216 research outputs found
Interleukin-33 regulates metabolic reprogramming of the retinal pigment epithelium in response to immune stressors
It remains unresolved how retinal pigment epithelial cell metabolism is regulated following immune activation to maintain retinal homeostasis and retinal function. We exposed retinal pigment epithelium (RPE) to several stress signals, particularly Toll-like receptor stimulation, and uncovered an ability of RPE to adapt their metabolic preference on aerobic glycolysis or oxidative glucose metabolism in response to different immune stimuli. We have identified interleukin-33 (IL-33) as a key metabolic checkpoint that antagonizes the Warburg effect to ensure the functional stability of the RPE. The identification of IL-33 as a key regulator of mitochondrial metabolism suggests roles for the cytokine that go beyond its extracellular “alarmin” activities. IL-33 exerts control over mitochondrial respiration in RPE by facilitating oxidative pyruvate catabolism. We have also revealed that in the absence of IL-33, mitochondrial function declined and resultant bioenergetic switching was aligned with altered mitochondrial morphology. Our data not only shed new light on the molecular pathway of activation of mitochondrial respiration in RPE in response to immune stressors but also uncover a potentially novel role of nuclear intrinsic IL-33 as a metabolic checkpoint regulator
Single-Band Model for Diluted Magnetic Semiconductors: Dynamical and Transport Properties and Relevance of Clustered States
Dynamical and transport properties of a simple single-band spin-fermion
lattice model for (III,Mn)V diluted magnetic semiconductors (DMS) is here
discussed using Monte Carlo simulations. This effort is a continuation of
previous work (G. Alvarez, Phys. Rev. Lett. 89, 277202 (2002)) where the static
properties of the model were studied. The present results support the view that
the relevant regime of J/t (standard notation) is that of intermediate
coupling, where carriers are only partially trapped near Mn spins, and locally
ordered regions (clusters) are present above the Curie temperature T_C. This
conclusion is based on the calculation of the resistivity vs. temperature, that
shows a soft metal to insulator transition near T_C, as well on the analysis of
the density-of-states and optical conductivity. In addition, in the clustered
regime a large magnetoresistance is observed in simulations. Formal analogies
between DMS and manganites are also discussed.Comment: Revtex4, 20 figures. References updated, minor changes to figures and
tex
Electronic structure and magnetism of Mn doped GaN
Mn doped semiconductors are extremely interesting systems due to their novel
magnetic properties suitable for the spintronics applications. It has been
shown recently by both theory and experiment that Mn doped GaN systems have a
very high Curie temperature compared to that of Mn doped GaAs systems. To
understand the electronic and magnetic properties, we have studied Mn doped GaN
system in detail by a first principles plane wave method. We show here the
effect of varying Mn concentration on the electronic and magnetic properties.
For dilute Mn concentration, states of Mn form an impurity band completely
separated from the valence band states of the host GaN. This is in contrast to
the Mn doped GaAs system where Mn states in the gap lie very close to the
valence band edge and hybridizes strongly with the delocalized valence band
states.
To study the effects of electron correlation, LSDA+U calculations have been
performed.
Calculated exchange interaction in (Mn,Ga)N is short ranged in contrary to
that in (Mn,Ga)As where the strength of the ferromagnetic coupling between Mn
spins is not decreased substantially for large Mn-Mn separation. Also, the
exchange interactions are anisotropic in different crystallographic directions
due to the presence or absence of connectivity between Mn atoms through As
bonds.Comment: 6 figures, submitted to Phys. Rev.
On-site Coulomb interaction and the magnetism of (GaMn)N and (GaMn)As
We use the local density approximation (LDA) and LDA+U schemes to study the
magnetism of (GaMn)As and (GaMn)N for a number of Mn concentrations and varying
number of holes. We show that for both systems and both calculational schemes
the presence of holes is crucial for establishing ferromagnetism. For both
systems, the introduction of increases delocalization of the holes and,
simultaneously, decreases the p-d interaction. Since these two trends exert
opposite influences on the Mn-Mn exchange interaction the character of the
variation of the Curie temperature (T) cannot be predicted without direct
calculation. We show that the variation of T is different for two systems.
For low Mn concentrations we obtain the tendency to increasing T in the
case of (GaMn)N whereas an opposite tendency to decreasing T is obtained
for (GaMn)As. We reveal the origin of this difference by inspecting the
properties of the densities of states and holes for both systems. The main body
of calculations is performed within a supercell approach. The Curie
temperatures calculated within the coherent potential approximation to atomic
disorder are reported for comparison. Both approaches give similar qualitative
behavior. The results of calculations are related to the experimental data.Comment: to appear in Physical Review
Sect and House in Syria: History, Architecture, and Bayt Amongst the Druze in Jaramana
This paper explores the connections between the architecture and materiality of houses and the social idiom of bayt (house, family). The ethnographic exploration is located in the Druze village of Jaramana, on the outskirts of the Syrian capital Damascus. It traces the histories, genealogies, and politics of two families, bayt Abud-Haddad and bayt Ouward, through their houses. By exploring the two families and the architecture of their houses, this paper provides a detailed ethnographic account of historical change in modern Syria, internal diversity, and stratification within the intimate social fabric of the Druze neighbourhood at a time of war, and contributes a relational approach to the anthropological understanding of houses
Ferromagnetic Semiconductors: Moving Beyond (Ga,Mn)As
The recent development of MBE techniques for growth of III-V ferromagnetic
semiconductors has created materials with exceptional promise in spintronics,
i.e. electronics that exploit carrier spin polarization. Among the most
carefully studied of these materials is (Ga,Mn)As, in which meticulous
optimization of growth techniques has led to reproducible materials properties
and ferromagnetic transition temperatures well above 150 K. We review progress
in the understanding of this particular material and efforts to address
ferromagnetic semiconductors as a class. We then discuss proposals for how
these materials might find applications in spintronics. Finally, we propose
criteria that can be used to judge the potential utility of newly discovered
ferromagnetic semiconductors, and we suggest guidelines that may be helpful in
shaping the search for the ideal material.Comment: 37 pages, 4 figure
Temperature-dependent magnetization in diluted magnetic semiconductors
We calculate magnetization in magnetically doped semiconductors assuming a
local exchange model of carrier-mediated ferromagnetic mechanism and using a
number of complementary theoretical approaches. In general, we find that the
results of our mean-field calculations, particularly the dynamical mean field
theory results, give excellent qualitative agreement with the experimentally
observed magnetization in systems with itinerant charge carriers, such as
Ga_{1-x}Mn_xAs with 0.03 < x < 0.07, whereas our percolation-theory-based
calculations agree well with the existing data in strongly insulating
materials, such as Ge_{1-x}Mn_x. We comment on the issue of non-mean-field like
magnetization curves and on the observed incomplete saturation magnetization
values in diluted magnetic semiconductors from our theoretical perspective. In
agreement with experimental observations, we find the carrier density to be the
crucial parameter determining the magnetization behavior. Our calculated
dependence of magnetization on external magnetic field is also in excellent
agreement with the existing experimental data.Comment: 17 pages, 15 figure
c-Src Regulates Akt Signaling in Response to Ghrelin via β-Arrestin Signaling-Independent and -Dependent Mechanisms
The aim of the present study was to identify the signaling mechanisms to ghrelin-stimulated activation of the serine/threonine kinase Akt. In human embryonic kidney 293 (HEK293) cells transfected with GHS-R1a, ghrelin leads to the activation of Akt through the interplay of distinct signaling mechanisms: an early Gi/o protein-dependent pathway and a late pathway mediated by β-arrestins. The starting point is the Gi/o-protein dependent PI3K activation that leads to the membrane recruitment of Akt, which is phosphorylated at Y by c-Src with the subsequent phosphorylation at A-loop (T308) and HM (S473) by PDK1 and mTORC2, respectively. Once the receptor is activated, a second signaling pathway is mediated by β-arrestins 1 and 2, involving the recruitment of at least β-arrestins, c-Src and Akt. This β-arrestin-scaffolded complex leads to full activation of Akt through PDK1 and mTORC2, which are not associated to the complex. In agreement with these results, assays performed in 3T3-L1 preadipocyte cells indicate that β-arrestins and c-Src are implicated in the activation of Akt in response to ghrelin through the GHS-R1a. In summary this work reveals that c-Src is crucially involved in the ghrelin-mediated Akt activation. Furthermore, the results support the view that β-arrestins act as both scaffolding proteins and signal transducers on Akt activation
Recent advances in understanding Cushing disease: resistance to glucocorticoid negative feedback and somatic USP8 mutations
Cushing’s disease is a rare disease with a characteristic phenotype due to significant hypercortisolism driven by over-secretion of adrenocorticotropic hormone and to high morbidity and mortality if untreated. It is caused by a corticotroph adenoma of the pituitary, but the exact mechanisms leading to tumorigenesis are not clear. Recent advances in molecular biology such as the discovery of somatic mutations of the ubiquitin-specific peptidase 8 (USP8) gene allow new insights into the pathogenesis, which could be translated into exciting and much-needed therapeutic applications
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