Частота встречаемости уреамикоплазменной инфекции новорожденных по данным педиатрического отделения для недоношенных детей

UREAPLASMA ИНФЕКЦИИMYCOPLASMATACEAE ИНФЕКЦИИМИКОПЛАЗМОЗЫMYCOPLASMA PNEUMONIAEМЛАДЕНЕЦ НЕДОНОШЕННЫЙ, БОЛЕЗН

Chemical genetic identification of CDKL5 substrates reveals its role in neuronal microtubule dynamics.

Loss-of-function mutations in CDKL5 kinase cause severe neurodevelopmental delay and early-onset seizures. Identification of CDKL5 substrates is key to understanding its function. Using chemical genetics, we found that CDKL5 phosphorylates three microtubule-associated proteins: MAP1S, EB2 and ARHGEF2, and determined the phosphorylation sites. Substrate phosphorylations are greatly reduced in CDKL5 knockout mice, verifying these as physiological substrates. In CDKL5 knockout mouse neurons, dendritic microtubules have longer EB3-labelled plus-end growth duration and these altered dynamics are rescued by reduction of MAP1S levels through shRNA expression, indicating that CDKL5 regulates microtubule dynamics via phosphorylation of MAP1S. We show that phosphorylation by CDKL5 is required for MAP1S dissociation from microtubules. Additionally, anterograde cargo trafficking is compromised in CDKL5 knockout mouse dendrites. Finally, EB2 phosphorylation is reduced in patient-derived human neurons. Our results reveal a novel activity-dependent molecular pathway in dendritic microtubule regulation and suggest a pathological mechanism which may contribute to CDKL5 deficiency disorder

A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets

Exosomal miRNA transfer is a mechanism for cell-cell communication that is important in the immune response, in the functioning of the nervous system and in cancer. Syncrip/hnRNPQ is a highly conserved RNA-binding protein that mediates the exosomal partition of a set of miRNAs. Here, we report that Syncrip's amino-terminal domain, which was previously thought to mediate protein-protein interactions, is a cryptic, conserved and sequence-specific RNA-binding domain, designated NURR (N-terminal unit for RNA recognition). The NURR domain mediates the specific recognition of a short hEXO sequence defining Syncrip exosomal miRNA targets, and is coupled by a non-canonical structural element to Syncrip's RRM domains to achieve high-affinity miRNA binding. As a consequence, Syncrip-mediated selection of the target miRNAs implies both recognition of the hEXO sequence by the NURR domain and binding of the RRM domains 5′ to this sequence. This structural arrangement enables Syncrip-mediated selection of miRNAs with different seed sequences. © 2018 The Author(s)

The Alcohol Use Disorders Identification Test (AUDIT): reliability and validity of the Greek version

<p>Abstract</p> <p>Background</p> <p>Problems associated with alcohol abuse are recognised by the World Health Organization as a major health issue, which according to most recent estimations is responsible for 1.4% of the total world burden of morbidity and has been proven to increase mortality risk by 50%. Because of the size and severity of the problem, early detection is very important. This requires easy to use and specific tools. One of these is the Alcohol Use Disorders Identification Test (AUDIT).</p> <p>Aim</p> <p>This study aims to standardise the questionnaire in a Greek population.</p> <p>Methods</p> <p>AUDIT was translated and back-translated from its original language by two English-speaking psychiatrists. The tool contains 10 questions. A score ≥ 11 is an indication of serious abuse/dependence. In the study, 218 subjects took part: 128 were males and 90 females. The average age was 40.71 years (± 11.34). From the 218 individuals, 109 (75 male, 34 female) fulfilled the criteria for alcohol dependence according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), and presented requesting admission; 109 subjects (53 male, 56 female) were healthy controls.</p> <p>Results</p> <p>Internal reliability (Cronbach α) was 0.80 for the controls and 0.80 for the alcohol-dependent individuals. Controls had significantly lower average scores (t test <it>P </it>< 0.001) when compared to the alcoholics. The questionnaire's sensitivity for scores >8 was 0.98 and its specificity was 0.94 for the same score. For the alcohol-dependent sample 3% scored as false negatives and from the control group 1.8% scored false positives. In the alcohol-dependent sample there was no difference between males and females in their average scores (t test <it>P </it>> 0.05).</p> <p>Conclusion</p> <p>The Greek version of AUDIT has increased internal reliability and validity. It detects 97% of the alcohol-dependent individuals and has a high sensitivity and specificity. AUDIT is easy to use, quick and reliable and can be very useful in detection alcohol problems in sensitive populations.</p

Bridge monitoring system based on vibration measurements

This work outlines the main algorithms involved in a proposed bridge monitoring system based on ambient and earthquake vibration measurements. The monitoring system can be used to predict the existence, location and size of structural modifications in the bridge by monitoring the changes in the modal characteristics and updating the finite element model of the bridge based on the modal characteristics. Sophisticated system identification methods, combining information from a sensor network with the theoretical information built into a fi-nite element model for simulating structural behaviour, are incorporated into the monitoring system in order to track structural changes and identify the location, type and extent of these changes. Emphasis in this work is given on presenting theoretical and computational issues relating to structural modal identification and structural model updating methods. Specifical-ly, the proposed work outlines the algorithms and software that has been developed for com-puting the modal properties using ambient and earthquake data, as well as recent methodologies and software for finite element model updating using the modal characteristics. Various issues encountered in the optimization problems involved in model updating are demonstrated, including the existence of multiple local optima and the effects of weight values in conventional weighted modal residual methods for selecting the optimal finite element model. Selected features are demonstrated using vibration measurements from a four-span bridge of the Egnatia Odos motorway in Greece

A cryptic RNA-binding domain mediates Syncrip recognition and exosomal partitioning of miRNA targets.

Exosomal miRNA transfer is a mechanism for cell–cell communication that is important in the immune response, in the functioning of the nervous system and in cancer. Syncrip/hnRNPQ is a highly conserved RNA-binding protein that mediates the exosomal partition of a set of miRNAs. Here, we report that Syncrip’s amino-terminal domain, which was previously thought to mediate protein–protein interactions, is a cryptic, conserved and sequence-specific RNA-binding domain, designated NURR (N-terminal unit for RNA recognition). The NURR domain mediates the specific recognition of a short hEXO sequence defining Syncrip exosomal miRNA targets, and is coupled by a non-canonical structural element to Syncrip’s RRM domains to achieve high-affinity miRNA binding. As a consequence, Syncrip-mediated selection of the target miRNAs implies both recognition of the hEXO sequence by the NURR domain and binding of the RRM domains 5′ to this sequence. This structural arrangement enables Syncrip-mediated selection of miRNAs with different seed sequences

The malaria parasite egress protease SUB1 is a calcium-dependent redox switch subtilisin.

Malaria is caused by a protozoan parasite that replicates within an intraerythrocytic parasitophorous vacuole. Release (egress) of malaria merozoites from the host erythrocyte is a highly regulated and calcium-dependent event that is critical for disease progression. Minutes before egress, an essential parasite serine protease called SUB1 is discharged into the parasitophorous vacuole, where it proteolytically processes a subset of parasite proteins that play indispensable roles in egress and invasion. Here we report the first crystallographic structure of Plasmodium falciparum SUB1 at 2.25 Å, in complex with its cognate prodomain. The structure highlights the basis of the calcium dependence of SUB1, as well as its unusual requirement for interactions with substrate residues on both prime and non-prime sides of the scissile bond. Importantly, the structure also reveals the presence of a solvent-exposed redox-sensitive disulphide bridge, unique among the subtilisin family, that likely acts as a regulator of protease activity in the parasite