Juvenile River Herring in Freshwater Lakes: Sampling Approaches for Evaluating Growth and Survival

River herring, collectively alewives (Alosa pseudoharengus) and blueback herring (A. aestivalis), have experienced substantial population declines over the past five decades due in large part to overfishing, combined with other sources of mortality, and disrupted access to critical freshwater spawning habitats. Anadromous river herring populations are currently assessed by counting adults in rivers during upstream spawning migrations, but no field-based assessment methods exist for estimating juvenile densities in freshwater nursery habitats. Counts of 4-year-old migrating adults are variable and prevent understanding about how mortality acts on different life stages prior to returning to spawn (e.g., juveniles and immature adults in lakes, rivers, estuaries, and oceans). This in turn makes it challenging to infer a link between adult counts and juvenile recruitment and to develop effective management policy. I used a pelagic purse seine to investigate juvenile river herring densities, growth, and mortality across 16 New England lakes. First, I evaluated the effectiveness and sampling precision of a pelagic purse seine for capturing juvenile river herring in lakes, since this sampling gear has not been systematically tested. Sampling at night in June or July resulted in highest catches. Precision, as measured by the coefficient of variation, was lowest in July (0.23) compared to June (0.32), August (0.38), and September (0.61). Simulation results indicated that the effort required to produce precise density estimates is largely dependent on lake size with small lakes (\u3c50 \u3eha) requiring up to 10 purse seine hauls and large lakes (\u3e50 ha) requiring 15–20 hauls. These results suggested that juvenile recruitment densities can be effectively measured using a purse seine at night in June or July with 10–20 hauls. Using juvenile fishes captured during purse seining in June–September 2015, I calculated growth and mortality rates from sagittal otoliths. Density, growth, and mortality were highly variable among lakes, and mixed-effects regression models explained 11%–76% of the variance in these estimates. Juvenile densities ranged over an order of magnitude and were inversely related to dissolved organic carbon. Juvenile growth rates were higher in productive systems (i.e., low secchi depth, high nutrients) and were strongly density-dependent, leading to much larger fish at age in productive lakes with low densities of river herring compared to high density lakes. Water temperature explained 56%–85% of the variation in juvenile growth rates during the first 30 days of life. Mortality was positively related to total phosphorous levels and inversely related to hatch date, with earlier hatching cohorts experiencing higher mortality. These results indicate the importance of water quality and juvenile densities in nursery habitats for determining juvenile growth and survival. This study encourages future assessments of juvenile river herring in freshwater and contributes to an understanding of factors explaining juvenile recruitment that can guide more effective and comprehensive management of river herring

Preventing Construct Subsidence Following Cervical Corpectomy: The Bump-stop Technique

Cervical corpectomy is a viable technique for the treatment of multilevel cervical spine pathology. Despite multiple advances in both surgical technique and implant technology, the rate of construct subsidence can range from 6% for single-level procedures to 71% for multilevel procedures. In this technical note, we describe a novel technique, the bump-stop technique, for cervical corpectomy. The technique positions the superior and inferior screw holes such that the vertebral bodies bisect them. This allows for fixation in the dense cortical bone of the endplate while providing a buttress to corpectomy cage subsidence. We then discuss a retrospective case review of 24 consecutive patients, who were treated using this approach, demonstrating a lower than previously reported cage subsidence rate

T granules in human platelets function in TLR9 organization and signaling

Human and murine platelets (PLTs) variably express toll-like receptors (TLRs), which link the innate and adaptive immune responses during infectious inflammation and atherosclerotic vascular disease. In this paper, we show that the TLR9 transcript is specifically up-regulated during pro-PLT production and is distributed to a novel electron-dense tubular system-related compartment we have named the T granule. TLR9 colocalizes with protein disulfide isomerase and is associated with either VAMP 7 or VAMP 8, which regulates its distribution in PLTs on contact activation (spreading). Preincubation of PLTs with type IV collagen specifically increased TLR9 and CD62P surface expression and augmented oligodeoxynucleotide (ODN) sequestration and PLT clumping upon addition of bacterial/viral ODNs. Collectively, this paper (a) tracks TLR9 to a new intracellular compartment in PLTs and (b) describes a novel mechanism of TLR9 organization and signaling in human PLTs

Cytoskeletal mechanics of proplatelet maturation and platelet release

New steps in the process of conversion of proplatelet extensions from megakaryocytes into mature platelets are defined

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment