM process induced variations on bending performance of composite Omega beams

Finite element simulation with cohesive contact is presented, to correlate the vacuum assisted RTM process and the bending performance of Omega beams. The model considers the process induced variations, including part thickness, resin rich pockets and voids. The bending performance prediction relies on cohesive contact to model delamination initiation and propagation. Computing efficiency is achieved by mesh scaling. The modelling approach applies to three variations of Omega beams with the different mode-mixture ratios. The finite element predictions result in a high degree of agreement with the experimental measurements

Pneumonia Incidence and Mortality in Mainland China: Systematic Review of Chinese and English Literature, 1985–2008

BACKGROUND: Pneumonia is a leading infectious disease killer worldwide, yet the burden in China is not well understood as much of the data is published in the non-English literature. METHODOLOGY/PRINCIPAL FINDINGS: We systematically reviewed the Chinese- and English-language literature for studies with primary data on pneumonia incidence and mortality in mainland China. Between 1985 and 2008, 37 studies met the inclusion criteria. The quality of the studies was highly variable. For children <5 years, incidence ranged from 0.06-0.27 episodes per person-year and mortality ranged from 184-1,223 deaths per 100,000 population. Overall incidence and mortality were stable or decreased over the study period and were higher in rural compared to urban areas. CONCLUSIONS/SIGNIFICANCE: Pneumonia continues to be a major public health challenge in young children in China, and estimates of pneumonia incidence and mortality vary widely. Reliable surveillance data and new prevention efforts may be needed to achieve and document additional declines, especially in areas with higher incidence and mortality such as rural settings

Experimental study on horizontal pressure of column-supported concrete group silos under earthquake force

The overpressure of silo wall caused by granular materials under earthquake is one of the main reasons of silo damage. Two shaking table model tests were carried out with column supported silos and independent single silos, respectively. The seismic response of silo granular materials was analyzed first, and then the dynamic lateral pressure of silo wall under different levels of earthquake and overpressure coefficient were obtained. The results showed that the interaction between the granular materials and the silo wall in the group silos is related to the position of the individual silo. The seismic response of granular materials is linked with the spectral characteristics of seismic waves. The overpressure coefficients of the corner silo and the side silo are greater than that of the independent single silo with a 7% and 9% higher value, respectively. Apparently, the seismic response characteristics of the independent single silo are totally different from that of the group silos. It was concluded that when designing the wall of the group bin, the position of the bin should also be considered

Characterization of complete chloroplast genome of Malus sylvestris L

The European wild apple (Malus sylvestris L.) is an important economical fruit crop. In this present study, we characterized the complete chloroplast (cp) genome sequence of Malus sylvestris L. The complete cp genome is 159,926 bp in length with a typical quadripartite structure, containing a large single-copy region (88,064 bp), a small single-copy region (26,353 bp) and a pair of inverted repeat regions (19,157 bp each). A total of 110 unique genes were found in the newly sequenced genome, including 78 protein-coding genes, 28 tRNA genes, and 4 rRNA genes. Of these, 6 protein-coding genes, 7 tRNA genes, and all 4 rRNA genes are duplicated in the inverted regions. A phylogenetic tree was reconstructed using the neighbor-joining method based on the full length of cp genomes within genus Malus. The result showed that M. sylvestris L. was clustered together with the cultivated apple. The complete cp genome could provide valuable information for understanding the phylogenetic relationships within the genus Malus

Genome-wide Identification and Expression Analysis of the Tubby-like Protein Family in the Malus domestica Genome

AbstractTubby-like proteins (TLPs), which have a highly conserved β-barrel tubby domain, have been found to be associated with some animal-specific characteristics. In the plant kingdom, more than 10 TLP family members were identified in Arabidopsis, rice and maize, and they were found to be involved in responses to stress. The publication of the apple genome makes it feasible to systematically study the TLP family in apple. In this investigation, 9 TLP encoding genes (TLPs for short) were identified. When combined with the TLPs from other plant species, the TLPs were divided into three groups (group A, B and C). Most plant TLP members in group A contained an additional F-box domain at the N-terminus. However, no common domain was identified other than tubby domain either in group B or in group C. An analysis of the tubby domains of MdTLPs identified three types of conserved motifs. Motif 1 and 2, the signature motifs in the confirmed TLPs, were always present in MdTLPs, while motif 3 was absent from group B. Homology modeling indicated that the tubby domain of most MdTLPs had a closed β barrel, as in animal tubby domains. Expression profiling revealed that the MdTLP genes were expressed in multiple organs and were abundant in roots, stems, and leaves but low in flowers. An analysis of cis-acting elements showed that elements related to the stress response were prevalent in the promoter sequences of MdTLPs. Expression profiling by qRT-PCR indicated that almost all MdTLPs were up-regulated at some extent under abiotic stress, exogenous ABA and H2O2 treatments in leaves and roots, though different MdTLP members exhibited differently in leaves and roots. The results and information above may provide a basis for further investigation of TLP function in plants