Juvenile Rockfish (Sebastes spp.) Community Composition and Habitat use of Yaquina Bay, Oregon

Estuaries, which provide viable habitat for a plethora of fish and invertebrate species, are being increasingly impacted by anthropogenic and natural forces. Estuaries are important nursery habitat for young-of-the-year (YOY) Pacific rockfish (Sebastes spp.). Yaquina Bay, a marine-dominated estuary on the central Oregon Coast, served as a study site for the estuarine use of juvenile rockfishes, and large numbers of juvenile rockfish have been captured in this bay. Nursery habitats must provide rearing habitat, adequate food resources and refuge. A vital but lacking connection in our understanding of estuaries as nursery habitat is how rockfishes use the different microhabitats within an estuarine ecosystem. As habitats structure biotic communities, determining the ecological requirements for juvenile rockfish habitats that minimize mortality, maximize growth and increase population numbers will assist managers and biologists in managing and protecting critical high-quality nursery areas. This study provides insight into Oregon rockfish life history, evaluating the spatial and temporal use of estuarine nursery habitat by juvenile rockfishes. The primary objectives were to (1) determine which species of rockfish utilize Yaquina Bay, (2) determine seasonal variations in abundance, and (3) assess the utilization of natural (eelgrass beds, Zostera marina) versus anthropogenic (piers) estuarine habitat. I conducted a mark-recapture study of juvenile rockfishes to begin to elucidate how these species may be using different habitats in the bay. This study provides evidence for the presence of previously undocumented rockfish species, the overwinter persistence of juvenile rockfish in the estuary, some degree of site fidelity, and apparent minimal movement of juvenile rockfish in the Yaquina Bay estuary during the period of this study, as well as a shift in rockfish community dominance from S. melanops to S. maliger and S. caurinus. The survival and recapture of juveniles in both natural (Z. marina) and anthropogenic (piers) habitat demonstrates rockfishes’ successful use of multiple Yaquina Bay habitat types as nursery grounds year-round. There is seasonal variability in rockfish use of the anthropogenic and natural habitat, with the anthropogenic habitats having an overall higher capture rate and a higher occurrence of larger rockfish. All eight species S. melanops, S. maliger, S. caurinus, S. paucispinis, S. flavidus, S. nebulosus, S. pinniger and S. auriculatus are present in the natural, Z. marina habitat. Sebastes pinniger and S. auriculatus are absent from anthropogenic, pier habitat. The implications of determining habitat parameters, community interactions, seasonal changes of the fish community, and ecosystem mechanisms may be invaluable to support further recreational and commercial fishing and help sustain or increase adult populations. My findings present a significant contribution towards the proper management and conservation of essential habitat for rockfish, a group of species with high commercial value and substantial recreational harvest

Evaluating Temporal Consistency in Marine Biodiversity Hotspots

With the ongoing crisis of biodiversity loss and limited resources for conservation, the concept of biodiversity hotspots has been useful in determining conservation priority areas. However, there has been limited research into how temporal variability in biodiversity may influence conservation area prioritization. To address this information gap, we present an approach to evaluate the temporal consistency of biodiversity hotspots in large marine ecosystems. Using a large scale, public monitoring dataset collected over an eight year period off the US Pacific Coast, we developed a methodological approach for avoiding biases associated with hotspot delineation. We aggregated benthic fish species data from research trawls and calculated mean hotspot thresholds for fish species richness and Shannon’s diversity indices over the eight year dataset. We used a spatial frequency distribution method to assign hotspot designations to the grid cells annually. We found no areas containing consistently high biodiversity through the entire study period based on the mean thresholds, and no grid cell was designated as a hotspot for greater than 50% of the time-series. To test if our approach was sensitive to sampling effort and the geographic extent of the survey, we followed a similar routine for the northern region of the survey area. Our finding of low consistency in benthic fish biodiversity hotspots over time was upheld, regardless of biodiversity metric used, whether thresholds were calculated per year or across all years, or the spatial extent for which we calculated thresholds and identified hotspots. Our results suggest that static measures of benthic fish biodiversity off the US West Coast are insufficient for identification of hotspots and that long-term data are required to appropriately identify patterns of high temporal variability in biodiversity for these highly mobile taxa. Given that ecological communities are responding to a changing climate and other environmental perturbations, our work highlights the need for scientists and conservation managers to consider both spatial and temporal dynamics when designating biodiversity hotspots

ER Stress Induces Anabolic Resistance in Muscle Cells through PKB-Induced Blockade of mTORC1

Anabolic resistance is the inability to increase protein synthesis in response to an increase in amino acids following a meal. One potential mediator of anabolic resistance is endoplasmic reticulum (ER) stress. The purpose of the present study was to test whether ER stress impairs the response to growth factors and leucine in muscle cells

Patterns and Variation in Benthic Biodiversity in a Large Marine Ecosystem

While there is a persistent inverse relationship between latitude and species diversity across many taxa and ecosystems, deviations from this norm offer an opportunity to understand the conditions that contribute to large-scale diversity patterns. Marine systems, in particular, provide such an opportunity, as marine diversity does not always follow a strict latitudinal gradient, perhaps because several hypothesized drivers of the latitudinal diversity gradient are uncorrelated in marine systems. We used a large scale public monitoring dataset collected over an eight year period to examine benthic marine faunal biodiversity patterns for the continental shelf (55–183 m depth) and slope habitats (184–1280 m depth) off the US West Coast (47°20′N—32°40′N). We specifically asked whether marine biodiversity followed a strict latitudinal gradient, and if these latitudinal patterns varied across depth, in different benthic substrates, and over ecological time scales. Further, we subdivided our study area into three smaller regions to test whether coast-wide patterns of biodiversity held at regional scales, where local oceanographic processes tend to influence community structure and function. Overall, we found complex patterns of biodiversity on both the coast-wide and regional scales that differed by taxonomic group. Importantly, marine biodiversity was not always highest at low latitudes. We found that latitude, depth, substrate, and year were all important descriptors of fish and invertebrate diversity. Invertebrate richness and taxonomic diversity were highest at high latitudes and in deeper waters. Fish richness also increased with latitude, but exhibited a hump-shaped relationship with depth, increasing with depth up to the continental shelf break, ~200 m depth, and then decreasing in deeper waters. We found relationships between fish taxonomic and functional diversity and latitude, depth, substrate, and time at the regional scale, but not at the coast-wide scale, suggesting that coast-wide patterns can obscure important correlates at smaller scales. Our study provides insight into complex diversity patterns of the deep water soft substrate benthic ecosystems off the US West Coast

The role of Lin28b in myeloid and mast cell differentiation and mast cell malignancy

Mast cells are critical components of the innate immune system and important for host 48 defense, allergy, autoimmunity, tissue regeneration, and tumor progression.Dysregulated 49 mastcell development leads to systemic mastocytosis, a clinically variable but often 50 devastating family of hematologic disorders. Here we report that induced expression of 51 Lin28, a heterochronic gene and pluripotency factor implicated in driving a fetal 52 hematopoietic program, caused mast cell accumulation in adult mice in target organs such 53 as the skin and peritoneal cavity. In vitro assays revealed a skewing of myeloid 54 commitment in LIN28B-­‐expressing hematopoietic progenitors, with increased levels of 55 LIN28B in common myeloid and basophil-­‐mast cell progenitors altering gene expression 56 patterns to favor cell fate choices that enhanced mast cell specification. In addition, 57 LIN28B-­‐induced mast cells appeared phenotypically and functionally immature, and in 58 vitro assays suggested a slowing of mast cell terminal differentiation in the context of 59 LIN28B upregulation. Finally, interrogation of human mast cell leukemia samples revealed 60 upregulation of LIN28B in abnormal mast cells from patients with systemic mastocytosis 61 (SM). This work identifies Lin28 as a novel regulator of innate immune function and a new 62 protein of interest in mast cell disease

Clonal Cytopenias of Undetermined Significance Are Common in Cytopenic Adults Evaluated for MDS in the National MDS Study

Introduction: Myelodysplastic syndromes (MDS) are a heterogenous group of blood disorders defined by peripheral cytopenia(s), bone marrow failure, morphological dysplasia, and risk of progression. To understand the genetic, epigenetic and biological factors associated with the initiation and progression of MDS, NHLBI created the National MDS Study (NCT02775383). This is a prospective cohort study conducted at 92 community hospitals and 29 academic centers enrolling patients undergoing diagnostic work up for suspected MDS or MDS/myeloproliferative neoplasm (MPN) overlap syndrome. Eligible patients have yet to receive any therapy directed at their cytopenias. Previously untreated cytopenic participants underwent centralized histopathology and data review at the time of enrollment for assignment into distinct subcategories: MDS, MDS/MPN overlap, AML, and Other. Targeted exon sequencing of 96 genes was performed using marrow specimens from the first 300 consecutive individuals in the study. Here we report the genetic mutations for this cohort. Methods: NovaSeq 6000 was used for deep sequencing at a mean coverage of 1,286X and mean breadth (bases covered at ≥100X) of 99.8%. Reads were aligned against build GRCh38 using BWA-MEM, and VarScan2 was used to detect SNVs and INDELS. Variants were filtered for those with an allele base quality of >25 in combination with rule-based and manual review criteria. Subjects in the Other category without an identified malignancy were considered clonal cytopenias of undetermined significance (CCUS) when a mutation or a clonal cytogenetic change was present. Fisher's exact and Wilcoxon rank sum tests in combination with Bonferroni correction were applied to compare groups. Results : A total of 350 putative nonsynonymous pathogenic variants in 36 genes with an allele frequency of >.05 were identified across 150 patients (50%). At least one variant was noted in the following proportion of individuals: 61/72 (85%) with MDS, 13/13 (100%) with MDS/MPN, 15/17 (88%) with AML, and 61/198 (31%) in the Other category, of which 48 were CCUS and 13 were other cancers. Two CCUS patients only had a cytogenetic abnormality. Table 1 shows the distribution of variants in each subcategory of patients for the most commonly mutated genes in our cohort of 300 subjects. Mutations in these genes were enriched in specific groups: SF3B1, STAG2,TP53, and ASXL1 in MDS; TET2 in MDS/MPN; and IDH2 and TP53 in AML (one-sided p<0.0012). None were enriched in the Other group. Within the CCUS subset, 21 genes were mutated, with 37 of 50 (74%) patients having a mutation in TET2, ASXL1, SRSF2, SF3B1, or DNMT3A. The heatmap presented in Figure 1 summarizes variants by subject and allele frequency. Pair-wise comparisons of baseline characteristics of subjects between MDS, MDS/MPN, AML, or CCUS groups revealed no significant differences for age or sex. The CCUS group had significantly higher hemoglobins than the MDS group with median hemoglobin levels of 11.35 and 9.40 g/dL, respectively (p 110x109/L , respectively, p<0.0084). All groups significantly differed in their median ANC with AML having the lowest (0.8x109/L), followed by MDS (1.5x109/L), CCUS (2.45x109/L), and MDS/MPN overlap (5.95x109/L) (p<0.0084). There was no difference in the median number of variants per patient between groups or correlation with age (rs=0.11, p=0.18). The maximum variant allele frequency (maxVAF) per patient was highest in the MDS/MPN group (median = 0.42, range = 0.38-0.91) and lowest in the CCUS group (median = 0.37, range =0.06-0.98) with the MDS/MPN group having a significantly higher maxVAF compared to the MDS and the CCUS groups (p<0.0084). The proportions of subjects with mutations was similar for those who had abnormal (92% [34/37]) and normal (91% [80/88]) cytogenetics. Conclusions: Incorporation of gene-panel sequencing in the comprehensive evaluation of 300 adult cytopenic patients identified half of the cohort with potentially pathogenic variants. Ultimately, a diagnosis of CCUS was possible in 48 of 183 subjects (26%) not diagnosed with MDS, MDS/MPN overlap syndrome, AML, other cancers or clonal cytogenetics. This study continues to serially bank samples from patients with CCUS, in addition to MDS, MDS/MPN, and ICUS, with the goal to better understand the natural history of these diseases and their progression. Disclosures Lindsley: Jazz Pharmaceuticals: Research Funding; Takeda Pharmaceuticals: Consultancy; Medlmmune: Research Funding. Bejar:Celgene: Consultancy; Takeda Pharmaceuticals: Research Funding; AbbVie/Genentech: Consultancy, Honoraria; Astex/Otsuka: Consultancy; Modus Outcomes: Consultancy; Daiichi-Sankyo: Consultancy. Al Baghdadi:Celgene: Consultancy, Honoraria; Heron: Consultancy, Honoraria; Tracon: Equity Ownership; Epizyme: Equity Ownership; Bristol Myer Squibb: Consultancy, Honoraria; Sunesis: Equity Ownership; Portola: Equity Ownership; Heron therapeutics: Equity Ownership; Cardinal health: Consultancy, Honoraria; Bristol Myer Squibb: Equity Ownership; Celgene: Equity Ownership; Spectrum pharmaceutical: Equity Ownership; Astrazeneca: Equity Ownership; Seattle genetics: Equity Ownership; Roche: Consultancy, Honoraria. DeZern:Astex Pharmaceuticals, Inc.: Consultancy; Celgene: Consultancy. Foran:Agios: Honoraria, Research Funding. Gore:Celgene Corporation: Consultancy, Research Funding. Komrokji:DSI: Consultancy; Agios: Consultancy; Novartis: Speakers Bureau; JAZZ: Speakers Bureau; pfizer: Consultancy; celgene: Consultancy; Incyte: Consultancy; JAZZ: Consultancy. Maciejewski:Alexion: Consultancy; Novartis: Consultancy. Starczynowski:Kurome Therapeutics: Consultancy. Sekeres:Millenium: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees