New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Computational cancer biology: education is a natural key to many locks

Background: Oncology is a field that profits tremendously from the genomic data generated by high-throughput technologies, including next-generation sequencing. However, in order to exploit, integrate, visualize and interpret such high-dimensional data efficiently, non-trivial computational and statistical analysis methods are required that need to be developed in a problem-directed manner.

Discussion: For this reason, computational cancer biology aims to fill this gap. Unfortunately, computational cancer biology is not yet fully recognized as a coequal field in oncology, leading to a delay in its maturation and, as an immediate consequence, an under-exploration of high-throughput data for translational research.

Summary: Here we argue that this imbalance, favoring 'wet lab-based activities', will be naturally rectified over time, if the next generation of scientists receives an academic education that provides a fair and competent introduction to computational biology and its manifold capabilities. Furthermore, we discuss a number of local educational provisions that can be implemented on university level to help in facilitating the process of harmonization.

Fungal stress biology: A preface to the Fungal Stress Responses special edition

There is currently an urgent need to increase global food security, reverse the trends of increasing cancer rates, protect environmental health, and mitigate climate change. Toward these ends, it is imperative to improve soil health and crop productivity, reduce food spoilage, reduce pesticide usage by increasing the use of biological control, optimize bioremediation of polluted sites, and generate energy from sustainable sources such as biofuels. This review focuses on fungi that can help provide solutions to such problems. We discuss key aspects of fungal stress biology in the context of the papers published in this Special Issue of Current Genetics. This area of biology has relevance to pure and applied research on fungal (and indeed other) systems, including biological control of insect pests, roles of saprotrophic fungi in agriculture and forestry, mycotoxin contamination of the food-supply chain, optimization of microbial fermentations including those used for bioethanol production, plant pathology, the limits of life on Earth, and astrobiology.

RNA interference in adult Ascaris suum - an opportunity for the development of a functional genomics platform that supports organism-, tissue- and cell-based biology in a nematode parasite

The sustainable control of animal parasitic nematodes requires the development of efficient functional genomics platforms to facilitate target validation and enhance anthelmintic discovery. Unfortunately, the utility of RNA interference (RNAi) for the validation of novel drug targets in nematode parasites remains problematic. Ascaris suum is an important veterinary parasite and a zoonotic pathogen. Here we show that adult A. suum is RNAi competent, and highlight the induction, spread and consistency of RNAi across multiple tissue types. This platform provides a new opportunity to undertake whole organism-, tissue- and cell-level gene function studies to enhance target validation processes for nematode parasites of veterinary/medical significance.

Not all jellyfish are equal: isotopic evidence for inter- and intraspecific variation in jellyfish trophic ecology

Jellyfish are highly topical within studies of pelagic food-webs and there is a growing realisation that their role is more complex than once thought. Efforts being made to include jellyfish within fisheries and ecosystem models are an important step forward, but our present understanding of their underlying trophic ecology can lead to their oversimplification in these models. Gelatinous zooplankton represent a polyphyletic assemblage spanning >2,000 species that inhabit coastal seas to the deep-ocean and employ a wide variety of foraging strategies. Despite this diversity, many contemporary modelling approaches include jellyfish as a single functional group feeding at one or two trophic levels at most. Recent reviews have drawn attention to this issue and highlighted the need for improved communication between biologists and theoreticians if this problem is to be overcome. We used stable isotopes to investigate the trophic ecology of three co-occurring scyphozoan jellyfish species (Aurelia aurita, Cyanea lamarckii and C. capillata) within a temperate, coastal food-web in the NE Atlantic. Using information on individual size, time of year and ;delta C-13 and delta N-15 stable isotope values, we examined: (1) whether all jellyfish could be considered as a single functional group, or showed distinct inter-specific differences in trophic ecology; (2) Were size-based shifts in trophic position, found previously in A. aurita, a common trait across species?; (3) When considered collectively, did the trophic position of three sympatric species remain constant over time? Differences in delta N-15 (trophic position) were evident between all three species, with size-based and temporal shifts in delta N-15 apparent in A. aurita and C. capillata. The isotopic niche width for all species combined increased throughout the season, reflecting temporal shifts in trophic position and seasonal succession in these gelatinous species. Taken together, these findings support previous assertions that jellyfish require more robust inclusion in marine fisheries or ecosystem models.

Parasite neuropeptide biology:Seeding rational drug target selection?

The rationale for identifying drug targets within helminth neuromuscular signalling systems is based on the premise that adequate nerve and muscle function is essential for many of the key behavioural determinants of helminth parasitism, including sensory perception/host location, invasion, locomotion/orientation, attachment, feeding and reproduction. This premise is validated by the tendency of current anthelmintics to act on classical neurotransmitter-gated ion channels present on helminth nerve and/or muscle, yielding therapeutic endpoints associated with paralysis and/or death. Supplementary to classical neurotransmitters, helminth nervous systems are peptide-rich and encompass associated biosynthetic and signal transduction components - putative drug targets that remain to be exploited by anthelmintic chemotherapy. At this time, no neuropeptide system-targeting lead compounds have been reported, and given that our basic knowledge of neuropeptide biology in parasitic helminths remains inadequate, the short-term prospects for such drugs remain poor. Here, we review current knowledge of neuropeptide signalling in Nematoda and Platyhelminthes, and highlight a suite of 19 protein families that yield deleterious phenotypes in helminth reverse genetics screens. We suggest that orthologues of some of these peptidergic signalling components represent appealing therapeutic targets in parasitic helminths.

(223)Ra and other bone-targeting radiopharmaceuticals-the translation of radiation biology into clinical practice

Osseous metastases are a source of significant morbidity for patients with a variety of cancers. Radiotherapy is well established as an effective means of palliating symptoms associated with such metastases. The role of external beam radiotherapy is limited where sites of metastases are numerous and widespread. Low linear energy transfer (LET) radionuclides have been utilized to allow targeted delivery of radiotherapy to disparate sites of disease, with evidence of palliative benefit. More recently, the bone targeting, high LET radionuclide (223)Ra has been shown to not only have a palliative effect but also a survival prolonging effect in metastatic, castration-resistant prostate cancer with bone metastases. This article reviews the different radionuclide-based approaches for targeting bone metastases, with an emphasis on (223)Ra, and key elements of the underlying radiobiology of these that will impact their clinical effectiveness. Consideration is given to the remaining unknowns of both the basic radiobiological and applied clinical effects of (223)Ra as targets for future research.

Studies on hemopoietic chimerism following allogeneic bone marrow transplantation in the molecular biology era

Donor hematopoiesis or donor chimerism in the host following allogeneic bone marrow transplantation (BMT) has appeared crucial to the engraftment process. However, as molecular techniques exploiting neutral variation in human genetic material have been used in the study of chimerism, the detection of residual host cells or mixed hemopoietic chimerism has indicated that donor chimerism is not obligatory following BMT. This review focuses on the detection and significance of mixed chimerism (MC) in patients transplanted for both malignant and non-malignant hemopoietic disease and attempts to tease out the contribution of MC to engraftment, leukemia relapse, graft rejection and long-term disease-free survival.

Report from the 2nd Summer School in Computational Biology organized by the Queen's University of Belfast

In this paper, we present a meeting report for the 2nd Summer School in Computational Biology organized by the Queen's University of Belfast. We describe the organization of the summer school, its underlying concept and student feedback we received after the completion of the summer school.