Pallesenmckinney2952

Finally, we propose a model for the control of petal size in rapeseed through ethylene and cytokinin signaling pathways. Our results provide insights into the genetic mechanisms regulating petal size in flowering plants.

Shift work is associated with increased cardiometabolic disease risk. This observation may be partly explained by cardiometabolic risk factors having a role in the selection of individuals into or out of shift work. We performed Mendelian randomization (MR) analyses in the UK Biobank (UKB) to test this hypothesis.

We used genetic risk scores (GRS) to proxy nine cardiometabolic risk factors and diseases (including educational attainment, body mass index (BMI), smoking, and alcohol consumption), and tested associations of each GRS with self-reported frequency of current shift work among employed UKB participants of European ancestry (n = 190573). We used summary-level MR sensitivity analyses to assess robustness of the identified effects, and we tested whether effects were mediated through sleep timing preference.

Genetically instrumented liability to lower educational attainment (odds ratio (OR) per 3.6 fewer years in educational attainment = 2.40, 95% confidence interval (CI) = 2.22-2.59, P = 4.84 × 10-20) and higher body mass index (OR per 4.7 kg/m2 higher BMI = 1.30, 95% CI = 1.14-1.47, P = 5.85 × 10-5) increased odds of reporting participation in frequent shift work. Results were unchanged in sensitivity analyses allowing for different assumptions regarding horizontal pleiotropy. No selection effects were evident for the remaining exposures, nor for any exposures on selection out of shift work. Sleep timing preference did not mediate the effects of BMI and educational attainment on selection into shift work.

Liability to lower educational attainment and higher BMI may influence selection into shift work. This phenomenon may bias epidemiological studies of shift work that are performed in the UKB.

Liability to lower educational attainment and higher BMI may influence selection into shift work. This phenomenon may bias epidemiological studies of shift work that are performed in the UKB.Maternal and perinatal death surveillance and response (MPDSR), or any form of maternal and/or perinatal death review or audit, aims to improve health services and pre-empt future maternal and perinatal deaths. With expansion of MPDSR across low- and middle-income countries (LMIC), we conducted a scoping review to identify and describe implementation factors and their interactions. The review adapted an implementation framework with four domains (intervention, individual, inner and outer settings) and three cross-cutting health systems lenses (service delivery, societal and systems). Literature was sourced from six electronic databases, online searches and key experts. Selection criteria included studies from LMIC published in English from 2004 to July 2018 detailing factors influencing implementation of MPDSR, or any related form of MPDSR. After a systematic screening process, data for identified records were extracted and analysed through content and thematic analysis. Of 1027 studies screened, the review fesearch using health policy and systems approaches, including the use of implementation frameworks.

We investigated the usefulness of a custom-designed 31-gene next-generation sequencing (NGS) panel implemented on a routine basis for the evaluation of low-grade lymphoproliferative disorders (LPDs).

In total, 147 blood, bone marrow, and tissue specimens were sequenced, including 81% B-cell, 15% T-cell, and 3% natural killer (NK)-cell neoplasms.

Of the cases, 92 (63%) of 147 displayed at least one pathogenic variant while 41 (28%) of 147 had two or more. Low mutation rates were noted in monoclonal B-cell lymphocytoses and samples with small T- and NK-cell clones of uncertain significance. Pathogenic molecular variants were described in specific disorders and classified according to their diagnostic, prognostic, and potential therapeutic value. Diagnostically, in addition to confirming the diagnosis of 15 of 15 lymphoplasmacytic lymphomas, 10 of 12 T large granular lymphocytic leukemias, and 2 of 2 hairy cell leukemias (HCLs), the panel helped resolve the diagnosis of 10 (62.5%) of 16 challenging cases lacking a specified diagnosis based on standard morphology, phenotype, and genetic analysis.

Overall, implementation of this targeted lymphoid NGS panel as part of regular hematopathology practice was found to be a beneficial adjunct in the evaluation of low-grade LPDs.

Overall, implementation of this targeted lymphoid NGS panel as part of regular hematopathology practice was found to be a beneficial adjunct in the evaluation of low-grade LPDs.Medulloblastoma is the most common malignant pediatric brain tumor. Amplification of c-MYC is a hallmark of a subset of poor-prognosis medulloblastoma. MYC upregulates glutamine metabolism across many types of cancer. We modified the naturally occurring glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON) by adding 2 promoeities to increase its lipophilicity and brain penetration creating the prodrug isopropyl 6-diazo-5-oxo-2-(((phenyl (pivaloyloxy) methoxy) - carbonyl) amino) hexanoate, termed JHU395. This prodrug was shown to have a 10-fold improved CSF-to-plasma ratio and brain-to-plasma ratio relative to DON. We hypothesized that JHU395 would have superior cell penetration compared with DON and would effectively and more potently kill MYC-expressing medulloblastoma. GPCR activator JHU395 treatment caused decreased growth and increased apoptosis in multiple human high-MYC medulloblastoma cell lines at lower concentrations than DON. Parenteral administration of JHU395 in Nu/Nu mice led to the accumulation of micromolar concentrations of DON in brain. Treatment of mice bearing orthotopic xenografts of human MYC-amplified medulloblastoma with JHU395 increased median survival from 26 to 45 days compared with vehicle control mice (p  less then  0.001 by log-rank test). These data provide preclinical justification for the ongoing development and testing of brain-targeted DON prodrugs for use in medulloblastoma.