Polymorphisms in the vascular endothelial growth factor gene and breast cancer in the Cancer Prevention Study II cohort

INTRODUCTION: Vascular endothelial growth factor (VEGF) plays a central role in promoting angiogenesis and is over-expressed in breast cancer. At least four polymorphisms in the VEGF gene have been associated with changes in VEGF expression levels: -2578C/A, -1154G/A and -634G/C are all located in the promoter region; and +936C/T is located in the 3'-untranslated region. METHOD: We examined the association between these four VEGF polymorphisms and risk for breast cancer among postmenopausal women in CPS-II (Cancer Prevention Study II) Nutrition Cohort. This cohort was established in 1992 and participants were invited to provide a blood sample between 1998 and 2001. Included in this analysis were 501 postmenopausal women who provided a blood sample and were diagnosed with breast cancer between 1992 and 2001 (cases). Control individuals were 504 cancer-free postmenopausal women matched to the cases with respect to age, race/ethnicity, and date of blood collection (controls). RESULTS: We found no association between any of the polymorphisms examined and overall breast cancer risk. However, associations were markedly different in separate analyses of invasive cancer (n = 380) and in situ cancer (n = 107). The -2578C and -1154G alleles, which are both hypothesized to increase expression of VEGF, were associated with increased risk for invasive breast cancer (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.00–2.14 for -2578 CC versus AA; OR 1.64, 95% CI 1.02–2.64 for -1154 GG versus AA) but they were not associated with risk for in situ cancer. The +936C allele, which is also hypothesized to increase VEGF expression, was not clearly associated with invasive breast cancer (OR 1.21, 95% CI 0.88–1.67 for +936 CC versus TT/CT), but it was associated with reduced risk for in situ cancer (OR 0.59, 95% CI 0.37–0.93 for CC versus TT/CT). The -634 C/G polymorphism was not associated with either invasive or in situ cancer. CONCLUSION: Our findings provide limited support for the hypothesis that the -2578C and -1154G VEGF alleles are associated with increased risk for invasive but not in situ breast cancer in postmenopausal women

Detecting the impact of temperature on transmission of Zika, dengue, and chikungunya using mechanistic models

Recent epidemics of Zika, dengue, and chikungunya have heightened the need to understand the seasonal and geographic range of transmission by Aedes aegypti and Ae. albopictus mosquitoes. We use mechanistic transmission models to derive predictions for how the probability and magnitude of transmission for Zika, chikungunya, and dengue change with mean temperature, and we show that these predictions are well matched by human case data. Across all three viruses, models and human case data both show that transmission occurs between 18–34°C with maximal transmission occurring in a range from 26–29°C. Controlling for population size and two socioeconomic factors, temperature-dependent transmission based on our mechanistic model is an important predictor of human transmission occurrence and incidence. Risk maps indicate that tropical and subtropical regions are suitable for extended seasonal or year-round transmission, but transmission in temperate areas is limited to at most three months per year even if vectors are present. Such brief transmission windows limit the likelihood of major epidemics following disease introduction in temperate zones

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

Characterization of two related <i>Erwinia</i> myoviruses that are distant relatives of the PhiKZ-like Jumbo phages

<div><p>Bacteriophages are a major force in the evolution of bacteria due to their sheer abundance as well as their ability to infect and kill their hosts and to transfer genetic material. Bacteriophages that infect the <i>Enterobacteriaceae</i> family are of particular interest because this bacterial family contains dangerous animal and plant pathogens. Herein we report the isolation and characterization of two jumbo myovirus <i>Erwinia</i> phages, RisingSun and Joad, collected from apple trees. These two genomes are nearly identical with Joad harboring two additional putative gene products. Despite mass spectrometry data that support the putative annotation, 43% of their gene products have no significant BLASTP hit. These phages are also more closely related to <i>Pseudomonas</i> and <i>Vibrio</i> phages than to published <i>Enterobacteriaceae</i> phages. Of the 140 gene products with a BLASTP hit, 81% and 63% of the closest hits correspond to gene products from <i>Pseudomonas</i> and <i>Vibrio</i> phages, respectively. This relatedness may reflect their ecological niche, rather than the evolutionary history of their host. Despite the presence of over 800 <i>Enterobacteriaceae</i> phages on NCBI, the uniqueness of these two phages highlights the diversity of <i>Enterobacteriaceae</i> phages still to be discovered.</p></div

RisingSun and Joad are unique phages whose proteomes contain novel proteins.

<p><b>A)</b> Distribution of proteins in RisingSun based upon BLASTP hits that are novel, have no known function, and putative function. <b>B)</b> Putative gene ontology in RisingSun. <b>C)</b> Percentage of RisingSun gene products with BLASTP hits to proteins in other phages/organisms.</p

Host range of phage Joad suggests narrow specificity towards <i>Erwinia amylovora</i> and the closely related <i>Pantoea vegans</i> bacteria.

<p>The bacteria tested is provided along with the plaque forming units from three independent assays.</p

Locations of one motif discovered in five different structural genes.

<p><b>A)</b> Exact location of motif sites, p and q-values, sequence of motifs (conserved nucleotides shown in red), and putative gene function. Logogram shows motif sequence and larger letters represent frequent conservation. <b>B)</b> Arrows show approximate location of motif site. Genes were analyzed from the RisingSun annotation and thus locations are shown in the RisingSun phamerator map.</p

Joad and RisingSun are a unique cluster of phages when compared to others using whole genomes, MCP amino acid sequences, and terminase amino acid sequences.

<p><b>2A)</b> Similarity of seven phage genomes according to Average Nucleotide Identity (ANI). <b>2B)</b> Percent identity of major capsid proteins (MCP) amongst seven phages. <b>2C)</b> Percent identity of terminase proteins amongst seven phages. Percent identity was determined by BLASTP analysis.</p

General characteristics of <i>Erwinia amylovora</i> phages Joad and RisingSun.

<p>General characteristics of <i>Erwinia amylovora</i> phages Joad and RisingSun.</p