Hsp27 reduces glycation-induced toxicity and aggregation of alpha-synuclein.

α-synuclein (aSyn) is a major player in Parkinson's disease and a group of other disorders collectively known as synucleinopathies, but the precise molecular mechanisms involved are still unclear. aSyn, as virtually all proteins, undergoes a series of posttranslational modifications during its lifetime, which can affect its biology and pathobiology. We recently showed that glycation of aSyn by methylglyoxal (MGO) potentiates its oligomerization and toxicity, induces dopaminergic neuronal cell loss in mice, and affects motor performance in flies. Small heat-shock proteins (sHsps) are molecular chaperones that facilitate the folding of proteins or target misfolded proteins for clearance. Importantly, sHsps were shown to prevent aSyn aggregation and cytotoxicity. Upon treating cells with increasing amounts of methylglyoxal, we found that the levels of Hsp27 decreased in a dose-dependent manner. Therefore, we hypothesized that restoring the levels of Hsp27 in glycating environments could alleviate the pathogenicity of aSyn. Consistently, we found that Hsp27 reduced MGO-induced aSyn aggregation in cells, leading to the formation of nontoxic aSyn species. Remarkably, increasing the levels of Hsp27 suppressed the deleterious effects induced by MGO. Our findings suggest that in glycating environments, the levels of Hsp27 are important for modulating the glycation-associated cellular pathologies in synucleinopathies.

Electron transfer between multihaem cytochromes c3 from Desulfovibrio africanus.

The tetrahaem type I cytochromes c3 from Desulfovibrionaceae shuttle electrons from a periplasmic hydrogenase to transmembrane electron transfer complexes. In D. africanus, it is believed that the electrons are received by another tetrahaem cytochrome c3, denoted type II, which is associated with the membrane complex. Thermodynamic measurements show that the type I cytochrome c3 has the potential to transfer two electrons at a time. This study uses two-dimensional NMR to investigate the exchange of electrons between type I and type II cytochromes c3 at equilibrium in intermediate stages of oxidation. The results indicate that the two proteins are physiological partners but that only single-electron transfers occur in solution.

Texture analysis of cone-beam computed tomography images assists the detection of furcal lesion.

BACKGROUND: The aim of this study was to apply texture analysis (TA) to cone-beam computed tomography (CBCT) scans of patients with grade C periodontitis for detection of non-visible changes in the image. METHODS: TA was performed on CBCT scans of 34 patients with grade C periodontitis. Axial sections of CBCT were divided into three groups as follows: Group L (lesion) in which there is a furcal lesion with periodontal bone loss; Group I (intermediate) in which the border of the furcal lesion has normal characteristics; and Group C (control) in which the area is healthy. Eleven texture parameters were extracted from the region of interest. Mann-Whitney U test was used to assess the differences in the texture between the three groups as follows: L versus I; L versus C, and I versus C. RESULTS: Statistically significant differences (P <0.05) were observed in almost all parameters in the intergroup analyses (i.e., L versus I and L versus C). However, statistical differences were smaller in groups I versus C in which only entropy of sum, entropy of difference, mean of sum, and variance of difference were statistically different (P < 0.05). CONCLUSION: TA can potentially provide prognostic information to improve the diagnostic accuracy in the grading of the tissue around the furcal lesion, thus potentially accelerating the treatment decision-making process.

MRI Texture Analysis Reveals Deep Gray Nuclei Damage in Amyotrophic Lateral Sclerosis.

BACKGROUND AND PURPOSE: Amyotrophic Lateral Sclerosis (ALS) is characterized by extensive corticospinal damage, but extrapyramidal involvement is suggested in pathological studies. Texture analysis (TA) is an image processing technique that evaluates the distribution of gray levels between pixels in a given region of interest (ROI). It provides quantitative data and has been employed in several neurodegenerative disorders. Here, we used TA to investigate possible deep gray nuclei (DGN) abnormalities in a cohort of ALS patients. METHODS: Thirty-two ALS patients and 32 healthy controls underwent MRI in a 3T scanner. The T1 volumetric sequence was used for DGN segmentation and extraction of 11 texture parameters using the MaZda software. Statistical analyses were performed using the Mann-Whitney non-parametric test, with a significance level set at α = 0.025 (FDR-corrected) for TA. RESULTS: Patients had significantly higher values for the parameter correlation (CO) in both thalami and in the right caudate nucleus compared to healthy controls. Also, the parameter Inverse Difference Moment or Homogeneity (IDM) presented significantly smaller values in the ALS group in both thalami. CONCLUSIONS: TA of T1 weighted images revealed DGN alterations in patients with ALS, namely in the thalami and caudate nuclei.

MRI-texture analysis of corpus callosum, thalamus, putamen, and caudate in Machado-Joseph disease.

BACKGROUND/PURPOSE: Texture analysis (TA) is a branch of image processing, which attempts to convey "texture" information from digital images, such as magnetic resonance images (MRI). Machado-Joseph disease (MJD) affects mainly cerebellum and brainstem, but recent studies have shown that other cerebral structures may also be affected. OBJECTIVE: To investigate subtle structural abnormalities in corpus callosum (CC), thalami, putamen, and caudate nuclei of patients with MJD using TA. METHODS: Eighteen healthy volunteers and 18 patients with MJD were studied (mean age at disease onset = 34.7 years; disease duration = 9.6 years; mean expanded CAG in the MJD1 gene = 73). A TA approach based on the gray-level cooccurrence matrix was applied to T1-MRI. Regions of interest were manually segmented for each subject, and texture parameters were computed for each of the aforementioned anatomical structures. RESULTS: TA parameters showed differences between the 2 groups for the caudate nuclei, thalami, and putamen. No differences were found for the CC. CONCLUSIONS: TA was capable of detecting tissue alterations in MRI of patients with MJD. These alterations were in areas already shown to be affected by histopathological studies. In addition, we confirmed the thalamic involvement in patients with MJD, which had only been demonstrated in volumetric studies.