Inhibition of HSP90 with Pochoximes: SAR and Structure‐Based Insights

The pochoximes, based on the radicicol pharmacophore, are potent inhibitors of heat shock protein 90 (HSP90) that retain their activity in vivo. Herein we report an extended library that broadly explores the structure–activity relationship (SAR) of the pochoximes with four points of diversity. Several modifications were identified that afford improved cellular efficacy, new opportunities for conjugation, and further diversifications. Cocrystal structures of pochoximes A and B with HSP90 show that pochoximes bind to a different conformation of HSP90 than radicicol and provide a rationale for the enhanced affinity of the pochoximes relative to radicicol and the pochonins.     

Measurement of Coarse Gravel and Cobble Transport Using Portable Bedload Traps

Portable bedload traps (0.3 by 0.2 m opening) were developed for sampling coarse bedload transport in mountain gravel-bed rivers during wadable high flows. The 0.9 m long trailing net can capture about 20 kg of gravel and cobbles. Traps are positioned on ground plates anchored in the streambed to minimize disturbance of the streambed during sampling. This design permits sampling times of up to 1 h, overcoming short-term temporal variability issues. Bedload traps were tested in two streams and appear to collect representative samples of gravel bedload transport. Bedload rating and flow competence curves are well-defined and steeper than those obtained by a Helley–Smith sampler. Rating curves from both samplers differ most at low flow but approach each other near bankfull flow. Critical flow determined from bedload traps is similar using the largest grain and the small transport rate method, suggesting suitability of bedload trap data for incipient motion studies.     

Questioning the Living/Nonliving Dichotomy: Evidence From a Patient With an Unusual Semantic Dissociation.

In this article the authors describe a patient (J.P.) whose category-specific naming deficit eluded the classical dichotomies between living versus nonliving items or visual versus functional attributes. At age 22, he had herpes simplex encephalitis followed by a left temporal lobectomy. J.P. was tested on measures of visual perception, category naming, fluency, and name-picture matching. He showed a severe impairment naming and identifying fruits, vegetables, and musical instruments. His performance with animals and birds was spared inconsistently, meaning that even the preserved categories were, at some point, affected. J.P.'s unusual deficit supports the hypothesis that semantic knowledge is organized in the brain on the basis of object properties, which can cut across the living-nonliving categorical distinction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Coping self-efficacy buffers psychological and physiological disturbances in HIV-infected men following a natural disaster.

The importance of coping self-efficacy (CSE) appraisals on psychological and physiological functioning for HIV seropositive patients facing a severe environmental stressor was tested comparing 37 HIV-infected gay men and 42 healthy male control participants following Hurricane Andrew. Results suggested that greater levels of CSE were related to lower emotional distress and posttraumatic stress disorder (PTSD) symptoms in both groups. In addition, greater CSE was associated with lower norepinephrine to cortisol ratios in the HIV group but not in the healthy control group. Results are discussed in relation to the coping process for HIV-infected individuals specifically and chronically ill populations in general who face severe environmental stressors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuropsychological functioning in posttraumatic stress disorder and alcohol abuse.

Studies have shown differences in neuropsychological functioning between groups with posttraumatic stress disorder (PTSD) and control participants. Because individuals with PTSD often have a history of comorbid alcohol abuse, the extent to which an alcohol confound is responsible for these differences remains a concern. The current study compares neuropsychological testing scores in 4 groups of veterans with and without PTSD (PTSD+ and PTSD-, respectively) and with and without a history of alcohol abuse (ETOH+ and ETOH-, respectively): n for PTSD+/ETOH- = 30, n for PTSD+/ETOH- = 37, n for PTSD-/ETOH+ = 30, and n for PTSD-/ETOH- = 31. Results showed that PTSD, when alcohol, educational level, vocabulary, and depression are controlled for, was associated with decreased verbal memory, attention, and processing speed performance. Alcohol abuse history was associated with decreased visual memory performance. By controlling for alcohol and depression, the authors can more conclusively demonstrate that verbal memory and attention differences are associated with PTSD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Synthesis of novel tricalcium phosphate-bioactive glass composite and functionalization with rhBMP-2

A functionalization is required for calcium phosphate-based bone substitute materials to achieve an entire bone remodeling. In this study it was hypothesized that a tailored composite of tricalcium phosphate and a bioactive glass can be loaded sufficiently with rhBMP-2 for functionalization. A composite of 40 wt% tricalcium phosphate and 60 wt% bioactive glass resulted in two crystalline phases, wollastonite and rhenanite after sintering. SEM analysis of the composite’s surface revealed a spongious bone-like morphology after treatment with different acids. RhBMP-2 was immobilized non-covalently by treating with chrome sulfuric acid (CSA) and 3-aminopropyltriethoxysilane (APS) and covalently by treating with CSA/APS, and additionally with 1,1′-carbonyldiimidazole. It was proved that samples containing non-covalently immobilized rhBMP-2 on the surface exhibit significant biological activity in contrast to the samples with covalently bound protein on the surface. We conclude that a tailored composite of tricalcium phosphate and bioactive glass can be loaded sufficiently with BMP-2.