A mathematical model of the human metabolic system and metabolic flexibility

In healthy subjects some tissues in the human body display metabolic flexibility, by this we mean the ability for the tissue to switch its fuel source between predominantly carbohydrates in the post prandial state and predominantly fats in the fasted state. Many of the pathways involved with human metabolism are controlled by insulin, and insulin- resistant states such as obesity and type-2 diabetes are characterised by a loss or impairment of metabolic flexibility. In this paper we derive a system of 12 first-order coupled differential equations that describe the transport between and storage in different tissues of the human body. We find steady state solutions to these equations and use these results to nondimensionalise the model. We then solve the model numerically to simulate a healthy balanced meal and a high fat meal and we discuss and compare these results. Our numerical results show good agreement with experimental data where we have data available to us and the results show behaviour that agrees with intuition where we currently have no data with which to compare

Public policy action and CCC implementation: benefits and hurdles

Policy change continues to be an increasingly effective means of advancing the agenda of comprehensive cancer control. Efforts have moved progressively from describing how public policy can enhance the comprehensive cancer control agenda to implementation of public policy best practices at both the state and federal levels. The current political and economic contexts bring additional challenges and opportunities to the efforts surrounding comprehensive cancer control and policy. The purpose of this paper is to highlight recent policy successes, to illustrate the importance of policy as a means of advancing the comprehensive cancer control agenda, and to discuss continued policy action as we move forward in a time of healthcare reform and continuing economic uncertainty

A Biomedically Enriched Collection of 7000 Human ORF Clones

We report the production and availability of over 7000 fully sequence verified plasmid ORF clones representing over 3400 unique human genes. These ORF clones were derived using the human MGC collection as template and were produced in two formats: with and without stop codons. Thus, this collection supports the production of either native protein or proteins with fusion tags added to either or both ends. The template clones used to generate this collection were enriched in three ways. First, gene redundancy was removed. Second, clones were selected to represent the best available GenBank reference sequence. Finally, a literature-based software tool was used to evaluate the list of target genes to ensure that it broadly reflected biomedical research interests. The target gene list was compared with 4000 human diseases and over 8500 biological and chemical MeSH classes in ∼15 Million publications recorded in PubMed at the time of analysis. The outcome of this analysis revealed that relative to the genome and the MGC collection, this collection is enriched for the presence of genes with published associations with a wide range of diseases and biomedical terms without displaying a particular bias towards any single disease or concept. Thus, this collection is likely to be a powerful resource for researchers who wish to study protein function in a set of genes with documented biomedical significance

The DNA Repair Gene APE1 T1349G Polymorphism and Risk of Gastric Cancer in a Chinese Population

Background: Apurinic/apyrimidinic endonuclease 1 (APE1) has a central role in the repair of apurinic apyrimidic sites through both its endonuclease and its phosphodiesterase activities. A common APE1 polymorphism, T1349G (rs3136820), was previously shown to be associated with the risk of cancers. Objective: We hypothesized that the APE1 T1349G polymorphism is also associated with risk of gastric cancer. Methods: In a hospital-based case-control study of 338 case patients with newly diagnosed gastric cancer and 362 cancerfree controls frequency-matched by age and sex, we genotyped the T1349G polymorphism and assessed its associations with risk of gastric cancer. Results: Compared with the APE1 TT genotype, individuals with the variant TG/GG genotypes had a significantly increased risk of gastric cancer (odds ratio = 1.69, 95 % confidence interval = 1.19–2.40), which was more pronounced among subgroups of aged #60 years, male, ever smokers, and ever drinkers. Further analyses revealed that the variant genotypes were associated with an increased risk for diffuse-type, low depth of tumor infiltration (T1 and T2), and lymph node metastasis gastric cancer. Conclusions: The APE1 T1349G polymorphism may be a marker for the development of gastric cancer in the Chinese population. Larger studies are required to validate these findings in diverse populations

The decline in stomach cancer mortality: exploration of future trends in seven European countries

Mortality from stomach cancer has fallen steadily during the past decades. The aim of this paper is to assess the implication of a possible continuation of the decline in stomach cancer mortality until the year 2030. Annual rates of decline in stomach cancer mortality from 1980 to 2005 were determined for the Netherlands, United Kingdom, France, and four Nordic countries on the basis of regression analysis. Mortality rates were extrapolated until 2030, assuming the same rate of decline as in the past, using three possible scenarios. The absolute numbers of deaths were projected taking into account data on the ageing of national populations. Stomach cancer mortality rates declined between 1980 and 2005 at about the same rate (3.6–4.9% per year) for both men and women in all countries. The rate of decline did not level off in recent years, and it was not smaller in countries with lower overall mortality rates in 1980. If this decline were to continue into the future, stomach cancer mortality rates would decline with about 66% between 2005 and 2030 in most populations, while the absolute number of stomach cancer deaths would diminish by about 50%. Thus, in view of the strong, stable and consistent mortality declines in recent decades, and despite population ageing, stomach cancer is likely to become far less important as a cause of death in Europe in the future

Maximal Extraction of Biological Information from Genetic Interaction Data

Targeted genetic perturbation is a powerful tool for inferring gene function in model organisms. Functional relationships between genes can be inferred by observing the effects of multiple genetic perturbations in a single strain. The study of these relationships, generally referred to as genetic interactions, is a classic technique for ordering genes in pathways, thereby revealing genetic organization and gene-to-gene information flow. Genetic interaction screens are now being carried out in high-throughput experiments involving tens or hundreds of genes. These data sets have the potential to reveal genetic organization on a large scale, and require computational techniques that best reveal this organization. In this paper, we use a complexity metric based in information theory to determine the maximally informative network given a set of genetic interaction data. We find that networks with high complexity scores yield the most biological information in terms of (i) specific associations between genes and biological functions, and (ii) mapping modules of co-functional genes. This information-based approach is an automated, unsupervised classification of the biological rules underlying observed genetic interactions. It might have particular potential in genetic studies in which interactions are complex and prior gene annotation data are sparse

The search for transient astrophysical neutrino emission with IceCube-DeepCore

We present the results of a search for astrophysical sources of brief transient neutrino emission using IceCube and DeepCore data acquired between 2012 May 15 and 2013 April 30. While the search methods employed in this analysis are similar to those used in previous IceCube point source searches, the data set being examined consists of a sample of predominantly sub-TeV muon-neutrinos from the Northern Sky (-5 degrees < delta < 90 degrees) obtained through a novel event selection method. This search represents a first attempt by IceCube to identify astrophysical neutrino sources in this relatively unexplored energy range. The reconstructed direction and time of arrival of neutrino events are used to search for any significant self-correlation in the data set. The data revealed no significant source of transient neutrino emission. This result has been used to construct limits at timescales ranging from roughly 1 s to 10 days for generic soft-spectra transients. We also present limits on a specific model of neutrino emission from soft jets in core-collapse supernovae

The Main Belt Comets and ice in the Solar System

We review the evidence for buried ice in the asteroid belt; specifically the questions around the so-called Main Belt Comets (MBCs). We summarise the evidence for water throughout the Solar System, and describe the various methods for detecting it, including remote sensing from ultraviolet to radio wavelengths. We review progress in the first decade of study of MBCs, including observations, modelling of ice survival, and discussion on their origins. We then look at which methods will likely be most effective for further progress, including the key challenge of direct detection of (escaping) water in these bodies

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics