Rapamycin induces transactivation of the EGFR and increases cell survival.

The mammalian target of rapamycin (mTOR) signaling network regulates cell growth, proliferation and cell survival. Deregulated activation of this pathway is a common event in diverse human diseases such as cancers, cardiac hypertrophy, vascular restenosis and nephrotic hypertrophy. Although mTOR inhibitor, rapamycin, has been widely used to inhibit the aberrant signaling due to mTOR activation that plays a major role in hyperproliferative diseases, in some cases rapamycin does not attenuate the cell proliferation and survival. Thus, we studied the mechanism(s) by which cells may confer resistance to rapamycin. Our data show that in a variety of cell types the mTOR inhibitor rapamycin activates extracellularly regulated kinases (Erk1/2) signaling. Rapamycin-mediated activation of the Erk1/2 signaling requires (a) the epidermal growth factor receptor (EGFR), (b) its tyrosine kinase activity and (c) intact autophosphorylation sites on the receptor. Rapamycin treatment increases tyrosine phosphorylation of EGFR without the addition of growth factor and this transactivation of receptor involves activation of c-Src. We also show that rapamycin treatment triggers activation of cell survival signaling pathway by activating the prosurvival kinases Erk1/2 and p90RSK. These studies provide a novel paradigm by which cells escape the apoptotic actions of rapamycin and its derivatives that inhibit the mTOR pathway

Polarization and temperature dependence of photoluminescence from zincblende and wurtzite InP nanowires

We use polarization-resolved and temperature-dependent photoluminescence of single zincblende (ZB) (cubic) and wurtzite (WZ) (hexagonal) InPnanowires to probe differences in selection rules and bandgaps between these two semiconductor nanostructures. The WZ nanowires exhibit a bandgap80meV higher in energy than the ZB nanowires. The temperature dependence of the PL is similar but not identical for the WZ and ZB nanowires. We find that ZB nanowires exhibit strong polarization parallel to the nanowire axis, while the WZ nanowires exhibit polarized emission perpendicular to the nanowire axis. This behavior is interpreted in terms of the different selection rules for WZ and ZB crystal structures.A.M., L.V.T., T.B.H., H.E.J., L.M.S., and J.M.Y.-R. acknowledge support from the Institute for Nanoscale Science and Technology of the University of Cincinnati and the National Science Foundation through Grant Nos. EEC/NUE 0532495 and ECCS 0701703. The Australian authors acknowledge support from the Australian Research Council. Y.K. acknowledges support by the Korean Science and Engineering Foundation KOSEF through Grant No. F01- 2007-000-10087-0

Atmospheric emissions from the deepwater Horizon spill constrain air-water partitioning, hydrocarbon fate, and leak rate

The fate of deepwater releases of gas and oil mixtures is initially determined by solubility and volatility of individual hydrocarbon species; these attributes determine partitioning between air and water. Quantifying this partitioning is necessary to constrain simulations of gas and oil transport, to predict marine bioavailability of different fractions of the gas-oil mixture, and to develop a comprehensive picture of the fate of leaked hydrocarbons in the marine environment. Analysis of airborne atmospheric data shows massive amounts (∼258,000 kg/day) of hydrocarbons evaporating promptly from the Deepwater Horizon spill; these data collected during two research flights constrain air-water partitioning, thus bioavailability and fate, of the leaked fluid. This analysis quantifies the fraction of surfacing hydrocarbons that dissolves in the water column (∼33% by mass), the fraction that does not dissolve, and the fraction that evaporates promptly after surfacing (∼14% by mass). We do not quantify the leaked fraction lacking a surface expression; therefore, calculation of atmospheric mass fluxes provides a lower limit to the total hydrocarbon leak rate of 32,600 to 47,700 barrels of fluid per day, depending on reservoir fluid composition information. This study demonstrates a new approach for rapid-response airborne assessment of future oil spills. Copyright 2011 by the American Geophysical Union

Adding control to arbitrary unknown quantum operations

While quantum computers promise significant advantages, the complexity of quantum algorithms remains a major technological obstacle. We have developed and demonstrated an architecture-independent technique that simplifies adding control qubits to arbitrary quantum operations-a requirement in many quantum algorithms, simulations and metrology. The technique is independent of how the operation is done, does not require knowledge of what the operation is, and largely separates the problems of how to implement a quantum operation in the laboratory and how to add a control. We demonstrate an entanglement-based version in a photonic system, realizing a range of different two-qubit gates with high fidelity.Comment: 9 pages, 8 figure

Using biomarkers to predict TB treatment duration (Predict TB): a prospective, randomized, noninferiority, treatment shortening clinical trial

Background : By the early 1980s, tuberculosis treatment was shortened from 24 to 6 months, maintaining relapse rates of 1-2%. Subsequent trials attempting shorter durations have failed, with 4-month arms consistently having relapse rates of 15-20%. One trial shortened treatment only among those without baseline cavity on chest x-ray and whose month 2 sputum culture converted to negative. The 4-month arm relapse rate decreased to 7% but was still significantly worse than the 6-month arm (1.6%, P<0.01).  We hypothesize that PET/CT characteristics at baseline, PET/CT changes at one month, and markers of residual bacterial load will identify patients with tuberculosis who can be cured with 4 months (16 weeks) of standard treatment.Methods: This is a prospective, multicenter, randomized, phase 2b, noninferiority clinical trial of pulmonary tuberculosis participants. Those eligible start standard of care treatment. PET/CT scans are done at weeks 0, 4, and 16 or 24. Participants who do not meet early treatment completion criteria (baseline radiologic severity, radiologic response at one month, and GeneXpert-detectable bacilli at four months) are placed in Arm A (24 weeks of standard therapy). Those who meet the early treatment completion criteria are randomized at week 16 to continue treatment to week 24 (Arm B) or complete treatment at week 16 (Arm C). The primary endpoint compares the treatment success rate at 18 months between Arms B and C.Discussion: Multiple biomarkers have been assessed to predict TB treatment outcomes. This study uses PET/CT scans and GeneXpert (Xpert) cycle threshold to risk stratify participants. PET/CT scans are not applicable to global public health but could be used in clinical trials to stratify participants and possibly become a surrogate endpoint. If the Predict TB trial is successful, other immunological biomarkers or transcriptional signatures that correlate with treatment outcome may be identified. TRIAL REGISTRATION: NCT02821832

A new interpretation of total column BrO during Arctic spring

Emission of bromine from sea-salt aerosol, frost flowers, ice leads, and snow results in the nearly complete removal of surface ozone during Arctic spring. Regions of enhanced total column BrO observed by satellites have traditionally been associated with these emissions. However, airborne measurements of BrO and O3 within the convective boundary layer (CBL) during the ARCTAS and ARCPAC field campaigns at times bear little relation to enhanced column BrO. We show that the locations of numerous satellite BrO "hotspots" during Arctic spring are consistent with observations of total column ozone and tropopause height, suggesting a stratospheric origin to these regions of elevated BrO. Tropospheric enhancements of BrO large enough to affect the column abundance are also observed, with important contributions originating from above the CBL. Closure of the budget for total column BrO, albeit with significant uncertainty, is achieved by summing observed tropospheric partial columns with calculated stratospheric partial columns provided that natural, short-lived biogenic bromocarbons supply between 5 and 10 ppt of bromine to the Arctic lowermost stratosphere. Proper understanding of bromine and its effects on atmospheric composition requires accurate treatment of geographic variations in column BrO originating from both the stratosphere and troposphere. Copyright 2010 by the American Geophysical Union

Myofibrillogenesis regulator 1 (MR-1) is a novel biomarker and potential therapeutic target for human ovarian cancer

<p>Abstract</p> <p>Background</p> <p>Myofibrillogenesis regulator 1 (MR-1) is overexpressed in human cancer cells and plays an essential role in cancer cell growth. However, the significance of MR-1 in human ovarian cancer has not yet been explored. The aim of this study was to examine whether MR-1 is a predictor of ovarian cancer and its value as a therapeutic target in ovarian cancer patients.</p> <p>Methods</p> <p>Reverse-transcription polymerase chain reaction (PCR) and quantitative real-time PCR were used to detect MR-1 mRNA levels in tissue samples from 26 ovarian cancer patients and 25 controls with benign ovarian disease. Anti-MR-1 polyclonal antibodies were prepared, tested by ELISA and western blotting, and then used for immunohistochemical analysis of the tissue samples. Adhesion and invasion of 292T cells was also examined after transfection of a pMX-MR-1 plasmid. Knockdown of MR-1 expression was achieved after stable transfection of SKOV3 cells with a short hairpin DNA pGPU6/GFP/Neo plasmid against the MR-1 gene. In addition, SKOV3 cells were treated with paclitaxel and carboplatin, and a potential role for MR-1 as a therapeutic target was evaluated.</p> <p>Results</p> <p>MR-1 was overexpressed in ovarian cancer tissues and SKOV3 cells. 293T cells overexpressed MR-1, and cellular spread and invasion were enhanced after transfection of the pMX-MR-1 plasmid, suggesting that MR-1 is critical for ovarian cancer cell growth. Knockdown of MR-1 expression inhibited cell adhesion and invasion, and treatment with anti-cancer drugs decreased its expression in cancer cells. Taken together, these results provide the first evidence of the cellular and molecular mechanisms by which MR-1 might serve as a novel biological marker and potential therapeutic target for ovarian cancer.</p> <p>Conclusions</p> <p>MR-1 may be a biomarker for diagnosis of ovarian cancer. It may also be useful for monitoring of the effects of anti-cancer therapies. Further studies are needed to clarify whether MR-1 is an early diagnostic marker for ovarian cancer and a possible therapeutic target.</p

S021-04 OA. A large-scale analysis of immunoglobulin sequences derived from plasmablasts/plasma cells in acute HIV-1 infection subjects

Background In acute HIV-1 infection (AHI) there are infectioninduced polyclonal shifts in blood and bone marrow Bcell subsets from naïve to memory cells and plasmablasts/ plasma cells (PCs) coupled with decreased numbers of naive B cells. To study the initial antibody response to HIV, we have used recombinant technology to create a database of PC antibody sequences derived from 3 early stage AHI subjects

Atrazine-induced apoptosis of splenocytes in BALB/C mice

<p>Abstract</p> <p>Background</p> <p>Atrazine (2-chloro-4-ethytlamino-6-isopropylamine-1,3,5-triazine; ATR), is the most commonly applied broad-spectrum herbicide in the world. Unintentional overspray of ATR poses an immune function health hazard. The biomolecular mechanisms responsible for ATR-induced immunotoxicity, however, are little understood. This study presents on our investigation into the apoptosis of splenocytes in mice exposed to ATR as we explore possible immunotoxic mechanisms.</p> <p>Methods</p> <p>Oral doses of ATR were administered to BALB/C mice for 21 days. The histopathology, lymphocyte apoptosis and the expression of apoptosis-related proteins from the Fas/Fas ligand (FasL) apoptotic pathway were examined from spleen samples.</p> <p>Results</p> <p>Mice administered ATR exhibited a significant decrease in spleen and thymus weight. Electron microscope histology of ultrathin sections of spleen revealed degenerative micromorphology indicative of apoptosis of splenocytes. Flow cytometry revealed that the percentage of apoptotic lymphocytes increased in a dose-dependent manner after ATR treatment. Western blots identified increased expression of Fas, FasL and active caspase-3 proteins in the treatment groups.</p> <p>Conclusions</p> <p>ATR is capable of inducing splenocytic apoptosis mediated by the Fas/FasL pathway in mice, which could be the potential mechanism underlying the immunotoxicity of ATR.</p