Structural analysis of substrate binding by the molecular chaperone DnaK

DnaK and other members of the 70-kilodalton heat-shock protein (hsp70) family promote protein folding, interaction, and translocation, both constitutively and in response to stress, by binding to unfolded polypeptide segments. These proteins have two functional units: a substrate-binding portion binds the polypeptide, and an adenosine triphosphatase portion facilitates substrate exchange. The crystal structure of a peptide complex with the substrate-binding unit of DnaK has now been determined at 2.0 angstroms resolution. The structure consists of a beta-sandwich subdomain followed by alpha-helical segments. The peptide is bound to DnaK in an extended conformation through a channel defined by loops from the beta sandwich. An alpha-helical domain stabilizes the complex, but does not contact the peptide directly. This domain is rotated in the molecules of a second crystal lattice, which suggests a model of conformation-dependent substrate binding that features a latch mechanism for maintaining long lifetime complexes.     

Serum HIV-1 RNA levels and time to development of AIDS in the Multicenter Hemophilia Cohort Study

Normal women produce small amounts of active androgens. When androgen levels are elevated, such as for example in the polycystic ovary syndrome, this is followed by the development of male physical characteristics and muscle mass, structure and function as well as android adipose tissue distribution and function. Psychological features and stress reactions also seem similar to those of men. Such women have an increased risk of developing hypertension, non-insulin-dependent diabetes mellitus and cardiovascular disease. Recent data have shown that these physical, and psychological characteristics, as well as risk of ill health, are also found in the population of women selected at random. Women in the lowest quintiles of levels of sex-hormone-binding globulin--an indicator inversely related to active androgens--are at risk of developing hypertension, non-insulin-dependent diabetes mellitus and cardiovascular mortality. The mechanism probably includes muscular insulin resistance, following a relative androgen excess. It is thus apparent that androgens, even within the highest levels of the nonselected population of women, are powerful predictors of serious disease development. The population at risk might be as large as about 20% of middle-aged women. This is an area of female disease risk which requires more attention in screening and intervention procedures.     

Antimicrobial prophylaxis for catheter-associated bacteriuria

We evaluated short-term systemic antimicrobial prophylaxis for catheter-associated bacteriuria in women undergoing elective gynecological operations in a prospective, controlled, double-masked study. Nine of 100 placebo-treated patients acquired bacteriuria during catheterization compared with 3 of 96 of the drug-treated group. However, at the time of hospital discharge, clean-voided urine specimens were positive as frequently in the drug-treated group (8 of 82 patients cultured) as in the placebo group (8 of 75 patients cultured). No difference in febrile morbidity due to bacteriuria was noted between the prophylaxis and placebo groups. The incidence of catheter-associated bacteriuria may be reduced by antimicrobial prophylaxis. However, because the protective effect is transient and is associated with the selection of resistant organisms, prophylaxis is not indicated for patients at low risk for acquired bacteriuria and in whom the sequelae of catheter-associated infections are infrequent.     

Collecting and processing records from the ultracentrifuge in "real-time" using an on-line computer

An analytical system consisting of an analytical cantrifuge coupled 'on-line' to a computer was assembled and tested. Collection of records from up to 9 solutions was achieved through programmes which sum readings to reduce noise as well as controlling the positioning of the scanner. With this system it was found that the limit on accuracy for molecular weights at concentrations less than 0.01 g cm-3 was +/- 3% estimated from sedimentation equilibrium experiments. The same system was used to collect records for similar concentrations from velocity experiments by employing a scanning schlieren. In this case the accuracy in estimating sedimentation coefficients was similar to those found when measuring photographs. Since the collection yields detailed information about the shape of the sedimenting boundary, the centroids of the boundary were routinely computed by second moment analysis rather than relying on the position of the maximum of the schlieren peak. In the same analysis estimates of diffusion coefficients were made routinely by calculating corrected height/area ratios for each scan. These calculations were made during the real-time of the experiment, so making available molecular parameters rather than records which must be evaluated some time after stopping the experiment.     

Superconducting properties of V3Si produced by reactive diffusion

We have made a study of the superconducting properties of specially prepared V₃Si films. The films studied were produced in two steps. Vanadium was first sputtered onto silica glass substrates; then the film and substrate were heated. Above a definite threshold temperature the vanadium combined with the silicon atoms in the glass to form V₃Si.This research was supported by the National Aeronautics and Space Administration.     

Some determinants of self-monitoring effects

Studied self-monitoring of eyeblink responses in 80 undergraduate volunteers to test hypotheses that (a) the direction of reactive effects is a function of the perceived value of the target behavior; (b) neither the behavior's value nor self-monitoring alone is sufficient to produce significant effects but that both are necessary; (c) self-monitoring is more reactive than monitoring by the E; (d) multiple reports of monitoring are more reactive than a single report of monitoring; and (e) self-monitoring effects are more reactive than a single report of merely attending to a particular behavior. Results provide general support for the 1st 2 hypotheses and suggestive support for the 3rd. Results pertaining to the 4th and 5th hypotheses took an unexpected twist and suggest the need for further study. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Thyroxine-induced activation of hypothalamo-hypophysial axis in neotenic salamander larvae

Thyroxine injected into the hypothalamus of neotenic Ambystoma tigrinum induces metamorphosis by activating hypothalamo-hypophysial stimulatory control of thyroid activity, thereby removing the hypothalamic block to metamorphosis.     

Early diagnosis of rheumatoid arthritis

On the basis of own observations of courses the author adopts a definite attitude to the early symptomatology of the rheumatoid arthritis. During the first weeks of the rheumatoid arthritis the following symptoms are found: articular syndromes, more frequently in form of obstinate polyarthralgias, mono-oligoarthritis, accompanied by morning rigidity and accelerated BSR as well as impairment of the general condition. In the majority of the patients only the tentative diagnosis rheumatoid arthritis may be made. After a one to three months' course of the disease the diagnosis becomes more probable. It is above all based on constancy and symmetry, characteristic localisation of the articular process, morning rigidity, radiologically paraarticular loosening of the structure and morphological symptoms of an acute and subacute synovialitis. 6 to 12 months after the beginning of the disease a clinical picture forms which allows to make the diagnosis of a certain or classical rheumatoid arthritis in accordance with the criteria of the ARA. The occurrence of a high activity of multiple affection of the joints (permanent symmetrical polyarthritis including the small joints of the hands and feet), distinctive morning rigidity, high fever and much accelerated BSR, beginning with the first weeks of the disease, speaks for the possibility of the development of an arthrovisceral form of the course of rheumatoid arthritis.