147 research outputs found
Título: Summa theologica
No full textNotas a pié de página a dos columnasTexto fileteado a dos columnasMarca tipográfica en la portadaNotas a pé páx. a dúas colTexto fileteado a dúas colMarca tip. en portContiene: Tomus primus, pars 1ª (768 p.) -- Tomus secundus, pars 1ª-2ª (732 p.) -- Tomus tertius, pars 2ª-2ªa Qu.I.usque ad Qu.CXXIII -- Tomus quartus, pars 2ª-2ae a Qu. CXXIV ad finem, pars 3ª a Qu. I ad LXII (819 p.) -- Tomus quintus, pars 3ª. a Qu. LXIII ad finem et supplementum 3ae partis (824 p) -- Tomus sextus. Indices et lexicon (438, 41* p.)Contén: Tomus primus, pars 1ª (768 p.) -- Tomus secundus, pars 1ª-2ª (732 p.) -- Tomus tertius, pars 2ª-2ªa Qu.I.usque ad Qu.CXXIII -- Tomus quartus, pars 2ª-2ae a Qu. CXXIV ad finem, pars 3ª a Qu. I ad LXII (819 p.) -- Tomus quintus, pars 3ª. a Qu. LXIII ad finem et supplementum 3ae partis (824 p) -- Tomus sextus. Indices et lexicon (438, 41* p.
[Summa Theologica]
No full textSignaturizadoMarca tipográfica na portadaTexto a dúas columnasContén: t. IV: Pars 2ª 2\pae\s a Qu. CXXIV ad finem, pars 3ª a Qu. I ad LXII, (819 p.) -- t. V: Pars 3ª a Qu. LXIII ad finem et supplementum 3\pae\s partis, (824 p.) -- t. VI (438, 41 p.
Oligophrenin-1 regulates synaptic activity dependent shuttling between synapses and nucleus of Rev-erbAalpha
No full textOligophrenin-1 (OPHN1) is a synaptic RhoGTPase-activating protein involved in X-linked mental
retardation that regulates dendritic spines shape and outgrowth of axons in brain (Govek et al., 2004).
By using the C-terminal fragment of Oligophrenin 1 as bait in a two-hybrid screening of a human fetal
brain cDNA library we identified as an interactor, NR1D1 (Rev-erbAalpha). Rev-erbAalpha is an
orphan nuclear receptor that constitutively suppresses gene transcription and regulates the circadian
clock in the CNS (Preitner et al. 2002). We confirmed the interaction in vitro and in vivo by
co-immunoprecipitation and GST-pull down.
In COS-7 cells we observed that overexpressed Oligophrenin-1 is able to recruit Rev-erbAalpha
(normally localized in the nucleus) to the cytoplasm. Furthermore, overexpression Oligophrenin-1
induces an accumulation of endogenous Rev-erbAalpha in dendritic spines in hippocampal neurons.
The Oligophrenin-1deltaC (deleted of C-terminus), a mutant that mimics the mutation present in the
XLMR patients, wasn’t able to induce this effect in COS7 and in hippocampal neurons. In HEK cells
we observed that Oligophrenin-1 protects Rev-erbAalpha from degradation by GSK3beta We also
have found that RNAi knockdown of Oligophrenin-1 inhibited the translocation of Rev-erbAalpha into
the dendritic spines. More remarkable, synaptic activity mediated by AMPA receptors induces
translocation of Rev-erbAalpha to the dendritic spines. RNAi experiments showed that Oligophrenin-1
is required for the translocation of Rev-erbAalpha in spines induced by synaptic activity. Moreover we
observed an alteration of Rev-erbAalpha expression in Oligophrenin-1 KO mouse: there is a reduction
of Rev-erbAalpha in hippocampus.
Our results demonstrate for the first time the interaction between an orphan receptor (Rev-erbAalpha)
and a synaptic protein (Oligophrenin-1). This interaction regulates the localization of Rev-erbAalpha
between synapse and nucleus induced by synaptic activation
Summary of the steps from the selection of slices to angle measurements.
No full text(A) The 3D model is segmented in several plane sections according to the methodology presented above. (B) After selecting the slices according to the anatomical description by Sakoma et al. [22] and in which a portion of the ILSS is “stamped”, the biomechanical model developed by Billuart et al. [20] (C) is used to carry out the angle measurements (D).</p
Pharmacological rescue of adult hippocampal neurogenesis in a mouse model of X-linked intellectual disability
No full textOligophrenin-1 (OPHN1) is a Rho GTPase activating protein whose mutations cause X-linked intellectual disability (XLID). How loss of function of Ophnl affects neuronal development is only partly understood. Here we have exploited adult hippocampal neurogenesis to dissect the steps of neuronal differentiation that are affected by Ophn1 deletion. We found that mice lacking Ophnl display a reduction in the number of newborn neurons in the dentate gyrus. A significant fraction of the Ophn1-deficient newly generated neurons failed to extend an axon towards CM, and showed an altered density of dendritic protrusions. Since Ophnl-deficient mice display overactivation of Rho-associated protein kinase (ROCK) and protein kinase A (PICA) signaling, we administered a clinically approved ROCK/PICA inhibitor (fasudil) to correct the neurogenesis defects. While administration of fasudil was not effective in rescuing axon formation, the same treatment completely restored spine density to control levels, and enhanced the long-term survival of adult-born neurons in mice lacking Ophn1. These results identify specific neurodevelopmental steps that are impacted by Ophn1 deletion, and indicate that they may be at least partially corrected by pharmacological treatment. (C) 2017 The Authors. Published by Elsevier Inc
Summa Summae S. Thomae sive Compendium Theologiae R. Patris Caroli Renati Billuart, Ordinis Fratrum Praedicatorum ... tomus II : tractatus de actibus humanis, peccatis, legibus et gratie.
No full textStahel trabaja ca. 1763-1787Sign. : A-Z\p8\s, 2A-2G\p8\sGrab. xil. en p. 4
Oligophrenin-1 regulates number, morphology and synaptic properties of adult-born inhibitory interneurons in the olfactory bulb
No full textAmong the X-linked genes associated with intellectual disability, Oligophrenin-1 (OPHN1) encodes for a Rho GTPase-activating protein, a key regulator of several developmental processes, such as dendrite and spine formation and synaptic activity. Inhibitory interneurons play a key role in the development and function of neuronal circuits. Whether a mutation of OPHN1 can affect morphology and synaptic properties of inhibitory interneurons remains poorly understood. To address these open questions, we studied in a well-established mouse model of X-linked intellectual disability, i.e. a line of mice carrying a null mutation of OPHN1, the development and function of adult generated inhibitory interneurons in the olfactory bulb. Combining quantitative morphological analysis and electrophysiological recordings we found that the adult generated inhibitory interneurons were dramatically reduced in number and exhibited a higher proportion of filopodia-like spines, with the consequences on their synaptic function, in OPHN1 ko mice. Furthermore, we found that olfactory behaviour was perturbed in OPHN1 ko mice. Chronic treatment with a Rho kinase inhibitor rescued most of the defects of the newly generated neurons. Altogether, our data indicated that OPHN1 plays a key role in regulating the number, morphology and function of adult-born inhibitory interneurons and contributed to identify potential therapeutic targets
A postsynaptic signaling pathway that may account for the cognitive defect due to IL1RAPL1 mutation
No full textBackground: Interleukin-1 receptor accessory protein-like 1
(IL1RAPL1) gene mutations are associated with cognitive
impairment ranging from nonsyndromic X-linked mental retardation
to autism. IL1RAPL1 belongs to a novel family of Toll/IL-
1 receptors, whose expression in the brain is upregulated by
neuronal activity. Currently, very little is known about the
function of this protein. We previously showed that IL1RAPL1
interacts with the neuronal calcium sensor NCS-1 and that it
regulates voltage-gated calcium channel activity in PC12 cells.
Results: Here we show that IL1RAPL1 is present in dendritic
spine where it interacts with PSD-95, a major component
of excitatory postsynaptic compartment. Using gain- and
loss-of-function experiments in neurons, we demonstrated
that IL1RAPL1 regulates the synaptic localization of PSD-95
by controlling c-Jun terminal kinase (JNK) activity and
PSD-95 phosphorylation. Mice carrying a null mutation of the
mouse Il1rapl1 gene show a reduction of both dendritic spine
density and excitatory synapses in the CA1 region of the hippocampus.
These structural abnormalities are associated with
specific deficits in hippocampal long-term synaptic plasticity. Conclusion: The interaction of IL1RAPL1 with PSD-95
discloses a novel pathophysiological mechanism of cognitive
impairment associated with alterations of the JNK pathway
leading to a mislocalization of PSD-95 and abnormal synaptic
organization and function
Summa Sancti Thomae hodiernis academiarum moribus accomodata
No full textIndicesDatos del editor: ColofónAntepTexto a duas colBiografía do autor, p. VIII-XIII do v.
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