The role of DnaJ-like proteins in glucocorticoid receptor.hsp90 heterocomplex assembly by the reconstituted hsp90.p60.hsp70 foldosome complex

The glucocorticoid receptor (GR) is recovered from hormone-free cells in a heterocomplex with the molecular chaperone hsp90, which is required to produce the proper folding state for steroid binding. GR.hsp90 heterocomplexes are formed by a multiprotein system that appears to exist in all eukaryotic cells. Recently, we have reconstituted a receptor.hsp90 heterocomplex assembly system with purified rabbit hsp90 and hsp70 and bacterially expressed human p23 and p60. We have shown that hsp90, p60, and hsp70 form an hsp90.p60. hsp70 complex that converts the GR from a non-steroid binding to a steroid binding form (Dittmar, K. D., and Pratt, W. B. (1997) J. Biol. Chem. 272, 13047-13054). The resulting GR.hsp90 heterocomplex rapidly disassembles unless p23 is present to bind to the ATP-dependent conformation of hsp90 and stabilize its association with the receptor (Dittmar, K. D., Demady, D. R., Stancato, L. F., Krishna, P., and Pratt, W. B. (1997) J. Biol. Chem. 272, 21213-21220). In the current work, we show that the purified rabbit hsp70 utilized in prior studies is contaminated with a small amount of the rabbit DnaJ homolog hsp40. Elimination of the hsp40 from the purified GR.hsp90 assembly system reduces assembly activity, and the activity is restored by addition of the purified yeast DnaJ homolog YDJ-1. hsp40 is a component of the hsp90.p60.hsp70 foldosome complex isolated from reticulocyte lysate with antibody against p60. Under conditions that promote binding of p23 to hsp90 (elevated temperature, ATP, Nonidet P-40, molybdate), a five-membered (p23. hsp90.p60.hsp70.hsp40) complex of chaperone proteins is formed in reticulocyte lysate or from purified proteins. The hsp40-free, purified assembly system has a modest level of assembly activity that is maximally potentiated by YDJ-1 when it is present at about one-twentieth the concentration of hsp70. Although hsp40 is not in the final GR.hsp90 heterocomplex isolated from L cell cytosol, it is in the GR.hsp90 heterocomplex assembled in reticulocyte lysate. We conclude that hsp40 is a component of the multiprotein hsp90-based chaperone system where it potentiates GR.hsp90 heterocomplex assembly.     

Smoking cessation with alternative methods

Almost every former smoker has ceased smoking by himself. Everybody has collected his own experience with it and tried different methods to avoid withdrawal symptoms and the urge to start smoking again. During the last decades, many different methods for the therapy of smoking cessation have been applied. These techniques were often developed with the help of individual experiences. Many times, there is a lack of a scientific ground and verifiable investigations for these activities. The most important parameter for the smoking cessation is the clear and strong intention to quit. This intention may be supported by different methods. The mental requirements are discussed and the numerous methods and drugs available to quit smoking are described.     

Astrocytic neurotransmitter receptors in situ and in vivo

In the brain, astrocytes are associated intimately with neurons and surround synapses. Due to their close proximity to synaptic clefts, astrocytes are in a prime location for receiving synaptic information from released neurotransmitters. Cultured astrocytes express a wide range of neurotransmitter receptors, but do astrocytes in vivo also express neurotransmitter receptors and, if so, are the receptors activated by synaptically released neurotransmitters? In recent years, considerable efforts has gone into addressing these issues. The experimental results of this effort have been compiled and are presented in this review. Although there are many different receptors which have not been identified on astrocytes in situ, it is clear that astrocytes in situ express a number of different receptors. There is evidence of glutamatergic, GABAergic, adrenergic, purinergic, serotonergic, muscarinic, and peptidergic receptors on protoplasmic, fibrous, or specialized (Bergmann glia, pituicytes, Müller glia) astrocytes in situ and in vivo. These receptors are functionally coupled to changes in membrane potential or to intracellular signaling pathways such as activation of phospholipase C or adenylate cyclase. The expression of neurotransmitter receptors by astrocytes in situ exhibits regional and intraregional heterogeneity and changes during development and in response to injury. There is also evidence that receptors on astrocytes in situ can be activated by neurotransmitter(s) released from synaptic terminals. Given the evidence of extra-synaptic signaling and the expression of neurotransmitter receptors by astrocytes in situ, direct communication between neurons and astrocytes via neurotransmitters could be a widespread form of communication in the brain which may affect many different aspects of brain function, such as glutamate uptake and the modulation of extracellular space.     

Social skills and cognitive-relaxation approaches to general anger reduction.

Inductive social skills training (ISST), skill assembly social skills training (SASST), and cognitive relaxation coping skills (CRCS) training were compared with a no-treatment control condition for general anger reduction. At 4-wk follow-up, compared with the control group, all treatment groups showed equivalent reductions of the amount of anger experienced in a wide range of situations. ISST and CRCS Ss reported less anger in their worst ongoing provocation than did control Ss, whereas SASST Ss did not differ from Ss of other groups. Treatment groups enhanced anger control equally relative to the control group, but only the CRCS group significantly lowered outward, negative expression of anger, and only the ISST group reduced anger suppression, although active treatment groups did not differ from one another on these measures. The ISST group lowered day-to-day anger more than other groups. No treatment effects were found for nontargeted trait anxiety and assertiveness. Results are discussed in terms of prior findings and the efficacy and flexibility of ISST. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cell recognition, signal induction, and symmetrical gene activation at the dorsal-ventral boundary of the developing Drosophila wing

Appendage formation in insects and vertebrates depends upon signals from both the anterior-posterior and dorsal-ventral (DV) axes. In Drosophila, wing formation is organized symmetrically around the DV boundary of the growing wing imaginal disc and requires interactions between dorsal and ventral cells. Compartmentalization of the wing disc, dorsal cell behavior, and the expression of two dorsally expressed putative signaling molecules, fringe (fng) and Serrate (Ser), are regulated by the apterous selector gene. Here, we demonstrate that fng and Ser have distinct roles in a novel cell recognition and signal induction process. fng serves as a boundary-determining molecule such that Ser is induced wherever cells expressing fng and cells not expressing fng are juxtaposed. Ser in turn triggers the expression of genes involved in wing growth and patterning on both sides of the DV boundary.     

Thrombolytic and endovascular treatment of peripartum iliac vein thrombosis: a case report

This case report details the multidisciplinary treatment of peripartum left iliac vein thrombosis using percutaneous catheter-directed urokinase thrombolysis and balloon thromboplasty. Enhanced chances for long-term patency and the normalization of venous function make these minimally invasive procedures accepted options for the treatment of iliofemoral deep venous thrombosis in selected peripartum patients.     

The orientation dependence of fatigue-crack growth in 8090 Al-Li plate

A series of fatigue-crack growth rate (FCGR) tests was carried out on 8090 Al-Li plate to examine the effects of specimen orientation on fatigue-crack growth. The directionality of fatigue fracture behavior is found to be related to the strong {110}〈112〉 texture in this alloy. Based on a previously developed transgranular FCGR model using restricted slip reversibility (RSR) concepts, [1] a mechanistic model is developed for transgranular fatigue-crack growth in highly textured materials. The model takes the form of the Paris relationship with a power law exponent of 3, and the material texture is shown to strongly influence the proportional factor. The effect of texture on FCGR is related through a geometric factor cos² ϕ, where ϕ defines the angle between the load axis and the normal of the favorable slip plane. The effect of specimen orientation on FCGR in 8090 Al-Li alloy is shown to be related to a combination of its anisotropic mechanical properties and the variation of angleϕ with specimen orientation. The model further predicts that fatigue-crack growth rates will be slower in many textured materials than texturefree materials becauseϕ > 0 and cos₂ ϕ < 1.