Structural similarity of loops in protein families: toward the understanding of protein evolution

BACKGROUND: Protein evolution and protein classification are usually inferred by comparing protein cores in their conserved aligned parts. Structurally aligned protein regions are separated by less conserved loop regions, where sequence and structure locally deviate from each other and do not superimpose well. RESULTS: Our results indicate that even longer protein loops can not be viewed as "random coils" and for the majority of protein families in our test set there exists a linear correlation between the measures of sequence similarity and loop structural similarity. Results suggest that distance matrices derived from the loop (dis)similarity measure may produce in some cases more reliable cluster trees compared to the distance matrices based on the conventional measures of sequence and structural (dis)similarity. CONCLUSIONS: We show that by considering "dissimilar" loop regions rather than only conserved core regions it is possible to improve our understanding of protein evolution

THE INFLUENCE OF SiC PARTICLE SIZE ON MECHANICAL PROPERTIES OF ALUMINIUM MATRIX COMPOSITES

The main aim of this study was to determine the influence of SiC particle size on the mechanical properties of aluminum matrix composites. The reinforcing phase was introduced into the aluminum matrix in two different particle sizes: a coarse fraction with particle size ranging from 40 to 60 μm, and a fine fraction with particle size of less than 2 μm. The SiC particles were added in various quantities equal to 2.5, 5, 7.5, and 10 wt% in order to determine the influence of different contents of the reinforcing phase on the density, hardness, and compressive strength of the obtained composite materials. By using scanning electron microscopy (SEM), the microstructure observations were performed and allowed for defining the influence of matrix/reinforcement particle size ratio (PSR) on the  distribution of reinforcement particles in the matrix. The Al-SiC composites were prepared through the conventional powder metallurgy technique, including compaction under a pressure of 300 MPa and a sintering process in a nitrogen atmosphere at 600°C. Applying the reinforcing phase with the particle size (40–60 μm) similar to matrix (<63 μm) allowed us to obtain a more-uniform distribution of SiC particles in the matrix than after introducing the fine fraction of reinforcement (2 μm). The mechanical properties of the Al-SiC composites increased with increases in the weight fraction of the reinforcing phase, wherein this effect is more visible for composites reinforced with SiC particles of finer gradation

Strength Estimation of Teeth Reinforced with Different Types of Post Systems

Posts are permanent, single-tooth and periodontal restorations. During chewing, forces make teeth with posts to undergo complex stresses. The aim of this work is to compare and estimate the upper medial incisors restored with custom posts and prefabricated composite posts reinforced with fibreglass using the finite element method. Modelling and numerical analyses provide the opportunity to evaluate the reconstruction of teeth using custom and prefabricated posts

Preclinical tests of endoprostheses of hip joint using finite element methods

W opracowaniu przedstawiono metodę wykonania testów przedklinicznych w aplikacjach endoprotezy stawu biodrowego w układzie anatomicznym. Metoda polegała na modelowaniu różnych konstrukcji endoprotez wykonanych z różnych biomateriałów i wirtualnym osadzaniu, w odwzorowanych na podstawie tomografii komputerowej (CT), strukturach kostnych. Wykorzystanie metody elementów skończonych pozwoliło na przeprowadzenie analiz numerycznych w zamodelowanych obiektach badań. W warunkach przenoszenia obciążeń lokomocyjnych dokonywana była wizualizacja rozkładów naprężeń, przemieszczeń i odkształceń w endoprotezie, kości miednicznej oraz w bliższym końcu kości udowej. Wyniki badań pozwoliły porównać rozwiązania konstrukcyjne endoprotez stawu biodrowego oraz ocenić charakter oddziaływania sztucznego stawu na otaczające tkanki kostne w warunkach indywidualnego pacjenta.The method of preclinical tests in application of endoprostheses of hip joint in the anatomical system is presented in this elaboration. The method is based on the modeling of different constructions of endoprostheses made from different biomaterials. The endoprostheses were virtually placed in natural bone structures and obtained from the computer tomography diagnostic (CT). The use of the finite element method allowed to carry on numerical analyses in modeled objects of tests. The visualization of distribution of stresses, displacements and deformations in endoprostheses, pelvis bone and femoral bone was conducted in the conditions of transfer of load. The results of tests let to compare the construction solutions of endoprostheses of hip joint and estimate the interaction of artificial hip joint on the surrounding bone tissues in individual patientconditions

Long-term trends in evolution of indels in protein sequences

BACKGROUND: In this paper we describe an analysis of the size evolution of both protein domains and their indels, as inferred by changing sizes of whole domains or individual unaligned regions or "spacers". We studied relatively early evolutionary events and focused on protein domains which are conserved among various taxonomy groups. RESULTS: We found that more than one third of all domains have a statistically significant tendency to increase/decrease in size in evolution as judged from the overall domain size distribution as well as from the size distribution of individual spacers. Moreover, the fraction of domains and individual spacers increasing in size is almost twofold larger than the fraction decreasing in size. CONCLUSION: We showed that the tolerance to insertion and deletion events depends on the domain's taxonomy span. Eukaryotic domains are depleted in insertions compared to the overall test set, namely, the number of spacers increasing in size is about the same as the number of spacers decreasing in size. On the other hand, ancient domain families show some bias towards insertions or spacers which grow in size in evolution. Domains from several Gene Ontology categories also demonstrate certain tendencies for insertion or deletion events as inferred from the analysis of spacer sizes

RIPK4 downregulation impairs Wnt3A-stimulated invasiveness via Wnt/β\beta-catenin signaling in melanoma cells and tumor growth in vivo

Purpose The role of Wnt signaling in oncogenesis and drug resistance is well known. Receptor-interacting protein kinase (RIPK4) contributing to the increased activity of many signaling pathways, including Wnt/$\beta$-catenin, may be an important target for designing new drugs for metastatic melanoma, but its role in melanoma is not fully understood. Methods We tested the effect of genetic manipulation of RIPK4 (CRISPR/Cas9) on xenograft growth. In addition, immunohistochemistry was used to detect active $\beta$-catenin, Ki67 and necrosis in xenografts. Wnt signaling pathway activity was examined using Western blot and Top-Flash. The effect of RIPK4 knockout on melanoma cells in vitro stimulated Wnt3A on wound overgrowth, migration and invasion ability was then evaluated. Results Our study showed that CRISPR/Cas9-mediated RIPK4 knockout (KO) significantly reduced tumor growth in a mouse model of melanoma, particularly of WM266.4 cells. RIPK4 KO tumors exhibited lower percentages of $Ki67^{+}$ cells as well as reduced necrotic area and decreased levels of active $\beta$-catenin. In addition, we observed that RIPK4 knockout impaired Wnt3A-induced activation of LRP6 and $\beta$-catenin, as manifested by a decrease in the transcriptional activity of $\beta$-catenin in Top-Flash in both tested melanoma cell lines, A375 and WM266.4. Prolonged incubation (48 h) with Wnt3A showed reduced level of MMP9, C-myc, and increased SOX10, proteins whose transcription is also dependent on $\beta$-catenin activity. Moreover, RIPK4 knockout led to the inhibition of scratch overgrowth, migration and invasion of these cells compared to their controls. Conclusion RIPK4 knockdown inhibits melanoma tumor growth and Wnt3A stimulated migration and invasion indicating that RIPK4 might be a potential target for melanoma therapy

Mammary gland anatomy and the role of mammography and ultrasonography in the early diagnostics of breast cancer. A case report

Progress in imaging techniques has brought a solution to the problem of the early diagnosis of breast cancer. An interesting case of breast cancer is presented here, pictures of the malignant tumour are demonstrated and the usefulness of new diagnostic methods analysed. The presentation of this case may contribute to greater effectiveness in early breast cancer detection

Symmetryduring the take-off phase of countermovement jump in fencers

[EN] Symmetry in the motion of the left and right sides of the body has important practical significance for the everyday functioning as well as sport actions

Deciphering the functional role of RIPK4 in melanoma

The receptor-interacting protein kinase 4 (RIPK4) plays an important role in the development and maintenance of various tissues including skin, but its role in melanoma has not been reported. Using patient-derived cell lines and clinical samples, we show that RIPK4 is expressed in melanomas at different levels. This heterogenous expression, together with very low level of RIPK4 in melanocytes, indicates that the role of this kinase in melanoma is context-dependent. While the analysis of microarray data has revealed no straightforward correlation between the stage of melanoma progression and RIPK4 expression in vivo, relatively high levels of RIPK4 are in metastatic melanoma cell lines. RIPK4 down-regulation by siRNA resulted in the attenuation of invasive potential as assessed by time-lapse video microscopy, wound-healing and transmigration assays. These effects were accompanied by reduced level of pro-invasive proteins such as MMP9, MMP2, and N-cadherin. Incubation of melanoma cells with phorbol ester (PMA) increased PKC-$1\beta$ level and hyperphosphorylation of RIPK4 resulting in degradation of RIPK4. Interestingly, incubation of cells with PMA for short and long durations revealed that cell migration is controlled by the NF-$\kappa$ signaling in a RIPK4-dependent ($RIPK4^{high}$) or independent ($RIPK4^{low}$) manner depending on cell origin (distant or lymph node metastasis) or phenotype (mesenchymal or epithelial)