130,792 research outputs found
Double-inhibitor and uncoupler-inhibitor titrations. 2. Analysis with a nonlinear model of chemiosmotic energy coupling.
No full textThe results of double-inhibitor and uncoupler-inhibitor titrations have been simulated and analyzed with a nonlinear model of delocalized protonic coupling obtained by linking two proton pump models of the kind studied by Pietrobon and Caplan [Pietrobon, D., & Caplan, S. R. (1985) Biochemistry 24, 5764-5776] through their common intermediate delta mu H. It is shown that the results predicted by a delocalized chemiosmotic model are highly dependent on the kind of relationships existing between rate of ATP synthesis, Jp, and delta mu H and rate of electron transfer, Je, and delta mu H. With nonlinear flow-force relationships all the results reported so far are not necessarily inconsistent with the delocalized chemiosmotic model provided that the relationships between rates and delta mu H satisfy the following requirements: Jp/delta mu H increases and/or Je/delta mu H decreases as (delta mu H) increases
Ion channels in migraine disorders
No full textMigraine is a complex brain disorder characterized by recurrent attacks of unilateral headache and a global dysfunction in multisensory information processing. Genetic studies implicate several ion channel genes in migraine, ether as causative of a monogenic subtype (FHM) or possible contributors. Here we mainly discuss functional studies in transgenic mice carrying a CaV2.1 mutation causing FHM, and the insights they provide into the disease mechanisms, in particular regarding susceptibility to cortical spreading depression (CSD), the phenomenon that underlies migraine aura and can trigger the headache mechanisms. We also discuss recent findings implicating the ATP-gated P2X7 receptor in initiation of experimental CSD, and review some properties of the channels identified by genome-wide association studies as having a potential role in migraine
Integrated Sachs-Wolfe effect from the cross correlation of WMAP 3 year and the NRAO VLA sky survey data: New results and constraints on dark energy
No full textWe cross correlate the new 3 year Wilkinson Microwave Anistropy Probe (WMAP) cosmic microwave background data with the NRAO VLA Sky Survey radio galaxy data and find further evidence of late integrated Sachs-Wolfe (ISW) effect taking place at late times in cosmic history. Our detection makes use of a novel statistical method (P. Baldi, G. Kerkyacharian, D. Marinucci, and D. Picard, math.ST/0606154 and P. Baldi, G. Kerkyacharian, D. Marinucci, D. Picard, math.ST/0606599) based on a new construction of spherical wavelets, called needlets. The null hypothesis (no ISW) is excluded at more than 99.7% confidence. When we compare the measured cross correlation with the theoretical predictions of standard, flat cosmological models with a generalized dark energy component parameterized by its density, Omega(DE), equation of state w and speed of sound c(s)(2), we find 0.3 <=Omega(DE)<= 0.8 at 95% C.L., independently of c(s)(2) and w. If dark energy is assumed to be a cosmological constant (w=-1), the bound on density shrinks to 0.41 <=Omega(DE)<= 0.79. Models without dark energy are excluded at more than 4 sigma. The bounds on w depend rather strongly on the assumed value of c(s)(2). We find that models with more negative equation of state (such as phantom models) are a worse fit to the data in the case c(s)(2)=1 than in the case c(s)(2)=0
Three novel types of voltage-dependent calcium channels in rat cerebellar neurons
No full textWith the aim of characterizing the functional and pharmacological properties of the different voltage-dependent Ca2+ channels expressed in a given type of CNS neuron, we obtained single Ca2+ channel recordings from rat cerebellar granule cells in primary culture. Our data show that three novel classes of voltage-dependent Ca2+ channels are coexpressed in cerebellar granule cells. They are pharmacologically distinct from dihydropyridine-sensitive L-type and omega-conotoxin-sensitive N-type channels, and their functional properties are different from those of P- and T-type channels. The three novel 21 pS G1-, 15 pS G2-, and 20 pS G3-type Ca2+ channels have similar inactivation properties. They show complete steady-state inactivation at -40 mV and their single-channel average currents have both sustained and decaying components. They differ in activation threshold (-40 mV for G2, -30 mV for G3, and -10 mV for G1, with 90 mM Ba2+ as charge carrier), mean open time (1.2 msec for G2, 1 msec for G3, 0.8 msec for G1), and single-channel currents (at 0 mV: 0.5 pA for G2, 0.8 pA for G3, and 1.4 pA for G1). Together with the previously characterized multiple L-type Ca2+ channels (Forti and Pietrobon, 1993), G1-, G2-, and G3-type channels constitute the large majority of Ca2+ channels of cerebellar granule cells in culture. The low activation threshold of G2-type channels and their inactivation properties suggest that they might be native counterparts of the recently expressed rat brain clone rbE-II (Soong et al., 1993)
Unified Dark Matter models with fast transition
No full textWe investigate the general properties of Unified Dark Matter (UDM) fluid models where the pressure and the energy density are linked by a barotropic equation of state (EoS) p = p(ρ) and the perturbations are adiabatic. The EoS is assumed to admit a future attractor that acts as an effective cosmological constant, while asymptotically in the past the pressure is negligible. UDM models of the dark sector are appealing because they evade the so-called ``coincidence problem'' and ``predict'' what can be interpreted as wDE ≈ −1, but in general suffer the effects of a non-negligible Jeans scale that wreak havoc in the evolution of perturbations, causing a large Integrated Sachs-Wolfe effect and/or changing structure formation at small scales. Typically, observational constraints are violated, unless the parameters of the UDM model are tuned to make it indistinguishable from ΛCDM. Here we show how this problem can be avoided, studying in detail the functional form of the Jeans scale in adiabatic UDM perturbations and introducing a class of models with a fast transition between an early Einstein-de Sitter CDM-like era and a later ΛCDM-like phase. If the transition is fast enough, these models may exhibit satisfactory structure formation and CMB fluctuations. To consider a concrete case, we introduce a toy UDM model and show that it can predict CMB and matter power spectra that are in agreement with observations for a wide range of parameter values
Uncoupling of oxidative phosphorylation. 2. Alternative mechanisms: intrinsic uncoupling or decoupling?
No full textThe mechanism of uncoupling of oxidative phosphorylation by carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP), oleic acid, and chloroform is further investigated by measuring in the presence of a certain concentration of each type of uncoupler (i) the mitochondrial P/O and respiratory control ratios upon progressive inhibition of the redox pumps and (ii) delta mu H and the rate of either electron transfer or adenosine 5'-triphosphate (ATP) hydrolysis in static head upon progressive inhibition of either the redox or the adenosine triphosphatase (ATPase) proton pumps. Chloroform exhibits in all the experiments a behavior very different from that of FCCP and oleic acid. For example, upon addition of antimycin to chloroform-supplemented mitochondria, the respiratory control ratio remains unchanged and the P/O ratio slightly increases (in a certain range of inhibition) instead of decreasing as expected for an increased membrane conductance (and as indeed measured in the presence of either FCCP or oleic acid). From the kinetic model of chemiosmotic free energy coupling described by Pietrobon and Caplan [Pietrobon, D., & Caplan, S.R. (1986) Biochemistry 25, 7690-7696] all the results can be simulated by making the assumptions that (i) chloroform acts specifically at the level of the proton pumps and intrinsically uncouples electron transfer and ATP hydrolysis/synthesis from proton translocation and (ii) FCCP and oleic acid have a mixed behavior and act both as protonophores and as intrinsic uncouplers of the redox pumps (but not of the ATPases). The consistency of the results with the alternative hypothesis that the three agents interfere either with localized energy coupling sites or with a direct interaction between proton pumps is discussed
Making the best of cosmological perturbations: theory and data analysis
No full textGrazie a esperimenti estremamente raffinati, la cosmologia moderna si trova oggi in quella che puo' essere defi nita l' epoca della precisione. I
cosmologi dispongono di una grande quatita' di strumenti per testare il cosiddetto modello cosmologico di concordanza e vincolarne i principali parametri. In particolare, la radiazione cosmica di fondo (CMB) ha svolto, e svolge
tutt'oggi, un ruolo chiave in questo ambito. Numerose domande rimangono
tuttavia ancora in attesa di una risposta, in particolare quelle che riguardano la fisica dell'inflazione, che ha governato l'Universo nelle prime fasi di
evoluzione, e la natura dell' accelerazione dell' espansione dell'Universo, che e' stata osservata negli ultimi anni.
La mia attivita' di ricerca ha contribuito ad approfondire lo studio e la conoscenza su entrambe le tematiche, che sono state accomunate dallo sviluppo
e dall'utilizzo delle needlets - una nuova "frame" sulla sfera - per analizzare
la CMB. Con questo strumento, abbiamo misurato l'effetto Sachs-Wolfe integrato, correlando i dati di WMAP e NVSS, e caratterizzato le proprieta'
della dark energy, seguendo un approccio fenomenologico che si basa sull'approssimazione
di fl uido perfetto. Stimolati dai risultati ottenuti, abbiamo studiato in dettaglio un modello unifi cato per le componenti di dark energy e dark matter,
che fa uso di un'equazione di stato affi ne, e investigato i vincoli sui parametri
di questo modello provenienti da WMAP e SDSS.
Abbiamo quindi applicato le needlets ai dati di WMAP 5-anni allo scopo
di studiare la gaussianita' della distribuzione delle perturbazioni della CMB.
Ci siamo dapprima concentrati sulle mappe, rilevando la presenza di regioni anomale, localizzate nell' emisfero meridionale, e studiando l'effetto che
queste regioni hanno sullo spettro di potenza angolare. Successivamente, abbiamo misurato la funzione di correlazione a tre punti (bispettro) delle needlets caratterizzandola in termini della sua ampiezza complessiva, descritta dal parametro fNL, e secondo la geometria delle configurazioni triangolari che contribuiscono al segnale totale. Abbiamo misurato una significativa anomalia nelle confi gurazioni isosceli, nuovamente presente nell'emisfero
meridionale.
Infine, ci siamo concentrati sulla costruzione di un estimatore per il bispettro delle needlets, includendo l'effetto spurio che puo' essere introdotto
dalla presenza di eventuale segnale residuo, proveniente da sorgenti di natura prevalentemente Galattica.Cosmology has entered the precision epoch thanks to several
very accurate experiments. Cosmologists now have access to an array of
tools to test the cosmological concordance model and constrain its parameters; the Cosmic Microwave Background radiation (CMB), in particular,
has been playing a crucial role in this ambition. Many questions remain
nonetheless unanswered, especially concerning the physics of the early Universe, the infl ationary mechanism which set the initial conditions for the
Universe expansion, and the nature of the late
time acceleration of the Universe expansion.
My research contributes to both of these sub jects, the common ground
being the development of a statistical tool - needlets, a new "frame" on the
sphere - to analyse the CMB. By means of needlets, we measure the Integrated Sachs Wolfe effect by cross-correlating WMAP and NVSS datasets
and characterise dark energy properties using a phenomenological fluid model.
Motivated by our findings, we study in detail a parameterisation of the dark
components, dark matter and dark energy, which makes use of an affine
equation of state, constraining the parameters of the model by combining
WMAP and SDSS datasets.
We apply needlets to the WMAP 5-year data release testing the Gaussianity of the CMB perturbations. Our approach is twofold: we first focus
on the maps, detecting anomalous spots located in the southern hemisphere
and check their effect on the angular power spectrum. We next measure
the needlet three-point correlation function (bispectrum) and characterise
it in terms of its overall amplitude, constraining the primordial
fNL parameter, and considering its properties according to the geometry of
the triangle configurations which contribute to the total power. We find a significant anomaly in the isosceles confi gurations, again in the southern
hemisphere.
Finally we focus on the construction of an optimal estimator for the
(needlets) bispectrum, taking into account foreground residuals due mainly to Galactic emission
Astrocytic Na+, K+ ATPases in physiology and pathophysiology
No full textThe Na+, K+ ATPases play a fundamental role in the homeostatic functions of astrocytes. After a brief historic prologue and discussion of the subunit composition and localization of the astrocytic Na+, K+ ATPases, the review focuses on the role of the astrocytic Na+, K+ pumps in extracellular K+ and glutamate homeostasis, intracellular Na+ and Ca2+ homeostasis and signaling, regulation of synaptic transmission and neurometabolic coupling between astrocytes and neurons. Loss-of-function mutations in the gene encoding the astrocytic α2 Na+, K+ ATPase cause a rare monogenic form of migraine with aura (familial hemiplegic migraine type 2). On the other hand, the α2 Na+, K+ ATPase is upregulated in spinal cord and brain samples from amyotrophic lateral sclerosis and Alzheimer disease patients, respectively. In the last part, the review focuses on i) the migraine relevant phenotypes shown by familial hemiplegic migraine type 2 knock-in mice with 50 % reduced expression of the astrocytic α2 Na+, K+ ATPase and the insights into the pathophysiology of migraine obtained from these genetic mouse models, and ii) the evidence that upregulation of the astrocytic α2 Na+, K+ ATPase in mouse models of amyotrophic lateral sclerosis and Alzheimer disease promotes neuroinflammation and contributes to progressive neurodegeneration
Migraine: a disorder of brain excitatory-inhibitory balance?
No full textMigraine is a common disabling brain disorder whose key manifestations are recurrent attacks of unilateral headache and interictal hypersensitivity to sensory stimuli. Migraine arises from a primary brain dysfunction that leads to episodic activation and sensitization of the trigeminovascular pain pathway and as a consequence to headache. Major open issues concern the molecular and cellular mechanisms of the primary brain dysfunction(s) and of migraine pain. We review here our current understanding of these mechanisms, focusing on recent advances regarding migraine genetics, headache mechanisms, and the primary brain dysfunction(s) underlying migraine onset and susceptibility to cortical spreading depression, the neurophysiological correlate of migraine aura. We also discuss insights obtained from the functional analysis of familial hemiplegic migraine mouse models
Recenti sviluppi sui sistemi galleggianti a rilascio di farmaco specifici per lo stomaco
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