Non-canonical Wnt signaling via the Ryk and Ror receptors in the drosophila nervous system

Wnt genes encode highly conserved glycoproteins that play a variety of roles at different stages of development. Their functions include the regulation of cell proliferation, cell fate specification, cell polarity, apoptosis, stem cell self-renewal, cell migration and tissue homeostasis. In the nervous system, Wnts act in neuronal migration, axon path finding, dendritic morphogenesis and synapse differentiation. Wnts serve as both attractive and repulsive cues during axon guidance, mediated through distinct mechanisms. The attractive responses to axonal growth are guided, at least in part, by the Frizzled receptors. Repulsive cues, on the other hand, can be mediated by the tyrosine kinase receptor Ryk. The aim of this thesis is the dissection of the basic biological and likely evolutionary conserved, functions of Wnt signaling through two different receptor families, the Ryks and Rors. We have employed genetic, biochemical, and electrophysiological approaches in order to understand the functions of these receptors and the pathways that they mediate. The studies in this thesis present novel insights into the biochemical mechanisms and the biological relevance of Wnt/Ror and Wnt/Ryk signaling for the development of a complex nervous system. Our findings can provide a starting point for the design of future therapeutic approaches for modulating the Wnt-Ryk and or Wnt-Ror pathways to treat post-injury nervous system lesions and aid neuronal regeneration.MCB department of the LUMC and ABN AMROUBL - phd migration 201

Service loading test as a source for the fatigue curve parameters’ estimation

Very important question of fatigue curve parameter estimation might be explored from the point of view of service loading. Comparative testing at varied stress levels with subsequent computation might reveal some peculiarities of fatigue curves and substantial changes of their parameters due to service loading factors.Проблема определения параметров кривой усталости может быть решена с учетом осо­бенностей эксплуатационного нагружения. Показано, что сравнительные испытания в условиях изменения уровня напряжений и учет полученных результатов в последу­ющих расчетах позволяют определить неко­торые особенности кривых усталости и су­щественные изменения их параметров, свя­занные с влиянием факторов эксплуатаци­онного нагружения

Защитное действие экстракта листьев черники в отношении эксайтотоксического действия глутамата на нейроны коры мозга крыс

The aqueous extract of blueberry leaves inhibits the glutamate-induced Ca2+ influx into the synaptosomes of rat brain neurons and the IC50 value of this process is close to the IC50 for MK-801, a well-known noncompetitive antagonist of glutamate NMDA subtype receptors. The aqueous extract of blueberry leaves protected the cultured neurons of the rat cerebral cortex from the neurotoxic effect of glutamate, and the inhibition intensity depended on the incubation time with the extract.Водный экстракт листьев черники ингибирует глутамат-индуцированный вход ионов Са2+ в синаптосомы нейронов мозга крыс, и IC50 этого процесса близка к IC50 для MK-801 – известного неконкурентного антагониста глутаматных рецепторов NMDA-подтипа. Водный экстракт листьев черники предохранял культивируемые нейроны коры мозга крысы от нейротоксического действия глутамата, причём выраженность ингибирования зависела от времени инкубации с экстрактом, на фоне которого действовал глутамат

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

A new semantics for overriding in description logics

Many modern applications of description logics (DLs, for short), such as biomedical ontologies and semantic web policies, provide fresh motivations for extending DLs with nonmonotonic inferences—a topic that has attracted a significant amount of attention along the years. Despite this, nonmonotonic inferences are not yet supported by DL technology due to a number of issues related to expressiveness, computational complexity, and optimizations. This paper contributes to the practical support of nonmonotonic inferences in description logics by introducing a new semantics expressly designed to address knowledge engineering needs. This formalism has appealing expressiveness, enjoys nice computational properties, and constitutes an interesting solution to an ample class of application needs. The formalism is validated through extensive comparison with the other nonmonotonic DLs, and systematic scalability tests. The test case generator and its novel validation methodology constitute a further contribution of this paper

Comorbidity development in patients with severe brain injury resulting in chronic critical condition (Review)

Advances in intensive care have enabled patients to survive an acute critical condition, producing a growing population of patients in a chronic critical condition with long-term dependence on intensive care. These patients make up 5–10% of all patients with acute respiratory failure and require a disproportionate share of re-sources in the intensive care units, with an overall yearly survival rate of 40–50%. The aim of review is to identify the impact of comorbid complications on the course and outcome of patients with severe brain injury. Ninety-six sources were selected according to the data characterizing the clinical (syndromic) model of the patient with consciousness disorders after coma of different etiologies. This model takes into account the stages and phases of the syndrome as well as a number of comorbid conditions that determine the course and outcome of the disease. The list of sources includes papers addressing the issues of comorbidity in patients with brain injury and conditions such as strokes, consequences of severe brain injury and brain surgery. The sources reflecting the most significant mechanisms of consistent development of comorbidities were examined. These include metabolic disorders with subsequent protein and energy deficiency and comorbidities of the gastrointestinal tract. The role of microbiome in the development of comorbidity in patients in chronic critical condition was also identified. Conclusion. The comorbidity development starts from the moment of brain injury and extends until sustained stabilization or multi-organ failure and death. Timely detection and correction of comorbidities allows optimizing treatment and increasing efficiency of rehabilitation in patients with severe brain injury. © 2020, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved

Analysis of microbiological and serological markers in laboratory diagnostics of animal listeriosis in a veterinary laboratory

The main goal of veterinary specialists is to prevent and eliminate particularly dangerous animal diseases, especially infections transmitted to humans. Listeriosis refers to natural focal diseases common to humans and animals and due to the fact that this infection can be asymptomatic, while the pathogen is stable in the environment, which is a risk of infection of animals and humans. The main task of veterinary specialists working in laboratories is to conduct research on regulatory documents and timely delivery of results. Laboratory diagnostics of animal listeriosis is the main link in preventing the spread of this disease, and proper selection and transportation of material can solve many problems of Listeria isolation and in some cases even reduce the time of diagnosis. The choice of the material research method also plays an important role

Wnt Signaling through the Ror Receptor in the Nervous System

Scientific Assessment and Innovation in Neurosurgical Treatment Strategie

The role of acute respiratory infections in the pathogenesis of distal limb infections in cattle

Acute respiratory diseases of infectious etiology of cattle occupy the second place in the nosological picture after diseases of the digestive system and cause huge economic damage, which in the Russian Federation is estimated at several billion rubles annually. Very often, respiratory pathology in highly productive cows is associated with infections of the distal extremities, primarily with necrobacteriosis, streptococcosis and staphylococcosis, which cause significant economic damage by reducing the productivity of animals. An important pathogenetic factor affecting the development of diseases of the distal extremities in cattle (cattle) are infections of the respiratory tract. According to our long-term observations, all farms in which outbreaks of necrobacteriosis were recorded were unfavorable for respiratory infections of cattle, such as infectious rhinotracheitis (IRT), viral diarrhea (VD), parainfluenza type 3 (PG-3), respiratory syncytial infection (RSI), pasteurellosis, chlamydia, salmonellosis and others