Filamentous Aggregates of Tau Proteins Fulfil Standard Amyloid Criteria Provided by the Fuzzy Oil Drop (FOD) Model.

Abnormal filamentous aggregates that are formed by tangled tau protein turn out to be classic amyloid fibrils, meeting all the criteria defined under the fuzzy oil drop model in the context of amyloid characterization. The model recognizes amyloids as linear structures where local hydrophobicity minima and maxima propagate in an alternating manner along the fibril's long axis. This distribution of hydrophobicity differs greatly from the classic monocentric hydrophobic core observed in globular proteins. Rather than becoming a globule, the amyloid instead forms a ribbonlike (or cylindrical) structure.

Effects of different rehabilitation models on erythrocyte deformability and nitrite plus nitrate as end-products of nitric oxide levels in elderly women.

AIM: The aim of the present study was to analyze the effects of two rehabilitation protocols, dance movement therapy exercises (DMT) and general rehabilitation exercises (GRE), on erythrocyte deformability and plasma levels of nitrite plus nitrate as end products of nitric oxide (NOx) in elderly women. METHODS: The study included 39 women aged 61-82 years, subjected to either GRE (n = 20) or DMT (n = 19). Women were subjected to 5-months programs of GRE and DMT, with each session lasting no longer than 45-50 min, and the intensity of exercising corresponding to no more than 40-60% of heart rate reserve. Plasma levels of NOx were determined spectrophotometrically before and at the end of the intervention. RESULTS: A significant increase in the total nitrate/nitrite concentration from 1.341 µmol/L to 1.590 µmol/L (7.3%) was observed in women subjected to the DMT rehabilitation program. Furthermore, an increase in erythrocyte deformability was observed in this group at shear stress 0.30. No significant difference was found between the pre- and post-rehabilitation NOx levels of women participating in the GRE program. CONCLUSIONS: Participation in DMT rehabilitation program might be reflected by an increase in plasma NOx levels and an improvement of erythrocyte deformability at lesser shear stress, and thus could potentially result in better vascular function. DMT should be offered to older adults, especially to persons who do not find conventional forms of rehabilitation as attractive, as they might refrain from physical activity and suffer from a faster decline in nitric oxide production. Geriatr Gerontol Int 2017; 17: 2479-2484.

Is the hydrophobic core a universal structural element in proteins?

The hydrophobic core, when subjected to analysis based on the fuzzy oil drop model, appears to be a universal structural component of proteins irrespective of their secondary, supersecondary, and tertiary conformations. A study has been performed on a set of nonhomologous proteins representing a variety of CATH categories. The presence of a well-ordered hydrophobic core has been confirmed in each case, regardless of the protein's biological function, chain length or source organism. In light of fuzzy oil drop (FOD) analysis, various supersecondary forms seem to share a common structural factor in the form of a hydrophobic core, emerging either as part of the whole protein or a specific domain. The variable status of individual folds with respect to the FOD model reflects their propensity for conformational changes, frequently associated with biological function. Such flexibility is expressed as variable stability of the hydrophobic core, along with specific encoding of potential conformational changes which depend on the properties of helices and ß-folds.

[Evaluation of influewnce of Dupuytryen contracture's operative treatment on increase of quality of hand's function basing on research in use DASH (disability of the arm, shoulder and hand) questionnaire - own experience]. / Ocena wplywu operacyjnego leczenia przykurczu Dupuytrena na poprawe funkcji reki w oparciu o badania przeprowadzone z zastosowaniem kwestionariusza DASH (disability of the arm, shoulder and hand) - doswiadczenia wlasne.

UNLABELLED: The essence of Dupuytryen's contracture is progressive process of fibrous overgrow of the subfascial sturctures of hand volar's surface. This is the reason of impaired range of the finger movement's and subsequent limitations of their function. MATERIAL AND METHODS: The study group consist of 95 patients treated because of Dupuytryen contracture in the 2nd Chair of Surgery, Medical College of JagielIonian University between 2006-2011. The subjective evalution of increase of hand's function quality was based on DASH (Disability of the Arm, Shoulder and Hand) questionnaire. THE AIM OF THE STUDY: The aim of the study was to determinate an influence of Dupuytren contracture's operative treatment on increase of quality of hand's function using the DASH questionnaire. RESULTS: Average value in DASH before operative treatment was 40.38 points (SD+/-12.53). In postoperative evaluation gradual increase was observed: after 3 month was 33.35 points (SD+/-16.39) and after one year - 32.57 points (SD+/-14.96). Statistically important differences between DASH test's results (P<0.01) were observed. Significantly superior results was before operation, results after 3 month and 1 year were nut statistically important. CONCLUSIONS: The research with the use of DASH questionnaire revealed the influence of Dupuytren's contracture severity on subjection evaluation of hand's function.

Expression of cyclins A and E in melanocytic skin lesions and its correlation with some clinicopathologic features.

Cyclins play a fundamental role in the cell cycle. Recent studies have focused on their role in the development of various malignancies. The objective of this study was to evaluate and compare the expression of cyclins A and E in common nevi, dysplastic nevi and malignant melanomas, and to investigate the relationship between cyclin expression and some pathological parameters such as tumor thickness, ulceration, regression, and mitotic rate, as well as several clinical and phenotypic parameters such as skin phototype, hair and eye color, number of nevi, personal or family melanoma history, and personal history of nonmelanoma skin cancer (NMSC). A total of 102 melanocytic skin lesions, including 30 common nevi, 38 dysplastic nevi and 34 melanomas, were examined. Expression of cyclins was detected by immunohistochemistry and quantified as a percentage of immunostained cell nuclei in each sample. Significant differences in expression of both cyclins were found between all lesion types: the median percentage of cyclin A-positive nuclei was 8.2% in melanomas, 3.4% in dysplastic nevi, and 0.95% in common nevi (p < 0.001). The corresponding percentages for cyclin E were 9.5%, 4.25% and 1.44% (p < 0.001). Expression of both cyclins was significantly higher among patients with a personal history of NMSC. Cyclin A was also significantly overexpressed in patients with a high total nevus count (TNC) compared to moderate and low TNC. Expression of cyclins did not significantly correlate with the other clinicopathologic features investigated. These findings indicate the possible involvement of cyclins A and E in the pathogenesis of malignant melanoma. Our results also show a potential diagnostic significance of these cyclins as markers allowing discrimination between dysplastic nevi and melanoma.

[An attempt to objectify the assessment of extension or recurrence of Dupuytren's disease on the basis of ultrasound]. / Próba obiektywizacji oceny nawrotu lub wznowy choroby Dupuytrena w oparciu o badanie ultrasonograficzne.

Dupuytren's contracture is a disease of unknown etiology, leading with time to decreased hand function caused by increasing contracture of fingers. Excision of contracted longitudinal palmar fascia constitutes the most important way of treatment. Due to fact that disease has progressive course in many patients recurrence (i.e. overgrowth of longitudinal palmar aponeurosis apart from the operated site) or extension (i.e. similar process affecting formerly operated site) occurs. An attempt to objectify the assessment of recurrence or extension of Dupuytren's disease on the basis of sonographic examination of palmar surface of the hand during distant (at least 24 months from surgery) followup constituted the aim of the study. 41 patients operated on from January 2000 to February 2009 in 2nd Department of General Surgery in Krakow due to Dupuytren's contracture constituted the study material. Mean age of the patients reached 62,78 years (SD +/- 9,32), and mean follow up time 5,74 years (SD +/- 2,90). Sonographic assessment was performed in 26 operated on left hands and 24 right hands. 9 patients had both hands operated on. In most of the patients during surgery the contralateral hand was also affected by the disease. Extension of Dupuytren's disease was found in 11 hands, recurrence--in 18 hands, while concurrent extension and recurrence was found in 17 hands. Extension usually was found on the radial side and affected mainly I interphalangeal space followed by disease affecting I and III ray of the hand. In one patient 2 independent foci of the disease were found within I interphalangeal space. Recurrences affected mainly ulnar side of the hand: V and IV rays of the hand. Concurrently found extension and recurrence affected 2 or 3 rays. In the cases of 3 rays affected extension dominated (2 rays vs. 1 ray of recurrence). On sonographic assessment mean diameters of lesions during distant follow- up were 12,69 x 4,62 x 3,95 [mm] with recurrent lesions being larger than mean values found in extensions. With partial fasciectomy being the most commonly performed operation in cases of Dupuytren's disease ultrasound can constitute very important technique of assessment of exacerbation of the lesions of palmar aponeurosis allowing for the choice of appropriate surgical technique for particular case, detection of postoperative extension and/or recurrence and for the cases clinically doubtful.

In silico structural study of random amino acid sequence proteins not present in nature.

The three-dimensional structures of a set of 'never born proteins' (NBP, random amino acid sequence proteins with no significant homology with known proteins) were predicted using two methods: Rosetta and the one based on the 'fuzzy-oil-drop' (FOD) model. More than 3000 different random amino acid sequences have been generated, filtered against the non redundant protein sequence data base, to remove sequences with significant homology with known proteins, and subjected to three-dimensional structure prediction. Comparison between Rosetta and FOD predictions allowed to select the ten top (highest structural similarity) and the ten bottom (the lowest structural similarity) structures from the ranking list organized according to the RMS-D value. The selected structures were taken for detailed analysis to define the scale of structural accordance and discrepancy between the two methods. The structural similarity measurements revealed discrepancies between structures generated on the basis of the two methods. Their potential biological function appeared to be quite different as well. The ten bottom structures appeared to be 'unfoldable' for the FOD model. Some aspects of the general characteristics of the NBPs are also discussed. The calculations were performed on the EUChinaGRID grid platform to test the performance of this infrastructure for massive protein structure predictions.

Never born proteins as a test case for ab initio protein structures prediction.

The number of natural proteins although large is significantly smaller than the theoretical number of proteins that can be obtained combining the 20 natural amino acids, the so-called "never born proteins" (NBPs). The study of the structure and properties of these proteins allows to investigate the sources of the natural proteins being of unique characteristics or special properties. However the structural study of NPBs can also been intended as an ideal test for evaluating the efficiency of software packages for the ab initio protein structure prediction. In this research, 10.000 three-dimensional structures of proteins of completely random sequence generated according to ROSETTA and FOD model were compared. The results show the limits of these software packages, but at the same time indicate that in many cases there is a significant agreement between the prediction obtained.

A tabular approach to the sequence-to-structure relation in proteins (tetrapeptide representation) for de novo protein design.

BACKGROUND: Experimental observations classify the protein-folding process as a multi-step event. The backbone conformation has been experimentally recognized as responsible for the early-stage structural forms of a polypeptide. The sequence-to-structure and structure-to-sequence relation is critical for predicting protein structure. A contingency table representing this relation for tetrapeptides in their early-stage is presented. Their correlation seems to be essential in protein-folding simulation. MATERIAL/METHODS: The polypeptide chains of all the proteins in the Protein Data Bank were transformed into their early-stage structural forms. The tetrapeptide was selected as the structural unit. Tetrapetide sequences and structures were expressed by letter codes. The transformation of a contingency table of any size (here: 160,000x2401) to a 2x2 table performed for each non-zero cell of the original table allowed calculation of the rho-coefficient measuring the strength of the relation. RESULTS: High values of the rho-coefficient extracted sequences of strong structural determinability and structures of high sequence selectivity. The web-site program to calculate the rho-coefficient ranking list was constructed to enable applying this method to any problem of contingency table analysis. CONCLUSIONS: The results revealed sequence-to-structure (and vice versa) correlation in early-stage folding. Surprisingly, the irregular structural forms of loops and bends appeared to be highly determined. Comparison of these results with another method based on information entropy revealed high accordance. The method oriented on interpretation of a large contingency table seems very useful especially for large-scale microarray analysis, a very popular technique in the post-genomic era.

Tandemly repeated trinucleotides - comparative analysis.

Characteristics of 64 possible tandem trinucleotide repeats (TSSR) from Homo sapiens (hs), Mus musculus (mm) and Rattus norvegicus (rn) genomes are presented. Comparative analysis of TSSR frequency depending on their repetitiveness and similarity of the TSSR length distributions is shown. Comparative analysis of TSSR sequence motifs and association between type of motif and its length (n) using rho-coefficient method (quantitatively measuring the association between variables in contingency tables) is presented. These analyses were carried out in the context of neurodegenerative diseases based on trinucleotide tandems. The length of these tandems and their relation to other TSSR is estimated. It was found that the higher repetitiveness (n) the lower frequency of trinucleotides tandems. Differences between genomes under consideration, especially in longer than n=9 TSSR were discussed. A significantly higher frequency off A- and T-rich tandems is observed in the human genome (as well as in human mRNA). This observation also applies to mm and rn, although lower abundant in proportion to human genomes was found. The origin of elongation (or shortening) of TSSR seems to be neither frequency nor length dependent. The results of TSSR analysis presented in this work suggest that neurodegenerative disease-related microsatellites do not differ versus the other except the lower frequency versus the other TSSR. CAG occurs with relatively high frequency in human mRNA, although there are other TSSR with higher frequency that do not cause comparable disease disorders. It suggests that the mechanism of TSSR instability is not the only origin of neurodegenerative diseases.