Vertical Distribution, Persistence, and Activity of Entomopathogenic Nematodes (Nematoda: Heterorhabditidae and Steinernematidae) in Alfalfa Snout Beetle- (Coleoptera: Curculionidae) Infested Fields

The vertical movement, persistence, and activity of four isolates of entomopathogenic nematodes, Heterorhabditis bacteriophora Poinar (Oswego), Heterorhabditis bacteriophora Poinar (NC), Steinernema carpocapsae (Weiser) (NY001),and an undescribed Steinernema species (NY008-2E), were evaluated for 24 mo at field locations in northern New York. Nematodes were released into three alfalfa fields naturally infested with alfalfa snout beetle, Otiorhynchus ligustici (L.). Each field differed in soil type and soil textural composition: silt loam, sandy loam, and loamy sand. Nematodes were recovered from soil using trap insects, Galleria mellonella larvae, and their vertical distribution was monitored at 5-cm intervals to depths of 20 cm for Steinernena species and 35 cm for Heterorhabditis species. All nematodes persisted (no significant reduction in percentage of infection of G. mellonella) for 6 mo after the initial application in all soil types. However, by the end of the second growing season (17 mo after application), all nematodes showed significant reductions in infection rates of G. mellonella except H. bacteriophora (Oswego) which showed high levels of infection for 24 mo. Nematode vertical movement was affected by soil type and varied by isolate. S. carpocapsae (NY00l)and Steinernema sp. (NY008-2E) remained primarily in soil depths <15 cm, whereas both heterorhabditids dispersed to soil depths of 35 cm. Vertical movement of H. bacteriophera (Oswego) was greatest in loamy sand and vertical movement of Steinernema sp. (NY008-2E) was greatest in sandy loam. Percentage of infection of G. mellonella by H. bacteriophora (Oswego) and S. carpocapsae (NY00l)was significantly correlated with rising soil temperatures in early spring. H. bacteriophora (Oswego) and S. carpocapsae (NYOOl)infected G. mellonella larvae in the field at soil temperatures between 15 and 18°C. Steinernema sp. (NY008-2E)infected G. mellonella larvae in the field at soil temperatures between 13 and 15°

Greenhouse and Field Evaluations of Entomopathogenic Nematodes (Nematode: Heterorhabditidae and Steinernematidae) for Control of Cabbage Maggot (Diopters: Anthomyiidae) on Cabbage

Entomb pathogenic nematodes-Heterorhabditis bacteriophora Poinar (Oswego strain), Steinenema carpocapsae (Weiser) (NY001 strain), Steinemema carpocapsae (25 strain), Steinemema feltiae Filipjev (=Neoaplectana carpocapsae Weiser) (369 strain), Steinernema feltiae (27 strain), and Steinernema riobravus Cabanillas and Poinar (355 strain)-were examined for pathogenicity against cabbage maggot, Delia radicum (L.), larvae in the greenhouse and field. Applications (per plant) of 3,000 and 4,000 infective juveniles of S. feltiae (369 strain), 30,000 infective juveniles of H. bacteriophora (Oswego strain), and 300 and 30,000 infective juveniles of S. feltiae (27 strain) reduced the number of D. radicum that developed to pupae on potted cabbage plants. H. bacteriophora (Oswego) at applications of 3,000 and 30,000 infective juveniles per plant and S. feltiae (27 strain) at applications of 30,000 (but not 3,000) infective juveniles per plant significantly reduced root damage caused by larvae of D. radicum. Logarithmically increased dosages between 100 and 100,000 infective juveniles per plant of S. feltiae (27 strain) linearly reduced the number of D. radicum pupae that developed on potted cabbage plants and the damage caused to the roots by D. radicullarvae. Root and stem dry weights of cabbage plants infested with D. radicum were significantly greater for plants inoculated with 100,000 infective juveniles of S. feltiae (27 strain) than for plants not inoculated with nematodes. Nematode inoculation did not prevent significant losses in root or stem dry weights at dosages less than 100,000 infective juveniles per plant. Soil surface applications of 100,000 and 200,000 infective juveniles per plant of S. feltiae (27 strain) were more effective than subsurface applications in preventing damage by natural or augmented populations of D. radicum larvae on cabbage in the field. However, mortality rates of wax moth larvae exposed to soil samples treated with S. feltiae (27 strain) suggested that this nematode showed greater persistence when applied beneath rather than on the soil surfac

Vacuolar and plasma membrane stripping and autophagic elimination of Toxoplasma gondii in primed effector macrophages

Apicomplexan protozoan pathogens avoid destruction and establish a replicative niche within host cells by forming a nonfusogenic parasitophorous vacuole (PV). Here we present evidence for lysosome-mediated degradation of Toxoplasma gondii after invasion of macrophages activated in vivo. Pathogen elimination was dependent on the interferon γ inducible-p47 GTPase, IGTP, required PI3K activity, and was preceded by PV membrane indentation, vesiculation, disruption, and, surprisingly, stripping of the parasite plasma membrane. Denuded parasites were enveloped in autophagosome-like vacuoles, which ultimately fused with lysosomes. These observations outline a series of mechanisms used by effector cells to redirect the fate of a classically nonfusogenic intracellular pathogen toward a path of immune elimination

The EphB4 Receptor Tyrosine Kinase Promotes Lung Cancer Growth: A Potential Novel Therapeutic Target

Despite progress in locoregional and systemic therapies, patient survival from lung cancer remains a challenge. Receptor tyrosine kinases are frequently implicated in lung cancer pathogenesis, and some tyrosine kinase inhibition strategies have been effective clinically. The EphB4 receptor tyrosine kinase has recently emerged as a potential target in several other cancers. We sought to systematically study the role of EphB4 in lung cancer. Here, we demonstrate that EphB4 is overexpressed 3-fold in lung tumors compared to paired normal tissues and frequently exhibits gene copy number increases in lung cancer. We also show that overexpression of EphB4 promotes cellular proliferation, colony formation, and motility, while EphB4 inhibition reduces cellular viability in vitro, halts the growth of established tumors in mouse xenograft models when used as a single-target strategy, and causes near-complete regression of established tumors when used in combination with paclitaxel. Taken together, these data suggest an important role for EphB4 as a potential novel therapeutic target in lung cancer. Clinical trials investigating the efficacy of anti-EphB4 therapies as well as combination therapy involving EphB4 inhibition may be warranted.</p

Comprehensive genetic diagnosis of tandem repeat expansion disorders with programmable targeted nanopore sequencing

More than 50 neurological and neuromuscular diseases are caused by short tandem repeat (STR) expansions, with 37 different genes implicated to date. We describe the use of programmable targeted long-read sequencing with Oxford Nanopore's ReadUntil function for parallel genotyping of all known neuropathogenic STRs in a single assay. Our approach enables accurate, haplotype-resolved assembly and DNA methylation profiling of STR sites, from a list of predetermined candidates. This correctly diagnoses all individuals in a small cohort (n = 37) including patients with various neurogenetic diseases (n = 25). Targeted long-read sequencing solves large and complex STR expansions that confound established molecular tests and short-read sequencing and identifies noncanonical STR motif conformations and internal sequence interruptions. We observe a diversity of STR alleles of known and unknown pathogenicity, suggesting that long-read sequencing will redefine the genetic landscape of repeat disorders. Last, we show how the inclusion of pharmacogenomic genes as secondary ReadUntil targets can further inform patient care

Evaluation Research and Institutional Pressures: Challenges in Public-Nonprofit Contracting

This article examines the connection between program evaluation research and decision-making by public managers. Drawing on neo-institutional theory, a framework is presented for diagnosing the pressures and conditions that lead alternatively toward or away the rational use of evaluation research. Three cases of public-nonprofit contracting for the delivery of major programs are presented to clarify the way coercive, mimetic, and normative pressures interfere with a sound connection being made between research and implementation. The article concludes by considering how public managers can respond to the isomorphic pressures in their environment that make it hard to act on data relating to program performance.This publication is Hauser Center Working Paper No. 23. The Hauser Center Working Paper Series was launched during the summer of 2000. The Series enables the Hauser Center to share with a broad audience important works-in-progress written by Hauser Center scholars and researchers

LSST: from Science Drivers to Reference Design and Anticipated Data Products

(Abridged) We describe here the most ambitious survey currently planned in the optical, the Large Synoptic Survey Telescope (LSST). A vast array of science will be enabled by a single wide-deep-fast sky survey, and LSST will have unique survey capability in the faint time domain. The LSST design is driven by four main science themes: probing dark energy and dark matter, taking an inventory of the Solar System, exploring the transient optical sky, and mapping the Milky Way. LSST will be a wide-field ground-based system sited at Cerro Pach\'{o}n in northern Chile. The telescope will have an 8.4 m (6.5 m effective) primary mirror, a 9.6 deg$^2$ field of view, and a 3.2 Gigapixel camera. The standard observing sequence will consist of pairs of 15-second exposures in a given field, with two such visits in each pointing in a given night. With these repeats, the LSST system is capable of imaging about 10,000 square degrees of sky in a single filter in three nights. The typical 5$\sigma$ point-source depth in a single visit in $r$ will be $\sim 24.5$ (AB). The project is in the construction phase and will begin regular survey operations by 2022. The survey area will be contained within 30,000 deg$^2$ with $\delta<+34.5^\circ$, and will be imaged multiple times in six bands, $ugrizy$, covering the wavelength range 320--1050 nm. About 90\% of the observing time will be devoted to a deep-wide-fast survey mode which will uniformly observe a 18,000 deg$^2$ region about 800 times (summed over all six bands) during the anticipated 10 years of operations, and yield a coadded map to $r\sim27.5$. The remaining 10\% of the observing time will be allocated to projects such as a Very Deep and Fast time domain survey. The goal is to make LSST data products, including a relational database of about 32 trillion observations of 40 billion objects, available to the public and scientists around the world.Comment: 57 pages, 32 color figures, version with high-resolution figures available from https://www.lsst.org/overvie

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

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