Proceedings of the National Academy of Sciences of the United States of America
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Proc. Natl. Acad. Sci. U.S.A. · Oct 2004
Bacteriolytic therapy can generate a potent immune response against experimental tumors.
When spores of the anaerobic bacterium Clostridium novyi-NT are systemically injected into animals, they germinate exclusively within the hypoxic regions of cancers. The germinated bacteria destroy adjacent tumor cells but spare a rim of well oxygenated tumor cells that subsequently expand. ⋯ Similar effects were observed in rabbits with intrahepatic tumors. It was particularly notable that the induced immune response, when combined with the bacteriolytic effects of C. novyi-NT, could eradicate large established tumors.
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Proc. Natl. Acad. Sci. U.S.A. · Oct 2004
Small interfering RNA targeting Fas protects mice against renal ischemia-reperfusion injury.
Fas-mediated apoptosis has been suggested to contribute to tubular cell death after renal ischemia-reperfusion injury. Here we investigate whether small interfering RNA (siRNA) duplexes targeting Fas protect mice from acute renal failure after clamping of the renal artery. Renal ischemia-reperfusion injury was induced by clamping the renal vein and artery for 15 or 35 min. ⋯ Moreover, postischemic injection through the renal vein protected 38% of mice from death. This study confirms the importance of Fas-mediated apoptosis in renal ischemia-reperfusion injury. Silencing Fas by systemic or local catheterization holds therapeutic promise to limit ischemia-reperfusion injury.
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Proc. Natl. Acad. Sci. U.S.A. · Oct 2004
Visual expertise with nonface objects leads to competition with the early perceptual processing of faces in the human occipitotemporal cortex.
Human electrophysiological studies have found that the processing of faces and other objects differs reliably at approximately 150 ms after stimulus onset, faces giving rise to a larger occipitotemporal field potential on the scalp, termed the N170. We hypothesize that visual expertise with nonface objects leads to the recruitment of early face-related categorization processes in the occipitotemporal cortex, as reflected by the N170. To test this hypothesis, the N170 in response to laterally presented faces was measured while subjects concurrently viewed centrally presented, novel, nonface objects (asymmetric "Greebles"). ⋯ Five subjects were tested during three event-related potential sessions interspersed throughout a training protocol during which they became experts with Greebles. After expertise training, the N170 in response to faces was substantially decreased ( approximately 20% decrease in signal relative to that when subjects were novices) when concurrently processing a nonface object in the domain of expertise, but not when processing untrained objects of similar complexity. Thus, faces and nonface objects in a domain of expertise compete for early visual categorization processes in the occipitotemporal cortex.
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We researched the lifespan of Drosophila under axenic conditions compared with customary procedure. The experiments revealed that the presence of bacteria during the first week of adult life can enhance lifespan, despite unchanged food intake. Later in life, the presence of bacteria can reduce lifespan. Certain long-lived mutants react in different ways, indicating an interplay between bacteria and longevity-enhancing genes.
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Proc. Natl. Acad. Sci. U.S.A. · Aug 2004
Nociceptor-specific gene deletion reveals a major role for Nav1.7 (PN1) in acute and inflammatory pain.
Nine voltage-gated sodium channels are expressed in complex patterns in mammalian nerve and muscle. Three channels, Na(v)1.7, Na(v)1.8, and Na(v)1.9, are expressed selectively in peripheral damage-sensing neurons. Because there are no selective blockers of these channels, we used gene ablation in mice to examine the function of Na(v)1.7 (PN1) in pain pathways. ⋯ A congenital pain syndrome in humans recently has been mapped to the Na(v)1.7 gene, SCN9A. Dominant Na(v)1.7 mutations lead to edema, redness, warmth, and bilateral pain in human erythermalgia patients, confirming an important role for Na(v)1.7 in inflammatory pain. Nociceptor-specific gene ablation should prove useful in understanding the role of other broadly expressed genes in pain pathways.