Structure of human TRPM8 channel.

TRPM8 is a non-selective cation channel permeable to both monovalent and divalent cations that is activated by multiple factors, such as temperature, voltage, pressure, and changes in osmolality. It is a therapeutic target for anticancer drug development, and its modulators can be utilized for several pathological conditions. Here, we present a cryo-electron microscopy structure of a human TRPM8 channel in the closed state that was solved at 2.

Trimethine Cyanine Dyes as NA-Sensitive Probes for Visualization of Cell Compartments in Fluorescence Microscopy.

We propose symmetrical cationic trimethine cyanine dyes with β-substituents in the polymethine chain based on modified benzothiazole and benzoxazole heterocycles as probes for the detection and visualization of live and fixed cells by fluorescence microscopy. The spectral-luminescent properties of trimethine cyanines have been characterized for free dyes and in the presence of nucleic acids (NA) and globular proteins. The studied cyanines are low to moderate fluorescent when free, but in the presence of NA, they show an increase in emission intensity up to 111 times; the most pronounced emission increase was observed for the dyes in the presence of dsDNA and with RNA.

Monomethine cyanine probes for visualization of cellular RNA by fluorescence microscopy.

We have studied spectral-luminescent properties of the monomethine cyanine dyes both in their free states and in the presence of either double-stranded deoxyribonucleic acids (dsDNAs) or single-stranded ribonucleic acids (RNAs). The dyes possess low fluorescence intensity in an unbound state, which is increased up to 479 times in the presence of the nucleic acids. In the presence of RNAs, the fluorescence intensity increase was stronger than that observed in the presence of dsDNA.

Sensing of Proteins by ICD Response of Iron(II) Clathrochelates Functionalized by Carboxyalkylsulfide Groups.

Recognition of elements of protein tertiary structure is crucial for biotechnological and biomedical tasks; this makes the development of optical sensors for certain protein surface elements important. Herein, we demonstrated the ability of iron(II) clathrochelates (-) functionalized with mono-, di- and hexa-carboxyalkylsulfide to induce selective circular dichroism (CD) response upon binding to globular proteins. Thus, inherently CD-silent clathrochelates revealed selective inducing of CD spectra when binding to human serum albumin (HSA) (, ), beta-lactoglobuline () and bovine serum albumin (BSA) ().

Far-red pentamethine cyanine dyes as fluorescent probes for the detection of serum albumins.

Benzothiazole based cyanine dyes with bridged groups in the pentamethine chain were studied as potential far-red fluorescent probes for protein detection. Spectral-luminescent properties were characterized for unbound dyes and in the presence of serum albumins (bovine (BSA), human (HSA), equine (ESA)), and globular proteins (β-lactoglobulin, ovalbumin). We have observed that the addition of albumins leads to a significant increase in dyes fluorescence intensity.

The atypical Rho GTPase RhoU interacts with intersectin-2 to regulate endosomal recycling pathways.

Rho GTPases play a key role in various membrane trafficking processes. RhoU is an atypical small Rho GTPase related to Rac/Cdc42, which possesses unique N- and C-terminal domains that regulate its function and its subcellular localization. RhoU localizes at the plasma membrane, on endosomes and in cell adhesion structures where it governs cell signaling, differentiation and migration.

Fluorescent β-ketoenole AmyGreen dye for visualization of amyloid components of bacterial biofilms.

Green-emitting water-soluble amino-ketoenole dye AmyGreen is proposed as an efficient fluorescent stain for visualization of bacterial amyloids in biofilms and the detection of pathological amyloids in vitro. This dye is almost non-fluorescent in solution, displays strong green emission in the presence of amyloid fibril of proteins. AmyGreen is also weakly fluorescent in presence to biomolecules that are components of cells, extracellular matrix or medium: nucleic acids, polysaccharides, lipids, and proteins.

Induced chirality of cage metal complexes switched by their supramolecular and covalent binding.

An ability of the ribbed-functionalized iron(ii) clathrochelates to induce a CD output in interactions with a protein, covalent bonding or supramolecular interactions with a low-molecular-weight chiral inductor, was discovered. The interactions of CD inactive, carboxyl-terminated iron(ii) clathrochelates with serum albumin induced their molecular asymmetry, causing an appearance of strong CD signals in the range of 350-600 nm, whereas methyl ester and amide clathrochelate derivatives remained almost CD inactive. The CD spectra of carboxyl-terminated clathrochelates on supramolecular interactions or covalent bonding with (R)-(+)-1-phenylethylamine gave a substantially lower CD output than with albumin, affected by both the solvent polarity and the isomerism of clathrochelate's ribbed substituents.

Activity of Zn and Mg phthalocyanines and porphyrazines in amyloid aggregation of insulin.

Formation of the deposits of protein aggregates-amyloid fibrils in an intracellular and intercellular space-is common to a large group of amyloid-associated disorders. Among the approaches to develop of therapy of such disorders is the use of agents preventing protein fibrillization. Polyaromatic complexes-porphyrins and phthalocyanines-are known as compounds possessing anti-fibrillogenic activity.

Autoantibody Response to ZRF1 and KRR1 SEREX Antigens in Patients with Breast Tumors of Different Histological Types and Grades.

. To investigate a frequency of antibody response to SEREX-identified medullary breast carcinoma autoantigens ZRF1 and KRR1 in sera of breast cancer patients taking into account clinical and molecular characteristics of tumors for opening of new perspectives in creation of minimally invasive immunological tests for cancer diagnostics. .

Cytotoxicity of electrophilic iron(II)-clathrochelates in human promyelocytic leukemia cell line.

We observed that electrophilic iron(II)-clathrochelates exhibit significant cytotoxicity in human promyelocytic leukemia cells (IC50=6.5±4.6μM), which correlates with the enhancement of intracellular oxidative stress (17-fold increase with respect to the cells treated with the solvent only).

Independent overexpression of the subunits of translation elongation factor complex eEF1H in human lung cancer.

Background: The constituents of stable multiprotein complexes are known to dissociate from the complex to play independent regulatory roles. The components of translation elongation complex eEF1H (eEF1A, eEF1Bα, eEF1Bβ, eEF1Bγ) were found overexpressed in different cancers. To gain the knowledge about novel cancer-related translational mechanisms we intended to reveal whether eEF1H exists as a single unit or independent subunits in different human cancers.

Study of anti-fibrillogenic activity of iron(II) clathrochelates.

The macrocyclic compounds mono- and bis-iron(II) clathrochelates were firstly studied as potential anti-fibrillogenic agents using fluorescent inhibitory assay, atomic force microscopy and flow cytometry. It is shown that presence of the clathrochelates leads to the change in kinetics of insulin fibrillization reaction and reduces the amount of formed fibrils (up to 70%). The nature of ribbed substituent could determine the activity of clathrochelates-the higher inhibitory effect is observed for compounds containing carboxybenzenesulfide groups, while the inhibitory properties only slightly depend on the size of complex species.

Interaction of the iron(II) cage complexes with proteins: protein fluorescence quenching study.

Interaction of the iron(II) mono- and bis-clathrochelates with bovine serum albumin (BSA), β-lactoglobulin, lysozyme and insulin was studied by the steady-state and time-resolved fluorescent spectroscopies. These cage complexes do not make significant impact on fluorescent properties of β-lactoglobulin, lysozyme and insulin. At the same time, the monoclathrochelates strongly quench a fluorescence intensity of BSA and substantially decrease its excited state lifetime due to their binding to this protein.

Identification of novel PTEN-binding partners: PTEN interaction with fatty acid binding protein FABP4.

PTEN is a tumor suppressor with dual protein and lipid-phosphatase activity, which is frequently deleted or mutated in many human advanced cancers. Recent studies have also demonstrated that PTEN is a promising target in type II diabetes and obesity treatment. Using C-terminal PTEN sequence in pEG202-NLS as bait, yeast two-hybrid screening on Mouse Embryo, Colon Cancer, and HeLa cDNA libraries was carried out.

Porous molecularly imprinted polymer membranes and polymeric particles.

Porous free-standing molecularly imprinted polymer membranes were synthesised by the method of in situ polymerisation using the principle of synthesis of interpenetrating polymer networks and tested in solid-phase extraction of triazine herbicides from aqueous solutions. Atrazine-specific MIP membranes were obtained by the UV-initiated co-polymerisation of methacrylic acid, tri(ethylene glycol) dimethacrylate, and oligourethane acrylate in the presence of a template (atrazine). Addition of oligourethane acrylate provided formation of the highly cross-linked MIP in a form of a free-standing 60 microm thick flexible membrane.