Mitonuclear interactions shape both direct and parental effects of diet on fitness and involve a SNP in mitoribosomal 16s rRNA.

Nutrition is a primary determinant of health, but responses to nutrition vary with genotype. Epistasis between mitochondrial and nuclear genomes may cause some of this variation, but which mitochondrial loci and nutrients participate in complex gene-by-gene-by-diet interactions? Furthermore, it remains unknown whether mitonuclear epistasis is involved only in the immediate responses to changes in diet, or whether mitonuclear genotype might modulate sensitivity to variation in parental nutrition, to shape intergenerational fitness responses. Here, in Drosophila melanogaster, we show that mitonuclear epistasis shapes fitness responses to variation in dietary lipids and amino acids. We also show that mitonuclear genotype modulates the parental effect of dietary lipid and amino acid variation on offspring fitness. Effect sizes for the interactions between diet, mitogenotype, and nucleogenotype were equal to or greater than the main effect of diet for some traits, suggesting that dietary impacts cannot be understood without first accounting for these interactions. Associating phenotype to mtDNA variation in a subset of populations implicated a C/T polymorphism in mt:lrRNA, which encodes the 16S rRNA of the mitochondrial ribosome. This association suggests that directionally different responses to dietary changes can result from variants on mtDNA that do not change protein coding sequence, dependent on epistatic interactions with variation in the nuclear genome.

Longevity is determined by ETS transcription factors in multiple tissues and diverse species.

Ageing populations pose one of the main public health crises of our time. Reprogramming gene expression by altering the activities of sequence-specific transcription factors (TFs) can ameliorate deleterious effects of age. Here we explore how a circuit of TFs coordinates pro-longevity transcriptional outcomes, which reveals a multi-tissue and multi-species role for an entire protein family: the E-twenty-six (ETS) TFs. In Drosophila, reduced insulin/IGF signalling (IIS) extends lifespan by coordinating activation of Aop, an ETS transcriptional repressor, and Foxo, a Forkhead transcriptional activator. Aop and Foxo bind the same genomic loci, and we show that, individually, they effect similar transcriptional programmes in vivo. In combination, Aop can both moderate or synergise with Foxo, dependent on promoter context. Moreover, Foxo and Aop oppose the gene-regulatory activity of Pnt, an ETS transcriptional activator. Directly knocking down Pnt recapitulates aspects of the Aop/Foxo transcriptional programme and is sufficient to extend lifespan. The lifespan-limiting role of Pnt appears to be balanced by a requirement for metabolic regulation in young flies, in which the Aop-Pnt-Foxo circuit determines expression of metabolic genes, and Pnt regulates lipolysis and responses to nutrient stress. Molecular functions are often conserved amongst ETS TFs, prompting us to examine whether other Drosophila ETS-coding genes may also affect ageing. We show that five out of eight Drosophila ETS TFs play a role in fly ageing, acting from a range of organs and cells including the intestine, adipose and neurons. We expand the repertoire of lifespan-limiting ETS TFs in C. elegans, confirming their conserved function in ageing and revealing that the roles of ETS TFs in physiology and lifespan are conserved throughout the family, both within and between species.

Rapamycin's lifespan effect is modulated by mito-nuclear epistasis in Drosophila.

The macrolide drug rapamycin is a benchmark anti-ageing drug, which robustly extends lifespan of diverse organisms. For any health intervention, it is paramount to establish whether benefits are distributed equitably among individuals and populations, and ideally to match intervention to recipients' needs. However, how responses to rapamycin vary is surprisingly understudied. Here we investigate how among-population variation in both mitochondrial and nuclear genetics shapes rapamycin's effects on lifespan. We show that epistatic "mito-nuclear" interactions, between mitochondria and nuclei, modulate the response to rapamycin treatment. Differences manifest as differential demographic effects of rapamycin, with altered age-specific mortality rate. However, a fitness cost of rapamycin early in life does not show a correlated response, suggesting that mito-nuclear epistasis can decouple costs and benefits of treatment. These findings suggest that a deeper understanding of how variation in mitochondrial and nuclear genomes shapes physiology may facilitate tailoring of anti-ageing therapy to individual need.

Intensive care unit length of stay and mortality comparison between on-pump and off-pump coronary artery bypass graft: a retrospective study.

BACKGROUND: Recently, coronary artery bypass graft (CABG) techniques, both on-pump (ONCABG) and off-pump (OPCABG), were compared to seek the most effective approach to reduce the cost of prolonged intensive care unit length of stay (ICU LOS) and mortality. This study aims to compare ICU LOS and mortality in ONCABG and OPCABG. RESULTS: Demographic data of 1569 patients show the variance of characteristics. The analysis shows significant and longer ICU LOS in OPCABG than ONCABG (2.151 ± 0.100 vs. 1.573 ± 0.246 days; p = 0.028). Similar results were demonstrated after adjustment of covariates effects (3.146 ± 0.281 vs. 2.548 ± 0.245 days; p = 0,022). Logistic regression shows no significant difference in mortality in OPCABG and ONCABG, both in the unadjusted (OR [CI 95%] 1.133 [0.485-2.800]; p = 0.733) and the adjusted models (OR [CI 95%] 1.133 [0.482-2.817]; p = 0,735). CONCLUSION: ICU LOS was significantly longer in OPCABG patients than in ONCABG patients in the author's centre. There was no significant difference in mortality between the two groups. This finding highlights a discrepancy between recently published theories and the practices observed in the author's centre.

Molecular characterization of Salmonella spp directly from snack and food commonly sold in Lagos, Nigeria.

Food borne Salmonella infection is an important cause of morbidity and mortality. A total of 200 food samples commonly sold in Lagos, Nigeria comprising raw and cooked meat as well as meat products and spoilt meat were analysed for the presence of Salmonella spp using REVEAL serology kit, culture methods employing RPVA (Rappaport Vassiliadis agar), SSA (Salmonella-Shigella agar) and BSA (brilliant sulphite agar) and PCR method for direct detection from samples using primer salm3/4 and ST11/ST15 sets. Using the REVEAL serology kit, 74% of the samples were positive for Salmonella spp, while culture methods showed only 19% to be Salmonella spp. The PCR method revealed that Salmonella spp was present in 62% and 54% of the samples using primer set salm3/4 and ST11/ST15, respectively. However, the primer set ST11/ST15 was more reliable in the identification of Salmonella spp directly from food samples. These tools should prove useful in the continuous monitoring and control strategies especially for ready-to-eat foods, as well as in retail meat outlets, slaughter houses, fast food restaurants for the prevention and reduction of this pathogen that is of significant importance in the food industry.