Deep Sequencing the Transcriptome Reveals Seasonal Adaptive Mechanisms in a Hibernating Mammal

Mammalian hibernation is a complex phenotype involving metabolic rate reduction, bradycardia, profound hypothermia, and a reliance on stored fat that allows the animal to survive for months without food in a state of suspended animation. To determine the genes responsible for this phenotype in the thirteen-lined ground squirrel (Ictidomys tridecemlineatus) we used the Roche 454 platform to sequence mRNA isolated at six points throughout the year from three key tissues: heart, skeletal muscle, and white adipose tissue (WAT). Deep sequencing generated approximately 3.7 million cDNA reads from 18 samples (6 time points ×3 tissues) with a mean read length of 335 bases. Of these, 3,125,337 reads were assembled into 140,703 contigs. Approximately 90% of all sequences were matched to proteins in the human UniProt database. The total number of distinct human proteins matched by ground squirrel transcripts was 13,637 for heart, 12,496 for skeletal muscle, and 14,351 for WAT. Extensive mitochondrial RNA sequences enabled a novel approach of using the transcriptome to construct the complete mitochondrial genome for I. tridecemlineatus. Seasonal and activity-specific changes in mRNA levels that met our stringent false discovery rate cutoff (1.0×10−11) were used to identify patterns of gene expression involving various aspects of the hibernation phenotype. Among these patterns are differentially expressed genes encoding heart proteins AT1A1, NAC1 and RYR2 controlling ion transport required for contraction and relaxation at low body temperatures. Abundant RNAs in skeletal muscle coding ubiquitin pathway proteins ASB2, UBC and DDB1 peak in October, suggesting an increase in muscle proteolysis. Finally, genes in WAT that encode proteins involved in lipogenesis (ACOD, FABP4) are highly expressed in August, but gradually decline in expression during the seasonal transition to lipolysis

Hemocompatibility of Silicon-Based Substrates for Biomedical Implant Applications

Silicon membranes with highly uniform nanopore sizes fabricated using microelectromechanical systems (MEMS) technology allow for the development of miniaturized implants such as those needed for renal replacement therapies. However, the blood compatibility of silicon has thus far been an unresolved issue in the use of these substrates in implantable biomedical devices. We report the results of hemocompatibility studies using bare silicon, polysilicon, and modified silicon substrates. The surface modifications tested have been shown to reduce protein and/or platelet adhesion, thus potentially improving biocompatibility of silicon. Hemocompatibility was evaluated under four categories—coagulation (thrombin–antithrombin complex, TAT generation), complement activation (complement protein, C3a production), platelet activation (P-selectin, CD62P expression), and platelet adhesion. Our tests revealed that all silicon substrates display low coagulation and complement activation, comparable to that of Teflon and stainless steel, two materials commonly used in medical implants, and significantly lower than that of diethylaminoethyl (DEAE) cellulose, a polymer used in dialysis membranes. Unmodified silicon and polysilicon showed significant platelet attachment; however, the surface modifications on silicon reduced platelet adhesion and activation to levels comparable to that on Teflon. These results suggest that surface-modified silicon substrates are viable for the development of miniaturized renal replacement systems

An online spike detection and spike classification algorithm capable of instantaneous resolution of overlapping spikes

For the analysis of neuronal cooperativity, simultaneously recorded extracellular signals from neighboring neurons need to be sorted reliably by a spike sorting method. Many algorithms have been developed to this end, however, to date, none of them manages to fulfill a set of demanding requirements. In particular, it is desirable to have an algorithm that operates online, detects and classifies overlapping spikes in real time, and that adapts to non-stationary data. Here, we present a combined spike detection and classification algorithm, which explicitly addresses these issues. Our approach makes use of linear filters to find a new representation of the data and to optimally enhance the signal-to-noise ratio. We introduce a method called “Deconfusion” which de-correlates the filter outputs and provides source separation. Finally, a set of well-defined thresholds is applied and leads to simultaneous spike detection and spike classification. By incorporating a direct feedback, the algorithm adapts to non-stationary data and is, therefore, well suited for acute recordings. We evaluate our method on simulated and experimental data, including simultaneous intra/extra-cellular recordings made in slices of a rat cortex and recordings from the prefrontal cortex of awake behaving macaques. We compare the results to existing spike detection as well as spike sorting methods. We conclude that our algorithm meets all of the mentioned requirements and outperforms other methods under realistic signal-to-noise ratios and in the presence of overlapping spikes

Automatic structure classification of small proteins using random forest

<p>Abstract</p> <p><b>Background</b></p> <p>Random forest, an ensemble based supervised machine learning algorithm, is used to predict the SCOP structural classification for a target structure, based on the similarity of its structural descriptors to those of a template structure with an equal number of secondary structure elements (SSEs). An initial assessment of random forest is carried out for domains consisting of three SSEs. The usability of random forest in classifying larger domains is demonstrated by applying it to domains consisting of four, five and six SSEs.</p> <p><b>Result</b>s</p> <p>Random forest, trained on SCOP version 1.69, achieves a predictive accuracy of up to 94% on an independent and non-overlapping test set derived from SCOP version 1.73. For classification to the SCOP <it>Class, Fold, Super-family </it>or <it>Family </it>levels, the predictive quality of the model in terms of Matthew's correlation coefficient (MCC) ranged from 0.61 to 0.83. As the number of constituent SSEs increases the MCC for classification to different structural levels decreases.</p> <p>Conclusions</p> <p>The utility of random forest in classifying domains from the place-holder classes of SCOP to the true <it>Class, Fold, Super-family </it>or <it>Family </it>levels is demonstrated. Issues such as introduction of a new structural level in SCOP and the merger of singleton levels can also be addressed using random forest. A real-world scenario is mimicked by predicting the classification for those protein structures from the PDB, which are yet to be assigned to the SCOP classification hierarchy.</p

To retain or remove the syndesmotic screw: a review of literature

Introduction: Syndesmotic positioning screws are frequently placed in unstable ankle fractures. Many facets of adequate placement techniques have been the subject of various studies. Whether or not the syndesmosis screw should be removed prior to weight-bearing is still debated. In this study, the recent literature is reviewed concerning the need for removal of the syndesmotic screw. Materials and methods: A comprehensive literature search was conducted in the electronic databases of the Cochrane Library, Pubmed Medline and EMbase from January 2000 to October 2010. Results: A total of seven studies were identified in the literature. Most studies found no difference in outcome between retained or removed screws. Patients with screws that were broken, or showed loosening, had similar or improved outcome compared to patients with removed screws. Removal of the syndesmotic screws, when deemed necessary, is usually not performed before 8-12 weeks. Conclusion: There is paucity in randomized controlled trials on the absolute need for removal of the syndesmotic screw. However, current literature suggests that it might be reserved for intact screws that cause hardware irritation or reduced range of motion after 4-6 months

Chinese organized crime and situational context: comparing human smuggling and synthetic drugs trafficking

This article criticizes the 'ethnic' conception of organized crime and puts forward an alternative view that does not put ethnicity first, but rather social networks and situational context. It focuses upon Chinese organized crime, a phenomenon where the preoccupation with ethnicity is paramount, and compares findings from extensive research into two different transnational criminal activities that are carried out by Chinese offenders in the Netherlands. The first topic, human smuggling, is well researched, whereas research into the second topic, trafficking in precursors (the basic ingredients for the production of synthetic drugs), is largely lacking. The article highlights the major theoretical and empirical similarities and differences between these two criminal activities and discusses the relevance of the main findings for theory and research

Risk Factors for Obesity and High Blood Pressure in Chinese American Children: Maternal Acculturation and Children’s Food Choices

The objective of this study is to explore risk factors associated with overweight and high blood pressure in Chinese American children. Students and their parents were recruited from Chinese language schools in the San Francisco Bay Area. Data were collected on 67 children and their mothers, and included children’s weight, height, waist and hip circumferences, blood pressure, level of physical activity, dietary intake, usual food choice, knowledge about nutrition and physical activity, and self-efficacy regarding diet and physical activity. Mothers completed questionnaires on demographic data and acculturation. About 46% of children had a body mass index exceeding the 85th percentile. Lower level of maternal acculturation is a risk factor for overweight and higher waist to hip ratio. Children’s unhealthy food choices were predictive of high body mass index and high systolic blood pressure, whereas older age and less physical activity in children were predictors of high diastolic blood pressure. Developing culturally sensitive and developmentally appropriate interventions to reduce overweight and high blood pressure is critical to reduce health disparities among minority children

The Future of Rheumatoid Arthritis and Hand Surgery - Combining Evolutionary Pharmacology and Surgical Technique

Rheumatoid arthritis is a systemic autoimmune disease of uncertain aetiology, which is characterized primarily by synovial inflammation with secondary skeletal destructions