Macrovipera lebetina obtusa Snake Venom as a Modulator of Antitumor Effect in S-180 Sarcoma Mouse Model

Molecular Biology - Macrovipera lebetina obtusa (MLO) is a venomous snake endemic to Middle East. Here we describe the therapeutic potential of the MLO snake venom. In S-180 sarcoma-bearing mouse...     

Expansion of Bacteriophages Is Linked to Aggravated Intestinal Inflammation and Colitis

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Spatial and Spectral Mapping and Decomposition of Neural Dynamics and Organization of the Mouse Brain with Multispectral Optoacoustic Tomography

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Auto-regulation of DNA degrading bacteriocins: molecular and ecological aspects

Colicins, proteinaceous antibiotics produced by Escherichia coli, specifically target competing strains killing them through one of a variety of mechanisms, including pore formation and nucleic acid degradation. The genes encoding colicins display a unique form of expression, which is tightly regulated, involving the DNA damage response regulatory system (the SOS response system), confined to stressful conditions and released by degradation of the producing cell. Given their lethal nature, colicin production has evolved a sophisticated system for repression and expression. While exploring the expression of 13 colicins we identified a novel means of induction unique to strains that kill by DNA degradation: these colicinogenic strains mildly poison themselves inflicting DNA damage that induces their DNA repair system (the SOS system), and their own expression. We established that among the four known DNase colicins (E2, E7, E8 and E9), three act to induce their own production. Using different stresses we show that this form of self-regulation entails high cost when growth conditions are not optimal, and is not carried out by individual cells but is a population-mediated trait. We discuss this novel form of colicins’ regulation and expression, and its possible molecular mechanism and evolutionary implications.     

Thermodynamics of interactions of TAlPyP4 and AgTAlPyP4 porphyrins with poly(rA)poly(rU) and poly(rI)poly(rC) duplexes

We employed UV light absorption and circular dichroism (CD) spectroscopic measurements to study the binding of novel water-soluble porphyrins meso-tetra-(4N-allylpyridyl)porphyrin [TAlPyP4], and its Ag containing derivative to the poly(rA)poly(rU) and poly(rI)poly(rC) RNA duplexes. Our results suggest that TAlPyP4 associate with the duplexes via intercalation, whereas the conservative CD spectra indicates that AgTAlPyP4 preferably binds via outside self-stacking mode. We used our determined binding isotherms for each ligand-RNA binding event to calculate the binding constant, Kb, and binding free energy, DeltaGb = -RTlnKb. By performing these experiments as a function of temperature, we evaluated the van't Hoff binding enthalpies, DeltaH. The binding entropies, DeltaSb, were calculated as DeltaSb = (DeltaHb - DeltaGb)/T. We interpret our data in terms of specific interactions that stabilize/destabilize each ligand-RNA complex studied in this work. Taken together, our data provide important new information about the thermodynamics of interactions of porphyrins with nucleic acids.     

Morphological Changes of Proteolipid Giant Unilamellar Vesicles Affected by Macrovipera lebetina obtusa Venom Visualized with Fluorescence Microscope

As a rule, zootoxins are complex and biologically active, and therefore the greater part of zootoxins is subjected to biotransformation and interacts with biological membranes. In this case, the interaction of different venom components with the membranes is not always the same. The present study shows how the giant unilamellar vesicles (GUV) from bovine brain proteolipids interact with Macrovipera lebetina obtusa venom. GUV (mean diameter 30 μm) were formed by the electroformation method. We used 8-anilino-1-naphthalenesulfonic acid and pyrene as fluorescence probes, which allowed us to quantify the fluidity changes in the membrane by measuring the fluorescence intensity.     

Stark fluorescence spectroscopy reveals two emitting sites in the dissipative state of FCP antennas

Diatoms are characterized by very efficient photoprotective mechanisms where the excess energy is dissipated as heat in the main antenna system constituted by fucoxanthin–chlorophyll (Chl) protein complexes (FCPs). We performed Stark fluorescence spectroscopy on FCPs in their light-harvesting and energy dissipating states. Our results show that two distinct emitting bands are created upon induction of energy dissipation in FCPa and possibly in FCPb. More specifically one band is characterized by broad red shifted emission above 700 nm and bears strong similarity with a red shifted band that we detected in the dissipative state of the major light-harvesting complex II (LHCII) of plants [26]. We discuss the results in the light of different mechanisms proposed to be responsible for photosynthetic photoprotection.     

Assessment of new cationic porphyrin binding to plasma proteins by planar microarray and spectroscopic methods

Porphyrins have a unique aromatic structure determining particular photochemical properties that make them promising photosensitizers for anticancer therapy. Previously, we synthesized a set of artificial porphyrins by modifying side-chain functional groups and introducing different metals into the core structure. Here, we have performed a comparative study of the binding properties of 29 cationic porphyrins with plasma proteins by using microarray and spectroscopic approaches. The porphyrins were noncovalently immobilized onto hydrogel-covered glass slides and probed to bio-conjugated human and bovine serum albumins, as well as to human hemoglobin. The signal detection was carried out at the near-infrared fluorescence wavelength (800?nm) that enabled the effect of intrinsic visible wavelength fluorescence emitted by the porphyrins tested to be discarded. Competition assays on porphyrin microarrays indicated that long-chain fatty acids (FAs) (palmitic and stearic acids) decrease porphyrin binding to both serum albumin and hemoglobin. The binding affinity of different types of cationic porphyrins for plasma proteins was quantitatively assessed in the absence and presence of FAs by fluorescent and absorption spectroscopy. Molecular docking analysis confirmed results that new porphyrins and long-chain FAs compete for the common binding site FA1 in human serum albumin and meso-substituted functional groups in porphyrins play major role in the modulation of conformational rearrangements of the protein.