The terrestrial evolution of metabolism and life – by the numbers

<p>Abstract</p> <p>Background</p> <p>Allometric scaling relating body mass to metabolic rate by an exponent of the former (<it>Kleiber's Law</it>), commonly known as quarter-power scaling (QPS), is controversial for claims made on its behalf, especially that of its universality for all life. As originally formulated, Kleiber was based upon the study of heat; metabolic rate is quantified in watts (or calories per unit time). Techniques and technology for metabolic energy measurement have been refined but the math has not. QPS is susceptible to increasing deviations from theoretical predictions to data, suggesting that there is no single, universal exponent relevant to all of life. QPS's major proponents continue to fail to make good on hints of the power of the equation for understanding aging.</p> <p>Essentialist-deductivist view</p> <p>If the equation includes a term for efficiency in the exponent, thereby ruling out thermogenesis as part of metabolism, its heuristic power is greatly amplified, and testable deductive inferences are generated. If metabolic rate is measured in watts and metabolic efficiency is a redox-coupling ratio, then the equation is essentially about the energy storage capacity of organic molecules. The equation is entirely about the essentials of all life: water, salt, organic molecules, and energy. The water and salt provide an electrochemical salt bridge for the transmission of energy into and through the organic components. The equation, when graphed, treats the organic structure as battery-like, and relates its recharge rate and electrical properties to its longevity.</p> <p>Conclusion</p> <p>The equation models the longevity-extending effects of caloric restriction, and shows where those effects wane. It models the immortality of some types of cells, and supports the argument for the origin of life being at submarine volcanic vents and black smokers. It clarifies how early life had to change to survive drifting to the surface, and what drove mutations in its ascent. It does not deal with cause and effect; it deals with variables in the essentials of all life, and treats life as an epiphenomenon of those variables. The equation describes how battery discharge into the body can increase muscle mass, promote fitness, and extend life span, among other issues.</p

Scale-Dependent Contributors to River Profile Geometry

Abstract: A range of complex hydraulic and geomorphic processes shape terrestrial landscapes. It remains unclear how these processes act to generate observed drainage networks across scales of interest. To address this issue, we transform observed and synthetic longitudinal river profiles into the spectral domain with a view to interrogating the different scales at which fluvial landscapes are generated. North American river profiles are characterized by red noise (i.e., spectral power, ϕ ∝ k−2, where k is wave number) at wavelengths >100 km and pink noise (ϕ ∝ k−1) at shorter wavelengths. This observation suggests that river profile geometries are scale‐dependent and using small‐scale observations to develop a general understanding of large‐scale landscape evolution is not straightforward. At wavelengths >100 km, river profile geometries appear to be controlled by smoothly varying patterns of regional uplift and slope‐dependent incision. Landscape simulations, based upon stream power that are externally forced by regional uplift do not exhibit a spectral transition from red to pink noise because these simulations do not incorporate heterogeneous erodibility. Spectral analysis of erodibility extracted from patterns of lithologic variation along river profiles suggests that the missing spectral transition is accounted for by heterogeneous substrates, which are characterized by white or blue noise (ϕ ∝ k0 or k1). Our results have implications for the way by which rivers record large‐scale tectonic forcing while incising through complex lithologic patterns

Interventions to increase the consumption of water among children

The aim of this study was to conduct a systematic review and meta-analysis on the effectiveness of interventions to increase children's water consumption. A systematic literature search was conducted in seven electronic databases. Studies published in English before 18 February 2019 that evaluated any type of intervention that measured change in water consumption among children aged 2 to 12 years by applying any type of design were included. Of the 47 interventions included in the systematic review, 24 reported a statistically significant increase in water consumption. Twenty-four interventions (17 randomized controlled trials and seven studies with other controlled designs) were included in the meta-analysis. On average, children in intervention groups consumed 29 mL/d (confidence interval [CI] = 13–46 mL/d) more water than did children in control groups. This effect was larger in eight interventions focused specifically on diet (MD = 73 mL/d, CI = 20–126 mL/d) than in 16 interventions focused also on other lifestyle factors (MD = 15 mL/d, CI = 1–29 mL/d). Significant subgroup differences were also found by study setting and socioecological level targeted but not by children's age group, intervention strategy, or study design. In conclusion, there is evidence that, on average, lifestyle interventions can lead to small increases in children's daily water consumption. More research is needed to further understand th

Evolutionary Toggling of Vpx/Vpr Specificity Results in Divergent Recognition of the Restriction Factor SAMHD1

SAMHD1 is a host restriction factor that blocks the ability of lentiviruses such as HIV-1 to undergo reverse transcription in myeloid cells and resting T-cells. This restriction is alleviated by expression of the lentiviral accessory proteins Vpx and Vpr (Vpx/Vpr), which target SAMHD1 for proteasome-mediated degradation. However, the precise determinants within SAMHD1 for recognition by Vpx/Vpr remain unclear. Here we show that evolution of Vpx/Vpr in primate lentiviruses has caused the interface between SAMHD1 and Vpx/Vpr to alter during primate lentiviral evolution. Using multiple HIV-2 and SIV Vpx proteins, we show that Vpx from the HIV-2 and SIVmac lineage, but not Vpx from the SIVmnd2 and SIVrcm lineage, require the C-terminus of SAMHD1 for interaction, ubiquitylation, and degradation. On the other hand, the N-terminus of SAMHD1 governs interactions with Vpx from SIVmnd2 and SIVrcm, but has little effect on Vpx from HIV-2 and SIVmac. Furthermore, we show here that this difference in SAMHD1 recognition is evolutionarily dynamic, with the importance of the N- and C-terminus for interaction of SAMHD1 with Vpx and Vpr toggling during lentiviral evolution. We present a model to explain how the head-to-tail conformation of SAMHD1 proteins favors toggling of the interaction sites by Vpx/Vpr during this virus-host arms race. Such drastic functional divergence within a lentiviral protein highlights a novel plasticity in the evolutionary dynamics of viral antagonists for restriction factors during lentiviral adaptation to its hosts. © 2013 Fregoso et al

NLO QCD corrections to tW' and tZ' production in forward-backward asymmetry models

We consider Z' and W' models recently proposed to explain the top forward-backward asymmetry at the Tevatron. We present the next-to-leading order QCD corrections to associated production of such vector bosons together with top quarks at the Large Hadron Collider, for centre-of-mass energies of 7 and 8 TeV. The corrections are significant, modifying the total production cross-section by 30-50%. We consider the effects of the corrections on the top and vector-boson kinematics. The results are directly applicable to current experimental searches, for both the ATLAS and CMS collaborations.Comment: 62 pages, 13 figures, 36 tables. v3 Updated to correspond to Journal version and incorporate supplementary materia

The Allometry of Host-Pathogen Interactions

Understanding the mechanisms that control rates of disease progression in humans and other species is an important area of research relevant to epidemiology and to translating studies in small laboratory animals to humans. Body size and metabolic rate influence a great number of biological rates and times. We hypothesize that body size and metabolic rate affect rates of pathogenesis, specifically the times between infection and first symptoms or death.We conducted a literature search to find estimates of the time from infection to first symptoms (t(S)) and to death (t(D)) for five pathogens infecting a variety of bird and mammal hosts. A broad sampling of diseases (1 bacterial, 1 prion, 3 viruses) indicates that pathogenesis is controlled by the scaling of host metabolism. We find that the time for symptoms to appear is a constant fraction of time to death in all but one disease. Our findings also predict that many population-level attributes of disease dynamics are likely to be expressed as dimensionless quantities that are independent of host body size.Our results show that much variability in host pathogenesis can be described by simple power functions consistent with the scaling of host metabolic rate. Assessing how disease progression is controlled by geometric relationships will be important for future research. To our knowledge this is the first study to report the allometric scaling of host/pathogen interactions

Androgen Receptor Copy Number Variation and Androgenetic Alopecia: A Case-Control Study

BACKGROUND: The functional polymorphism that explains the established association of the androgen receptor (AR) with androgenetic alopecia (AGA) remains unidentified, but Copy Number Variation (CNV) might be relevant. CNV involves changes in copy number of large segments of DNA, leading to the altered dosage of gene regulators or genes themselves. Two recent reports indicate regions of CNV in and around AR, and these have not been studied in relation to AGA. The aim of this preliminary case-control study was to determine if AR CNV is associated with AGA, with the hypothesis that CNV is the functional AR variant contributing to this condition. METHODOLOGY/PRINCIPAL FINDINGS: Multiplex Ligation-dependent Probe Amplification was used to screen for CNV in five AR exons and a conserved, non-coding region upstream of AR in 85 men carefully selected as cases and controls for maximal phenotypic contrast. There was no evidence of CNV in AR in any of the cases or controls, and thus no evidence of significant association between AGA and AR CNV. CONCLUSIONS/SIGNIFICANCE: The results suggest this form of genomic variation at the AR locus is unlikely to predispose to AGA

Malaria treatment failures after artemisinin-based therapy in three expatriates: could improved manufacturer information help to decrease the risk of treatment failure ?

BACKGROUND: Artemisinin-containing therapies are highly effective against Plasmodium falciparum malaria. Insufficient numbers of tablets and inadequate package inserts result in sub-optimal dosing and possible treatment failure. This study reports the case of three, non-immune, expatriate workers with P. falciparum acquired in Africa, who failed to respond to artemisinin-based therapy. Sub-therapeutic dosing in accordance with the manufacturers' recommendations was the probable cause. METHOD: Manufacturers information and drug content included in twenty-five artemisinin-containing specialities were reviewed. RESULTS: A substantial number of manufacturers do not follow current WHO recommendations regarding treatment duration and doses. CONCLUSION: This study shows that drug packaging and their inserts should be improved