Endogenous Isoquinoline Alkaloids Agonists of Acid-Sensing Ion Channel Type 3

Acid-sensing ion channels (ASICs) ASIC3 expressed mainly in peripheral sensory neurons play an important role in pain perception and inflammation development. In response to acidic stimuli, they can generate a unique biphasic current. At physiological pH 7.4, human ASIC3 isoform (hASIC3) is desensitized and able to generate only a sustained current. We found endogenous isoquinoline alkaloids (EIAs), which restore hASIC3 from desensitization and recover the transient component of the current. Similarly, rat ASIC3 isoform (rASIC3) can also be restored from desensitization (at pH < 7.0) by EIAs with the same potency. At physiological pH and above, EIAs at high concentrations were able to effectively activate hASIC3 and rASIC3. Thus, we found first endogenous agonists of ASIC3 channels that could both activate and prevent or reverse desensitization of the channel. The decrease of EIA levels could be suggested as a novel therapeutic strategy for treatment of pain and inflammation

Evolutionarily new sequences expressed in tumors

BACKGROUND: Earlier we suggested the concept of the positive evolutionary role of tumors. According to this concept, tumors provide conditions for the expression of evolutionarily new and/or sleeping genes in their cells. Thus, tumors are considered as evolutionary proving ground or reservoir of expression. To support this concept we have previously characterized in silico and experimentally a new class of human tumor-related transcribed sequences. RESULTS: In this article we describe results of further studies of previously described tumor-related sequences. The results of molecular phylogeny studies, Southern hybridization experiments and computational comparison with genomes of other species are presented. CONCLUSION: These results suggest that these previously described tumor-related human transcripts are also relatively evolutionarily new

Discrete Nonholonomic LL Systems on Lie Groups

This paper applies the recently developed theory of discrete nonholonomic mechanics to the study of discrete nonholonomic left-invariant dynamics on Lie groups. The theory is illustrated with the discrete versions of two classical nonholonomic systems, the Suslov top and the Chaplygin sleigh. The preservation of the reduced energy by the discrete flow is observed and the discrete momentum conservation is discussed.Comment: 32 pages, 13 figure

Disruptive Selection of Human Immunostimulatory and Immunosuppressive Genes Both Provokes and Prevents Rheumatoid Arthritis, Respectively, as a Self-Domestication Syndrome

Using our previously published Web service SNP_TATA_Comparator, we conducted a genome-wide study of single-nucleotide polymorphisms (SNPs) within core promoters of 68 human rheumatoid arthritis (RA)-related genes. Using 603 SNPs within 25 genes clinically associated with RA-comorbid disorders, we predicted 84 and 70 candidate SNP markers for overexpression and underexpression of these genes, respectively, among which 58 and 96 candidate SNP markers, respectively, can relieve and worsen RA as if there is a neutral drift toward susceptibility to RA. Similarly, we predicted natural selection toward susceptibility to RA for 8 immunostimulatory genes (e.g., IL9R) and 10 genes most often associated with RA (e.g., NPY). On the contrary, using 25 immunosuppressive genes, we predicted 70 and 109 candidate SNP markers aggravating and relieving RA, respectively (e.g., IL1R2 and TGFB2), suggesting that natural selection can simultaneously additionally yield resistance to RA. We concluded that disruptive natural selection of human immunostimulatory and immunosuppressive genes is concurrently elevating and reducing the risk of RA, respectively. So, we hypothesize that RA in human could be a self-domestication syndrome referring to evolution patterns in domestic animals. We tested this hypothesis by means of public RNA-Seq data on 1740 differentially expressed genes (DEGs) of pets vs. wild animals (e.g., dogs vs. wolves). The number of DEGs in the domestic animals corresponding to worsened RA condition in humans was significantly larger than that in the related wild animals (10 vs. 3). Moreover, much less DEGs in the domestic animals were accordant to relieved RA condition in humans than those in the wild animals (1 vs. 8 genes). This indicates that the anthropogenic environment, in contrast to a natural one, affects gene expression across the whole genome (e.g., immunostimulatory and immunosuppressive genes) in a manner that likely contributes to RA. The difference in gene numbers is statistically significant as confirmed by binomial distribution (p < 0.01), Pearson’s χ2 (p < 0.01), and Fisher’s exact test (p < 0.05). This allows us to propose RA as a candidate symptom within a self-domestication syndrome. Such syndrome might be considered as a human’s payment with health for the benefits received during evolution

Real-time laser speckle contrast imaging for intraoperative neurovascular blood flow assessment: animal experimental study

The use of various blood flow control methods in neurovascular interventions is crucial for reducing postoperative complications. Neurosurgeons worldwide use different methods, such as contact Dopplerography, intraoperative indocyanine videoangiography (ICG) video angiography, fluorescein angiography, flowmetry, intraoperative angiography, and direct angiography. However, there is no noninvasive method that can assess the presence of blood flow in the vessels of the brain without the introduction of fluorescent substances throughout the intervention. The real-time laser-speckle contrast imaging (LSCI) method was studied for its effectiveness in controlling blood flow in standard cerebrovascular surgery cases in rat common carotid arteries, such as proximal occlusion, trapping, reperfusion, anastomosis, and intraoperative vessel thrombosis. The real-time LSCI method is a promising method for use in neurosurgical practice. This approach allows timely diagnosis of intraoperative disturbance of blood flow in vessels in cases of clip occlusion or thrombosis. Additionally, LSCI allows us to reliably confirm the functioning of the anastomosis and reperfusion after removal of the clips and thrombolysis in real time. An unresolved limitation of the method is noise from movements, but this does not reduce the value of the method. Additional research is required to improve the quality of the data obtained

Investigation of blood microcirculation parameters in patients with rheumatic diseases by videocapillaroscopy and laser Doppler flowmetry during cold pressor test

Videocapillaroscopy (VCS) and laser Doppler flowmetry (LDF) are non-invasive methods for evaluating microcirculation parameters. The VCS method is based on a high-speed video recording of capillaries in the nailfold. The recorded video frames are processed using a specialized algorithm to determine the red blood cells velocity. The LDF technique is based on the analysis of the Doppler shift of back-scattered laser radiation from moving red blood cells. In this work, simultaneous measurements of VCS and LDF have been performed in healthy volunteers and rheumatic patient. The study was conducted using a cold pressor test. Changes were recorded in response to cold exposure in rheumatic diseases

Brain metabolism changes in cases of impaired breathing or blood circulation in rodents evaluated by real time optical spectroscopy methods

The aim of the study was to compare the metabolic activity of brain cortex after the acute hypoxia caused by the impairment of breathing or blood circulation. Male Wistar rats were randomized in two groups: impaired breathing and blood circulation failure groups. Fluorescence under 365 and 450 nm excitation and diffuse reflectance intensity at 550-820 nm range were estimated. We found that after long-term hypoxic conditions, notable metabolic changes occur. We suppose that oxygen deficiency causes an activation of the GABA shunt mechanism. In cases of blood circulation failure, fluorescence intensity changes faster than in cases of breathing impairment

New Nanostructured Carbon Coating Inhibits Bacterial Growth, but Does Not Influence on Animal Cells

An electrospark technology has been developed for obtaining a colloidal solution containing nanosized amorphous carbon. The advantages of the technology are its low cost and high performance. The colloidal solution of nanosized carbon is highly stable. The coatings on its basis are nanostructured. They are characterized by high adhesion and hydrophobicity. It was found that the propagation of microorganisms on nanosized carbon coatings is significantly hindered. At the same time, eukaryotic animal cells grow and develop on nanosized carbon coatings, as well as on the nitinol medical alloy. The use of a colloidal solution as available, cheap and non-toxic nanomaterial for the creation of antibacterial coatings to prevent biofilm formation seems to be very promising for modern medicine, pharmaceutical and food industries

Herbivory on the pedunculate oak along an urbanization gradient in Europe : Effects of impervious surface, local tree cover, and insect feeding guild

Urbanization is an important driver of the diversity and abundance of tree-associated insect herbivores, but its consequences for insect herbivory are poorly understood. A likely source of variability among studies is the insufficient consideration of intra-urban variability in forest cover. With the help of citizen scientists, we investigated the independent and interactive effects of local canopy cover and percentage of impervious surface on insect herbivory in the pedunculate oak (Quercus robur L.) throughout most of its geographic range in Europe. We found that the damage caused by chewing insect herbivores as well as the incidence of leaf-mining and gall-inducing herbivores consistently decreased with increasing impervious surface around focal oaks. Herbivory by chewing herbivores increased with increasing forest cover, regardless of impervious surface. In contrast, an increase in local canopy cover buffered the negative effect of impervious surface on leaf miners and strengthened its effect on gall inducers. These results show that-just like in non-urban areas-plant-herbivore interactions in cities are structured by a complex set of interacting factors. This highlights that local habitat characteristics within cities have the potential to attenuate or modify the effect of impervious surfaces on biotic interactions.Peer reviewe