Developmental and Activity-Dependent miRNA Expression Profiling in Primary Hippocampal Neuron Cultures

MicroRNAs (miRNAs) are evolutionarily conserved non-coding RNAs of ∼22 nucleotides that regulate gene expression at the level of translation and play vital roles in hippocampal neuron development, function and plasticity. Here, we performed a systematic and in-depth analysis of miRNA expression profiles in cultured hippocampal neurons during development and after induction of neuronal activity. MiRNA profiling of primary hippocampal cultures was carried out using locked nucleic-acid-based miRNA arrays. The expression of 264 different miRNAs was tested in young neurons, at various developmental stages (stage 2–4) and in mature fully differentiated neurons (stage 5) following the induction of neuronal activity using chemical stimulation protocols. We identified 210 miRNAs in mature hippocampal neurons; the expression of most neuronal miRNAs is low at early stages of development and steadily increases during neuronal differentiation. We found a specific subset of 14 miRNAs with reduced expression at stage 3 and showed that sustained expression of these miRNAs stimulates axonal outgrowth. Expression profiling following induction of neuronal activity demonstrates that 51 miRNAs, including miR-134, miR-146, miR-181, miR-185, miR-191 and miR-200a show altered patterns of expression after NMDA receptor-dependent plasticity, and 31 miRNAs, including miR-107, miR-134, miR-470 and miR-546 were upregulated by homeostatic plasticity protocols. Our results indicate that specific miRNA expression profiles correlate with changes in neuronal development and neuronal activity. Identification and characterization of miRNA targets may further elucidate translational control mechanisms involved in hippocampal development, differentiation and activity-depended processes.     

MicroRNA expression profiling in neurogenesis of adipose tissue-derived stem cells

Adipose tissue-derived stem cells (ADSCs) are one population of adult stem cells that can self renew and differentiate into multiple lineages. Because of advantages in method and quantity of acquisition, ADSCs are gaining attention as an alternative source of bone marrow mesenchymal stem cells. In this study, we performed microRNA profiling of undifferentiated and of neurally-differentiated ADSCs to identify the responsible microRNAs in neurogenesis using this type of stem cell. MicroRNAs from four different donors were analysed by microarray. Compared to the undifferentiation control, we identified 39–101 microRNAs with more than two-fold higher expression and 3–9 microRNAs with two-fold lower expression. The identified microRNAs were further analysed in terms of gene ontology (GO) in relation with neurogenesis, based on their target mRNAs predicted by computational analysis. This study revealed the specific microRNAs involved in neurogenesis via microRNA microarray, and may provide the basic information for genetic induction of adult stem cell differentiation using microRNAs.     

Ethical,legal and social aspects of the approach in Sudan

The global malaria situation, especially in Africa, and the problems frequently encountered in chemical control of vectors such as insecticide resistance, emphasize the urgency of research, development and implementation of new vector control technologies that are applicable at regional and local levels. The successful application of the sterile insect technique (SIT) for the control of the New World screwworm Cochliomyia hominivorax and several species of fruit flies has given impetus to the use of this method for suppression or elimination of malaria vectors in some areas of Africa including Northern State of Sudan. The research and development phase of the Northern State feasibility study has been started. Sudanese stakeholders are working side-by-side with the International Atomic Energy Agency in the activities of this important phase. Several ethical, legal and social issues associated with this approach arose during this phase of the project. They need to be seriously considered and handled with care. In this paper, these issues are described, and the current and proposed activities to overcome potential hurdles to ensure success of the project are listed.     

Novel advances in cardiac rehabilitation: Position paper from the Working Group on Preventive Cardiology and Cardiac Rehabilitation of the Netherlands Society of Cardiology

Cardiac rehabilitation (CR) has evolved as an important part of the treatment of patients with cardiovascular disease. However, to date, its full potential is fairly underutilised. This review discusses new developments in CR aimed at improving participation rates and long-term effectiveness in the general cardiac population. It consecutively highlights new or challenging target groups, new delivery modes and new care pathways for CR programmes. These new or challenging target groups include patients with atrial fibrillation, obesity and cardiovascular disease, chronic coronary syndromes, (advanced) chronic heart failure with or without intracardiac devices, women and frail elderly patients. Also, the current evidence regarding cardiac telerehabilitation and loyalty programmes is discussed as new delivery modes for CR. Finally, this paper discusses novel care pathways with the integration of CR in residual risk management and transmural care pathways. These new developments can help to make optimal use of the benefits of CR. Therefore we should seize the opportunities to reshape current CR programmes, broaden their applicability and incorporate them into or combine them with other cardiovascular care programmes/pathways.     

Mannose-binding lectin deficiency is associated with early onset of polyarticular juvenile rheumatoid arthritis: a cohort study

Background  

Mannose-binding lectin (MBL) is an innate immune protein. The aim of our study was to determine whether genetically determined MBL deficiency is associated with susceptibility to juvenile rheumatoid arthritis (JRA) and whether MBL2 genotypes are associated with JRA severity.     

Dobutamine stress magnetic resonance imaging suffices for the demonstration of myocardial ischaemia and viability

We report three patients in whom dobutamine stress magnetic imaging (DS-MRI) was essential in assessing myocardial ischaemia. Two patients were referred to the cardiologist because of chest pain. Patient A had typical exertional angina and a normal resting electrocardiogram (ECG). Patient B had typical exercise-induced angina and had recently experienced an attack of severe chest pain at rest for 15 minutes. The ECG showed a complete left bundle branch block (LBBB). Patient C was referred for heart failure of unknown origin. There were no symptoms of chest pain during rest or exercise. Echocardiography in this patient demonstrated global left ventricular (LV) dilatation, systolic dysfunction and a small dyskinetic segment in the inferior wall. In all these patients exercise stress testing had failed to demonstrate myocardial ischaemia. Patients A and C produced normal findings whereas in patient B the abnormal repolarisation due to pre-existent LBBB precluded a diagnosis of ischaemia.Breath-hold DS-MRI was performed to study LV wall motion and wall thickening at rest through increasing doses of dobutamine. A test was considered positive for myocardial ischaemia if wall motion abnormalities developed at high-dose levels of the drug (20 μg/kg/min or more with a maximum of 40 μg/kg/min) in previously normal vascular territories or worsened in a segment that was normal at baseline. Recovery of wall thickening in a previously hypokinetic or akinetic segment at a low dose of dobutamine (5-10 μg/kg/min) was taken as proof of viability.Patients A and B developed hypokinesia progressing into akinesia at high-dose dobutamine in the anteroseptal area of the LV indicative of ischaemia. These findings were corroborated by coronary angiography demonstrating severe coronary artery disease which led to coronary artery bypass grafting (CABG) in patient A and balloon angioplasty in patient B. In patient C global recovery of LV contractions during low-dose dobutamine was followed by hypokinesia in the inferoseptal area during high-dose dobutamine. This biphasic response indicates myocardial viability as well as ischaemia. CABG was carried out because of multiple stenoses in the left coronary artery. Post-operatively LV function normalised.DS-MRI is a valuable method for detecting myocardial ischaemia and viability in patients with suspected coronary artery, and can be applied in every hospital with MRI equipment at its disposal.     

Contribution of explant carbohydrate reserves and sucrose in the medium to bulb growth of lily regenerated on scale segments in vitro

Bulb size is an important factor determining phase change in Lilium : phase change only occurs in bulblets over a certain threshold weight. After phase change has occurred, bulblets sprout with a stem with many leaves. Juvenile bulblets sprout with only a few leaves. The factors contributing to bulb size were studied during in vitro regeneration of bulblets on scale segments. The larger the explants, the larger the regenerated bulblets. Explant size influenced bulb growth during the complete culture period. Bulb growth was stimulated by a high sucrose concentration. The contribution of the medium and the explant reserves to bulb growth were studied in large and small explants using labelled sucrose. Sucrose was mainly taken up through the cut surfaces. In freshly cut explants, the rate of uptake was correlated with the size of the contact area, but at later stages, when regenerating organs were present, the difference in uptake rate of small and large explants almost disappeared. Small explants had a larger sink activity than large ones. Explants with regenerating organs took up more sucrose than freshly cut explants. Sucrose uptake and bulb growth were rather constant in the later phases and doubled when the sucrose concentration was doubled. Partitioning of label from the sucrose over the various organs, was also rather constant in time: approximately 25% was accumulated in the bulblets, 35–45% in the explant and 30–35% was converted to CO₂. About half of the label in the explant was recovered at the proximal side where regeneration takes place. Sucrose, once incorporated in the storage pools in the explant, either remained in the explant or was converted to CO₂. Redistribution to the growing bulblets hardly occurred. The percentage of bulb growth that could be attributed to uptake of medium components was constant over the regeneration period: 45–50% for large and 65–75% for small explants.     

The glucose transport system of the hyperthermophilic anaerobic bacterium Thermotoga neapolitana

The glucose transport system of the extremely thermophilic anaerobic bacterium Thermotoga neapolitana was studied with the nonmetabolizable glucose analog 2-deoxy-D-glucose (2-DOG). T. neapolitana accumulated 2-DOG against a concentration gradient in an intracellular free sugar pool that was exchangeable with external source of energy, such as pyruvate, and was inhibited by arsenate and gramicidin D. There was no phosphoenolpyruvate-dependent phosphorylation of glucose, 2-DOG, or fructose by cell extracts or toluene-treated cells, indicating the absence of a phosphoenolpyruvate:sugar phosphotransferase system. These data indicate that D-glucose is taken up by T. neapolitana via an active transport system that is energized by an ion gradient generated by ATP, derived from substrate-level phosphorylation.