The impact of bilingualism in within-language conflict resolution: an ERP study.

We compared Spanish (L1)-English (L2) bilinguals and Spanish monolinguals in a semantic judgment relationship task in L1 that produced within-language conflict due to the coactivation of the two meanings of a Spanish homophone (e.g., "hola" and "ola" meaning "hello" and "a wave" in English). In this task, participants indicated if pairs of words were related or not ("agua-hola," "water-hello"). Conflict arose because a word ("agua," "water") not related to the orthographic form of a homophone ("hola," "hello") was related to the alternative orthographic form ("ola," "wave"). Compared to a control condition with unrelated word pairs ("peluche-hola," "teddy-hello"), the behavioral results revealed greater behavioral interference in monolinguals compared to bilinguals. In addition, electrophysiological results revealed N400 differences between monolinguals and bilinguals. These results are discussed around the impact of bilingualism on conflict resolution.

Can exercise shape your brain? A review of aerobic exercise effects on cognitive function and neuro-physiological underpinning mechanisms.

It is widely accepted that physical exercise can be used as a tool for the prevention and treatment of various diseases or disorders. In addition, in the recent years, exercise has also been successfully used to enhance people's cognition. There is a large amount of research that has supported the benefits of physical exercise on human cognition, both in children and adults. Among these studies, some have focused on the acute or transitory effects of exercise on cognition, while others have focused on the effects of regular physical exercise. However, the relation between exercise and cognition is complex and we still have limited knowledge about the moderators and mechanisms underlying this relation. Most of human studies have focused on the behavioral aspects of exercise-effects on cognition, while animal studies have deepened in its possible neuro-physiological mechanisms. Even so, thanks to advances in neuroimaging techniques, there is a growing body of evidence that provides valuable information regarding these mechanisms in the human population. This review aims to analyze the effects of regular and acute aerobic exercise on cognition. The exercise-cognition relationship will be reviewed both from the behavioral perspective and from the neurophysiological mechanisms. The effects of exercise on animals, adult humans, and infant humans will be analyzed separately. Finally, physical exercise intervention programs aiming to increase cognitive performance in scholar and workplace environments will be reviewed.

Differential role of human choline kinase alpha and beta enzymes in lipid metabolism: implications in cancer onset and treatment.

BACKGROUND: The Kennedy pathway generates phosphocoline and phosphoethanolamine through its two branches. Choline Kinase (ChoK) is the first enzyme of the Kennedy branch of synthesis of phosphocholine, the major component of the plasma membrane. ChoK family of proteins is composed by ChoKalpha and ChoKbeta isoforms, the first one with two different variants of splicing. Recently ChoKalpha has been implicated in the carcinogenic process, since it is over-expressed in a variety of human cancers. However, no evidence for a role of ChoKbeta in carcinogenesis has been reported. METHODOLOGY/PRINCIPAL FINDINGS: Here we compare the in vitro and in vivo properties of ChoKalpha1 and ChoKbeta in lipid metabolism, and their potential role in carcinogenesis. Both ChoKalpha1 and ChoKbeta showed choline and ethanolamine kinase activities when assayed in cell extracts, though with different affinity for their substrates. However, they behave differentially when overexpressed in whole cells. Whereas ChoKbeta display an ethanolamine kinase role, ChoKalpha1 present a dual choline/ethanolamine kinase role, suggesting the involvement of each ChoK isoform in distinct biochemical pathways under in vivo conditions. In addition, while overexpression of ChoKalpha1 is oncogenic when overexpressed in HEK293T or MDCK cells, ChoKbeta overexpression is not sufficient to induce in vitro cell transformation nor in vivo tumor growth. Furthermore, a significant upregulation of ChoKalpha1 mRNA levels in a panel of breast and lung cancer cell lines was found, but no changes in ChoKbeta mRNA levels were observed. Finally, MN58b, a previously described potent inhibitor of ChoK with in vivo antitumoral activity, shows more than 20-fold higher efficiency towards ChoKalpha1 than ChoKbeta. CONCLUSION/SIGNIFICANCE: This study represents the first evidence of the distinct metabolic role of ChoKalpha and ChoKbeta isoforms, suggesting different physiological roles and implications in human carcinogenesis. These findings constitute a step forward in the design of an antitumoral strategy based on ChoK inhibition.

Generation and characterization of monoclonal antibodies against choline kinase alpha and their potential use as diagnostic tools in cancer.

Choline kinase alpha (ChoKalpha) is a metabolic enzyme involved in the synthesis of phosphatidylcholine, recently implicated in cancer onset since it is overexpressed in a variety of human cancers such as mammary, lung, colorectal and prostate adenocarcinomas. Furthermore, overexpression of ChoKalpha in human HEK293T cells confers them oncogenic properties with the induction of tumors after subcutaneous injection in nude mice. ChoKalpha levels in tumor samples have been analyzed using polyclonal antibodies and Western blotting. These techniques have considerable limitations and do not allow for a precise and efficient evaluation of the real significance of ChoK overexpression in human carcinogenesis. We developed a set of monoclonal antibodies with high specificity and sensitivity against ChoKalpha, and characterized their properties. We provide evidence that the newly generated MoAbs against ChoKalpha have potential use in cancer diagnosis by conventional immunohistochemistry techniques.

Inhibition of choline kinase as a specific cytotoxic strategy in oncogene-transformed cells.

Cancer treatment is in the need of selective drugs that can interfere specifically with signalling pathways affected during the carcinogenic process. Identification of new potential molecular targets is the key event in the design of new anticancer strategies. Once identified, attempts for the generation of specific molecules to regulate their function can be achieved. The relevance of deregulation of choline kinase (ChoK, E.C. 2.7.1.32) in oncogene-driven cell transformation has been previously demonstrated. Here we provide strong evidence that MN58b, a selective inhibitor of ChoK, is rather specific to this enzyme, with no effect on a variety of oncogene-activated signalling pathways involved in the regulation of cell proliferation. MN58b does not affect MAPKs, PI3K, and other enzymes involved in the regulation of phospholipid metabolism such as phospholipases C, D, and A2, CTP:phosphocholine cytidylyltransferase, or diacylglycerol choline-phosphotransferase. Consistent with this specificity, ectopic expression of ChoK resulted in resistance to its inhibitor. Finally, nontransformed cells were able to resume cell proliferation after removal of the drug, while transformed cells were irreversibly affected. These results indicate that inhibition of ChoK is a rather specific strategy for the cytotoxic treatment of transformed cells.

Modulation of autoantibody production by mycophenolate mofetil: effects on the development of SLE in (NZB x NZW)F1 mice.

BACKGROUND: Mycophenolate mofetil (MMF) has been successfully used to improve or prevent the development of systemic lupus erythematosus (SLE) in both humans and in several lupus-prone mice. In the present study, we evaluated mechanisms through which MMF may exert its therapeutic effect on the development of systemic autoimmunity. METHODS: (NZBxNZW)F(1) female mice were continuously treated with 100 mg/kg/day (high dose) or 30 mg/kg/day (low dose) MMF beginning at 3 months of age. The development of an autoimmune syndrome was evaluated by measuring immunoglobulin (Ig) isotypes of autoantibodies and their levels, as well as by evaluating immunopathological kidney abnormalities and mortality curves. RESULTS: At both doses, MMF efficiently modulated the development of SLE. Although the higher dose of MMF directly inhibited the production of autoantibodies, 30 mg/kg/day MMF promoted qualitative but not quantitative changes in autoantibodies in (NZB x NZW)F(1) female mice. These qualitative changes were manifested as a selective reduction in total or antigen-specific IgG2a antibody levels. CONCLUSIONS: The mechanisms through which MMF controls the development of SLE in (NZB x NZW)F(1) females is highly dependent upon immunosuppressor dose. Interestingly, lower dose MMF selectively reduced IgG2a antibody levels, suggesting that this dose may modulate T(H1) CD4+ activity.

Increased choline kinase activity in human breast carcinomas: clinical evidence for a potential novel antitumor strategy.

Choline kinase (ChoK) and its product, phosphocholine (PCho), have been implicated in human carcinogenesis. Inhibition of this enzyme has been shown to be an efficient antitumor strategy in vivo. The aim of this study was to assess the relationship between the regulation of ChoK and clinical features in patients with breast cancer. To that end, normal and tumoral tissues from 53 patients with breast carcinomas were analysed for ChoK activity and expression, and compared to some clinical parameters. We report a relevant increase in ChoK activity in 38.5% of the tumoral tissues analysed when compared to the normal levels in healthy tissues. Furthermore, some clinical features were found significant versus ChoK status. First, an association of choline enzymatic activity with histological tumor grade was observed (P<0.001). In addition, increased ChoK activity was also associated with ER-negative breast carcinomas (P=0.037). A significant association between ChoK overexpression and both high histologic tumor grade (P=0.017) and ER-negative tumors (P=0.003) was found. Finally, ChoK overexpression was found in 17% of the samples and all corresponded with those that display the highest increase in ChoK activity (P<0.001). Here we provide evidence that ChoK may be related to the development of human breast cancer, suggesting that this finding may constitute the basis for the development of a novel antitumoral strategy for these patients.