Bioinformatics and expression analysis of the Xeroderma Pigmentosum complementation group C (XPC) of Trypanosoma evansi in Trypanosoma cruzi cells

Nucleotide excision repair (NER) acts repairing damages in DNA, such as lesions caused by cisplatin. Xeroderma Pigmentosum complementation group C (XPC) protein is involved in recognition of global genome DNA damages during NER (GG-NER) and it has been studied in different organisms due to its importance in other cellular processes. In this work, we studied NER proteins in Trypanosoma cruzi and Trypanosoma evansi, parasites of humans and animals respectively. We performed three-dimensional models of XPC proteins from T. cruzi and T. evansi and observed few structural differences between these proteins. In our tests, insertion of XPC gene from T. evansi (TevXPC) in T. cruzi resulted in slower cell growth under normal conditions. After cisplatin treatment, T. cruzi overexpressing its own XPC gene (TcXPC) was able to recover cell division rates faster than T. cruzi expressing TevXPC gene. Based on these tests, it is suggested that TevXPC (being an exogenous protein in T. cruzi) interferes negatively in cellular processes where TcXPC (the endogenous protein) is involved. This probably occurred due interaction of TevXPC with some endogenous molecules or proteins from T.cruzi but incapacity of interaction with others. This reinforces the importance of correctly XPC functioning within the cell.

Shear bond strength of ceramic laminate veneers to finishing surfaces with different percentages of preserved enamel under a digital guided method

Background The purpose of this in vitro study was to evaluate the effect of the percentages of preserved enamel on ceramic laminate veneers’ (CLVs) shear bond strength (SBS). Methods Seventy extracted human maxillary central incisors were scanned and reconstructed into three-dimensional models. The extracted teeth were then embedded and randomly divided into seven groups (n = 10 per group). Based on digital analyses of the three-dimensional models, guided tooth preparation and bonding procedures were performed individually to form seven different percentages (100%, 80%, 60% 50%, 40%, 20% and 0%) of remaining enamel thickness on the bonding surface. Finally, the SBS test was performed, and the data were statistically analysed by one-way ANOVA with LSD post hoc test (α = 0.05). Results The complete enamel surface exhibited the highest SBS (19.93 ± 4.55 MPa), followed by 80% enamel (19.03 ± 3.66 MPa), 60% enamel (18.44 ± 3.65 MPa), 50% enamel (18.18 ± 3.41 MPa), 40% enamel (17.83 ± 3.01 MPa) and 20% enamel (11.32 ± 3.42 MPa) group. The lowest SBS (9.63 ± 3.46 MPa) was detected in 0% enamel group. No significant difference was observed among the 40–100% enamel groups, while the 20% or 0% enamel group demonstrated a significantly lower mean SBS than the 40% enamel group (p < 0.05). Conclusion The SBS value of CLVs bonded to 100% enamel on the finishing surfaces (nearly 20 MPa) was twice that which bonded to 0% enamel (nearly 10 MPa). Bonding to 100% enamel is the most reliable treatment. When dentin exposure is inevitable, enamel should be preserved as much as possible to maintain good bonding. In addition, 40% of preserved enamel on the bonding surface was the minimal acceptable value to fulfil the requirements of good bonding strength.

Synthesis of Novel Suramin Analogs With Anti-Proliferative Activity via FGF1 and FGFRD2 Blockade

A promising approach in cancer therapy is the inhibition of cell proliferation using small molecules. In this study, we report the synthesis of suramin derivatives and their applications. We used NMR spectroscopy and docking simulations to confirm binding sites and three-dimensional models of the ligand-protein complex. The WST-1 assay was used to assess cell viability and cell proliferation in vitro to evaluate the inhibition of protein–protein interactions and to investigate the anti-proliferative activities in a breast cancer cell line. All the suramin derivatives showed anti-proliferative activity by blocking FGF1 binding to its receptor FGFRD2. The dissociation constant was measured by fluorescence spectroscopy. The suramin compound derivatives synthesized herein show potential as novel therapeutic agents for their anti-proliferative activity via the inhibition of protein–protein interactions. The cytotoxicity of these suramin derivatives was lower than that of the parent suramin compound, which may be considered a significant advancement in this field. Thus, these novel suramin derivatives may be considered superior anti-metastasis molecules than those of suramin.

Prediction of the Iron–Sulfur Binding Sites in Proteins Using the Highly Accurate Three-Dimensional Models Calculated by AlphaFold and RoseTTAFold

AlphaFold and RoseTTAFold are deep learning-based approaches that predict the structure of proteins from their amino acid sequences. Remarkable success has recently been achieved in the prediction accuracy of not only the fold of the target protein but also the position of its amino acid side chains. In this article, I question the accuracy of these methods to predict iron–sulfur binding sites. I analyze three-dimensional models calculated by AlphaFold and RoseTTAFold of Fe–S–dependent enzymes, for which no structure of a homologous protein has been solved experimentally. In all cases, the amino acids that presumably coordinate the cluster were gathered together and facing each other, which led to a quite accurate model of the Fe–S cluster binding site. Yet, cysteine candidates were often involved in intramolecular disulfide bonds, and the number and identity of the protein amino acids that should ligate the cluster were not always clear. The experimental structure determination of the protein with its Fe–S cluster and in complex with substrate/inhibitor/product is still needed to unambiguously visualize the coordination state of the cluster and understand the conformational changes occurring during catalysis.

Building stone quarries: resource evaluation by block modelling and unmanned aerial photogrammetric surveys

The production of building stones shown an exponential growth in last decades as consequences of the demand and developments in the extraction and processing techniques. From the several conditioning factors affecting this industry, the geological constrains at quarry scale stands out as one of most important. Globalization and increasing competition in the building stone market require large raw material blocks to keep further processing as cost-effective as possible. Therefore, the potential extraction volume of in-situ stone blocks plays an important role in the yield of a dimensional stone quarry. The full characterization of the fracturing in the quarries comes up as fundamental in the assessment of the in-situ blocks volume/shape and potential extracted raw blocks. Identify the joint sets present, their spacing and the differences across the quarry demands a continuous assess during the quarry live span. Information from unmanned aerial vehicles helps in the field survey, namely trough digital surface models, orthophotos, and three-dimensional models. Also, the fracturing modelling by specific software programs is crucial to improve the block size assessment and the increase the quarry yield. In this research fracturing of twenty-one quarries of granite, limestone, marble, and slate from Portugal were assessed by combining field surveys with new techniques. From the studied quarries several cases were selected and presented to highlight the importance of this combined methodology in the fracturing assessment and how they can be helpful in the maximization of the resources and quarry management.

Synthesis and Computer Study of Population Dynamics Controlled Models Using Methods of Numerical Optimization, Stochastization and Machine Learning

The problems of synthesis and analysis of multidimensional controlled models of population dynamics are of both theoretical and applied interest. The need to solve numerical optimization problems for such a class of models is associated with the expansion of ecosystem control requirements. The need to solve the problem of stochastization is associated with the emergence of new problems in the study of ecological systems properties under the influence of random factors. The aim of the work is to develop a new approach to studying the properties of population dynamics systems using methods of numerical optimization, stochastization and machine learning. The synthesis problems of nonlinear three-dimensional models of interconnected species number dynamics, taking into account trophic chains and competition in prey populations, are studied. Theorems on the asymptotic stability of equilibrium states are proved. A qualitative and numerical study of the models is carried out. Using computational experiments, the results of an analytical stability and permanent coexistence study are verified. The search for equilibrium states belonging to the stability and permanent coexistence region is made using the developed intelligent algorithm and evolutionary calculations. The transition is made from the model specified by the vector ordinary differential equation to the corresponding stochastic model. A comparative analysis of deterministic and stochastic models with competition and trophic chains is carried out. New effects are revealed that are characteristic of three-dimensional models, taking into account the competition in populations of prey. The formulation of the optimal control problem for a model with competition and trophic chains is proposed. To find optimal trajectories, new generalized algorithms for numerical optimization are developed. A methods for the synthesis of controllers based on the use of artificial neural networks and machine learning are developed. The results on the search for optimal trajectories and generation of control functions are presented.The obtained results can be used in modeling problems of ecological, demographic, socio-economic and chemical kinetics systems.

Implementation of use of hand-made three-dimensional models to teach Anatomy with supplement to traditional methods with limited resources

The status of anatomical education in modern medical programs is a cornerstone of medicine. Anatomy is one of the basic subjects in First Year MBBS curriculum. Apart from important it is also a lengthy subject to complete in allocated time duration of First MBBS. There are various subdivisions of anatomy like gross anatomy, developmental anatomy, microscopic anatomy, genetics, surface anatomy, radiological anatomy etc. Out of which gross anatomy is difficult to understand as time constraint is there in duration of First MBBS. In medical and allied branches total hours allocated for anatomy teaching and laboratory practical hours have reduced. Result in triggered the emergence of innovative ideas to maximize students learning. While studying the gross anatomy three-dimensional orientation is must to learn actual structure and relation with other viscera and vessels. Traditional way of teaching anatomy uses wall charts, books, slides, anatomical specimens, and practical anatomy as teaching resources and methods. It is fact that in most institutes, three dimensional models are available in their Anatomy Museum, but many Anatomists have complained about fault in exact structure, labelling and it’s relationship in these models because sometime these models are made by amateur technicians. As the medical education expanded and the reduction in human anatomical specimens due to shortage of dead body donations, as well as the limitations of time, place and other resources for anatomical training, the quality of anatomy teaching has been seriously affected. Apart from shortage of these resources, another big issue with development of skill laboratory which is now mandatory as per new NMC guidelines. Establishment of skill lab requires ample amount of finance. Though, skill lab can provide excellent resources to meet the existing lacunae in teaching Anatomy to students by virtual media and simulations. Latest innovations in better teaching aids in Anatomy, in market virtual dissection table is available now, which can provide in depth understanding and orientation of three-dimensional body structures. But as mentioned above, the cost of this virtual dissection table is too high that every institute can not able to afford it. In this situation, to provide better understanding and three-dimensional orientation to students making hand made models from cheap and easily available materials are better options for teachers and students as they can make themselves.Anatomy is a discipline where spatial visualization is of importance. Even anatomy textbooks and atlases provide two-dimensional static anatomical illustrations. To teach some anatomical structures by traditional cadaveric dissection or by traditional lectures is difficult. Some of the structures like gross anatomy of urinary bladder or facial nerve anatomy are difficult to learn by textbook which cannot give exact perception of real anatomy. Additionally, many structure get distorted while removing from cadaver or not able to trace even. In some cases, specific models are also not available for instance course of facial nerve from origin to its termination where hand-made models give excellent three-dimensional understanding. For students’ proper anatomical knowledge of anatomy/organs help them to improve surgical skills. Finally, surgical outcome will be better with less morbidity and mortality.

Morphology of the cephalothorax integument of Bryocamptus pygmaeus (Copepoda: Harpacticoida: Canthocamptidae), based on a new research method

The number and location of sensilla and pores of the cephalothorax integument of the species Bryocamptus pygmaeus (G.O. Sars, 1863) (Copepoda, Canthocamptidae) were studied for the first time on the material from several European regions: the southeastern part of the Bolshezemelskaya tundra (Ne­nets Autonomous District), the north of the Komi Republic, the Republic of Karelia, and the central part of European Russia (Udmurt Republic). In the samples examined, two groups of populations differing in the characters of cephalothorax integument were recognised. These differences were found to correlate with the variability of the endopod of fourth pair of female legs, which bears four setae in specimens of the eastern form, while a specimen examined from Karelia has five setae. Pore maps are composed for both groups of morphotypes. A statistical analysis was carried out based on a new technique using three-dimensional models of the cephalothorax. As a result of this analysis, a high similarity between individuals of the eastern form and differences of the latter from the Karelian specimen were revealed.

AlphaFold-Predicted Structures of KCTD Proteins Unravel Previously Undetected Relationships among the Members of the Family

One of the most striking features of KCTD proteins is their involvement in apparently unrelated yet fundamental physio-pathological processes. Unfortunately, comprehensive structure–function relationships for this protein family have been hampered by the scarcity of the structural data available. This scenario is rapidly changing due to the release of the protein three-dimensional models predicted by AlphaFold (AF). Here, we exploited the structural information contained in the AF database to gain insights into the relationships among the members of the KCTD family with the aim of facilitating the definition of the structural and molecular basis of key roles that these proteins play in many biological processes. The most important finding that emerged from this investigation is the discovery that, in addition to the BTB domain, the vast majority of these proteins also share a structurally similar domain in the C-terminal region despite the absence of general sequence similarities detectable in this region. Using this domain as reference, we generated a novel and comprehensive structure-based pseudo-phylogenetic tree that unraveled previously undetected similarities among the protein family. In particular, we generated a new clustering of the KCTD proteins that will represent a solid ground for interpreting their many functions.