The role of survivin in angiogenesis during zebrafish embryonic development

<p>Abstract</p> <p>Background</p> <p>Survivin is the smallest member of the inhibitor of apoptosis (IAP) gene family. Recently, the zebrafish <it>survivin-1 </it>gene has been cloned, showing remarkable sequence identity and similarity over the BIR domain compared with human and mouse <it>survivin </it>gene. Here we investigated the role of survivin in angiogenesis during zebrafish development. Morpholinos (MOs) targeting the 5' untranslated region (UTR) (Sur_UTR) and sequences flanking the initiation codon (Sur_ATG) of zebrafish <it>survivin-1 </it>gene were injected into embryos at 1–4 cell stage. Vasculature was examined by microangiography and GFP expression in <it>Tg(fli1:EGFP)</it>^<it>y</it>1embryos. Results: In embryos co-injected with Sur_UTRand Sur_ATG-MOs, vasculogenesis was intact but angiogenesis was markedly perturbed, especially in the inter-segmental vessels (ISV) and dorsal longitudinal anastomotic vessels (DLAV) of the trunk, the inner optic circle and optic veins of developing eyes and the sub-intestinal vessels. Apoptosis was increased, as shown by TUNEL staining and increase in caspase-3 activity. Efficacy of Sur_UTRand Sur_ATG-MOs was demonstrated by translation inhibition of co-injected 5'UTR survivin:GFP plasmids. The phenotypes could be recapitulated by splice-site MO targeting the exon2-intron junction of <it>survivin </it>gene and rescued by <it>survivin </it>mRNA. Injection of human vascular endothelial growth factor (VEGF) protein induced ectopic angiogenesis and increased survivin expression, whereas treatment with a VEGF receptor inhibitor markedly reduced angiogenesis and suppressed survivin expression. Conclusion: Survivin is involved in angiogenesis during zebrafish development and may be under VEGF regulation.</p

Disparities in self-reported postpartum depression among Asian, Hawaiian, and Pacific Islander women in Hawai‘i: Pregnancy, Risk, Assessment, and Monitoring System (PRAMS), 2004-2007

Postpartum depression affects 10–20% of women and causes significant morbidity and mortality among mothers, children, families, and society, but little is known about postpartum depression among the individual Asian and Pacific Islander racial/ethnic groups. This study sought to identify the prevalence of postpartum depression among common Asian and Pacific Islander racial/ethnic groups. Data from the Hawaii Pregnancy Risk Assessment and Monitoring System (PRAMS), a population-based surveillance system on maternal behaviors and experiences before, during, and after the birth of a live infant, were analyzed from 2004 through 2007 and included 7,154 women. Questions on mood and interest in activities since giving birth were combined to create a measure of Self-reported Postpartum Depressive Symptoms (SRPDS). A series of generalized logit models with maternal race or ethnicity adjusted for other sociodemographic characteristics evaluated associations between SRPDS and an intermediate level of symptoms as possible indicators of possible SRPDS. Of all women in Hawaii with a recent live birth, 14.5% had SRPDS, and 30.1% had possible SRPDS. The following Asian and Pacific Islander racial or ethnic groups were studied and found to have higher odds of SRPDS compared with white women: Korean (adjusted odds ratio [AOR] = 2.8;95% confidence interval [CI]: 2.0–4.0), Filipino (AOR = 2.2;95% CI: 1.7–2.8), Chinese (AOR = 2.0;95% CI: 1.5–2.7), Samoan (AOR = 1.9;95% CI: 1.2–3.2), Japanese (AOR = 1.6;95% CI: 1.2–2.2), Hawaiian (AOR = 1.7;95% CI: 1.3–2.1), other Asian (AOR = 3.3;95% CI: 1.9–5.9), other Pacific Islander (AOR = 2.2;95% CI: 1.5–3.4), and Hispanic (AOR = 1.9;95% CI: 1.1–3.4). Women who had unintended pregnancies (AOR = 1.4;95% CI: 1.2–1.6), experienced intimate partner violence (AOR = 3.7;95% CI: 2.6–5.5), smoked (AOR = 1.5;95% CI: 1.2–2.0), used illicit drugs (AOR = 1.9;95% CI: 1.3–3.9), or received Women, Infant, and Children (WIC) benefits during pregnancy (AOR = 1.4;95% CI: 1.2–2.6) were more likely to have SRPDS. Several groups also were at increased risk for possible SRPDS, although this risk was not as prominent as seen with the risk for SRPDS. One in seven women reported SRPDS, and close to a third reported possible SRPDS. Messages about postpartum depression should be incorporated into current programs to improve screening, treatment, and prevention of SRPDS for women at risk

Draft genome sequence of the Tibetan antelope

The Tibetan antelope (Pantholops hodgsonii) is endemic to the extremely inhospitable high-altitude environment of the Qinghai-Tibetan Plateau, a region that has a low partial pressure of oxygen and high ultraviolet radiation. Here we generate a draft genome of this artiodactyl and use it to detect the potential genetic bases of highland adaptation. Compared with other plain-dwelling mammals, the genome of the Tibetan antelope shows signals of adaptive evolution and gene-family expansion in genes associated with energy metabolism and oxygen transmission. Both the highland American pika, and the Tibetan antelope have signals of positive selection for genes involved in DNA repair and the production of ATPase. Genes associated with hypoxia seem to have experienced convergent evolution. Thus, our study suggests that common genetic mechanisms might have been utilized to enable high-altitude adaptation

Subtype-Specific and Co-Occurring Genetic Alterations in B-cell Non-Hodgkin Lymphoma

B-cell non-Hodgkin lymphoma (B-NHL) encompasses multiple clinically and phenotypically distinct subtypes of malignancy with unique molecular etiologies. Common subtypes of B-NHL, such as diffuse large B-cell lymphoma, have been comprehensively interrogated at the genomic level, but rarer subtypes, such as mantle cell lymphoma, remain less extensively characterized. Furthermore, multiple B-NHL subtypes have thus far not been comprehensively compared using the same methodology to identify conserved or subtype-specific patterns of genomic alterations. Here, we employed a large targeted hybrid-capture sequencing approach encompassing 380 genes to interrogate the genomic landscapes of 685 B-NHL tumors at high depth, including diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, and Burkitt lymphoma. We identified conserved hallmarks of B-NHL that were deregulated in the majority of tumors from each subtype, including frequent genetic deregulation of the ubiquitin proteasome system. In addition, we identified subtype-specific patterns of genetic alterations, including clusters of co-occurring mutations and DNA copy number alterations. The cumulative burden of mutations within a single cluster were more discriminatory of B-NHL subtypes than individual mutations, implicating likely patterns of genetic cooperation that contribute to disease etiology. We therefore provide the first cross-sectional analysis of mutations and DNA copy number alterations across major B-NHL subtypes and a framework of co-occurring genetic alterations that deregulate genetic hallmarks and likely cooperate in lymphomagenesis

Effect of Broccoli Sprouts and Live Attenuated Influenza Virus on Peripheral Blood Natural Killer Cells: A Randomized, Double-Blind Study

Enhancing antiviral host defense responses through nutritional supplementation would be an attractive strategy in the fight against influenza. Using inoculation with live attenuated influenza virus (LAIV) as an infection model, we have recently shown that ingestion of sulforaphane-containing broccoli sprout homogenates (BSH) reduces markers of viral load in the nose. To investigate the systemic effects of short-term BSH supplementation in the context of LAIV-inoculation, we examined peripheral blood immune cell populations in non-smoking subjects from this study, with a particular focus on NK cells. We carried out a randomized, double-blinded, placebo-controlled study measuring the effects of BSH (N = 13) or placebo (alfalfa sprout homogenate, ASH; N = 16) on peripheral blood mononuclear cell responses to a standard nasal vaccine dose of LAIV in healthy volunteers. Blood was drawn prior to (day-1) and post (day2, day21) LAIV inoculation and analyzed for neutrophils, monocytes, macrophages, T cells, NKT cells, and NK cells. In addition, NK cells were enriched, stimulated, and assessed for surface markers, intracellular markers, and cytotoxic potential by flow cytometry. Overall, LAIV significantly reduced NKT (day2 and day21) and T cell (day2) populations. LAIV decreased NK cell CD56 and CD158b expression, while significantly increasing CD16 expression and cytotoxic potential (on day2). BSH supplementation further increased LAIV-induced granzyme B production (day2) in NK cells compared to ASH and in the BSH group granzyme B levels appeared to be negatively associated with influenza RNA levels in nasal lavage fluid cells. We conclude that nasal influenza infection may induce complex changes in peripheral blood NK cell activation, and that BSH increases virus-induced peripheral blood NK cell granzyme B production, an effect that may be important for enhanced antiviral defense responses

Spitzer catalog of Herschel-selected ultrared dusty, star-forming galaxies

The largest Herschel extragalactic surveys, H-ATLAS and HerMES, have selected a sample of "ultrared" dusty, star-forming galaxies (DSFGs) with rising SPIRE flux densities ($S_{500} > S_{350} > S_{250}$; so-called "500 $\mu$m-risers") as an efficient way for identifying DSFGs at higher redshift ($z > 4$). In this paper, we present a large Spitzer follow-up program of 300 Herschel ultrared DSFGs. We have obtained high-resolution ALMA, NOEMA, and SMA data for 63 of them, which allow us to securely identify the Spitzer/IRAC counterparts and classify them as gravitationally lensed or unlensed. Within the 63 ultrared sources with high-resolution data, $\sim$65% appear to be unlensed, and $\sim$27% are resolved into multiple components. We focus on analyzing the unlensed sample by directly performing multi-wavelength spectral energy distribution (SED) modeling to derive their physical properties and compare with the more numerous $z \sim 2$ DSFG population. The ultrared sample has a median redshift of 3.3, stellar mass of 3.7 $\times$ 10$^{11}$ $M_{\odot}$, star formation rate (SFR) of 730 $M_{\odot}$yr$^{-1}$, total dust luminosity of 9.0 $\times$ 10$^{12}$ $L_{\odot}$, dust mass of 2.8 $\times$ 10$^9$ $M_{\odot}$, and V-band extinction of 4.0, which are all higher than those of the ALESS DSFGs. Based on the space density, SFR density, and stellar mass density estimates, we conclude that our ultrared sample cannot account for the majority of the star-forming progenitors of the massive, quiescent galaxies found in infrared surveys. Our sample contains the rarer, intrinsically most dusty, luminous and massive galaxies in the early universe that will help us understand the physical drivers of extreme star formation

Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH -Mutant Molecular Profiles

Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance

Analyses of pig genomes provide insight into porcine demography and evolution

For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars ∼1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model