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Lysosomal enzymes are synthesized in the endoplasmic reticulum (ER) and transferred to the Golgi complex by interaction with the Batten disease protein CLN8 (ceroid lipofuscinosis, neuronal, 8). Here we investigated the relationship of this pathway with CLN6, an ER-associated protein of unknown function that is defective in a different Batten disease subtype. Experiments focused on protein interaction and trafficking identified CLN6 as an obligate component of a CLN6-CLN8 complex (herein referred to as EGRESS: ER-to-Golgi relaying of enzymes of the lysosomal system), which recruits lysosomal enzymes at the ER to promote their Golgi transfer. Mutagenesis experiments showed that the second luminal loop of CLN6 is required for the interaction of CLN6 with the enzymes but dispensable for interaction with CLN8. In vitro and in vivo studies showed that CLN6 deficiency results in inefficient ER export of lysosomal enzymes and diminished levels of the enzymes at the lysosome. Mice lacking both CLN6 and CLN8 did not display aggravated pathology compared with the single deficiencies, indicating that the EGRESS complex works as a functional unit. These results identify CLN6 and the EGRESS complex as key players in lysosome biogenesis and shed light on the molecular etiology of Batten disease caused by defects in CLN6.

Macrophages and neutrophils generate a potent burst of reactive oxygen and nitrogen species as a key aspect of the antimicrobial response. While most successful pathogens, including the fungus Candida albicans, encode enzymes for the detoxification of these compounds and repair of the resulting cellular damage, some species actively modulate immune function to suppress the generation of these toxic compounds. We report here that C. albicans actively inhibits macrophage production of nitric oxide (NO). NO production was blocked in a dose-dependent manner when live C. albicans were incubated with either cultured or bone marrow-derived mouse macrophages. While filamentous growth is a key virulence trait, yeast-locked fungal cells were still capable of dose-dependent NO suppression. C. albicans suppresses NO production from macrophages stimulated by exposure to IFN-γ and LPS or cells of the non-pathogenic Saccharomyces cerevisiae. The NO inhibitory activity was produced only when the fungal cells were in direct contact with macrophages, but the compound itself was secreted into the culture media. LPS/IFNγ stimulated macrophages cultured in cell-free conditioned media from co-cultures showed reduced levels of iNOS enzymatic activity and lower amounts of iNOS protein. Initial biochemical characterization of this activity indicates that the inhibitor is a small, aqueous, heat-stable compound. In summary, C. albicans actively blocks NO production by macrophages via a secreted mediator; these findings expand our understanding of phagocyte modulation by this important fungal pathogen and represent a potential target for intervention to enhance antifungal immune responses. [ABSTRACT FROM AUTHOR]

The article discusses the quality of urban life in context of population density, household crowding and social problems. The usual assumption is that these forms of congestion are stressful to individuals and that the resultant stress is manifested in increased rates of physical, psychological and social disorders. Researches in this field indicate that crowding associated with heightened neurological activity and hormonal aberration, a decrease in normal reproductive behavior, increased aggression, and higher morbidity and mortality rates. Speculation about, and research into, the associations between human densities and pathologies have flourished in the past few years. The article also cites findings of the research done in the field of quality of life in urban areas. These findings lend partial support to the general proposition that population density is directly related to stress pathologies. Relative severity of the disorders used as dependent variables in this study does not preclude the consideration of milder forms of stress-reactions resulting from crowded conditions. The study is limited to New Zealand urban areas, which are neither severely crowded nor highly dense by world standards.

Data from a 1973-74 survey and a five year follow-up survey in 1979, both conducted in New Zealand, are analyzed with regard to gender differences in role obligations, privacy and psychological well-being. The findings support the hypothesis that women are the primary providers of nurturance to family members. Women, more than men reported reductions in privacy because of their role obligations. Reduced privacy in turn caused a reduction in psychological well-being.Les données de l'enquête de 1973-74, et ceux d'une autre en 1979, poursuivie pendant 5 ans sont analysées. Les deux enquêtes réalisees à la Nouvelle Zelande. Ces données concernent les differences entre les sexes quant aux rôles d'obligation, l'intimité et le bien-être psychologique. Les conclusions soutiennent l'hypothèse selon laquelle les femmes sont les principales fournisseuses de soins aux membres de la famille. L'intimité des femmes est réduite plus que les hommes; ceçi étant dû aux r6les d'obligation. L'intimité diminuée, à son tour provoque une baisse dans le bien-être psychologique. [ABSTRACT FROM PUBLISHER]

Examines the relationship between spatial characteristics of a human population and stress in urban areas in New Zealand. Advantages in using psychotropic drugs as a primary dependent variable; Importance of household composition in relation to the use of psychotropic drugs; Impact of household composition on psychotropic drug prescriptions.

Data from an australian survey of 1,050 elderly men and women were analyzed with regard to sex differences in life satisfaction and its determinants. Men and women had very similar levels of education, health, financial satisfaction, subjective social integration, and morale. Little difference between sexes was found in the causal process determining life satisfaction. There was little or no interaction between sex and the other variables examined. [ABSTRACT FROM PUBLISHER]