Monomerization and ER Relocalization of GRASP Is a Requisite for Unconventional Secretion of CFTR

Induction of endoplasmic reticulum (ER)‐to‐Golgi blockade or ER stress induces Golgi reassembly stacking protein (GRASP)‐mediated, Golgi‐independent unconventional cell‐surface trafficking of the folding‐deficient ΔF508‐cystic fibrosis transmembrane conductance regulator (CFTR). However, molecular mechanisms underlying this process remain elusive. Here, we show that phosphorylation‐dependent dissociation of GRASP homotypic complexes and subsequent relocalization of GRASP to the ER play a critical role in the unconventional secretion of CFTR. Immunolocalization analyses of mammalian cells revealed that the Golgi protein GRASP55 was redistributed to the ER by stimuli that induce unconventional secretion of ΔF508‐CFTR, such as induction of ER‐to‐Golgi blockade by the Arf1 mutant. Notably, the same stimuli also induced phosphorylation of regions near the C‐terminus of GRASP55 and dissociation of GRASP homomultimer complexes. Furthermore, phosphorylation‐mimicking mutations of GRASP55 induced the monomerization and ER relocalization of GRASP55, and these changes were nullified by phosphorylation‐inhibiting mutations. These results provide mechanistic insights into how GRASP accesses the ER‐retained ΔF508‐CFTR and mediates the ER stress‐induced unconventional secretion pathway.      

Two 17beta-hydroxysteroid dehydrogenases (17HSDs) of estradiol biosynthesis: 17HSD type 1 and type 7.

Two 17β-hydroxysteroid dehydrogenases (17HSDs), type 1 and type 7, are enzymes of estradiol biosynthesis, in addition to which rodent type 1 enzymes are also able to catalyze androgens. Both of the 17HSDs are abundantly expressed in ovaries, the type 1 enzyme in granulosa cells and type 7 in luteinized cells. The expression of 17HSD7, which has also been described as a prolactin receptor-associated protein (PRAP), is particularly up-regulated in corpus luteum during the second half of rodent pregnancy. A moderate or slight signal for mouse 17HSD7/PRAP mRNA has also been demonstrated in samples of placenta and mammary gland, for example. Human, but not rodent, 17HSD1 is expressed in placenta, breast epithelium and endometrium in addition to ovaries. A cell-specific enhancer, silencer and promoter in the hHSD17B1 gene participate in the regulation of type 1 enzyme expression. The enhancer consists of several subunits, including a retinoic acid response element, the silencer has a binding motif for GATA factors, and the proximal promoter contains adjacent and competing AP-2 and Sp binding sites.     

Improvement of bioactive compound accumulation in adventitious root cultures of an endangered plant species, <Emphasis Type="Italic">Oplopanax elatus</Emphasis>

Efficiently culturing adventitious roots (ARs) has become an alternative route for the protection and utilization of endangered plant resources. In the present study, to improve accumulation of bioactive compounds (polysaccharides, phenolics, and flavonoids) in AR cultures of endangered plant species—Oplopanax elatus—effects of methyl jasmonate (MeJA) and salicylic acid (SA) were investigated. The optimal concentration of MeJA was 200 μM and SA was 100 μM for enhancement of polysaccharide, phenolic, and flavonoid contents. In addition, MeJA (200 μM) was more suitable than SA (100 μM) for polysaccharide and flavonoid production, but both elicitors were equally favorable for phenolic production. During AR bioreactor culture, MeJA was as an elicitor to study the effect of its addition time and contact time. Contents of polysaccharides, phenolics, and flavonoids increased when MeJA was added to culture medium after 40 days of culture, but the increased degree was lower and the AR biomass significantly inhibited. However, when MeJA was added to culture medium after 30 days of culture, polysaccharide, phenolic, and flavonoid contents dramatically increased without AR biomass decrease; the maximum productivity of three bioactive compounds was found on day 8 after the MeJA treatment. Therefore, a novel elicitation method during bioreactor culture of O. elatus ARs was established in the present study, the method could be applied to commercial production of O. elatus products in the future.     

Assessment of Zinc Status in School-Age Children from Rural Areas in China Nutrition and Health Survey 2002 and 2012

Zinc is an essential trace element for growth and development in children, but zinc deficiency is a serious nutritional problem worldwide. Our study aimed to assess the zinc status of school-age children living in rural areas of China and to examine the change of zinc status based on the China Nutrition and Health Survey 2002 and 2012. We used the probability proportional to size sampling method for subject selection, and a total of 3407 school-age children were included in this study. Zinc status was assessed by three items of indicators recommended by the World Health Organization (WHO), the United Nations Children’s Fund (UNICEF), the International Atomic Energy Agency (IAEA), and the International Zinc Nutrition Consultative Group (IZiNCG). The concentration of serum zinc was 718.2 μg/L, and 44.4% of children being zinc deficiency in 2002, while 846.8 μg/L and 10.4% in 2012. Zinc intake was 7.8 mg/day with a 7.6% inadequate zinc intake in 2002, together with 6.9 mg/day and 38.2% in 2012. Height-for-age Z score was ?1.06 and 19.1% of children being stunting in 2002, as well as ?0.15 and 6.8% in 2012. In conclusion, the zinc status of school-age children living in rural areas of China has been significantly improved in addition to zinc intake over the past 10 years. However, the zinc deficiency still observed in poor rural areas of China in 2012. In addition, we suggested that the zinc bioavailability should be taken into account when assessing zinc status in population.     

The effects of simulated nitrogen deposition on extracellular enzyme activities of litter and soil among different-aged stands of larch

Aims Nitrogen (N) addition could affect the rate of forest litter and soil organic matter decomposition by regulating extracellular enzyme activity (EEA). The impact of N addition on EEA may differ across different age stands with different organic matter quality. We were interested in whether the impact of N addition on EEA in litter and mineral soil during the growing season was dependent on stand age of a larch plantation in North China.Methods We added three levels of N (0, 20 and 50kg N ha^-1 year^-1) in three age stands (11, 20 and 45 years old) of Larix principis-rupprechtii plantation in North China. We measured potential activities of β-1,4-glucosidase (BG), cellobiohydrolase (CB), β-1,4-N-acetyl-glucosaminidase (NAG) and phenol oxidase (PO) in litter (organic horizon) and mineral soil (0–10cm) during the second growing season after N amendment. We also measured C and N concentrations, microbial biomass C and N, and KCl-extractable ammonium and nitrate in both litter and mineral soil.Important findings We observed unimodal patterns of EEA during the growing season in all three stands, consistent with the seasonal variations of soil temperature. Stand age had a strong effect on EEA in both litter and mineral soil, and this effect differed between litter and mineral soil as well as between different enzymes. N addition did not significantly affect the activities of BG or CB but significantly suppressed the activity of NAG in litter. We also found stand age-specific responses of PO activity to N addition in both litter and mineral soil. N addition suppressed PO activity of the high C:N ratio litters in 20- and 45-year-old stands but had no significant effect on PO activity of the low C:N ratio litter in 11-year-old stand. Moreover, N addition inhibited PO activity of the high C:N ratio soil in 20-year-old stand but had no significant impact on PO activity of the low C:N ratio soils in 11- and 45-year-old stands. Overall, stand age had a greater effect on EEA in litter and mineral soil compared to 2 years of N addition. Moreover, the effect of N addition on PO activity is stand age dependent, which may affect the long-term soil carbon storage in this forest.     

长白山森林动态监测样地鸟兽的红外相机初步监测

<正>长白山国家级自然保护区(41o41′49″–42o25′18″N,127o42′55″–128o16′48″E)位于吉林省东部,面积为196,465 ha,设立于1960年,并于1980年被列为联合国教科文组织世界生物圈自然保护区。保护区内植被垂直带明显,包括针阔混交林(1,100 m以下)、暗针叶林(1,100–1,800 m)、亚高山岳桦(Betula ermanii)林(1,800–2,000 m)和高山苔原(2,000–2,700m)等4个植被带,其中阔叶红松林为该区域的地带性植被(代力民等,2004)。长白山地区野生动植物资源十分丰富,有被子植物98科454属1,190种,兽类     

Novel diaroylhydrazine ligands as iron chelators: coordination chemistry and biological activity

The search for orally effective drugs for the treatment of iron overload disorders is an important goal in improving the health of patients suffering diseases such as β-thalassemia major. Herein, we report the syntheses and characterization of some new members of a series of N-aroyl-N′-picolinoyl hydrazine chelators (the H₂IPH analogs). Both 1:1 and 1:2 Fe^III:L complexes were isolated and the crystal structures of Fe(HPPH)Cl₂, Fe(4BBPH)Cl₂, Fe(HAPH)(APH) and Fe(H3BBPH)(3BBPH) were determined (H₂PPH=N,N′-bis-picolinoyl hydrazine; H₂APH=N-4-aminobenzoyl-N′-picolinoyl hydrazine, H₂3BBPH=N-3-bromobenzoyl-N′-picolinoylhydrazine and H₂4BBPH=N-(4-bromobenzoyl)-N′-(picolinoyl)hydrazine). In each case, a tridentate N,N,O coordination mode of each chelator with Fe was observed. The Fe^III complexes of these ligands have been synthesized and their structural, spectroscopic and electrochemical characterization are reported. Five of these new chelators, namely H₂BPH (N-(benzoyl)-N′-(picolinoyl)hydrazine), H₂TPH (N-(2-thienyl)-N′-(picolinoyl)-hydrazine), H₂PPH, H₂3BBPH and H₂4BBPH, showed high efficacy at mobilizing ⁵⁹Fe from cells and inhibiting ⁵⁹Fe uptake from the serum Fe transport protein, transferrin (Tf). Indeed, their activity was much greater than that found for the chelator in current clinical use, desferrioxamine (DFO), and similar to that observed for the orally active chelator, pyridoxal isonicotinoyl hydrazone (H₂PIH). The ability of the chelators to inhibit ⁵⁹Fe uptake could not be accounted for by direct chelation of ⁵⁹Fe from ⁵⁹Fe–Tf. The most effective chelators also showed low antiproliferative activity which was similar to or less than that observed with DFO, which is important in terms of their potential use as agents to treat Fe-overload disease.