Synaptic tagging and capture : differential role of distinct calcium/calmodulin kinases in protein synthesis-dependent long-term potentiation

Weakly tetanized synapses in area CA1 of the hippocampus that ordinarily display long-term potentiation lasting ~3 h (called early-LTP) will maintain a longer-lasting change in efficacy (late-LTP) if the weak tetanization occurs shortly before or after strong tetanization of an independent, but convergent, set of synapses in CA1. The synaptic tagging and capture hypothesis explains this heterosynaptic influence on persistence in terms of a distinction between local mechanisms of synaptic tagging and cell-wide mechanisms responsible for the synthesis, distribution, and capture of plasticity-related proteins (PRPs). We now present evidence that distinct CaM kinase (CaMK) pathways serve a dissociable role in these mechanisms. Using a hippocampal brain-slice preparation that permits stable long-term recordings in vitro for >10 h and using hippocampal cultures to validate the differential drug effects on distinct CaMK pathways, we show that tag setting is blocked by the CaMK inhibitor KN-93 (2-[N-(2-hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)amino-N-(4-chlorocinnamyl)-N-methylbenzylamine) that, at low concentration, is more selective for CaMKII. In contrast, the CaMK kinase inhibitor STO-609 [7H-benzimidazo(2,1-a)benz(de)isoquinoline-7-one-3-carboxylic acid] specifically limits the synthesis and/or availability of PRPs. Analytically powerful three-pathway protocols using sequential strong and weak tetanization in varying orders and test stimulation over long periods of time after LTP induction enable a pharmacological dissociation of these distinct roles of the CaMK pathways in late-LTP and so provide a novel framework for the molecular mechanisms by which synaptic potentiation, and possibly memories, become stabilized

The Application Design of Interactive Multimedia of IT-based Mathematics Learning on Strengtening Students' Characters

This research aims to develop interactive multimedia application of Coordinate System-based on the strengthening of Grade VIII Junior High students’ characters. The development model used in this study refers to the 4-D model proposed by Thiagarajan, Semmel and Semmel consisting of Define, Design, Develop, and Disseminate stages. Product development was tested on 20 students and field test was conducted in three junior high schools namely SMPN 3 Gorontalo, SMPN 1 Kabila Bone Bolango District and SMPN 11 Gorontalo City. The results of this study indicate that interactive multimedia Coordinate System that has been developed: (1) Categorized valid and feasible according to the expert; (2) Multimedia interactive coordinate system is easy to use and improves learners' response in learning. In addition, the implementation of learning by using multimedia coordinate system is in very good criteria, (3) Multimedia can improve the activity and learning outcomes of learners which based on observations obtained the percentage of student activities by 89.75% for limited and average trial class percentage for the field trial class of 94.87% with very good criteria.Students' learning outcomes provide classical completeness data for the limited trial class of 87.50% and field trial classes obtained by an average percentage of 89.33% with very good criteria, (4) Improving character based on the above, the interactive Multimedia coordinate system developed has been said to be valid, practical and effective so that it can be used in the process of Mathematics learning at grade VIII Junior High School

The Development of Character Building-Based Two-Dimensional Shapes Multimedia on Junior High School Students in Gorontalo Province, Indonesia

Mathematics is a branch of natural sciences that is capable of developing character and ability to think systematically, logically, and critically in expressing ideas or solving problems. To develop student

Assessing Smoking Behaviour and Tobacco Smoke Exposure: Definitions and Methods

AbstractIn recent years, the increased availability of tobacco products other than conventional cigarettes, the use of puffing topography devices for smoking behaviour studies and the use of biomarkers to study smoke constituents exposure have generated the need for a more comprehensive set of definitions concerning smoking behaviour and exposure to smoke. The definitions offered in this paper are based on many years of practical experience and on consensus within a broad group of scientists working in these areas. It is intended that, with wider and more consistent usage, these definitions should reduce any misunderstandings and facilitate interpretation of future studies

Cosmic ray tests of a GEM-based TPC prototype operated in Ar-CF4-isobutane gas mixtures

Argon with an admixture of CF4 is expected to be a good candidate for the gas mixture to be used for a time projection chamber (TPC) in the future linear collider experiment because of its small transverse diffusion of drift electrons especially under a strong magnetic field. In order to confirm the superiority of this gas mixture over conventional TPC gases we carried out cosmic ray tests using a GEM-based TPC operated mostly in Ar-CF4-isobutane mixtures under 0 - 1 T axial magnetic fields. The measured gas properties such as gas gain and transverse diffusion constant as well as the observed spatial resolution are presented.Comment: 22 pages, 18 figures. Published in Nuclear Instruments and Methods in Physics Research A. Fig. 3 in the introduction was corrected since it had not been properly normalized. Minor corrections and no changes in the conclusio

Synaptic activity-responsive element (SARE):A unique genomic structure with an unusual sensitivity to neuronal activity

Formation of a new memory requires plasticity at the synaptic level. However, it has also been shown that the consolidation and the maintenance of such a new memory involve processes that necessitate active mRNA at the nucleus of the cell. How can robust changes in synaptic efficacy specifically drive new transcription and translation of new gene transcripts, and thus transform an otherwise transient plasticity into a long-lasting and stable one? In this article, we highlight the conceptual advance that was gained by the discovery of a potent Synaptic Activity-Responsive Element (SARE) found ∼7 kb upstream of the transcription initiation site of the neuronal immediate early gene Arc. The unique genomic structure of SARE, which contained adjacent and cooperative binding sites for three major activity-dependent transcription factors within a 100-bp locus, was associated with an unusual responsiveness to neuronal stimuli. Taken together, these findings shed light on a new class of transcriptional sensor with enhanced sensitivity to synaptic activity

Microbiological control of parenteral dosage forms

The microbiological control of injectable forms aims to ensure that the product does not contain any microorganisms that may be pathogenic or induce pathological symptoms after administration. Thus, the study of techniques that allow the elimination and prevention of microorganisms is extremely important. In this field, there are classic techniques that are used to evaluate certain drugs, and novel techniques are currently under development. These new approaches have advantages over the previous ones since they have a higher level of efficacy and accuracy. This review presents a simple description of the main techniques available (from the classic to the most recent) for microbiological control of parenteral dosage forms. It can be regarded as a useful practical tool for all professionals already working (or aiming to work) in this area

Subcellular heterogeneity of ryanodine receptor properties in ventricular myocytes with low T-tubule density

Rationale: In ventricular myocytes of large mammals, not all ryanodine receptor (RyR) clusters are associated with T-tubules (TTs); this fraction increases with cellular remodeling after myocardial infarction (MI). Objective: To characterize RyR functional properties in relation to TT proximity, at baseline and after MI. Methods: Myocytes were isolated from left ventricle of healthy pigs (CTRL) or from the area adjacent to a myocardial infarction (MI). Ca2+ transients were measured under whole-cell voltage clamp during confocal linescan imaging (fluo-3) and segmented according to proximity of TTs (sites of early Ca2+ release, F>F50 within 20 ms) or their absence (delayed areas). Spontaneous Ca2+ release events during diastole, Ca2+ sparks, reflecting RyR activity and properties, were subsequently assigned to either category. Results: In CTRL, spark frequency was higher in proximity of TTs, but spark duration was significantly shorter. Block of Na+/Ca2+ exchanger (NCX) prolonged spark duration selectively near TTs, while block of Ca2+ influx via Ca2+ channels did not affect sparks properties. In MI, total spark mass was increased in line with higher SR Ca2+ content. Extremely long sparks (>47.6 ms) occurred more frequently. The fraction of near-TT sparks was reduced; frequency increased mainly in delayed sites. Increased duration was seen in near-TT sparks only; Ca2+ removal by NCX at the membrane was significantly lower in MI. Conclusion: TT proximity modulates RyR cluster properties resulting in intracellular heterogeneity of diastolic spark activity. Remodeling in the area adjacent to MI differentially affects these RyR subpopulations. Reduction of the number of sparks near TTs and reduced local NCX removal limit cellular Ca2+ loss and raise SR Ca2+ content, but may promote Ca2+ waves