Aging modulated by the Drosophila insulin receptor through distinct structure-defined mechanisms

Mutations of the Drosophila melanogaster insulin/IGF signaling system slow aging, while also affecting growth and reproduction. To understand this pleiotropy, we produced an allelic series of single codon substitutions in the Drosophila insulin receptor, InR. We generated InR substitutions using homologous recombination and related each to emerging models of receptor tyrosine kinase structure and function. Three mutations when combined as trans-heterozygotes extended lifespan while retarding growth and fecundity. These genotypes reduced insulin-stimulated Akt phosphorylation, suggesting they impede kinase catalytic domain function. Among these genotypes, longevity was negatively correlated with egg production, consistent with life-history trade-off theory. In contrast, one mutation (InR³⁵³) was located in the kinase insert domain, a poorly characterized element found in all receptor tyrosine kinases. Remarkably, wild-type heterozygotes with InR³⁵³ robustly extended lifespan without affecting growth or reproduction and retained capacity to fully phosphorylate Akt. The Drosophila insulin receptor kinase insert domain contains a previously unrecognized SH2 binding motif. We propose the kinase insert domain interacts with SH2-associated adapter proteins to affect aging through mechanisms that retain insulin sensitivity and are independent of reproduction.     

Fine-scale mapping of natural variation in fly fecundity identifies neuronal domain of expression and function of an aquaporin

To gain insight into the molecular genetic basis of standing variation in fitness related traits, we identify a novel factor that regulates the molecular and physiological basis of natural variation in female Drosophila melanogaster fecundity. Genetic variation in female fecundity in flies derived from a wild orchard population is heritable and largely independent of other measured life history traits. We map a portion of this variation to a single QTL and then use deficiency mapping to further refine this QTL to 5 candidate genes. Ubiquitous expression of RNAi against only one of these genes, an aquaporin encoded by Drip, reduces fecundity. Within our mapping population Drip mRNA level in the head, but not other tissues, is positively correlated with fecundity. We localize Drip expression to a small population of corazonin producing neurons located in the dorsolateral posterior compartments of the protocerebrum. Expression of Drip-RNAi using both the pan-neuronal ELAV-Gal4 and the Crz-Gal4 drivers reduces fecundity. Low-fecundity RILs have decreased Crz expression and increased expression of pale, the enzyme encoding the rate-limiting step in the production of dopamine, a modulator of insect life histories. Taken together these data suggest that natural variation in Drip expression in the corazonin producing neurons contributes to standing variation in fitness by altering the concentration of two neurohormones.     

Determination of tianeptine in human plasma using high-performance liquid chromatography with fluorescence detection

A new, selective and sensitive high-performance liquid chromatography (HPLC) method with fluorimetric detection was developed for the determination of tianeptine (TIA) in human plasma using solid phase extraction (SPE) procedures. The method is based on the derivatization of TIA with 4-chloro-7-nitrobenzofurazan (NBD-Cl) in borate buffer of pH 8.5 to yield a yellow, fluorescent product. The HPLC separation was achieved on a Phenomenex C(18) column (250 mm x 4.6 mm) using a mobile phase of acetonitrile-10mM orthophosphoric acid (pH 2.5) (77:23, v/v) solvent system at 1 mL/min flow rate. Gabapentin (GA) was used as the internal standard. The fluorometric detector was operated at 458 nm (excitation) and 520 nm (emission). The assay was linear over the concentration range of 5-300 ng/mL. The detection limit (LOD) was found to be 2 ng/mL. The mean recovery was determined to be 88.6%. The proposed method was applied for pharmacokinetic study of 12.5mg TIA in a healthy volunteer.     

西双版纳尚勇自然保护区野生印支虎及其三种主要有蹄类猎物种群现状调查

中国野生印支虎及其猎物种群状况的野外实地研究一直处于空白。本研究使用足迹鉴别法、粪堆计数法,首次对西双版纳尚勇自然保护区野生印支虎种群数量现状及该区域内的虎猎物种群状况进行了调查研究。结果显示:2004 ～ 2009 年间,确认西双版纳保护区存在3 只成年印支虎个体(2 雌1 雄),西双版纳尚勇保护区拥有比较丰富的有蹄类种群,其中虎的主要猎物:水鹿平均密度为7.63 (7.40 ～ 9.23)只/ km² ;赤麂平均密度为17. 39 (11.33 ～24.94)只/ km² ,野猪平均密度为10.26 (7.69 ～ 14.51) 只/ km² ,该区域虎猎物生物量为1 715. 74 kg/ km² 。本研究还探讨了该区域印支虎种群的保护前景以及中国境内开展虎种群调查的适用办法等。     

Morphogenic Regulation of Pathotoxin Synthesis in Cochliobolus carbonum

The fungus Cochliobolus carbonum causes leaf spot disease of maize. Highly virulent isolates of the pathogen produce a host-selective, peptide toxin that is active against susceptible genotypes of maize. Prior to infection, spores must germinate and differentiate appressoria, structures specialized for leaf penetration. Analysis of spore germination fluids by plasma desorption mass spectrometry, which allowed detection of as little as 0.5 ng toxin, revealed that spores induced to form appressoria in vitro synthesized and released the toxin at a time coincident with maturation of appressoria. Spores incubated under conditions that did not induce appressorium formation failed to produce toxin. These observations indicate that synthesis of the host-selective toxin, which is essential for successful pathogenesis of maize by C. carbonum, is regulated by infection-related morphogenesis.     

Blood pressure in patients after unilateral adrenalectomy for aldosterone producing adrenal adenoma]

Forty five patients (35 women and 10 men) who underwent adrenalectomy for aldosterone-producing adrenal adenoma were followed up for 5.7 +/- 4.7 years (1-17 years). Stable normalization of blood pressure was noted in 27 (60%) patients. In 16 patients the primary hypertension and in 1 patient the second adrenal adenoma were diagnosed after surgery. Statistically significant decrease in daily excretion of adrenaline and noradrenaline with the urine, reduced adrenaline/noradrenaline ratio and reduced catecholamines and their metabolites ratio were noted in the operated patients in comparison to healthy volunteers indicating catecholamines metabolism disorders. Surgical treatment of adrenal adenoma besides normalization of blood pressure diminishes biochemical abnormalities. Development of the primary blood hypertension may be expected in some patients.