657 research outputs found
Author response: The synaptic ribbon is critical for sound encoding at high rates and with temporal precision
No full textWe studied the role of the synaptic ribbon for sound encoding at the synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in mice lacking RIBEYE (RBEKO/KO). Electron and immunofluorescence microscopy revealed a lack of synaptic ribbons and an assembly of several small active zones (AZs) at each synaptic contact. Spontaneous and sound-evoked firing rates of SGNs and their compound action potential were reduced, indicating impaired transmission at ribbonless IHC-SGN synapses. The temporal precision of sound encoding was impaired and the recovery of SGN-firing from adaptation indicated slowed synaptic vesicle (SV) replenishment. Activation of Ca2+-channels was shifted to more depolarized potentials and exocytosis was reduced for weak depolarizations. Presynaptic Ca2+-signals showed a broader spread, compatible with the altered Ca2+-channel clustering observed by super-resolution immunofluorescence microscopy. We postulate that RIBEYE disruption is partially compensated by multi-AZ organization. The remaining synaptic deficit indicates ribbon function in SV-replenishment and Ca2+-channel regulation
Quantitative optical nanophysiology of Ca2 signaling at inner hair cell active zones
No full textCa2+ influx triggers the release of synaptic vesicles at the presynaptic active zone (AZ). A quantitative characterization of presynaptic Ca2+ signaling is critical for understanding synaptic transmission. However, this has remained challenging to establish at the required resolution. Here, we employ confocal and stimulated emission depletion (STED) microscopy to quantify the number (20–330) and arrangement (mostly linear 70 nm × 100–600 nm clusters) of Ca2+ channels at AZs of mouse cochlear inner hair cells (IHCs). Establishing STED Ca2+ imaging, we analyze presynaptic Ca2+ signals at the nanometer scale and find confined elongated Ca2+ domains at normal IHC AZs, whereas Ca2+ domains are spatially spread out at the AZs of bassoon-deficient IHCs. Performing 2D-STED fluorescence lifetime analysis, we arrive at estimates of the Ca2+ concentrations at stimulated IHC AZs of on average 25 µM. We propose that IHCs form bassoon-dependent presynaptic Ca2+-channel clusters of similar density but scalable length, thereby varying the number of Ca2+ channels amongst individual AZs
Differential regulation of Ca/calmodulin-dependent protein kinase II (CaMKII) in cardiac hypertrophy in the mouse: Pressure overload versus volume overload
No full textPathogenicity of porcine intestinal spirochetes in gnotobiotic pigs
No full textTwelve intestinal spirochete strains of porcine origin were characterized on the basis of their phenotypic properties, by multilocus enzyme electrophoresis, and by pathogenicity testing in gnotobiotic pigs. The spirochetes used included two strains of Serpulina hyodysenteriae (B204 and P18A), two strains of Serpulina innocens (B256 and 4/71), one strain from the proposed new genus and species "Anguillina coli" (P43/6/78), and seven non-S. hyodysenteriae strains recently isolated from United Kingdom pig herds with a history of nonspecific diarrhea and typhlocolitis. By multilocus enzyme electrophoresis, five of these were identified as S. innocens, one was identified as an unspecified Serpulina sp., and one was identified as "A. coli." S. hyodysenteriae B204 and P18A, "A. coli" P43/6/78 and 2/7, and three (22/7, P280/1, and 14/5) of the five S. innocens field isolates induced mucoid feces and typhlocolitis in gnotobiotic pigs. None of the other spirochetes produced clinical signs or large intestinal pathology in this model. The "A. coli" strains induced a more watery diarrhea, with lesions present more proximally in the large intestine, than did the other pathogenic spirochetes. S. innocens 22/7 was also tested for pathogenicity in hysterotomy-derived pigs that had previously been artificially colonized with a spirochete-free intestinal flora and shown to be susceptible to swine dysentery. Despite effective colonization, strain 22/7 did not produce any disease, nor was there any exacerbation of large intestinal pathology or clinical signs when pigs with an experimentally induced existing colitis caused by Yersinia pseudotuberculosis were superinfected with strain 22/7. Certain non-S. hyodysenteriae spirochetes are therefore capable of inducing disease in gnotobiotic pigs, but their role as primary or opportunistic pathogens in conventional pigs remains equivocal
Constitutively active phosphatase inhibitor-1 improves cardiac contractility in young mice but is deleterious after catecholaminergic stress and with aging
No full textPhosphatase inhibitor-1 (I-1) is a distal amplifier element of beta-adrenergic signaling that functions by preventing dephosphorylation of downstream targets. I-1 is downregulated in human failing hearts, while overexpression of a constitutively active mutant form (I-1c) reverses contractile dysfunction in mouse failing hearts, suggesting that I-1c may be a candidate for gene therapy. We generated mice with conditional cardiomyocyte-restricted expression of I-1c (referred to herein as dTGI-1c mice) on an I-1-deficient background. Young adult dTGI-1c mice exhibited enhanced cardiac contractility but exaggerated contractile dysfunction and ventricular dilation upon catecholamine infusion. Telemetric ECG recordings revealed typical catecholamine-induced ventricular tachycardia and sudden death. Doxycycline feeding switched off expression of cardiomyocyte-restricted I-1c and reversed all abnormalities. Hearts from dTGI-1c mice showed hyperphosphorylation of phospholamban and the ryanodine receptor, and this was associated with an increased number of catecholamine-induced Ca2+ sparks in isolated myocytes. Aged dTGI-1c mice spontaneously developed a cardiomyopathic phenotype. These data were confirmed in a second independent transgenic mouse line, expressing a full-length I-1 mutant that could not be phosphorylated and thereby inactivated by PKC-alpha (I-1S67A). In conclusion, conditional expression of I-1c or I-1S67A enhanced steady-state phosphorylation of 2 key Ca2+-regulating sarcoplasmic reticulum enzymes. This was associated with increased contractile function in young animals but also with arrhythmias and cardiomyopathy after adrenergic stress and with aging. These data should be considered in the development of novel therapies for heart failure
KIF14 and citron kinase act together to promote efficient cytokinesis
No full textMultiple mitotic kinesins and microtubule-associated proteins (MAPs) act in concert to direct cytokinesis (Glotzer, M. 2005. Science. 307:1735-1739). In anaphase cells, many of these proteins associate with an antiparallel array of microtubules termed the central spindle. The MAP and microtubule-bundling protein PRC1 (protein-regulating cytokinesis 1) is one of the key molecules required for the integrity of this structure (Jiang, W., G. Jimenez, N.J. Wells, T.J. Hope, G.M. Wahl, T. Hunter, and R. Fukunaga. 1998. Mol. Cell. 2:877-885; Mollinari, C., J.P. Kleman, W. Jiang, G. Schoehn, T. Hunter, and R.L. Margolis. 2002. J. Cell Biol. 157:1175-1186). In this study, we identify an interaction between endogenous PRC1 and the previously uncharacterized kinesin KIF14 as well as other mitotic kinesins (MKlp1/CHO1, MKlp2, and KIF4) with known functions in cytokinesis (Hill, E., M. Clarke, and F.A. Barr. 2000. EMBO J. 19:5711-5719; Matuliene, J., and R. Kuriyama. 2002. Mol. Biol. Cell. 13:1832-1845; Kurasawa, Y., W.C. Earnshaw, Y. Mochizuki, N. Dohmae, and K. Todokoro. 2004. EMBO J. 23:3237-3248). We find that KIF14 targets to the central spindle via its interaction with PRC1 and has an essential function in cytokinesis. In KIF14-depleted cells, citron kinase but not other components of the central spindle and cleavage furrow fail to localize. Furthermore, the localization of KIF14 and citron kinase to the central spindle and midbody is codependent, and they form a complex depending on the activation state of citron kinase. Contrary to a previous study (Di Cunto, F., S. Imarisio, E. Hirsch, V. Broccoli, A. Bulfone, A. Migheli, C. Atzori, E. Turco, R. Triolo, G.P. Dotto, et al. 2000. Neuron. 28:115-127), we find a general requirement for citron kinase in human cell division. Together, these findings identify a novel pathway required for efficient cytokinesis
Improving the quality of life of senior citizens in their living environment based on the example of homes for the elderly
No full textThe subject of the article is the study of the importance and complexity of shaping the living environment for senior citizens based on the example of homes for the elderly. The aim is to show that programming and designing such places must take into consideration the therapeutic function of living space. Functional solutions are important to consider but so are the adaptive capabilities and needs of the elderly, who are at the stage of their life when living environment stability and personal safety are crucial. It is also necessary for the designers to be aware that they need to consider the spatial competence of the target users, the importance of human capital senior citizens represent in our society and the standardization of cultural norms contained in the living practice of the elderly. The above constitute the factors which make it possible to organize the use of living space properly. Moreover, the subject of designing, especially designing functional living space in buildings with the elderly in mind, is closely connected with environmental psychology and the concept of adapting the living space to the needs of the elderly.Iwona Benek - dr inż. arch., Katedra Teorii Projektowania i Historii Architektury, Wydział Architektury Politechniki Śląskiej w Gliwicach. Działalność naukowa związana z problematyką projektowania dla osób starszych z ich percepcją oraz potrzebami. Autorka około 30 artykułów, współautorka 3 monografii, prac koncepcyjnych oraz ekspertyz dotyczących obiektów dla osób starszych (domy seniora, wzorcowe mieszkanie seniora, ogrody terapeutyczne).Bańka A., Społeczna psychologia środowiskowa, Wydawnictwo Naukowe Scholar, Warszawa 2002.Bell P. A., Greene Th. C., Fisher J. D., Baum A., Psychologia środowiska, Gdańskie Wydawnictwo Psychologiczne, Gdańsk 2004.Bielak M., Optymalne środowisko życia i zamieszkania w ośrodkach pobytu stałego dla osób starszych, Wydawnictwo Politechniki Śląskiej, Gliwice 2011.Kawczyńska-Butrym Z., Niepełnosprawność – specyfika pomocy społecznej, Wydawnictwo Śląsk, Katowice 1998.Lawton M. P., An Environmental Psychologist Ages, Environment and Behavior Studies: Emergence of Intellectual Traditions, 1999.Maslow A., Motywacja i osobowość, PWN, Warszawa 2013.Max-Neef M., Elizade A., Hopenhazn M., Human Scale Development. Conception, Application and Futher Reflections, The Apex Press, London, New York 1991.Niezabitowska E. E., Masły D., Oceny jakości środowiska zbudowanego i ich znaczenie dla rozwoju koncepcji budynku zrównoważonego, Wyd. Politechniki Śląskiej, Gliwice 2007.Nowa Karta Ateńska 2003. Wizja Miast XXI wieku – La Nouvelle Charte d’Athennes 2003, The New Charter of Athens, Alinea, Firenze 2003, Redakcja polska: Towarzystwo Urbanistów Polskich.Passini R., Wayfinding in Architecture, Van Nostrand reihold, New York 1984.Sanoff H., Integrowanie projektowania, ewaluacji i partycypacji w środowisku architektonicznym, Stowarzyszenie Psychologia i Architektura, Poznań 1999.Steele F., Physical Setting and organizational Development, Addison-Wesley, London 1973.Szweda-Lewandowska Z., Popyt na miejsca w domach pomocy społecznej wśród seniorów w Polsce w perspektywie 2035 roku, Acta Universitatis Lodziensis, Folia Oeconomica 231, Łódź 2009.Venturi R., Complexity and Contradiction in Architecture, MoMA, New York 1984.Kwiatkowska W., Szczepańska J., Woźniewski M., Greń G., Zaburzenia poznawcze u osób starszych w świetle oceny metablicznych czynników ryzyka chorób sercowo-naczyniowych, „Acta Angiol”, 2005, t.11, nr 1, s. 38-39.J.M. Tornington, P. R. Tregenza, Lighting for people with Dementia, “Lighting res. Technology”, 2007 nr (39) s. 81-97.Rozporządzenie Ministra Infrastruktury z dnia 12 kwietnia 2002 r. w sprawie warunków technicznych, jakim powinny odpowiadać budynki i ich usytuowanie. (Dz.U. z 2012 r. nr 75 poz. 690 z późn.).Rozporządzenie Ministra Pracy i polityki Społecznej z dnia 23 sierpnia 2012 r. w sprawie domów pomocy społecznej (Dz.U. z 2012 r. poz. 964).Ustawa z dnia 7 lipca 1994 r. Prawo budowlane.Ustawa z dnia 12 marca 2004 r. o pomocy społecznej (Dz. U. z 2013 r. poz. 182).34135
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