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

Deskripsi Penggunaan Multimedia Interaktif pada Pembelajaran Matematika Bangun Ruang Sisi Lengkung Tabung

Penelitian ini bertujuan untuk mendeskripsikan penggunaan multimedia interaktif pada pembelajaran matematika bangun ruang sisi lengkung. Bangun ruang sisi lengkung yang dibahas, difokuskan pada topik tabung dengan siswa SMP Negeri 2 Gorontalo sebagai subjek penelitian. Data penelitian diperoleh melalui observasi proses pembelajaran dan melalui angket respon peserta didik. Hasil penelitian menunjukkan bahwa penggunaan multimedia interaktif pada pembelajaran matematika bangun ruang sisi lengkung tabung mencapai kategori “sangat baik”, dengan indikator: kemampuan guru dalam menggunakan multimedia interaktif dalam pembelajaran sebesar 84%, aktifitas peserta didik dalam pembelajaran menggunakan multimedia interaktif sebesar 84%, dan respon positif peserta didik terhadap multimedia interaktif sebesar 85%

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

Long-term Maintenance of Reduced Intraocular Pressure by Daily or Twice Daily Topical Application of Prostaglandins to Cat or Rhesus Monkey Eyes

Substantial evidence indicates that a single topical application of prostaglandins (PGs) can reduce intraocular pressure (IOP) in the eyes of several species. However, earlier literature, dealing with ocular hypertensive and inflammatory responses, shows the development of tachyphylaxis to subsequent doses of PGs. If similar tolerance developed to the ocular hypotensive effects of PGs, it would preclude the use of these agents in the treatment of chronic glaucoma. The present study shows, however, that although tachyphylaxis to the ocular hypotensive effects of PGs develops in rabbits, this is not a typical response among mammals. Significant IOP reduction was maintained in cats for up to 9 months by topical application of PGE 2 at 12-, 24-, or 48-hr intervals. The IOP reduction was jeopardized seriously only when the PG was applied every other day for several days or when, on a few occasions, 3 days were allowed to elapse between PGE 2 applications. Ocular hypotension was also maintained during the course of topical treatment of rhesus monkey eyes with PGF 2a . Short periods of pupillary constriction followed the application of each dose of PGF 2a to cat eyes, but the miotic response of rhesus monkeys to PGF 2a and cats to PGE 2 was negligible. Other apparent side effects were noted, but none of these were severe or progressive. These results clearly demonstrate that tachyphylaxis, or tolerance, is not expected to present an obstacle to the development of eicosanoids and/or their derivatives as therapeutic agents for the long-term treatment of ocular hypertension and chronic glaucoma. Invest Ophthalmol Vis Sci 24: [312][313][314][315][316][317][318][319] 1983 Early studies on the effects of prostaglandins (PGs) on the eye, primarily designed to determine the role of these autacoids in the ocular irritative response, concluded that exogenous PGs can produce increased intraocular pressure (IOP) and breakdown of the blood-aqueous barrier. 1 It has recently been shown, however, that appropriate doses of PGF 2a topically applied to the eyes of rabbits, 2 owl monkeys, 3 rhesus monkeys, and cats 4 can, in fact, reduce rather than increase IOP. In the rabbit there is only a narrow margin between the hypotensive dose of PGF 2a and a dose that causes initial hypertension. 2 Ten-to 100-fold higher PGF 2a doses than those that reduce IOP in the rabbit are required to produce the same effect in owl monkeys, rhesus monkeys, and cats, but eve

Photochemistry of the PAH pyrene in water ice: the case for ion-mediated solid-state astrochemistry

Context. Icy dust grains play an important role in the formation of complex inter- and circumstellar molecules. Observational studies show that polycyclic aromatic hydrocarbons (PAHs) are abundantly present in the ISM in the gas phase. It is likely that these non-volatile species freeze out onto dust grains as well and participate in the astrochemical solid-state network, but experimental PAH ice studies are largely lacking. Methods. Near UV/VIS spectroscopy is used to track the in situ VUV driven photochemistry of pyrene containing ices at temperatures ranging from 10 to 125 K. Results. The main photoproducts of VUV photolyzed pyrene ices are spectroscopically identified and their band positions are listed for two host ices, \water and CO. Pyrene ionisation is found to be most efficient in \water ices at low temperatures. The reaction products, triplet pyrene and the 1-hydro-1-pyrenyl radical are most efficiently formed in higher temperature water ices and in low temperature CO ice. Formation routes and band strength information of the identified species are discussed. Additionally, the oscillator strengths of Py, Py^+ and PyH are derived and a quantitative kinetic analysis is performed by fitting a chemical reaction network to the experimental data. Conclusions. Pyrene is efficiently ionised in water ice at temperatures below 50 K. Hydrogenation reactions dominate the chemistry in low temperature CO ice with trace amounts of water. The results are put in an astrophysical context by determining the importance of PAH ionisation in a molecular cloud. The photoprocessing of a sample PAH in ice described in this manuscript indicates that PAH photoprocessing in the solid state should also be taken into account in astrochemical models.Comment: 11 pages, 8 figures, accepted for publication in A&

Computer-Based Training (CBT): Innovation and Influence Towards Teaching-Learning Process at JBLFMU-Molo

This study determined the level of assessment of subjects with CBT (Computer-Based-Training) application among marine engineering students of John B. Lacson Foundation Maritime University-Molo, Iloilo City. The participants in this study were the randomly selected one hundred and thirty-three (133) marine engineering students of JBLFMU-Molo, Iloilo City who had taken subjects with CBTs. The present study employed quantitative-qualitative research design by Creswell (2013). Results reveal the following: (1) review with CBT or CBTR review is the mostly utilized subject because this is needed in the marine engineering licensure examinations; (2) level of assessment of CBTs is excellent; (3) no significant differences in the assessment of CBTs were found out among marine engineering students as classified according to different variables such as academic performance, students’ classification, type of students, and section

Attitudes and behaviors of Japanese physicians concerning withholding and withdrawal of life-sustaining treatment for end-of-life patients: results from an Internet survey

<p>Abstract</p> <p>Background</p> <p>Evidence concerning how Japanese physicians think and behave in specific clinical situations that involve withholding or withdrawal of medical interventions for end-of-life or frail elderly patients is yet insufficient.</p> <p>Methods</p> <p>To analyze decisions and actions concerning the withholding/withdrawal of life-support care by Japanese physicians, we conducted cross-sectional web-based internet survey presenting three scenarios involving an elderly comatose patient following a severe stroke. Volunteer physicians were recruited for the survey through mailing lists and medical journals. The respondents answered questions concerning attitudes and behaviors regarding decision-making for the withholding/withdrawal of life-support care, namely, the initiation/withdrawal of tube feeding and respirator attachment.</p> <p>Results</p> <p>Of the 304 responses analyzed, a majority felt that tube feeding should be initiated in these scenarios. Only 18% felt that a respirator should be attached when the patient had severe pneumonia and respiratory failure. Over half the respondents felt that tube feeding should not be withdrawn when the coma extended beyond 6 months. Only 11% responded that they actually withdrew tube feeding. Half the respondents perceived tube feeding in such a patient as a "life-sustaining treatment," whereas the other half disagreed. Physicians seeking clinical ethics consultation supported the withdrawal of tube feeding (OR, 6.4; 95% CI, 2.5–16.3; P < 0.001).</p> <p>Conclusion</p> <p>Physicians tend to harbor greater negative attitudes toward the withdrawal of life-support care than its withholding. On the other hand, they favor withholding invasive life-sustaining treatments such as the attachment of a respirator over less invasive and long-term treatments such as tube feeding. Discrepancies were demonstrated between attitudes and actual behaviors. Physicians may need systematic support for appropriate decision-making for end-of-life care.</p