Empirical and Phenomenological Studies of Embodied Cognition

This surveys central results in empirical and phenomenological studies of embodied cognition. The central effort is to show how Husserl's phenomenology and emphasis on kinaesthesis leads to an argument that cognition must inherently be embodied

Dimers of Nostocarboline with Potent Antibacterial Activity

&lt;i&gt;Objectives:&lt;/i&gt; In this study, the in vitro antimicrobial activity and spectrum of new dimeric compounds derived from the cyanobacterial alkaloid nostocarboline were investigated. The mechanism of action and selectivity to bacteria were studied and compared to the cationic antiseptic chlorhexidine. &lt;i&gt;Methods:&lt;/i&gt;Minimal inhibitory concentrations were determined against clinical isolates and against a panel of microbial reference strains using the CLSI microdilution method. Bacterial membrane damage was addressed by measuring ATP leakage and the mode of action was investigated in &lt;i&gt;Escherichia coli&lt;/i&gt; reporter strains. Selectivity was tested by a cytotoxicity assay using MTS. &lt;i&gt;Results:&lt;/i&gt; The antimicrobial potency of dimers varied with length of the hydrophobic linker. The most potent compounds, NCD9 and NCD10, had a C10 and C12 linker, respectively, and showed strong activity against Gram-positive bacteria, notably methicillin-resistant &lt;i&gt;Staphylococcus aureus&lt;/i&gt; strains. Similar to chlorhexidine, these compounds showed a rapid concentration-dependent bactericidal effect, which correlated with membrane damage as indicated by ATP leakage. NCD9, in contrast to NCD10 and chlorhexidine, lacked activity against yeast strains and showed low cytotoxicity in CHO cells indicating a high degree of selectivity. In &lt;i&gt;E. coli&lt;/i&gt; reporter strains, NCD9 induced the DegP response pathway as well as the SOS response, suggesting interaction with both the cell envelope and DNA metabolism. &lt;i&gt;Conclusions:&lt;/i&gt; The results presented in this report indicate the potential of this new class of cationic antimicrobial compounds for the design of potent and selective antibacterials with low cytotoxicity.</jats:p

Antimalarial and antitubercular nostocarboline and eudistomin derivatives: Synthesis, in vitro and in vivo biological evaluation

The synthesis of nine nostocarboline derivatives with substitutions of the 2-methyl group by alkyl, aryl and functionalized residues, 10 symmetrical bis cationic dimers linking 6-Cl-norharmane through the 2-position and fifteen derivatives of the marine alkaloids eudistomin N and O is reported. These compounds were evaluated in vitro against four parasites (Trypanosoma brucei rhodesiense STIB 900, Trypanosoma cruzi Tulahuen C2C4, Leishmania donovani MHOM-ET-67/L82 axenic amastigotes, and Plasmodium falciparum K1 strain), against Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis mc(2)155 and Corynebacterium glutamicum ATCC13032, and cytotoxicity was determined against L6 rat myoblast cells. Nostocarboline and derivatives displayed potent and selective in vitro inhibition of P. falciparum with weak cytotoxicity. The dimers displayed submicromolar inhibition of L. donovani and T. brucei, and nanomolar activity against P. falciparum, albeit with pronounced cytotoxicity. One dimer showed a MIC(99) value against M. tuberculosis of 2.5mug/ml. The alkylated eudistomin N and O derivatives displayed activities down to 18nM against P. falciparum for N-Me Eudistomin N. Four dimers, nostocarboline and three eudostomin derivatives were evaluated in an in vivo Plasmodium berghei mouse model. No significant activity was observed for the dimers, but a 50% reduction in parasitaemia was observed at 4x50mg/kg ip for nostocarbolin