Increased expression of co-chaperone HOP with HSP90 and HSC70 and complex formation in human colonic carcinoma

Co-chaperone HOP (also called stress-inducible protein 1) is a co-chaperone that interacts with the cytosolic 70-kDa heat shock protein (HSP70) and 90-kDa heat shock protein (HSP90) families using different tetratricopeptide repeat domains. HOP plays crucial roles in the productive folding of substrate proteins by controlling the chaperone activities of HSP70 and HSP90. Here, we examined the levels of HOP, HSC70 (cognate of HSP70, also called HSP73), and HSP90 in the tumor tissues from colon cancer patients, in comparison with the non-tumor tissues from the same patients. Expression level of HOP was significantly increased in the tumor tissues (68% of patients, n = 19). Levels of HSC70 and HSP90 were also increased in the tumor tissues (95% and 74% of patients, respectively), and the HOP level was highly correlated with those of HSP90 (r = 0.77, p < 0.001) and HSC70 (r = 0.68, p < 0.01). Immunoprecipitation experiments indicated that HOP complexes with HSC70 or HSP90 in the tumor tissues. These data are consistent with increased formation of co-chaperone complexes in colon tumor specimens compared to adjacent normal tissue and could reflect a role for HOP in this process.     

Highly differentiated population structure of a Mangrove species, Bruguiera gymnorhiza (Rhizophoraceae) revealed by one nuclear GapCp and one chloroplast intergenic spacer trnF–trnL

To evaluate the genetic diversity of a mangrove species and clarify the genetic structure of its populations, we studied nucleotide polymorphism in two DNA regions of Bruguiera gymnorhiza collected from the southern islands of Japan, Thailand, Malaysia, Indonesia, Micronesia, and India. The two DNA sequences were the chloroplast (cp) intergenic spacer between trnL and trnF genes (ca. 300 bp), and a part (ca. 550 bp) of the nuclear gene coding for glyceraldehyde-3-phosphate dehydrogenase (GapCp). Little polymorphism was found within each of the three geographical regions, Pacific Ocean, Bay of Bengal and Arabian Sea. Throughout the vast regions east of the Malay peninsula including Indonesia, Thailand, Micronesia and the southern islands of Japan (Pacific Ocean), essentially only one haplotype (apart from variation in number of a T repeat) was present. A second haplotype was present on the western coast of Malay Peninsula and the eastern coast of India (Bay of Bengal). On the southwest of Malay Peninsula both of these haplotypes were present. Finally a third haplotype was found only on the western coast of India (Arabian Sea). When taken over all geographic populations, total nucleotide variation within the species was large (μ = 0.006, average of the two genes). Our results are consistent with the hypothesis that this low genetic diversity within any local population and differentiation between the different oceans or regions are caused by very low gene flow between each of the different oceans coupled with frequent fluctuation of population sizes due to the change in sea level. The significance of these results is discussed from evolutionary point of the mangrove forests.     

BMP and Hh signaling affects primordial germ cell division in Drosophila

The germline is segregated from the remainder of the soma during early embryonic development in metazoan species. In Drosophila, female primordial germ cells (PGCs) continue to proliferate during larval development, and become germline stem cells at the early pupal stage. To elucidate the roles of growth factors in larval PGC division, we examined expression patterns of a bone morphogenetic protein (BMP) growth factor, Decapentaplegic (Dpp), and Hedgehog (Hh), along with factors downstream of each, in the ovary during larval development. Dpp signaling appeared in the ovarian soma from early larval development, and was prominent in the terminal filament cells at late larval stage, whereas Hh appeared in the ovarian soma and PGCs from the third instar larval stage. The number of PGCs decreased when components of these signal transduction pathways were abrogated by RNAi in the PGCs, indicating that both Dpp and Hh signals directly regulate PGC proliferation. Experiments on the up- and down-regulation of Dpp and Hh with a tissue-specific Gal4 driver indicated that Dpp and Hh act as extrinsic and autocrine growth factors. Furthermore, heat-pulse experiments with hs-Gal4 showed that Dpp is active in PGC proliferation throughout larval development, whereas Hh has effects only during late larval development. In addition to Dpp, the reduction of Glass bottom boat (Gbb), another BMP molecule, caused a decrease in the number of PGCs and initiation of larval PGCs differentiation into cystocytes, indicating that Gbb functions to promote PGC division and repress differentiation.     

Phosphodiesterase 4 inhibitor GPD-1116 markedly attenuates the development of cigarette smoke-induced emphysema in senescence-accelerated mice P1 strain

Phosphodiesterase 4 (PDE4) is an intracellular enzyme specifically degrading cAMP, a second messenger exerting inhibitory effects on many inflammatory cells. To investigate whether GPD-1116 (a PDE4 inhibitor) prevents murine lungs from developing cigarette smoke-induced emphysema, the senescence-accelerated mouse (SAM) P1 strain was exposed to either fresh air or cigarette smoke for 8 wk with or without oral administration of GPD-1116. We confirmed the development of smoke-induced emphysema in SAMP1 [air vs. smoke (means +/- SE); the mean linear intercepts (MLI), 52.9 +/- 0.8 vs. 68.4 +/- 4.2 microm, P < 0.05, and destructive index (DI), 4.5% +/- 1.3% vs. 16.0% +/- 0.4%, P < 0.01]. Emphysema was markedly attenuated by GPD-1116 (MLI = 57.0 +/- 1.4 microm, P < 0.05; DI = 8.2% +/- 0.6%, P < 0.01) compared with smoke-exposed SAMP1 without GPD-1116. Smoke-induced apoptosis of lung cells were also reduced by administration of GPD-1116. Matrix metalloproteinase (MMP)-12 activity in bronchoalveolar lavage fluid (BALF) was increased by smoke exposure (air vs. smoke, 4.1 +/- 1.1 vs. 40.5 +/- 16.2 area/microg protein; P < 0.05), but GPD-1116 significantly decreased MMP-12 activity in smoke-exposed mice (5.3 +/- 2.1 area/microg protein). However, VEGF content in lung tissues and BALF decreased after smoke exposure, and the decrease was not markedly restored by oral administration of GPD-1116. Our study suggests that GPD-1116 attenuates smoke-induced emphysema by inhibiting the increase of smoke-induced MMP-12 activity and protecting lung cells from apoptosis, but is not likely to alleviate cigarette smoke-induced decrease of VEGF in SAMP1 lungs.     

Impact of chemical components of organic wastes on L(+)-lactic acid production

Lactic acid production from several organic wastes that had different chemical compositions was examined, and the factors strongly impacting yield were determined. The bioconversion of sugars to lactic acid was affected by the ratio of total sugars to total nitrogen content (the TS/N ratio), and was improved by nitrogen supplementation to adjust the TS/N ratio > or =10. Lactic acid yield was also affected by the fermentable sugars contents, i.e. various oligosaccharides constituted of mainly C6-sugars. The estimation of the fermentable sugars was determined by the total sugars content in starchy materials, such as kitchen wastes, but in lignocellulosic materials, the estimation was affected by the hemicellulose contents. The estimation model of the fermentable sugars was proposed by multivariate analysis using organic components as variables.     

Abnormal taste perception in mice lacking the type 3 inositol 1,4,5-trisphosphate receptor

Inositol 1,4,5-trisphosphate receptor (IP3R) is one of the important calcium channels expressed in the endoplasmic reticulum and has been shown to play crucial roles in various physiological phenomena. Type 3 IP3R is expressed in taste cells, but the physiological relevance of this receptor in taste perception in vivo is still unknown. Here, we show that mice lacking IP3R3 show abnormal behavioral and electrophysiological responses to sweet, umami, and bitter substances that trigger G-protein-coupled receptor activation. In contrast, responses to salty and acid tastes are largely normal in the mutant mice. We conclude that IP3R3 is a principal mediator of sweet, bitter, and umami taste perception and would be a missing molecule linking phospholipase C beta2 to TRPM5 activation.     

Genetic control of a transition from black to straw-white seed hull in rice domestication

The genetic mechanism involved in a transition from the black-colored seed hull of the ancestral wild rice (Oryza rufipogon and Oryza nivara) to the straw-white seed hull of cultivated rice (Oryza sativa) during grain ripening remains unknown. We report that the black hull of O. rufipogon was controlled by the Black hull4 (Bh4) gene, which was fine-mapped to an 8.8-kb region on rice chromosome 4 using a cross between O. rufipogon W1943 (black hull) and O. sativa indica cv Guangluai 4 (straw-white hull). Bh4 encodes an amino acid transporter. A 22-bp deletion within exon 3 of the bh4 variant disrupted the Bh4 function, leading to the straw-white hull in cultivated rice. Transgenic study indicated that Bh4 could restore the black pigment on hulls in cv Guangluai 4 and Kasalath. Bh4 sequence alignment of all taxa with the outgroup Oryza barthii showed that the wild rice maintained comparable levels of nucleotide diversity that were about 70 times higher than those in the cultivated rice. The results from the maximum likelihood Hudson-Kreitman-Aguade test suggested that the significant reduction in nucleotide diversity in rice cultivars could be caused by artificial selection. We propose that the straw-white hull was selected as an important visual phenotype of nonshattered grains during rice domestication.