A New Cofilin-Dependent Mechanism for the Regulation of Brain Mitochondria Biogenesis and Degradation.

The aim Was to study the role of post-translational modifications of cofilin in the regulation of respiration and autophagy in murine brain mitochondria. MATERIALS AND METHODS: The experiments were performed with C57BL/6 mice. To obtain cytoplasmic and mitochondrial fractions of the brain tissue, differential centrifugation was used. Expressions of cofilin, phospho-cofilin, K48- and K63-associated chains of ubiquitin, and the autophagy marker LC3B were determined using electrophoresis, immunoprecipitation and Western blot methods. To study the processes of ubiquitination, we used PR619 - the inhibitor of deubiquitinating enzymes. Respiratory activity of brain mitochondria was evaluated using high-resolution fluorespirometry. RESULTS: Modification of cofilin by non-canonical K63 multiubiquitin chains in the cytoplasm and mitochondria from murine brain was demonstrated. Different levels of phospho-cofilin, cofilin, and its ubiquitinated proteoforms were found. PR619, the inhibitor of deubiquitinating enzymes, affects the expression of phosphorylated and ubiquitinated forms of cofilin in the mitochondria and cytoplasm, at the same time it changes the activity of tissue respiration and mitophagy. CONCLUSION: The sensitivity of cofilin to the inhibitor of deubiquitinating enzymes indicates the existence of a new non-catabolic mechanism of cofilin modification, which may be involved in the regulation of mitochondrial functions, specifically, the mitochondrial respiration and autophagy. The data help understand the molecular mechanisms of mitochondrial function in normal and pathological conditions, which may be useful in developing novel methods for the treatment of diseases of the nervous system.

[Organizational and therapeutic aspects of the elimination of the medical consequences of chemical accidents].

During the liquidation of consequences of chemical accidents the main task is minimization o the population losses and the provision of effective medical care to. the victims. Training experience related to chemical accidents, shows the need for constant readiness of health facilities in the area of the chemical industry accommodation, planning of the medical forces and resources reserve. The most important elements of medical care in chemical accidents are affected sorting, intensive therapy and reanimation in cases of severe injuries, the organization of the observation of persons with initial minor manifestations of intoxication. Emergency assistance should be provided in full volume as soon as possible. It .is essential to provide enough oxygen and required. drugs (hormonal drugs, diuretics, antibiotics, anticonvulsants, analgesics, and others). Multistage evacuation should be excluded and should be:done the planned training within the medical service stuff with toxicological profile.

Evaluation of biocidal efficacy of copper alloy coatings in comparison with solid metal surfaces: generation of organic copper phosphate nanoflowers.

AIMS: To analyse the biocidal efficacy of thermal sprayed copper surfaces. METHODS AND RESULTS: Copper alloy sheet metals containing >60% copper have been shown to exhibit potent biocidal activity. Surface biocidal activity was assessed by epifluorescence microscopy. After 2-h exposure at 20 °C in phosphate-buffered saline (PBS), contact killing of Gram-negative Escherichia coli and Gram-positive Staphylococcus epidermidis by brass sheet metal and phosphor bronze was 3-4-times higher than that by stainless steel. SEM observations revealed that the surface membranes of both bacterial strains were slightly more irregular when exposed to brass sheet metal than stainless steel. However, when exposed to phosphor bronze coating, E. coli were 3-4 times larger with irregular membrane morphology. In addition, the majority of the cells were associated with spherical carbon-copper-phosphate crystalline nanostructures characteristic of nanoflowers. The membranes of many of the S. epidermidis exhibited blebbing, and a small subset was also associated with nanoflowers. CONCLUSIONS: Our data indicate that increasing the surface roughness of copper alloys had a pronounced impact on the membrane integrity of Gram-positive and, to a lesser degree, Gram-negative bacteria. In the presence of PBS, carbon-copper-phosphate-containing nanoflowers were formed, likely nucleated by components derived from killed bacteria. The intimate association of the bacteria with the nanoflowers and phosphor bronze coating likely contributed to their nonreversible adhesion. SIGNIFICANCE AND IMPACT OF THE STUDY: Thermal spraying of copper alloys provides a strategy for the rapid coating of three-dimensional organic and inorganic surfaces with biocidal copper alloys. Our study demonstrates that the macroscale surface roughness generated by the thermal spray process enhances the biocidal activity of copper alloys compared with the nanoscale surface roughness of copper sheet metals. Moreover, the coating surface topography provides conditions for the rapid formation of organic copper phosphate nanocrystals/nanoflowers.

Bernas ion source discharge simulation.

As the technology and applications continue to grow up, the development of plasma and ion sources with clearly specified characteristic is required. Therefore comprehensive numerical studies at the project stage are the key point for ion implantation source manufacturing (especially for low energy implantation). Recently the most commonly encountered numerical approach is the Monte Carlo particle-in-cell (MCPIC) method also known as particle-in-cell method with Monte Carlo collisions. In ITEP the 2D3V numerical code PICSIS-2D realizing MCPIC method was developed in the framework of the joint research program. We present first results of the simulation for several materials interested in semiconductors. These results are compared with experimental data obtained at the ITEP ion source test bench.

Front-end simulation of injector for terawatt accumulator.

A terawatt accumulator (TWAC) accelerator/storage ring complex with the laser ion source is in progress at ITEP. The new injector I4 based on the radio frequency quadrupole (RFQ) and interdigital H-mode (IH) linear accelerator is under construction. The front end of the new TWAC injector consists of a laser ion source, an extraction system, and a low energy beam transport (LEBT). The KOBRA3-INP was used for the simulation and optimization of the ion source extraction system. The optimization parameter is the maximum brightness of the beam generated by the laser ion source. Also the KOBRA3-INP code was used for LEBT investigation. The LEBT based on electrostatic grid lenses is chosen for injector I4. The results of the extraction system and LEBT investigations for ion beam matching with RFQ are presented.

Status of ITEP decaborane ion source program.

The joint research and development program is continued to develop steady-state ion source of decaborane beam for ion implantation industry. Both Freeman and Bernas ion sources for decaborane ion beam generation were investigated. Decaborane negative ion beam as well as positive ion beam were generated and delivered to the output of mass separator. Experimental results obtained in ITEP are presented.

Ion sources for energy extremes of ion implantation.

For the past four years a joint research and development effort designed to develop steady state, intense ion sources has been in progress with the ultimate goal to develop ion sources and techniques that meet the two energy extreme range needs of meV and hundreads of eV ion implanters. This endeavor has already resulted in record steady state output currents of high charge state of antimony and phosphorus ions: P(2+) [8.6 pmA (particle milliampere)], P(3+) (1.9 pmA), and P(4+) (0.12 pmA) and 16.2, 7.6, 3.3, and 2.2 pmA of Sb(3+)Sb(4+), Sb(5+), and Sb(6+) respectively. For low energy ion implantation, our efforts involve molecular ions and a novel plasmaless/gasless deceleration method. To date, 1 emA (electrical milliampere) of positive decaborane ions was extracted at 10 keV and smaller currents of negative decaborane ions were also extracted. Additionally, boron current fraction of over 70% was extracted from a Bernas-Calutron ion source, which represents a factor of 3.5 improvement over currently employed ion sources.

[Aminostigmine-a novel drug against home poisoning]. / Primenenie novogo lekarstvennogo sredstva aminostigmina v terapii bytovykh otravlenii.

Aminostigmin, a novel reversible inhibitor of cholinesterase developed in Russia, has been tried in management of poisoning with cholinolytyics, antihistamine drugs, tricycle antidepressants and derivatives of 1,4-benzodiazepine. The treatment of 144 patients with aminostigmin and 20 patients with galantamin showed close to similar efficacy of these drugs. The scheme of aminostigmin administration is proposed warranting fast relief of cholinolytic syndrome in subjects poisoned with cholinolytics, antihistamine drugs and antidepressants. Benzodiazepines poisoning was unresponsive to aminostigmin. Rare side effects were caused by overdose. Aminostigmin is an effective antidote in cholinolytic poisoning.

[Flow cytofluorimetric analysis of the proliferative activity of lymphocytes in a culture with phytohemagglutinin]. / Protochno-tsitofliuorometricheskii analiz proliferativnoi aktivnosti limfotsitov v kul'ture s fitogemaggliutininom.

Phytohemagglutinin (PHA)-effected lymphocyte blastogenesis test (LBGT) in culture has been assessed by flow cytofluorometry in 63 normal subjects and in 160 patients suffering from various pulmonary diseases. An algorithm for the estimation of cellular distribution in accordance with the mitotic cycle stages is suggested, and a computer program for the analysis of the results, based on the mitotic cycle stages, has been compiled. The lymphocyte proliferative activities have been estimated with various PHA doses. The findings have been in good correlation with the results of radionuclide studies (3H thymidine label). The described approach to LBGT assessment yields reliable results and may be used in diagnostic studies.