Molecular mechanisms of vertebrate photoreceptor light adaptation.

An important recent advance in the understanding of vertebrate photoreceptor light adaptation has come from the discovery that as many as eight distinct molecular mechanisms may be involved, and the realization that one of the principal mechanisms is not dependent on calcium. Quantitative analysis of these mechanisms is providing new insights into the nature of rod photoreceptor light adaptation.     

Morphological and Cytochemical Studies on Lymphocytic Choriomeningitis Virus

Lymphocytic choriomeningitis (LCM) virus was observed by electron microscopy in thin sections of infected tissue cultures. The particles were pleomorphic and varied greatly in size. The smaller particles (50 to 200 nm) appeared to be spherical, whereas the largest (over 200 nm) were often cup-shaped. All particles contained one to eight or more electron-dense granules which were removed by ribonuclease. The particles were formed by budding from the plasma membrane and appeared to have spikes. The morphological evidence suggests that LCM should be considered as belonging to the presently unclassified group of lipoprotein-enveloped ribonucleic acid viruses.     

An association between the acute phase response and patterns of antigen induced T cell proliferation in juvenile idiopathic arthritis

The aim of this research was to determine whether all memory T cells have the same propensity to migrate to the joint in patients with juvenile idiopathic arthritis. Paired synovial fluid and peripheral blood mononuclear cell proliferative responses to a panel of antigens were measured and the results correlated with a detailed set of laboratory and clinical data from 39 patients with juvenile idiopathic arthritis. Two distinct patterns of proliferative response were found in the majority of patients: a diverse pattern, in which synovial fluid responses were greater than peripheral blood responses for all antigens tested; and a restricted pattern, in which peripheral blood responses to some antigens were more vigorous than those in the synovial fluid compartment. The diverse pattern was generally found in patients with a high acute phase response, whereas patients without elevated acute phase proteins were more likely to demonstrate a restricted pattern. We propose that an association between the synovial fluid T cell repertoire and the acute phase response suggests that proinflammatory cytokines may influence recruitment of memory T cells to an inflammatory site, independent of their antigen specificity. Additionally, increased responses to enteric bacteria and the presence of αEβ7 T cells in synovial fluid may reflect accumulation of gut associated T cells in the synovial compartment, even in the absence of an elevated acute phase response. This is the first report of an association between the acute phase response and the T cell population recruited to an inflammatory site.     

Inequalities in women's health: looking at mortality differentials using an alternative approach

Data obtained from follow up of the 1971 census sample in the Office of Population Censuses and Surveys longitudinal study of England and Wales were used to look at women''s mortality differentials at ages 15-59. Women were grouped by combining information on marital state, own occupation, husband''s occupation (if married), economic activity, and indicators of household wealth (housing tenure and access to a car). Large groups were found with considerable differences in mortality. High mortality was associated with working in manual occupations and living in rented housing with no car in the household. In contrast, low mortality was associated with non-manual occupations and living in owner occupied housing with a car. Among married housewives and single women these extreme groups contributed 44% of expected deaths, the disadvantaged group experiencing death rates two and a half times that of the advantaged group. Smaller differences were found among married women with an occupational class.These findings are further evidence of the “health divide” in England and Wales and show that accurately to reflect the relation between a woman''s life circumstances and mortality it is necessary to utilise other measures than those based solely on occupation.     

Sensitivity to antimicrobial agents of some mercury-sensitive and mercury-resistant strains of Gram-negative bacteria

The sensitivity and resistance of some Gram-negative mercury (Hg²⁺)-sensitive and-resistant strains to chemotherapeutic agents and to disinfectants and preservatives are described.Escherichia coli andPseudomonas aeruginosa strains harboring plasmid pUB 1351 [pUB 367:Tn 501] andE. coli bearing R100-1 were resistant to inorganic mercury and to various antibiotics, but were not more resistant to organic mercury and other preservatives and disinfectants than plasmidless strains.     

Solution structure of RING finger-like domain of retinoblastoma-binding protein-6 (RBBP6) suggests it functions as a U-box

Retinoblastoma-binding protein-6 (RBBP6) plays a facilitating role, through its RING finger-like domain, in the ubiquitination of p53 by Hdm2 that is suggestive of E4-like activity. Although the presence of eight conserved cysteine residues makes it highly probable that the RING finger-like domain coordinates two zinc ions, analysis of the primary sequence suggests an alternative classification as a member of the U-box family, the members of which do not bind zinc ions. We show here that despite binding two zinc ions, the domain adopts a homodimeric structure highly similar to those of a number of U-boxes. Zinc ions could be replaced by cadmium ions without significantly disrupting the structure or the stability of the domain, although the rate of substitution was an order of magnitude slower than any previous measurement, suggesting that the structure is particularly stable, a conclusion supported by the high thermal stability of the domain. A hallmark of U-box-containing proteins is their association with chaperones, with which they cooperate in eliminating irretrievably unfolded proteins by tagging them for degradation by the proteasome. Using a yeast two-hybrid screen, we show that RBBP6 interacts with chaperones Hsp70 and Hsp40 through its N-terminal ubiquitin-like domain. Taken together with the structural similarities to U-box-containing proteins, our data suggest that RBBP6 plays a role in chaperone-mediated ubiquitination and possibly in protein quality control.