四川江油马鞍塘上三叠统天井山组Glossifungites遗迹相

首次在四川江油马鞍塘天井山组顶部发现Thalassinoides suevicus,属于Glossifungites遗迹相,属滨海或潮下带在未完全石化的、处于半固结状态的沉积底质上所产生的遗迹化石组合,发育在停积面上,因受到下伏硬底构造的限制,仅产于上表面,没有向下发展,是该地区从开阔海台地相转变为局限海台地相的证据。     

The nuclear dot protein sp100, characterization of domains necessary for dimerization, subcellular localization, and modification by small ubiquitin-like modifiers

The Sp100 and promyelocytic leukemia proteins (PML) are constituents of nuclear domains, known as nuclear dots (NDs) or PML bodies, and are both covalently modified by the small ubiquitin-related protein SUMO-1. NDs play a role in autoimmunity, virus infections, and in the etiology of acute promyelocytic leukemia. To date, little is known about the function of the Sp100 protein. Here we analyzed Sp100 domains that determine its subcellular localization, dimerization, and SUMOylation. A functional nuclear localization signal and an ND-targeting region that coincides with an Sp100 homodimerization domain were mapped. Sequences similar to the Sp100 homodimerization/ND-targeting region occur in several other proteins and constitute a novel protein motif, termed HSR domain. The lysine residue of the Sp100 protein, to which SUMO-1 is covalently linked, was mapped within and may therefore modulate the previously described HP1 protein-binding site. A consensus sequence for SUMOylation of proteins in general is suggested. SUMOylation strictly depended on a functional nuclear localization signal but was not necessary for nuclear import or ND targeting. A three-dimensional structure of Sp100, which supports the mapping data and provides additional information on Sp100 structure/function relationships, was generated by computer modeling. Taken together, our studies indicate the existence of well defined Sp100 domains with functions in ND targeting, nuclear import, nuclear SUMOylation, and protein-protein interaction.     

Novel factor Xa inhibitors based on a benzoic acid scaffold and incorporating a neutral P1 ligand

A series of novel, highly potent, achiral factor Xa inhibitors based on a benzoic acid scaffold and containing a chlorophenethyl moiety directed towards the protease S1 pocket is described. A number of structural features, such as the requirements of the P1, P4 and ester-binding pocket ligands were explored with respect to inhibition of factor Xa. Compound 46 was found to be the most potent compound in a series of antithrombotic secondary assays.     

Purified U7 snRNPs lack the Sm proteins D1 and D2 but contain Lsm10, a new 14 kDa Sm D1-like protein

U7 snRNPs were isolated from HeLa cells by biochemical fractionation, followed by affinity purification with a biotinylated oligonucleotide complementary to U7 snRNA. Purified U7 snRNPs lack the Sm proteins D1 and D2, but contain additional polypeptides of 14, 50 and 70 kDa. Microsequencing identified the 14 kDa polypeptide as a new Sm-like protein related to Sm D1 and D3. Like U7 snRNA, this protein, named Lsm10, is enriched in Cajal bodies of the cell nucleus. Its incorporation into U7 snRNPs is largely dictated by the special Sm binding site of U7 snRNA. This novel type of Sm complex, composed of both conventional Sm proteins and the Sm-like Lsm10, is most likely to be important for U7 snRNP function and subcellular localization.     

四川江油渔洞子下三叠统飞仙关组巨鲕灰岩中疑似蓝细菌及早三叠世疑似蓝细菌的双幕式爆发

二叠纪末海洋生态环境的恶化导致海洋底栖生物的大灭绝及早三叠世蓝细菌的爆发,有关这一时期我国华南蓝细菌化石的报道主要来自早三叠世早期的微生物岩。四川江油渔洞子剖面下三叠统飞仙关组下部巨鲕灰岩中首次发现有丰富的疑似蓝细菌,在种类和结构上与以往所报道的蓝细菌有着明显区别。疑似蓝细菌在巨鲕内和围岩中的富集,表明巨鲕灰岩的成因与疑似蓝细菌的活动有关,与飞仙关组底部微生物岩在成因上有着密切联系,显示早三叠世早期在这一地区发生了疑似蓝细菌的双幕式爆发,同时,暗示着这一地区二叠纪-三叠纪之交至少发生了两次海洋环境恶化及动物灭绝事件。疑似蓝细菌的爆发性生长,对于海洋生态环境的修复和海洋含氧条件的改善,进而为早三叠世末、中三叠世的生物全面复苏、辐射有着重要意义。     

CNNM2, encoding a basolateral protein required for renal Mg2+ handling, is mutated in dominant hypomagnesemia

Familial hypomagnesemia is a rare human disorder caused by renal or intestinal magnesium (Mg(2+)) wasting, which may lead to symptoms of Mg(2+) depletion such as tetany, seizures, and cardiac arrhythmias. Our knowledge of the physiology of Mg(2+) (re)absorption, particularly the luminal uptake of Mg(2+) along the nephron, has benefitted from positional cloning approaches in families with Mg(2+) reabsorption disorders; however, basolateral Mg(2+) transport and its regulation are still poorly understood. Here, by using a candidate screening approach, we identified CNNM2 as a gene involved in renal Mg(2+) handling in patients of two unrelated families with unexplained dominant hypomagnesemia. In the kidney, CNNM2 was predominantly found along the basolateral membrane of distal tubular segments involved in Mg(2+) reabsorption. The basolateral localization of endogenous and recombinant CNNM2 was confirmed in epithelial kidney cell lines. Electrophysiological analysis showed that CNNM2 mediated Mg(2+)-sensitive Na(+) currents that were significantly diminished in mutant protein and were blocked by increased extracellular Mg(2+) concentrations. Our data support the findings of a recent genome-wide association study showing the CNNM2 locus to be associated with serum Mg(2+) concentrations. The mutations found in CNNM2, its observed sensitivity to extracellular Mg(2+), and its basolateral localization signify a critical role for CNNM2 in epithelial Mg(2+) transport.     

An anthocyanin/polyphenolic-rich fruit juice reduces oxidative DNA damage and increases glutathione level in healthy probands

Oxidative cell damage is involved in the pathogenesis of atherosclerosis, cancer, diabetes and other diseases. Uptake of fruit juice with especially high content of antioxidant flavonoids/polyphenols, might reduce oxidative cell damage. Therefore, an intervention study was performed with a red mixed berry juice [trolox equivalent antioxidative capacity (TEAC): 19.1 mmol/L trolox] and a corresponding polyphenol-depleted juice (polyphenols largely removed, TEAC 2.4 mmol/L trolox), serving as control. After a 3-week run-in period, 18 male probands daily consumed 700 mL juice, and 9 consumed control juice, in a 4-week intervention, followed by a 3-week wash-out. Samples were collected weekly to analyze DNA damage (comet assay), lipid peroxidation (plasma malondialdehyde: HPLC/fluorescence; urinary isoprostanes: GC-MS), blood glutathione (photometrically), DNA-binding activity of nuclear factor-kappaB (ELISA) and plasma carotenoid/alpha-tocopherol levels (HPLC-DAD). During intervention with the fruit juice, a decrease of oxidative DNA damage (p<5x10(-4)) and an increase of reduced glutathione (p<5x10(-4)) and of glutathione status (p<0.05) were observed, which returned to the run-in levels in the subsequent wash-out phase. The other biomarkers were not significantly modulated by the juice supplement. Intervention with the control juice did not result in reduction of oxidative damage. In conclusion, the fruit juice clearly reduces oxidative cell damage in healthy probands.     

Cuticular lipid profiles of fertile and non-fertile Cardiocondyla ant queens

Both mating and reproduction strongly affect the physiology of insect females. In the ant Cardiocondyla obscurior, a comparison among virgin queens, mated queens, and queens mated with sterilized males ("sham-mated") allows to separate the different effects of mating and egg laying. Here, we investigate whether and how different mating status is reflected in the cuticular lipid profiles of queens, i.e., the blend of chemicals that is thought to signal a queen's fertility. Surprisingly, discriminant analyses failed to reliably distinguish among virgin, mated, and sham-mated queens. A generalized linear model on individual substances showed only very subtle differences. While mating appeared to be positively associated with the proportions of 3-MeC(25,) 11-/13-MeC(27), 5-MeC(27), 3-MeC(27), and 12-/14-MeC(28) and negatively with C(27:1), fecundity was negatively associated with C(29:1), C(31:1), and a sterol derivative. We discuss these results in the light of the special life history of C. obscurior, with completely sterile workers and low egg laying rates in queens.