The Swift Ultra-Violet/Optical Telescope

The UV/Optical Telescope (UVOT) is one of three instruments flying aboard the Swift Gamma-ray Observatory. It is designed to capture the early (approximately 1 minute) UV and optical photons from the afterglow of gamma-ray bursts in the 170-600 nm band as well as long term observations of these afterglows. This is accomplished through the use of UV and optical broadband filters and grisms. The UVOT has a modified Ritchey-Chretien design with micro-channel plate intensified charged-coupled device detectors that record the arrival time of individual photons and provide sub-arcsecond positioning of sources. We discuss some of the science to be pursued by the UVOT and the overall design of the instrument.Comment: 55 Pages, 28 Figures, To be published in Space Science Review

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Scrutinizing the scaffolds of marine biosynthetics from different source organisms: Gram-negative cultured bacterial products enter center stage.

Compounds from macro marine organisms are presumed to owe their biosynthetic origins to associated microbial symbionts, although few definitive examples exist. An upsurge in the recent literature from 2012 to 2013 has shown that four compounds previously reported from macro marine organisms are in fact biosynthesized by non-photosynthetic Gram-negative bacteria (NPGNB). Structural parallels between compounds isolated from macro marine organisms and NPGNB producers form the basis of this review. Although less attention has been given to investigating the chemistry of NPGNB sources, there exists a significant list of structural parallels between NPGNB and macro marine organism-derived compounds. Alternatively, of the thousands of compounds isolated from Gram-positive actinomycetes, few structural parallels with macro marine organisms are known. A summary of small molecules isolated from marine NPGNB sources is presented, including compounds isolated from marine myxobacteria. From this assemblage of structural parallels and diverse chemical structures, it is hypothesized that the potential for the discovery of inspirational molecules from NPGNB sources is vast and that the recent spike in the literature of macro marine compounds owing their biosynthetic origin to NPGNB producers represents a turning point in the field

Potential of Plant-Derived Natural Products in the Treatment of Leukemia and Lymphoma

Hematologic malignancies account for a substantial percentage of cancers worldwide, and the heterogeneity and biological characteristics of leukemias and lymphomas present unique therapeutic challenges. Although treatment options exist for most of these diseases, many types remain incurable and the emergence of drug resistance is pervasive. Thus, novel treatment approaches are essential to improve outcome. Nearly half of the agents used in cancer therapy today are either natural products or derivatives of natural products. The e l,normous chemical diversity in nature, coupled with millennia of biological selection, has generated a vast and underexplored reservoir of unique chemical structures with biologic activity. This review will describe the investigation and application of natural products derived from higher plants in the treatment of leukemia and lymphoma and the rationale behind these efforts. In addition to the approved vinca alkaloids and the epipodophyllotoxin derivatives, a number of other plant compounds have shown promise in clinical trials and in preclinical investigations. In particular, we will focus on the discovery and biological evaluation of the plant- derived agent silvestrol, which shows potential for additional development as a new therapeutic agent for B-cell malignancies including chronic lymphocytic leukemia

Synthesis and Antitumor Activity of Ellagic Acid Peracetate

Ellagic acid (<b>1</b>) was synthesized for the first time from methyl gallate through α-pentagalloylglucose (α-PGG), and ellagic acid peracetate (3,4,3′,4′-tetra-<i>O</i>-acetylellagic acid, <b>2</b>) was derived from <b>1</b> by acetylation. Oral administration of <b>2</b> suppressed melanoma growth significantly in C7BL/6 immunocompetent mice without having any effect on natural killer (NK) cell activity. Comparison of the immunoenhancing activities of <b>1</b> and <b>2</b> indicated that the latter compound increased white blood cell quantities in peripheral blood and immune cells enriched from the bone marrow and liver of mice. Therefore, both the antitumor efficacy and the immunity enhancement by <b>2</b> were greater than those by <b>1</b>. In addition, on oral administration, neither <b>1</b> nor <b>2</b> resulted in whole body, liver, or spleen weight changes of normal, tumor-free mice, indicating that these compounds are potentially nontoxic to mice. It was shown that ellagic acid peracetate (<b>2</b>) inhibits B16 melanoma cell growth in vitro and induces B16 cell apoptosis, corresponding to BCL-2 down-regulation. Collectively, the present data imply that <b>2</b> can suppress tumor growth by enhancing mouse immunity and inducing tumor cell apoptosis without apparent side effects

Alkaloids from <i>Microcos paniculata</i> with Cytotoxic and Nicotinic Receptor Antagonistic Activities

<i>Microcos paniculata</i> is a large shrub or small tree that grows in several countries in South and Southeast Asia. In the present study, three new piperidine alkaloids, microgrewiapines A–C (<b>1</b>–<b>3</b>), as well as three known compounds, inclusive of microcosamine A (<b>4</b>), 7′-(3′,4′-dihydroxyphenyl)-<i>N</i>-[4-methoxyphenyl)­ethyl]­propenamide (<b>5</b>), and liriodenine (<b>6</b>), were isolated from cytotoxic fractions of the separate chloroform-soluble extracts of the stem bark, branches, and leaves of <i>M. paniculata</i>. Compounds <b>1</b>–<b>6</b> and <b>1a</b> (microgrewiapine A 3-acetate) showed a range of cytotoxicity values against the HT-29 human colon cancer cell line. When evaluated for their effects on human α3β4 or α4β2 nicotinic acetylcholine receptors (nAChRs), several of these compounds were shown to be active as nAChR antagonists. As a result of this study, microgrewiapine A (<b>1</b>) was found to be a selective cytotoxic agent for colon cancer cells over normal colon cells and to exhibit nicotinic receptor antagonistic activity for both the hα3β4 and hα4β2 receptor subtypes

Genetic inactivation of ANGPTL4 improves glucose homeostasis and is associated with reduced risk of diabetes

Angiopoietin-like 4 (ANGPTL4) is an endogenous inhibitor of lipoprotein lipase that modulates lipid levels, coronary atherosclerosis risk, and nutrient partitioning. We hypothesize that loss of ANGPTL4 function might improve glucose homeostasis and decrease risk of type 2 diabetes (T2D). We investigate protein-altering variants in ANGPTL4 among 58,124 participants in the DiscovEHR human genetics study, with follow-up studies in 82,766 T2D cases and 498,761 controls. Carriers of p.E40K, a variant that abolishes ANGPTL4 ability to inhibit lipoprotein lipase, have lower odds of T2D (odds ratio 0.89, 95% confidence interval 0.85-0.92, p = 6.3 x 10(-10)), lower fasting glucose, and greater insulin sensitivity. Predicted loss-of-function variants are associated with lower odds of T2D among 32,015 cases and 84,006 controls (odds ratio 0.71, 95% confidence interval 0.49-0.99, p = 0.041). Functional studies in Angptl4-deficient mice confirm improved insulin sensitivity and glucose homeostasis. In conclusion, genetic inactivation of ANGPTL4 is associated with improved glucose homeostasis and reduced risk of T2D.Peer reviewe