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 ρ-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

The use of supramolecular structures as protein ligands

Congo red dye as well as other eagerly self-assembling organic molecules which form rod-like or ribbon-like supramolecular structures in water solutions, appears to represent a new class of protein ligands with possible wide-ranging medical applications. Such molecules associate with proteins as integral clusters and preferentially penetrate into areas of low molecular stability. Abnormal, partly unfolded proteins are the main binding target for such ligands, while well packed molecules are generally inaccessible. Of particular interest is the observation that local susceptibility for binding supramolecular ligands may be promoted in some proteins as a consequence of function-derived structural changes, and that such complexation may alter the activity profile of target proteins. Examples are presented in this paper

Silver ions as EM marker of congo red ligation sites in amyloids and amyloid-like aggregates

Congo red (CR) is a known selective amyloid ligand. The focus of our work is identification (by EM imaging) of dye binding sites and their distribution in amyloids and amyloid-like aggregates formed in vitro. In order to produce the required contrast, CR has been indirectly combined with metal via including Titan yellow (TY) by intercalation which exhibits a relatively strong affinity for silver ions. The resulting combined ligand retains its ability to bind to proteins (which it owes to CR) and can easily be detected in EM studies thanks to TY. We have found, however, that in protein aggregates where unfolding is stabilized by aggregation and therefore is irreversible, TY alone may serve as both, the ligand and the metal carrier. The formation of ordered structures in amyloids was studied using IgG light chains with amyloidogenic properties, converted into amyloids by shaking. The resulting EM images were subjected to interpretation on the basis of the authors' earlier research on the CR/light chain complexation process. Our results indicate that dimeric light chains, which are the subject of our study, produce amyloids or amyloid-like complexes with chain-like properties and strong helicalization tendencies. Cursory analysis suggests that the edge polypeptide loops belonging to unstable light chains form intermolecular bridges which promote creation of loose gel deposits, or are otherwise engaged in the swapping processes leading to higher structural ordering

PDIA iminosugar influence on subcutaneous Staphylococcus aureus and Pseudomonas aeruginosa infections in mice

IntroductionBiofilm-associated infections persist as a therapeutic challenge in contemporary medicine. The efficacy of antibiotic therapies is ineffective in numerous instances, necessitating a heightened focus on exploring novel anti-biofilm medical strategies. Among these, iminosugars emerge as a distinctive class of compounds displaying promising biofilm inhibition properties.MethodsThis study employs an in vivo wound infection mouse model to evaluate the effectiveness of PDIA in treating biofilm-associated skin wound infections caused by Staphylococcus aureus and Pseudomonas aeruginosa. Dermic wounds in mice were infected with biofilm-forming strains, specifically S. aureus 48 and P. aeruginosa 5, which were isolated from patients with diabetic foot, and are well-known for their strong biofilm formation. The subsequent analysis included clinical, microbiological, and histopathological parameters. Furthermore, an exploration into the susceptibility of the infectious strains to hydrogen peroxide was conducted, acknowledging its potential presence during induced inflammation in mouse dermal wounds within an in vivo model.ResultsThe findings revealed the efficacy of PDIA iminosugar against the S. aureus strain, evidenced by a reduction in bacterial numbers within the wound and the inflammatory focus.DiscussionThis study suggests that PDIA iminosugar emerges as an active and potentially effective antibiofilm agent, positioning it as a viable treatment option for staphylococcal infections

The use of supramolecular structures as protein ligands

Congo red dye as well as other eagerly self-assembling organic molecules which form rod-like or ribbon-like supramolecular structures in water solutions, appears to represent a new class of protein ligands with possible wide-ranging medical applications. Such molecules associate with proteins as integral clusters and preferentially penetrate into areas of low molecular stability. Abnormal, partly unfolded proteins are the main binding target for such ligands, while well packed molecules are generally inaccessible. Of particular interest is the observation that local susceptibility for binding supramolecular ligands may be promoted in some proteins as a consequence of function-derived structural changes, and that such complexation may alter the activity profile of target proteins. Examples are presented in this paper

Pomiar mechanicznych parametrów dróg oddechowych metodą wymuszania krótkotrwałych, ujemnych impulsów ciśnienia rozprawa doktorska /

Tyt. z ekranu tytułowego.Praca doktorska. Akademia Górniczo-Hutnicza im. Stanisława Staszica (Kraków), 2007.Bibliogr.Dostępna także w wersji drukowanej.Tryb dostępu: Internet.Układ oddechowy człowieka, budowa, mechaniczne właściwości, fizyczna interpretacja właściwości mechanicznych układu oddechowego, układ oddechowy jako system nieliniowy, elektryczne ekwiwalentne modele mechanicznych właściwości, patologia, wybrane metody pomiarowe stosowane w diagnostyce, badania spirometryczne, pomiar MIP, maximal inspiratory pressure, MEP, maximal expiratory pressure, pomiary techniką NEP, negative expiratory pressure, identyfikacja parametrów mechanicznych, pomiar metodami częstotliwościowymi, metodą przerwanego przepływu powietrza, natężonego wydechu, metoda wymuszenia krótkotrwałych ujemnych impulsów ciśnienia, model matematyczny, symulacyjny metody, model obiektu odniesienia, sygnału wymuszenia, czujnika ciśnienia, przepływu, multipleksera, przetwornika A/C, wyznaczany w procesie identyfikacji, algorytm identyfikacji, badania symulacyjne metody pomiaru, weryfikacja modelu odniesienia, wpływ czasu wystąpienia wymuszającego impulsu ciśnienia, wpływu czasu trwania wymuszającego impulsu ciśnienia, wpływ częstotliwości próbkowania sygnałów pomiarowych, wartości wybranych parametrów układu oddechowego, modelu odniesienia, eksperymenty pomiarowe, system pomiarowy, identyfikacja parametrów układu oddechowego przy wykorzystaniu różnych modeli, wpływ częstotliwości granicznej filtra, czasu trwania sygnału pomiarowego, nieliniowego charakteru rezystancji Raw na wyniki identyfikacji przy estymowanej, nie estymowanej podatności i Cg, dołączonego dodatkowego oporu pneumatycznego, pomiary wykonywane w masce, z podtrzymaniem policzków w celu ograniczenia wpływu pozatorakalnych dróg oddechowych, czułość, swoistość metody pomiarowe

Regularization and grouping -omics data by GCA method: A transcriptomic case.

The paper presents the application of Grade Correspondence Analysis (GCA) and Grade Correspondence Cluster Analysis (GCCA) for ordering and grouping -omics datasets, using transcriptomic data as an example. Based on gene expression data describing 256 patients with Multiple Myeloma it was shown that the GCA method could be used to find regularities in the analyzed collections and to create characteristic gene expression profiles for individual groups of patients. GCA iteratively permutes rows and columns to maximize the tau-Kendall or rho-Spearman coefficients, which makes it possible to arrange rows and columns in such a way that the most similar ones remain in each other's neighbourhood. In this way, the GCA algorithm highlights regularities in the data matrix. The ranked data can then be grouped using the GCCA method, and after that aggregated in clusters, providing a representation that is easier to analyze-especially in the case of large sets of gene expression profiles. Regularization of transcriptomic data, which is presented in this manuscript, has enabled division of the data set into column clusters (representing genes) and row clusters (representing patients). Subsequently, rows were aggregated (based on medians) to visualise the gene expression profiles for patients with Multiple Myeloma in each collection. The presented analysis became the starting point for characterisation of differentiated genes and biochemical processes in which they are involved. GCA analysis may provide an alternative analytical method to support differentiation and analysis of gene expression profiles characterising individual groups of patients