Comparing DNA enrichment of proliferating cells following administration of different stable isotopes of heavy water.

Deuterated water (HO) is a label commonly used for safe quantitative measurement of deuterium enrichment into DNA of proliferating cells. More recently, it has been used for labeling proteins and other biomolecules. Our in vitro - in vivo research reports important stable isotopic labeling enrichment differences into the DNA nucleosides and their isotopologues (e.

FLT3 ligand regulates thymic precursor cells and hematopoietic stem cells through interactions with CXCR4 and the marrow niche.

Impaired immune reconstitution after hematopoietic stem cell transplantation (HSCT) is attributed in part to impaired thymopoiesis. Recent data suggest that precursor input may be a point of regulation for the thymus. We hypothesized that administration of FLT3 ligand (FLT3L) would enhance thymopoiesis after adoptive transfer of aged, FLT3L-treated bone marrow (BM) to aged, Lupron-treated hosts by increasing murine HSC (LinSca1c-Kit [LSK] cells) trafficking and survival.

Adult Spinal Deformity: Contemporary Treatment and Patient Outcomes.

The incidence of symptomatic adult spinal deformity (ASD) is increasing due to aging of the population, iatrogenic factors, and an increasingly active elderly population. Spinal deformity in the adult population can produce major functional disability. Patients with less severe forms of ASD can generally be managed without operative intervention.

High levels of IL-7 cause dysregulation of thymocyte development.

IL-7 signaling is required for thymocyte development and its loss has a severe deleterious effect on thymus function. Thymocyte-stromal cell interactions and other mechanisms tightly regulate IL-7 expression. We show that disruption of that regulation by over-expression of IL-7 inhibits T-cell development and promotes extensive B-cell lymphopoiesis in the thymus.

An abundance of small exoplanets around stars with a wide range of metallicities.

The abundance of heavy elements (metallicity) in the photospheres of stars similar to the Sun provides a 'fossil' record of the chemical composition of the initial protoplanetary disk. Metal-rich stars are much more likely to harbour gas giant planets, supporting the model that planets form by accumulation of dust and ice particles. Recent ground-based surveys suggest that this correlation is weakened for Neptunian-sized planets.

An in vivo IL-7 requirement for peripheral Foxp3+ regulatory T cell homeostasis.

All T cells are dependent on IL-7 for their development and for homeostasis. Foxp3(+) regulatory T cells (Tregs) are unique among T cells in that they are dependent on IL-2. Whether such IL-2 dependency is distinct from or in addition to an IL-7 requirement has been a confounding issue, particularly because of the absence of an adequate experimental system to address this question.

Antigen-independent differentiation and maintenance of effector-like resident memory T cells in tissues.

Differentiation and maintenance of recirculating effector memory CD8 T cells (T(EM)) depends on prolonged cognate Ag stimulation. Whether similar pathways of differentiation exist for recently identified tissue-resident effector memory T cells (T(RM)), which contribute to rapid local protection upon pathogen re-exposure, is unknown. Memory CD8αβ(+) T cells within small intestine epithelium are well-characterized examples of T(RM), and they maintain a long-lived effector-like phenotype that is highly suggestive of persistent Ag stimulation.

Complications of anterior lumbar surgery.

The incidence of anterior lumbar surgery is increasing. Although adverse events are uncommon, several have been described. Complications can be categorized based on the time of occurrence (ie, intraoperative, postoperative), patient positioning, surgical exposure, and spinal procedure.

Extended high circular polarization in the Orion massive star forming region: implications for the origin of homochirality in the solar system.

We present a wide-field (approximately 6' x 6') and deep near-infrared (K(s) band: 2.14 mum) circular polarization image in the Orion nebula, where massive stars and many low-mass stars are forming. Our results reveal that a high circular polarization region is spatially extended (approximately 0.

Signaling by intrathymic cytokines, not T cell antigen receptors, specifies CD8 lineage choice and promotes the differentiation of cytotoxic-lineage T cells.

Immature CD4(+)CD8(+) (double-positive (DP)) thymocytes are signaled via T cell antigen receptors (TCRs) to undergo positive selection and become responsive to intrathymic cytokines such as interleukin 7 (IL-7). We report here that cytokine signaling is required for positively selected thymocytes to express the transcription factor Runx3, specify CD8 lineage choice and differentiate into cytotoxic-lineage T cells. In DP thymocytes genetically engineered to be cytokine responsive, IL-7 signaling induced TCR-unsignaled DP thymocytes to express Runx3 and to differentiate into mature CD8(+) T cells, completely circumventing positive selection.

Single cell analysis of complex thymus stromal cell populations: rapid thymic epithelia preparation characterizes radiation injury.

Thymic epithelial cells (TECs) and dendritic cells are essential for the maintenance of thymopoiesis. Because these stromal elements define the progenitor niche, provide critical survival signals and growth factors, and direct positive and negative selection, detailed study of these populations is necessary to understand important elements for thymic renewal after cytotoxic injury. Study of TEC is currently hindered by lengthy enzymatic separation techniques with decreased viability.

CCL25 increases thymopoiesis after androgen withdrawal.

Although studies have demonstrated that androgen withdrawal increases thymic size, molecular mechanisms underlying this expansion remain largely unknown. We show that decreased androgen signaling leads to enhanced immigration of bone marrow T-cell precursors, as manifested by both an early increase of early thymic progenitors (ETP) and improved uptake of adoptively transferred quantified precursors into congenic castrated hosts. We provide evidence that the ETP niche is enhanced after androgen withdrawal by proliferation of UEA(+) thymic epithelial cells (TEC) and increased TEC production of CCL25, a ligand critical for ETP entry.

Circular polarimetry reveals helical magnetic fields in the young stellar object HH 135-136.

Magnetic fields are believed to have a vital role in regulating and shaping the flow of material onto and away from protostars during their initial mass accretion phase. It is becoming increasingly accepted that bipolar outflows are generated and collimated as material is driven along magnetic field lines and centrifugally accelerated off a rotating accretion disk. However, the precise role of the magnetic field is poorly understood and evidence for its shape and structure has not been forthcoming.

'Coreceptor tuning': cytokine signals transcriptionally tailor CD8 coreceptor expression to the self-specificity of the TCR.

T cell immunity requires the long-term survival of T cells that are capable of recognizing self antigens but are not overtly autoreactive. How this balance is achieved remains incompletely understood. Here we identify a homeostatic mechanism that transcriptionally tailors CD8 coreceptor expression in individual CD8+ T cells to the self-specificity of their clonotypic T cell receptor (TCR).

TGF-beta regulates pathology but not tissue CD8+ T cell dysfunction during experimental Trypanosoma cruzi infection.

Infection with the protozoan parasite Trypanosoma cruzi leads to chronic infection, with parasite persistence primarily in muscle tissue. CD8(+) T cells isolated from muscle tissue of T. cruzi-infected mice display decreased production of IFN-gamma in response to T cell receptor engagement.

Dysregulation of IL-15-mediated T-cell homeostasis in TGF-beta dominant-negative receptor transgenic mice.

T-cell subpopulations, defined by their expression of CD4, CD8, naive, and memory cell-surface markers, occupy distinct homeostatic compartments that are regulated primarily by cytokines. CD8+ memory T cells, as defined by CD44(hi) surface expression, are dependent on IL-15 as a positive regulator of their homeostatic maintenance. Manipulation of IL-15 signaling through gene aberration, overexpression, or receptor alterations has been shown to dramatically affect T-cell homeostasis, with overexpression leading to fatal leukemia.

B7+ iris pigment epithelium induce CD8+ T regulatory cells; both suppress CTLA-4+ T cells.

Ocular pigment epithelia contribute to immune privilege by suppressing T cell activation and converting T cells into regulatory T regulatory cells (Tregs) that inhibit bystander T cell activation. Iris pigment epithelium (IPE) does so through direct cell-cell contact with naive T cells, and this suppressive contact is via interactions between B7 expressed constitutively on IPE cells and CTLA-4 expressed on a subpopulation of CD8+ T cells. We have now examined whether TGFbeta is required in this process.

TGF-{beta}-dependent CD103 expression by CD8(+) T cells promotes selective destruction of the host intestinal epithelium during graft-versus-host disease.

Destruction of the host intestinal epithelium by donor effector T cell populations is a hallmark of graft-versus-host disease (GVHD), but the underlying mechanisms remain obscure. We demonstrate that CD8(+) T cells expressing CD103, an integrin conferring specificity for the epithelial ligand E-cadherin, play a critical role in this process. A TCR transgenic GVHD model was used to demonstrate that CD103 is selectively expressed by host-specific CD8(+) T cell effector populations (CD8 effectors) that accumulate in the host intestinal epithelium during GVHD.

Ontogeny and regulation of IL-7-expressing thymic epithelial cells.

Epithelial cells in the thymus produce IL-7, an essential cytokine that promotes the survival, differentiation, and proliferation of thymocytes. We identified IL-7-expressing thymic epithelial cells (TECs) throughout ontogeny and in the adult mouse thymus by in situ hybridization analysis. IL-7 expression is initiated in the thymic fated domain of the early primordium by embryonic day 11.

Transforming growth factor-beta pathway serves as a primary tumor suppressor in CD8+ T cell tumorigenesis.

Tumorigenesis in rodents, as well as in humans, has been shown to be a multistep process, with each step reflecting an altered gene product or gene regulatory process leading to autonomy of cell growth. Initial genetic mutations are often associated with dysfunctional growth regulation, as is demonstrated in several transgenic mouse models. These changes are often followed by alterations in tumor suppressor gene function, allowing unchecked cell cycle progression and, by genomic instability, additional genetic mutations responsible for tumor metastasis.

Dynamic regulation of IL-7 receptor expression is required for normal thymopoiesis.

Interleukin-7 receptor (IL-7R) levels are tightly controlled during ontogeny: high on double-negative (DN) cells, absent on double-positive (DP) cells, and high once again on thymocytes undergoing positive selection. To determine if loss of IL-7-mediated survival signals in DP cells is necessary for normal antigen-specific selection, we created T-lineage-specific IL-7R alpha chain (IL-7Ralpha) transgenic (Tg) mice in which IL-7R is expressed throughout ontogeny. There was no effect of the IL-7Ralpha Tg on negative selection.