86,913 research outputs found
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
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
Unified Dark Matter scalar field models with fast transition
No full textWe investigate the general properties of Unified Dark Matter (UDM) scalar field models with Lagrangians with a non-canonical kinetic term, looking specifically for models that can produce a fast transition between an early Einstein-de Sitter CDM-like era and a later Dark Energy like phase, similarly to the barotropic fluid UDM models in JCAP01(2010)014. However, while the background evolution can be very similar in the two cases, the perturbations are naturally adiabatic in fluid models, while in the scalar field case they are necessarily non-adiabatic. The new approach to building UDM Lagrangians proposed here allows to escape the common problem of the fine-tuning of the parameters which plague many UDM models. We analyse the properties of perturbations in our model, focusing on the the evolution of the effective speed of sound and that of the Jeans length. With this insight, we can set theoretical constraints on the parameters of the model, predicting sufficient conditions for the model to be viable. An interesting feature of our models is that what can be interpreted as wDE can be < −1 without violating the null energy conditions
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
Il mosaico incerto degli ordinamenti giuridici operanti nel Kosovo, secondo il parere della Corte internazionale di giustizia
No full textHeterogeneity of astrocytic and neuronal GLT-1 at cortical excitatory synapses, as revealed by its colocalization with Na+/K+-ATPase α isoforms
No full textGLT-1, the major glutamate transporter, is expressed at perisynaptic astrocytic processes (PAP) and axon terminals (AxT). GLT-1 is coupled to Na+/K+-ATPase (NKA) α1–3 isoforms, whose subcellular distribution and spatial organization in relationship to GLT-1 are largely unknown. Using several microscopy techniques, we showed that at excitatory synapses α1 and α3 are exclusively neuronal (mainly in dendrites and in some AxT), while α2 is predominantly astrocytic. GLT-1 displayed a differential colocalization with α1–3. GLT-1/α2 and GLT-1/α3 colocalization was higher in GLT-1 positive puncta partially (for GLT-1/α2) or almost totally (for GLT-1/α3) overlapping with VGLUT1 positive terminals than in nonoverlapping ones. GLT-1 colocalized with α2 at PAP, and with α1 and α3 at AxT. GLT-1 and α2 gold particles were ~1.5–2 times closer than GLT-1/α1 and GLT-1/α3 particles. GLT-1/α2 complexes (edge to edge interdistance of gold particles ≤50 nm) concentrated at the perisynaptic region of PAP membranes, whereas neuronal GLT-1/α1 and GLT-1/α3 complexes were fewer and more uniformly distributed in AxT. These data unveil different composition of GLT-1 and α subunits complexes in the glial and neuronal domains of excitatory synapses. The spatial organization of GLT-1/α1–3 complexes suggests that GLT-1/NKA interaction is more efficient in astrocytes than in neurons, further supporting the dominant role of astrocytic GLT-1 in glutamate homeostasis
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