Red meat intake-induced increases in fecal water genotoxicity correlate with pro-carcinogenic gene expression changes in the human colon

Red meat consumption is associated with an increased colorectal cancer (CRC) risk, which may be due to an increased endogenous formation of genotoxic N-nitroso compounds (NOCs). To assess the impact of red meat consumption on potential risk factors of CRC, we investigated the effect of a 7-day dietary red meat intervention in human subjects on endogenous NOC formation and fecal water genotoxicity in relation to genome-wide transcriptomic changes induced in colonic tissue. The intervention showed no effect on fecal NOC excretion but fecal water genotoxicity significantly increased in response to red meat intake. Colonic inflammation caused by inflammatory bowel disease, which has been suggested to stimulate endogenous nitrosation, did not influence fecal NOC excretion or fecal water genotoxicity. Transcriptomic analyses revealed that genes significantly correlating with the increase in fecal water genotoxicity were involved in biological pathways indicative of genotoxic effects, including modifications in DNA damage repair, cell cycle, and apoptosis pathways. Moreover, WNT signaling and nucleosome remodeling pathways were modulated which are implicated in human CRC development. We conclude that the gene expression changes identified in this study corroborate the genotoxic potential of diets high in red meat and point towards a potentially increased CRC risk in humans.

Ensuring the right to the city: pro-poor housing, urban development and tenure legalization in São Paulo, Brazil

São Paulo is one of Latin America’s most modern and developed cities, yet around one-third of its 10 million inhabitants live in poor-quality housing in sub-standard settlements. This paper describes the response of the São Paulo municipal government that took office in 2001. Through its Secretariat of Housing and Urban Development, it designed a new policy framework with a strong emphasis on improving the quantity and quality of housing for low-income groups. Supported by new legislation, financial instruments and partnerships with the private sector, the mainstays of the new policy are integrated housing and urban development, modernization of the administrative system, and public participation in all decision-making and implementation processes. The programmes centre on upgrading and legalizing land tenure in informal settlements, and regeneration of the city centre. The new focus on valuing the investments that low-income groups have already made in their housing and settlements has proved to be more cost-effective than previous interventions, leading to improvements on an impressive scale.

Effects of fermentation products of pro- and prebiotics on trans-epithelial electrical resistance in an in vitro model of the colon

Evidence from in vivo and in vitro studies suggests that the consumption of pro- and prebiotics may inhibit colon carcinogenesis; however, the mechanisms involved have, thus far, proved elusive. There are some indications from animal studies that the effects are being exerted during the promotion stage of carcinogenesis. One feature of the promotion stage of colorectal cancer is the disruption of tight junctions, leading to a loss of integrity across the intestinal barrier. We have used the Caco-2 human adenocarcinoma cell line as a model for the intestinal epithelia. Trans-epithelial electrical resistance measurements indicate Caco-2 monolayer integrity, and we recorded changes to this integrity following exposure to the fermentation products of selected probiotics and prebiotics, in the form of nondigestible oligosaccharides (NDOs). Our results indicate that NDOs themselves exert varying, but generally minor, effects upon the strength of the tight junctions, whereas the fermentation products of probiotics and NDOs tend to raise tight junction integrity above that of the controls. This effect was bacterial species and oligosaccharide specific. Bifidobacterium Bb 12 was particularly effective, as were the fermentation products of Raftiline and Raftilose. We further investigated the ability of Raftilose fermentations to protect against the negative effects of deoxycholic acid (DCA) upon tight junction integrity. We found protection to be species dependent and dependent upon the presence of the fermentation products in the media at the same time as or after exposure to the DCA. Results suggest that the Raftilose fermentation products may prevent disruption of the intestinal epithelial barrier function during damage by tumor promoters.

Structural and morphological studies of the dipeptide based L-Pro-L-Val organocatalytic gels and their rheological behaviour

Organocatalytic gels based on the dipeptide sequence L-Pro-L-Val have been studied by two different FTIR techniques. This suggests a different arrangement of the gelator molecules in the self-assembled fibers depending on the organic solvent employed. In acetonitrile and nitromethane the structure of the supramolecular aggregates is similar and provides similar catalytic properties (supramolecularenhancement of basicity). In contrast, the self-assembled fibers obtained in toluene clearly presented a different molecular arrangement consistent with its different catalytic behaviour (enamine-based catalysis). In addition these gels have been studied by microscopy and rheology.

Influence of diluent alkyl substitution on the extraction of Am(III) and Eu(III) by a 6,6'-bis(1,2,4-triazinyl)-2,2'-bipyridine ligand dissolved in alkylated cyclohexanone diluents

Several alkylated cyclohexanones were investigated as potential diluents for the selective extraction of Am(III) and Eu(III) from nitric acid solutions by the CyMe4-BTBP ligand. No significant extraction of either of the metal ions was observed for these diluents themselves. In the extractions from 1 M HNO3, 3-methylcyclohexanone and 4-methylcyclohexanone gave comparable results to cyclohexanone whereas in the extractions from 4 M HNO3, 2-methylcyclohexanone, 3-methylcyclohexanone and 4-methylcyclohexanone all gave superior results. For the monomethylated diluents, DAm and SFAm/Eu decreased in the order of alkyl substitution 2 > 4 ~ 3. However, alkyl substitution of cyclohexanone significantly slows down the extraction kinetics compared to cyclohexanone, and the position of alkyl substitution was found to play an important role in the solvents properties. 3-Methylcyclohexanone was identified as the most promising of the diluents.

Suppression of a pro-apoptotic K+ channel as a mechanism for hepatitis C virus persistence

An estimated 3% of the global population are infected with hepatitis C virus (HCV), and the majority of these individuals will develop chronic liver disease. As with other chronic viruses, establishment of persistent infection requires that HCV-infected cells must be refractory to a range of pro-apoptotic stimuli. In response to oxidative stress, amplification of an outward K(+) current mediated by the Kv2.1 channel, precedes the onset of apoptosis. We show here that in human hepatoma cells either infected with HCV or harboring an HCV subgenomic replicon, oxidative stress failed to initiate apoptosis via Kv2.1. The HCV NS5A protein mediated this effect by inhibiting oxidative stress-induced p38 MAPK phosphorylation of Kv2.1. The inhibition of a host cell K(+) channel by a viral protein is a hitherto undescribed viral anti-apoptotic mechanism and represents a potential target for antiviral therapy.

Brill Greek, Adobe Arno Pro, Adobe Text/Brevier Greek typefaces

Typeface design: a series of collaborative projects commissioned by Adobe, Inc. and Brill to develop extensive polytonic Greek typefaces. The two Adobe typefaces can be seen as extension of previous research for the Garamond Premier Pro family (2005), and concludes a research theme started in 1998 with work for Adobe’s Minion Pro Greek. These typefaces together define the state of the art for text-intensive Greek typesetting for wide character set texts (from classical texts, to poetry, to essays, to prose). They serve both as exemplar for other developers, and as vehicles for developing the potential of Greek text typography, for example with the parallel inclusion of monotonic and polytonic characters, detailed localised punctuation options, fluid handling of case-conversion issues, and innovative options such as accented small caps (originally requested by bibliographers, and subsequently rolled out to a general user base). The Brill typeface (for the established academic publisher) has an exceptionally wide character set to cover several academic disciplines, and is intended to differentiate sufficiently from its partner Latin typeface, while maintaining a clear texture in both offset and low-resolution print-on-demand reproduction. This work involved substantial amounts of testing and modifying the design, especially of diacritics, to maintain clarity the readability of unfamiliar words. All together these typefaces form a study in how Greek typesetting meets contemporary typographic requirements, while resonating with historically accurate styles, where these are present. Significant research in printing archives helped to identify appropriate styles, as well as originate variants that are coherent stylistically, even when historical equivalents were absent.

Panaméricas Utópicas: entranced and transient nations in 'I Am Cuba' and 'Land in Trance'

This Chapter looks at two political films, Land in Trance (Glauber Rocha, 1967) and I Am Cuba (Mikhail Kalatozov, 1964), which address the subject of the nation through the enactment of trance. Rejecting all forms of naturalistic account, both films adopt a series of anti-realist devices, such as poetic language, synecdoche, personification, parable and allegory, as a means of expanding the concept of the nation beyond territorial borders and conveying the meaning of revolution through the film form rather than its content.

Paraméricas Utópicas: entranced and transient nations in "I Am Cuba" (1964) and "Land in Anguish" (1967)

This article examines the astonishing similarities between two political films, Land in Trance (Glauber Rocha, 1967) and I Am Cuba (Mikhail Kalatozov, 1964). Both address the subject of revolution through the enactment of trance. Both reject all forms of naturalistic account, adopting a series of anti-realist devices, such as poetic language, synecdoche, personification, parable and allegory, as a means of expanding the concept of the nation beyond territorial borders and conveying the meaning of revolution through the film form, rather than its content. Because there is no evidence that Glauber Rocha had seen I Am Cuba before he shot Land in Trance, these coincidences are treated as an intellectual 'transit' between film-makers whose art was fuelled by cinephilia and the belief in the reality of the film medium.