Impact of insecticide programs on pests, the predatory mite Phytoseiulus persimilis, and staked tomato profitability.

Background: Various insecticides are available to manage diverse pest complexes in commercial vegetable production, but knowledge gaps exist regarding their overall performance in pest suppression, profitability, and compatibility with biological control. We conducted trials in staked tomatoes in western North Carolina in 2017-2018 to compare how different insecticide programs managed key pests and their interactions with Phytoseiulus persimilis Athias-Henriot, a predator of the twospotted spider mite (TSSM, Tetranychus urticae Koch). Treatments compared no insecticides to broad-spectrum ('hard') foliar applications, selective ('soft') foliar applications, and to chemigation of selective systemic insecticides.

Banks Grass Mite (Acari: Tetranychidae) Suppression May Add to the Benefit of Drought-Tolerant Corn Hybrids Exposed to Water Stress.

Spider mite (Acari: Tetranychidae) outbreaks are common on corn grown in the arid West. Hot and dry conditions reduce mite development time, increase fecundity, and accelerate egg hatch. Climate change is predicted to increase drought incidents and produce more intense temperature patterns.

Cerambycid Communities and Their Associated Hymenopteran Parasitoids From Major Hardwood Trees in Delaware: Implications for Biocontrol of Invasive Longhorned Beetles.

Cerambycidae provide important ecological services in forests yet cause economic damage when they infest living trees. Parasitoids can regulate woodborer populations, providing considerable control of pest cerambycids. Identifying parasitoids of native cerambycids may be useful in managing cerambycid outbreaks and aid in new-association biocontrol of exotic invasive cerambycids.

Rational Design of 5-(4-(Isopropylsulfonyl)phenyl)-3-(3-(4-((methylamino)methyl)phenyl)isoxazol-5-yl)pyrazin-2-amine (VX-970, M6620): Optimization of Intra- and Intermolecular Polar Interactions of a New Ataxia Telangiectasia Mutated and Rad3-Related (ATR) Kinase Inhibitor.

The DNA damage response (DDR) is a DNA damage surveillance and repair mechanism that can limit the effectiveness of radiotherapy and DNA-damaging chemotherapy, commonly used treatment modalities in cancer. Two related kinases, ataxia telangiectasia mutated (ATM) and ATM and Rad3-related kinase (ATR), work together as apical proteins in the DDR to maintain genome stability and cell survival in the face of potentially lethal forms of DNA damage. However, compromised ATM signaling is a common characteristic of tumor cells, which places greater reliance on ATR to mediate the DDR.

Effects of Legume Species and Plant Growth Stage on Attraction, Fecundity, and Development of the Kudzu Bug (Heteroptera: Plataspidae).

The kudzu bug, Megacopta cribraria (F.) (Heteroptera: Plataspidae), is an invasive pest of soybeans in the southeastern United States. Two greenhouse choice assays evaluated crop species and growth stage-specific orientation preference of kudzu bug adults to six different legume species (Fabales: Fabaceae) at four plant growth stages (V2, V4, R1, and R5).

Influence of Temperature on the Reproductive and Developmental Biology of Ontsira mellipes (Hymenoptera: Braconidae): Implications for Biological Control of the Asian Longhorned Beetle (Coleoptera: Cerambycidae).

Ontsira mellipes Ashmead (Hymenoptera: Braconidae) is a North American parasitoid species that develops on the invasive pest, Anoplophora glabripennis (Moltschulsky) (Coleoptera: Cerambycidae), under laboratory conditions and is currently being considered as a potential new-association biocontrol agent. To develop mass-rearing protocols and field-release strategies for this parasitoid, information on its reproductive biology in relation to temperature is needed. We determined the effect of temperature (10, 15, 20, 25, and 30 °C) on development, survivorship, and sex ratio, and its effect on the longevity, fecundity, and host attack rates (parasitism) of adults.

Life History, Reproductive Biology, and Larval Development of Ontsira mellipes (Hymenoptera: Braconidae), a Newly Associated Parasitoid of the Invasive Asian Longhorned Beetle (Coleoptera: Cerambycidae).

The invasive Asian longhorned beetle, Anoplophora glabripennis (Motschulsky), is a destructive xylophagous forest pest species originating from Asia. Several endemic North American hymenopteran (Braconidae) species in the mid-Atlantic region were capable of attacking and reproducing on A. glabripennis larvae in laboratory bioassays.

Clinical development of new drug-radiotherapy combinations.

In countries with the best cancer outcomes, approximately 60% of patients receive radiotherapy as part of their treatment, which is one of the most cost-effective cancer treatments. Notably, around 40% of cancer cures include the use of radiotherapy, either as a single modality or combined with other treatments. Radiotherapy can provide enormous benefit to patients with cancer.

Potentiation of tumor responses to DNA damaging therapy by the selective ATR inhibitor VX-970.

Platinum-based DNA-damaging chemotherapy is standard-of-care for most patients with lung cancer but outcomes remain poor. This has been attributed, in part, to the highly effective repair network known as the DNA-damage response (DDR). ATR kinase is a critical regulator of this pathway, and its inhibition has been shown to sensitize some cancer, but not normal, cells in vitro to DNA damaging agents.

Structure of human Bloom's syndrome helicase in complex with ADP and duplex DNA.

Bloom's syndrome is an autosomal recessive genome-instability disorder associated with a predisposition to cancer, premature aging and developmental abnormalities. It is caused by mutations that inactivate the DNA helicase activity of the BLM protein or nullify protein expression. The BLM helicase has been implicated in the alternative lengthening of telomeres (ALT) pathway, which is essential for the limitless replication of some cancer cells.

Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR.

Here we report a comprehensive biological characterization of a potent and selective small-molecule inhibitor of the DNA damage response (DDR) kinase ATR. We show a profound synthetic lethal interaction between ATR and the ATM-p53 tumor suppressor pathway in cells treated with DNA-damaging agents and establish ATR inhibition as a way to transform the outcome for patients with cancer treated with ionizing radiation or genotoxic drugs.

Discovery of potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase as potential anticancer agents.

DNA-damaging agents are among the most frequently used anticancer drugs. However, they provide only modest benefit in most cancers. This may be attributed to a genome maintenance network, the DNA damage response (DDR), that recognizes and repairs damaged DNA.

VX-166: a novel potent small molecule caspase inhibitor as a potential therapy for sepsis.

Introduction: Prevention of lymphocyte apoptosis by caspase inhibition has been proposed as a novel treatment approach in sepsis. However, it has not been clearly demonstrated that caspase inhibitors improve survival in sepsis models when dosed post-insult. Also, there are concerns that caspase inhibitors might suppress the immune response.

The discovery of the potent aurora inhibitor MK-0457 (VX-680).

The identification of a novel series of Aurora kinase inhibitors and exploitation of their SAR is described. Replacement of the initial quinazoline core with a pyrimidine scaffold and modification of substituents led to a series of very potent inhibitors of cellular proliferation. MK-0457 (VX-680) has been assessed in Phase II clinical trials in patients with treatment-refractory chronic myelogenous leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) containing the T315I mutation.

VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo.

The Aurora kinases are essential for the regulation of chromosome segregation and cytokinesis during mitosis. Aberrant expression and activity of these kinases occur in a wide range of human tumors, and lead to aneuploidy and tumorigenesis. Here we report the discovery of a highly potent and selective small-molecule inhibitor of Aurora kinases, VX-680, that blocks cell-cycle progression and induces apoptosis in a diverse range of human tumor types.

Novel inhibitors of plasminogen activator inhibitor-1: development of new templates from diketopiperazines.

Several isoquinoline-based templates were identified from the studies of the conformational effects of the diketopiperazine structures for PAI-1 inhibition. Moderate to good activity was retained with the elimination of unattractive characteristics in the diketopiperazine template.

Design, synthesis and in vitro evaluation of potent, novel, small molecule inhibitors of plasminogen activator inhibitor-1.

We have synthesized and evaluated a series of tetramic acid-based and hydroxyquinolinone-based inhibitors of plasminogen activator inhibitor-1 (PAI-1). These studies resulted in the identification of several compounds which showed excellent potency against PAI-1. The design, synthesis and SAR of these compounds are described.