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51.
Gliomas are often resistant to the induction of apoptotic cell death as a result of the development of survival mechanisms during astrocyte malignant transformation. In particular, the overexpression of Bcl-2-family members interferes with apoptosis initiation by DNA-damaging agents (e.g., cisplatin) or soluble death ligands (e.g., TRAIL). Using low-passage-number cultures of glioma cells, we have shown that parvovirus H-1 is able to induce death in cells resistant to TRAIL, cisplatin, or both, even when Bcl-2 is overexpressed. Parvovirus H-1 triggers cell death through both the accumulation of lysosomal cathepsins B and L in the cytosol of infected cells and the reduction of the levels of cystatin B and C, two cathepsin inhibitors. The impairment of either of these effects protects glioma cells from the viral lytic effect. In normal human astrocytes, parvovirus H-1 fails to induce a killing mechanism. In vivo, parvovirus H-1 infection of rat glioma cells intracranially implanted into recipient animals triggers cathepsin B activation as well. This report identifies for the first time cellular effectors of the killing activity of parvovirus H-1 against malignant brain cells and opens up a therapeutic approach which circumvents their frequent resistance to other death inducers.  相似文献   
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The analytical study of two hot-water extracts from the mushrooms Inonotus hispidus (Bull.) P. Karst and Sparassis crispa Wulf.:Fr was performed by NMR, HPLC-PAD-MS and GC-MS. The simultaneous use of different analytical techniques highlighted the diverse classes of natural products contained in these extracts. This study describes an attempt to adapt a useful phytochemical method to the direct investigation of plant water extracts, which represent the typical traditional manner for the administration of natural remedies. The heritage concerning plant processing procedures, known as traditional pharmaceutical knowledge, could play an important role in future research on medicinal species. This kind of study could be used as an update for current and future perspectives in this research field.  相似文献   
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Benucci A  Frazor RA  Carandini M 《Neuron》2007,55(1):103-117
The visual cortex represents stimuli through the activity of neuronal populations. We measured the evolution of this activity in space and time by imaging voltage-sensitive dyes in cat area V1. Contrast-reversing stimuli elicit responses that oscillate at twice the stimulus frequency, indicating that signals originate mostly in complex cells. These responses stand clear of the noise, whose amplitude decreases as 1/frequency, and yield high-resolution maps of orientation preference and retinotopy. We first show how these maps are combined to yield the responses to focal, oriented stimuli. We then study the evolution of the oscillating activity in space and time. In the orientation domain, it is a standing wave. In the spatial domain, it is a traveling wave propagating at 0.2-0.5 m/s. These different dynamics indicate a fundamental distinction in the circuits underlying selectivity for position and orientation, two key stimulus attributes.  相似文献   
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The association between iron, an oxidant catalyst, and atherosclerosis is controversial. In particular, it is unknown whether: (1) stored iron, namely serum ferritin, is correlated with catalytic iron and oxidant damage of human atherosclerotic plaques; (2) catalytic iron is related to oxidative injury within such plaques; (3) plaque oxidant burden is associated with the severity of atherosclerosis. Thus, we assessed low molecular weight iron (LMWI), which represents the metal catalytically active form, together with fluorescent damage products of lipid peroxidation (FDPL) and lipid hydroperoxides (LOOH), in 38 atherosclerotic plaques surgically removed from 38 patients who had undergone selective carotid endarterectomy. In each patient, the levels of serum ferritin were measured and correlated with those of plaque LMWI and lipoperoxides by the Spearman rank correlation test with Spearman rank correlation coefficient (r(S)) calculation. Moreover, in patients selected from the same study population, we compared plaque analyte levels between two groups with different severity of atherosclerotic carotid stenosis, i.e., <90% (group A, n = 25) or > or =90% (group B, n = 13), and between another two groups without (group C, n = 27) and with (group D, n = 11) associated contralateral carotid stenosis > or =50%, indicative of "extensive" and more severe atherosclerotic disease. In group A patients, serum ferritin was directly and significantly correlated with plaque LMWI (r(S) = 0.46, P < 0.025) and FDPL (r(S) = 0.58, P < 0.005), while its correlation with plaque LOOH, albeit direct, did not attain statistical significance. Moreover, a direct and significant relationship was evident between the plaque content of LMWI and that of both FDPL (r(S) = 0.61, P < 0.0025) and LOOH (r(S) = 0.51, P < 0.025), suggesting a prooxidant role of catalytic iron within human atherosclerotic plaques. Considering the 13 patients of group B, a positive and significant correlation was observed between the levels of serum ferritin and those of plaque LMWI (r(S) = 0.83, P < 0.0001); on the other hand, serum ferritin, as well as plaque LMWI, showed no significant correlation with either plaque FDPL or LOOH, conceivably reflecting the small number of patients belonging to group B. Finally, plaque LMWI, FDPL, and LOOH content was significantly higher in group B than in group A, and in group D than in group C. These data suggest a role for catalytic iron in atherosclerotic plaque oxidation and in the severity of atherosclerosis, which appears indeed associated with plaque oxidant burden.  相似文献   
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Defects in the structure or function of the primary cilium, an antennae-like structure whose functional integrity has been linked to the suppression of uncontrolled kidney epithelial cell proliferation, are a common feature of genetic disorders characterized by kidney cysts. However, the mechanisms by which primary cilia are maintained remain poorly defined. von Hippel-Lindau (VHL) disease is characterized by the development of premalignant renal cysts and arises because of functional inactivation of the VHL tumour suppressor gene product, pVHL. Here, we show that pVHL and glycogen synthase kinase (GSK)3beta are key components of an interlinked signalling pathway that maintains the primary cilium. Although inactivation of either pVHL or GSK3beta alone did not affect cilia maintenance, their combined inactivation leads to loss of cilia. In VHL patients, GSK3beta is subjected to inhibitory phosphorylation in renal cysts, but not in early VHL mutant lesions, and these cysts exhibit reduced frequencies of primary cilia. We propose that pVHL and GSK3beta function together in a ciliary-maintenance signalling network, disruption of which enhances the vulnerability of cells to lose their cilia, thereby promoting cyst formation.  相似文献   
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Background  

Calcium is commonly involved as intracellular messenger in the transduction by plants of a wide range of biotic stimuli, including signals from pathogenic and symbiotic fungi. Trichoderma spp. are largely used in the biological control of plant diseases caused by fungal phytopathogens and are able to colonize plant roots. Early molecular events underlying their association with plants are relatively unknown.  相似文献   
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A new class of bioactive and biodegradable soybean-based bone fillers   总被引:1,自引:0,他引:1  
The reconstruction of large bone defects in periodontal, maxillofacial, and orthopedic surgery relies on the implantation of biomaterials able to support the growth of new tissue. None of the materials currently available is able to combine all the properties required, which are (i) easy handling, (ii) biodegradation, (iii) low immunogenicity, and more importantly, (iv) induction of tissue regeneration. A new class of biodegradable biomaterials has been obtained by simple thermosetting of defatted soybean curd. The final material can be processed into films, porous scaffolds, and granules for different surgical needs. When incubated in physiological solutions the material shows water uptake of 80%, elongation at break of 0.9 mm/mm, and 25% (w/w) degradation in 7 days. Soybean-based biomaterial granules are shown to reduce the activity of the monocytes/macrophages and of the osteoclasts and to induce osteoblast differentiation in vitro, thus demonstrating a bone regeneration potential suitable for many clinical applications.  相似文献   
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