Regulation of the intermediate filament protein nestin at rodent neuromuscular junctions by innervation and activity

The intermediate filament nestin is localized postsynaptically at rodent neuromuscular junctions. The protein forms a filamentous network beneath and between the synaptic gutters, surrounds myofiber nuclei, and is associated with Z-discs adjacent to the junction. In situ hybridization shows that nestin mRNA is synthesized selectively by synaptic myonuclei. Although weak immunoreactivity is present in myelinating Schwann cells that wrap the preterminal axon, nestin is not detected in the terminal Schwann cells (tSCs) that cover the nerve terminal branches. However, after denervation of muscle, nestin is upregulated in tSCs and in SCs within the nerve distal to the lesion site. In contrast, immunoreactivity is strongly downregulated in the muscle fiber. Transgenic mice in which the nestin neural enhancer drives expression of a green fluorescent protein (GFP) reporter show that the regulation in SCs is transcriptional. However, the postsynaptic expression occurs through enhancer elements distinct from those responsible for regulation in SCs. Application of botulinum toxin shows that the upregulation in tSCs and the loss of immunoreactivity in muscle fibers occurs with blockade of transmitter release. Extrinsic stimulation of denervated muscle maintains the postsynaptic expression of nestin but does not affect the upregulation in SCs. Thus, a nestin-containing cytoskeleton is promoted in the postsynaptic muscle fiber by nerve-evoked muscle activity but suppressed in tSCs by transmitter release. Nestin antibodies and GFP driven by nestin promoter elements serve as excellent markers for the reactive state of SCs. Vital imaging of GFP shows that SCs grow a dynamic set of processes after denervation

Atomistic simulations of self-trapped exciton formation in silicon nanostructures: The transition from quantum dots to nanowires

Using an approximate time-dependent density functional theory method, we calculate the absorption and luminescence spectra for hydrogen passivated silicon nanoscale structures with large aspect ratio. The effect of electron confinement in axial and radial directions is systematically investigated. Excited state relaxation leads to significant Stokes shifts for short nanorods with lengths less than 2 nm, but has little effect on the luminescence intensity. The formation of self-trapped excitons is likewise observed for short nanostructures only; longer wires exhibit fully delocalized excitons with neglible geometrical distortion at the excited state minimum.Comment: 10 pages, 4 figure

Assessment results professional development of medical specialists of an average link

In article the substantiation of the method of formalized individual assessment of results of professional development of medical specialists of an average link was given. Systematic multi-factor data analysis of the test survey, characterizing the level of development of additional professional programs, educational activity of specialist was conducted. The values of integral indicators, of influence coefficient, determining the most significant factors for the development of continuing medical education and a particular specialist in particular were obtained.В статье приведено обоснование формализованного метода индивидуальной оценки результатов профессионального развития медицинских специалистов среднего звена. Выполнен системный многофакторный анализ данных тест-опроса, характеризующего уровень освоения дополнительных профессиональных программ, образовательной активности специалиста. Получены значения интегральных показателей, коэффициентов влияния, определяющих наиболее значимые факторы развития системы непрерывного медицинского образования и конкретного специалиста в частности

Simulation of dimensionality effects in thermal transport

The discovery of nanostructures and the development of growth and fabrication techniques of one- and two-dimensional materials provide the possibility to probe experimentally heat transport in low-dimensional systems. Nevertheless measuring the thermal conductivity of these systems is extremely challenging and subject to large uncertainties, thus hindering the chance for a direct comparison between experiments and statistical physics models. Atomistic simulations of realistic nanostructures provide the ideal bridge between abstract models and experiments. After briefly introducing the state of the art of heat transport measurement in nanostructures, and numerical techniques to simulate realistic systems at atomistic level, we review the contribution of lattice dynamics and molecular dynamics simulation to understanding nanoscale thermal transport in systems with reduced dimensionality. We focus on the effect of dimensionality in determining the phononic properties of carbon and semiconducting nanostructures, specifically considering the cases of carbon nanotubes, graphene and of silicon nanowires and ultra-thin membranes, underlying analogies and differences with abstract lattice models.Comment: 30 pages, 21 figures. Review paper, to appear in the Springer Lecture Notes in Physics volume "Thermal transport in low dimensions: from statistical physics to nanoscale heat transfer" (S. Lepri ed.

Comparison of the composition and metabolic potential of the reindeer’s rumen microbiome in the Yamal-Nenets and Nenets autonomous district of the Russian Arctic

The adaptive ability of reindeer to the harsh conditions of the Russian Arctic is not determined solely by the genome of the macroorganism and, of course, includes an extensive genetic and metabolic repertoire of the microbiome.The aim. To compare the taxonomic and predicted metabolic profiles of the rumen microbiome of adult reindeer living in the natural pastures of the Yamalo-Nenets and Nenets Autonomous districts of the Russian Federation.Materials and methods. Expeditions to the Yamal-Nenets and Nenets Autonomous districts of the Russian Arctic in 2017 were carried out to take samples of the rumen. The contents of the rumen were taken from clinically healthy reindeer individuals (at least 3 times repetition). To analyze the animal scar microbiota and determine metabolic profiles, 16S rRNA NGS sequencing was performed on a MiSeq device (Illumina, USA). Bioinformatic data analysis was performed using QIIME2 software ver. 2020.8. The noise sequences were filtered by DADA2. Silva 138 reference database was used for taxonomy analysis. Reconstruction and prediction of the functional content of the metagenome was carried out using the software complex PICRUSt2 (v. 2.3.0).Results. During NGS sequencing, a total of 223 768 sequences of the 16S rRNA gene of the reindeer scarring microbiome were studied. Significant (p ≤ 0.05) differences between the groups in 10 bacterial phyla and superphyla were revealed: Actinobacteriota, Spirochaetes, Chloroflexi, Verrucomicrobia, Bdellovibrionota, Synergistetes, Fusobacteriota, Myxococcota, Cyanobacteria, Campilobacterota. The results of the reconstruction and prediction of the functional content of the metagenome using the PICRUSt2 bioinformatic analysis made it possible to identify 328 potential metabolic pathways. Differences between the groups were revealed in 16 predicted metabolic pathways, among which the pathways of chlorophyllide and amino acid biosynthesis dominated

The role of nelarabine in the treatment of T-cell acute lymphoblastic leukemia: literature review and own experience

Aim. The analysis of experience of nelarabine use in refractory/relapsed T-cell acute lymphoblastic leukemia (T-ALL) depending on the immunophenotype and the line of therapy. Materials and methods. All the patients with relapsed or refractory T-ALL aged from 0 to 18 years who received treatment with nelarabine as a part of the therapeutic element R6 were included in the study. For all patients a detailed immunological analysis of leukemia cells with discrimination of immunological variants TI, TII, TIII or TIV was performed. Patients administered with nelarabine as a first therapeutic element were referred to the first-line therapy group, other patients were referred to the second-line therapy group. Nelarabine was administered as intravenous infusion at a dose of 650 mg/m2, on days 1-5. Allogeneic hematopoietic stem cells transplantation (allo-HSCT) was considered for all patients. Results. From 2009 to 2017, 54 patients with refractory/relapsed T-ALL were treated with nelarabine. Five-year event-free survival (EFS) and overall survival (OS) was 28% for all patients, cumulative risk of relapse (CIR) was 27%. EFS was significantly higher in nelarabine first-line therapy group in comparison with second-line therapy group (34±8% vs 8±8%, p=0,05). In patients after allo-HSCT EFS, OS and CIR were 51±10%, 50±10% and 39,1±9,5% accordingly. The best results were achieved in patients with TI immunophenotype. No toxicity-related mortality as well as severe neurologic complications or discontinuation of therapy associated with use of nelarabine were reported. Conclusion. The use of nelarabine is an effective strategy for the treatment of relapsed and refractory T-ALL. The best treatment outcomes were obtained in patients with TI immunophenotype and in the first-line therapy group. Optimal dosage regimens can be established during controlled clinical trials

Methodological advances in imaging intravital axonal transport.

Axonal transport is the active process whereby neurons transport cargoes such as organelles and proteins anterogradely from the cell body to the axon terminal and retrogradely in the opposite direction. Bi-directional transport in axons is absolutely essential for the functioning and survival of neurons and appears to be negatively impacted by both aging and diseases of the nervous system, such as Alzheimer's disease and amyotrophic lateral sclerosis. The movement of individual cargoes along axons has been studied in vitro in live neurons and tissue explants for a number of years; however, it is currently unclear as to whether these systems faithfully and consistently replicate the in vivo situation. A number of intravital techniques originally developed for studying diverse biological events have recently been adapted to monitor axonal transport in real-time in a range of live organisms and are providing novel insight into this dynamic process. Here, we highlight these methodological advances in intravital imaging of axonal transport, outlining key strengths and limitations while discussing findings, possible improvements, and outstanding questions

Gene expression in farm poultry under the influence of T-2 toxin and the use of biological preparations

Background. Feed-borne T-2 toxin may inhibit innate immune system function in birds.The aim. To evaluate the effect of T-2 toxin, artificially introduced with feed, on the expression level of a number of immunity-related genes in the tissues of the broiler digestive system.Materials and methods. The experiments were carried out in the vivarium of the FSC “VNITIP” RAS broilers of the Smena 8 cross from 33 to 47-day old. Experimental contamination of feed T-2 toxin was performed. The birds were divided into 4 groups of 5 animals each: I – control, receiving a diet without the introduction of T-2 toxin, II experimental – receiving a diet with the addition of T-2 toxin, III experimental – receiving a diet with the addition of T-2 toxin and the sorbent Zaslon2+, IV experimental – receiving a diet with the addition of T-2 toxin, the same sorbent Zaslon2+and Axtra Pro enzyme. The level of mRNA expression was analyzed by quantitative reverse transcription PCR.Results. The data obtained indicated the impact of T-2 toxin contamination of broiler feed on the modulation of the level of expression of genes associated with the functioning of the immune system in the cecum and pancreas. Exposure to T-2 toxin (group II) led to an increase in the expression of the pro-inflammatory gene IL-6 in the tissues of the caecum by 10.8 times and IL-8 in the pancreas by 3.89 times (p ≤ 0.05) compared with control group I. The effect of the sorbent, as well as the complex, including the sorbent and the enzyme, on the expression of broiler genes was positive. The sorbent without the enzyme showed greater efficiency than with the additional introduction of the enzyme