Intrauterine growth restriction leads to changes in sulfur amino acid metabolism, but not global DNA methylation, in Yucatan miniature piglets

Intrauterine growth restriction (IUGR), in both animals and humans, has been linked to metabolic syndrome later in life. There has been recent evidence that perturbations in sulfur amino acid metabolism may be involved in this early programming phenomenon. Methionine is the precursor for cellular methylation reactions and for the synthesis of cysteine. It has been suggested that the mechanism behind the "fetal origins" of adult diseases may be epigenetic, involving DNA methylation. Because we have recently demonstrated the fetal origins phenomenon in Yucatan miniature swine, we hypothesized that sulfur amino acid metabolism is altered in IUGR piglets. In this study, metabolites and the activities of sulfur amino acid cycle enzymes were analyzed in liver samples of 3- to 5-day-old runt (IUGR: 0.85±0.13 kg) and large (1.36±0.21 kg) Yucatan miniature pig littermates (n=6 pairs). The IUGR piglets had significantly lower specific and total activities of betaine-homocysteine methyltransferase (BHMT) and cystathionine γ-lyase (CGL) than larger littermates (P<.05). Expression of CGL (but not BHMT) mRNA was also lower in IUGR piglets (P<.05). This low CGL reduced cysteine and taurine concentrations in IUGR pigs and led to an accumulation of hepatic cystathionine, with lower homocysteine concentrations. Methylation index and liver global DNA methylation were unaltered. Reduced prenatal growth in Yucatan miniature piglets impairs their remethylation capacity as well as their ability to remove cystathionine and synthesize cysteine and taurine, which could have important implications on long-term health outcomes of IUGR neonates.     

Feeding by omnivores increases food available to consumers

Consumers are usually thought of as negatively affecting producers, but they can affect them positively by releasing nutrients (nutrient regeneration). The net effects of consumers on producers should depend on the balance between the effects of consumption and nutrient regeneration. In aquatic habitats, nutrient regeneration by consumers may increase microbial activity on leaf detritus as well as algal production, which in turn may stimulate further nutrient release and benefit herbivores or detritivores by increasing food quantity or quality. Omnivores can regenerate nutrients from animals, algae and detritus, creating diverse nutrient pathways. Many tadpoles are omnivores, and their nutrient regeneration may be important in aquatic food webs. To reveal the nutrient pathways created by tadpoles and examine whether omnivorous tadpoles can have positive effects on producers and consumers, we experimentally examined the effects of nutrient regeneration by three densities of tadpoles on primary producers, leaf litter, and other consumers in tank mesocosms. Tadpole exclosures were placed inside each mesocosm, allowing us to separate direct consumption effects from indirect nutrient regeneration effects. Nutrient regeneration caused by the herbivorous and carnivorous feeding activities of tadpoles positively affected rates of production of benthic algae, phytoplankton, and herbivorous benthic chironomid larvae, and rates of mineralization of leaf litter. The increased production of benthic algae and chironomid larvae was consumed by the tadpoles themselves, leaving no net change in the standing biomass of these resources. Our experiment thus demonstrated that omnivores created complicated nutrient pathways and accelerated rates of primary production and growth rates of other consumers, leading to increased rates of food availability to the omnivores themselves. Interactions of this nature may be common in many systems and could strongly moderate the effects of consumers on their resources and each other.     

Overstory and understory vegetation interact to alter soil community composition and activity

Aim

To test if there is an interactive effect between tree and understory species on the soil microbial community (SMC), community level physiological profiles (CLPP) and soil micro-fauna.

Method

A replicate pot experiment with five sapling tree species (Betula pendula, Betula pubescens, Sorbus aucuparia, Quercus petraea and Pinus sylvestris) and a no-tree treatment with and without Calluna vulgaris was established. After 21?months samples were taken for phospholipid fatty acid (PLFA) analysis, CLPP and soil microfauna assessment.

Results

There was an interactive effect of tree species and Calluna on the SMC, CLPP and nematode densities. Calluna addition changed the SMC composition (increase in fungal PLFAs) and the CLPP (lower utilisation of most carbon sources but greater utilisation of phenolic acids). A multivariate test for homogeneity of dispersion showed that while Calluna addition resulted in the presence of an altered microbial composition, it did not result in there being less variability among the samples with Calluna than among the samples without Calluna. Sapling trees with Calluna present grew less well than trees without Calluna. Structural equation modelling showed that it is possible that Calluna had an indirect effect on the SMC via below-ground tree biomass as well as a direct effect.

Conclusion

Interactions between trees and understory vegetation can impact on the composition of soil biota and their activity.     

Low genetic diversity in tepui summit vertebrates

The Pantepui region of South America, located in southern Venezuela, northern Brazil, and western Guyana, is characterized by table mountains (tepuis) made of Proterozoic (> 1.5 billion years old) sandstone - the highest reaching nearly 3 km - that are isolated from their surroundings by up to 1000 m high vertical cliffs (Figure 1A). Tepuis are among the most inaccessible places on earth (Supplemental information), and the majority of their summits have been visited less than the moon. Due to its age and topography [1,2], this region has been assumed to be an ideal nursery of speciation and a potential inland counterpart to oceanic islands [3,4]. High endemism has been reported for the flora (25% in vascular plants) and fauna (68.5% in amphibians and reptiles) of single tepuis [5,6], and an ancient origin has been postulated for some of these organisms. But, it has also been suggested that a few taxa living in habitats extending from lowlands to summits (e.g., savannah) invaded some of the more accessible tepuis only recently [6-8]. Taken at face value, the overall timing and extent of biotic interchange between tepui summits has remained unstudied. Here, we show that recent faunal interchange among currently isolated tepui summits has been extensive, and affected even taxa living in some of the most tepui-specific habitats and on the most inaccessible summits.     

Simplified proteomics approach to discover protein-ligand interactions

Identifying targets of biologically active small molecules is an essential but still challenging task in drug research and chemical genetics. Energetics-based target identification is an approach that utilizes the change in the conformational stabilities of proteins upon ligand binding in order to identify target proteins. Different from traditional affinity-based capture approaches, energetics-based methods do not require any labeling or immobilization of the test molecule. Here, we report a surprisingly simple version of energetics-based target identification, which only requires ion exchange chromatography, SDS PAGE, and minimal use of mass spectrometry. The complexity of a proteome is reduced through fractionation by ion exchange chromatography. Urea-induced unfolding of proteins in each fraction is then monitored by the significant increase in proteolytic susceptibility upon unfolding in the presence and the absence of a ligand. Proteins showing a different degree of unfolding with the ligand are identified by SDS PAGE followed by mass spectrometry. Using this approach, we identified ATP-binding proteins in the Escherichia coli proteome. In addition to known ATP-binding proteins, we also identified a number of proteins that were not previously known to interact with ATP. To validate one such finding, we cloned and purified phosphoglyceromutase, which was not previously known to bind ATP, and confirmed that ATP indeed stabilizes this protein. The combination of fractionation and pulse proteolysis offers an opportunity to investigate protein-drug or protein-metabolite interactions on a proteomic scale with minimal instrumentation and without modification of a molecule of interest.     

Membrane association of the PTEN tumor suppressor: molecular details of the protein-membrane complex from SPR binding studies and neutron reflection

The structure and function of the PTEN phosphatase is investigated by studying its membrane affinity and localization on in-plane fluid, thermally disordered synthetic membrane models. The membrane association of the protein depends strongly on membrane composition, where phosphatidylserine (PS) and phosphatidylinositol diphosphate (PI(4,5)P₂) act pronouncedly synergistic in pulling the enzyme to the membrane surface. The equilibrium dissociation constants for the binding of wild type (wt) PTEN to PS and PI(4,5)P₂ were determined to be K_d∼12 µM and 0.4 µM, respectively, and K_d∼50 nM if both lipids are present. Membrane affinities depend critically on membrane fluidity, which suggests multiple binding sites on the protein for PI(4,5)P₂. The PTEN mutations C124S and H93R show binding affinities that deviate strongly from those measured for the wt protein. Both mutants bind PS more strongly than wt PTEN. While C124S PTEN has at least the same affinity to PI(4,5)P₂ and an increased apparent affinity to PI(3,4,5)P₃, due to its lack of catalytic activity, H93R PTEN shows a decreased affinity to PI(4,5)P₂ and no synergy in its binding with PS and PI(4,5)P₂. Neutron reflection measurements show that the PTEN phosphatase “scoots" along the membrane surface (penetration <5 Å) but binds the membrane tightly with its two major domains, the C2 and phosphatase domains, as suggested by the crystal structure. The regulatory C-terminal tail is most likely displaced from the membrane and organized on the far side of the protein, ∼60 Å away from the bilayer surface, in a rather compact structure. The combination of binding studies and neutron reflection allows us to distinguish between PTEN mutant proteins and ultimately may identify the structural features required for membrane binding and activation of PTEN.     

Mirror,Mirror on the Wall,How Does My Brain Recognize My Image at All?

For decades researchers have used mirrors to study self-recognition. However, attempts to identify neural processes underlying this ability have used photographs instead. Here we used event related potentials (ERPs) to compare self-face recognition in photographs versus mirrors and found distinct neural signatures. Measures of visual self-recognition are therefore not independent of the medium employed.     

Breast cancer biomarkers predict weight loss after gastric bypass surgery

Background

Infections with polyomavirus BK virus (BKV) are a common cause of renal dysfunction after renal transplantation and may also be harmful in surgical patients with shock. The aim of the present study was to determine the frequency of BKV viremia in critically ill surgical patients with septic or hemorrhagic shock, and, if viremia is detectable, whether viremia may be associated with renal dysfunction.

Findings

A total of 125 plasma samples from 44 critically ill surgical patients with septic or hemorrhagic shock were tested by real-time polymerase chain reaction (PCR) for BKV DNA during their stay on the intensive care unit (ICU). BKV viremia occurred in four patients, i.e. in three of the septic and in one of the hemorrhagic shock group. There was no association between viremia and renal dysfunction. All positive samples contained a low viral load (< 500 copies/ml).

Conclusions

Since BK viremia was rarely found and with low viral load only in critically ill surgical patients with shock, it is very unlikely that BK viremia results in BK nephropathy later on.     

Obesity negatively impacts aerobic capacity improvements both acutely and 1-year following cardiac rehabilitation

Cardiac rehabilitation (CR) produces a host of health benefits related to modifiable cardiovascular risk factors. The purpose of the present investigation was to determine the influence of body weight, assessed through BMI, on acute and long-term improvements in aerobic capacity following completion of CR. Three thousand nine hundred and ninety seven subjects with coronary artery disease (CAD) participated in a 12-week multidisciplinary CR program. Subjects underwent an exercise test to determine peak estimated metabolic equivalents (eMETs) and BMI assessment at baseline, immediately following CR completion and at 1-year follow-up. Normal weight subjects at 1-year follow-up demonstrated the greatest improvement in aerobic fitness and best retention of those gains (gain in peak METs: 0.95 ± 1.1, P < 0.001). Although the improvement was significant (P < 0.001), subjects who were initially classified as obese had the lowest aerobic capacity and poorest retention in CR fitness gains at 1-year follow-up (gain in peak eMETs: 0.69 ± 1.2). Subjects initially classified as overweight by BMI had a peak eMET improvement that was also significantly better (P < 0.05) than obese subjects at 1-year follow-up (gain in peak eMETs: 0.82 ± 1.1). Significant fitness gains, one of the primary beneficial outcomes of CR, can be obtained by all subjects irrespective of BMI classification. However, obese patients have poorer baseline fitness and are more likely to "give back" fitness gains in the long term. Obese CAD patients may therefore benefit from additional interventions to enhance the positive adaptations facilitated by CR.