The results of follow-up study of children who had active cytomegalovirus infection during the first months of life

Follow-up observation of 44 patients who had cytomegalovirus infection (CMV) in the first months of life with the assessment of the health status of these children in terms was conducted during more than 7 years (control group consisted of healthy children). The study of course and outcomes of CMV infection of the first months of life showed that up to school period 43 % of patients had formed chronic pathology and 14,2 % of children at early age formed group of "children with disability". The structure formed chronic pathology up to school period in almost all parameters values. In main group central nervous system pathology occurred 4 times more often (р < 0,001), allergy - 3 times more often (p = 0,05), the pathology of the cardiovascular system - 3 times more often, endocrine pathology - 3 times more often, pathology of gastrointestinal tract and hepatobiliary system - 5 times more often

Prediction of outcomes of cytomegalovirus infection of the initial few months of life

The research was based on the data of 155 newborns with manifestations of cytomegalovirus infection (CMV) appeared in the initial few months of life and on the results of the 7-years follow-up of this group of patients. While studying the courses and outcomes of CMV appeared in the initial few months of life in 155 patients of the tender age the disability is set for 22 (14,2 %) children. On the basis of discriminant analysis with the use of the most significant factors the model of prognosis of the outcomes of the carried infection was created in severe residual-organic disorders, dictating the necessity of determination of disability for children. This model can predict development of severe organ pathology in children of tender age after citomegalovirus infection appeared in the initial few months that will allow to select patients with high probability of disability and to realize for them individual rehabilitation measures to save their health in proper time

Combination of hypomorphic mutations of the Drosophila homologues of aryl hydrocarbon receptor and nucleosome assembly protein family genes disrupts morphogenesis, memory and detoxification

Aryl hydrocarbon receptor is essential for biological responses to endogenous and exogenous toxins in mammals. Its Drosophila homolog spineless plays an important role in fly morphogenesis. We have previously shown that during morphogenesis spineless genetically interacts with CG5017 gene, which encodes a nucleosome assembly factor and may affect cognitive function of the fly. We now demonstrate synergistic interactions of spineless and CG5017 in pathways controlling oxidative stress response and long-term memory formation in Drosophila melanogaster. Oxidative stress was induced by low doses of X-ray irradiation of flies carrying hypomorphic mutation of spineless, mutation of CG5017, and their combination. To determine the sensitivity of these mutants to pharmacological modifiers of the irradiation effect, we irradiated flies growing on standard medium supplemented by radiosensitizer furazidin and radioprotector serotonin. The effects of irradiation were investigated by analyzing leg and antenna morphological structures and by using real-time PCR to measure mRNA expression levels for spineless, Cyp6g1 and Gst-theta genes. We also examined long-term memory in these mutants using conditioned courtship suppression paradigm. Our results show that the interaction of spineless and CG5017 is important for regulation of morphogenesis, long-term memory formation, and detoxification during oxidative stress. Since spineless and CG5017 are evolutionary conserved, these results must be considered when evaluating the risk of combining similar mutations in other organisms, including humans

Parent-of-origin effects on nuclear chromatin organization and behavior in a Drosophila model for Williams–Beuren Syndrome

Prognosis of neuropsychiatric disorders in progeny requires consideration of individual (1) parent-of-origin effects (POEs) relying on (2) the nerve cell nuclear 3D chromatin architecture and (3) impact of parent-specific miRNAs. Additionally, the shaping of cognitive phenotypes in parents depends on both learning acquisition and forgetting, or memory erasure. These processes are independent and controlled by different signal cascades: the first is cAMPdependent, the second relies on actin remodeling by small GTPase Rac1 – LIMK1 (LIM-kinase 1). Simple experimental model systems such as Drosophila help probe the causes and consequences leading to human neurocognitive pathologies. Recently, we have developed a Drosophila model for Williams–Beuren Syndrome (WBS): a mutant agnts3 of the agnostic locus (X:11AB) harboring the dlimk1 gene. The agnts3 mutation drastically increases the frequency of ectopic contacts (FEC) in specific regions of intercalary heterochromatin, suppresses learning/memory and affects locomotion. As is shown in this study, the polytene X chromosome bands in reciprocal hybrids between agnts3 and the wild type strain Berlin are heterogeneous in modes of FEC regulation depending either on maternal or paternal gene origin. Bioinformatic analysis reveals that FEC between X:11AB and the other X chromosome bands correlates with the occurrence of short (~30 bp) identical DNA fragments partly homologous to Drosophila 372-bp satellite DNA repeat. Although learning acquisition in a conditioned courtship suppression paradigm is similar in hybrids, the middle-term memory formation shows patroclinic inheritance. Seemingly, this depends on changes in miR-974 expression. Several parameters of locomotion demonstrate heterosis. Our data indicate that the agnts3 locus is capable of trans-regulating gene activity via POEs on the chromatin nuclear organization, thereby affecting behavior

Диагностические возможности сочетанной детекции амидолитической активности хепсина и метилирования гена GSTP1 при раке и других заболеваниях предстательной железы

We have assessed the implication of analysis of amydolitic activity of hepsin, which is a trans-membrane serine protease of II type, in the detection of prostate cancer diagnosis. According to literature review over-expression of hepsin is characteristic for prostate cancer whereas prostatic cells do not express this protease in normal states and benign tumors of prostate. Our results have demonstrated the value of screening for hepsin activity in the diagnosis of prostatic pathologies which possibly is an adequate substitution for widely used test of prostate specific antigen determination.

Glutenase and Collagenase Activities of Wheat Cysteine Protease Triticain-Α: Feasibility for Enzymatic Therapy Assays

Insufficient and/or improper protein degradation is associated with the development of various human pathologies. Enzymatic therapy with proteolytic enzymes aimed to improve insufficient proteolytic activity was suggested as a treatment of protease deficiency-induced disorders. Since in many cases human degradome is incapable of degrading the entire target protein(s), other organisms can be used as a source of proteases exhibiting activities distinct from human enzymes, and plants are perspective candidates for this source. In this study recombinant wheat cysteine protease Triticain-α was shown to refold in vitro into an autocatalytically activated proteolytic enzyme possessing glutenase and collagenase activities at acidic (or close to neutral) pH levels at the temperature of human body. Mass-spectrometry analysis of the products of Triticain-α-catalyzed gluten hydrolysis revealed multiple cleavage sites within the sequences of gliadin toxic peptides, in particular, in the major toxic 33-mer α-gliadin-derived peptide initiating inflammatory responses to gluten in celiac disease (CD) patients. Triticain-α was found to be relatively stable in the conditions simulating stomach environment. We conclude that Triticain-α can be exploited as a basic compound for development of (i) pharmaceuticals for oral administration aimed at release of the active enzyme into the gastric lumen for CD treatment, and (ii) topically active pharmaceuticals for wound debridement applications

Diagnostic potentials of combined detection of amidolytic activity of hepsin and <i>GSTP1</i> gene methylation in patients with malignant and other prostate diseases

We have assessed the implication of analysis of amydolitic activity of hepsin, which is a trans-membrane serine protease of II type, in the detection of prostate cancer diagnosis. According to literature review over-expression of hepsin is characteristic for prostate cancer whereas prostatic cells do not express this protease in normal states and benign tumors of prostate. Our results have demonstrated the value of screening for hepsin activity in the diagnosis of prostatic pathologies which possibly is an adequate substitution for widely used test of prostate specific antigen determination