Excitatory synaptic transmission is accompanied by a local surge in interstitial lactate that occurs despite adequate oxygen availability, a puzzling phenomenon termed aerobic glycolysis. In addition ...to its role as an energy substrate, recent studies have shown that lactate modulates neuronal excitability acting through various targets, including NMDA receptors and G-protein-coupled receptors specific for lactate, but little is known about the cellular and molecular mechanisms responsible for the increase in interstitial lactate. Using a panel of genetically encoded fluorescence nanosensors for energy metabolites, we show here that mouse astrocytes in culture, in cortical slices, and in vivo maintain a steady-state reservoir of lactate. The reservoir was released to the extracellular space immediately after exposure of astrocytes to a physiological rise in extracellular K(+) or cell depolarization. Cell-attached patch-clamp analysis of cultured astrocytes revealed a 37 pS lactate-permeable ion channel activated by cell depolarization. The channel was modulated by lactate itself, resulting in a positive feedback loop for lactate release. A rapid fall in intracellular lactate levels was also observed in cortical astrocytes of anesthetized mice in response to local field stimulation. The existence of an astrocytic lactate reservoir and its quick mobilization via an ion channel in response to a neuronal cue provides fresh support to lactate roles in neuronal fueling and in gliotransmission.
Microglial cells are the main HIV-1 targets in the central nervous system (CNS) and constitute an important reservoir of latently infected cells. Establishment and persistence of these reservoirs ...rely on the chromatin structure of the integrated proviruses. We have previously demonstrated that the cellular cofactor CTIP2 forces heterochromatin formation and HIV-1 gene silencing by recruiting HDAC and HMT activities at the integrated viral promoter. In the present work, we report that the histone demethylase LSD1 represses HIV-1 transcription and viral expression in a synergistic manner with CTIP2. We show that recruitment of LSD1 at the HIV-1 proximal promoter is associated with both H3K4me3 and H3K9me3 epigenetic marks. Finally, our data suggest that LSD1-induced H3K4 trimethylation is linked to hSET1 recruitment at the integrated provirus.
Please cite this paper as: Moss E, Pearmain P, Askew S, Owen G, Reynolds T, Prabakar I, Douce G, Parkes J, Menon V, Todd R, Redman C. Implementing the national invasive cervical cancer audit: a local ...perspective. BJOG 2010;117:1411–1416.
Objective To monitor the effectiveness of the cervical screening programme and identify suboptimal management in order to improve patient care.
Design Retrospective study.
Setting A university hospital serving a population of 1 million people.
Population All women diagnosed with a cervical cancer between 2003 and 2006.
Methods Analysis of data from invasive cervical cancer reviews.
Main outcome measure Categorisation of cervical cancer cases according to the Invasive Cervical Cancer Audit classification.
Results Eighty‐seven women were diagnosed with cervical cancer during the 3‐year study period. The ‘lapsed attender’ group accounted for the greatest number of cases (30%), followed by screen detected (26%), interval cancers (13%), never attended (12%), lost to follow‐up (10%) and never invited (9%). Women who had never attended for cytology presented with higher stage disease, stage‐II or above, compared with the screen‐detected cases: 60% were stage II or above, compared with 13.0%, Chi‐square P = 0.018. The most frequently identified screening programme problem was patient compliance, which was determined to be the principle contributing factor in 39 cases (45%) and a secondary factor in a further ten cases.
Conclusions The categorisation of cervical cancer cases has the potential of yielding invaluable information for improving programme effectiveness. Patient compliance is the greatest challenge to the screening programme, and the need for regular screening and adherence to follow‐up regimens needs to be reinforced in order to maximise the efficacy of the national screening programme.
We have previously shown that infection of mice with
H. pylori can be prevented by oral immunization with
H. pylori antigens given together with
E. coli heat-labile enterotoxin (LT) as adjuvant. ...Since LT cannot be used in humans because of its unacceptable toxicity, we investigated whether protection of mice could be achieved by co-administration of antigens with non-toxic LT mutants. Here we show that CD1/SPF mice are protected against infection after oral vaccination with either purified
H. pylori antigens (native and recombinant VacA, urease and CagA), or whole-cell vaccine formulations, given together with the non-toxic mutant LTK63 as a mucosal adjuvant. Furthermore we show that such protection is antigen-specific since immunization with recombinant or native VacA plus LTK63 conferred protection against infection by an
H. pylori Type I strain, which expresses VacA, but not against challenge with a Type II strain which is not able to express this antigen. These results show that:
1.
protection against
H. pylori can be achieved in the mouse model of infection using subunit recombinant constructs plus non-toxic mucosal adjuvants; and
2.
this mouse model is an useful tool in testing
H. pylori vaccine formulations for eventual use in humans.
The authors describe one approach to the supervision of novice clinical supervisors. A central feature of this group approach to supervising supervisors is the eight recurring supervisory issues: ...supervisor anxiety, intervention choices, group cohesion, responsibility, parallel process, power struggles, individual differences, and sexual attraction. Our experience suggests that assessing and successfully confronting these supervisory issues seem to be an integral part of supervisor supervision. Suggestions for addressing these issues are offered.
La gestion integree d' un cours d' eau implique la comprehension de son fonctionnement global. Par souci d' economie de moyens et de temps, il est cependant rarement possible de realiser une etude ...detaillee sur tout le lineaire de la riviere ainsi que son bassin versant. Une methode typologique permet d' identifier des secteurs correspondant chacun a un type de fonctionnement et ainsi de choisir correctement les sites d' etude approfondie. La typologie presentee consiste en une synthese de donnees courantes concernant la geomorphologie et l' hydrobiologie. Une analyse descriptive et objective fait apparaitre de grands troncons de cours d' eau et les variables les plus discriminantes pour leur identification. Il s' agit de la pente du profil en long, de la largeur du lit a pleins-bords et de la geologie du bassin versant. Ce resultat valide l' utilisation de la puissance specifique pour la sectorisation longitudinale des cours d' eau. Cette sectorisation fonctionnelle permet d' associer des modes de gestion a chacun des troncons retenus: l' exemple presente est celui du Vidourle, fleuve cotier mediterraneen situe dans la partie orientale du Languedoc.
PDF
