Ablation of Myeloid Cell MRP8 Ameliorates Nephrotoxic Serum-induced Glomerulonephritis by Affecting Macrophage Characterization through Intraglomerular Crosstalk

Toll-like receptor 4 (TLR4) and one of its endogenous ligands myeloid-related protein 8 (MRP8 or S100A8), especially expressed in macrophages, play an important role in diabetic nephropathy and autoimmune disorders. However, detailed mechanisms and consequence of MRP8 expression remain unknown, partly due to embryonic lethality of MRP8 knockout mice. In this study, Myeloid lineage cell-specific MRP8 knockout mice were generated, and nephrotoxic serum-induced glomerulonephritis was developed. Mice with conditional ablation of MRP8 gene in myeloid cells exhibited less severe histological damage, proteinuria and inflammatory changes compared to control mice. Mechanism of MRP8 upregulation was investigated using cultured cells. Co-culture of macrophages with mesangial cells or mesangial cell-conditioned media, but not with proximal tubules, markedly upregulated MRP8 gene expression and inflammatory M1 phenotype in macrophages, which was attenuated in MRP8-deleted bone marrow-derived macrophages. Effects of MRP8 deletion was further studied in the context of macrophage-inducible C-type lectin (Mincle), which is critically involved in maintenance of M1 phenotype of macrophages. MRP8 ablation in myeloid cells suppressed the induction of Mincle expression on macrophages in glomerulonephritis. Thus, we propose that intraglomerular crosstalk between mesangial cells and macrophages plays a role in inflammatory changes in glomerulonephritis, and MRP8-dependent Mincle expression in macrophage may be involved in the process

Slc3a2 Mediates Branched-Chain Amino-Acid-Dependent Maintenance of Regulatory T Cells

Foxp3+ regulatory T (Treg) cells, which suppress immune responses, are highly proliferative in vivo. However, it remains unclear how the active replication of Treg cells is maintained in vivo. Here, we show that branched-chain amino acids (BCAAs), including isoleucine, are required for maintenance of the proliferative state of Treg cells via the amino acid transporter Slc3a2-dependent metabolic reprogramming. Mice fed BCAA-reduced diets showed decreased numbers of Foxp3+ Treg cells with defective in vivo proliferative capacity. Mice lacking Slc3a2 specifically in Foxp3+ Treg cells showed impaired in vivo replication and decreased numbers of Treg cells. Slc3a2-deficient Treg cells showed impaired isoleucine-induced activation of the mTORC1 pathway and an altered metabolic state. Slc3a2 mutant mice did not show an isoleucine-induced increase of Treg cells in vivo and exhibited multi-organ inflammation. Taken together, these findings demonstrate that BCAA controls Treg cell maintenance via Slc3a2-dependent metabolic regulation

High testosterone levels in prostate tissue obtained by needle biopsy correlate with poor-prognosis factors in prostate cancer patients

Background: There is currently no consensus on the correlations between androgen concentrations in prostate tissue and blood and stage and pathological grade of prostate cancer. In this study, we used a newly-developed ultra-sensitive liquid-chromatography tandem mass spectrometry method to measure testosterone (T) and dihydrotestosterone (DHT) concentrations in blood and needle biopsy prostate specimens from patients with prostate cancer.Methods: We analyzed androgen levels in 196 men diagnosed with prostate cancer. All patients had undergone systematic needle biopsy, and an additional needle biopsy from the peripheral zone was conducted for the simultaneous determination of T and DHT. We analyzed the relationships between T and DHT levels in tissue and blood and Gleason score, clinical stage, and percentage of positive biopsy cores, using multivariate analysis. Results: The median T and DHT levels in blood were 3551.0 pg/mL and 330.5 pg/mL, respectively. There was a strong correlation between serum T and DHT. The median T and DHT levels in prostate tissue were 0.5667 pg/mg and 7.0625 pg/mg, respectively. In multivariate analysis, serum prostate-specific antigen and tissue T levels were significantly associated with poor prognosis; high T levels in prostate tissue were significantly related to high Gleason score (p = 0.041), advanced clinical stage (p = 0.002), and a high percentage of positive biopsy cores (p = 0.001). Conclusions: The results of this study indicate that high T levels in prostate tissue are related to high Gleason score, advanced clinical stage, and a high percentage of positive biopsy cores in patients with prostate cancer. T level in needle biopsy specimens may therefore be a useful prognostic factor in prostate cancer patients

Searching for Mobile Intruders in a Polygonal Region by a Group of Mobile Searchers

The problem of searching for mobile intruders in a polygonal region by mobile searchers is considered. A searcher can move continuously inside a polygon holding a flashlight that emits a single ray of light whose direction can be changed continuously. The visibility of a searcher at any time instant is limited to the points on the ray. The intruders can move continuously with unbounded speed. We denote by ps(P ) the polygon search number of a simple polygon P , which is the number of searchers necessary and sufficient to search P . Let n, r, b and g be the number of edges, the number of reflex vertices, the bushiness, and the size of a minimum guard set of P , respectively. In this paper, we present matching upper and (worst case) lower bounds of 1 + blog 3 (2b + 1)c on ps(P ). Also upper bounds on ps(P ) in terms of n; r and g are presented; ps(P ) 1 + blog 3 (n \Gamma 3)c; ps(P ) 1 + blog 3 rc, and ps(P ) 2 + dlog 2 ge. These upper bounds are tight or almost tight in the worst c..

Rotational and vibrational state distribution of H_2 activated on a heated tungsten filament

The rotational and vibrational state distributions of H_2 activated on a heated tungsten filament were determined by employing a coherent anti-Stokes Raman scattering technique to examine the contribution to the catalytic chemical vapor deposition process. The rotational excitation could be confirmed and the distribution was Boltzmann-like. When the filament temperature was 2700 K and the H_2 pressure was over 1.3 kPa, the rotational temperature monitored 5 cm under the filament was around 1200 K; it showed a sharp decrease below 670 Pa and it was 700 K at 67 Pa. This decrease in the rotational temperature suggests the importance of relaxation processes on the chamber walls. The first vibrationally excited H_2 molecules could also be identified at pressures over 670 Pa and the vibrational temperature was not much different from the rotational one. This vibrational temperature is much lower than those in typical H_2 plasma, showing that the direct vibrational excitation of H_2 on hot filaments is inefficient compared to its dissociation to two H atoms

Coating techniques of metal chambers for remote catalytic chemical vapor deposition applications

autho

Direct detection of H atoms in the catalytic chemical vapor deposition of the SiH_4/H_2 system

The absolute densities of H atoms produced in catalytic chemical vapor deposition (Cat-CVD or hot-wire CVD) processes were determined by employing two-photon laser-induced fluorescence and vacuum ultraviolet absorption techniques. The H-atom density in the gas phase increases exponentially with increases in the catalyzer temperature in the presence of pure H_2. When the catalyzer temperature was 2200 K, the absolute density in the presence of 5.6 Pa of H_2 (150 sccm in flow rate) was as high as 1.5×10^ cm^ at a point 10 cm from the catalyzer. This density is one or two orders of magnitude higher than those observed in typical plasma-enhanced chemical vapor-deposition processes. The H-atom density decreases sharply with the addition of SiH_4. When 0.1 Pa of SiH_4 was added, the steady-state density decreased to 7×10^ cm^. This sharp decrease can primarily be ascribed to the loss processes on chamber walls