High Connectivity in the Deepwater Snapper Pristipomoides filamentosus (Lutjanidae) across the Indo-Pacific with Isolation of the Hawaiian Archipelago

In the tropical Indo-Pacific, most phylogeographic studies have focused on the shallow-water taxa that inhabit reefs to approximately 30 m depth. Little is known about the large predatory fishes, primarily snappers (subfamily Etelinae) and groupers (subfamily Epinephelinae) that occur at 100–400 m. These long-lived, slow-growing species support fisheries across the Indo-Pacific, yet no comprehensive genetic surveys within this group have been conducted. Here we contribute the first range-wide survey of a deepwater Indo-Pacific snapper, Pristipomoides filamentosus, with special focus on Hawai'i. We applied mtDNA cytochrome b and 11 microsatellite loci to 26 samples (N = 1,222) collected across 17,000 km from Hawai'i to the western Indian Ocean. Results indicate that P. filamentosus is a highly dispersive species with low but significant population structure (mtDNA ΦST = 0.029, microsatellite FST = 0.029) due entirely to the isolation of Hawai'i. No population structure was detected across 14,000 km of the Indo-Pacific from Tonga in the Central Pacific to the Seychelles in the western Indian Ocean, a pattern rarely observed in reef species. Despite a long pelagic phase (60–180 days), interisland dispersal as adults, and extensive gene flow across the Indo-Pacific, P. filamentosus is unable to maintain population connectivity with Hawai'i. Coalescent analyses indicate that P. filamentosus may have colonized Hawai'i 26 K–52 K y ago against prevailing currents, with dispersal away from Hawai'i dominating migration estimates. P. filamentosus harbors low genetic diversity in Hawai'i, a common pattern in marine fishes, and our data indicate a single archipelago-wide stock. However, like the Hawaiian Grouper, Hyporthodus quernus, this snapper had several significant pairwise comparisons (FST) clustered around the middle of the archipelago (St. Rogatien, Brooks Banks, Gardner) indicating that this region may be isolated or (more likely) receives input from Johnston Atoll to the south

Systematic Identification of Novel, Essential Host Genes Affecting Bromovirus RNA Replication

Positive-strand RNA virus replication involves viral proteins and cellular proteins at nearly every replication step. Brome mosaic virus (BMV) is a well-established model for dissecting virus-host interactions and is one of very few viruses whose RNA replication, gene expression and encapsidation have been reproduced in the yeast Saccharomyces cerevisiae. Previously, our laboratory identified ∼100 non-essential host genes whose loss inhibited or enhanced BMV replication at least 3-fold. However, our isolation of additional BMV-modulating host genes by classical genetics and other results underscore that genes essential for cell growth also contribute to BMV RNA replication at a frequency that may be greater than that of non-essential genes. To systematically identify novel, essential host genes affecting BMV RNA replication, we tested a collection of ∼900 yeast strains, each with a single essential gene promoter replaced by a doxycycline-repressible promoter, allowing repression of gene expression by adding doxycycline to the growth medium. Using this strain array of ∼81% of essential yeast genes, we identified 24 essential host genes whose depleted expression reproducibly inhibited or enhanced BMV RNA replication. Relevant host genes are involved in ribosome biosynthesis, cell cycle regulation and protein homeostasis, among other cellular processes. BMV 2aPol levels were significantly increased in strains depleted for a heat shock protein (HSF1) or proteasome components (PRE1 and RPT6), suggesting these genes may affect BMV RNA replication by directly or indirectly modulating 2aPol localization, post-translational modification or interacting partners. Investigating the diverse functions of these newly identified essential host genes should advance our understanding of BMV-host interactions and normal cellular pathways, and suggest new modes of virus control

Structure and evolution of the plant cation diffusion facilitator family of ion transporters

Peer reviewedPublisher PD

A national survey of U.S. pharmacists in 2000: Assessing nonresponse bias of a survey methodology

The first objective of this study was to assess the existence of nonresponse bias to a national survey of licensed pharmacists conducted in 2000. Three methods were used to assess nonresponse bias. The second objective of the study was to examine reasons why sampled licensed pharmacists did not respond to the national survey of licensed pharmacists. We used data from 2204 respondents to a national survey of pharmacists and from 521 respondents to a survey of nonrespondents to the national survey. We made comparisons between respondents for 5 variables: employment status, gender, age, highest academic degree, and year of initial licensure. Chi-square tests were used to examine differences in the 5 variables between respondents to the first mailing and second mailing of the survey, early and late respondents to the survey, and respondents to the survey and respondents to the nonrespondent survey. There were no significant differences between first mailing and second mailing respondents, but there were differences in each variable except year of licensure between early and late respondents. These differences likely were due to regional bias possibly related to differences in mailing times. There were differences between respondents and nonrespondents in terms of employment status and year of licensure. The main reasons for not responding to the survey were that it was too long or that it was too intrusive. Overall, the survey methodology resulted in a valid sample of licensed pharmacists. Nonresponse bias should be assessed by surveying nonrespondents. Future surveys of pharmacists should consider the length of the survey and the address where it is sent

XIAP discriminates between type I and type II FAS-induced apoptosis

FAS (also called APO-1 and CD95) and its physiological ligand, FASL, regulate apoptosis of unwanted or dangerous cells, functioning as a guardian against autoimmunity and cancer development. Distinct cell types differ in the mechanisms by which the 'death receptor' FAS triggers their apoptosis. In type I cells, such as lymphocytes, activation of 'effector caspases' by FAS-induced activation of caspase-8 suffices for cell killing, whereas in type II cells, including hepatocytes and pancreatic beta-cells, caspase cascade amplification through caspase-8-mediated activation of the pro-apoptotic BCL-2 family member BID (BH3 interacting domain death agonist) is essential. Here we show that loss of XIAP (X-chromosome linked inhibitor of apoptosis protein) function by gene targeting or treatment with a second mitochondria-derived activator of caspases (SMAC, also called DIABLO; direct IAP-binding protein with low pI) mimetic drug in mice rendered hepatocytes and beta-cells independent of BID for FAS-induced apoptosis. These results show that XIAP is the critical discriminator between type I and type II apoptosis signalling and suggest that IAP inhibitors should be used with caution in cancer patients with underlying liver conditions