Overproduction of PDR3 Suppresses Mitochondrial Import Defects Associated with a TOM70 Null Mutation by Increasing the Expression of TOM72 in Saccharomyces cerevisiae

Most mitochondrial proteins are synthesized with cleavable amino-terminal targeting signals that interact with the mitochondrial import machinery to facilitate their import from the cytosol. We previously reported that the presequence of the F1-ATPase beta subunit precursor (pre-F1beta ) acts as an intramolecular chaperone that maintains the precursor in an import-competent conformation prior to import (P. Hajek, J. Y. Koh, L. Jones, and D. M. Bedwell, Mol. Cell. Biol. 17:7169-7177, 1997). We also found that a mutant form of pre-F1beta with a minimal targeting signal (Delta 1,2 pre-F1beta) is inefficiently imported into mitochondria because it rapidly folds into an import-incompetent conformation. We have now analyzed the consequences of reducing the pre-F1beta targeting signal to a minimal unit in more detail. We found that Delta 1,2 pre-F1beta is more dependent upon the Tom70p receptor for import than WT pre-F1beta is, resulting in a growth defect on a nonfermentable carbon source at 15°C. Experiments using an in vitro mitochondrial protein import system suggest that Tom70p functions to maintain a precursor containing the Delta 1,2 pre-F1beta import signal in an import-competent conformation. We also identified PDR3, a transcriptional regulator of the pleiotropic drug resistance network, as a multicopy suppressor of the mitochondrial import defects associated with Delta 1,2 pre-F1beta in a tom70Delta strain. The overproduction of PDR3 mediated this effect by increasing the import of Delta 1,2 pre-F1beta into mitochondria. This increased the mitochondrial ATP synthase activity to the extent that growth of the mutant strain was restored under the selective conditions. Analysis of the transcription patterns of components of the mitochondrial outer membrane import machinery demonstrated that PDR3 overproduction increased the expression of TOM72, a little studied TOM70 homologue. These results suggest that Tom72p possesses overlapping functions with Tom70p and that the pleiotropic drug resistance network plays a previously unappreciated role in mitochondrial biogenesis

The Adaptive Significance of Natural Genetic Variation in the DNA Damage Response of Drosophila melanogaster.

Despite decades of work, our understanding of the distribution of fitness effects of segregating genetic variants in natural populations remains largely incomplete. One form of selection that can maintain genetic variation is spatially varying selection, such as that leading to latitudinal clines. While the introduction of population genomic approaches to understanding spatially varying selection has generated much excitement, little successful effort has been devoted to moving beyond genome scans for selection to experimental analysis of the relevant biology and the development of experimentally motivated hypotheses regarding the agents of selection; it remains an interesting question as to whether the vast majority of population genomic work will lead to satisfying biological insights. Here, motivated by population genomic results, we investigate how spatially varying selection in the genetic model system, Drosophila melanogaster, has led to genetic differences between populations in several components of the DNA damage response. UVB incidence, which is negatively correlated with latitude, is an important agent of DNA damage. We show that sensitivity of early embryos to UVB exposure is strongly correlated with latitude such that low latitude populations show much lower sensitivity to UVB. We then show that lines with lower embryo UVB sensitivity also exhibit increased capacity for repair of damaged sperm DNA by the oocyte. A comparison of the early embryo transcriptome in high and low latitude embryos provides evidence that one mechanism of adaptive DNA repair differences between populations is the greater abundance of DNA repair transcripts in the eggs of low latitude females. Finally, we use population genomic comparisons of high and low latitude samples to reveal evidence that multiple components of the DNA damage response and both coding and non-coding variation likely contribute to adaptive differences in DNA repair between populations

Creel Survey on Newton Lake

Final Report issued May 1, 2001Report issued on: May 1, 2001INHS Technical Report prepared for Ameren Corporatio

Companion animals and well-being in palliative care nursing: a literature review

Aims and objectives To evaluate and critique current knowledge regarding the role of animals in palliative care. To explore the impact that animals may have on the well-being of individuals and to identify gaps in the evidence base. Background There is recognition that having a companion animal will affect patient experience. Similarly, there has been some previous exploration on the use of specific animal assisted therapies for patients with different healthcare needs. Design A literature review was conducted to identify published and unpublished research about companion animals or animal-assisted therapy in palliative and/or end-of-life care. The primary objective was to explore the impact of animals on well-being at the end of life. Methods A search for literature was carried out using a variety of databases and different combinations of search terms linked to animals in palliative care. Included works were critically appraised and thematically analysed. Results A limited range of literature was identified. From the small number of studies included in the review (n = 4), it appears that there is some evidence of animals (either companion animals or those used specifically to enhance care) having a positive impact on the patient experience. Conclusion This study suggests that animals play a large part in the lives of people receiving palliative care. Using animals to support care may also offer some benefits to the patient experience. However, there appears to be a dearth of high-quality literature in this area. More research is therefore required. Relevance to clinical practice Nurses providing palliative care need to be aware of the part that a companion animal may play in the life of patients. There may also be the opportunity for nurses in some settings to integrate animal therapy into their provision of palliative care

Monovision LASIK in emmetropic presbyopic patients.

BackgroundTo evaluate the efficacy and patient satisfaction of laser in situ keratomileusis (LASIK) monovision correction in presbyopic emmetropic patients.MethodsA retrospective review of 294 patients who underwent LASIK for monovision was conducted. All patients had preoperative uncorrected distance visual acuity in each eye of 20/25 or better in both eyes and underwent primary LASIK treatment in one eye with a near target; 82 patients underwent surgery in the distant eye for hypermetropia. Patients completed a patient-reported-outcome questionnaire at their one-month postoperative visit. Analysis was performed on a per patient basis with a logistic regression model.ResultsPatients achieved a postoperative mean spherical equivalent of -0.05 diopters (D) in the distant eye and -1.92 D in the near eye. Prior to surgery, 64.7% (n=178) of patients reported they were satisfied or very satisfied with their vision; postoperatively, this increased to 85.4% (n=251). The greatest predictor of dissatisfaction after surgery was severe patient-reported visual phenomena (glare, halos, starbursts, ghosting) (odds ratio 1.18, P=0.001).ConclusionsLASIK monovision for presbyopic patients with low refractive error and good preoperative uncorrected distance visual acuity is both safe and effective with high patient satisfaction. Patients who were dissatisfied in the postoperative period tended to be those with postoperative visual symptoms

Informed consent in refractive surgery: in-person vs telemedicine approach.

Purpose:The aim of this study was to compare the quality of consent process in refractive surgery between patients who had a preoperative consent discussion with the surgeon using a telemedicine approach and those who had a face-to-face discussion. Methods:Patients treated between January and December 2017 (8,184 laser vision correction [LVC] and 3,754 refractive lens exchange [RLE] patients) that attended day 1 and 1-month postoperative visit were retrospectively reviewed. Preoperative consent preparation included a consultation with an optometrist, observation of an educational video, and written information. Patients then selected either a face-to-face appointment with their surgeon (in-clinic group) or a telemedicine appointment (remote group) for their consent discussion, according to their preference. Patient experience questionnaire and clinical data were included in a multivariate model to explore factors associated with consent quality. Results:Prior to surgery, 80.1% of LVC and 47.9% of RLE patients selected remote consent. Of all LVC patients, 97.5% of in-clinic and 98.3% of remote patients responded that they were adequately consented for surgery (P=0.04). Similar percentages in the RLE group were 97.6% for in-clinic and 97.9% for remote patients (P=0.47). In a multivariate model, the major predictor of patient's satisfaction with the consent process was postoperative satisfaction with visual acuity, responsible for 80.4% of variance explained by the model. Other significant contributors were postoperative visual phenomena and dry eyes, difficulty with night driving, close-up and distance vision, postoperative uncorrected distance visual acuity, change in corrected distance visual acuity, and satisfaction with the surgeon's approach. The type of consent (remote or in-clinic) had no impact on patient's perception of consent quality in the regression model. Conclusion:The majority of patients opted for telemedicine-assisted consent. Those who chose it were equally satisfied as those who had a face-to-face meeting with their surgeon. Dissatisfaction with surgical outcome was the major factor affecting patient's perception of consent quality, regardless of the method of their consent