Development of electrochemical sensor based on aptamer specific to lung cancer tumor marker

Electrochemical aptasensor is a sensor based on an indicator electrode covered with a layer of an aptamer that is able to bind target molecules with high specificity. In this work, DNA-aptamer LC-2108 specific to lung cancer tumor marker was immobilized onto the surface of golden screen-printed and disc electrodes. The electrodes were studied by conventional electrochemical methods–cyclic voltammetry and electrochemical impedance spectroscopy. The current increase and electron transfer resistance decrease were registered. It seems as if the aptamer presence facilitated the electron transfer through the electrode-solution boundary. As the possible reasons of such an unusual electrochemical behavior we proposed the unordinary or irregular structure of the aptamer layer on the Au surface or the specific electrochemical properties of the aptamer itself

The Inhibition of CDK8/19 Mediator Kinases Prevents the Development of Resistance to EGFR-Targeting Drugs

Drug resistance is the main obstacle to achieving cures with both conventional and targeted anticancer drugs. The emergence of acquired drug resistance is initially mediated by non-genetic transcriptional changes, which occur at a much higher frequency than mutations and may involve population-scale transcriptomic adaptation. CDK8/19 kinases, through association with transcriptional Mediator complex, regulate transcriptional reprogramming by co-operating with different signal-responsive transcription factors. Here we tested if CDK8/19 inhibition could prevent adaptation to drugs acting on epidermal growth factor receptor (EGFR/ERBB1/HER1). The development of resistance was analyzed following long-term exposure of BT474 and SKBR3 breast cancer cells to EGFR-targeting small molecules (gefitinib, erlotinib) and of SW48 colon cancer cells to an anti-EGFR monoclonal antibody cetuximab. In all cases, treatment of small cell populations (~10 cells) with a single dose of the drug initially led to growth inhibition that was followed by the resumption of proliferation and development of drug resistance in the adapted populations. However, this adaptation was always prevented by the addition of selective CDK8/19 inhibitors, even though such inhibitors alone had only moderate or no effect on cell growth. These results indicate that combining EGFR-targeting drugs with CDK8/19 inhibitors may delay or prevent the development of tumor resistance to therapy

Иммуноферментный анализ метаболитов витамина D3

We report herein improved version of the synthesis of hapten based on cholecalciferol and its active metabolite 25-hydroxycholecalcalferol. The methodology of obtaining high-molecular immunogenic conjugates of vitamin D3 derivatives with bovine serum albumin and horseradish peroxidase conjugates for direct ELISA was optimized. Immunisation of rabbits was carried out and polyclonal antibodies to 25-hydroxycholecalceferol were obtained and tested in an enzyme-linked immunosorbent assay. To improve the accuracy of the method, the sample preparation procedure was optimized, including the release of vitamin D3 and its active metabolites from complexes with vitamin D-binding protein.Описан улучшенный вариант синтеза гаптена на основе холекальциферола и его активного метаболита 25-гидроксихолекальцеферола. Оптимизирована методика получения высокомолекулярных иммуногенных конъюгатов производных витамина D3 с бычьим сывороточным альбумином, а также конъюгатов с пероксидазой хрена для прямого ИФА. Проведена иммунизация кроликов, выделены поликлональные антитела к 25-гидроксихолекальцеферолу, которые испытаны в иммуноферментном анализе. Для повышения точности метода оптимизирован процесс пробоподготовки, включающий высвобождение витамина D3 и его активных метаболитов из комплексов с витамин D-связывающим белком

Topology of the spaces of Morse functions on surfaces

Let $M$ be a smooth closed orientable surface, and let $F$ be the space of Morse functions on $M$ such that at least $\chi(M)+1$ critical points of each function of $F$ are labeled by different labels (enumerated). Endow the space $F$ with $C^\infty$-topology. We prove the homotopy equivalence $F\sim R\times{\widetilde{\cal M}}$ where $R$ is one of the manifolds ${\mathbb R}P^3$, $S^1\times S^1$ and the point in dependence on the sign of $\chi(M)$, and ${\widetilde{\cal M}}$ is the universal moduli space of framed Morse functions, which is a smooth stratified manifold. Morse inequalities for the Betti numbers of the space $F$ are obtained.Comment: 15 pages, in Russia

Methamphetamine withdrawal induces activation of CRF neurons in the brain stress system in parallel with an increased activity of cardiac sympathetic pathways.

Methamphetamine (METH) addiction is a major public health problem in some countries. There is evidence to suggest that METH use is associated with increased risk of developing cardiovascular problems. Here, we investigated the effects of chronic METH administration and withdrawal on the activation of the brain stress system and cardiac sympathetic pathways. Mice were treated with METH (2 mg/kg, i.p.) for 10 days and left to spontaneous withdraw for 7 days. The number of corticotrophin-releasing factor (CRF), c-Fos, and CRF/c-Fos neurons was measured by immunohistochemistry in the paraventricular nucleus of the hypothalamus (PVN) and the oval region of the bed nucleus of stria terminalis (ovBNST), two regions associated with cardiac sympathetic control. In parallel, levels of catechol-o-methyl-transferase (COMT), tyrosine hydroxylase (TH), and heat shock protein 27 (Hsp27) were measured in the heart. In the brain, chronic-METH treatment enhanced the number of c-Fos neurons and the CRF neurons with c-Fos signal (CRF+/c-Fos+) in PVN and ovBNST. METH withdrawal increased the number of CRF+neurons. In the heart, METH administration induced an increase in soluble (S)-COMT and membrane-bound (MB)-COMT without changes in phospho (p)-TH, Hsp27, or pHsp27. Similarly, METH withdrawal increased the expression of S- and MB-COMT. In contrast to chronic treatment, METH withdrawal enhanced levels of (p)TH and (p)Hsp27 in the heart. Overall, our results demonstrate that chronic METH administration and withdrawal activate the brain CRF systems associated with the heart sympathetic control and point towards a METH withdrawal induced activation of sympathetic pathways in the heart. Our findings provide further insight in the mechanism underlining the cardiovascular risk associated with METH use and proposes targets for its treatment

Collins and Sivers transverse-spin asymmetries in inclusive muoproduction of ρ0\rho^0 mesons

The production of vector mesons in deep inelastic scattering is an interesting yet scarsely explored channel to study the transverse spin structure of the nucleon and the related phenomena. The COMPASS collaboration has performed the first measurement of the Collins and Sivers asymmetries for inclusively produced $\rho^0$ mesons. The analysis is based on the data set collected in deep inelastic scattering in $2010$ using a $160\,\,\rm{GeV}/c$ $\mu^+$ beam impinging on a transversely polarized $\rm{NH}_3$ target. The $\rho^{0}$ mesons are selected from oppositely charged hadron pairs, and the asymmetries are extracted as a function of the Bjorken-$x$ variable, the transverse momentum of the pair and the fraction of the energy $z$ carried by the pair. Indications for positive Collins and Sivers asymmetries are observed

High-statistics measurement of Collins and Sivers asymmetries for transversely polarised deuterons

New results are presented on a high-statistics measurement of Collins and Sivers asymmetries of charged hadrons produced in deep inelastic scattering of muons on a transversely polarised $^6$LiD target. The data were taken in 2022 with the COMPASS spectrometer using the 160 \gevv\ muon beam at CERN, balancing the existing data on transversely polarised proton targets. The first results from about two-thirds of the new data have total uncertainties smaller by up to a factor of three compared to the previous deuteron measurements. Using all the COMPASS proton and deuteron results, both the transversity and the Sivers distribution functions of the $u$ and $d$ quark, as well as the tensor charge in the measured $x$-range are extracted. In particular, the accuracy of the $d$ quark results is significantly improved

Spin Density Matrix Elements in Exclusive ρ0\rho ^0 Meson Muoproduction

We report on a measurement of Spin Density Matrix Elements (SDMEs) in hard exclusive $\rho ^0$ meson muoproduction at COMPASS using 160~GeV/$c$ polarised $\mu ^{+}$ and $\mu ^{-}$ beams impinging on a liquid hydrogen target. The measurement covers the kinematic range 5.0~GeV/$c^2$ $< W <$ 17.0~GeV/$c^2$, 1.0 (GeV/$c$)$^2$ $< Q^2 <$ 10.0 (GeV/$c$)$^2$ and 0.01 (GeV/$c$)$^2$ $< p_{\rm{T}}^2 <$ 0.5 (GeV/$c$)$^2$. Here, $W$ denotes the mass of the final hadronic system, $Q^2$ the virtuality of the exchanged photon, and $p_{\rm{T}}$ the transverse momentum of the $\rho ^0$ meson with respect to the virtual-photon direction. The measured non-zero SDMEs for the transitions of transversely polarised virtual photons to longitudinally polarised vector mesons ($\gamma^*_T \to V^{ }_L$) indicate a violation of $s$-channel helicity conservation. Additionally, we observe a dominant contribution of natural-parity-exchange transitions and a very small contribution of unnatural-parity-exchange transitions, which is compatible with zero within experimental uncertainties. The results provide important input for modelling Generalised Parton Distributions (GPDs). In particular, they may allow one to evaluate in a model-dependent way the role of parton helicity-flip GPDs in exclusive $\rho ^0$ production

Metagenomic profiling of viral and microbial communities from the pox lesions of lumpy skin disease virus and sheeppox virus-infected hosts

IntroductionIt has been recognized that capripoxvirus infections have a strong cutaneous tropism with the manifestation of skin lesions in the form of nodules and scabs in the respective hosts, followed by necrosis and sloughing off. Considering that the skin microbiota is a complex community of commensal bacteria, fungi and viruses that are influenced by infections leading to pathological states, there is no evidence on how the skin microbiome is affected during capripoxvirus pathogenesis.MethodsIn this study, shotgun metagenomic sequencing was used to investigate the microbiome in pox lesions from hosts infected with lumpy skin disease virus and sheep pox virus.ResultsThe analysis revealed a high degree of variability in bacterial community structures across affected skin samples, indicating the importance of specific commensal microorganisms colonizing individual hosts. The most common and abundant bacteria found in scab samples were Fusobacterium necrophorum, Streptococcus dysgalactiae, Helcococcus ovis and Trueperella pyogenes, irrespective of host. Bacterial reads belonging to the genera Moraxella, Mannheimia, Corynebacterium, Staphylococcus and Micrococcus were identified.DiscussionThis study is the first to investigate capripox virus-associated changes in the skin microbiome using whole-genome metagenomic profiling. The findings will provide a basis for further investigation into capripoxvirus pathogenesis. In addition, this study highlights the challenge of selecting an optimal bioinformatics approach for the analysis of metagenomic data in clinical and veterinary practice. For example, direct classification of reads using a kmer-based algorithm resulted in a significant number of systematic false positives, which may be attributed to the peculiarities of the algorithm and database selection. On the contrary, the process of de novo assembly requires a large number of target reads from the symbiotic microbial community. In this work, the obtained sequencing data were processed by three different approaches, including direct classification of reads based on k-mers, mapping of reads to a marker gene database, and de novo assembly and binning of metagenomic contigs. The advantages and disadvantages of these techniques and their practicality in veterinary settings are discussed in relation to the results obtained