Accurate rate coefficients for molecular vibrational transitions due to collisions with H 2 , critical for interpreting infrared astronomical observations, are lacking for most molecules. Quantum calculations are the primary source of such data, but reliable values that consider all internal degrees of freedom of the collision complex have only been reported for H 2 -H 2 due to the difficulty of the computations. Here we present essentially exact, full-dimensional dynamics computations for rovibrational quenching of CO due to H 2 impact. Using a high-level six-dimensional potential surface, time-independent scattering calculations, within a full angular momentum coupling formulation, were performed for the de-excitation of vibrationally excited CO. Agreement with experimentally determined results confirms the accuracy of the potential and scattering computations, representing the largest of such calculations performed to date. This investigation advances computational quantum dynamical studies representing initial steps towards obtaining CO-H 2 rovibrational quenching data needed for astrophysical modelling.

Epithelial-mesenchymal transition (EMT) is a crucial mechanism for the acquisition of migratory and invasive capabilities by epithelial cancer cells. By conducting quantitative proteomics in experimental models of human prostate cancer (PCa) metastasis, we observed strikingly decreased expression of EPLIN (epithelial protein lost in neoplasm; or LIM domain and actin binding 1, LIMA-1) upon EMT. Biochemical and functional analyses demonstrated that EPLIN is a negative regulator of EMT and invasiveness in PCa cells. EPLIN depletion resulted in the disassembly of adherens junctions, structurally distinct actin remodeling, and activation of β-catenin signaling. Microarray expression analysis identified a subset of putative EPLIN target genes associated with EMT, invasion and metastasis. By immunohistochemistry EPLIN downregulation was also demonstrated in lymph node metastases of human solid tumors including PCa, breast cancer, colorectal cancer and squamous cell carcinoma of the head and neck. This study reveals a novel molecular mechanism for converting cancer cells into a highly invasive and malignant form, and has important implications in prognosing and treating metastasis at early stages.

The regulatory proteins of human immunodeficiency virus may represent important vaccine targets. Here we assessed the role of Tat-specific cytotoxic T lymphocytes (CTL) in controlling pathogenic simian immunodeficiency virus SIVmac239 replication after using a DNA-prime, vaccinia virus Ankara-boost vaccine regimen. Despite the induction of Tat-specific CTL, there was no significant reduction in either peak or viral set point compared to that of controls.Recent reports have suggested that immune responses directed against the smaller regulatory proteins might be able to control human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication (7,8,10,17,19,21,22). We have recently shown that Mamu-A*01-positive rhesus macaques mount an immunodominant cytotoxic T-lymphocyte (CTL) response to an epitope in Tat (Tat 28-35 SL8) (1). This CTL response exerts significant selective pressure by eliminating wild-type virus replication by 4 weeks postinfection (p.i.) in the majority of Mamu-A*01-positive macaques. Additionally, the HIV Tat protein is highly variable, suggesting that CTL exert selective pressure on this region of the virus (12, 13). We therefore assessed whether vaccine-induced Tat-specific CTL might prove effective in controlling SIVmac239 replication.Induction of Tat 28-35 SL8-specific CTL by DNA/MVA. We employed a DNA-prime, attenuated vaccinia virus Ankara (MVA)-boost vaccination regimen to induce Tat-specific CTL in three Mamu-A*01-positive (animal 96016, 1975, and 97085) and one Mamu-A*01-negative (animal 97007) rhesus macaques. Four Mamu-A*01-positive macaques (animal 96111, 95086, 93057, and 85013) served as controls. Vaccinees were immunized three times with DNA at 6-week intervals as previously described (2). Two DNA vectors were employed. One vector encoded full-length SIVmac239 Tat, and the second vector encoded a single Mamu-A*01-restricted CTL epitope Tat 28-35 SL8 (STPESANL) inserted within the immunodominant region of hepatitis B core antigen. A gene gun was used to deliver gold particles coated with plasmid DNA into the epidermis. Each immunization consisted of a total of 32 g of DNA administered at eight skin sites over the abdominal and inguinal lymph nodes, as previously described (2) Following the final DNA immunization, tetramer analysis detected Tat 28-35 SL8-specific CTL in fresh peripheral blood mononuclear cells (PBMC) of two of the three Mamu-A*01-positive vaccinees (4.7 and 0.64% of all CD3/CD8 T lymphocytes) (Fig. 1A). Background tetramer staining in control animals was less than 0.08%. Surprisingly, in one of these animals (macaque 1975), the Tat 28-35 SL8 response reached levels in excess of 4%, a magnitude of CTL response not previously observed in rhesus macaques following DNA vaccination alone (2-5, 11).One month after receiving the last DNA immunization, rhesus macaques were then boosted intradermally with 5 ϫ 10 8

We report the first full-dimensional potential energy surface (PES) and quantum mechanical close-coupling calculations for scattering of SiO due to H 2. The full-dimensional interaction potential surface was computed using the explicitly correlated coupled-cluster (CCSD(T)-F12b) method and fitted using an invariant polynomial approach. Pure rotational quenching cross sections from initial states v 1 = 0, j 1 =1-5 of SiO in collision with H 2 are calculated for collision energies between 1.0 and 5000 cm −1. State-to-state rotational rate coefficients are calculated at temperatures between 5 and 1000 K. The rotational rate coefficients of SiO with para-H 2 are compared with previous approximate results which were obtained using SiO-He PESs or scaled from SiO-He rate coefficients. Rovibrational state-to-state and total quenching cross sections and rate coefficients for initially excited SiO(v 1 = 1, j 1 =0 and 1) in collisions with para-H 2 (v 2 = 0, j 2 = 0) and ortho-H 2 (v 2 = 0, j 2 = 1) were also obtained. The application of the current collisional rate coefficients to astrophysics is briefly discussed.

In muscles of rats with metabolic acidosis, branched-chain alpha-ketoacid dehydrogenase (BCKAD) activity is increased. Potential stimulatory signals include acidemia and/or glucocorticoids. It is unclear whether the signal(s) increases BCKAD activity by changing the activation state of the enzyme or by increasing the amount of enzyme. To separate the influences of extracellular pH and glucocorticoids on leucine catabolism, maximal BCKAD flux and the activation state (the ratio of basal to total flux) were measured in two cell types: 1) cells that do not express glucocorticoid receptors and 2) cells stably transfected to express glucocorticoid receptors. Acidification (pH 6.95) increased 1) the activation state from 67.2% at pH 7.4 to 82.8% at pH 6.95, 2) maximal BCKAD flux by 50%, and 3) the BCKAD subunit contents in both cell types (57, 410, and 270% for E2, E1 alpha, and E1 beta, respectively). Dexamethasone increased the BCKAD activation state from 67.2 to 82.3% in cells expressing glucocorticoid receptors, whereas dexamethasone plus acidification increased the activation state to 98%. The time course of stimulation by dexamethasone was slower than that by acidification. These results demonstrate that BCKAD is differentially regulated by extracellular pH and glucocorticoids.