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RUNX1 (also known as AML1) is a DNA-binding transcription factor that functions as a tumor suppressor and developmental determinant in hematopoietic cells. Target promoters have been identified primarily through the use of differential expression strategies and candidate gene approaches but not biochemical screens. Using a chromatin immunoprecipitation screen, we identified protein kinase C␤ as a direct RUNX1 target gene and demonstrate that endogenous RUNX1 binds the chromatinized protein kinase C␤ promoter of U937 cells. A phylogenetically conserved RUNX1-binding site within the PKC␤ promoter binds RUNX1 in electrophoretic mobility shift analyses and confers RUNX1 responsiveness on a heterologous promoter. Changes in RUNX1 activity affect endogenous protein kinase C␤ expression, and a dominant-negative form of RUNX1 protects U937 cells from apoptotic stimuli previously shown to be dependent on protein kinase C␤. This protection can be reversed by the ectopic expression of protein kinase C␤. Together these findings demonstrate that protein kinase C␤ is a direct, downstream target of RUNX1 and links RUNX1 to a myeloid apoptotic pathway.

An evaluation is presented of the microstructural characteristics and mechanical properties of welds in 20 mm thickness high strength low alloy steel HSLA 80, of Australian manufacture. In total, nine butt joints were prepared using the double tandem (four wire) submerged arc welding process in which both heat input and travel speed were varied. The inclusion size distribution was determined for selected welds and showed that heat input had a major effect. Colour etching techniques were used to reveal the solidification structure, which in turn correlated with welding parameters. As the heat input increased, the cooling rate decreased resulting in a larger cellular dendritic cell spacing, decreased acicular ferrite content, and coarser acicular ferrite laths. The effect of travel speed on delta ferrite cell spacing and prior austenite grain size was found to be co-dependent on the heat input and the thermal profile resulting from multiple electrode welding. These results show that increased deposition rates can be achieved by increasing the travel speed and current density without sacrificing joint quality.

Bone marrow kinase in the X chromosome, a member of the Tec family of tyrosine kinases, plays a role in both monocyte ⁄ macrophage trafficking as well as cytokine secretion. Although the structures of Tec family kinases Bruton's tyrosine kinase and IL-2-inducible T-cell kinase are known, the crystal structures of other Tec family kinases have remained elusive. We report the X-ray crystal structures of bone marrow kinase in the X chromosome in complex with dasatinib at 2.4 Å resolution and PP2 at 1.9 Å resolution. The bone marrow kinase in the X chromosome structures reveal a typical kinase protein fold; with well-ordered protein conformation that includes an open ⁄ extended activation loop and a stabilized DFG-motif rendering the kinase in an inactive conformation. Dasatinib and PP2 bind to bone marrow kinase in the X chromosome in the ATP binding pocket and display similar binding modes to that observed in other Tec and Src protein kinases. The bone marrow kinase in the X chromosome structures identify conformational elements of the DFG-motif that could potentially be utilized to design potent and ⁄ or selective bone marrow kinase in the X chromosome inhibitors.

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Metabolic syndrome (MS) is a collection of pathological metabolic conditions that includes insulin resistance, central or abdominal obesity, dyslipidemia, and hypertension. It affects large populations worldwide, and its prevalence is rising exponentially. There is no specific mechanism that leads to the development of MS. Proposed hypotheses range from visceral adiposity being a key factor to an increase in very-low-density lipoprotein and fatty acid synthesis as the primary cause of MS. Numerous pharmaceutical therapies are widely available in the market for the treatment of the individual components of MS. The relationship between MS and vitamin B complex supplementation, specifically folic acid and vitamin B12, has been a subject of investigation worldwide, with several trials reporting a positive impact with vitamin supplementation on MS.In this study, an all-language literature search was conducted on Medline, Cochrane, Embase, and Google Scholar till September 2021. The following search strings and Medical Subject Headings (MeSH) terms were used: "Vitamin B12," "Folate," "Metabolic Syndrome," and "Insulin Resistance." We explored the literature on MS for its epidemiology, pathophysiology, newer treatment options, with a special focus on the effectiveness of supplementation with vitamins B9 and B12.According to the literature, vitamin B12 and folate supplementation, along with a host of novel therapies, has a considerable positive impact on MS. These findings must be kept in mind while designing newer treatment protocols in the future.

Summary points• Stereotactic body radiotherapy for early stage non-small-cell lung cancer has become the standard of care for inoperable patients.• Furthermore, empiric treatment of presumed early stage lung cancer without biopsy is increasingly popular, although it is unclear if radiographic and clinical data alone are sufficient to direct management.• We therefore compared the outcomes of 96 biopsy-proven and 100 clinically diagnosed early stage non-small-cell lung cancers treated with stereotactic body radiotherapy.• Empirically treated lesions were smaller (1.6 cm) compared to biopsy-proven ones (2.2 cm) and patients treated empirically had poorer pulmonary function.• The local control and overall survival at 2 years was 94% and 58% for all patients, with no difference between groups and no grade 3 or higher toxicities.• Our study confirms that stereotactic body radiotherapy is a safe and effective treatment for medically inoperable non-small-cell lung cancer.• Oncologic outcomes for empirically treated lesions were similar to the biopsy-proven group, suggesting that modern imaging and clinical history can substitute a tissue diagnosis in a high risk population.Aim: Herein, we compare outcomes in patients treated with lung stereotactic body radiotherapy (SBRT) with and without tissue confirmation. Methods: We reviewed 196 patients that underwent lung SBRT for presumed (100 patients) or proven non-small-cell lung cancer (96 patients) over a 10-year period and compared outcomes. Results: A total of 196 patients with a median age of 76 underwent lung SBRT to a median dose of 48 Gy in four fractions. Median follow up was 17 months. Local control and overall survival at 3 years was 94 and 58% for the entire group. There was no difference in overall survival, local control, regional control or distant control between the cohorts. Conclusion: SBRT is a safe and effective treatment for patients with non-small-cell lung cancer that are medically inoperable with comparable results in empirically treated patients.