Sex Differences in a Semantic Fluency Task?

It is a well-documented empirical fact that men and women perform differently in language tasks involving various semantic categories. The sex-by-category effect has been reported in several languages and through different tasks. The results of these studies agree that some semantic categories are preferentially male while others are preferentially female, but which categories are associated with one gender or the other varies across studies. In our study, we tested a group of undergraduate native Spanish speakers from Argentina on a written semantic fluency task. Participants were tested on ten semantic categories, five from the Living Things domain (LT) and five from the Non-Living Things domain (NLT). While women retrieved more items than men across categories, differential output was only significant in five categories: animals, vegetables (LT), furniture and utensils (NLT) for females and tools (NLT) for males

The Neural Basis of Decision-Making and Reward Processing in Adults with Euthymic Bipolar Disorder or Attention-Deficit/Hyperactivity Disorder (ADHD)

Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) share DSM-IV criteria in adults and cause problems in decision-making. Nevertheless, no previous report has assessed a decision-making task that includes the examination of the neural correlates of reward and gambling in adults with ADHD and those with BD

Rapamycin-induced Akt activation accelerates the repair of radiation-induced DNA-DSBs.

<p><b>(A-B)</b> Cells grown to confluency on glass slides were treated with MK2206 (A549: 5 μM; H460: 2.5 μM) and rapamycin (100 nM) or were pretreated with MK2206 (A549: 5 μM; H460: 2.5 μM) for 1 hour and followed by treatment with rapamycin (100 nM) for 2 h. <b>(C-D)</b> Cells grown on glass slides were transfected with control-siRNA (siCON) or AKT1-siRNA (siAKT1) (A549: 50 nM; H460: 150 nM). Seventy-two hours after transfection, cells were treated with rapamycin (100 nM) for 3 hours. In the experiments described above, control cells received the appropriate concentrations of DMSO. Following the treatment procedures described above, cells were irradiated with the indicated doses of X-ray, and γ-H2AX foci assays were performed 24 h after irradiation, as described in <i>Materials and Methods</i>. The frequency of residual γ-H2AX foci was counted in indicated number of cells and experiments (exp.) per treatment condition. The mean number of foci/cell ± SEM was calculated and graphed. Asterisks indicate statistically significant enhancement of residual γ-H2AX foci under the indicated conditions (*, P < 0.05; **, P < 0.01; ***, P < 0.001). (<b>E</b>) Data represent the mean value of GFP expression from 7 data obtained from 4 independent experiments after 24 h treatment with DMSO, MK2206 (MK /5 μM), Rapamycin (Rapa / 100 nM) or the combination of MK2206 with rapamycin in the NHEJ assay performed in A549 cells expressing NHEJ assay platform, as described in the <i>Materials and Methods</i> section (*, P < 0.05; **, P < 0.01).</p

Rapamycin treatment induces Akt1 activation through PI3K in a cell line-dependent manner.

<p>Cells were treated with rapamycin (100 nM) for the indicated time points <b>(A)</b> or for 6 h <b>(B)</b>. (<b>C)</b> After 1 h pretreatment with LY294002 (10 μM), cells were treated with rapamycin (100 nM) for 2 hours. Control cells received the appropriate concentrations of DMSO. Thereafter, protein samples were isolated and the phosphorylation patterns of mTOR, S6, Akt, PRAS40 and GSK3α/β were analyzed by Western blotting. Blots were stripped and incubated with antibodies against total proteins. Densitometry values represent the ratio of phosphorylated protein to total protein, which was normalized to 1 for the control condition. Densitometry values represented in part B are at least from 3 independent experiments.</p

Akt targeting promotes the radiosensitizing effect of rapamycin in <i>non-responder</i> cells.

<p><b>(A)</b> Cells were treated with MK2206 (A549: 5 μM; H460: 2.5 μM) for 1 h, followed by treatment with rapamycin (100 nM) for 2 h. Control cells received the appropriate concentrations of DMSO. Thereafter, P-Akt (S473, T308) and P-Akt2 (S474) levels were analyzed in protein samples by Western blotting. Blots were stripped and incubated with anti-Akt1 or anti-Akt2 antibodies. The densitometry data represent the mean ratio of phosphorylated Akt1 to Akt1 based on 2 biologically independent experiments; the control conditions were normalized to 1. The densitometry values for phospho-Akt2 represent the mean ratio of phospho-S474 to Akt2 normalized to 1 for the control condition. For colony formation assays, 24 h after pre-plating, cells were treated with MK2206 (A549: 5 μM; H460: 2.5 μM) for 1 h, followed by treatment with rapamycin (100 nM) for 2 h. Control cells received the appropriate concentrations of DMSO. The cultures were irradiated after rapamycin treatment and incubated for colony growth. Data represent the mean SF ± SD of 18 data from three biologically independent experiments in A549 cells and of 12 data from two biologically independent experiments in H460 cells. In <i>non-responder</i> A549 cells, asterisks indicate a significant difference between the radiosensitizing effect produced by the combination of MK2206 and rapamycin compared to the effects of single treatment with rapamycin alone (**, P < 0.01; ***, P < 0.001). <b>(B)</b> Cells were plated in culture dishes and were transfected with non-target-siRNA (siCON) or AKT1-siRNA (siAKT1) after 24 hours at concentrations of 50 nM (A549) and 150 nM (H460). At the indicated time points after transfection, Akt1 knockdown efficiency was tested by Western blotting. GAPDH was used as a loading control. Densitometry values represent the mean ratio of Akt1 to GAPDH from three independent experiments; the control conditions were normalized to 1. In parallel, 2 days after transfection, cells were trypsinized and seeded for clonogenic assays. Twenty-four hours later, cells were treated with rapamycin (100 nM) for 2 hours, followed by irradiation with single doses of 0 to 4 Gy. The clonogenic assay was performed as described in <i>Materials and Methods</i>. Data represent the mean SF ± SD of four biologically independent experiments (21 data) in A549 cells and 6 parallel experiments in H460 cells. In <i>non-responder</i> A549 cells, asterisks indicate a significant difference between the radiosensitizing effect produced by the combination of AKT1-siRNA with rapamycin compared to the effects of single treatment with rapamycin alone (***, P < 0.001). DMF: Dose modification factor.</p

The effect of Akt2 on DNA-DSB repair is more robust than the effect of Akt1 in H460 cells.

<p>H460 cells that were grown on glass slides were transfected with 50 nM of control-siRNA (siCON), AKT1-siRNA (siAKT1) or AKT2-siRNA (siAKT2). Forty-eight hours (24 h time-point) and 64 h (8 h time-point) after transfection, cells were irradiated with 4 Gy and γ-H2AX assay was performed as described in <i>Materials and Methods</i>. The data represent the mean number of γ-H2AX foci ± SEM from at least 140 cells in two biologically independent experiments. Asterisks indicate statistically significant enhancement of residual γ-H2AX foci following transfection with AKT1- and AKT2-siRNA at the indicated conditions (*, P < 0.05; **, P < 0.01; ***, P < 0.001).</p

Dual Targeting of Akt and mTORC1 Impairs Repair of DNA Double-Strand Breaks and Increases Radiation Sensitivity of Human Tumor Cells

<div><p>Inhibition of mammalian target of rapamycin-complex 1 (mTORC1) induces activation of Akt. Because Akt activity mediates the repair of ionizing radiation-induced DNA double-strand breaks (DNA-DSBs) and consequently the radioresistance of solid tumors, we investigated whether dual targeting of mTORC1 and Akt impairs DNA-DSB repair and induces radiosensitization. Combining mTORC1 inhibitor rapamycin with ionizing radiation in human non-small cell lung cancer (NSCLC) cells (H661, H460, SK-MES-1, HTB-182, A549) and in the breast cancer cell line MDA-MB-231 resulted in radiosensitization of H661 and H460 cells <i>(responders)</i>, whereas only a very slight effect was observed in A549 cells, and no effect was observed in SK-MES-1, HTB-182 or MDA-MB-231 cells (<i>non-responders</i>). In <i>responder</i> cells, rapamycin treatment did not activate Akt1 phosphorylation, whereas in <i>non-responders</i>, rapamycin mediated PI3K-dependent Akt activity. Molecular targeting of Akt by Akt inhibitor MK2206 or knockdown of Akt1 led to a rapamycin-induced radiosensitization of <i>non-responder</i> cells. Compared to the single targeting of Akt, the dual targeting of mTORC1 and Akt1 markedly enhanced the frequency of residual DNA-DSBs by inhibiting the non-homologous end joining repair pathway and increased radiation sensitivity. Together, lack of radiosensitization induced by rapamycin was associated with rapamycin-mediated Akt1 activation. Thus, dual targeting of mTORC1 and Akt1 inhibits repair of DNA-DSB leading to radiosensitization of solid tumor cells.</p></div

Schematics illustrating the potential pathways by which dual targeting of Akt and mTORC1 enhances the frequency of residual DNA-DSBs and increases radiation sensitivity.

<p>Schematics illustrating the potential pathways by which dual targeting of Akt and mTORC1 enhances the frequency of residual DNA-DSBs and increases radiation sensitivity.</p