Migration patterns of dendritic cells in the mouse. Traffic from the blood, and T cell-dependent and -independent entry to lymphoid tissues.

Dendritic cells (DC) are critical accessory cells for primary immune responses and they may be important stimulators of transplantation reactions, but little is known of their traffic into the tissues. We have studied the migration of purified splenic DC and T lymphocytes, labeled with 111Indium-tropolone, in syngeneic and allogeneic mice. First we demonstrate that DC can migrate from the blood into some lymphoid and nonlymphoid tissues. Immediately after intravenous administration, radio-labeled DC were sequestered in the lungs, but they actively migrated into the liver and spleen and reached equilibrium levels between 3 and 24 h after transfer. At least half of the radiolabel accumulated in the liver, but the spleen was the principal site of DC localization in terms of specific activity (radiolabel per weight of tissue). DC were unable to enter Peyer's patches, or mesenteric and other peripheral lymph nodes from the bloodstream. This was also true in splenectomized recipients, where the otherwise spleen-seeking DC were quantitatively diverted to the liver. In contrast, T cells homed readily to the spleen and lymph nodes of normal mice and increased numbers were present in these tissues in splenectomized mice. Thus, unlike T cells, DC cannot recirculate from blood to lymph via the nodes. We then show that migration of DC from the blood into the spleen is dependent on the presence of T cells: DC did not enter the spleens of nude mice, but when they were reconstituted with T cells the numbers entering the spleen resembled those in euthymic mice. In nude mice, as in splenectomized recipients, the DC that would normally enter the spleen were quantitatively diverted to the liver. These findings suggest that there is a spleen-liver equilibrium for DC, that may be akin to that existing between spleen and lymph node for T cells. Finally, we followed the traffic of radiolabeled DC via the afferent lymphatics after subcutaneous footpad inoculation. DC accumulated in the popliteal nodes but did not migrate further to the inguinal nodes. There was no difference between euthymic and nude mice, showing that unlike traffic to the spleen, this route probably does not require T cells. These migration patterns were not affected by major histocompatibility barriers, and were only seen with viable, but not glutaraldehyde-fixed, DC.(ABSTRACT TRUNCATED AT 400 WORDS

Migration patterns of dendritic cells in the mouse. Homing to T cell-dependent areas of spleen, and binding within marginal zone.

Using quantitative techniques we have shown elsewhere that dendritic cells (DC) migrate from blood into the spleen, under the control of T cells. Here we traced the localization of DC within the spleen and sought to explain the means by which they entered. DC were labeled with a fluorochrome, Hoescht 33342, and injected intravenously. Spleens were removed 3 or 24 h later and DC were visualized within particular areas that were defined by mAbs and FITC anti-Igs. At 3 h most DC were in the red pulp, whereas by 24 h the majority had homed to T-dependent areas of the white pulp and may have become interdigitating cells. Lymphoid DC, isolated from spleen and perhaps normally present in blood, may thus be a migratory stage distinct from the relatively fixed interdigitating cells. We also developed a frozen section assay to investigate the interaction of DC with various lymphoid elements. When DC were incubated on sections of spleen, at 37 degrees C but not at 4 degrees C they attached specifically within the marginal zone and did not bind to T areas; in contrast, macrophages attached only to red pulp and T cells did not bind specifically. However, DC did not bind to sections of mesenteric lymph node, whereas T cells localized in particular regions at 4 degrees C but not at 37 degrees C, probably the high endothelial venules. DC may thus express "homing receptors," similar to those of T cells, for certain endothelia. We propose that T cells can modify the vascular endothelium in certain areas to allow egress of DC from the bloodstream

Direct imaging of short-range order and its impact on deformation in Ti-6Al.

Chemical short-range order (SRO) within a nominally single-phase solid solution is known to affect the mechanical properties of alloys. While SRO has been indirectly related to deformation, direct observation of the SRO domain structure, and its effects on deformation mechanisms at the nanoscale, has remained elusive. Here, we report the direct observation of SRO in relation to deformation using energy-filtered imaging in a transmission electron microscope (TEM). The diffraction contrast is enhanced by reducing the inelastically scattered electrons, revealing subnanometer SRO-enhanced domains. The destruction of these domains by dislocation planar slip is observed after ex situ and in situ TEM mechanical testing. These results confirm the impact of SRO in Ti-Al alloys on the scale of angstroms. The direct confirmation of SRO in relationship to dislocation plasticity in metals can provide insight into how the mechanical behavior of concentrated solid solutions by the material's thermal history

Mapping the complete glycoproteome of virion-derived HIV-1 gp120 provides insights into broadly neutralizing antibody binding

The surface envelope glycoprotein (SU) of Human immunodeficiency virus type 1 (HIV-1), gp120SU plays an essential role in virus binding to target CD4+ T-cells and is a major vaccine target. Gp120 has remarkably high levels of N-linked glycosylation and there is considerable evidence that this “glycan shield” can help protect the virus from antibody-mediated neutralization. In recent years, however, it has become clear that gp120 glycosylation can also be included in the targets of recognition by some of the most potent broadly neutralizing antibodies. Knowing the site-specific glycosylation of gp120 can facilitate the rational design of glycopeptide antigens for HIV vaccine development. While most prior studies have focused on glycan analysis of recombinant forms of gp120, here we report the first systematic glycosylation site analysis of gp120 derived from virions produced by infected T lymphoid cells and show that a single site is exclusively substituted with complex glycans. These results should help guide the design of vaccine immunogens

Mixed pathologies including chronic traumatic encephalopathy account for dementia in retired Association football (soccer) players

In retired professional Association football (soccer) players with a past history of repetitive head impacts, chronic traumatic encephalopathy (CTE) is a potential neurodegenerative cause of dementia and motor impairments. From 1980 to 2010, 14 retired footballers with dementia were followed up regularly until death. Their clinical data, playing career and concussion history were prospectively collected. Next-of-kin consented for six to have post-mortem brain examination. Of the 14 male participants, 13 were professional and 1 was a committed amateur. All were skilled headers of the ball and had played football for an average of 26 years. Concussion rate was limited in six cases to one episode each during their careers. All cases developed progressive cognitive impairment with an average age at onset of 63.6 years and disease duration of 10 years. Neuropathological examination revealed septal abnormalities in all six post-mortem cases, supportive of a history of chronic repetitive head impacts. Four cases had pathologically confirmed CTE; concomitant pathologies included Alzheimer’s disease (N=6), TDP-43 (N=6), cerebral amyloid angiopathy (N=5), hippocampal sclerosis (N=2), corticobasal degeneration (N=1), dementia with Lewy bodies (N=1) and vascular pathology (N=1), all would have contributed synergistically to the clinical manifestations. The pathological diagnosis of CTE was established in four individuals according to the latest consensus diagnostic criteria. This finding is probably related to their past prolonged exposure to repetitive head impacts from head-to-player collisions and heading the ball thousands of time throughout their careers. Alzheimer’s disease and TDP-43 pathologies are common concomitant findings in CTE, both of which are increasingly considered as part of the CTE pathological entity in older individuals. Association Football is the most popular sport in the world and the potential link between repetitive head impacts from playing football and CTE as indicated from our findings is of considerable public health interest. Clearly a definitive link cannot be established in this clinico-pathological series, but our findings support the need for further systematic investigation including large scale case-control studies to identify at risk groups of footballers which will justify for the implementation of protective strategies

Haptic guidance improves the visuo-manual tracking of trajectories

BACKGROUND: Learning to perform new movements is usually achieved by following visual demonstrations. Haptic guidance by a force feedback device is a recent and original technology which provides additional proprioceptive cues during visuo-motor learning tasks. The effects of two types of haptic guidances-control in position (HGP) or in force (HGF)-on visuo-manual tracking ("following") of trajectories are still under debate. METHODOLOGY/PRINCIPALS FINDINGS: Three training techniques of haptic guidance (HGP, HGF or control condition, NHG, without haptic guidance) were evaluated in two experiments. Movements produced by adults were assessed in terms of shapes (dynamic time warping) and kinematics criteria (number of velocity peaks and mean velocity) before and after the training sessions. CONCLUSION/SIGNIFICANCE: These results show that the addition of haptic information, probably encoded in force coordinates, play a crucial role on the visuo-manual tracking of new trajectories

Small-sided soccer in school reduces postprandial lipaemia in adolescent boys

Purpose: While laboratory based moderate- to high-intensity exercise reduces postprandial lipaemia in adolescents this exercise differs to the free-living physical activities in which young people typically engage. This study compared the effect of free-living afterschool soccer activity and treadmill exercise on in-school postprandial lipaemia in adolescent boys. Methods: Fifteen boys (12.6 (0.5) years) completed three, 2-day experimental trials. On Day 1, participants either: rested (CON); exercised for 48 min on a treadmill at 60% peak V[Combining Dot Above]O2 (TM); played 48 min of 5-a-side soccer (SOC). On Day 2, participants attended school where a capillary blood sample determined fasting triacylglycerol ([TAG]) and glucose ([glucose]) concentrations. Participants then consumed a standardised breakfast (0 h) and lunch (4.5 h) and blood samples were taken postprandially at 2.5, 5.0 and 7.0 h. Results: Reductions in fasting [TAG] were small-moderate after TM (-16%, 95% CI = -27 to -2%, ES = 0.46), but large after SOC (-30%, 95% CI = -40 to -20%, ES = 1.00) compared with CON; the concentration was also lower in SOC compared with TM (-18%, 95% CI = -29 to -5%, ES = 0.53). Based on ratios of geometric means, the area under the TAG versus time curve was 18% lower after TM (95% CI = -29 to -5%, ES = 0.51) and 25% lower after SOC (95% CI = -35 to -13%, ES = 0.76,) compared with CON. In contrast, SOC and TM were not significantly different (-9%, 95% CI = -21 to 5%, ES = 0.25). Conclusion: Compared with duration-matched inactivity (CON), after-school small sided soccer (SOC) and treadmill exercise (TM) resulted in a similar, moderate reduction of postprandial lipaemia in adolescent boys

A gentle introduction to the functional renormalization group: the Kondo effect in quantum dots

The functional renormalization group provides an efficient description of the interplay and competition of correlations on different energy scales in interacting Fermi systems. An exact hierarchy of flow equations yields the gradual evolution from a microscopic model Hamiltonian to the effective action as a function of a continuously decreasing energy cutoff. Practical implementations rely on suitable truncations of the hierarchy, which capture nonuniversal properties at higher energy scales in addition to the universal low-energy asymptotics. As a specific example we study transport properties through a single-level quantum dot coupled to Fermi liquid leads. In particular, we focus on the temperature T=0 gate voltage dependence of the linear conductance. A comparison with exact results shows that the functional renormalization group approach captures the broad resonance plateau as well as the emergence of the Kondo scale. It can be easily extended to more complex setups of quantum dots.Comment: contribution to Les Houches proceedings 2006, Springer styl