tNOX is both necessary and sufficient as a cellular target for the anticancer actions of capsaicin and the green tea catechin (-)-epigallocatechin-3-gallate

Capsaicin and the principal green tea catechin, (-)-epigallocatechin-3-gallate (EGCg), target tNOX, a tumor (cancer)-specific surface hydroquinone (NADH) oxidase with protein disulfide-thiol interchange activity (ECTO-NOX protein). Accordingly vector-forced over expression of tNOX in MCF-10A mammary epithelia or COS cells that lack tNOX or in COS cells that underexpress tNOX enhanced the susceptibility of growth and apoptosis to both EGCg and capsaicin. Additionally, the tNOX-transfected MCF-10A cells proliferated in Matrigel, a measure of invasiveness. In contrast, oligomeric antisense tNOX DNA abrogated growth inhibition by EGCg and capsaicin and reduced anchorage-dependent growth of HeLa (human cervical carcinoma) cells that naturally overexpress tNOX. The findings show cell surface expression of tNOX as both necessary and sufficient for the cellular anticancer activities attributed to both EGCg and capsaicin.     

Fellow travellers: a concordance of colonization patterns between mice and men in the North Atlantic region

Background

In the Calvin cycle of eubacteria, the dephosphorylations of both fructose-1, 6-bisphosphate (FBP) and sedoheptulose-1, 7-bisphosphate (SBP) are catalyzed by the same bifunctional enzyme: fructose-1, 6-bisphosphatase/sedoheptulose-1, 7-bisphosphatase (F/SBPase), while in that of eukaryotic chloroplasts by two distinct enzymes: chloroplastic fructose-1, 6-bisphosphatase (FBPase) and sedoheptulose-1, 7-bisphosphatase (SBPase), respectively. It was proposed that these two eukaryotic enzymes arose from the divergence of a common ancestral eubacterial bifunctional F/SBPase of mitochondrial origin. However, no specific affinity between SBPase and eubacterial FBPase or F/SBPase can be observed in the previous phylogenetic analyses, and it is hard to explain why SBPase and/or F/SBPase are/is absent from most extant nonphotosynthetic eukaryotes according to this scenario.

Results

Domain analysis indicated that eubacterial F/SBPase of two different resources contain distinct domains: proteobacterial F/SBPases contain typical FBPase domain, while cyanobacterial F/SBPases possess FBPase_glpX domain. Therefore, like prokaryotic FBPase, eubacterial F/SBPase can also be divided into two evolutionarily distant classes (Class I and II). Phylogenetic analysis based on a much larger taxonomic sampling than previous work revealed that all eukaryotic SBPase cluster together and form a close sister group to the clade of epsilon-proteobacterial Class I FBPase which are gluconeogenesis-specific enzymes, while all eukaryotic chloroplast FBPase group together with eukaryotic cytosolic FBPase and form another distinct clade which then groups with the Class I FBPase of diverse eubacteria. Motif analysis of these enzymes also supports these phylogenetic correlations.

Conclusions

There are two evolutionarily distant classes of eubacterial bifunctional F/SBPase. Eukaryotic FBPase and SBPase do not diverge from either of them but have two independent origins: SBPase share a common ancestor with the gluconeogenesis-specific Class I FBPase of epsilon-proteobacteria (or probably originated from that of the ancestor of epsilon-proteobacteria), while FBPase arise from Class I FBPase of an unknown kind of eubacteria. During the evolution of SBPase from eubacterial Class I FBPase, the SBP-dephosphorylation activity was acquired through the transition ??from specialist to generalist??. The evolutionary substitution of the endosymbiotic-origin cyanobacterial bifunctional F/SBPase by the two light-regulated substrate-specific enzymes made the regulation of the Calvin cycle more delicate, which contributed to the evolution of eukaryotic photosynthesis and even the entire photosynthetic eukaryotes.     

Diallyl sulfide, diallyl disulfide and diallyl trisulfide affect drug resistant gene expression in colo 205 human colon cancer cells in vitro and in vivo

To elevate chemo-resistance of human cancer cells is a major obstacle in the treatment and management of malignant cancers. Diallyl sulfide (DAS), diallyl disulfide (DADS) and diallyl trisulfide (DATS) are presented in the Alliaceae family particularly in garlic. Although DAS, DADS and DATS have been shown to exhibit anticancer activities, there is little information on effects of these compounds on drug resistant genes in human colon cancer cells in vitro and in vivo. Herein, we are the first to show that DAS, DADS and DATS at 25 μM for 24-h and 48-h incubations promoted expression of drug resistant genes in colo 205 human colon cancer cells. In vitro experiments indicated that DATS promoted gene expression of multidrug resistant 1 (Mdr1) (p<0.05), and DAS and DADS promoted MRP3 gene expression and DATS alone stimulated gene expression of multidrug resistance-associated protein-1 (MRP1) (p<0.05) in colo 205 cells. In vivo studies demonstrated that DADS and DATS induced Mdr1 and MRP1 gene expression (p<0.05). DADS promoted MRP3 gene expression (p<0.05) as well as DADS and DATS increased MRP4 and MRP6 gene expression (p<0.05) in the colo 205 xenograft mice. Based on our in vitro and in vivo results, diallyl polysulfides (DAS, DADS and DATS) affected the gene expression of the multidrug resistance in colo 205 human colon cancer cells in vitro and in vivo.     

Psychophysiology and psychoacoustics of music: Perception of complex sound in normal subjects and psychiatric patients

Perception of complex sound is a process carried out in everyday life situations and contributes in the way one perceives reality. Attempting to explain sound perception and how it affects human beings is complicated. Physics of simple sound can be described as a function of frequency, amplitude and phase. Psychology of sound, also termed psychoacoustics, has its own distinct elements of pitch, intensity and tibre. An interconnection exists between physics and psychology of hearing.Music being a complex sound contributes to communication and conveys information with semantic and emotional elements. These elements indicate the involvement of the central nervous system through processes of integration and interpretation together with peripheral auditory processing.Effects of sound and music in human psychology and physiology are complicated. Psychological influences of listening to different types of music are based on the different characteristics of basic musical sounds. Attempting to explain music perception can be simpler if music is broken down to its basic auditory signals. Perception of auditory signals is analyzed by the science of psychoacoustics. Differences in complex sound perception have been found between normal subjects and psychiatric patients and between different types of psychopathologies.