沃度保兒謨ニ因セル濕疹

Evaluation of CNA-IC50 correlations by known cancer driver mutations. Distributions of PCCs for cancer cell lines with mutated or wild-type proto-oncogenes or tumor suppressors as depicted in each figure. The rank position of negatively correlated drugs (p < 0.10) is shown. (EPS 975 kb

Sleep architecture of elite soccer players surrounding match days as measured by WHOOP straps

This study aimed to quantify and compare sleep architecture before and after home and away matches in elite soccer players from the English Premier League. Across two seasons, 6 male players (age 28 ± 5 y; body mass 85.1 ± 9.5 kg; height 1.86 ± 0.09 m) wore WHOOP straps to monitor sleep across 13 matches that kicked off before 17:00 h. For each, sleep was recorded the night before (MD−1), after (MD) and following the match (MD +1). Across these 3 days total sleep time (TST), sleep efficiency (SE), sleep disturbances, wake time, light sleep, deep sleep, REM sleep, sleep and wake onsets, alongside external load, were compared. TST was reduced after MD versus MD +1 (392.9 ± 76.4 vs 459.1 ± 66.7 min, p = 0.003) but no differences existed in any other sleep variables between days (p > 0.05). TST did not differ after home (386.9 ± 75.7 min) vs. away matches (401.0 ± 78.3 min) (p = 0.475), nor did other sleep variables (p > 0.05). GPS-derived external load peaked on MD (p < 0.05). In conclusion, despite reduced TST on MD, sleep architecture was unaffected after matches played before 17:00 h, suggesting sleep quality was not significantly compromised.</p

Mechanically demanding eccentric exercise increases nuclear factor erythroid 2-related factor 2 activity in human peripheral blood mononuclear cells

This study examined whether eccentric exercise increases nuclear factor erythroid 2-related factor 2 (NRF2) activity in peripheral blood mononuclear cells (PBMCs). Twenty-six recreationally active males (mean [SD]; age 25 [5] y, height 178.4 [6.9] cm, body mass 77.6 [7.4] kg) were allocated to either an exercise (n = 16) or non-exercise (resting) control (n = 10) group. Eccentric exercise involved performing 100 drop jumps from a 0.6 m box. Blood was collected pre-, immediately post- and 1 h post-exercise or rest. NRF2/antioxidant response element (ARE) binding was measured in PBMCs; glutathione reductase (GR) and peroxidase (GPX) were measured in plasma. NRF2/ARE binding was greater immediately post- and 1 h post in the exercise vs. rest group (p  0.05 for all). Eccentric exercise increases NRF2/ARE binding in PBMCs compared to rest.</p

Mechanically demanding eccentric exercise increases nuclear factor erythroid 2-related factor 2 activity in human peripheral blood mononuclear cells

This study examined whether eccentric exercise increases nuclear factor erythroid 2-related factor 2 (NRF2) activity in peripheral blood mononuclear cells (PBMCs). Twenty-six recreationally active males (mean [SD]; age 25 [5] y, height 178.4 [6.9] cm, body mass 77.6 [7.4] kg) were allocated to either an exercise (n = 16) or non-exercise (resting) control (n = 10) group. Eccentric exercise involved performing 100 drop jumps from a 0.6 m box. Blood was collected pre-, immediately post- and 1 h post-exercise or rest. NRF2/antioxidant response element (ARE) binding was measured in PBMCs; glutathione reductase (GR) and peroxidase (GPX) were measured in plasma. NRF2/ARE binding was greater immediately post- and 1 h post in the exercise vs. rest group (p  0.05 for all). Eccentric exercise increases NRF2/ARE binding in PBMCs compared to rest.</p

MOESM2 of Drug resistant integrase mutants cause aberrant HIV integrations

Additional file 2. Structure of the aberrant proviruses isolated from cells treated with suboptimal concentrations of EVG (Table S1); from cells infected with viruses harboring RAL resistant mutations and treated with suboptimal doses of RAL (Tables S2–S4). The inhibitory concentrations of EVG or RAL used to treat the cells are indicated. The aberrations in the viral LTRs and in the integrated host chromosome(s) are indicated. U-LTR: the LTR adjacent to the primer binding site; D-LTR: the LTR adjacent to the polypurine tract

MOESM1 of Drug resistant integrase mutants cause aberrant HIV integrations

Additional file 1: Figure S1. Structure of DNAs used to generate the HIV-1 vectors. At the top is a diagram of the DNA used to generate the genomic RNA that is packaged into the viral vector. When the vector infects human cells, a DNA copy of vector genome is inserted into host DNA. This allows the expression of GFP, which is under the control of a CMV promoter. The vector genome also carries an E. coli plasmid origin of replication (Ori) and a zeocin resistance gene that allows circular DNA forms of the vector genome to replicate and be selected in E. coli. The other three DNAs express Gag–Pol, Rev, and VSV-G. Rev is expressed from an RSV promoter; Gag–Pol and VSVG are expressed from CMV promoters. All four DNAs are grown in E. coli as plasmids. The plasmids encode ampicillin resistance (Ampr)

MOESM1 of Rilpivirine analogs potently inhibit drug-resistant HIV-1 mutants

Additional file 1: Table S1–S4. The IC50 values (nM) of RPV and the RPV analogs were determined against the NNRTI resistant mutants were measured by using a single round infection assay, n = 4. The concentrations (nM) are measured by reductions in luciferase reporter activity followed by the standard deviations. In parenthesis is the fold-change that describes the difference between the IC50 value of the NNRTI resistant mutant relative to WT

A screen identifies PDMP as a drug that can synergistically inhibit the growth of human leukemia cells when combined with ABT-263.

<p>(<b>A</b>) Three human leukemia cell lines were screened against the LOPAC1280 compound library with and without the IC30 of ABT-737. A synergy score was calculated for each compound in the library and the scores of each compound are plotted as a component of each cell line. A lower score indicates a higher level of synergy. U937 cells are plotted on the x-axis, RPMI8226 cells are plotted on the y-axis and HL60 cells are plotted on the z-axis. The point on the graph representing PDMP is indicated. (<b>B</b>) Dose response curves of U937 cells were determined by treating the cells with either increasing doses of PDMP (350 nM to 45 µM) plus vehicle or increasing doses of PDMP (350 nM to 45 µM) and a constant dose of ABT-263 (2 µM). Inset values are the calculated IC50 from each curve. (<b>C</b>) Dose response curves of U937 cells were determined by treating the cells with either increasing doses of ABT-263 (8 nM to 18 µM) plus vehicle or increasing doses of ABT-263 (8 nM to 18 µM) and a constant dose of PDMP (45 µM). Arrows in (<b>B</b>) and (<b>C</b>) represent the equivalent doses of the respective drugs (2 µM ABT-263, 45 µM PDMP) and isobologram analysis indicated that the combination of the two drugs was synergistic with CI = <0.1. Inset values are the calculated IC50 from each curve. (<b>D</b>) Cells were treated with ABT-263 (2 µM), PDMP (45 µM) or the combination of drugs for 2, 4, or 8 hours and western blots for cleaved CASP3 were performed. (<b>E</b>) Cells were treated with either ABT-263 (2 µM), PDMP (45 µM) or the combination of drugs and 24 hours post treatment cells were stained with anti-AnnexinV antibody and 7AAD to determine the percent of cells undergoing apoptosis.</p

Increased ceramide and sphingosine are important for synergy with ABT-263.

<p>(<b>A</b>) Summary of the lipids that are altered following treatment of U937 cells with various inhibitors. (<b>B</b>) IC50 values of ABT-263 for individual human leukemia cell lines. Values were calculated in prism as the result of dose response curves determined by alamar blue assay 48 hours after ABT-263 treatment. (<b>C</b>) Total levels of basal ceramide (Cer) and sphingosine-1-phosphate (S1P) in four different cell lines as determined by HPLC-MS/MS. Data are normalized to the levels of lipids in U937. (<b>D</b>) Model depicting how different inhibitors affect sphingolipid metabolism.</p

Treatment of U937 cells with PDMP, but not AMP-DNM causes accumuliation of ceramide and sphingosine and a decrease in glucosylceramide.

<p>(<b>A</b>) U937 cells were treated with ABT-263 (2 µM), PDMP (45 µM) or the combination of both drugs from two hours. Cells were harvested, lipids were extracted and the amounts of ceramide (Cer), hexosyceramine (HexCer) and lactosylceramide (LacCer) were quantitated. (<b>B</b>) U937 cells were treated with ABT-263 (2 µM), PDMP (45 µM) or the combination of both drugs from two hours. Cells were harvested, lipids were extracted and the amounts of sphingosine (Sph) and spingosine-1 phosphate (S1P) were quantitated. (<b>C</b>) U937 cells were treated with ABT-263 (2 µM), AMP-DNM (45 µM) or the combination of both drugs from two hours. Cells were harvested, lipids were extracted and the amounts of ceramide (Cer), hexosyceramine (HexCer) and lactosylceramide (LacCer) were quantitated. (<b>D</b>) U937 cells were treated with ABT-263 (2 µM), AMP-DNM (45 µM) or the combination of both drugs from two hours. Cells were harvested, lipids were extracted and the amounts of sphingosine (Sph) and spingosine-1 phosphate (S1P) were quantitated.</p