Local and systemic targets of the MtCLE35-SUNN pathway in the roots of Medicago truncatula.

CLE (CLAVATA3/ENDOSPERM SURROUNDING REGION-related) peptides are systemic regulators of legume-rhizobium symbiosis that negatively control the number of nitrogen-fixing nodules. CLE peptides are produced in the root in response to rhizobia inoculation and/or nitrate treatment and are transported to the shoot where they are recognized by the CLV1-like (CLAVATA1-like) receptor kinase. As a result, a shoot-derived signaling pathway is activated that inhibits subsequent nodule development in the root. In Medicago truncatula, MtCLE35 is activated in response to rhizobia and nitrate treatment and the overexpression of this gene systemically inhibits nodulation. The inhibitory effect of MtCLE35 overexpression is dependent on the CLV1-like receptor kinase MtSUNN (SUPER NUMERIC NODULES), suggesting that MtSUNN could be involved in the reception of the MtCLE35 peptide. Yet little is known about the downstream genes regulated by a MtCLE35-activated response in the root. In order to identify genes whose expression levels could be regulated by the MtCLE35-MtSUNN pathway, we performed a MACE-Seq (Massive Analysis of cDNA Ends) transcriptomic analysis of MtCLE35-overexpressing roots. Among upregulated genes, the gene MtSUNN that encodes a putative receptor of MtCLE35 was detected. Moreover, we found that MtSUNN, as well as several other differentially expressed genes, were upregulated locally in MtCLE35-overexpressing roots whereas the MtTML1 and MtTML2 genes were upregulated systemically. Our data suggest that MtCLE35 has both local and systemic effects on target genes in the root.

[Current concepts about autonomic dysfunction in patients with epilepsy]. / Sovremennye predstavleniya o vegetativnoi disfunktsii u patsientov s epilepsiei.

Autonomic dysfunction is frequently observed in people with epilepsy. Ictal and postictal dysautonomia is not only manifestation of autonomic seizures, but could be a life threatening condition in some cases and contribute to sudden unexpected death (SUDEP). Interictal decrease of autonomic activity is associated with duration and severity of epilepsy, it is the most prominent in focal and drug-resistant epilepsy. Progress in our understanding of the underlying mechanisms, development of the autonomic assessment methods, and its integration in novel technical solutions for seizure detection will improve the quality of care for people with epilepsy.

Effects of Screen Time and Season on Cardiovascular System Indicators in Primary Schoolchildren.

Indicators of the cardiovascular system, including heart rate (HR) and blood pressure (BP) variability parameters, were analyzed in primary school students with different computer screen times. The study included 4084 students of grades 1-4 (age 7-12 years) from 66 Moscow schools. The screen time at school and out of school was assessed by teachers, based on the national Sanitary Rules and Regulations: 0, no screen time; 1, screen time matching hygienic standards; 2, screen time at least twice greater than recommended. Physiological examinations were carried out by spiroarteriocardiorhythmography with a face mask, the conditions corresponding to the functional stress test (mild hypercapnia/hypoxia). Testing took place in spring and autumn (independent samples). Statistical data processing was performed using nonparametric criteria. It was revealed that the introduction of computer technologies in school lessons within the limits of hygienic standards was accompanied by an increase, within the normal range, of systolic BP in girls at the end of grade 2 and 4 and in boys at the beginning and end of grade 4. Screen time at least twice higher than the hygienic standard did not have an additional effect on BP, but provoked shifts in the function of autonomic regulation. Boys were more sensitive to the influence of this environmental factor. Their pattern of seasonal variability in total power (TP) of the HR variability spectrum was reversed compared to that of children who did not use computers at school; i.e., higher TP values were observed in spring. In grade 4, the process was accompanied by an increase in spontaneous arterial baroreflex sensitivity and a decrease in the relative power of the LF range in the variability spectrum of systolic BP. The changes were assumed to reflect the adaptive response to changes in educational environment.

[Principles of diagnosis and treatment of tinnitus]. / Printsipy diagnostiki i lecheniya shuma v ushakh.

Tinnitus is one of the most common otological symptoms and can be defined as the conscious perception of sound lasting more than 5 minutes in the absence of an external auditory stimulus. Based on the review of articles, a comparative analysis of modern methods of diagnosis and treatment of tinnitus was carried out in order to substantiate the most effective and promising algorithms for providing care to patients. Diagnosis of tinnitus includes taking anamnesis, assessing the severity of tinnitus using questionnaires, otoscopy, hearing examination, and performing additional tests. In case of secondary murmur, etiotropic therapy should be started as soon as possible to prevent hearing loss and other complications. For primary noise, the most effective treatments are cognitive-behavioral therapy, tinnitus maskers and sound therapy, transcutaneous electrical stimulation, and biofeedback. Magnetic stimulation, invasive neuromodulation, drug therapy have a lower level of effectiveness and evidence base.

Regenerative Potential of a Suspension and Spheroids of Multipotent Mesenchymal Stromal Cells from Human Umbilical Cord on the Model of Myocardial Infarction in Rats.

Regenerative potential of multipotent mesenchymal stromal cells from the human umbilical cord (MMSC-UC) in the suspension and spheroid form was revealed during the progression of experimental small focal myocardial infarction in rats. In isoproterenol-induced myocardial infarction, foci of necrosis and inflammatory infiltrate and at later terms fibrosis foci were found mainly in the left ventricle of rat heart. In rats receiving MMSC-UC, destructive changes in the myocardium, fibrous scars, and inflammatory process were less pronounced. MMSC-UC also contributed to normalization of the morphofunctional parameters of the heart. Spheroids exhibited higher efficiency in comparison with cell suspension.

[The causes of late diagnostics of vestibular shwannomas]. / Prichiny pozdnei diagnostiki vestibuliarnykh shvannom.

AIM: The objective of the present study was to elucidate the causes of late diagnostics of vestibular shwannomas based on the results of the analysis of the medical histories of the patients admitted to the Academician N.N. Burdenko National Medical Research Centre of Neurosurgery for the management of this condition. MATERIAL AND METHODS: We undertook the retrospective review of a series of 192 cases of vestibular shwannomas in the patients treated based at the N.N. Burdenko National Medical Research Centre of Neurosurgery in 2015. The study included the analysis of demographic characteristics of the patients as well as their anamnestic and clinical data. RESULTS AND DISCUSSION: A total of 55 (29%) patients were found to have small tumours (Samii T1-T3) whereas 137 (71%) ones presented with giant neoplasms including T4a and T4b tumours (in accordance with the Samii classification) in 63 (33%) and 74 (38%) patients respectively. The duration of the disease from the appearance of its first clinical symptoms up to the establishment of the definitive diagnosis was 41 months on the average. 37 (19%) patients appeared to have paid no attention to the unilateral impairment of hearing. 46 (24%) patients applied for the medical assistance to the therapists and neurologists. 56 (29%) patients had remained for a long time under the supervision of the ENT specialists and surdologists based at the local outpatient facilities. CONCLUSION: More than 2/3 of the examined patients presenting with vestibular shwannomas apply for the medical assistance at the late stages of the disease. Such situation can be attributed to the low level of oncological alertness among the general population and health providers, the poor awareness of the general practitioners and otorhinolaryngologists about this pathology, the unavailability or inefficient application of the modern neurovisualization technologies, in the first place magnetic resonance imaging. The problems encountered in connection with the performance of screening studies give evidence of the necessity of the introduction of up-to-date otoneurological and audiological investigations as well as the neurovisualization techniques into the everyday clinical practice for the comprehensive examination of all the patients suffering from unilateral hearing loss.

[Age-related changes of the latent period of simple sensorimotor reaction to the light stimuli in both men and women with different body mass index].

The study of the relationship of the latent period of simple sensorimotor reaction to the light stimulus and body mass index (BMI) in males and females aged 30-60 years (n = 507) was done. The boundary between the low (below Me - 1SD) and middle (from Me - 1SD to Me + 1SD) BMI was the value of 22.74 kg/m2, the boundary between the middle and high (above Me + 1SD) BMI - 33.16kg/m2. It is shown thatthere isan increase inthe proportion of people with high BMI with age (faster and more pronounced - in women). Sensorimotor reaction latency to the light stimuli does not change in men, and declines with agein women. However the data obtained indicate that developed with age alimentary obesity does not adversely affect neurophysiological parameters of the sensorimotor reactivity.

KNOTTED1-LIKE HOMEOBOX 3: a new regulator of symbiotic nodule development.

KNOX transcription factors (TFs) regulate different aspects of plant development essentially through their effects on phytohormone metabolism. In particular, KNOX TF SHOOTMERISTEMLESS activates the cytokinin biosynthesis ISOPENTENYL TRANSFERASE (IPT) genes in the shoot apical meristem. However, the role of KNOX TFs in symbiotic nodule development and their possible effects on phytohormone metabolism during nodulation have not been studied to date. Cytokinin is a well-known regulator of nodule development, playing the key role in the regulation of cell division during nodule primordium formation. Recently, the activation of IPT genes was shown to take place during nodulation. Therefore, it was hypothesized that KNOX TFs may regulate nodule development and activate cytokinin biosynthesis upon nodulation. This study analysed the expression of different KNOX genes in Medicago truncatula Gaertn. and Pisum sativum L. Among them, the KNOX3 gene was upregulated in response to rhizobial inoculation in both species. pKNOX3::GUS activity was observed in developing nodule primordium. KNOX3 ectopic expression caused the formation of nodule-like structures on transgenic root without bacterial inoculation, a phenotype similar to one described previously for legumes with constitutive activation of the cytokinin receptor. Furthermore, in transgenic roots with MtKNOX3 knockdown, downregulation of A-type cytokinin response genes was found, as well as the MtIPT3 and LONELYGUY2 (MtLOG2) gene being involved in cytokinin activation. Taken together, these findings suggest that KNOX3 gene is involved in symbiotic nodule development and may regulate cytokinin biosynthesis/activation upon nodule development in legume plants.

[Transcription Factors in Developmental Genetics and the Evolution of Higher Plants].

Transcription factors play an essential role in controlling various developmental programs in plants, coordinating the action of any genetic network. Among the most important groups of plant transcription factors are the homeodomain-containing transcription factors, in particular, those belonging to the KNOX and WOX families, the functions of which are associated with regulation of the meristem activity, development of the aboveground and underground parts of plants, and control of embryogenesis. This review examines the role of KNOX and WOX transcription factors in various developmental programs, as well as in the evolutionary complication of the body plan in terrestrial plants.

[Meristematic characteristics of tumors initiated by Agrobacterium tumefaciens in pea plants].

It is known that two key groups of plant hormones--auxins and cytokinins--play an important role in plant tumor development. The formation of Agrobacterium-induced tumors results from the horizontal transfer of bacterial oncogenes involved in the biosynthesis of these hormones in the plant genome. The role of transcriptional factors in plant tumor development is poorly investigated. It can be assumed that tumor development associated with abnormal cell proliferation can be controlled by the same set of transcription factors that control normal cell proliferation and, in particular, transcription factors that regulate meristem activity. In the present study, we analyzed the histological organization and distribution of proliferating cells in tumors induced by Agrobacterium tumefaciens on pea hypocotyls. In addition, the expression of a set of meristem-specific genes with Agrobacterium tumefaciens-induced tumor development was analyzed. In general, our results indicate that meristematic structures are present in A. tumefaciens-induced tumors and that the development of such tumors is associated with increased expression of a key gene regulating the root apical meristem--the WOX5 gene.

[Expression of the WOX and PIN Genes in the Course of Somatic and Zygotic Embryogenesis of a Medicago truncatula].

Comparative analysis of the expression of the WOXand PINgenes in ovules and in the course of somatic embryogenesis of Medicago truncatula Gaertn was performed. It was shown that some WOX and PIN genes that had an increased expression level in ovules (MtWOX11-like, STENOFOLIA, MTR_2g015000, and MtPIN10) were also activated in the course of somatic embryogenesis. At the same time, the WOX and PIN genes, the expression level of which was low in ovules, did not show transcription activation associated with somatic embryogenesis. These data allow the assumption that the same regulatory mechanisms can be involved in the control of the early stages of somatic and zygotic embryogenesis.

Switching intermolecular interactions by confinement in carbon nanotubes.

The encapsulation of trityl-functionalised C60 molecules inside carbon nanotubes drastically affects the intermolecular interactions for this species. Whilst the orientations of molecules in the crystal are often controlled by thermodynamics, the molecular orientations in nanotubes are a result of kinetic control imposed by the mechanism of entry into and encapsulation within the nanotube.

[The role of autonomic dysfunction in pathogenesis of irritable bowel syndrome].

This article presents the results of a comparative study of autonomic disorders in patients with differernt types of irritable bowel syndrome (IBS). We used several clinical and instrumental methods, including the Veyn questionnaire, Kerdo autonomic index, skin sympathetic response and heart rate variability analysis. The results show a prevalence of sympathetic tone in all groups of patients (more pronounced in IBS with constipation), as well as an elevated stress index and decreased arterial baroreflex sensitivity. In the IBS with diarrhea group there was a reliable increase of power spectral density alvery low frequency and a lowered respiratory sinus arrhythmia.

[Features of the pharmacokinetics of ceftriaxone during the antiorthostatic hypokinesia in rats].

This study was designed to investigate the effects of simulated microgravity on the plasma kinetics of ceftriaxone in rats. Comparative analysis of pharmacokinetic parameters in control and experimental groups has revealed the influence of antiorthostatic hypokinesia (ANOH) on the pharmacokinetics of ceftriaxone. Decreased level of maximum plasma concentration (C(max)) and bioavailability of ceftriaxone after single intramuscular (IM) injection were revealed in rats with antiorthostatic hypokinesia. The rate of absorption of the drug was higher respectively.

[Cerebrovascular pharmacology of separate and combined vascular pathology of brain and heart].

The effect of nimodipine, mexidol, melatonin, afobazole, 5-hydroxy-adanamtan-2-one, and GABA conjugates with arachidonic acid and docosahexaenoyl dopamine on the cerebral circulation has been studied in intact rats and those with global transient cerebral ischemia, experimental myocardial infarction, and combined vascular pathology of brain and heart. The most pronounced vasodilation activity in rats with global transient cerebral ischemia is exhibited by nimodipine, mexidol, melatonin, afobazole, 5-hydroxy-adanamtan-2-one, and GABA-containing lipid derivatives. This effect of all these drugs (except for nimodipine) is not manifested on the background of GABA receptor blocker bicuculline. In rats with experimental myocardial infarction and combined vascular pathology of brain and heart not all of the compounds mentioned acbove with GABA-ergic mechanism of action stimulate the cerebral blood flow. Thus, both similarity and differences in cerebrovascular effects of these compounds have been found, which depend on the initial state of organism and the vascular pathology of brain and/or heart. The obtained results show good prospects for this direction of research.

[No support for the hypothesis of chronic cerebrospinal venous insufficiency in multiple sclerosis]. / Nedokazannost' gipotezy khronicheskoi tserebrospinal'noi venoznoi nedostatochnosti pri rasseiannom skleroze.

Objective. To evaluate the jugular veins (IJV) using duplex sonography in patients with multiple sclerosis (MS). Material and methods. The study included 21 MS patients with different disease course, degree of disability and disease duration. A control group consisted of 8 healthy volunteers. Results. IJV changes that meet the CCSVI criteria have not been found. These findings are consistent with the results of recently published large studies. Possible reasons of non-confirmation of this hypothesis are discussed. Conclusion. Currently vascular intervention in MS is not recommended.

[Respiratory and cardiovascular responses to hypoxia under activation or blockade inhibitory transmission].

Respiratory rhythm changes and hypoxic ventilatory responses were studied in anesthetized albino rats after administration GABA and adenosine receptor antagonists. Intracisternal microinjection of picrotoxin induced pathological periodic breathing. Picrotoxin intravenous administration caused the increase of individual resistance to acute hypoxia. Aminophylline administration exerted the opposite effect. After pretreatment of hydroxybutyrate we observed different types of respiratory reactions to adenosine antagonist injection, which probably depended on the value of arterial blood pressure and cerebral hemodynamics.

[Integrated assessment of serum homeostasis shifts in experimental myocardial infarction].

Dynamic changes in serum homeostasis of rats with experimental myocardial infarction evolution using the method of laser correlation spectroscopy were studied. The presence of necrotic myocardial damage was confirmed by electrocardiographic, histological and biochemical methods. Increased contribution of small particles in the acute period of myocardial infarction was detected, which indicates products of catabolism accumulation in serum and changing the level of some proteins. Comparison of subfractional content of sera from rats with varying degrees of extension of myocardial necrosis through the ventricular wall revealed the predominance of particles of low molecular size (up to 10 nm) in animals with transmural infarction and middle-size fraction (50-120 nm) in animals with non-transmural infarction. These results are consistent with the clinical data obtained by this method in patients with Q-wave and non-Q-wave myocardial infarction.

[Cardiac pathology and autonomic dysfunction in patients with vertebral and spinal cord injury].

The disturbances of cardiovascular function were examined in 103 patients with vertebral and spinal cord injury. To evaluate myocardial conduction time and regulation of heart rate we used the method of spiroarteriocardiorythmography. Comparative power spectral and time domain analyses of heart rate variability were carried out in patient and healthy individuals. The autonomic nervous system dysfunction revealed in patients result in severe cardiovascular complications and is associated with high risk of heart diseases.

[Peculiarities of cerebrovascular effects of GABA conjugate with docosahexaenoyl dopamine under conditions of separate and combined vascular pathology of brain and heart].

A GABA conjugate with docosahexaenoyl dophamine (DHED) enhanced local cerebral blood flow in rats under conditions of global transient cerebral ischemia, experimental myocardial infarction, and combined vascular pathology of brain and heart. At the same time, the GABA-DHED conjugate did not influence brain hemoperfusion in intact animals. The cerebrovascular effect of this conjugate is determined by its direct action on the vascular tone, since no changes in blood pressure have been observed. Under conditions of the combined vascular pathology of brain and heart, the cerebrovascular effect of GABA-DHED conjugate is inhibited by bicuculline, which is evidence for the involvement of GABAergic mechanisms in the drug action upon cerebrovascular tone.