In most patients with systemic mastocytosis (SM), including aggressive SM and mast cell leukemia (MCL), neoplastic cells express the oncogenic KIT mutation D816V. KIT D816V is associated with constitutive tyrosine kinase (TK) activity and thus represents an attractive drug target. However, imatinib and most other TK inhibitors fail to block the TK activity of KIT D816V. We show that the novel T...

IgA nephropathy (IgAN), the most common primary glomerulonephritis in the world, is characterized by IgA immune complex-mediated mesangial cell proliferation. The transferrin receptor (TfR) was identified previously as an IgA1 receptor, and it was found that, in biopsies of patients with IgAN, TfR is overexpressed and co-localizes with IgA1 mesangial deposits. Here, it is shown that purified po...

5-Hydroxymethylcytosine (5-hmC) was recently identified as a relatively frequent base in eukaryotic genomes. Its physiological function is still unclear, but it is supposed to serve as an intermediate in DNA de novo demethylation. Using X-ray diffraction, we solved five structures of four variants of the d(CGCGAATTCGCG) dodecamer, containing either 5-hmC or 5-methylcytosine (5-mC) at position 3...

BACKGROUND/AIMS Microglia are the resident immune cells in the brain and play a pivotal role in immune surveillance in the central nervous system (CNS). Brain mast cells are activated in CNS disorders and induce the release of several mediators. Thus, brain mast cells, rather than microglia, are the "first responders" due to injury. However, the functional aspects of mast cell-microglia interac...

Hybrid Monte Carlo (HMC) is a rigorous sampling method that uses molecular dynamics (MD) as a global Monte Carlo move. The acceptance rate of HMC decays exponentially with system size. The shadow hybrid Monte Carlo (SHMC) was previously introduced to reduce this performance degradation by sampling instead from the shadow Hamiltonian defined for MD when using a symplectic integrator. SHMC's perf...

The chemokines are a large group of cytokines that are recognized to be important mediators of inflammation. In this study we show that the human mast cell leukemia line HMC-1 is a source of multiple chemokines, including I-309, monocyte chemoattractant protein 1, macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta, RANTES, and interleukin-8. I-309 and MCP-1 transcri...

The compositions of the nucleic acids of the T even bacteriophages, T2, T4, and T6 have been shown to be identical with respect to their purine and pyrimidine bases within the accuracy of existing analytical methods for these bases (1). However these viruses contain the unusual pyrimidine, 5-hydroxymethyl cytosine, which provides a unique opportunity for chemical variability in the composition ...

the human prefrontal cortex differs from all other mammals: the seat of complex cognition, abstract thinking, planning and future forecasting, and behavioral inhibition. using our prefrontal cortex is a significant energy drain on the body, so despite its impressive capabilities, it’s daily capacity is limited. some researchers estimate a mere 2-3 hours per day of activity depletes the prefront...

We propose a modification of the Hybrid Monte Carlo (HMC) algorithm that overcomes topological freezing two-dimensional $U(1)$ gauge theory with and without fermion content. This includes reversible jumps between sectors$-$winding steps$-$combined standard HMC steps. The full is referred to as winding (wHMC), it shows an improved behaviour autocorrelation time towards continuum limit. find exce...

Processing cereal grains generally increases starch digestion and improves feed efficiency and/or gain. However, the supply and cost effectiveness of using either wet corn gluten feed (WCGF) or wet distillers grains plus solubles (WDGS) is likely to increase in the future. Therefore, understanding how grain processing interacts with these byproducts will be critical for feedlots. Feeding wet by...