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We have proposed a theory in which pathways ascending from the brainstem reticular formation control sensory centers in the dorsal thalamus and neocortex. We assumed that the sensory messages received at a given level are transformed by a stochastic process, called Alopex, in a way which maximizes responses in central feature analyzers. Perception is seen as a process involving a close cyclic interaction between brainstem and sensory relays. We discuss the specific case of visual information flow and the proposed modification of visual images at the level of the dorsal lateral geniculate nucleus (dLGN). Computer simulations of a simple model, representing the dLGN and reafferent control emanating from the reticular formation, show that sensory features are effectively enhanced and--in the absence of sensory input--quasi-sensory features may be generated by feedback of a simple scalar variable that is formed by the non-linear superposition of the responses of any number of feature analyzers. The model proposes a specific mechanism for such processes as visual imagery, hallucinations, and dreaming, and provides a framework for further studies into the nature of cognitive brain functions.  相似文献   
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The opportunistic pathogen Staphylococcus aureus is one of the major causes of health care-associated infections. S. aureus is primarily an extracellular pathogen, but it was recently reported to invade and replicate in several host cell types. The ability of S. aureus to persist within cells has been implicated in resistance to antimicrobials and recurrent infections. However, few staphylococcal proteins that mediate intracellular survival have been identified. Here we examine if EsxA and EsxB, substrates of the ESAT-6-like secretion system (Ess), are important during intracellular S. aureus infection. The Esx proteins are required for staphylococcal virulence, but their functions during infection are unclear. While isogenic S. aureus esxA and esxB mutants were not defective for epithelial cell invasion in vitro, a significant increase in early/late apoptosis was observed in esxA mutant-infected cells compared to wild-type-infected cells. Impeding secretion of EsxA by deleting C-terminal residues of the protein also resulted in a significant increase of epithelial cell apoptosis. Furthermore, cells transfected with esxA showed an increased protection from apoptotic cell death. A double mutant lacking both EsxA and EsxB also induced increased apoptosis but, remarkably, was unable to escape from cells as efficiently as the single mutants or the wild type. Thus, using in vitro models of intracellular staphylococcal infection, we demonstrate that EsxA interferes with host cell apoptotic pathways and, together with EsxB, mediates the release of S. aureus from the host cell.  相似文献   
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Purpose

JWH-424, (8-bromo-1-naphthyl)(1-pentyl-1H-indol-3-yl)methanone, is a synthetic cannabinoid, which is a brominated analogue of JWH-018, one of the best-known synthetic cannabinoids. Despite the structural similarity to JWH-018, little is known about JWH-424 including its metabolism. The aim of the study was to compare human liver microsomes (HLM) and the fungus Cunninghamella elegans as the metabolism catalysts for JWH-424 to better understand the characteristic actions of the fungus in the synthetic cannabinoid metabolism.

Methods

JWH-424 was incubated with HLM for 1 h and Cunninghamella elegans for up to 72 h. The HLM incubation mixtures were diluted with methanol and fungal incubation mixtures were extracted with dichloromethane and reconstituted in methanol before analyses by liquid chromatography–high-resolution mass spectrometry (LC-HRMS).

Results

HLM incubation resulted in production of ten metabolites through dihydrodiol formation, hydroxylation, and/or ipso substitution of the bromine with a hydroxy group. Fungal incubation led to production of 23 metabolites through carboxylation, dihydrodiol formation, hydroxylation, ketone formation, glucosidation and/or sulfation.

Conclusions

Generally, HLM models give good predictions of human metabolites and structural analogues are metabolised in a similar fashion. However, major hydroxy metabolites produced by HLM were those hydroxylated at naphthalene instead of pentyl moiety, the major site of hydroxylation for JWH-018. Fungal metabolites, on the other hand, had undergone hydroxylation mainly at pentyl moiety. The metabolic disagreement suggests the necessity to verify the human metabolites in authentic urine samples, while H9 and H10 (hydroxynaphthalene), H8 (ipso substitution), F22 (hydroxypentyl), and F17 (dihydroxypentyl) are recommended for monitoring of JWH-424 in urinalysis.

  相似文献   
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Background:

Organ transplantation is the most preferred treatment modality for end-stage organ diseases. The need for the transplants is higher than the availability. Prerequisites for the success of transplantation program include awareness and positive attitudes.

Aim:

To assess the perceptions and attitudes of the people seeking health care in tertiary care centers towards organ donation in Mangalore, India.

Settings and Design:

This cross-sectional study included 863 people seeking general healthcare as outpatients.

Materials and Methods:

Face to face interviews were carried out using pretested tools which included the socio demographic data. Data was analyzed using Statistical Package for Social Sciences version 11.5.

Results:

Overall, 59.6% participants showed the willingness to donate organs. Females (64.1%) and participants from upper socio economic status (62.7%) had higher willingness rates for organ donations. Hindus (63.6%) and Christians (63.3%) had higher willingness rates for organ donations than Muslims (38.2%). Also, 23.7% participants showed willingness to donate eyes and 33.6% wished to donate any organ after death. Most of the participants (67%) were aware that money should not be accepted for donating organs, and 58.1% were aware that it is an offence to accept any benefit for organ donations. Forty percent participants had perceived risks associated with organ donation. Regarding donor cards, 42.3% of the participants knew about it and 3.7% already possessed it.

Conclusion:

It is apparent from the study that though there was high level of awareness about organ donation, a high proportion of the participants did not have positive attitudes towards organ donation.  相似文献   
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