Premise: In 1879, Dr. William Beal buried 20 glass bottles filled with seeds and sand at a single site at Michigan State University. The goal of the experiment was to understand seed longevity in the soil, a topic of general importance in ecology, restoration, conservation, and agriculture, by periodically assaying germinability of these seeds over 100 years.
View Article and Find Full Text PDFKASP is commonly used to genotype bi-allelic SNPs and In/Dels, and the standard protocol works well when both alleles are nearly equally prevalent in the DNA template. To detect rare alleles in bulked samples or to distinguish more than three genotypes, such as tri-allelic loci or mutations across orthologous genes in polyploids, adjustments to the protocol and/or data analysis are required. In this chapter, we present modified protocols for these non-traditional applications, including reaction conditions that enhance the fluorophore signal from rare alleles, resulting in increased KASP assay sensitivity.
View Article and Find Full Text PDFThymic stromal lymphopoietin (TSLP), an epithelial cell-derived cytokine, acts as a key mediator in airway inflammation and modulates the function of multiple cell types, including dendritic cells and group 2 innate lymphoid cells. TSLP plays a role in asthma pathogenesis as an upstream cytokine, and data suggest that TSLP blockade with the anti-TSLP monoclonal antibody, tezepelumab, could be efficacious in a broad asthma population. Currently approved asthma biologic therapies target allergic or eosinophilic disease and require phenotyping; therefore, an unmet need exists for a therapy that can address Type 2 (T2)-high and T2-low inflammation in asthma.
View Article and Find Full Text PDFRoot hair cells are important sensors of soil conditions. They grow towards and absorb water-soluble nutrients. This fast and oscillatory growth is mediated by continuous remodeling of the cell wall.
View Article and Find Full Text PDFBacterial spot, caused by Xanthomonas arboricola pv. pruni (Xap), is a serious peach disease with symptoms that traverse severe defoliation and black surface pitting, cracking or blemishes on peach fruit with global economic impacts. A management option for control and meeting consumer demand for chemical-free, environmentally friendly fruit production is the development of resistant or tolerant cultivars.
View Article and Find Full Text PDFA diaryl ketone series was identified as vanin-1 inhibitors from a high-throughput screening campaign. While this novel scaffold provided valuable probe that was used to build target confidence, concerns over the ketone moiety led to the replacement of this group. The successful replacement of this moiety was achieved with pyrimidine carboxamides derived from cyclic secondary amines that were extensively characterized using biophysical and crystallographic methods as competitive inhibitors of vanin-1.
View Article and Find Full Text PDFObjective: To investigate the role of PF-06650833, a highly potent and selective small-molecule inhibitor of interleukin-1-associated kinase 4 (IRAK4), in autoimmune pathophysiology in vitro, in vivo, and in the clinical setting.
Methods: Rheumatoid arthritis (RA) inflammatory pathophysiology was modeled in vitro through 1) stimulation of primary human macrophages with anti-citrullinated protein antibody immune complexes (ICs), 2) RA fibroblast-like synoviocyte (FLS) cultures stimulated with Toll-like receptor (TLR) ligands, as well as 3) additional human primary cell cocultures exposed to inflammatory stimuli. Systemic lupus erythematosus (SLE) pathophysiology was simulated in human neutrophils, dendritic cells, B cells, and peripheral blood mononuclear cells stimulated with TLR ligands and SLE patient ICs.
Indirect defenses are plant phenotypes that reduce damage by attracting natural enemies of plant pests and pathogens to leaves. Despite their economic and ecological importance, few studies have investigated the genetic underpinnings of indirect defense phenotypes. Here, we present a genome-wide association study of five phenotypes previously determined to increase populations of beneficial (fungivorous and predacious) mites on grape leaves (genus ): leaf bristles, leaf hairs, and the size, density, and depth of leaf domatia.
View Article and Find Full Text PDFPurpose: Bundled payments have been touted as mechanisms to optimize quality and costs. A recent feasibility study evaluating bundled payments for screening mammography episodes predated widespread adoption of digital breast tomosynthesis (DBT). We explore a similar model reflecting emerging acceptance of DBT in breast cancer screening.
View Article and Find Full Text PDFBackground And Aims: Determining seed longevity by identifying chemical changes that precede, and may be linked to, seed mortality, is an important but difficult task. The standard assessment, germination proportion, reveals seed longevity by showing that germination proportion declines, but cannot be used to predict when germination will be significantly compromised. Assessment of molecular integrity, such as RNA integrity, may be more informative about changes in seed health that precede viability loss, and has been shown to be useful in soybean.
View Article and Find Full Text PDFPatients often receive axillary ultrasound-biopsy (AUS-B) before clinical evaluation. One positive biopsy in the absence of palpable disease rarely indicates additional nodal involvement, but it eliminates patients from being managed by the American College of Surgeons Oncology Group Z0011 trial criteria. To determine which patients may benefit from AUS-B, we analyzed whether characteristics on AUS were associated with large-volume axillary disease and, thus, the need for axillary lymph node (LN) dissection.
View Article and Find Full Text PDFSeeds exist in the vulnerable state of being unable to repair the chemical degradation all organisms suffer, which slowly ages seeds and eventually results in death. Proposed seed aging mechanisms involve all classes of biological molecules, and degradation of total RNA has been detected contemporaneously with viability loss in dry-stored seeds. To identify changes specific to mRNA, we examined the soybean (Glycine max) seed transcriptome, using new, whole-molecule sequencing technology.
View Article and Find Full Text PDFRationale And Objectives: The present study aims to assess associations of Medicare beneficiary screening mammography rates with local mammography facility and radiologist availability.
Materials And Methods: Mammography screening rates for Medicare fee-for-service beneficiaries were obtained for US counties using the County Health Rankings data set. County-level certified mammography facility counts were obtained from the United States Food and Drug Administration.
Many diseases are believed to be driven by pathological levels of reactive oxygen species (ROS) and oxidative stress has long been recognized as a driver for inflammatory disorders. Apoptosis signal-regulating kinase 1 (ASK1) has been reported to be activated by intracellular ROS and its inhibition leads to a down regulation of p38-and JNK-dependent signaling. Consequently, ASK1 inhibitors may have the potential to treat clinically important inflammatory pathologies including renal, pulmonary and liver diseases.
View Article and Find Full Text PDFRationale And Objectives: To assess associations between screening mammography utilization and Medicare beneficiaries' relationships with, and impressions of, their primary care physicians.
Materials And Methods: Using the Medicare Current Beneficiary Survey Access to Care Public Use File, we retrospectively studied responses from a national random cross section of Medicare beneficiaries surveyed in 2013 regarding perceptions of their primary care physicians and their screening mammography utilization. Statistical analysis accounted for subject weighting factors to estimate national screening utilization.
Purpose: The 2015 conversion of the International Classification of Diseases (ICD) system from the ninth revision (ICD-9) to the 10th revision (ICD-10) was widely projected to adversely impact physician practices. We aimed to assess code conversion impact factor (CCIF) projections and revenue delay impact to help radiology groups better prepare for eventual conversion to ICD, 11th revision (ICD-11).
Methods: Studying 673,600 claims for 179 radiologists for the first year after ICD-10's implementation, we identified primary ICD-10 codes for the top 90th percentile of all examinations for the entire enterprise and each subspecialty division.
Interleukin-1 receptor-associated kinase 4 (IRAK4) plays a critical role in innate immune signaling by Toll-like receptors (TLRs), and loss of IRAK4 activity in mice and humans increases susceptibility to bacterial infections and causes defects in TLR and IL1 ligand sensing. However, the mechanism by which IRAK4 activity regulates the production of downstream inflammatory cytokines is unclear. Using transcriptomic and biochemical analyses of human monocytes treated with a highly potent and selective inhibitor of IRAK4, we show that IRAK4 kinase activity controls the activation of interferon regulatory factor 5 (IRF5), a transcription factor implicated in the pathogenesis of multiple autoimmune diseases.
View Article and Find Full Text PDFJ Am Coll Radiol
August 2017
Purpose: Prior studies have shown higher screening mammography rates for beneficiaries in capitated managed care Medicare Advantage (MA) plans compared with traditional fee-for-service Medicare. The aim of this study was to explore variation in screening mammography rates at the level of MA managed care plans.
Methods: Using the 2016 MA Healthcare Effectiveness Data and Information Set Public Use File, screening mammography rates were identified for all 385 reporting MA plans.
The invasive aquatic plant Eurasian watermilfoil ( L.) can hybridize with the related North American native species northern watermilfoil ( Kom.).
View Article and Find Full Text PDFBackground: Indaziflam is a cellulose-biosynthesis-inhibiting (CBI) herbicide that is a unique mode of action for resistance management and has broad spectrum activity at low application rates. This research further explores indaziflam's activity on monocotyledons and dicotyledons and evaluates indaziflam's potential for restoring non-crop sites infested with invasive winter annual grasses.
Results: Treated Arabidopsis, downy brome, feral rye and kochia were all susceptible to indaziflam in a dose-dependent manner.
This study investigates the relationship between germination ability and damage to RNA in soybean seeds (cv 'Williams 82') stored dry at 5 °C for 1-27 years. Total germination of 14 age cohorts harvested between 2015 and 1989 ranged from 100% to 3%. Germination decline followed classic seed viability kinetics, with symptomatic seed aging beginning after 17 years of storage.
View Article and Find Full Text PDF