Parkinson's Disease DJ-1 L166P Alters rRNA Biogenesis by Exclusion of TTRAP from the Nucleolus and Sequestration into Cytoplasmic Aggregates via TRAF6

Mutations in PARK7/DJ-1 gene are associated to autosomal recessive early onset forms of Parkinson's disease (PD). Although large gene deletions have been linked to a loss-of-function phenotype, the pathogenic mechanism of missense mutations is less clear. The L166P mutation causes misfolding of DJ-1 protein and its degradation. L166P protein may also accumulate into insoluble cytoplasmic aggregates with a mechanism facilitated by the E3 ligase TNF receptor associated factor 6 (TRAF6). Upon proteasome impairment L166P activates the JNK/p38 MAPK apoptotic pathway by its interaction with TRAF and TNF Receptor Associated Protein (TTRAP). When proteasome activity is blocked in the presence of wild-type DJ-1, TTRAP forms aggregates that are localized to the cytoplasm or associated to nucleolar cavities, where it is required for a correct rRNA biogenesis. In this study we show that in post-mortem brains of sporadic PD patients TTRAP is associated to the nucleolus and to Lewy Bodies, cytoplasmic aggregates considered the hallmark of the disease. In SH-SY5Y neuroblastoma cells, misfolded mutant DJ-1 L166P alters rRNA biogenesis inhibiting TTRAP localization to the nucleolus and enhancing its recruitment into cytoplasmic aggregates with a mechanism that depends in part on TRAF6 activity. This work suggests that TTRAP plays a role in the molecular mechanisms of both sporadic and familial PD. Furthermore, it unveils the existence of an interplay between cytoplasmic and nucleolar aggregates that impacts rRNA biogenesis and involves TRAF6

Raman and FTIR imaging of lung tissue: methodology for controlsamples

The paper describes Raman and FTIR images of normal lung tissue of an infant patient which is a prerequisite to understand the biochemical changes that accompany pediatric lung pathologies and malformations. A Raman image of 3420 spectra was recorded from a 5.7 mm x 6 mm tissue section in mapping mode using 785 nm excitation laser and a step size of 100 mu m. A Fourier transform infrared (FTIR) image of 4096 spectra was recorded from the same sample at a lateral resolution of 63 mu m using a spectrometer coupled to a focal plane array detector. Whereas the analysis of the FTIR image was complicated by dispersion artifacts, the analysis of the Raman image was impaired by intense spectral contributions of hemoglobin which overlap with spectral contributions of other proteins, lipids and nucleic acids. Data analysis procedures were optimized to reduce these effects. A multiplicative signal correction was performed to normalize the spectra within each dataset. Then, pseudo color images were constructed using cluster analyses. The most significant variations within both images were assigned to different concentrations of red blood cells. Furthermore, mucus and blood vessels were identified in the vibrational spectroscopic images. The different sensitivity of Raman and FTIR imaging for lung tissue constituents supports the combined use of both modalities

Raman and FTIR microscopic imaging of colon tissue: a comparative study

Colon tissue constitutes a valid model for the comparative analysis of soft tissue by Raman and Fourier transform infrared (FTIR) imaging because it contains four major tissue types such as muscle tissue, connective tissue, epithelium and nerve cells. Raman microscopic images were recorded in the mapping mode using 785 nm laser excitation and a step size of 10 mm from three regions within a thin section that encompassed mucus, mucosa, submucosa, and longitudinal and circular muscle layers. FTIR microscopic images that were composed of 4, 8 and 9 individual images of 4096 spectra each were recorded from the same regions using a FTIR spectrometer coupled to a microscope with a focal plane array detector. Furthermore, Raman microscopic images were recorded at a step size of 2.5 mm from three ganglia that belong to the myenteric plexus. The results are discussed with respect to lateral resolution, spectral resolution, acquisition time and sensitivity of both modalities

Raman and FTIR Imaging of lung tissue: congenital cystic adenomatoid malformation

Congenital cystic adenomatoid malformations (CCAMs) are benign masses of non-functional lung tissue developing from an overgrowth of the terminal bronchioles with subsequent suppressing of alveolar growth. For the first time CCAMs are studied by Raman mapping and Fourier transform infrared (FTIR) imaging. Both vibrational spectroscopic methods are able to analyze the biochemical composition of tissues and their pathological changes at the molecular level. Cryosections were prepared on calcium fluoride substrates from CCAMs and from normal lung tissue of two infant patients who underwent surgery. Raman maps were collected at a step size of 100 lm in order to assess the whole tissue section and at a smaller step size of 10 lm in order to resolve details in selected areas. FTIR images were collected in the macroscopic and microscopic modes. Data sets were segmented by cluster analysis and the mean spectra of each cluster were compared

Meckel's diverticulum masked by a long period of intermittent recurrent subocclusive episodes

Meckel’s diverticulum (MD) is the most frequent congenital abnormality of the small bowel and it is often difficult to diagnose. It is usually asymptomatic but approximately 4% are symptomatic with complications such as bleeding, intestinal obstruction, and inflammation. The authors report a case of a 7-year-old boy with a one-year history of recurrent periumbilical colicky pain with associated alimentary vomiting, symptoms erroneously related to a cyclic vomiting syndrome but not to MD. The clinical features and the differential diagnostic methods employed for diagnosis of MD are discussed

Raman Spectroscopy and Imaging: Promising Optical Diagnostic Tools in Pediatrics

5This review focuses on the use of Raman spectroscopy, an analytical technique based on the inelastic scattering of harmless laser light with biological tissues, as an innovative diagnostic tool in pediatrics. After a brief introduction to explain the fundamental concepts behind Raman spectroscopy and imaging, a short summary is given of the most important and common issues arising when handling spectral data with multivariate statistics. Then, the most relevant papers in which Raman spectroscopy or imaging has been applied with diagnostic purposes to pediatric patients are reviewed, and grouped according to the type of pathology: neoplastic, inflammatory, allergic, malformative as well as other kinds. Raman spectroscopy has been used both in vivo, mostly using optical fibers for tissue illumination, as well as on ex vivo tissue sections in a microscopic imaging approach defined as “spectral histopathology”. According to the results reported so far, this technique showed a huge potential for mini- or non-invasive real-time, bedside and intra-operatory diagnosis, as well as for an ex vivo imaging tool in support to pathologists. Despite many studies are limited by the small sample size, this technique is extremely promising in terms of sensitivity and specificitynonemixedC. Beleites; A. Bonifacio; D. Codrich; C. Krafft; V. SergoC., Beleites; Bonifacio, Alois; D., Codrich; C., Krafft; Sergo, Valte

Meckel's diverticulum masked by a long period of intermittent recurrent subocclusive episodes

Meckel's diverticulum (MD) is the most frequent congenital abnormality of the small bowel and it is often difficult to diagnose. It is usually asymptomatic but approximately 4% are symptomatic with complications such as bleeding, intestinal obstruction, and inflammation. The authors report a case of a 7-year-old boy with a one-year history of recurrent periumbilical colicky pain with associated alimentary vomiting, symptoms erroneously related to a cyclic vomiting syndrome but not to MD. The clinical features and the differential diagnostic methods employed for diagnosis of MD are discussed. © 2009 The WJG Press and Baishideng. All rights reserved

A boy with unexplained recurrent abdominal pain.

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