Effect of aging on the cardiovascular regulatory systems in healthy women

Aging, independently from the hormonal status, is a major risk factor for cardiovascular morbidity in healthy women. Therefore, we studied the effect of healthy aging on the cardiovascular homeostatic mechanisms in premenopausal and postmenopausal women with similar estrogen levels. Twelve healthy postmenopausal women, confirmed by follicular-stimulating hormone (FSH) and luteal hormone (LH) levels, were compared with 14 normally menstruating women during the early follicular phase (young-EF), to avoid as much as possible the effects of estrogen. Systolic BP was 108 +/- 1.5 vs. 123 +/- 2.5 (P < 0.001), supine norepinephrine was 260 +/- 30 vs. 216 +/- 45 and upright 640 +/- 100 vs. 395 +/- 50 pg/ml (P = 0.05) in young-EF vs. postmenopausal, respectively. Plasma renin activity and aldosterone remained unchanged. Vagal cardiac tone indices decreased significantly with aging (young-EF vs. postmenopausal): high-frequency (HF) band, root mean square successive differences (rMSSD) and proportion of R-R intervals >50 ms (PNN50%) were 620 +/- 140 vs. 270 +/- 70 (P = 0.04), 53 +/- 7 vs. 30 +/- 3 (P = 0.02), and 23 +/- 5 vs. 10 +/- 3 (P = 0.04), respectively. LF to HF ratio was 0.85 +/- 0.17 in young-EF and became 1.5 +/- 0.22 in postmenopausal (P = 0.03). Both arms of the baroreflex, +BRS (29 +/- 5 vs. 13.5 +/- 2.5, P = 0.01) and -BRS (26 +/- 4 vs. 15 +/- 1.5, P = 0.02) decreased with aging. Cardiovascular alpha(1)-adrenoreceptor responsiveness significantly increased and beta-decreased in postmenopausal compared with young EF (P < 0.001, both). The corrected QT intervals (QTc) were similar, whereas corrected JT intervals (JTc) and JTc to QTc ratio were prolonged in the postmenopausal group. We conclude that in young women, parasympathetic control is the main regulator of the cardiovascular system and in postmenopausal women, sympathetic tone dominates. The transition from parasympathetic to sympathetic control may contribute to the increased cardiovascular morbidity with aging.     

Synthetic viability genomic screening defines Sae2 function in DNA repair

DNA double-strand break (DSB) repair by homologous recombination (HR) requires 3′ single-stranded DNA (ssDNA) generation by 5′ DNA-end resection. During meiosis, yeast Sae2 cooperates with the nuclease Mre11 to remove covalently bound Spo11 from DSB termini, allowing resection and HR to ensue. Mitotic roles of Sae2 and Mre11 nuclease have remained enigmatic, however, since cells lacking these display modest resection defects but marked DNA damage hypersensitivities. By combining classic genetic suppressor screening with high-throughput DNA sequencing, we identify Mre11 mutations that strongly suppress DNA damage sensitivities of sae2Δ cells. By assessing the impacts of these mutations at the cellular, biochemical and structural levels, we propose that, in addition to promoting resection, a crucial role for Sae2 and Mre11 nuclease activity in mitotic DSB repair is to facilitate the removal of Mre11 from ssDNA associated with DSB ends. Thus, without Sae2 or Mre11 nuclease activity, Mre11 bound to partly processed DSBs impairs strand invasion and HR.     

土生空团菌对白云母的风化作用及解钾特性

摘要:【目的】为了提高森林土壤含钾硅酸盐矿物利用率和改善树木钾素营养,探讨外生菌根真菌对白云母矿物的解钾及风化效应。【方法】通过5种外生菌根真菌在贫钾条件下与白云母的相互作用,考察了3种常用培养基对菌株解钾能力的影响;采用解钾效果最高的土生空团菌在Modified Melin-Norkrans(MMN)培养基条件下,进一步研究了21d浸出过程中主要矿质元素的释放量、生物量、剩余葡萄糖量、产生的小分子有机酸种类及含量、菌丝-矿物微环境的改变,利用扫描电子显微镜观测白云母被风化的痕迹。【结果】培养基对不同外生菌根真菌解钾能力的影响各异,其中土生空团菌在MMN培养基条件下解钾能力最强,其解钾量与生物量、剩余葡萄糖量、pH值显著相关。土生空团菌能够分泌有助于菌丝-矿物粘附的胞外多糖以形成菌丝-矿物微环境,并富集有机酸,促进微环境内钾的释放;菌丝不仅能够粘附在白云母表面产生刻蚀作用,还能破坏矿物深入其内部。【结论】外生菌根真菌具有促进白云母风化并释放钾素的能力,这种能力可能与菌丝、有机酸、多糖的协同作用有关。     

Sand fly fauna (Diptera: Psychodidae) from the Goytacazes National Forest and surrounding areas of southeastern Brazil

Most studies of the sand fly fauna in southeastern Brazil are conducted in the peridomiciliary environment of leishmaniasis endemic regions. Therefore, to increase the knowledge about diversity and richness of sand fly conservation areas, we describe here the sand fly fauna from the National Forest of Goytacazes (NFG), state of Espírito Santo, Brazil, and its surroundings areas. We also used sand fly fauna records from eight conservations units within the state of Espírito Santo to understand the similarity and relationships among them. The sand flies were simultaneously collected from June, 2008 to May, 2009 in two different environments: a preserved environment represented by the NFG and a modified environment represented by a peridomicile. To establish the similarity among the conservation units, we used a method very similar to parsimony analysis of endemism. We collected 2,466 sand fly specimens belonging to 13 species. Pressatia choti and Nyssomyia intermedia were the most abundant sand fly species. Ny. intermedia is a known vector of Leishmania braziliensis and epidemiological surveillance must be conducted in the area. We discuss aspects regarding the diversity of sand flies as well as the risk of transmission of Leishmania parasites in the area. We also provide for the first time a hypothesis of similarity relationships among conservation units within the state of Espírito Santo.     

Pre-clinical and clinical significance of heparanase in Ewing's sarcoma

Heparanase is an endoglycosidase that specifically cleaves heparan sulphate side chains of heparan sulphate proteoglycans, activity that is strongly implicated in cell migration and invasion associated with tumour metastasis, angiogenesis and inflammation. Heparanase up-regulation was documented in an increasing number of human carcinomas, correlating with reduced post-operative survival rate and enhanced tumour angiogenesis. Expression and significance of heparanase in human sarcomas has not been so far reported. Here, we applied the Ewing's sarcoma cell line TC71 and demonstrated a potent inhibition of cell invasion in vitro and tumour xenograft growth in vivo upon treatment with a specific inhibitor of heparanase enzymatic activity (compound SST0001, non-anticoagulant N-acetylated, glycol split heparin). Next, we examined heparanase expression and cellular localization by immunostaining of a cohort of 69 patients diagnosed with Ewing's sarcoma. Heparanase staining was noted in all patients. Notably, heparanase staining intensity correlated with increased tumour size (P = 0.04) and with patients' age (P = 0.03), two prognostic factors associated with a worse outcome. Our study indicates that heparanase expression is induced in Ewing's sarcoma and associates with poor prognosis. Moreover, it encourages the inclusion of heparanase inhibitors (i.e. SST0001) in newly developed therapeutic modalities directed against Ewing's sarcoma and likely other malignancies.     

Uric acid deposits and estivation in the invasive apple-snail, Pomacea canaliculata

The physiological ability to estivate is relevant for the maintenance of population size in the invasive Pomacea canaliculata. However, tissue reoxygenation during arousal from estivation poses the problem of acute oxidative stress. Uric acid is a potent antioxidant in several systems and it is stored in specialized tissues of P. canaliculata. Changes in tissue concentration of thiobarbituric acid reactive substances (TBARS), uric acid and allantoin were measured during estivation and arousal in P. canaliculata. Both TBARS and uric acid increased two-fold during 45 days estivation, probably as a consequence of concomitant oxyradical production during uric acid synthesis by xanthine oxidase. However, after arousal was induced, uric acid and TBARS dropped to or near baseline levels within 20 min and remained low up to 24h after arousal induction, while the urate oxidation product allantoin continuously rose to a maximum at 24h after induction, indicating the participation of uric acid as an antioxidant during reoxygenation. Neither uric acid nor allantoin was detected in the excreta during this 24h period. Urate oxidase activity was also found in organs of active snails, but activity shut down during estivation and only a partial and sustained recovery was observed in the midgut gland.