Sequencing the genome of the Burmese python (Python molurus bivittatus) as a model for studying extreme adaptations in snakes

The Consortium for Snake Genomics is in the process of sequencing the genome and creating transcriptomic resources for the Burmese python. Here, we describe how this will be done, what analyses this work will include, and provide a timeline

Patient-derived xenograft (PDX) models in basic and translational breast cancer research

Patient-derived xenograft (PDX) models of a growing spectrum of cancers are rapidly supplanting long-established traditional cell lines as preferred models for conducting basic and translational preclinical research. In breast cancer, to complement the now curated collection of approximately 45 long-established human breast cancer cell lines, a newly formed consortium of academic laboratories, currently from Europe, Australia, and North America, herein summarizes data on over 500 stably transplantable PDX models representing all three clinical subtypes of breast cancer (ER+, HER2+, and "Triple-negative" (TNBC)). Many of these models are well-characterized with respect to genomic, transcriptomic, and proteomic features, metastatic behavior, and treatment response to a variety of standard-of-care and experimental therapeutics. These stably transplantable PDX lines are generally available for dissemination to laboratories conducting translational research, and contact information for each collection is provided. This review summarizes current experiences related to PDX generation across participating groups, efforts to develop data standards for annotation and dissemination of patient clinical information that does not compromise patient privacy, efforts to develop complementary data standards for annotation of PDX characteristics and biology, and progress toward "credentialing" of PDX models as surrogates to represent individual patients for use in preclinical and co-clinical translational research. In addition, this review highlights important unresolved questions, as well as current limitations, that have hampered more efficient generation of PDX lines and more rapid adoption of PDX use in translational breast cancer research

An evaluation of long-term preservation methods for brown bear (\u3ci\u3eUrsus arctos\u3c/i\u3e) faecal DNA samples

Relatively few large-scale faecal DNA studies have been initiated due to difficulties in amplifying low quality and quantity DNA template. To improve brown bear faecal DNA PCR amplification success rates and to determine post collection sample longevity, five preservation methods were evaluated: 90% ethanol, DETs buffer, silica-dried, oven-dried stored at room temperature, and oven-dried stored at –20 ◦C. Preservation effectiveness was evaluated for 50 faecal samples by PCR amplification of a mitochondrial DNA (mtDNA) locus (∼146 bp) and a nuclear DNA (nDNA) locus (∼200 bp) at time points of one week, one month, three months and six months. Preservation method and storage time significantly impacted mtDNA and nDNA amplification success rates. For mtDNA, all preservation methods had ≥ 75% success at one week, but storage time had a significant impact on the effectiveness of the silica preservation method. Ethanol preserved samples had the highest success rates for both mtDNA (86.5%) and nDNA (84%). Nuclear DNA amplification success rates ranged from 26–88%, and storage time had a significant impact on all methods but ethanol. Preservation method and storage time should be important considerations for researchers planning projects utilizing faecal DNA. We recommend preservation of faecal samples in 90% ethanol when feasible, although when collecting in remote field conditions or for both DNA and hormone assays a dry collection method may be advantageous

The Physician and Pharmacist Team: An Effective Approach to Cholesterol Reduction

OBJECTIVE: To assess the effect of a program that encourages teamwork between physicians and pharmacists on attempts to lower total cholesterol levels and to meet recommended goals proposed by the National Cholesterol Education Program (NCEP). DESIGN: A single-blind, randomized, controlled trial lasting 6 months. SETTING: An ambulatory primary care center. PATIENTS: A sample of 94 patients with total cholesterol levels of 240 mg/dL (6.2 mmol/L) or higher. INTERVENTION: Equal numbers of patients were randomly assigned to a control arm in which standard medical care was received and an intervention arm which implemented close interaction between physicians and pharmacists. MEASUREMENTS AND MAIN RESULTS: Absolute change in total cholesterol levels from baseline values and the percentage of patients who achieved an NCEP goal after 6 months of intervention were determined. The rate of success in achieving NCEP goals in the intervention arm was double the rate in the control arm (43% vs 21%, p < .05). Total cholesterol levels in the intervention arm declined 44 +/- 47 mg/dL (1.1 +/- 1.2 mmol/L) versus 13 +/- 51 mg/dL (0.3 +/- 1.3 mmol/L) in the control arm (p < .01). The effect of intervention on reducing total cholesterol levels was similar for men and women and did not appear to be altered by age. The effect of intervention was greatest in patients with coronary heart disease (p < .01) followed by those without disease but with two or more coronary heart disease risk factors (p < .05). An effect of intervention was absent in patients without coronary heart disease and with fewer than two risk factors. CONCLUSIONS: Attempts to lower total cholesterol levels and achieve NCEP goals are likely to be more successful when combined with programs that include teamwork between physicians and pharmacists. Some programs, however, may be more successful for high-risk patients, for whom it is often easier to provide more aggressive therapies. Although altering adverse lipid profiles in lower-risk patients may be difficult, achieving optimal cholesterol levels could have an important impact on preventing movement to higher risk strata

An apple genome sequencing initiative

International audienceApple is a unique biological system belonging to Rosaceae, a family representing several important fruit and flower crops. In order to gain a holistic understanding of the structure and function of its genes, we have initiated sequencing of the apple genome. Our approach employs sequencing of a genetically simpler double haploid Golden Delicious apple and is based on obtaining de-novo draft genome assemblies by largely utilizing next-generation sequencing approaches. We have generated a 6X BAC library of the Double Haploid Apple. The genomic scaffold will be generated via directed sequencing of 27,000 BAC ends using 454 Titanium. The data will be utilized for genome assembly as well as organizing the BACs into a minimal tiling path using custom computational tools. Additional Scaffold will be generated by end-sequencing of 10,000 BACs. The resulting scaffold will be utilized to perform de-novo assembly of the apple genome utilizing over 4X shotgun coverage of the complex genome obtained with the GS FLX platform. This information is expected to serve as a foundation for developing healthier, value-added and nutritionally enhanced apple varieties for the public. This research is also expected to create educational, training and outreach avenues for undergraduate students, graduate students and the general public in the area of horticultural genomics

Why Is Tetradentate Coordination Essential for Potential Copper Homeostasis Regulators in Alzheimer's Disease?

International audienceResearch of effective drugs against Alzheimer's disease (AD) is currently one of the most challenging topics in medicinal chemistry. Despite the documented detrimental effect of the disruption of copper ion homeostasis in AD, this potential pharmacological target has been weakly explored. The design of chelators as drug candidates for copper regulation in AD brain should meet critical coordination chemistry requirements, in addition to requested biological parameters (membrane crossing, activity, …). Among the various possibilities offered by the diversity of metal ligands, we found that N4-tetradentate 8-aminoquinoline ligands able to generate stricly square planar Cu(II) complexes, are the most suitable for the transfer of copper from metal-amyloids to metal-carrier proteins, and are able to inhibit the catalytic reduction of dioxygen produced by copper-loaded amyloids exposed to a biological reductant. In vivo, such tetradentate ligands are able to inhibit the loss of episodic memory in non-transgenic amyloid-impaired mice