Role of prostaglandin H2 synthase 2 in murine parturition: study on ovariectomy-induced parturition in prostaglandin F receptor-deficient mice

To determine the prostaglandin (PG) H2 synthase (generally referred to as cyclooxygenase [COX]) isozyme responsible for producing uterotonic PGs during parturition, we used PGF2alpha receptor-deficient mice, which exhibit parturition failure due to impaired withdrawal of serum progesterone at term. On ovariectomy-induced parturition in these mice, uterine COX-2 mRNA expression was drastically induced in the myometrium, whereas COX-1 mRNA expression in the endometrial epithelium decreased. The concomitant administration of progesterone with ovariectomy resulted in a delay in parturition and the disappearance of both the increase in COX-2 mRNA and the decrease in COX-1 mRNA. Thus, the expression of myometrial COX-2 and the occurrence of parturition are closely associated in this model. Furthermore, administration of the COX-nonselective inhibitor, indomethacin, or the COX-2-selective inhibitor, Dup-697 or JTE-522, effectively delayed ovariectomy-induced parturition in these mice. These findings suggest that COX-2-derived PGs contribute to the onset of parturition after the decrease in serum progesterone level.     

Determination of normal ranges of mitochondrial respiratory activities by mtDNA transfer from 54 Human subjects to mtDNA-less HeLa cells for identification of the pathogenicities of mutated mtDNAs

To determine the pathogenicities of mutated mtDNAs in patients with respiration defects, the possible involvement of nuclear DNA mutations has to be excluded, since respiratory function is controlled by both nuclear DNA and mtDNA. This was achieved by showing that the mutated mtDNAs and respiration defects were co-transferred from patients to mtDNA-less human cells, and the resultant cybrid clones carrying mutated mtDNAs expressed respiration defects. To decide whether the cybrid clones expressed respiration defects, in this study the lowest limits of normal respiratory function were evaluated by transfer of mtDNAs from 54 normal subjects to mtDNA-less HeLa cells. The resultant cybrid clones showed that 71% respiratory function was the lowest limit of mtDNAs from normal subjects. On the other hand, cybrid clones carrying pathogenic mtDNAs from patients with mitochondrial diseases showed 0-64% respiratory function, suggesting that less than 71% respiratory function in cybrid clones should be a reliable indicator of whether the mutated mtDNAs of the patients were pathogenic.     

Association of HK2 and NCK2 with Normal Tension Glaucoma in the Japanese Population

Although family studies and genome-wide association studies have shown that genetic factors play a role in glaucoma, it has been difficult to identify the specific genetic variants involved. We tested 669 single nucleotide polymorphisms (SNPs) from the region of chromosome 2 that includes the GLC1B glaucoma locus for association with primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG) in the Japanese population. We performed a two-stage case-control study. The first cohort consisted of 123 POAG cases, 121 NTG cases and 120 controls: the second cohort consisted of 187 POAG cases, 286 NTG cases, and 271 controls. Out of six SNPs showing significant association with POAG in the first round screening, seven SNPs were tested in the second round. Rs678350 in the HK2 gene coding sequence showed significant allelic (p = 0.0027 in Stage Two, 2.7XE-4 in meta-analysis) association with POAG, and significant allelic (p = 4.7XE-4 in Stage Two, 1.0XE-5 in meta-analysis) association with NTG. Although alleles in the TMEM182 gene did not show significant association with glaucoma in the second round, subjects with the A/A allele in TMEM182 rs869833 showed worse visual field mean deviation (p = 0.01). Even though rs2033008 in the NCK2 gene coding sequence did not show significant association in the first round, it had previously shown association with NTG so it was tested for association with NTG in round 2 (p = 0.0053 in Stage Two). Immunohistochemistry showed that both HK2 and NCK2 are expressed in the retinal ganglion cell layer. Once multi-testing was taken into account, only HK2 showed significant association with POAG and NTG in Stage Two. Our data also support previous reports of NCK2 association with NTG, and raise questions about what role TMEM182 might play in phenotypic variability. Our data suggest that HK2 may play an important role in NTG in the Japanese population.     

Prostaglandin receptors: advances in the study of EP3 receptor signaling

Prostaglandin (PG) E(2) produces a broad range of physiological and pharmacological actions in diverse tissues through specific receptors on plasma membranes for maintenance of local homeostasis in the body. PGE receptors are divided into four subtypes, EP1, EP2, EP3, and EP4, which have been identified and cloned. These EP receptors are members of the G-protein coupled receptor family. Among these subtypes, the EP3 receptor is unique in its ability to couple to multiple G proteins. EP3 receptor signals are primarily involved in inhibition of adenylyl cyclase via G(i) activation, and in Ca(2+)-mobilization through G(beta)(gamma) from G(i). Along with G(i) activation, the EP3 receptor can stimulate cAMP production via G(s) activation. Recent evidence indicates that the EP3 receptor can augment G(s)-coupled receptor-stimulated adenylyl cyclase activity, and can also be coupled to the G(13) protein, resulting in activation of the small G protein Rho followed by morphological changes in neuronal cells. This article focuses on recent studies on the novel pathways of EP3 receptor signaling.     

Growth, maturation and photosynthesis of the brackish water alga Rhizoclonium sp. (Cladophoraceae, Chlorophyta) in relation to salinity

The effects of salinity on growth, maturation and photosynthesis were examined in the filamentous alga Rhizoclonium sp. (Cladophoraceae, Chlorophyta) growing in a brackish water habitat in a canal draining into Tokyo Bay, Japan. In this habitat Rhizoclonium sp. was exposed to a wide salinity range, both daily, 5–23‰ during November 1996, and hourly, 6–24‰ during the spring tide day. From the results of culture experiments, growth and maturation of Rhizoclonium sp. occurred in the wide salinity range of 10–40‰ at 20 μmol photons m‐²s‐¹ at 20°C, but did not occur at salinity of 0‰. Light saturation on the photosynthesis‐irradiance curve at 20°C at 20‰ was reached at 100 μmol photons m‐²s‐¹, which is characteristic for shade‐adapted algae. On the photosynthesis‐salinity curve at 20°C at saturated irradiance (160 μmol photons m‐²s‐¹), the net photosynthetic rate increased with increasing salinity up to 30‰ but decreased at 40‰. On the photosynthesis–salinity curve at 20°C at 20 μmol photons m‐²s‐¹ (at near in situ irradiance), the photosynthetic rates were almost the same in the salinity range from 0 to 40‰. Therefore, this species is able to grow, reproduce and photosynthesize with a relative efficiency in a wide salinity range, which shows that it is well adapted to a brackish water environment.     

Recovery of activated carbon catalyst,calcium, nitrogen and phosphate from effluent following supercritical water gasification of poultry manure

A new method for suspending a fine, activated carbon catalyst in a biomass feedstock used for a supercritical water gasification (SCWG) continuous reactor is proposed. In a previous study, the organic matter in poultry manure was shown to be completely converted into gases such as H₂, CO₂ and CH₄ using SCWG. In practice, however, since the feedstock is not only composed of organic matter, but also contains inorganic material, water and catalyst, products such as gas, solid and liquid are produced during SCWG. The aim of this work was to investigate SCWG by-product utilization. This paper describes fundamental studies on the recovery of materials from SCWG products to develop a novel and simple recycling process that utilizes the by-products. A major portion of the activated carbon, monetite and ammonium sulfate can be isolated from the SCWG effluent.     

Do pollen diets vary among adjacent bumble bee colonies?

Central-place foragers, such as bumble bees, are often constrained by their location when collecting resources to provide their young. We compared the resource use (pollen diets) among seven feral colonies of Bombus ardens located in an area of 2.5 × 2.5 km². Because this area was likely to be within their maximum foraging distance, most floral resources could have been accessible to all colonies alike. Similarities in pollen diets among these colonies may suggest that the surrounding resources determine resources use, while deviations from this could reveal other factors that affect resources use among colonies. We examined if colonies showed similarities in pollen diets and if colonies do differ in pollen diets, we investigated whether factors, such as establishment year, colony size, and location, affected the colony pollen diets. We found that while the choices of floral resources were similar, the proportional use of the floral resources were significantly different, suggesting that the surrounding resources do not solely determine resource use among colonies. Further analyses showed that the dissimilarity of pollen diets between two colonies increased as spatial distance decreased, as the temporal distances increased, and as the difference in colony size increased. We found that other than differences in annual variances of resources distribution, colony size was the prominent factor that affected the resource use of our seven colonies. We propose that colony-size-dependent work-force differences and other unidentified colony-size-related factors could have significant effects on floral use among colonies overlapping spatially and temporally.     

CD73-generated adenosine restricts lymphocyte migration into draining lymph nodes

After an inflammatory stimulus, lymphocyte migration into draining lymph nodes increases dramatically to facilitate the encounter of naive T cells with Ag-loaded dendritic cells. In this study, we show that CD73 (ecto-5'-nucleotidase) plays an important role in regulating this process. CD73 produces adenosine from AMP and is expressed on high endothelial venules (HEV) and subsets of lymphocytes. Cd73(-/-) mice have normal sized lymphoid organs in the steady state, but approximately 1.5-fold larger draining lymph nodes and 2.5-fold increased rates of L-selectin-dependent lymphocyte migration from the blood through HEV compared with wild-type mice 24 h after LPS administration. Migration rates of cd73(+/+) and cd73(-/-) lymphocytes into lymph nodes of wild-type mice are equal, suggesting that it is CD73 on HEV that regulates lymphocyte migration into draining lymph nodes. The A(2B) receptor is a likely target of CD73-generated adenosine, because it is the only adenosine receptor expressed on the HEV-like cell line KOP2.16 and it is up-regulated by TNF-alpha. Furthermore, increased lymphocyte migration into draining lymph nodes of cd73(-/-) mice is largely normalized by pretreatment with the selective A(2B) receptor agonist BAY 60-6583. Adenosine receptor signaling to restrict lymphocyte migration across HEV may be an important mechanism to control the magnitude of an inflammatory response.