Variations in eastern North Pacific demersal fish biomass based on the U.S. west coast groundfish bottom trawl survey (2003–2010)

In response to declining biomass of Northeast Pacific groundfish in the late 1990s and to improve the scientific basis for management of the fishery, the Northwest Fisheries Science Center standardized and enhanced their annual bottom trawl survey in 2003. The survey was expanded to include the entire area along the U.S. west coast at depths of 55–1280 m. Coast-wide biomass and species richness significantly decreased during the first eight years (2003–10) of this fishery-independent survey. We observed an overall tendency toward declining biomass for 62 dominant taxa combined (fishery target and nontarget species) and four of seven subgroups (including cartilaginous fish, flatfishes, shelf rockfishes, and other shelf species), despite increasing or variable biomass trends in individual species. These decreases occurred during a period of reduced catch for groundfish along the shelf and upper slope regions relative to historical rates. We used information from multiple stock assessments to aggregate species into three groups: 1) with strong recruitment, 2) without strong recruitment in 1999, and 3) with unknown recruitment level. For each group, we evaluated whether declining biomass was primarily related to depletion (using year as a proxy) or environmental factors (i.e., variation in the Pacific Decadal Oscillation). According to Akaike’s information criterion, changes in aggregate biomass for species with strong recruitment were more closely related to year, whereas those with no strong recruitment were more closely related to climate. The significant decline in biomass for species without strong recruitment confirms that factors other than depletion of the exceptional 1999 year class may be responsible for the observed decrease in biomass along the U.S. west coast

Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.

Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

A novel Alzheimer disease locus located near the gene encoding tau protein

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordAPOE ε4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ε4+ (10 352 cases and 9207 controls) and APOE ε4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ε4 status. Suggestive associations (P<1 × 10-4) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ε4+: 1250 cases and 536 controls; APOE ε4-: 718 cases and 1699 controls). Among APOE ε4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10-9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ε4+ subjects (CR1 and CLU) or APOE ε4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10-7) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P≤1.3 × 10-8), frontal cortex (P≤1.3 × 10-9) and temporal cortex (P≤1.2 × 10-11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10-6) and temporal cortex (P=2.6 × 10-6). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ε4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted

Large-Scale Genotyping-by-Sequencing Indicates High Levels of Gene Flow in the Deep-Sea Octocoral <i>Swiftia simplex</i> (Nutting 1909) on the West Coast of the United States

<div><p>Deep-sea corals are a critical component of habitat in the deep-sea, existing as regional hotspots for biodiversity, and are associated with increased assemblages of fish, including commercially important species. Because sampling these species is so difficult, little is known about the connectivity and life history of deep-sea octocoral populations. This study evaluates the genetic connectivity among 23 individuals of the deep-sea octocoral <i>Swiftia simplex</i> collected from Eastern Pacific waters along the west coast of the United States. We utilized high-throughput restriction-site associated DNA (RAD)-tag sequencing to develop the first molecular genetic resource for the deep-sea octocoral, <i>Swiftia simplex</i>. Using this technique we discovered thousands of putative genome-wide SNPs in this species, and after quality control, successfully genotyped 1,145 SNPs across individuals sampled from California to Washington. These SNPs were used to assess putative population structure across the region. A STRUCTURE analysis as well as a principal coordinates analysis both failed to detect any population differentiation across all geographic areas in these collections. Additionally, after assigning individuals to putative population groups geographically, no significant F_ST values could be detected (F_ST for the full data set 0.0056), and no significant isolation by distance could be detected (p = 0.999). Taken together, these results indicate a high degree of connectivity and potential panmixia in <i>S</i>. <i>simplex</i> along this portion of the continental shelf.</p></div

Maximum parsimony phylogeny obtained with the <i>MutS</i> sequence.

<p>The arrow indicates the branch containing all <i>S</i>. <i>simplex</i> individuals. Additional species are from our voucher collection (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0165279#pone.0165279.s002" target="_blank">S1 Table</a>). Colored dots after each individual correspond to putative population groupings indicated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0165279#pone.0165279.g001" target="_blank">Fig 1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0165279#pone.0165279.t001" target="_blank">Table 1</a>. Numbers at branch nodes are bootstrap values from 1,000 replicates. While there are four haplotypes of <i>S</i>. <i>simplex</i>, there is no correspondence with geographic grouping. Branch lengths are not scaled.</p

Principal components analysis on RAD-tag genotypes.

<p>Colors correspond to putative geographic population groupings in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0165279#pone.0165279.g001" target="_blank">Fig 1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0165279#pone.0165279.t001" target="_blank">Table 1</a>. A. Includes all 23 individuals. The three outliers are the three individuals with the most missing loci. PC1 and PC2 explain 10.5% and 5.5% of the total variance respectively. B. PCA after removing the three individuals with excess missing markers. The separations along PC1 in both cases are driven by missing genotypes. After removal PC1 and PC2 explain 6.7% and 6.6% of the variance.</p

Map of collection locations for all 29 individuals initially included in this study.

<p>Colored triangles indicate individuals included in the population analysis, with the individual colors representing putative geographic populations. Population one individuals are red, two are gold, three are blue and four are green. White circles are individuals that failed to pass quality control and were excluded from the population analysis.</p

Collection metadata for the twenty-nine individuals initially included in this study.

<p>Collection metadata for the twenty-nine individuals initially included in this study.</p

AMOVA between putative populations.

<p>AMOVA between putative populations.</p