Does menarche mark a period of elevated resting metabolic rate?

Resting metabolic rate (RMR) and body composition were measured in 44 initially nonoverweight girls at three time points relative to menarche: premenarche (Tanner stage 1 or 2), menarche (+/-6 mo), and 4 yr after menarche. Mean absolute RMR was 1,167, 1,418, and 1,347 kcal/day, respectively. Absolute RMR was statistically significantly higher at menarche than at 4 yr after menarche despite statistically significantly less fat-free mass (FFM) and fat mass (FM), suggesting an elevation in RMR around the time of menarche. The pattern of change in RMR, adjusted for FFM, log transformed FM, age, race, parental overweight, and two interactions (visit by parental overweight, parental overweight by FFM), was also considered. Adjusted RMR did not differ statistically between the visits for girls with two normal-weight parents. For girls with at least one overweight parent, adjusted RMR was statistically significantly lower 4 yr after menarche than at premenarche or menarche. Thus parental overweight may influence changes that occur in RMR during adolescence in girls.     

Do method and species lifestyle affect measures of maximum metabolic rate in fishes?

The rate at which active animals can expend energy is limited by their maximum aerobic metabolic rate (MMR). Two methods are commonly used to estimate MMR as oxygen uptake in fishes, namely during prolonged swimming or immediately following brief exhaustive exercise, but it is unclear whether they return different estimates of MMR or whether their effectiveness for estimating MMR varies among species with different lifestyles. A broad comparative analysis of MMR data from 121 fish species revealed little evidence of different results between the two methods, either for fishes in general or for species of benthic, benthopelagic or pelagic lifestyles.     

Vascular memory: can we broaden the concept of the metabolic memory?

ABSTRACT: Based on the results of recent randomized, controlled clinical trials and analyses of their follow-up periods the concept of metabolic memory cannot be restricted to antihyperglycaemic treatment only, rather it can be extended to lipid-lowering and antihypertensive treatment and even life-style modification. This broadened concept can be designated as vascular memory. According to this new concept, not only immediate and short-term but long-term effects of the metabolic and cardiovascular risk milieu are of great importance. Consequently, early and intensive lifestyle interventions, treatment of hyperglycaemia, lipid abnormalities and hypertension can result in beneficial effects on cardiovascular outcomes even in the long run. On the contrary, failing in target-oriented treatment from early detection of abnormalities can be associated with life-threatening cardiovascular events subsequently. Additional experimental studies are needed to characterize the exact pathomechanism of vascular memory and further clinical trials are also essential to explore its real clinical significance.     

The prognosis of latent tuberculosis: can disease be predicted?

In humans, Mycobacterium tuberculosis persists for long periods in a clinically latent state, creating a huge reservoir of 'silent' tuberculosis (TB) (roughly one-third of the global population) from which new cases continually arise. A prognostic marker for active TB would enable targeted treatment of the small fraction of infected individuals who are most at risk of developing contagious TB, contributing greatly to TB control efforts. Here, we propose that TB-specific interferon-gamma release assays might be useful for identifying individuals with progressive infections who are likely to develop the disease. This might provide an unprecedented advantage for TB control, namely targeted preventive therapy for individuals who are most at risk of developing active contagious TB.     

Can the false-discovery rate be misleading?

The decoy-database approach is currently the gold standard for assessing the confidence of identifications in shotgun proteomic experiments. Here, we demonstrate that what might appear to be a good result under the decoy-database approach for a given false-discovery rate could be, in fact, the product of overfitting. This problem has been overlooked until now and could lead to obtaining boosted identification numbers whose reliability does not correspond to the expected false-discovery rate. To overcome this, we are introducing a modified version of the method, termed a semi-labeled decoy approach, which enables the statistical determination of an overfitted result.     

When can the cause of a population decline be determined?

Inferring the factors responsible for declines in abundance is a prerequisite to preventing the extinction of wild populations. Many of the policies and programmes intended to prevent extinctions operate on the assumption that the factors driving the decline of a population can be determined. Exogenous factors that cause declines in abundance can be statistically confounded with endogenous factors such as density dependence. To demonstrate the potential for confounding, we used an experiment where replicated populations were driven to extinction by gradually manipulating habitat quality. In many of the replicated populations, habitat quality and density dependence were confounded, which obscured causal inference. Our results show that confounding is likely to occur when the exogenous factors that are driving the decline change gradually over time. Our study has direct implications for wild populations, because many factors that could drive a population to extinction change gradually through time.     

Challenges of the utilization of wood polymers: how can they be overcome?

Diminishing fossil fuel resources as well as growing environmental and energy security concerns, in parallel with growing demands on raw materials and energy, have intensified global efforts to utilize wood biopolymers as a renewable resource to produce biofuels and biomaterials. Wood is one of the most abundant biopolymer composites on earth that can be converted into biofuels as well as used as a platform to produce bio-based materials. The major biopolymers in wood are cellulose, hemicelluloses, and lignin which account for >90% of dry weight. These polymers are generally associated with each other in wood cell walls resulting in an intricate and dynamic cell wall structure. This mini-review provides an overview of major wood biopolymers, their structure, and recent developments in their utilization to develop biofuels. Advances in genetic modifications to overcome the recalcitrance of woody biomass for biofuels are discussed and point to a promising future.     

Statistical analysis of structural compensatory growth: how can we reduce the rate of false detection?

Compensatory growth (CG) is a key issue in work aiming at a full understanding of the adaptive significance of growth plasticity and its carryover effects on life-history. The number of studies addressing evolutionary explanations for CG has increased rapidly during the last few years, but there has not been a parallel gain in our understanding of the methodological difficulties associated with the analysis of CG. We point out two features of growth that can have serious consequences for detecting CG: (1) size dependence of growth rates, which causes nonlinearity of growth trajectories, and; (2) temporal overlapping of structural growth and replenishment of energy reserves after a period of famine. We show that the currently used methods can be prone to spurious detection of CG (Type I error) under conditions of nonlinear growth, and therefore lead to the accumulation of a significant amount of false “empirical support.” True and simulated growth data provided consistent results suggesting that a substantial fraction of the existing evidence for CG may be spurious. A small curvature in the growth trajectory can lead to spurious “detection” of CG when control and manipulated trajectories are compared over the same time interval (the “simultaneous” approach). We present a novel, robust method (the “asynchronous” approach) based on the accurate selection of control trajectories and comparison of control and treatment growth rates at different times. This method enables a reliable test to be performed for compensation under asymptotic growth. While the general results of our simulations do not support the application of conventional methods to the general case of nonlinear growth trajectories under the simultaneous approach, simple methods may prove valid if the experimental design allows for asynchronous comparisons. We advocate an alternative approach to deal with “safe” detection of CG that overcomes the problems associated with the occurrence of nonlinear and asymptotic growth, and provide recommendations for improving CG study designs. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Renal excretion ofγ-carboxyglutamic acid and metabolic rate in 3–18 years old humans

Summary The modified amino acid y-carboxyglutamic acid (Gla) occurs in several proteins such as prothrombin, blood coagulation factors VII, IX and X, proteins C, S and Z as well as matrix Gla protein and osteocalcin. The amount of Gla excreted in urine is a common indicator of the whole-body degradation of these proteins. We have determined the renal excretion rates of Gla in 3, 6,10,14 and 18 years old male and female human subjects (n = 14 per age group and sex) and calculated the respective resting metabolic rates (RMR) on the basis of the body weights using published formulas. We found high correlations between the excretion rates of Gla (µmol/d/kg body weight) and the RMR (kJ/d/kg body weight) in the females (n = 70) of r = 0.70 (y = 0.003x + 0.29) and in the males (n = 70) of r = 0.70 (y = 0.0038x + 0.27) and in all subjects (n = 140) of r = 0.69 (y = 0.0035x + 0.27); p < 0.01. We postulate that in children and adolescents a causal relationship exists between the whole-body degradation rate of Gla containing proteins and the metabolic rate.     

Oxidative stress and antioxidative defense in cephalopods: a function of metabolic rate or age?

Activities of the antioxidative enzymes superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX) and glutathione reductase (GR) were measured in the cephalopods Sepia officinalis and Lolliguncula brevis. Maximal enzyme activities were higher in gill tissue than in the mantle musculature of both species. Activities were generally lower in tissues of L. brevis than in S. officinalis. Comparison with other ectothermic animals showed both cephalopod species to have a low enzymatic antioxidative status despite their high metabolic rate. Furthermore, changes in antioxidative enzyme activities were measured in the cuttlefish S. officinalis with increasing age. The concentrations of malondialdehyde (MDA) and lipofuscin were determined as indicators of lipid peroxidation. Investigated animals were between 1.5 months and over 12 months old. Changes of antioxidative enzyme activities with age were not uniform. SOD and GPX activities increased with age, while catalase activity declined. In contrast, GR activity remained almost unchanged in all age groups. The low level of antioxidative defense might allow for the significant age-induced rise in MDA levels in gills and mantle musculature and for the increase in lipofuscin levels in mantle and brain tissue. It might thereby contribute to increased oxidative damage and a short life span in these cephalopods.     

Is there evidence for an age-related reduction in metabolic rate?

To determinewhether the age-related reduction in basal metabolic rate (BMR) isexplained by a quantitative and/or qualitative change in thecomponents of lean tissue, we conducted a cross-sectional study ingroups of young (n = 38, 18-35yr) and older (n = 24, 50-77 yr)healthy individuals. BMR was measured by indirect calorimetry. Bodycomposition was obtained by using dual-energy X-ray absorptiometry (DEXA), which permitted four compartments to be quantified [bone mineral mass, fat mass (FM), appendicular lean tissue mass(A_LTM), and nonappendicular leantissue mass (NA_LTM)].Absolute BMR and A_LTM were lower,whereas FM was significantly higher in the older, compared with young,subjects. BMR, adjusted for differences in FM,A_LTM, andNA_LTM, was significantly lower inthe older subjects by 644 kJ/day. In separate regression analyses ofBMR on body compartments, older subjects had significantly lowerregression coefficients for A_LTMand NA_LTM, compared with youngsubjects. Hence, the age-related decline in BMR is partly explained bya reduction in the quantity, as well as the metabolic activity, ofDEXA-derived lean tissue components.

     

Innate immune deficiency of extremely premature neonates can be reversed by interferon-γ

Background

Bacterial sepsis is a major threat in neonates born prematurely, and is associated with elevated morbidity and mortality. Little is known on the innate immune response to bacteria among extremely premature infants.

Methodology/Principal Findings

We compared innate immune functions to bacteria commonly causing sepsis in 21 infants of less than 28 wks of gestational age, 24 infants born between 28 and 32 wks of gestational age, 25 term newborns and 20 healthy adults. Levels of surface expression of innate immune receptors (CD14, TLR2, TLR4, and MD-2) for Gram-positive and Gram-negative bacteria were measured in cord blood leukocytes at the time of birth. The cytokine response to bacteria of those leukocytes as well as plasma-dependent opsonophagocytosis of bacteria by target leukocytes was also measured in the presence or absence of interferon-γ. Leukocytes from extremely premature infants expressed very low levels of receptors important for bacterial recognition. Leukocyte inflammatory responses to bacteria and opsonophagocytic activity of plasma from premature infants were also severely impaired compared to term newborns or adults. These innate immune defects could be corrected when blood from premature infants was incubated ex vivo 12 hrs with interferon-γ.

Conclusion/Significance

Premature infants display markedly impaired innate immune functions, which likely account for their propensity to develop bacterial sepsis during the neonatal period. The fetal innate immune response progressively matures in the last three months in utero. Ex vivo treatment of leukocytes from premature neonates with interferon-γ reversed their innate immune responses deficiency to bacteria. These data represent a promising proof-of-concept to treat premature newborns at the time of delivery with pharmacological agents aimed at maturing innate immune responses in order to prevent neonatal sepsis.     

How well can the accuracy of comparative protein structure models be predicted?

Comparative structure models are available for two orders of magnitude more protein sequences than are experimentally determined structures. These models, however, suffer from two limitations that experimentally determined structures do not: They frequently contain significant errors, and their accuracy cannot be readily assessed. We have addressed the latter limitation by developing a protocol optimized specifically for predicting the Calpha root-mean-squared deviation (RMSD) and native overlap (NO3.5A) errors of a model in the absence of its native structure. In contrast to most traditional assessment scores that merely predict one model is more accurate than others, this approach quantifies the error in an absolute sense, thus helping to determine whether or not the model is suitable for intended applications. The assessment relies on a model-specific scoring function constructed by a support vector machine. This regression optimizes the weights of up to nine features, including various sequence similarity measures and statistical potentials, extracted from a tailored training set of models unique to the model being assessed: If possible, we use similarly sized models with the same fold; otherwise, we use similarly sized models with the same secondary structure composition. This protocol predicts the RMSD and NO3.5A errors for a diverse set of 580,317 comparative models of 6174 sequences with correlation coefficients (r) of 0.84 and 0.86, respectively, to the actual errors. This scoring function achieves the best correlation compared to 13 other tested assessment criteria that achieved correlations ranging from 0.35 to 0.71.