Sarcopenia is more than a muscular deficit

Sarcopenia is a complex process that appears in aged muscle associated with a decrease in mass, strength, and velocity of contraction. This process is the result of many molecular, cellular and functional alterations. It has been suggested that sarcopenia may be triggered by reactive oxygen species (ROS) that have accumulated throughout one's lifetime. We found a significant increase in oxidation of DNA and lipids in the elderly muscle, more evident in males, and a reduction in catalase and glutathione transferase activities. Experiments on Ca2+ transport showed an abnormal functional response of aged muscle after exposure to caffeine, which increases the opening of Ca2+ channels, as well a reduced activity of the Ca2+ pump in elderly males. From these results we concluded that oxidative stress play an important role in muscle aging and that oxidative damage is much more evident in elderly males, suggesting a gender difference may be related to hormonal factors. The progression of sarcopenia is directly related to a significant reduction of the regenerative potential of muscle normally due to a type of adult stem cells, known as satellite cells, which lie outside the sarcolemma and remain quiescent until external stimuli trigger as growth factors (IGF-1 or mIGF-1) their re-entry into the cell cycle. One possibility is that the anti oxidative capacity of satellite cells could also be altered and this, in turn, determines the decrease of their regenerative capacity. Data concerning this hypothesis are discussed     

The future of genomic medicine is here

A report on the 6th annual Future of Genomic Medicine conference, held at the Scripps Seaside Forum, La Jolla, CA, USA, March 7-8, 2013.On his flight over to San Diego to lead the Future of Genomic Medicine (FoGM) conference, Dr Eric Topol (Scripps Translational Science Institute, USA) used a heart monitor device attached to his smartphone to diagnose a distressed passenger with atrial fibrillation. Already, mobile technologies such as this one are beginning to transform medicine, and genome sequencing, with its rapidly decreasing costs, is no exception. As we get closer to mini-sequencers and what George Church (Harvard Medical School, USA) termed ''wearable sequencing'', a future of genomically informed medicine becomes possible. The FoGM conference integrated the patient-oriented perspective of genomic medicine, along with cutting-edge technologies and data integration, and developing methods and models in the aim of clinical utility.     

The thalamus is more than just a relay

The lateral geniculate nucleus and pulvinar are examples of two different types of relay: the former is a first order relay, transmitting information from a subcortical source (retina), while the latter is mostly a higher order relay, transmitting information from layer 5 of one cortical area to another cortical area. First and higher order thalamic relays can also be recognized for much of the rest of thalamus, and most of thalamus seems to be comprised of higher order relays. Higher order relays seem especially important to general corticocortical communication, and this challenges and extends the conventional view that such communication is based on direct corticocortical connections.     

Nursing stimulation is more than tactile sensation: It is a multisensory experience

Novel sensory experiences, particularly those associated with epochal developmental events like nursing alter cortical representation, affecting memory, perception and behavior. Functional MRI was used here to test whether the sensoricortical map of the ventrum is modified during lactation. Three stimuli were used to drive cortical activation in primiparous rats: natural, artificial suckling stimulation and general mechanical rubbing of the skin of the ventrum. These stimuli significantly activated the somatosensory cortex of dams. Of the three stimuli, artificial and pup suckling robustly activated much of the cerebrum, most notably the visual, auditory and olfactory cortices. Surprisingly, activation occurred even in the absence of pups, with artificial suckling. This finding suggests that incoming information from a single modality was sufficient to drive activity of others. Enhanced sensitivity across the cortical mantle during nursing may help the dam to perceive, process, and remember stimuli critical to the care and protection of her young.     

R-etodolac is a more potent Wnt signaling inhibitor than enantiomer,S-etodolac

Etodolac is an FDA-approved nonsteroidal anti-inflammatory drug (NSAID) used to treat a variety of inflammatory diseases. The drug is administered as a racemate (50/50 mixture of R- and S- enantiomers), however, studies have shown that the two enantiomers have distinct biologic and pharmacokinetic differences. Wnt signaling, which plays key roles in cell proliferation, polarity, and differentiation, has been shown to be inhibited by R-etodolac; however, comparative analyses of R- and S-etodolac in this function have not been conducted. We used in silico molecular docking and TOPflash functional biologic assays to compare R- and S-enantiomers effect on Wnt signaling inhibition. Further, we used a cultivated limbal stem epithelial cell (cLSCs) model to investigate enantiospecific changes in the colony-forming efficiency (CFE) of cLSCs. The data shows that R-etodolac is a more potent inhibitor of Wnt signaling. In addition, consistently, while both enantiomers demonstrate a dose-dependent decrease in CFE of cLSCs, R-etodolac is a more potent inhibitor.     

The CXXC motif is more than a redox rheostat

The CXXC active-site motif of thiol-disulfide oxidoreductases is thought to act as a redox rheostat, the sequence of which determines its reduction potential and functional properties. We tested this idea by selecting for mutants of the CXXC motif in a reducing oxidoreductase (thioredoxin) that complement null mutants of a very oxidizing oxidoreductase, DsbA. We found that altering the CXXC motif affected not only the reduction potential of the protein, but also its ability to function as a disulfide isomerase and also impacted its interaction with folding protein substrates and reoxidants. It is surprising that nearly all of our thioredoxin mutants had increased activity in disulfide isomerization in vitro and in vivo. Our results indicate that the CXXC motif has the remarkable ability to confer a large number of very specific properties on thioredoxin-related proteins.     

Survivability is more fundamental than evolvability

For a lineage to survive over long time periods, it must sometimes change. This has given rise to the term evolvability, meaning the tendency to produce adaptive variation. One lineage may be superior to another in terms of its current standing variation, or it may tend to produce more adaptive variation. However, evolutionary outcomes depend on more than standing variation and produced adaptive variation: deleterious variation also matters. Evolvability, as most commonly interpreted, is not predictive of evolutionary outcomes. Here, we define a predictive measure of the evolutionary success of a lineage that we call the k-survivability, defined as the probability that the lineage avoids extinction for k generations. We estimate the k-survivability using multiple experimental replicates. Because we measure evolutionary outcomes, the initial standing variation, the full spectrum of generated variation, and the heritability of that variation are all incorporated. Survivability also accounts for the decreased joint likelihood of extinction of sub-lineages when they 1) disperse in space, or 2) diversify in lifestyle. We illustrate measurement of survivability with in silico models, and suggest that it may also be measured in vivo using multiple longitudinal replicates. The k-survivability is a metric that enables the quantitative study of, for example, the evolution of 1) mutation rates, 2) dispersal mechanisms, 3) the genotype-phenotype map, and 4) sexual reproduction, in temporally and spatially fluctuating environments. Although these disparate phenomena evolve by well-understood microevolutionary rules, they are also subject to the macroevolutionary constraint of long-term survivability.     

Life is more than a computer running DNA software

In his recent interview for the Guardian Craig Venter is elaborating about a household appliance for the future, Digital Biological Converter(DBC). Current prototype, which can produce DNA, is a box attached to the computer which receives DNA sequences over the internet to synthesize DNA; later in future also viruses, proteins, and living cells. This would help the household members to produce, e.g., insulin, virus vaccines or phages that fight antibiotic resistant bacteria. In more distant future, Craig Venter's hope is that the DBC will generate living cells via so-called Universal Recipient Cell. This platform will allow digitally transformed genomes, downloaded from the internet, to form new cells fitted for the particular needs such as therapeutics, food, fuel or cleaning water. In contrast to this, the authors propose that DNA sequences of genomes do not represent 1:1 depictions of unequivocal coding structures such as genes. In light of the variety of epigenetic markings, DNA can store a multitude of further meanings hidden under the superficial grammar of nucleic acid sequences.     

Why genomics is more than genomes

A report on the 2004 meeting on Molecular Genetics of Bacteria and Bacteriophages, Cold Spring Harbor, USA, 25-29 August 2004.     

Forest restoration is more than firing seeds from a drone

We are witnessing a rapid increase in news sending the message that drone seeding is a promising technological solution to implement forest restoration at large spatial scales. However, there are neither reports regarding success nor peer-reviewed studies to support these assertions. Once in the ground, the seeds and the seedlings and saplings that they generate have to face biotic and abiotic hazards that can strongly reduce regeneration potential. Successful forest restoration, therefore, cannot be achieved by simply dropping seeds from the air. We summarize some aspects to take into account before considering drone seeding as an efficient and widely applicable technology for forest restoration. A first step should be to increase the precision of drone seeding—contrary to the current massive firing of seeds—in order to concentrate the efforts in the best microsites for establishment and reduce the number of seeds needed and the cost of the whole operation.