Network of general and specialty J protein chaperones of the yeast cytosol

J proteins are obligate cochaperones of Hsp70s, stimulating their ATPase activity and thus allowing them to function in multiple cellular processes. In most cellular compartments, an Hsp70 works with multiple, structurally divergent J proteins. To better understand the functional specificity of J proteins and the complexity of the Hsp70:J protein network, we undertook a comprehensive analysis of 13 J proteins of the cytosol of the yeast Saccharomyces cerevisiae. Phenotypes caused by the absence of four proteins, Sis1, Jjj1, Jjj3, and Cwc23, could not be rescued by overexpression of any other cytosolic J protein, demonstrating the distinctive nature of J proteins. In one case, that of Zuo1, the phenotypic effects of the absence of a J protein could be rescued by overexpression of only one other J protein, Jjj1, which, like Zuo1, is ribosome-associated. In contrast, the severe growth phenotype caused by the absence of the cytosol's most abundant J protein, Ydj1, was substantially rescued by expression of J domain-containing fragments of many cytosolic J proteins. We conclude that many functions of Hsp70 chaperone machineries only require stimulation of Hsp70's ATPase activity by J protein partners. However, a subset of Hsp70 functions requires specific J protein partners, likely demanding either sublocalization within the compartment or binding to specific client proteins.     

Perceived causes of suicide attempts by U.K. South Asian women

Perceived causes of suicide attempts were examined in 180 ethnic South Asian women living in the London area. The 3 factors endorsed most frequently and strongly as causes of suicide attempts in South Asian women were violence by the husband, being trapped in an unhappy family situation, and depression.     

Causal explanations of distress and general practitioners' assessments of common mental disorder among Punjabi and English attendees

Background: The literature on the primary care assessment of mental distress among Indian sub-continent origin patients suggests frequent presentations to general practitioner, but rarely for recognisable psychiatric disorders. This study investigates whether cultural variations in patients' causal explanatory models account for cultural variations in the assessment of non-psychotic mental disorders in primary care. Methods In a two-phase survey, 272 Punjabi and 269 English subjects were screened. The second phase was completed by 209 and 180 subjects, respectively. Causal explanatory models were elicited as explanations of two vignette scenarios. One of these emphasised a somatic presentation and the other anxiety symptoms. Psychiatric disorder was assessed by GPs on a Likert scale and by a psychiatrist on the Clinical Interview Schedule. Results Punjabis more commonly expressed medical/somatic and religious beliefs. General practitioners were more likely to assess any subject giving psychological explanations to vignette A and English subjects giving religious explanations to vignette B as having a significant psychiatric disorder. Where medical/somatic explanations of distress were most prevalent in response to the somatic vignette, psychological, religious and work explanations were less prevalent among Punjabis but not among English subjects. Causal explanations did not fully explain cultural differences in assessments. Conclusions General practitioners' assessments and causal explanations are related and influenced by culture, but causal explanations do not fully explain cultural differences in assessments. Accepted: 18 September 2001     

The nonsteady state modeling of freeze drying: in-process product temperature and moisture content mapping and pharmaceutical product quality applications

INTRODUCTION: Theoretical models of the freeze-drying process are potentially useful to guide the design of a freeze-drying process as well as to obtain information not readily accessible by direct experimentation, such as moisture distribution and glass transition temperature, Tg, within a vial during processing. Previous models were either restricted to the steady state and/or to one-dimensional problems. While such models are useful, the restrictions seriously limit applications of the theory. An earlier work from these laboratories presented a nonsteady state, two-dimensional model (which becomes a three-dimensional model with an axis of symmetry) of sublimation and desorption that is quite versatile and allows the user to investigate a wide variety of heat and mass transfer problems in both primary and secondary drying. The earlier treatment focused on the mathematical details of the finite element formulation of the problem and on validation of the calculations. The objective of the current study is to provide the physical rational for the choice of boundary conditions, to validate the model by comparison of calculated results with experimental data, and to discuss several representative pharmaceutical applications. To validate the model and evaluate its utility in studying distribution of moisture and glass transition temperature in a representative product, calculations for a sucrose-based formulation were performed, and selected results were compared with experimental data. THEORETICAL MODEL: The model is based on a set of coupled differential equations resulting from constraints imposed by conservation of energy and mass, where numerical results are obtained using finite element analysis. Use of the model proceeds via a "modular software package" supported by Technalysis Inc. (Passage/ Freeze Drying). This package allows the user to define the problem by inputing shelf temperature, chamber pressure, container properties, product properties, and numerical analysis parameters required for the finite element analysis. Most input data are either available in the literature or may be easily estimated. Product resistance to water vapor flow, mass transfer coefficients describing secondary drying, and container heat transfer coefficients must normally be measured. Each element (i.e., each small subsystem of the product) may be assigned different values of product resistance to accurately describe the nonlinear resistance behavior often shown by real products. During primary drying, the chamber pressure and shelf temperature may be varied in steps. During secondary drying, the change in gas composition from pure water to mostly inert gas is calculated by the model from the instantaneous water vapor flux and the input pumping capacity of the freeze dryer. RESULTS: Comparison of the theoretical results with the experiment data for a 3% sucrose formulation is generally satisfactory. Primary drying times agree within two hours, and the product temperature vs. time curves in primary drying agree within about +/-1 degrees C. The residual moisture vs. time curve is predicted by the theory within the likely experimental error, and the lack of large variation in moisture within the vial (i.e., top vs. side vs. bottom) is also correctly predicted by theory. The theoretical calculations also provide the time variation of "Tg-T" during both primary and secondary drying, where T is product temperature and Tg is the glass transition temperature of the product phase. The calculations demonstrate that with a secondary drying protocol using a rapid ramp of shelf temperature, the product temperature does rise above Tg during early secondary drying, perhaps being a factor in the phenomenon known as "cake shrinkage." CONCLUSION: The theoretical results of in-process product temperature, primary drying time, and moisture content mapping and history are consistent with the experimental results, suggesting the theoretical model should be useful in process development and "trouble-shooting" applications.     

Insight in people with psychosis: the influence of culture

The assessment of insight is a part of the routine clinical examination for people with mental illness. Such assessment, by psychiatrists, is based on the current definitions of insight, which rely on western notions of health and illness. This paper discusses the recent findings of explanatory models of people with a variety of physical diseases in Vellore, India. It also summaries the results of studies on insight in schizophrenia, which examined explanatory models of illness among patients, relatives, and the general population, in Vellore. The findings argue for the fact that the assessment of insight should be against the local cultural standards rather than universal yardsticks.