1,721,219 research outputs found
Clearance mechanisms of aggregated TDP-43 responsible for ALS/FTD diseases
No full textIncreasing biochemical and genetic evidence have suggested that Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two related neurodegenerative diseases, with a continuous clinical spectrum. Even if the neuronal population affected may differ between ALS and FTD, a common feature is the mislocalization and aggregation of the TAR DNA binding protein 43 (TDP-43), in affected cells. TDP-43 aggregates contain C-terminal TDP-43 fragments of 35 kDa (TDP-35) and 25 kDa (TDP-25), that are highly aggregation-prone, and are thought to be neurotoxic. We have investigated the role of protein quality control (PQC) system and extracellular vesicles in the clearance of TDP-43 and its C-terminal fragments. We have demonstrated that all TDP-43 species are cleared by proteasome, but TDP-25 impairs autophagy. We found that the routing of TDP fragments to proteasome or to autophagy decreased the accumulation of both TDP43 fragments, possibly reducing their toxicity. Moreover, we observed that all TDP-43 species are secreted in EVs, mainly in MVs
MISFOLDING PROTEICO E NEURODEGENERAZIONE : STUDIO DEL COINVOLGIMENTO DELLA PROTEINA CHAPERONE HEAT SHOCK PROTEIN B8
No full textnul
CELL BLOCKS OF CANINE AND FELINE EFFUSION
No full textABSTRACT
Valentina Crippa
Cell Blocks from canine and feline effusions
Objective: To evaluate the sensitivity and specificity of a panel of markers in distinguishing mesothelial cells from metastatic adenocarcinoma cells in Cell blocks from canine and feline effusion.
Methods: This study included 28 effusion specimens from dogs and cats with a cytological diagnosis of reactive effusion or malignancy of non-hematopoietic origin. Cell Blocks were stained with a standard panel of Vimentin, panCK (MNF116), CK 5/6 and HBME-1 as mesothelial cell markers; Desmin as marker of benign mesothelial cells; Claudin 4 as epithelial marker and CK7/CK20 as a marker of metastasis. Malignancy was confirmed by histologic evaluation; non-malignant conditions were confirmed by histopathology or follow up. Sensitivities, specificities, predictive values and accuracy were calculated.
Results: CK5/6 demonstrated a high specificity (100%) for mesothelium. For the detection of canine and feline mesothelial cells the coexpression of panCK and VIM displayed the best sensibility (94,1%) while HBME-1 was the antibody that presented highest accuracy. Claudin 4 demonstrated a very low sensibility versus canine and feline epithelial cells.
Conclusion: The most specific marker, with for the identification of mesothelial cells in canine and effusion, is the Vim/CK coexpression, being CK5/6 the most specific and HBME-1 the marker with the highest overall accuracy. Desmin is a useful marker in discriminating between benign and malignant mesothelial cells. The coordinate expression of CK7/CK20+ has not proved to be useful on the identification of metastatic cells on effusion. The study of Claudin 4 necessitate to be deepened in veterinary medicine. In conclusion, the combination of both cytology and immunohistochemistry studies can greatly enhance the diagnostic accuracy, sensitivity and specificity in malignant effusions
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Different behaviour of mutant SOD1 in motorneuronal and muscle cellular models of Amyotrophic Lateral Sclerosis
No full textPHARMACOLOGICAL AND MOLECULAR APPROACHES TO REMOVE MUTANT MISFOLDED ANDROGEN RECEPTOR IN SPINAL AND BULBAR MUSCULAR ATROPHY
No full textA new sand pluviator to reconstitute specimens of well graded silty sands
No full textA new travelling sand pluviator to reconstitute small specimens far laboratory tests was developed in joint research be tween the Research Center of the ltalian National Electricity Board (ENEL CRIS) of Milano and the Department of Structural Engineering of the Politecnico di Torino.
The pluviator proved satisfactory in reconstituting small-size specimens because it provided a very high degree of spatial uniformity of density and grain-size distribution.
Furthermore, it was shown that a traveling pluviator is preferable to a stationary one even in reconstituting large-size specimens to achieve a higher degree of spatial uniformity.
The above advantages were mainly evident when dealing with well- graded silty sands.
A noteworthy feature of the new traveling pluviator that sets it apart from existing ones is its ability to accommodate pluviation under evacuated conditions
The role of small heat shock protein B8 (HspB8) in the removal of mutant androgen receptor in spinal and bulbar muscular atrophy
No full textSpinal and bulbar muscular atrophy (SBMA) is a motorneuronal disease, caused by a polyglutamine (polyQ) expansion in the androgen receptor (AR) protein. SBMA is characterized by conformational changes in ARpolyQ that result in misfolding and protein aggregation. Using SBMA in vitro models expressing mutant AR (AR.Q46), we observed that the inactive and soluble AR.Q46 impairs the UPS activity, while Testosterone-activated AR.Q46 induced cytoplasmic aggregation leading to UPS desaturation and removing AR.Q46 from the soluble compartment into the aggregates waiting for an alternative clearance, as autophagy. It is known that chaperones facilitate the removal of misfolded proteins. We thus tested the potential of a small Heat Shock Protein (HSPB8) to facilitate mutant protein turnover and its effect on the degradative systems. HSPB8 overexpression decreased the AR.Q46 levels without affecting the proteasome and the inhibition of the proteasomal function did not block the HspB8. HspB8 might facilitate the AR.Q46 clearance acting through the macroautophagy. In fact, HspB8 stimulated the formation of LC3-II increasing the number of autophagosomes and the LC3 silencing correlated with the loss of HspB8 prodegradative effects on AR.Q46. Finally, we tested the effects of HspB8 overexpression on a longer polyQ tract (AR.Q112) because AR with Q46 and Q112 showed different biochemical properties and AR.Q112 has a higher tendency to aggregate than AR.Q46. Using transient and stable transfections with AR.Q112, which recapitulates the nuclear accumulation and aggregation observed in SBMA patients, we found that HspB8 was unable to induce AR.Q112 clearance and to counteract aggregation.
All these data suggest that assisting protein folding with HspB8 we might reduce protein aggregation, stimulating the misfolded protein autophagic removal. Notably, HspB8 fail to suppress AR.Q112 aggregation suggesting that AR.Q46 and AR.Q112 might involve different mechanisms of neurotoxicity
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