Live cell imaging reveals 3 '-UTR dependent mRNA sorting to synapses

mRNA transport restricts translation to specific subcellular locations, which is the basis for many cellular functions. However, the precise process of mRNA sorting to synapses in neurons remains elusive. Here we use Rgs4 mRNA to investigate 3'-UTR-dependent transport by MS2 live-cell imaging. The majority of observed RNA granules display 3'-UTR independent bidirectional transport in dendrites. Importantly, the Rgs4 3'-UTR causes an anterograde transport bias, which requires the Staufen2 protein. Moreover, the 3'-UTR mediates dynamic, sustained mRNA recruitment to synapses. Visualization at high temporal resolution enables us to show mRNA patrolling dendrites, allowing transient interaction with multiple synapses, in agreement with the sushi-belt model. Modulation of neuronal activity by either chemical silencing or local glutamate uncaging regulates both the 3'-UTR-dependent transport bias and synaptic recruitment. This dynamic and reversible mRNA recruitment to active synapses would allow translation and synaptic remodeling in a spatially and temporally adaptive manner

Role of pathogenic oral flora in postoperative pneumonia following brain surgery

<p>Abstract</p> <p>Background</p> <p>Post-operative pulmonary infection often appears to result from aspiration of pathogens colonizing the oral cavity. It was hypothesized that impaired periodontal status and pathogenic oral bacteria significantly contribute to development of aspiration pneumonia following neurosurgical operations. Further, the prophylactic effects of a single dose preoperative cefazolin on the oral bacteria were investigated.</p> <p>Methods</p> <p>A matched cohort of 18 patients without postoperative lung complications was compared to 5 patients who developed pneumonia within 48 hours after brain surgery. Patients waiting for elective operation of a single brain tumor underwent dental examination and saliva collection before surgery. Bacteria from saliva cultures were isolated and periodontal disease was scored according to type and severity. Patients received 15 mg/kg cefazolin intravenously at the beginning of surgery. Serum, saliva and bronchial secretion were collected promptly after the operation. The minimal inhibitory concentrations of cefazolin regarding the isolated bacteria were determined. The actual antibiotic concentrations in serum, saliva and bronchial secretion were measured by capillary electrophoresis upon completion of surgery. Bacteria were isolated again from the sputum of postoperative pneumonia patients.</p> <p>Results</p> <p>The number and severity of coexisting periodontal diseases were significantly greater in patients with postoperative pneumonia in comparison to the control group (p = 0.031 and p = 0.002, respectively). The relative risk of developing postoperative pneumonia in high periodontal score patients was 3.5 greater than in patients who had low periodontal score (p < 0.0001). Cefazolin concentration in saliva and bronchial secretion remained below detectable levels in every patient.</p> <p>Conclusion</p> <p>Presence of multiple periodontal diseases and pathogenic bacteria in the saliva are important predisposing factors of postoperative aspiration pneumonia in patients after brain surgery. The low penetration rate of cefazolin into the saliva indicates that its prophylactic administration may not be sufficient to prevent postoperative aspiration pneumonia. Our study suggests that dental examination may be warranted in order to identify patients at high risk of developing postoperative respiratory infections.</p

An Intracellular Transmission Control Protocol: assembly and transport of ribonucleoprotein complexes

International audienc

Control of RNP motility and localization by a splicing-dependent structure in oskar mRNA

International audienc

HorkaD, a Chromosome Instability-Causing Mutation in Drosophila, Is a Dominant-Negative Allele of lodestar

Correct segregation of chromosomes is particularly challenging during the rapid nuclear divisions of early embryogenesis. This process is disrupted by HorkaD, a dominant-negative mutation in Drosophila melanogaster that causes female sterility due to chromosome tangling and nondisjunction during oogenesis and early embryogenesis. HorkaD also renders chromosomes unstable during spermatogenesis, which leads to the formation of diplo//haplo mosaics, including the gynandromorphs. Complete loss of gene function brings about maternal-effect lethality: embryos of the females without the HorkaD-identified gene perish due to disrupted centrosome function, defective spindle assembly, formation of chromatin bridges, and abnormal chromosome segregation during the cleavage divisions. These defects are indicators of mitotic catastrophe and suggest that the gene product acts during the meiotic and the cleavage divisions, an idea that is supported by the observation that germ-line chimeras exhibit excessive germ-line and cleavage function. The gene affected by the HorkaD mutation is lodestar, a member of the helicase-related genes. The HorkaD mutation results in replacement of Ala777 with Thr, which we suggest causes chromosome instability by increasing the affinity of Lodestar for chromatin

Ecdysone Induced Gene Expression Is Associated with Acetylation of Histone H3 Lysine 23 in Drosophila melanogaster

Posttranslational modification of histones regulates transcription but the exact role that acetylation of specific lysine residues plays in biological processes in vivo is still not clearly understood. To assess the contribution of different histone modifications to transcriptional activation in vivo, we determined the acetylation patterns on the ecdysone induced Eip74EF and Eip75B genes in Drosophila melanogaster larvae by chromatin immunoprecipitation. We found that acetylation of histone H3 lysine 23 is localized to promoters and correlates with endogenous ecdysone induced gene activation. In contrast, acetylation of lysines 8, 12 and 16 of histone H4 and lysine 9 of histone H3 showed minor differences in their distribution on the regulatory and transcribed regions tested, and had limited or no correlation with ecdysone induced transcriptional activity. We found that dCBP, which is encoded by the nejire gene, acetylates H3 lysine 23 in vivo, and silencing of nejire leads to reduced expression of the Eip74EF and Eip75B genes. Our results suggest that acetylation of specific lysine residues of histones contribute specifically to the dynamic regulation of transcription. Furthermore, along with previous studies identify CBP dependent H3 lysine 23 acetylation as an evolutionarily conserved chromatin modification involved in steroid induced gene activation