Abstract. SSH1, a newly identified member of the heat shock protein (hsp70) multigene family of the budding yeast Saccharomyces cerevisiae, encodes a protein localized to the mitochondrial matrix. Deletion of the SSH1 gene results in extremely slow growth at 23°C or 30°C, but nearly wild-type growth at 37°C. The matrix of the mitochondria contains another hsp70, Sscl, which is essential for growth and required for translocation of proteins into mitochondria. Unlike SSC1 mutants, an SSH1 mutant showed no detectable defects in import of several proteins from the cytosol to the matrix compared to wild type. Increased expression of Sscl partially suppressed the cold-sensitive growth defect of the SSHI mutant, suggesting that when present in increased amounts, Sscl can at least partially carry out the normal functions of Sshl. Spontaneous suppressors of the cold-sensitive phenotype of an SSH1 null mutant were obtained at a high frequency at 23°C, and were all found to be respiration deficient. 15 of 16 suppressors that were analyzed lacked mitochondrial DNA, while the 16th had reduced amounts. We suggest that Sshl is required for normal mitochondrial DNA replication, and that disruption of this process in sshl cells results in a defect in mitochondrial function at low temperatures. HEAT shock proteins of the hsp70 class are found in all organisms and play essential roles as molecular chaperones (for reviews see 7,18,20). Related hsp70s are found in cellular compartments such as the cytosol, ER, and mitochondria (5). The cytosol of yeast contains two functionally distinct classes of hsp70s, the SSA and SSB proteins (9). The SSA proteins, besides being involved in the regulation of expression of heat-inducible genes, are required for normal rates of translocation of some proteins into the ER or mitochondria. The SSB proteins associate with translating ribosomes, and they are required for normal protein translation. The presence of both SSA and SSB classes of hsp70s in the same cellular compartment illustrates the evolution of related but functionally distinct types of hsp70s.To date, Sscl has been the only hsp70 identified in the mitochondria matrix, and Kar2 has been the sole family member identified in the ER (8,30,36). In the yeast Saccharomyces cerevisiae, Sscl is required for the translocation of proteins from the cytosol into the matrix and is involved in their subsequent folding, maturation, and proteolysis (16,21,22,40,49). Sscl is proposed to bind to

In 2019, there were multiple outbreaks of measles in the United States. In the context of the public awareness of these outbreaks, we performed an intervention with the intent to improve the rate of measles immunization in our pediatric population. Pediatric patients that were lacking adequate measles immunization were identified by electronic medical record (EMR) survey. Charts were reviewed and updated if records were found to be incomplete. Parents of the remaining children were sent a letter, personally signed by the child’s primary care provider, encouraging measles immunization. A measles fact sheet, produced by the United States Center for Disease Control, was also included with the letter. There were 44 patients in the study group whose parents received a letter and measles fact sheet. As a result, 5 of these children were brought in for a measles, mumps, and rubella (MMR) immunization. The 44 patients whose parents received a letter included 20 patients whose parents had previously expressed intent to not vaccinate their children as documented in the EMR. None of these children received an MMR immunization. Although small in scope, this project provides a glimpse into the importance of personal provider guidance to parents who are inclined to immunize their children. Unfortunately, it also demonstrated that provider advice did not change the opinions of parents who had already taken a stance against vaccination, even in the context of an urgent public health situation that had garnered widespread coverage in the lay press and social media.

This article brings to bear aspects of Nietzsche's understanding of the affirmation of life on R. Jay Wallace's account in The View from Here (2013). While Wallace takes as a sufficient condition for an individual to affirm her life (what I call “self-affirmation”) that she prefer on balance the life she actually lived over the alternative of not having lived at all, he claims that, because of the lamentable past conditions causally connected to our lives, the normative bases for self-affirmation are generally absent. I propose an interpretation of Nietzsche on which achieving self-affirmation is not simply a matter of forming certain preferences regarding one's life; instead, achieving the warrant for self-affirmation involves the sort of life one has lived, namely a life engaged in the pursuit of growth (the exercise of the will to power), in part through confrontation with the problematic and questionable aspects of life.

No abstract

No abstract