The C-terminal segment of Leishmania major HslU: Toward potential inhibitors of LmHslVU activity.

It is urgent to develop less toxic and more efficient treatments for leishmaniases and trypanosomiases. We explore the possibility to target the parasite mitochondrial HslVU protease, which is essential for growth and has no analogue in the human host. For this, we develop compounds potentially inhibiting the complex assembly by mimicking the C-terminal (C-ter) segment of the ATPase HslU. We previously showed that a dodecapeptide derived from Leishmania major HslU C-ter segment (LmC12-U2, Cpd 1) was able to bind to and activate the digestion of a fluorogenic substrate by LmHslV. Here, we present the study of its structure-activity relationships. By replacing each essential residue with related non-proteinogenic residues, we obtained more potent analogues. In particular, a cyclohexylglycine residue at position 11 (cpd 24) allowed a more than three-fold gain in potency while reducing the size of compound 24 from twelve to six residues (cpd 50) without significant loss of potency, opening the way toward short HslU C-ter peptidomimetics as potential inhibitors of HslV proteolytic function. Finally, conjugates constituted of LmC6-U2 analogues and a mitochondrial penetrating peptide were found to penetrate into the promastigote form of L. infantum and to inhibit the parasite growth without showing toxicity toward human THP-1 cells at the same concentration (i.e. 30 µM).

High-Porosity Polymer Composite for Removing Oil Spills in Cold Regions.

In this work, polyvinyl chloride (PVC)/clay nanofiber composites with various contents were fabricated by the electrospinning process. The morphology, porosity, density, and mechanical properties of the nanofiber mats were investigated. In addition, PVC/clay nanofiber mats were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. Moreover, the influence of the clay content in the nanofiber mats and its effect on oil sorption capacity were also evaluated. The results show that the clay particle diameter affects the fabrication, morphology, porosity, density, mechanical properties, and sorption capacity of the nanofiber mats. Adding clay in nanofiber composite materials leads to higher porosity and a higher oil sorption capacity. PVC/clay nanofiber mats have a high oil sorption capacity at low temperatures. They exhibit a high potential to be used as materials to eliminate oil spills under arctic conditions.

Breast cancer detection by ATR-FTIR spectroscopy of blood serum and multivariate data-analysis.

Detection of breast cancer has particular importance for the diagnosis of cancer diseases. This is the most common type of cancer among women. Breast cancer is a malignant tumor of the glandular tissue of the breast. It is proposed to use infrared spectroscopy of blood serum as a simple and quick way to detect breast cancer. The paper presents the results of research using the methods of multivariate processing of IR spectra of human blood serum obtained by ATR-FTIR spectroscopy. The paper presents the results of research using the methods of multivariate processing of IR spectra of human blood serum obtained by ATR-FTIR spectroscopy. A sufficiently large sample of patients and healthy donors was diagnosed. Blood samples are examined from 66 patients who are clinically diagnosed with breast cancer and 80 healthy volunteers. A feature of the applied approach was a combination of the method of principal component analysis (PCA) and principal component regression (PCR) for processing the IR spectra of blood serum. The PCA method allows us to determine the spectral bands referring for the intensity differences between the control group and the patient group. Shown, that the range of 1306-1250cm-1 in the IR spectrum of blood serum is diagnostically significant for breast cancer. This range corresponds to the vibrations of several functional groups of DNA and RNA, which play a key role in discrimination in breast cancer screening using ATR-FTIR spectroscopy. It is shown that the proposed method has advantages in ease of use for clinical diagnosis and gives good results for the identification of breast cancer. The values of sensitivity (92.3%) and specificity (87.1%) obtained using the PCR method are close to those of mammography and ultrasound. This indicates the possibility of using this method in real clinical laboratory diagnostics.