Selective inhibition of prostaglandin biosynthesis by gold salts and phenylbutazone

Gold salts and phenylbutazone selectively inhibit the synthesis of PGF_2α and PGE₂ respectively. Lowered production of one prostaglandin species is accompanied by an increased production of the other. Selective inhibition by these drugs was observed in the presence of adrenaline, reduced glutathione and copper sulphate under conditions when most anti-inflammatory compounds inhibited PGE₂ and PGF_2α syntheses equally. It is postulated that selective inhibitors may have a different mode of action and beneficial effects may be related to the endogenous ratio of PGE to PGF required for normal function.     

Radiation of the Tnt1 retrotransposon superfamily in three Solanaceae genera

Background  

Tnt1 was the first active plant retrotransposon identified in tobacco after nitrate reductase gene disruption. The Tnt1 superfamily comprises elements from Nicotiana (Tnt1 and Tto1) and Lycopersicon (Retrolyc1 and Tlc1) species. The study presented here was conducted to characterise Tnt1-related sequences in 20 wild species of Solanum and five cultivars of Solanum tuberosum.     

Genetic diversity and population structure of the endangered ripon barbel,Barbus altianalis (Boulenger, 1900) in Lake Victoria catchment,Kenya based on mitochondrial DNA sequences

Approximately 850 bp of the mitochondrial control region was used to assess the genetic diversity, population structure and demographic expansion of the endangered cyprinid Barbus altianalis, a species known to be potamodramous in the Lake Victoria drainage system. The 196 samples taken from the four main rivers draining the Lake Victoria catchment (Nzoia, Yala, Nyando and Sondu–Miriu) yielded 49 mitochondrial DNA haplotypes; 83.7% thereof were private haplotypes restricted to particular rivers. The overall mean haplotype diversity was high (0.93663 ± 0.008) and ranged between 0.566 (Sondu – Miriu) and 0.944 (Nzoia). The overall mean nucleotide diversity was low (0.01322 ± 0.00141), ranging from 0.0342 (Sondu – Miriu) to 0.0267 (Nzoia). Population differentiation tests revealed strong and highly significant (P ≤ 0.001) segregation of populations in the four river basins. F_ST values among the four river‐based populations ranged from 0.05202 to 0.44352. The samples formed two main haplotype networks based on a 95% parsimony criterion, each exhibiting a strong signature of past population expansion. The smaller network was restricted to the River Nzoia, whereas the larger network contained representatives from all four rivers; within this the central haplotypes were found in more than one river, whereas the peripheral haplotypes tended to be river‐specific. The degree of population differentiation and the number of river‐specific haplotypes are too high to be explained by recent anthropogenic impacts alone and suggest that the species has probably existed in the Lake Victoria catchment as two populations: the now ‘extinct’ migratory population and the extant river restricted non‐migratory populations.     

Safety,Pharmacokinetic, and Functional Effects of the Nogo-A Monoclonal Antibody in Amyotrophic Lateral Sclerosis: A Randomized,First-In-Human Clinical Trial

The neurite outgrowth inhibitor, Nogo-A, has been shown to be overexpressed in skeletal muscle in amyotrophic lateral sclerosis (ALS); it is both a potential biomarker and therapeutic target. We performed a double-blind, two-part, dose-escalation study, in subjects with ALS, assessing safety, pharmacokinetics (PK) and functional effects of ozanezumab, a humanized monoclonal antibody against Nogo-A. In Part 1, 40 subjects were randomized (3∶1) to receive single dose intravenous ozanezumab (0.01, 0.1, 1, 5, or 15 mg/kg) or placebo. In Part 2, 36 subjects were randomized (3∶1) to receive two repeat doses of intravenous ozanezumab (0.5, 2.5, or 15 mg/kg) or placebo, approximately 4 weeks apart. The primary endpoints were safety and tolerability (adverse events [AEs], vital signs, electrocardiogram (ECG), and clinical laboratory tests). Secondary endpoints included PK, immunogenicity, functional endpoints (clinical and electrophysiological), and biomarker parameters. Overall, ozanezumab treatment (0.01–15 mg/kg) was well tolerated. The overall incidence of AEs in the repeat dose 2.5 mg/kg and 15 mg/kg ozanezumab groups was higher than in the repeat dose placebo group and repeat dose 0.5 mg/kg ozanezumab group. The majority were considered not related to study drug by the investigators. Six serious AEs were reported in three subjects receiving ozanezumab; none were considered related to study drug. No study drug-related patterns were identified for ECG, laboratory, or vital signs parameters. One subject (repeat dose 15 mg/kg ozanezumab) showed a weak, positive anti-ozanezumab-antibody result. PK results were generally consistent with monoclonal antibody treatments. No apparent treatment effects were observed for functional endpoints or muscle biomarkers. Immunohistochemical staining showed dose-dependent co-localization of ozanezumab with Nogo-A in skeletal muscle. In conclusion, single and repeat dose ozanezumab treatment was well tolerated and demonstrated co-localization at the site of action. These findings support future studies with ozanezumab in ALS.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00875446","term_id":"NCT00875446"}}NCT00875446 GSK-ClinicalStudyRegister.com GSK ID 111330     

海洋浮游藻类细胞质膜氧化还原活性与细胞外CA活性的关系

海洋浮游藻类除通过吸收和释放分子与离子来改变其环境的化学成分外,还可通过细胞外表面一些酶的作用引起质膜外化学物质变化。在这方面,海洋浮游藻类一个主要的细胞外表面酶-碳酸酐酶(CA),在经胰蛋白酶处理从细胞质膜上释放出来后,仍保留其催化活性。当细胞外表面CA(简称细胞外CA)具活性时,可催化质膜外HCO_3~-与CO_2的相互转化,为Rubisco(磷酸核酮糖羧化酶)提供一稳定的CO_2流量环境,以维持正常的光合作用。     

Expression,localization and possible functions of aquaporins 3 and 8 in rat digestive system

Although aquaporins (AQPs) play important roles in transcellular water movement, their precise quantification and localization remains controversial. We investigated expression levels and localizations of AQP3 and AQP8 and their possible functions in the rat digestive system using real-time polymerase chain reactions, western blot analysis and immunohistochemistry. We investigated the expression levels and localizations of AQP3 and AQP8 in esophagus, forestomach, glandular stomach, duodenum, jejunum, ileum, proximal and distal colon, and liver. AQP3 was expressed in the basolateral membranes of stratified epithelia (esophagus and forestomach) and simple columnar epithelia (glandular stomach, ileum, and proximal and distal colon). Expression was particularly abundant in the esophagus, and proximal and distal colon. AQP8 was found in the subapical compartment of columnar epithelial cells of the jejunum, ileum, proximal colon and liver; the most intense staining occurred in the jejunum. Our results suggest that AQP3 and AQP8 play significant roles in intestinal function and/or fluid homeostasis and may be an important subject for future investigation of disorders that involve disruption of intestinal fluid homeostasis, such as inflammatory bowel disease and irritable bowel syndrome.     

Genetic structure and gene flow in an endangered native tilapia fish (Oreochromis esculentus) compared to invasive Nile tilapia (Oreochromis niloticus) in Yala swamp, East Africa

The introduction of invasive Nile tilapia (Oreochromis niloticus), and the rapacious predator Nile perch (Lates niloticus), into Lake Victoria resulted in a decline in population sizes, genetic diversity and even extirpation of native species which were previously the mainstay of local fisheries. However, remnant populations of native fish species, including tilapia, still persist in satellite lakes around Lake Victoria where they may coexist with O. niloticus. In this study we assessed population genetic structure, diversity, and integrity of the native critically endangered Singidia tilapia (O. esculentus) in its refugial populations in the Yala swamp, Kenya, and contrasted this diversity with populations of the invasive tilapia O. niloticus in satellite lakes (Kanyaboli, Namboyo and Sare) and Lake Victoria. Based on mtDNA control region sequences and eight nuclear microsatellite loci, we did not detect any mtDNA introgression between the native and the invasive species in Lakes Kanyaboli and Namboyo, but did find low levels of nuclear admixture, primarily from O. niloticus to O. esculentus. Some genetic signal of O. esculentus in O. niloticus was found in Lake Sare, where O. esculentus is not found, suggesting it has recently been extirpated by the O. niloticus invasion. In both species, populations in the satellite lakes are significantly genetically isolated from each other, with private mtDNA haplotypes and microsatellite alleles. For O. niloticus, genetic diversity in satellite lakes was similar to that found in Lake Victoria. Our data imply a low frequency of immigration exchange between the two populations of O. esculentus and we suggest that the populations of this endangered species and important fisheries resource should be conserved separately in Lakes Kanyaboli and Namboyo and with high priority.