Myelin basic protein peptide 45–89 induces the release of nitric oxide from microglial cells.

Continuous (24 h) exposure of mixed oligodendrocyte/microglial cells to peptides 45–89 derived from citrullinated C8 isoforms of myelin basic protein (MBP) induces cell death. In contrast, MBP-C8 at the same molecular concentration is not toxic to oligodendrocyte/microglial cells as detected by the MTT test and trypan blue exclusion method. The loss of oligodendrocyte/microglial cells resulted in the release of cytochrome c from mitochondria, suggesting MBP 45–89-induced apoptosis. On the other hand, peptides 45–89 stimulated the secretion of nitric oxide from microglial cells only via induction of iNOS. The addition of peptide 45–89 to the microglial cells led to a decrease of the level of the inhibitory protein IkB, indicating that activation of the transcription factor NF-kB is involved in these processes. We propose that the immunodominant peptide 45–89 induces damage of oligodendrocytes by activation of microglial cells and subsequent generation of nitric oxide, and that this may be the first step in the initiation of autoimmunity

Adhesive Properties and Inflammatory Potential of Citrullinated Myelin Basic Protein Peptide 45-89

Deimination of arginyl residue of myelin basic protein (MBP) reduces cationicity of MBP and impedes the normal myelin membrane assembly. Less ordered structure of MBP is more susceptible to proteolytic attack that may lead to the release of highly immunogenic deiminated peptides into extracellular milieu. We have studied the association of peptides 45-89 derived from citrullinated MBP (C8 isomer) and phosphorylated MBP (C3 isomer) with the myelin lipids in a model membrane system using optical waveguide lightmode spectrometry. The analysis of association/dissociation kinetics to planar lipids under controlled hydrodynamic conditions has shown that MBP 45-89 peptide from citrullinated C8 isomer is less effectively adsorbed on the lipid membrane, than peptide from phosphorylated C3 isomer and packing densities for phosphorylated 45-89 MBP peptide is higher than for citrullinated forms. On the other hand, our results shown that continuous (24h) exposure of mixed oligodendrocyte/microglial cells to peptides 45-89 from MBP-C8 induces apoptosis via mitochondrial pathway. In addition, peptides 45-89 stimulated the secretion of nitric oxide from microglial cells via induction of iNOS and decreased the level of the inhibitory protein IkB, indicating involvement of the transcription factor NF-kB in these processes. Our results suggest that some citrullinated peptides, initially released from oligodendrocytes, might activate microglia, which produces reactive nitrogen species and generates in turn fatal feedbacks that kill oligodendrocyte

Microclimate of Grape Bunch and Sunburn of White Grape Berries: Effect on Wine Quality.

This research aimed to evaluate the composition of wines made with white grapes which are particularly susceptible to sunburn symptoms due to the absence of anthocyanin. Sunburn is a complex physiological dysfunction leading to browning or necrosis of berry tissues. In vintage 2021, the canopy of ‘Verdeca’ grapevines grown in Salento, South Italy, was differently managed by sun exposing or shading the bunches. Micrometeorological conditions were studied at different levels. Grapes were vinified, comparing the winemaking with and without skin maceration. The vegetative-productive balance of plants was not substantially modified. On the contrary, a significant effect was observed on the quality and quantity of grapes produced: smaller berries with sunburn symptoms were found on unshaded bunches. This influenced the percentage distribution among skin, pulp and seeds, causing a decrease in must yield of up to 30%. The pH was significantly higher in macerated wines made using shaded grapes, due to a lower titratable acidity and to significant impacts on the acid profile. Obviously, maceration produced a higher extraction of phenolics in wines, which reached their maximum in wines made with sunburned grapes. The absorbance at 420 nm, index of yellow color, was also significantly higher in sunburned grapes, indicating greater oxidation. Even though excessive grape sun-exposure could negatively affect the perception of white wines made without maceration (resulting in more oxidative character), the sensory quality of orange/amber wines was not significantly impacted by the presence of sunburned grapes. Thus, this winemaking technique could be particularly interesting to set up a production strategy adapted to viticultural regions strongly affected by climate change

Wine, Beer, Snuff, Medicine, and Loss of Diversity - Ethnobotanical travels in the Georgian Caucasus

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Detection of CFTR protein in human leukocytes by flow cytometry.

Leukocytes have previously been shown to express detectable levels of the protein cystic fibrosis transmembrane conductance regulator (CFTR). This study aims to evaluate the application of flow cytometric (FC) analysis to detect CFTR expression, and changes thereof, in these cells. Aliquots (200 \u3bcL) of peripheral whole blood from 12 healthy control volunteers (CTRLs), 12 carriers of a CFTR mutation (CFC), and 40 patients with cystic fibrosis (CF) carrying various combinations of CFTR mutations were incubated with specific fluorescent probes recognizing CFTR protein expressed on the plasma membrane of leukocytes. FC was applied to analyze CFTR expression in monocytes, lymphocytes, and polymorphonuclear (PMN) cells. CFTR protein was detected in monocytes and lymphocytes, whereas inconclusive results were obtained from the analysis of PMN cells. Mean fluorescence intensity (MFI) ratio value and %CFTR-positive cells above a selected threshold were the two parameters selected to quantify CFTR expression in cells. Lowest variability and the highest reproducibility were obtained when analyzing monocytes. ANOVA results indicated that both parameters were able to discriminate monocytes of healthy controls and CF individuals according to CFTR mutation classes with high accuracy. Significantly increased MFI ratio values were recorded in CFTR-defective cells that were also able to improve CFTR function after ex vivo treatment with PTC124 (Ataluren), an investigative drug designed to permit the ribosome to read through nonsense CFTR mutations. The method described is minimally invasive and may be used in the monitoring of responses to drugs whose efficacy can depend on increased CFTR protein expression levels

The Role of Citrullinated Proteins Suggests a Novel Mechanism in the Pathogenesis of Multiple Sclerosis

The pathogenesis of MS is unknown. In our studies, we have demonstrated an important role for citrullinated myelin basic protein (MBP). The accompanying loss of positive charge compromises the ability of MBP to interact with the lipid bilayer. The conversion of arginine to citrulline in brain is carried out by an enzyme peptidyl arginine deiminase (PAD) 2. The amount of PAD 2 in brain was increased in MS normal-appearing white matter. The mechanism responsible for this increase involved hypomethylation of the promoter region in the PAD 2 gene in MS, but no change (compared to normal) was found in thymus tissue DNA from the same MS patients. In addition, no change was observed in other neurological diseases, including Alzheimer’s, Parkinson’s, and Huntington’s. We propose that citrullinated MBP, resulting from elevated levels of PAD 2 represents an important biochemical pathway in the pathogenesis of MS

Nutritional value and bioactivity assessment methods of beverage and wines

In recent times, beverages are more widely regarded as functional food. There has been growing recognition of the key role of foods and beverages in disease prevention, treatment and its important role in assessing the medicinal properties is due to the biologically active substances of beverages, such as phenolic compounds, organic acids, amino acids, etc. Beverages are an excellent source for nutrients and bioactive compounds, including plant extracts, fiber, prebiotics and probiotics, vitamins, minerals, antioxidants, ω‐3 fatty acids. Bioactive compounds have an effect on the body as whole or specific tissues or cells. Bioactive compounds are capable of modulating metabolic processes and demonstrate positive properties such as antioxidant effect, inhibition of receptor activities, inhibition or induction of enzyme, and induction and inhibition of gene expression. Nowadays, increasing attention to polyphenols is due to the prevention of cancer, oxidative stress-associated diseases. Apart from antioxidant activities, polyphenols are a key role in biological functions, including cardiovascular diseases and modulation of carcinogenesis. The food and nutritional sciences can further help us to understand the influence of food on disease risk, pathogenesis, progression, and outcomes in obesogenic, carcinogenic, atherosclerotic, atherogenic, toxic and teratogenic environments. Nutritional value and biologically active compounds concentration differs in alcoholic or non-alcoholic beverages and depends on biotic/abiotic factors, fermentation, and overall technology types For bioactivity assessment, Capillary Electrophoresis, HPLC for oligomers and polymers separation, Liquid chromatography-mass spectrometry method, and spectrophotometry methods were used. We examined the total polyphenols content in beer wort, beer, wines, fresh and commercial juices, by Folin–Ciocalteu/Denis’ method, flavonoids by AlCl3 method in different types of wines, and Elements in white and red wines with Inductively Coupled Plasma Optical Emission spectroscopy.Pastaruoju metu gėrimai plačiau vertinami kaip funkcinis maistas. Vis labiau pripažįstamas pagrindinis maisto produktų ir gėrimų vaidmuo ligų prevencijoje, gydyme, o svarbų vaidmenį vertinant gydomąsias savybes lemia biologiškai aktyvios gėrimų medžiagos, tokios kaip fenolio junginiai, organinės rūgštys, amino rūgštys ir kt. Gėrimai yra puikus maistinių medžiagų ir bioaktyvių junginių, įskaitant augalų ekstraktus, skaidulas, prebiotikus ir probiotikus, vitaminus, mineralus, antioksidantus, ω - 3 riebalų rūgštis, šaltinis. Bioaktyvūs junginiai turi poveikį visam kūnui arba tam tikriems audiniams ar ląstelėms. Bioaktyvūs junginiai gali moduliuoti medžiagų apykaitos procesus ir pasižymi tokiomis teigiamomis savybėmis kaip antioksidacinis poveikis, receptorių veiklos slopinimas, fermentų slopinimas ar indukcija ir genų ekspresijos indukcija bei slopinimas. Šiais laikais vis daugiau dėmesio polifenoliams lemia vėžio, su oksidaciniu stresu susijusių ligų prevencija. Be antioksidacinės veiklos, polifenoliai yra pagrindinis vaidmuo atliekant biologines funkcijas, įskaitant širdies ir kraujagyslių ligas bei kancerogenezės moduliavimą. Maisto ir mitybos mokslai gali mums padėti suprasti maisto įtaką ligų rizikai, patogenezei, progresavimui ir nutukimo, kancerogeno, aterosklerozės, aterogeno, toksiškumo pasekmėms teratogeninėje aplinkoje. Paprastai mitybos vertinimo metodai yra pagrįsti dietiniais, laboratoriniais-biocheminiais, antropometriniais ir klinikiniais stebėjimais. Maisto ir mitybos mokslai gali mums padėti suprasti maisto įtaką ligų rizikai, patogenezei, ligų progresavimui ir nutukimo, kancerogeno, aterosklerozės, aterogeno, toksiškumo pasekmėms teratogeninėje aplinkoje. Maistinė vertė ir biologiškai aktyvių junginių koncentracija skiriasi alkoholiniuose ar nealkoholiniuose gėrimuose. Tai taip priklauso nuo biotinių ir abiotinių veiksnių, fermentacijos bei gamybos technologijos rūšių. Bioaktyvumui įvertinti buvo naudojama kapiliarinė elektroforezė, HPLC oligomerų ir polimerų atskyrimui, skysčių chromatografijos - masių spektrometrijos ir spektrofotometrijos metodai. Mes ištyrėme bendrą polifenolių kiekį alaus misoje, aluje, vynuose, šviežiose ir komercinėse sultyse Folin – Ciocalteu / Denis metodu, flavonoidus AlCl3 metodu skirtingų tipų vynuose ir elementus baltuose ir raudonuose vynuose su induktyviai sujungta plazmos emisijos spektroskopija.Gamtos mokslų fakultetasBiologijos katedr

Phosphorilation of the main protein myelin and its peptides

The experiments have been performed on the not-pedigree albino laboratory rats. The purpose of the work: revealing the role of the phosphorilation reaction in the main protein myelin proteolysis and study of the action of the obtained protein fragments on the definite receptor apparatus of the neurons. It has been show that the cAMP-dependent proteinkinase, the modified form of the myelin main protein, possesses the more sensibility to the tripsinolysis. Fragments 74-92 and 61-112 cause the modulation of bonding (33H1) haloperydol, and fragments 74-140 and 93-135 bonding (33H1) dilthiazema with the synaptic membranes. Revealation of the receptor-modulating properties of the definite fragments of the main protein of myelin can have an essential significance in understanding of mechanisms of the autoantigen and post-infection sensibilization of thenervous and T-cells called forth by the proteins similar to the main protein of myelin, and in revealation of the etiology of the autoimmune pathologies of the central nervous systemAvailable from VNTIC / VNTIC - Scientific & Technical Information Centre of RussiaSIGLERURussian Federatio