A chronobiological analysis of the lymphocyte dehydrogenase activity in the peripheral blood of rats with Walker 256 carcinosarcoma

In a series of experiments the alpha-glycerophosphate dehydrogenase and succinate dehydrogenase (SDH) activities were daily determined simultaneously by the cytochemical method in peripheral blood lymphocytes of normal rats and those with the Walker carcinosarcoma. Using an original algorithm a hierarchy of biorhythms was singled out by a computer according to individual changes in the dehydrogenase activity for each rat. The mean level of succinate dehydrogenase activity was higher than that of alpha-glycerophosphate dehydrogenase. A set of discovered biorhythms and their representation were identical in the both enzymes. The tumor transplantation caused changes in the phase coordination of investigated dehydrogenases in all rhythms and promoted an increase of the succinate dehydrogenase amplitude as compared with the alpha-glycerophosphate dehydrogenase amplitude in certain rhythms. It is concluded that biorhythmological parameters of these enzymes may be used for characterization of the tumor-bearing host.     

Ge/Si(001) heterostructures with dense arrays of Ge quantum dots: morphology, defects, photo-emf spectra and terahertz conductivity

ABSTRACT: Morphology and defects: Issues of Ge hut cluster array formation and growth at low temperatures on the Ge/Si(001) wetting layer are discussed on the basis of explorations performed by high resolution STM and in-situ RHEED. Dynamics of the RHEED patterns in the process of Ge hut array formation is investigated at low and high temperatures of Ge deposition. Dfferent dynamics of RHEED patterns during the deposition of Ge atoms in different growth modes is observed, which reflects the difference in adatom mobility and their 'condensation' fluxes from Ge 2D gas on the surface for different modes, which in turn control the nucleation rates and densities of Ge clusters. Data of HRTEM studies of multilayer Ge/Si heterostructures are presented with the focus on low-temperature formation of perfect films. Photo-emf spectroscopy: Heteroepitaxial Si p-i-n-diodes with multilayer stacks of Ge/Si(001) quantum dot dense arrays built in intrinsic domains have been investigated and found to exhibit the photo-emf in a wide spectral range from 0.8 to 5 mcm. An effect of wide-band irradiation by infrared light on the photo-emf spectra has been observed. Photo-emf in different spectral ranges has been found to be differently affected by the wide-band irradiation. A significant increase in photo-emf is observed in the fundamental absorption range under the wide-band irradiation. The observed phenomena are explained in terms of positive and neutral charge states of the quantum dot layers and the Coulomb potential of the quantum dot ensemble. A new design of quantum dot infrared photodetectors is proposed. Terahertz spectroscopy: By using a coherent source spectrometer, first measurements of terahertz dynamical conductivity (absorptivity) spectra of Ge/Si(001) heterostructures were performed at frequencies ranged from 0.3 to 1.2 THz in the temperature interval from 300 to 5 K. The effective dynamical conductivity of the heterostructures with Ge quantum dots has been discovered to be significantly higher than that of the structure with the same amount of bulk germanium (not organized in an array of quantum dots). The excess conductivity is not observed in the structures with the Ge coverage less than 8 A. When a Ge/Si(001) sample is cooled down the conductivity of the heterostructure decreases.     

Minor Changes in Erythrocyte Osmotic Fragility in Trace Amine-Associated Receptor 5 (TAAR5) Knockout Mice

Trace amine-associated receptors (TAARs) are a group of G protein-coupled receptors that are expressed in the olfactory epithelium, central nervous system, and periphery. TAAR family generally consists of nine types of receptors (TAAR1-9), which can detect biogenic amines. During the last 5 years, the TAAR5 receptor became one of the most intriguing receptors in this subfamily. Recent studies revealed that TAAR5 is involved not only in sensing socially relevant odors but also in the regulation of dopamine and serotonin transmission, emotional regulation, and adult neurogenesis by providing significant input from the olfactory system to the limbic brain areas. Such results indicate that future antagonistic TAAR5-based therapies may have high pharmacological potential in the field of neuropsychiatric disorders. TAAR5 is known to be expressed in leucocytes as well. To evaluate potential hematological side effects of such future treatments we analyzed several hematological parameters in mice lacking TAAR5. In these mutants, we observed minor but significant changes in the osmotic fragility test of erythrocytes and hematocrit levels. At the same time, analysis of other parameters including complete blood count and reticulocyte levels showed no significant alterations in TAAR5 knockout mice. Thus, TAAR5 gene knockout leads to minor negative changes in the erythropoiesis or eryptosis processes, and further research in that field is needed. The impact of TAAR5 deficiency on other hematological parameters seems minimal. Such negative, albeit minor, effects of TAAR5 deficiency should be taken into account during future TAAR5-based therapy development.     

A novel approach to composite preparation by direct synthesis of carbon nanomaterial on matrix or filler particles

Carbon nanotubes (CNTs), nanofibers (CNFs) and graphene are promising components for next-generation high-performance structural and multifunctional composite materials. One of the largest obstacles to creating strong, electrically or thermally conductive CNT/CNF or graphene composites is the difficulty of achieving a good dispersion of the carbon nanomaterials in a matrix. Typically, time-consuming steps of carbon nanomaterial purification, ultrasound treatment and functionalization are required. We utilized a novel approach to fabricate composite materials by growing CNTs/CNFs directly on the surface of matrix, matrix precursor or filler particles. As the precursor matrix and fillers we utilized cement (clinker), copper powder, fly ash particles, calcinated soil and sand. Carbon nanomaterials were successfully grown on these materials without additional catalyst. Investigations of the physical properties of the composite materials based on these carbon-modified particles revealed enhanced mechanical and electrical properties. The improvement in the mechanical properties of the C/Cu-based composite materials is attributed the crystallite or grain formation of the matrix material.     

Marine Two-Headed Sphingolipid-Like Compound Rhizochalin Inhibits EGF-Induced Transformation of JB6 P<Superscript>+</Superscript> Cl41 Cells

Rhizochalin [(2R,3R,26R,27R)-2,27-diamino-3-hydroxy-26-[(2R,3R,4S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy]octacosan-11-one], an antimicrobial and cytotoxic marine two-headed sphingolipid-like natural product, isolated from the sponge Rhizochalina incrustata, and some related compounds were studied as anticarcinogenic and proapoptotic agents. The corresponding effects were tested on the mouse skin epidermal JB6 P⁺ Cl 41 cell line, its stable transfectants, THP-1, HeLa, and SNU-C4 human tumor cells using a variety of assessments, including cell viability (MTS), flow cytometry, anchorage-independent soft agar, and luciferase assays. At 5–10 μM concentrations, rhizochalin was effective as an inhibitor of the malignant transformation of JB6 P⁺ Cl 41 cells or colony formation of human tumor cells, which exerted its action, at least in part, through the induction of p53-dependent apoptosis. Structure–activity relationship study showed aglycon of rhizochalin to be the most active while peracetylated aglycon was the least active among the compounds studied.     

Swelling Behavior and Complex Formation Ability of Ternary Amphoteric Gels based on Allylamine Derivatives and Maleic Acid

Summary: The swelling behavior of an amphoteric gel composed of 50 mol‐% of maleic acid (MA), 25 mol‐% of N,N′‐dimethyldiallylammonium chloride (DMDAAC) and 25 mol‐% of diallylamine (DAA) was studied in aqueous and aqueous‐salt solutions. The isoelectric point (IEP) of the MA‐DMDAAC‐DAA gel determined from swelling experiments was about pH 4.6. Considerable gel swelling with increasing ionic strength was observed at the IEP. Dynamic swelling properties of the amphoteric gel in water with and without added salt were measured at various pH values including the IEP. The swelling behavior of the amphoteric gel was found to depend on the ionization state of the functional groups. It can be described by either a relaxation‐controlled or non‐Fickian (anomalous) mechanism. Swelling‐deswelling properties of the amphoteric gel were also studied in mixtures of water and organic solvents. The amphoteric gel was able to complex sodium poly(styrene sulfonate), sodium lauryl sulfate, the cationic drug richlocain, and the bivalent transition metal ions Cu²⁺, Ni²⁺, Co²⁺, and Zn²⁺. The sorption of polyelectrolyte, surfactant, drug, and metal ions by the amphoteric gel is accompanied by the contraction of the gel network. Partial release of the cationic drug molecules entrapped into the gel volume takes place at the IEP of the amphoteric gel with low activation energy, while neither the anionic polyelectrolyte nor the surfactants are released from the gel interior at the IEP. The swelling‐shrinking behavior of gel‐polyelectrolyte and gel‐surfactant complexes in dependence of pH and ionic strength of the outer solution is similar.

     

Cytotoxic Activity of LLO Y406A Is Targeted to the Plasma Membrane of Cancer Urothelial Cells

Identification of novel agents for bladder cancer treatment is highly desirable due to the high incidence of tumor recurrence and the risk of progression to muscle-invasive disease. The key feature of the cholesterol-dependent toxin listeriolysin O mutant (LLO Y406A) is its preferential activity at pH 5.7, which could be exploited either directly for selective targeting of cancer cells or the release of accumulated therapeutics from acidic endosomes. Therefore, our goal was to compare the cytotoxic effect of LLO Y406A on cancer cells (RT4) and normal urothelial cells (NPU), and to identify which cell membranes are the primary target of LLO Y406A by viability assays, life-cell imaging, fluorescence, and electron microscopy. LLO Y406A decreased viability, altered cell morphology, provoked membrane blebbing, and induced apoptosis in RT4 cells, while it did not affect NPU cells. LLO Y406A did not cause endosomal escape in RT4 cells, while the plasma membrane of RT4 cells was revealed as the primary target of LLO Y406A. It has been concluded that LLO Y406A has the ability to selectively eliminate cancer urothelial cells through pore-forming activity at the plasma membrane, without cytotoxic effects on normal urothelial cells. This promising selective activity merits further testing as an anti-cancer agent.