Heat shock response and ageing: mechanisms and applications

Ageing is associated with a decrease in the ability of cells to cope with environmental challenges. This is due partly to the attenuation of a primordial stress response, the so-called heat shock (HS) response, which induces the expression of heat shock proteins (HSPs), composed of chaperones and proteases. The attenuation of the HS response during ageing may be responsible for the accumulation of damaged proteins as well as abnormal regulation of cell death. Maintenance of the HS response by repeated mild heat stress causes anti-ageing hormetic effects on cells and organisms. Here, we describe the molecular mechanism and the state of the HS response as well as the role of specific HSPs during ageing, and discuss the possibility of hormetic modulation of ageing and longevity by repeated mild stress.     

The pro-apoptotic Ras effector Nore1 may serve as a Ras-regulated tumor suppressor in the lung

Ras oncoproteins mediate multiple biological effects by activating multiple effectors. Classically, Ras activation has been associated with enhanced cellular growth and transformation. However, activated forms of Ras may also inhibit growth by inducing senescence, apoptosis, and differentiation. Induction of apoptosis by Ras may be mediated by its effector RASSF1, which appears to function as a tumor suppressor. We now show that the Ras effector Nore1, which is structurally related to RASSF1, can also mediate a Ras-dependent apoptosis. Moreover, an analysis of Nore1 protein expression showed that it is frequently down-regulated in lung tumor cell lines and primary lung tumors. Like RASSF1, this correlates with methylation of the Nore1 promoter rather than gene deletion. Finally, re-introduction of Nore1, driven by its own promoter, impairs the growth in soft agar of a human lung tumor cell line. Consequently, we propose that the Ras effector Nore1 is a member of a family of Ras effector/tumor suppressors that includes RASSF1.     

A DNA test for routine prediction in breeding of peach blush,Ppe-R<Subscript>f</Subscript>-SSR

Blush, the proportion of red overcolor on the skin surface of fruit, is highly variable in peach breeding germplasm and is important in the marketing of peach fruit. The fresh market peach industry demands a high level of blush to entice consumers, while the processing peach industry requires minimal blush. Therefore, blush is a major selection criterion in breeding programs. The use of DNA-based information could improve breeding efficiency and accuracy for fruit blush coverage, but a predictive DNA test is required. The objective of this study was to develop a DNA test for the prediction of blush coverage by targeting the major locus, R _f , associated with blush variation. Initially, haplotypes were developed based on five SNP markers associated with variation in blush coverage. To convert the 5-SNP haplotype test into a single, simple PCR-based assay, 11 simple sequence repeat markers were designed and used to screen individuals representing all SNP haplotypes. The most informative assay, named Ppe-R_f-SSR, was chosen to screen 200 individuals of the RosBREED peach reference germplasm set that incorporated germplasm from four breeding programs. Ppe-R_f-SSR accurately differentiated individuals with high-, medium-, and low-blush coverage in most lineages. Outcomes highlighted that DNA tests can be quite predictive for some breeding programs or specific germplasm sets, while for others the predictiveness can falter. Therefore, the confirmation of genotype effects for any DNA test is recommended in new germplasm before routine use. The prediction accuracy and breeding utility of Ppe-R_f-SSR in the University of Arkansas breeding program were subsequently confirmed by screening 443 seedlings, independent of the initial DNA test development process, derived from 18 cross-combinations of 28 parents. Ppe-R_f-SSR can be used to efficiently and accurately predict fruit blush coverage, especially in fresh market germplasm, and has been deployed for routine use in the University of Arkansas peach breeding program.     

Aging and caloric restriction impact adipose tissue,adiponectin, and circulating lipids

Adipose tissue expansion has been associated with system‐wide metabolic dysfunction and increased vulnerability to diabetes, cancer, and cardiovascular disease. A reduction in adiposity is a hallmark of caloric restriction (CR), an intervention that extends longevity and delays the onset of these same age‐related conditions. Despite these parallels, the role of adipose tissue in coordinating the metabolism of aging is poorly defined. Here, we show that adipose tissue metabolism and secretory profiles change with age and are responsive to CR. We conducted a cross‐sectional study of CR in adult, late‐middle‐aged, and advanced‐aged mice. Adiposity and the relationship between adiposity and circulating levels of the adipose‐derived peptide hormone adiponectin were age‐sensitive. CR impacted adiposity but only levels of the high molecular weight isoform of adiponectin responded to CR. Activators of metabolism including PGC‐1a, SIRT1, and NAMPT were differentially expressed with CR in adipose tissues. Although age had a significant impact on NAD metabolism, as detected by biochemical assay and multiphoton imaging, the impact of CR was subtle and related to differences in reliance on oxidative metabolism. The impact of age on circulating lipids was limited to composition of circulating phospholipids. In contrast, the impact of CR was detected in all lipid classes regardless of age, suggesting a profound difference in lipid metabolism. These data demonstrate that aspects of adipose tissue metabolism are life phase specific and that CR is associated with a distinct metabolic state, suggesting that adipose tissue signaling presents a suitable target for interventions to delay aging.     

Total lactate dehydrogenase activity of tail muscle is not cold-adapted in nocturnal lizards from cool-temperate habitats

The dependence of metabolic processes on temperature constrains the behavior, physiology and ecology of many ectothermic animals. The evolution of nocturnality in lizards, especially in temperate regions, requires adaptations for activity at low temperatures when optimal body temperatures are unlikely to be obtained. We examined whether nocturnal lizards have cold-adapted lactate dehydrogenase (LDH). LDH was chosen as a representative metabolic enzyme. We measured LDH activity of tail muscle in six lizard species (n = 123: three nocturnal, two diurnal and one crepuscular) between 5 and 35 °C and found no differences in LDH-specific activity or thermal sensitivity among the species. Similarly, the specific activity and thermal sensitivity of LDH were similar between skinks and geckos. Similar enzyme activities among nocturnal and diurnal lizards indicate that there is no selection of temperature specific LDH enzyme activity at any temperature. As many nocturnal lizards actively thermoregulate during the day, LDH may be adapted for a broad range of temperatures rather than adapted specifically for the low temperatures encountered when the animals are active. The total activity of LDH in tropical and temperate lizards is not cold-adapted. More data are required on biochemical adaptations and whole animal thermal preferences before trends can be established.     

An essential role for katanin p80 and microtubule severing in male gamete production

Katanin is an evolutionarily conserved microtubule-severing complex implicated in multiple aspects of microtubule dynamics. Katanin consists of a p60 severing enzyme and a p80 regulatory subunit. The p80 subunit is thought to regulate complex targeting and severing activity, but its precise role remains elusive. In lower-order species, the katanin complex has been shown to modulate mitotic and female meiotic spindle dynamics and flagella development. The in vivo function of katanin p80 in mammals is unknown. Here we show that katanin p80 is essential for male fertility. Specifically, through an analysis of a mouse loss-of-function allele (the Taily line), we demonstrate that katanin p80, most likely in association with p60, has an essential role in male meiotic spindle assembly and dissolution and the removal of midbody microtubules and, thus, cytokinesis. Katanin p80 also controls the formation, function, and dissolution of a microtubule structure intimately involved in defining sperm head shaping and sperm tail formation, the manchette, and plays a role in the formation of axoneme microtubules. Perturbed katanin p80 function, as evidenced in the Taily mouse, results in male sterility characterized by decreased sperm production, sperm with abnormal head shape, and a virtual absence of progressive motility. Collectively these data demonstrate that katanin p80 serves an essential and evolutionarily conserved role in several aspects of male germ cell development.     

The seasonal timing of warming that controls onset of the growing season

Forecasting how global warming will affect onset of the growing season is essential for predicting terrestrial productivity, but suffers from conflicting evidence. We show that accurate estimates require ways to connect discrete observations of changing tree status (e.g., pre‐ vs. post budbreak) with continuous responses to fluctuating temperatures. By coherently synthesizing discrete observations with continuous responses to temperature variation, we accurately quantify how increasing temperature variation accelerates onset of growth. Application to warming experiments at two latitudes demonstrates that maximum responses to warming are concentrated in late winter, weeks ahead of the main budbreak period. Given that warming will not occur uniformly over the year, knowledge of when temperature variation has the most impact can guide prediction. Responses are large and heterogeneous, yet predictable. The approach has immediate application to forecasting effects of warming on growing season length, requiring only information that is readily available from weather stations and generated in climate models.     

Farm Scale Evaluations of spring-sown genetically modified herbicide-tolerant crops: a statistical assessment

Primary results from the Farm Scale Evaluations (FSEs) of spring-sown genetically modified herbicide-tolerant crops were published in 2003. We provide a statistical assessment of the results for count data, addressing issues of sample size (n), efficiency, power, statistical significance, variability and model selection. Treatment effects were consistent between rare and abundant species. Coefficients of variation averaged 73% but varied widely. High variability in vegetation indicators was usually offset by large n and treatment effects, whilst invertebrate indicators often had smaller n and lower variability; overall, achieved power was broadly consistent across indicators. Inferences about treatment effects were robust to model misspecification, justifying the statistical model adopted. As expected, increases in n would improve detectability of effects whilst, for example, halving n would have resulted in a loss of significant results of about the same order. 40% of the 531 published analyses had greater than 80% power to detect a 1.5-fold effect; reducing n by one-third would most likely halve the number of analyses meeting this criterion. Overall, the data collected vindicated the initial statistical power analysis and the planned replication. The FSEs provide a valuable database of variability and estimates of power under various sample size scenarios to aid planning of more efficient future studies.