1,269 research outputs found
Alloactivation of naïve CD4<sup>+</sup> CD8<sup>−</sup> CD25<sup>+</sup>T regulatory cells: Expression of CD8α identifies potent suppressor cells that can promote transplant tolerance induction
Therapy with alloantigen-specific CD4+ CD25+ T regulatory cells (Treg) for induction of transplant tolerance is desirable, as naïve thymic Treg (tTreg) are not alloantigen-specific and are weak suppressor cells. Naïve tTreg from DA rats cultured with fully allogeneic PVG stimulator cells in the presence of rIL-2 express IFN-gamma receptor (IFNGR) and IL-12 receptor beta2 (IL-12Rβ2) and are more potent alloantigen-specific regulators that we call Ts1 cells. This study examined additional markers that could identify the activated alloantigen-specific Treg as a subpopulation within the CD4+ CD25+ Foxp3+ Treg. After culture of naïve DA CD4+ CD8− CD25+ T cells with rIL-2 and PVG alloantigen, or rIL-2 without alloantigen, CD8α was expressed on 10–20% and CD8β on <5% of these cells. These cells expressed ifngr and Il12rb2. CD8α+ cells had increased Ifngr that characterizes Ts1 cells as well was Irf4, a transcription factor induced by TCR activation. Proliferation induced by re-culture with rIL-12 and alloantigen was greater with CD4+ CD8α+ CD25+ Treg consistent with the CD8α+ cells expressing IL-12R. In MLC, the CD8α+ fraction suppressed responses against allogeneic stimulators more than the mixed Ts1 population, whereas the CD4+ CD8− CD25+ T cells were less potent. In an adoptive transfer assay, rIL-2 and alloantigen activated Treg suppress rejection at a ratio of 1:10 with naïve effector cells, whereas alloantigen and rIL-2 activated tTreg depleted of the CD8α+ cells were much less effective. This study demonstrated that expression of CD8α by rIL-2 and alloantigen activation of CD4+ CD8− CD25+ Foxp3+ T cells was a marker of activated and potent Treg that included alloantigen-specific Treg
Characteristic Evolution and Matching
I review the development of numerical evolution codes for general relativity
based upon the characteristic initial value problem. Progress in characteristic
evolution is traced from the early stage of 1D feasibility studies to 2D
axisymmetric codes that accurately simulate the oscillations and gravitational
collapse of relativistic stars and to current 3D codes that provide pieces of a
binary black hole spacetime. Cauchy codes have now been successful at
simulating all aspects of the binary black hole problem inside an artificially
constructed outer boundary. A prime application of characteristic evolution is
to extend such simulations to null infinity where the waveform from the binary
inspiral and merger can be unambiguously computed. This has now been
accomplished by Cauchy-characteristic extraction, where data for the
characteristic evolution is supplied by Cauchy data on an extraction worldtube
inside the artificial outer boundary. The ultimate application of
characteristic evolution is to eliminate the role of this outer boundary by
constructing a global solution via Cauchy-characteristic matching. Progress in
this direction is discussed.Comment: New version to appear in Living Reviews 2012. arXiv admin note:
updated version of arXiv:gr-qc/050809
Does caffeine ingestion before a short-term sprint interval training promote body fat loss?
We investigated the effect of caffeine ingestion combined with a 2-wk sprint interval training (SIT) on training-induced reductions in body adiposity. Twenty physically-active men ingested either 5 mg/kg of cellulose as a placebo (PLA, n=10) or 5 mg/kg of caffeine (CAF, n=10) 60 min before each SIT session (13×30 s sprint/15 s of rest). Body mass and skinfold thickness were measured pre- and post-training. Energy expenditure was measured at rest, during exercise, and 45 min after exercise in the first SIT session. Body fat was similar between PLA and CAF groups at pre-training (P\u3e0.05). However, there was a significant decrease in body fat after training in the CAF group (−5.9±4.2%, P\u3c0.05) but not in PLA (1.5±8.0%, P\u3e0.05). There was no difference in energy expenditure at rest and during exercise between PLA and CAF groups (P\u3e0.05), but the post-exercise energy expenditure was 18.3±21.4% greater in the CAF than in the PLA group (P\u3c0.05). In conclusion, caffeine ingestion before SIT sessions induced a body fat loss that may be associated with higher post-exercise energy expenditure
Postcopulatory sexual selection
The female reproductive tract is where competition between the sperm of different males takes place, aided and abetted by the female herself. Intense postcopulatory sexual selection fosters inter-sexual conflict and drives rapid evolutionary change to generate a startling diversity of morphological, behavioural and physiological adaptations. We identify three main issues that should be resolved to advance our understanding of postcopulatory sexual selection. We need to determine the genetic basis of different male fertility traits and female traits that mediate sperm selection; identify the genes or genomic regions that control these traits; and establish the coevolutionary trajectory of sexes
Warped Riemannian metrics for location-scale models
The present paper shows that warped Riemannian metrics, a class of Riemannian
metrics which play a prominent role in Riemannian geometry, are also of
fundamental importance in information geometry. Precisely, the paper features a
new theorem, which states that the Rao-Fisher information metric of any
location-scale model, defined on a Riemannian manifold, is a warped Riemannian
metric, whenever this model is invariant under the action of some Lie group.
This theorem is a valuable tool in finding the expression of the Rao-Fisher
information metric of location-scale models defined on high-dimensional
Riemannian manifolds. Indeed, a warped Riemannian metric is fully determined by
only two functions of a single variable, irrespective of the dimension of the
underlying Riemannian manifold. Starting from this theorem, several original
contributions are made. The expression of the Rao-Fisher information metric of
the Riemannian Gaussian model is provided, for the first time in the
literature. A generalised definition of the Mahalanobis distance is introduced,
which is applicable to any location-scale model defined on a Riemannian
manifold. The solution of the geodesic equation is obtained, for any Rao-Fisher
information metric defined in terms of warped Riemannian metrics. Finally,
using a mixture of analytical and numerical computations, it is shown that the
parameter space of the von Mises-Fisher model of -dimensional directional
data, when equipped with its Rao-Fisher information metric, becomes a Hadamard
manifold, a simply-connected complete Riemannian manifold of negative sectional
curvature, for . Hopefully, in upcoming work, this will be
proved for any value of .Comment: first version, before submissio
Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity.
Most monogenic cases of obesity in humans have been linked to mutations in genes encoding members of the leptin-melanocortin pathway. Specifically, mutations in MC4R, the melanocortin-4 receptor gene, account for 3-5% of all severe obesity cases in humans1-3. Recently, ADCY3 (adenylyl cyclase 3) gene mutations have been implicated in obesity4,5. ADCY3 localizes to the primary cilia of neurons 6 , organelles that function as hubs for select signaling pathways. Mutations that disrupt the functions of primary cilia cause ciliopathies, rare recessive pleiotropic diseases in which obesity is a cardinal manifestation 7 . We demonstrate that MC4R colocalizes with ADCY3 at the primary cilia of a subset of hypothalamic neurons, that obesity-associated MC4R mutations impair ciliary localization and that inhibition of adenylyl cyclase signaling at the primary cilia of these neurons increases body weight. These data suggest that impaired signaling from the primary cilia of MC4R neurons is a common pathway underlying genetic causes of obesity in humans
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