Influence of oestradiol on protein expression and methionine utilization during morphogenesis of Paracoccidioides brasiliensis

The temporal sequence of cytosolic protein expression during phase transition of Paracoccidioides brasiliensis was examined. Electrophoretic analysis of cytosol proteins by one-dimensional SDS-PAGE revealed numerous differences between the mycelial and yeast forms as well as alterations induced by 17 beta-oestradiol. Using either protein staining or fluorography of [35S]methionine-labelled proteins 30 phase-specific bands were detected, 12 mycelial-associated bands (range 30 to 140 kDa) and 18 yeast-associated bands (range 22 to 127 kDa). In cells undergoing mycelial to yeast transition after a shift from 25 degrees C to 37 degrees C, the protein patterns showed a temporal progression toward the yeast profile with the accumulation of yeast bands prior to observable morphogenesis. Five novel protein bands (range 23 to 50 kDa) were detected by silver staining during transition. Treatment of temperature-shifted mycelial cultures with 2.6 x 10(-7) M-oestradiol altered observed profiles; 4 of 12 mycelial-associated bands were maintained whereas the appearance of the 5 novel transition bands and 9 of 18 yeast-associated bands was blocked or delayed. Analysis of [35S]methionine-labelled proteins revealed that oestradiol induced label uptake by mycelial cells, blocked the synthesis of a 92 kDa yeast-specific band 72 h into transition, and diminished label incorporation 120 h into transition. In conjunction with these steroid-induced alterations of protein expression, little or no morphological transformation occurred. These results support our hypothesis that, analogous to mammalian steroid receptor action, the functional responses of P. brasiliensis to oestradiol are related to regulation of protein expression, presumably mediated via a specific binding protein-ligand complex.     

Comparative effects of trichothecene mycotoxins on bovine platelet function: Acetyl T-2 toxin,a more potent inhibitor than T-2 toxin

The effects of the trichothecene mycotoxins (acetyl T-2 toxin, T-2 toxin, HT-2 toxin, palmityl T-2 toxin, diacetoxyscirpenol (DAS), deoxynivalenol (DON), and T-2 tetraol) on bovine platelet function were examined in homologous plasma stimulated with platelet activating factor (PAF). The mycotoxins inhibited platelet function with the following order of potency: acetyl T-2 toxin > palmityl T-2 toxin = DAS > HT-2 toxin = T-2 toxin. While T-2 tetraol was completely ineffective as an inhibitor, DON exhibited minimal inhibitory activity at concentrations above 10×10^?4M. The stability of the platelet aggregates formed was significantly reduced in all mycotoxin treated platelets compared to that of the untreated PAF controls. It is suggested that the increased sensitivity of PAF stimulated bovine platelets to the more lipophilic mycotoxins may be related to their more efficient partitioning into the platelet membrane compared to the more hydrophilic compounds.     

Ventilatory and hematopoietic responses to chronic hypoxia in two rat strains.

Hilltop (H) and Madison (M) strains of Sprague-Dawley rats exhibit strikingly different susceptibilities to the effects of chronic altitude exposure. The H rats develop greater polycythemia, hypoxemia, and pulmonary hypertension. We studied ventilation, pulmonary gas exchange, tissue oxygenation, and hematologic adaptations in the two rat strains during a 50-day exposure to a simulated altitude (HA) of 5,500 m (18,000 ft). There were no strain differences among the variables we studied under sea level (SL) conditions. Within the first 14 days of hypoxic exposure, the only significant strain differences were that erythropoietin (EPO) rose much higher and erythroid activity was greater in the H rats, even though arterial Po2 and PCo2 (Pao2 and PaCo2, respectively), renal venous PO2 (Prvo2), and ventilation (VE) were equivalent in the two strains during this time. By day 14 at HA, the H rats had significantly higher erythroid activity, hematocrit (Hct), and EPO levels, significantly lower PaO2 and PrvO2, but equivalent VE and PaCO2. These changes persisted for the remainder of the exposure, except that the Hct continued to rise and the increase was greater in H rats. Despite the greater O2-carrying capacity of H rats in the later stages of hypoxic exposure, PaO2 and PrvO2 were significantly lower in H rats. There were no strain differences at either SL or HA in ventilatory responses to hypercapnia or hypoxia, in blood O2 affinity or 2,3-diphosphoglycerate, in extrarenal production of EPO, or in EPO clearance. We conclude that early in the hypoxic exposure the H rats produce more EPO at apparently equivalent levels of hypoxia, and this is the first step in the pathogenesis of the maladaptation to HA manifest by H rats. We find no consistent evidence that differences in VE contribute to the variable susceptibility to hypoxia in the two rat strains.     

Aspergillus fumigatus Invasion Increases with Progressive Airway Ischemia

Despite the prevalence of Aspergillus-related disease in immune suppressed lung transplant patients, little is known of the host-pathogen interaction. Because of the mould’s angiotropic nature and because of its capacity to thrive in hypoxic conditions, we hypothesized that the degree of Aspergillus invasion would increase with progressive rejection-mediated ischemia of the allograft. To study this relationship, we utilized a novel orthotopic tracheal transplant model of Aspergillus infection, in which it was possible to assess the effects of tissue hypoxia and ischemia on airway infectivity. Laser Doppler flowmetry and FITC-lectin were used to determine blood perfusion, and a fiber optic microsensor was used to measure airway tissue oxygen tension. Fungal burden and depth of invasion were graded using histopathology. We demonstrated a high efficacy (80%) for producing a localized fungal tracheal infection with the majority of infection occurring at the donor-recipient anastomosis; Aspergillus was more invasive in allogeneic compared to syngeneic groups. During the study period, the overall kinetics of both non-infected and infected allografts was similar, demonstrating a progressive loss of perfusion and oxygenation, which reached a nadir by days 10-12 post-transplantation. The extent of Aspergillus invasion directly correlated with the degree of graft hypoxia and ischemia. Compared to the midtrachea, the donor-recipient anastomotic site exhibited lower perfusion and more invasive disease; a finding consistent with clinical experience. For the first time, we identify ischemia as a putative risk factor for Aspergillus invasion. Therapeutic approaches focused on preserving vascular health may play an important role in limiting Aspergillus infections.     

The Glove-like Structure of the Conserved Membrane Protein TatC Provides Insight into Signal Sequence Recognition in Twin-Arginine Translocation

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Highlights? Crystal structures of TatC from the thermophile Aquifex aeolicus are presented ? The architecture of TatC generates a glove-shaped pocket buried in the bilayer ? Molecular dynamics reveal destabilization of the membrane around the pocket ? Correlation to biochemical results suggest the signal sequence binds in this pocket     

吐鲁番市胃食管反流病发生相关危险因素分析（附280例报道）

目的：探讨280例胃食管反流病（GERD）的分布特点及危险因素。方法：对临床诊断和胃镜确诊的280例GERD患者进行临床和风险因子相关性分析。结果：不论汉族还是维族,男性患者比例均明显高于女性;汉族患者高发年龄段早于维族患者（z=-2．939,P=0．003,）;汉族和维族患者占反流性食管炎和Barrett食管比例分别为42．4％、81_3％及56．5％、18．8％,其中汉族患者Barrett食管比例较高（X2=14．358,P=0．000）;肥胖、习惯性便秘、重体力活动者、饮食习惯不良在维族患者中的比例较高（P〈0．001）。结论：GERD与性别、年龄密切相关,男性多于女性,汉族患者发病年龄高峰旱于维族患者;汉族患者Barrett食管发生比例高于维族患者;肥胖、习惯性便秘、重体力活动、饮食习惯不良可能是GERD尤其是维族人群GERD的危险因素。     

Genotypic Differences of Candida albicans and C. dubliniensis Isolates Related to Ethnic/Racial Differences within the Same Geographic Area

Candida albicans and C. dubliniensis genotype differences among Israeli ethnic groups were assessed. Isolates from Jews (51), Arabs (35) and Druze (25) were genotyped. The distributions among ethnic groups were not different, however they differed (p = 0.002) from global populations. Therefore, C. albicans and C. dubliniensis genotype distribution differences in Israel are related to changes in all ethnic groups.     

Relationships between the flexed-arm hang and select measures of muscular fitness

The flexed-arm hang (FAH) has been used to assess arm and shoulder girdle strength for 35 years despite little evidence to support its use. The purpose of this study was to determine what muscular fitness component, if any, was related to the FAH. The traditional overgrip chin-above-bar test and 5 different variations were compared with absolute strength (1 repetition maximum [1RM] lat pull down), relative strength (1RM.mass(-1)), and muscle endurance (repetitions to failure at 70% of the 1RM). Sixty college-age women volunteered for the study. Relationships were examined using Pearson Product Moment Correlation. No significant relationship was found between any of the FAH variations and absolute strength or muscle endurance; however, all FAH variations correlated significantly with relative strength (1RM.mass(-1)). The strongest relationship was with the undergrip FAH timed to 90 degrees of elbow extension (r = 0.72). Investigators concluded that the FAH is a test of weight-relative muscular strength and appears unrelated to absolute strength or muscle endurance.