Enriched environment reduces glioma growth through immune and non-immune mechanisms in mice

Mice exposed to standard (SE) or enriched environment (EE) were transplanted with murine or human glioma cells and differences in tumour development were evaluated. We report that EE exposure affects: (i) tumour size, increasing mice survival; (ii) glioma establishment, proliferation and invasion; (iii) microglia/macrophage (M/Mφ) activation; (iv) natural killer (NK) cell infiltration and activation; and (v) cerebral levels of IL-15 and BDNF. Direct infusion of IL-15 or BDNF in the brain of mice transplanted with glioma significantly reduces tumour growth. We demonstrate that brain infusion of IL-15 increases the frequency of NK cell infiltrating the tumour and that NK cell depletion reduces the efficacy of EE and IL-15 on tumour size and of EE on mice survival. BDNF infusion reduces M/Mφ infiltration and CD68 immunoreactivity in tumour mass and reduces glioma migration inhibiting the small G protein RhoA through the truncated TrkB.T1 receptor. These results suggest alternative approaches for glioma treatment

On Modeling Depths of Power Electronic Circuits for Real-Time Simulation – A Comparative Analysis for Power Systems

Investigations of the dynamic behaviour of power electronic components integrated into electric networks require suitable and established simulation methodologies. Real-time simulation represents a frequently applied methodology for analyzing the steady-state and transient behavior of electric power systems. This work introduces a guideline on how to model power electronics converters in digital real time simulators, taking into account the trade-off between model accuracy and the required computation time. Based on this concept, possible execution approaches with respect to the usage of central processing unit and field-programmable gate array components are highlighted. Simulation test scenario, such as primary frequency regulation and low voltage ride through, have been performed and accuracy indices are discussed for each implemented real-time model and each test scenario, respectively. Finally, a run-time analysis of presented real-time setups is given and real-time simulation results are compared. This manuscript demonstrates important differences in real-time simulation modelling, providing useful guidelines for the decision making of power engineers

On Modeling Depths of Power Electronic Circuits for Real-Time Simulation – A Comparative Analysis for Power Systems

Investigations of the dynamic behaviour of power electronic components integrated into electric networks require suitable and established simulation methodologies. Real-time simulation represents a frequently applied methodology for analyzing the steady-state and transient behavior of electric power systems. This work introduces a guideline on how to model power electronics converters in digital real time simulators, taking into account the trade-off between model accuracy and the required computation time. Based on this concept, possible execution approaches with respect to the usage of central processing unit and field-programmable gate array components are highlighted. Simulation test scenario, such as primary frequency regulation and low voltage ride through, have been performed and accuracy indices are discussed for each implemented real-time model and each test scenario, respectively. Finally, a run-time analysis of presented real-time setups is given and real-time simulation results are compared. This manuscript demonstrates important differences in real-time simulation modelling, providing useful guidelines for the decision making of power engineers

Encephalitis due to rabies secondary to the bite of a cat infected with a rabies virus of silvester origen

La rabia es una enfermedad viral zoonótica, producida por un virus del genero Lyssavirus de la Familia Rhabdoviridae, cuya principal fuente de transmisión es la mordedura de animales a humanos. Es una enfermedad fatal y se han descrito casos por ciclos urbanos y rurales. El caso que reportamos es el de una joven de 22 años, quien ingresa por un cuadro de dolor de características neuropáticas en el miembro superior derecho, con antecedente de mordedura por un gato de varios meses atrás, hospitalizada por el servicio de Neurología por sospecha de lesión de plejo braquial, con resonancia de columna cervical y líquido cefalorraquídeo (LCR) normales, quien posteriormente presenta deterioro clínico tórpido a un proceso encefalopático que en pocos días la llevó a la muerte. Se confirmó que la paciente presentó una encefalitis por un virus de rabia. Expondremos cómo fue el manejo de la paciente y todos los nexos epidemiológicos.Q1Reporte de caso167-170Rabies is a zoonotic viral disease, caused by a virus of the genus Lyssavirus of the Rhabdoviridae family. Its main source is transmission from animals to humans bite. The disease is fatal and has been reported to occur in rural and urban cycles. This reported case is a 22-year old, who was admitted with symptoms of neuropathic pain in the right arm, with a history of being bitten by a cat a few months earlier. The patient was hospitalized in the Neurology Department for suspected brachial plexopathy, and normal spinal MRI and cerebrospinal fluid (CSF) were found. The patient subsequently presented encephalopathic decline that resulted in death within a few days. It was confirmed that the patient had encephalitis due to the rabies virus. We present the management of the patient and all epidemiological links

Renal stem cells: fact or science fiction?

The kidney is widely regarded as an organ without regenerative abilities. However, in recent years this dogma has been challenged on the basis of observations of kidney recovery following acute injury, and the identification of renal populations that demonstrate stem cell characteristics in various species. It is currently speculated that the human kidney can regenerate in some contexts, but the mechanisms of renal regeneration remain poorly understood. Numerous controversies surround the potency, behaviour and origins of the cell types that are proposed to perform kidney regeneration. The present review explores the current understanding of renal stem cells and kidney regeneration events, and examines the future challenges in using these insights to create new clinical treatments for kidney disease

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

The Multifunctional Role of the Chemokine System in Arthritogenic Processes

TPURPOSE OF REVIEW: The involvement of chemokines and their receptors in the genesis and perpetuation of rheumatoid arthritis, spondyloarthritis, and osteoarthritis has been clearly recognized for a long time. Nevertheless, the complexity of their contribution to these diseases is now becoming evident and this review focuses on published evidence on their mechanism of action. RECENT FINDINGS: Studies performed on patients and in vivo models have identified a number of chemokine-mediated pathways involved in various aspects of arthritogenic processes. Chemokines promote leukocyte infiltration and activation, angiogenesis, osteoclast differentiation, and synoviocyte proliferation and activation and participate to the generation of pain by regulating the release of neurotransmitters. A number of chemokines are expressed in a timely controlled fashion in the joint during arthropathies, regulating all the aspects of inflammation as well as the equilibrium between damage and repair and between relief and pain. Thus, the targeting of specific chemokine/chemokine receptor interactions is considered a promising tool for therapeutic intervention

Real-Time Simulation-Based Testing of Modern Energy Systems: A Review and Discussion

One can define an energy system as a system that converts one or more energy fluxes into other energy fluxes of a different kind. This definition may describe a relatively small system, for instance, a power plant, a chemical plant, or the heating and cooling apparatus of a single-family house, as well as one covering larger energy needs, for example, those of a city, a country, or even a continent. As energy systems are developed through the centuries, the way we structure these systems goes through changes affected by contextual conditions. Recently, concerns about the availability of traditional fossil energy sources and their environmental effects are revolutionizing the way energy systems are planned, designed, and operated

KLRG1+ NK Cells Include Two Distinct Populations Lined by CX3CR1 Expression

Background: Expression of chemotactic molecules in the bone marrow (BM) microenvironment may deeply influence NK cell maturation by controlling their positioning into specific niches. In the present study, we functionally characterized CX3CR1 expressing NK cell subsets. Methods: CX3CR1 expression was assessed by FACS analysis and the functions of NK cells by migration, IFN-gamma intracellular staining and citotoxicity assays. Results: Using CX3CR1+/GFP mice, we showed that CX3CR1 is prevalently expressed by the KLRG1+ NK cell subset that is considered a quiescent and terminally differentiated NK cell population with reduced effector functions. Within KLRG1+ NK cells, CX3CR1+ cells evidenced reduced CXCR4 expression and function that was associated with different positioning within BM as compared to the CX3CR1- NK cells. In addition, CX3CR1+ NK cells displayed impaired capability to produce IFN-gamma and to lyse YAC-1 target cells. By means of adoptive transfer experiments we observed that CX3CR1 expression can be acquired by KLRG1+/CX3CR1- NK cells, while KLRG1+/CX3CR1+ NK cells stably expressed CX3CR1. We also analyzed the role of CX3CR1 during NK cell maturation, comparing NK cell tissue distribution in heterozygous CX3CR1+/GFP and in CX3CR1-deficient CX3CR1GFP/GFP mice. We observed tissue accumulation of GFP+ NK cells in CX3CR1GFP/GFP mice that was associated to anincreased number of BM NK cells during steady state and to a defective BM NK cell mobilization during POLY I:C –induced inflammation. Conclusions: All together, our findings show that CX3CR1 is a marker of a KLRG1+ NK cell subset with impaired effector functions that can irreversibly differentiate from the CX3CR1- cells under steady state conditions

CX3CR1 Regulates the Maintenance of KLRG1+ NK Cells into the Bone Marrow by Promoting Their Entry into Circulation

NK cell differentiation mainly occurs in the bone marrow (BM) where a critical role in the regulation of developing lymphocyte distribution is played by members of the chemokine receptor family. In mouse, the chemokine receptor CX3CR1 identifies a late stage of NK cell development characterized by decreased effector functions and expression of the inhibitory receptor KLRG1. The role of CX3CR1 in the regulation of differentiation and positioning of NK cell subsets in the BM is not known. In this study, we found that CX3CR1 deficiency leads to accumulation of KLRG1(+) NK cells in BM during steady-state conditions. The NK cell subset that expresses the receptor in wild-type mice was expanded in several tissues of CX3CR1-deficient mice, and NK cell degranulation in response to sensitive target cell stimulation was enhanced, suggesting a regulatory role of CX3CR1 in NK cell positioning and differentiation in BM. Indeed, the observed NK cell expansion was not due to altered turnover rate, whereas it was associated with preferential accumulation in the BM parenchyma. In addition, a role of CX3CR1 in NK cell trafficking from BM and spleen was evidenced also during inflammation, as CX3CR1-deficient NK cells were more prompt to exit the BM and did not decrease in spleen in response to polyinosinic-polycytidylic acid-promoted hepatitis. Overall, our results evidenced a relevant role of CX3CR1 in the regulation of NK cell subset exit from BM during homeostasis, and suggest that defect in the CX3CR1/CX3CL1 axis alters NK cell trafficking and functional response during inflammatory conditions