A genetic validation study reveals a role of vitamin D metabolism in the response to interferon-alfa-based therapy of chronic hepatitis C

Background

To perform a comprehensive study on the relationship between vitamin D metabolism and the response to interferon-α-based therapy of chronic hepatitis C.

Methodology/Principal Findings

Associations between a functionally relevant polymorphism in the gene encoding the vitamin D 1α-hydroxylase (CYP27B1-1260 rs10877012) and the response to treatment with pegylated interferon-α (PEG-IFN-α) and ribavirin were determined in 701 patients with chronic hepatitis C. In addition, associations between serum concentrations of 25-hydroxyvitamin D₃ (25[OH]D₃) and treatment outcome were analysed. CYP27B1-1260 rs10877012 was found to be an independent predictor of sustained virologic response (SVR) in patients with poor-response IL28B genotypes (15% difference in SVR for rs10877012 genotype AA vs. CC, p = 0.02, OR = 1.52, 95% CI = 1.061–2.188), but not in patients with favourable IL28B genotype. Patients with chronic hepatitis C showed a high prevalence of vitamin D insufficiency (25[OH]D₃<20 ng/mL) during all seasons, but 25(OH)D₃ serum levels were not associated with treatment outcome.

Conclusions/Significance

Our study suggests a role of bioactive vitamin D (1,25[OH]₂D₃, calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D₃ is not a suitable predictor of treatment outcome.     

Shared human-chimpanzee pattern of perinatal femoral shaft morphology and its implications for the evolution of hominin locomotor adaptations

Background

Acquisition of bipedality is a hallmark of human evolution. How bipedality evolved from great ape-like locomotor behaviors, however, is still highly debated. This is mainly because it is difficult to infer locomotor function, and even more so locomotor kinematics, from fossil hominin long bones. Structure-function relationships are complex, as long bone morphology reflects phyletic history, developmental programs, and loading history during an individual’s lifetime. Here we discriminate between these factors by investigating the morphology of long bones in fetal and neonate great apes and humans, before the onset of locomotion.

Methodology/Principal Findings

Comparative morphometric analysis of the femoral diaphysis indicates that its morphology reflects phyletic relationships between hominoid taxa to a greater extent than taxon-specific locomotor adaptations. Diaphyseal morphology in humans and chimpanzees exhibits several shared-derived features, despite substantial differences in locomotor adaptations. Orangutan and gorilla morphologies are largely similar, and likely represent the primitive hominoid state.

Conclusions/Significance

These findings are compatible with two possible evolutionary scenarios. Diaphyseal morphology may reflect retained adaptive traits of ancestral taxa, hence human-chimpanzee shared-derived features may be indicative of the locomotor behavior of our last common ancestor. Alternatively, diaphyseal morphology might reflect evolution by genetic drift (neutral evolution) rather than selection, and might thus be more informative about phyletic relationships between taxa than about locomotor adaptations. Both scenarios are consistent with the hypothesis that knuckle-walking in chimpanzees and gorillas resulted from convergent evolution, and that the evolution of human bipedality is unrelated to extant great ape locomotor specializations.     

Altitudinal Change in the Photosynthetic Capacity of Tropical Trees: A Case Study from Ecuador and a Pantropical Literature Analysis

In tropical mountains, trees are the dominant life form from sea level to above 4,000-m altitude under highly variable thermal conditions (range of mean annual temperatures: <8 to >28°C). How light-saturated net photosynthesis of tropical trees adapts to variation in temperature, atmospheric CO₂ concentration, and further environmental factors, that change along elevation gradients, is not precisely known. With gas exchange measurements in mature trees, we determined light-saturated net photosynthesis at ambient temperature (T) and [CO₂] (A _sat) of 40 tree species from 21 families in tropical mountain forests at 1000-, 2000-, and 3000-m elevation in southern Ecuador. We tested the hypothesis that stand-level averages of A _sat and leaf dark respiration (R _D) per leaf area remain constant with elevation. Stand-level means of A _sat were 8.8, 11.3, and 7.2?μmol?CO₂?m^?2?s^?1; those of R _D 0.8, 0.6, and 0.7?μmol?CO₂?m^?2?s^?1 at 1000-, 2000-, and 3000-m elevation, respectively, with no significant altitudinal trend. We obtained coefficients of among-species variation in A _sat and R _D of 20–53% (n?=?10–16 tree species per stand). Examining our data in the context of a pan-tropical A _sat data base for mature tropical trees (c. 170 species from 18 sites at variable elevation) revealed that area-based A _sat decreases in tropical mountains by, on average, 1.3?μmol?CO₂?m^?2?s^?1?per?km altitude increase (or by 0.2?μmol?CO₂?m^?2?s^?1 per K temperature decrease). The A _sat decrease occurred despite an increase in leaf mass per area with altitude. Local geological and soil fertility conditions and related foliar N and P concentrations considerably influenced the altitudinal A _sat patterns. We conclude that elevation is an important influencing factor of the photosynthetic activity of tropical trees. Lowered A _sat together with a reduced stand leaf area decrease canopy C gain with elevation in tropical mountains.     

Self-organizing ontology of biochemically relevant small molecules

Background  

The advent of high-throughput experimentation in biochemistry has led to the generation of vast amounts of chemical data, necessitating the development of novel analysis, characterization, and cataloguing techniques and tools. Recently, a movement to publically release such data has advanced biochemical structure-activity relationship research, while providing new challenges, the biggest being the curation, annotation, and classification of this information to facilitate useful biochemical pattern analysis. Unfortunately, the human resources currently employed by the organizations supporting these efforts (e.g. ChEBI) are expanding linearly, while new useful scientific information is being released in a seemingly exponential fashion. Compounding this, currently existing chemical classification and annotation systems are not amenable to automated classification, formal and transparent chemical class definition axiomatization, facile class redefinition, or novel class integration, thus further limiting chemical ontology growth by necessitating human involvement in curation. Clearly, there is a need for the automation of this process, especially for novel chemical entities of biological interest.     

MetaboLights: towards a new COSMOS of metabolomics data management

Exciting funding initiatives are emerging in Europe and the US for metabolomics data production, storage, dissemination and analysis. This is based on a rich ecosystem of resources around the world, which has been build during the past ten years, including but not limited to resources such as MassBank in Japan and the Human Metabolome Database in Canada. Now, the European Bioinformatics Institute has launched MetaboLights, a database for metabolomics experiments and the associated metadata (http://www.ebi.ac.uk/metabolights). It is the first comprehensive, cross-species, cross-platform metabolomics database maintained by one of the major open access data providers in molecular biology. In October, the European COSMOS consortium will start its work on Metabolomics data standardization, publication and dissemination workflows. The NIH in the US is establishing 6?C8 metabolomics services cores as well as a national metabolomics repository. This communication reports about MetaboLights as a new resource for Metabolomics research, summarises the related developments and outlines how they may consolidate the knowledge management in this third large omics field next to proteomics and genomics.     

An information-carrying and knowledge-producing molecular machine. A Monte-Carlo simulation

The concept called Knowledge is a measure of the quality of genetically transferred information. Its usefulness is demonstrated quantitatively in a Monte-Carlo simulation on critical steps in a origin of life model. The model describes the origin of a bio-like genetic apparatus by a long sequence of physical-chemical steps: it starts with the presence of a self-replicating oligomer and a specifically structured environment in time and space that allow for the formation of aggregates such as assembler-hairpins-devices and, at a later stage, an assembler-hairpins-enzyme device—a first translation machine.     

Remote sensing to map influence of light pollution on Cory’s shearwater in São Miguel Island,Azores Archipelago

Global economic and population growth increase the extent and intensity of artificial night lighting. From an ecological perspective, this is light pollution, which causes changes in reproductive physiology, migration and foraging of many species and ultimately leads to loss of biodiversity. Some seabirds are intimately linked with the light features of their environments because they are nocturnally active. We report light-induced groundings of Cory’s shearwater (Calonectris diomedea) during a 2-year study (2008 and 2009) in São Miguel Island, in the Azores archipelago, and investigate the spatial correlation of locations of grounded birds with an annual composite of remotely sensed stable lights. Results indicate that 16.7% of fledglings are attracted to lights. The exposure of shearwater colonies in the study area to artificial night lighting is low overall. Four colonies account for 87% of the grounded birds. The distance each bird was found from the closest colony was best explained by the ratio of the satellite-measured light levels at the grounding spot to the light levels at the assigned colony of origin. These results demonstrate that satellite-observed nighttime lights are sufficient to assess risk to marine birds at the scale of oceanic islands and indicate their utility for monitoring the effectiveness of programs to manage lighting to reduce risk for these species and conducting global assessments of species vulnerability. To minimize the impact on Cory’s shearwater and other marine birds, we recommend measures such as reduction and control of lighting intensity near colony locations, while continuing and re-enforcing rescue campaigns.