MicroRNAs mir‐184 and let‐7 alter Drosophila metabolism and longevity

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140032/1/acel12673.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/140032/2/acel12673-sup-0002-FigS1-S8.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/140032/3/acel12673_am.pd

Accuracy of recall of musculoskeletal injuries in elite military personnel: a cross-sectional study

Background Self-reported data are often used in research studies among military populations. Objective The accuracy of self-reported musculoskeletal injury data among elite military personnel was assessed for issues with recall. Design Cross-sectional study. Setting Applied research laboratory at a military installation. Participants A total of 101 subjects participated (age 28.5±5.6 years). Study participants were active duty military personnel, with no conditions that precluded them from full duty. Primary and secondary outcome measures Self-reported and medical record reviewed injuries that occurred during a 1-year period were matched by anatomic location, injury side (for extremity injuries), and injury year and type. The accuracy of recall was estimated as the per cent of medical record reviewed injuries correctly recalled in the self-report. The effect of injury anatomic location, injury type and severity and time since injury, on recall, was also assessed. Injuries were classified as recent (≤4 years since injury) or old injuries (\u3e4 years since injury). Recall proportions were compared using Fisher’s exact tests. Results A total of 374 injuries were extracted from the subjects’ medical records. Recall was generally low (12.0%) and was not different between recent and old injuries (P=0.206). Injury location did not affect recall (P=0.418). Recall was higher for traumatic fractures as compared with less severe non-fracture injuries (P values 0.001 to \u3c0.001). Recall for non-fracture injuries was higher for recent as compared with old injuries (P=0.033). This effect of time since injury on recall was not observed for fractures (P=0.522). Conclusions The results of this study highlight the importance of weighing the advantages and disadvantages of self-reported injury data before their use in research studies in military populations and the need for future research to identify modifiable factors that influence recall

Mitochondrial thioredoxin reductase 2 is elevated in long‐lived primate as well as rodent species and extends fly mean lifespan

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137684/1/acel12596-sup-0001-SupInfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137684/2/acel12596.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137684/3/acel12596_am.pd

Lifespan extension in female mice by early, transient exposure to adult female olfactory cues

Several previous lines of research have suggested, indirectly, that mouse lifespan is particularly susceptible to endocrine or nutritional signals in the first few weeks of life, as tested by manipulations of litter size, growth hormone levels, or mutations with effects specifically on early-life growth rate. The pace of early development in mice can also be influenced by exposure of nursing and weanling mice to olfactory cues. In particular, odors of same-sex adult mice can in some circumstances delay maturation. We hypothesized that olfactory information might also have a sex-specific effect on lifespan, and we show here that the lifespan of female mice can be increased significantly by odors from adult females administered transiently, that is from 3 days until 60 days of age. Female lifespan was not modified by male odors, nor was male lifespan susceptible to odors from adults of either sex. Conditional deletion of the G protein Gαo in the olfactory system, which leads to impaired accessory olfactory system function and blunted reproductive priming responses to male odors in females, did not modify the effect of female odors on female lifespan. Our data provide support for the idea that very young mice are susceptible to influences that can have long-lasting effects on health maintenance in later life, and provide a potential example of lifespan extension by olfactory cues in mice

Insulin Signaling Mediates Sexual Attractiveness in Drosophila

Sexually attractive characteristics are often thought to reflect an individual's condition or reproductive potential, but the underlying molecular mechanisms through which they do so are generally unknown. Insulin/insulin-like growth factor signaling (IIS) is known to modulate aging, reproduction, and stress resistance in several species and to contribute to variability of these traits in natural populations. Here we show that IIS determines sexual attractiveness in Drosophila through transcriptional regulation of genes involved in the production of cuticular hydrocarbons (CHC), many of which function as pheromones. Using traditional gas chromatography/mass spectrometry (GC/MS) together with newly introduced laser desorption/ionization orthogonal time-of-flight mass spectrometry (LDI-MS) we establish that CHC profiles are significantly affected by genetic manipulations that target IIS. Manipulations that reduce IIS also reduce attractiveness, while females with increased IIS are significantly more attractive than wild-type animals. IIS effects on attractiveness are mediated by changes in CHC profiles. Insulin signaling influences CHC through pathways that are likely independent of dFOXO and that may involve the nutrient-sensing Target of Rapamycin (TOR) pathway. These results suggest that the activity of conserved molecular regulators of longevity and reproductive output may manifest in different species as external characteristics that are perceived as honest indicators of fitness potential

Genome-Wide Analysis of Binding Sites and Direct Target Genes of the Orphan Nuclear Receptor NR2F1/COUP-TFI

Identification of bona fide direct nuclear receptor gene targets has been challenging but essential for understanding regulation of organismal physiological processes.We describe a methodology to identify transcription factor binding sites and target genes in vivo by intersecting microarray data, computational binding site queries, and evolutionary conservation. We provide detailed experimental validation of each step and, as a proof of principle, utilize the methodology to identify novel direct targets of the orphan nuclear receptor NR2F1 (COUP-TFI). The first step involved validation of microarray gene expression profiles obtained from wild-type and COUP-TFI(-/-) inner ear tissues. Secondly, we developed a bioinformatic tool to search for COUP-TFI DNA binding sites in genomes, using a classification-type Hidden Markov Model trained with 49 published COUP-TF response elements. We next obtained a ranked list of candidate in vivo direct COUP-TFI targets by integrating the microarray and bioinformatics analyses according to the degree of binding site evolutionary conservation and microarray statistical significance. Lastly, as proof-of-concept, 5 specific genes were validated for direct regulation. For example, the fatty acid binding protein 7 (Fabp7) gene is a direct COUP-TFI target in vivo because: i) we identified 2 conserved COUP-TFI binding sites in the Fabp7 promoter; ii) Fapb7 transcript and protein levels are significantly reduced in COUP-TFI(-/-) tissues and in MEFs; iii) chromatin immunoprecipitation demonstrates that COUP-TFI is recruited to the Fabp7 promoter in vitro and in vivo and iv) it is associated with active chromatin having increased H3K9 acetylation and enrichment for CBP and SRC-1 binding in the newborn brain.We have developed and validated a methodology to identify in vivo direct nuclear receptor target genes. This bioinformatics tool can be modified to scan for response elements of transcription factors, cis-regulatory modules, or any flexible DNA pattern

A novel bifunctional oxygen GDE for alkaline secondary batteries

AbstractThis paper describes a novel procedure for the fabrication of a gas diffusion electrode (GDE) suitable for use as a bifunctional oxygen electrode in alkaline secondary batteries. The electrode is fabricated by pre-forming a PTFE-bonded nickel powder layer on a nickel foam substrate followed by deposition of NiCo2O4 spinel electrocatalyst by dip coating in a nitrate solution and thermal decomposition. The carbon-free composition avoids concerns over carbon corrosion at the potentials for oxygen evolution. The electrode shows acceptable overpotentials for both oxygen evolution and oxygen reduction at current densities up to 100mAcm−2. Stable performance during >100 successive, 1h oxygen reduction/evolution cycles at a current density of 20mAcm−2 in 8M NaOH at 333K was achieved

A novel bifunctional oxygen GDE for alkaline secondary batteries

This paper describes a novel procedure for the fabrication of a gas diffusion electrode (GDE) suitable for use as a bifunctional oxygen electrode in alkaline secondary batteries. The electrode is fabricated by pre-forming a PTFE-bonded nickel powder layer on a nickel foam substrate followed by deposition of NiCo2O4 spinel electrocatalyst by dip coating in a nitrate solution and thermal decomposition. The carbon-free composition avoids concerns over carbon corrosion at the potentials for oxygen evolution. The electrode shows acceptable overpotentials for both oxygen evolution and oxygen reduction at current densities up to 100 mA cm−2. Stable performance during >100 successive, 1 h oxygen reduction/evolution cycles at a current density of 20 mA cm−2 in 8 M NaOH at 333 K was achieved.European Commissio

Dietary yeast influences ethanol sedation in Drosophila via serotonergic neuron function

Abuse of alcohol is a major clinical problem with far- reaching health consequences. Understanding the environmental and genetic factors that contribute to alcohol- related behaviors is a potential gateway for developing novel therapeutic approaches for patients that abuse the drug. To this end, we have used Drosophila melanogaster as a model to investigate the effect of diet, an environmental factor, on ethanol sedation. Providing flies with diets high in yeast, a routinely used component of fly media, increased their resistance to ethanol sedation. The yeast- induced resistance to ethanol sedation occurred in several different genetic backgrounds, was observed in males and females, was elicited by yeast from different sources, was readily reversible, and was associated with increased nutrient intake as well as decreased internal ethanol levels. Inhibition of serotonergic neuron function using multiple independent genetic manipulations blocked the effect of yeast supplementation on ethanol sedation, nutrient intake, and internal ethanol levels. Our results demonstrate that yeast is a critical dietary component that influences ethanol sedation in flies and that serotonergic signaling is required for the effect of dietary yeast on nutrient intake, ethanol uptake/elimination, and ethanol sedation. Our studies establish the fly as a model for diet- induced changes in ethanol sedation and raise the possibility that serotonin might mediate the effect of diet on alcohol- related behavior in other species.Flies fed a high yeast diet consume more nutrients, have decreased levels of internal ethanol when exposed to ethanol vapor and require longer exposure to ethanol to become sedated (ie, increased ST50). Our studies implicate serotonergic neurons as key regulators of nutrient consumption and therefore, the effect of dietary yeast on ethanol sedation in flies.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155987/1/adb12779.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155987/2/adb12779_am.pd