Life-span Extension With Reduced Somatotrophic Signaling: Moderation of Aging Effect by Signal Type, Sex, and Experimental Cohort.

Reduced somatotrophic signaling through the growth hormone (GH) and insulin-like growth factor pathways (IGF1) can delay aging, although the degree of life-extension varies markedly across studies. By collating data from previous studies and using meta-analysis, we tested whether factors including sex, hormonal manipulation, body weight change and control baseline mortality quantitatively predict relative lifeextension. Manipulations of GH signaling (including pituitary and direct GH deficiencies) generate significantly greater extension in median life span than IGF1 manipulations (including IGF1 production, reception, and bioactivity), producing a consistent shift in mortality risk of mutant mice. Reduced Insulin receptor substrate (IRS) expression produces more similar life-extension to reduced GH, although effects are more heterogeneous and appear to influence the demography of mortality differently. Life-extension with reduced IGF1 signaling, but neither GH nor IRS signaling, increases life span significantly more in females than males, and in cohorts where control survival is short. Our results thus suggest that reduced GH signaling has physiological benefits to survival outside of its actions on circulating IGF1. In addition to these biological moderators, we found an overrepresentation of small sample sized studies that report large improvements in survival, indicating potential publication bias. We discuss how this could potentially confound current conclusions from published work, and how this warrants further study replication

Comparative idiosyncrasies in life extension by reduced mTOR signalling and its distinctiveness from dietary restriction.

Reduced mechanistic target of rapamycin (mTOR) signalling extends lifespan in yeast, nematodes, fruit flies and mice, highlighting a physiological pathway that could modulate aging in evolutionarily divergent organisms. This signalling system is also hypothesized to play a central role in lifespan extension via dietary restriction. By collating data from 48 available published studies examining lifespan with reduced mTOR signalling, we show that reduced mTOR signalling provides similar increases in median lifespan across species, with genetic mTOR manipulations consistently providing greater life extension than pharmacological treatment with rapamycin. In contrast to the consistency in changes in median lifespan, however, the demographic causes for life extension are highly species specific. Reduced mTOR signalling extends lifespan in nematodes by strongly reducing the degree to which mortality rates increase with age (aging rate). By contrast, life extension in mice and yeast occurs largely by pushing back the onset of aging, but not altering the shape of the mortality curve once aging starts. Importantly, in mice, the altered pattern of mortality induced by reduced mTOR signalling is different to that induced by dietary restriction, which reduces the rate of aging. Effects of mTOR signalling were also sex dependent, but only within mice, and not within flies, thus again species specific. An alleviation of age-associated mortality is not a shared feature of reduced mTOR signalling across model organisms and does not replicate the established age-related survival benefits of dietary restriction

Tussen sociale en regionale variatie: n-deletie bij 18de-eeuwse briefschrijfsters in het Brieven als buit-corpus

Descriptive and Comparative Linguistic

De reductievocaal in zeventiende- en achttiende-eeuwse sailing letters: onzichtbare spelling, dubbele spelling en palatale uitspraak

Descriptive and Comparative Linguistic

Negation in Seventeenth- and Eighteenth-Century Dutch. A Historical-Sociolinguistic Perspective

Descriptive and Comparative Linguistic

Heritability and social brood effects on personality in juvenile and adult life-history stages in a wild passerine

How has evolution led to the variation in behavioural phenotypes (personalities) in a population? Knowledge of whether personality is heritable, and to what degree it is influenced by the social environment, is crucial to understanding its evolutionary significance, yet few estimates are available from natural populations. We tracked three behavioural traits during different life-history stages in a pedigreed population of wild house sparrows. Using a quantitative genetic approach, we demonstrated heritability in adult exploration, and in nestling activity after accounting for fixed effects, but not in adult boldness. We did not detect maternal effects on any traits, but we did detect a social brood effect on nestling activity. Boldness, exploration and nestling activity in this population did not form a behavioural syndrome, suggesting that selection could act independently on these behavioural traits in this species, although we found no consistent support for phenotypic selection on these traits. Our work shows that repeatable behaviours can vary in their heritability, and that social context influences personality traits. Future efforts could separate whether personality traits differ in heritability because they have served specific functional roles in the evolution of the phenotype, or because our concept of personality and the stability of behaviour needs to be revised

Temporal fluctuations of waves in weakly nonlinear disordered media

We consider the multiple scattering of a scalar wave in a disordered medium with a weak nonlinearity of Kerr type. The perturbation theory, developed to calculate the temporal autocorrelation function of scattered wave, fails at short correlation times. A self-consistent calculation shows that for nonlinearities exceeding a certain threshold value, the multiple-scattering speckle pattern becomes unstable and exhibits spontaneous fluctuations even in the absence of scatterer motion. The instability is due to a distributed feedback in the system "coherent wave + nonlinear disordered medium". The feedback is provided by the multiple scattering. The development of instability is independent of the sign of nonlinearity.Comment: RevTeX, 15 pages (including 5 figures), accepted for publication in Phys. Rev.

Knowledge-based energy functions for computational studies of proteins

This chapter discusses theoretical framework and methods for developing knowledge-based potential functions essential for protein structure prediction, protein-protein interaction, and protein sequence design. We discuss in some details about the Miyazawa-Jernigan contact statistical potential, distance-dependent statistical potentials, as well as geometric statistical potentials. We also describe a geometric model for developing both linear and non-linear potential functions by optimization. Applications of knowledge-based potential functions in protein-decoy discrimination, in protein-protein interactions, and in protein design are then described. Several issues of knowledge-based potential functions are finally discussed.Comment: 57 pages, 6 figures. To be published in a book by Springe

Water Management Solution of Reservoir Storage Function Under Condition of Measurement Uncertainties in Hydrological Input Data

AbstractThe paper describes a possible procedure of the rate uncertainty implementation to the continuous water stage measurement and uncertainties of state - discharge rating curve point positions, which the stage -discharge rating curves were fitted into the uncertainties of the real discharge series members. Then the members of discharge series under uncertainty impact were tested on the calculated values of the reservoir storage volume. The next step was the implementation of the uncertainties of the real discharge series members on the generation of the artificial discharge series of mean monthly discharge using the AR and ARMA generators and the determination of their impact on the calculated values of the reservoir storage volume