Ghrelin receptors in human gastrointestinal tract during prenatal and early postnatal development

The aim of our study was to investigate the appearance, density and distribution of ghrelin cells and GHS-R1a and GHS-R1b in the human stomach and duodenum during prenatal and early postnatal development. We examined chromogranin-A and ghrelin cells in duodenum, and GHS-R1a and GHS-R1b expression in stomach and duodenum by immunohistochemistry in embryos, fetuses, and infants. Chromogranin-A and ghrelin cells were identified in the duodenum at weeks 10 and 11 of gestation. Ghrelin cells were detected individually or clustered within the base of duodenal crypts and villi during the first trimester, while they were presented separately within the basal and apical parts of crypts and villi during the second and third trimesters. Ghrelin cells were the most numerous during the first (∼11%) and third (∼10%) trimesters of gestation development. GHS-R1a and GHS-R1b were detected at 11 and 16 weeks of gestation, showed the highest level of expression in Brunner's gland and in lower parts of duodenal crypts and villi during the second trimester in antrum, and during the third trimester in corpus and duodenum. Our findings demonstrated for the first time abundant duodenal expression of ghrelin cells and ghrelin receptors during human prenatal development indicating a role of ghrelin in the regulation of growth and differentiation of human gastrointestinal tract.     

STRUCTURE—FUNCTION RELATIONSHIPS OF NA+/K+-PUMPS EXPRESSED INXENOPUSOOCYTES

During the last years we have examined structure—function relationships in the Na⁺/K⁺-ATPase with respect to interactions of the external cations with the pump molecule. We have analysed in voltage-clamp experiments the influence of extracellular Na⁺and K⁺on the current generated by Na⁺/K⁺-pumps expressed inXenopusoocytes. Our results demonstrated that external Na⁺and K⁺have to pass an access channel in the electrical field of the membrane to reach their binding sites. This external access, therefore, is voltage-dependent and is affected by lysine residues within the cytoplasmic N-terminus, by glutamic acid residues in intramembraneous domains, the ouabain sensitivity and phosphorylation by protein kinases.     

Solution structures of purine base analogues 9-deazaguanine and 9-deazahypoxanthine

Deaza analogues of nucleobases are potential drugs against infectious diseases caused by parasites. A caveat is that apart from binding their target parasite enzymes, they also bind and inhibit enzymes of the host. In order to design derivatives of deaza analogues which specifically bind target enzymes, knowledge of their molecular structure, protonation state, and predominant tautomers at physiological conditions is essential. We have employed resonance Raman spectroscopy at an excitation wavelength of 260 nm, to decipher solution structure of 9-deazaguanine (9DAG) and 9-deazahypoxanthine (9DAH). These are analogues of guanine and hypoxanthine, respectively, and have been exploited to study static complexes of nucleobase binding enzymes. Such enzymes are known to perturb pK_a of their ligands, and thus, we also determined solution structures of these analogues at two, acidic and alkaline, pH. Structure of each possible protonation state and tautomer was computed using density functional theoretical calculations. Species at various pHs were identified based on isotopic shifts in experimental wavenumbers and by comparing these shifts with corresponding computed isotopic shifts. Our results show that at physiological pH, N1 of pyrimidine ring in 9DAG and 9DAH bears a proton. At lower pH, N3 is place of protonation, and at higher pH, deprotonation occurs at N1 position. The proton at N7 of purine ring remains intact even at pH 12.5. We have further compared these results with naturally occurring nucleotides. Our results identify key vibrational modes which can report on hydrogen bonding interactions, protonation and deprotonation in purine rings upon binding to the active site of enzymes.     

四川雅安常见住区蝇类密度监测

根据全国常见住区蝇类密度监测课题组关于“全国常见住区蝇类密度监测实施计划”安排,雅安地区定力全国七个监测点之一,作者承担了这一任务。该项工作尚在继续进行中,现将1988年监测结果报道如下。     

Association between blood cadmium level and bone mineral density reduction modified by renal function in young and middle-aged men

The association between cadmium exposure and bone mineral density (BMD) has not been well studied in young and middle-aged men. This study examined the relationship between the level of blood Cd (BCd) and BMD in a young to middle-aged representative male population while considering renal function. Using data from the 4th Korea National Health and Nutrition Examination Survey, 2008–2009, 1275 adult men aged 20–64 years were analyzed. BCd was measured by atomic absorption spectrophotometry and renal function was assessed by the estimated glomerular filtration rate (eGFR) with CKD-EPI formula. The risk of lower bone density was increased according to the increase in BCd levels after adjusting for eGFR and covariates, in which a significant interaction between BCd and eGFR existed. Significant negative associations between BCd and BMD were found: beta (p-value) were −0.03 (0.02), −0.04 (0.004) and −0.03 (0.04) in total femur, lumbar spine and femoral neck, respectively, which were limited to the people with eGFR ≤ lower 25%. Although, a causal relationship could not be determined because of a cross-sectional design in the present study, the results suggest low level Cd toxicity to bone via low eGFR and that measures to reduce environmental Cd exposure may be helpful to prevent bone loss in men.     

Density dependence of Anaphes sordidatus (Hymenoptera: Mymaridae) parasitism on eggs of Listronotus oregonensis (Coleoptera: Curculionidae)

Listronotus oregonensis (LeConte) (Coleoptera: Curculionidae) oviposits in carrot leaves and the larvae feed in carrot roots. Its eggs are parasitized by Anaphes sordidatus (Girault) (Hymenoptera: Mymaridae) throughout its oviposition period. This parasitoid is the major biotic mortality factor for L. oregonensis. Parasitism by A. sordidatus was studied for three years in sequentially sown plots of carrots, Daucus carota var. sativa. Over the scason, significantly fewer L. oregonensis eggs were oviposited in later sown carrots than in earlier sown carrots because oviposition started later in late sown plots of carrots. A positive temporal density-dependent relationship was observed each year between parasitism rates and host densities. This positive density dependence occurred in early and mid-summer for earlysown carrots where host density reached 1–2 host eggs per plant but disappeared in late summer when host density decreased while parasitism remained high. Latesown carrots had low host egg density (0.2 host egg per plant) and contributed little to the total number of eggs. In these late sown plots, parasitism increased rapidly to over 80% but no density dependence was observed. Spatially, few statistically significant regressions were found but all indicated a positive spatial density-dependence. Most non-significant regressions occurred because the range of egg density was too small between plots for a given date.