Pubmed du 26/12/08

lundi 5 janvier 2009

1. Flavell SW, Kim TK, Gray JM, Harmin DA, Hemberg M, Hong EJ, Markenscoff-Papadimitriou E, Bear DM, Greenberg ME. Genome-wide analysis of MEF2 transcriptional program reveals synaptic target genes and neuronal activity-dependent polyadenylation site selection. Neuron ;2008 (Dec 26) ;60(6):1022-1038.

Although many transcription factors are known to control important aspects of neural development, the genome-wide programs that are directly regulated by these factors are not known. We have characterized the genetic program that is activated by MEF2, a key regulator of activity-dependent synapse development. These MEF2 target genes have diverse functions at synapses, revealing a broad role for MEF2 in synapse development. Several of the MEF2 targets are mutated in human neurological disorders including epilepsy and autism spectrum disorders, suggesting that these disorders may be caused by disruption of an activity-dependent gene program that controls synapse development. Our analyses also reveal that neuronal activity promotes alternative polyadenylation site usage at many of the MEF2 target genes, leading to the production of truncated mRNAs that may have different functions than their full-length counterparts. Taken together, these analyses suggest that the ubiquitously expressed transcription factor MEF2 regulates an intricate transcriptional program in neurons that controls synapse development.

2. Kameshita I, Sekiguchi M, Hamasaki D, Sugiyama Y, Hatano N, Suetake I, Tajima S, Sueyoshi N. Cyclin-dependent kinase-like 5 binds and phosphorylates DNA methyltransferase 1. Biochem Biophys Res Commun ;2008 (Dec 26) ;377(4):1162-1167.

DNA methyltransferase 1 (Dnmt1) is an enzyme that recognizes and methylates hemimethylated CpG after DNA replication to maintain methylation patterns. Although the N-terminal region of Dnmt1 is known to interact with various proteins, such as methyl-CpG-binding protein 2 (MeCP2), the associations of protein kinases with this region have not been reported. In the present study, we found that a 110-kDa protein kinase in mouse brain could bind to the N-terminal domain of Dnmt1. This 110-kDa kinase was identified as cyclin-dependent kinase-like 5 (CDKL5) by LC-MS/MS analysis. CDKL5 and Dnmt1 were found to colocalize in nuclei and appeared to interact with each other. Catalytically active CDKL5, CDKL5(1-352), phosphorylated the N-terminal region of Dnmt1 in the presence of DNA. Considering that defects in the MeCP2 or CDKL5 genes cause Rett syndrome, we propose that the interaction between Dnmt1 and CDKL5 may contribute to the pathogenic processes of Rett syndrome.

3. Messieha Z, Cruz-Gonzalez W, Hakim MI. Retrospective outcomes evaluation of 100 parenteral moderate and deep sedations conducted in a general practice dental residency. Anesth Prog ;2008 (Winter) ;55(4):116-120.

An abstract of this study was presented at the American Association for Dental Research (AADR) Dental Anesthesiology Research Group in Honolulu, Hawaii, in March of 2004. This study was conducted to correlate the intraoperative and postoperative morbidity associated with moderate and deep sedation, also known as monitored anesthesia care (MAC), provided in a General Practice Residency (GPR) clinic under the supervision of a dentist anesthesiologist. After internal review board approval was obtained, 100 parenteral moderate and deep sedation cases performed by the same dentist anesthesiologist in collaboration with second year GPR residents were randomly selected and reviewed by 2 independent evaluators. Eleven morbidity criteria were assessed and were correlated with patient age, gender, American Society of Anesthesiology Physical Status Classification (ASAPS), duration of procedure, and anesthetic protocol. A total of 39 males and 61 females were evaluated. Patients’ ASAPS were classified as I, II, and III, with the average ASAPS of 1.61 and the standard deviation (STDEV) of 0.584. No ASPS IV or V was noted. Average patient age was 33.8 years (STDEV, 14.57), and the average duration of procedure was 97.5 minutes (STDEV, 42.39). Three incidents of postoperative nausea and vomiting were reported. All 3 incidents involved the ketamine-midazolam-propofol anesthetic combination. All patients were treated and were well controlled with ondansetron. One incident of tongue biting in an autistic child was regarded as an effect of local anesthesia. One patient demonstrated intermittent premature atrial contractions (PACs) intraoperatively but was stable. Moderate and deep sedation, also known as MAC, is safe and beneficial in an outpatient GPR setting with proper personnel and monitoring. This study did not demonstrate a correlation between length of procedure and morbidity. Ketamine was associated with all reported nausea and vomiting incidents because propofol and midazolam are rarely associated with such events.

4. Mrozek-Budzyn D, Kieltyka A. [The relationship between MMR vaccination level and the number of new cases of autism in children]. Przegl Epidemiol ;2008 ;62(3):597-604.Zaleznosc miedzy realizacja szczepien skojarzona szczepionka przeciw odrze swince i rozyczce a liczba rozpoznawanych przypadkow autyzmu u dzieci.

The MMR vaccination coverage in Malopolskie voivodeship improved rapidly and finally reached a high level during last years. The number of new cases of autism spectrum disorders in children during that time revealed a slightly rising but not significant trend, while the number of childhood autism were stable. Ecological study showed no correlation between MMR vaccination and an increased risk of childhood autism and autism spectrum disorders in children.


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