The Rules of Human T Cell Fate in vivo.

The processes governing lymphocyte fate (division, differentiation, and death), are typically assumed to be independent of cell age. This assumption has been challenged by a series of elegant studies which clearly show that, for murine cells in vitro, lymphocyte fate is age-dependent and that younger cells (i.e., cells which have recently divided) are less likely to divide or die. Here we investigate whether the same rules determine human T cell fate in vivo. We combined data from in vivo stable isotope labeling in healthy humans with stochastic, agent-based mathematical modeling. We show firstly that the choice of model paradigm has a large impact on parameter estimates obtained using stable isotope labeling i.e., different models fitted to the same data can yield very different estimates of T cell lifespan. Secondly, we found no evidence in humans in vivo to support the model in which younger T cells are less likely to divide or die. This age-dependent model never provided the best description of isotope labeling; this was true for naïve and memory, CD4+ and CD8+ T cells. Furthermore, this age-dependent model also failed to predict an independent data set in which the link between division and death was explored using Annexin V and deuterated glucose. In contrast, the age-independent model provided the best description of both naïve and memory T cell dynamics and was also able to predict the independent dataset

Human Stem Cell-like Memory T Cells Are Maintained in a State of Dynamic Flux.

Adaptive immunity requires the generation of memory T cells from naive precursors selected in the thymus. The key intermediaries in this process are stem cell-like memory T (TSCM) cells, multipotent progenitors that can both self-renew and replenish more differentiated subsets of memory T cells. In theory, antigen specificity within the TSCM pool may be imprinted statically as a function of largely dormant cells and/or retained dynamically by more transitory subpopulations. To explore the origins of immunological memory, we measured the turnover of TSCM cells in vivo using stable isotope labeling with heavy water. The data indicate that TSCM cells in both young and elderly subjects are maintained by ongoing proliferation. In line with this finding, TSCM cells displayed limited telomere length erosion coupled with high expression levels of active telomerase and Ki67. Collectively, these observations show that TSCM cells exist in a state of perpetual flux throughout the human lifespan

Primary skin fibroblasts as a model of Parkinson's disease

Parkinson's disease is the second most frequent neurodegenerative disorder. While most cases occur sporadic mutations in a growing number of genes including Parkin (PARK2) and PINK1 (PARK6) have been associated with the disease. Different animal models and cell models like patient skin fibroblasts and recombinant cell lines can be used as model systems for Parkinson's disease. Skin fibroblasts present a system with defined mutations and the cumulative cellular damage of the patients. PINK1 and Parkin genes show relevant expression levels in human fibroblasts and since both genes participate in stress response pathways, we believe fibroblasts advantageous in order to assess, e.g. the effect of stressors. Furthermore, since a bioenergetic deficit underlies early stage Parkinson's disease, while atrophy underlies later stages, the use of primary cells seems preferable over the use of tumor cell lines. The new option to use fibroblast-derived induced pluripotent stem cells redifferentiated into dopaminergic neurons is an additional benefit. However, the use of fibroblast has also some drawbacks. We have investigated PARK6 fibroblasts and they mirror closely the respiratory alterations, the expression profiles, the mitochondrial dynamics pathology and the vulnerability to proteasomal stress that has been documented in other model systems. Fibroblasts from patients with PARK2, PARK6, idiopathic Parkinson's disease, Alzheimer's disease, and spinocerebellar ataxia type 2 demonstrated a distinct and unique mRNA expression pattern of key genes in neurodegeneration. Thus, primary skin fibroblasts are a useful Parkinson's disease model, able to serve as a complement to animal mutants, transformed cell lines and patient tissues

Evidence for the η_b(1S) Meson in Radiative Υ(2S) Decay

We have performed a search for the η_b(1S) meson in the radiative decay of the Υ(2S) resonance using a sample of 91.6 × 10^6 Υ(2S) events recorded with the BABAR detector at the PEP-II B factory at the SLAC National Accelerator Laboratory. We observe a peak in the photon energy spectrum at E_γ = 609.3^(+4.6)_(-4.5)(stat)±1.9(syst) MeV, corresponding to an η_b(1S) mass of 9394.2^(+4.8)_(-4.9)(stat) ± 2.0(syst) MeV/c^2. The branching fraction for the decay Υ(2S) → γη_b(1S) is determined to be [3.9 ± 1.1(stat)^(+1.1)_(-0.9)(syst)] × 10^(-4). We find the ratio of branching fractions B[Υ(2S) → γη_b(1S)]/B[Υ(3S) → γη_b(1S)]= 0.82 ± 0.24(stat)^(+0.20)_(-0.19)(syst)

Artistas sobre outras obras

A pós modernidade encerra a interrogação crítica do homem sobre o homem: a linguagem ameaça o que é significante, o que é corpo. O sujeito é falado, e assim constituído depois da linguagem (Althusser, 1976). O jovem Arthur Rimbaud sintetiza-o, aos dezassete anos, numa carta ao seu professor de retórica Georges Izambard, datada de 13 de maio 1871: «C’est faux de dire: je pense: on devrait dire on me pense. Pardon du jeu de mots. Je est un autre». (Rimbaud, 1999: 237) A identidade resiste à linguagem dos homens. A linguagem é transmitida entre as gerações e com ela transporta os sujeitos, ou, o que é dizer o mesmo, a possível interrogação: quem me fala? É esta também a perplexidade que motivou o tema desta revista Estúdio. Reuniram-se, nesta edição, 22 artigos, provenientes de diferentes autores da Argentina, Brasil, Portugal e Espanha, que se debruçam sobre artistas cuja identidade se mostra e merece ser interrogada: são espaços ‘ex-cêntricos,’ para se descobrir.info:eu-repo/semantics/publishedVersio

Evidence for X(3872) → Ψ (2S)y in B^± → X(3872)K^± Decays and a Study of B → ccyK

In a search for B → ccyK decays with the BABAR detector, where cc includes J/Ψ and Ψ (2S), and K includes K^±, K^0_S , and K^*(892), we find evidence for X(3872) → J/Ψy and X(3872) → Ψ (2S) with 3:6σ and 3:5σ significance, respectively. We measure the product of branching fractions B(B^± → X(3872)K^±)B(X(3872) → J/Ψy)= [2:8 ± 0:8(stat) ± 0:1(syst)]X 10^(-6) and B(B^± → X(3872)K^±) X B(X(3872) → Ψ (2S)y) = [9:5 ± 2:7(stat) ± 0:6(syst)] X 10^(-6)

Measurement of D^0-D̅ ^0 Mixing from a Time-Dependent Amplitude Analysis of D^0→K^+π^-π^0 Decays

We present evidence of D^0-D̅ ^0 mixing using a time-dependent amplitude analysis of the decay D^0→K^+π^-π^0 in a data sample of 384  fb^(-1) collected with the BABAR detector at the PEP-II e^+e^- collider at the Stanford Linear Accelerator Center. Assuming CP conservation, we measure the mixing parameters x_(Kππ)^(0′)=[2.61_(-0.68)^(+0.57)(stat)±0.39(syst)]%, y_(Kππ)^(0′)=[-0.06_(-0.64)^(+0.55)(stat)±0.34(syst)]%. This result is inconsistent with the no-mixing hypothesis with a significance of 3.2 standard deviations. We find no evidence of CP violation in mixing

Player migration and opportunity: examining the efficacy of the UEFA home-grown rule in six European football leagues.

The introduction of UEFAs home-grown rule occurred for the start of the 2006–2007 season with the full quota in place from the 2008–2009 season, which imposed quotas on European clubs. From 2008, clubs are required to have at least 8 players classified as home-grown in the 25-player squad, up from 4 in 2006–2007 and 6 in 2007–2008. This study examines the efficacy of this rule across the six major European leagues (England, France, Germany, Holland, Italy and Spain) in relation to playing opportunities (minutes played and appearances) between 1999 and 2015. This was also examined in relation to age. Since the home-grown rule was introduced for the six nations hosting the major leagues, the rule had different impacts by nationality. Only Germany saw significant increases in the proportion of minutes played by their players when comparing the periods before and after the home-grown rules were imposed. Holland, albeit seeing a slight decrease overall, saw significant increases for playing time for under 21s and 22- to 25-year olds. England and Italy were the two nations where statistically significant decreases in indigenous playing opportunities were recorded since the home-grown rules were introduced

Constraints on the CKM angle gamma in B^0-->[overline D]0K^(*0) and B^0-->D^0K^(*0) from a Dalitz analysis of D^0 and [overline D]^0 decays to K_Sπ^+π^-

We present constraints on the angle gamma of the unitarity triangle with a Dalitz analysis of neutral D decays to K_Sπ^+π^- from the processes B^0-->[overline D]^0K^(*0) ([overline B]^0-->D^0[overline K]^(*0)) and B^0-->D^0K^(*0) ([overline B]^0-->[overline D]^0[overline K]^(*0)) with K^(*0)-->K^+π^- ([overline K]^(*0)-->K-π^+). Using a sample of 371×10^6 B[overline B] pairs collected with the BABAR detector at PEP-II, we constrain the angle gamma as a function of r_S, the magnitude of the average ratio between b-->u and b-->c amplitudes