A dual function for chaperones SSB-RAC and the NAC nascent polypeptide-associated complex on ribosomes.

The yeast Hsp70/40 system SSB-RAC (stress 70 B-ribosome-associated complex) binds to ribosomes and contacts nascent polypeptides to assist cotranslational folding. In this study, we demonstrate that nascent polypeptide-associated complex (NAC), another ribosome-tethered system, is functionally connected to SSB-RAC and the cytosolic Hsp70 network. Simultaneous deletions of genes encoding NAC and SSB caused conditional loss of cell viability under protein-folding stress conditions.

Structural analysis of the ribosome-associated complex (RAC) reveals an unusual Hsp70/Hsp40 interaction.

Yeast Zuotin and Ssz are members of the conserved Hsp40 and Hsp70 chaperone families, respectively, but compared with canonical homologs, they atypically form a stable heterodimer termed ribosome-associated complex (RAC). RAC acts as co-chaperone for another Hsp70 to assist de novo protein folding. In this study, we identified the molecular basis for the unusual Hsp70/Hsp40 pairing using amide hydrogen exchange (HX) coupled with mass spectrometry and mutational analysis.

Par-4-mediated recruitment of Amida to the actin cytoskeleton leads to the induction of apoptosis.

Par-4 (prostate apoptosis response-4) sensitizes cells to apoptotic stimuli, but the exact mechanisms are still poorly understood. Using Par-4 as bait in a yeast two-hybrid screen, we identified Amida as a novel interaction partner, a ubiquitously expressed protein which has been suggested to be involved in apoptotic processes. Complex formation of Par-4 and Amida occurs in vitro and in vivo and is mediated via the C-termini of both proteins, involving the leucine zipper of Par-4.

A national program to restructure local public health agencies in the United States.

This paper proposes a national program to restructure local public health services in the United States which are still characterized by an excessive number of very small health units. It reviews past proposals to correct this situation, and recommends specific programmatic, organizational and financial measures to strengthen the public health infrastructure and achieve an effective national network of federal, state and local public health agencies.

The future of public health: a local health department view.

This is an examination of factors responsible for the "disarray" in public health activities as described in the Institute of Medicine report on The Future of Public Health. It approaches the problem primarily from the viewpoint of the local health agency. Three contributing factors are discussed: disproportionate national expenditures for medical care as compared to public health funding; structural flaws in organization leading to functional difficulties; and medical profession opposition to an expanded role for local health departments.