Omental and pleural milky spots: different reactivity patterns in mice infected with Schistosoma mansoni reveals coelomic compartmentalisation

In vertebrate animals, pleural and peritoneal cavities are repositories of milky spots (MS), which constitute an organised coelom-associated lymphomyeloid tissue that is intensively activated by Schistosoma mansoni infection. This study compared the reactive patterns of peritoneal MS to pleural MS and concluded from histological analysis that they represent independent responsive compartments. Whole omentum, lungs and the entire mediastinum of 54 S. mansoni-infected mice were studied morphologically. The omental MS of infected animals were highly activated, modulating from myeloid-lymphocytic (60 days of infection) to lymphomyeloid (90 days of infection) and lymphocytic or lymphoplasmacytic (160 days of infection) types. The non-lymphoid component predominated in the acute phase of infection and was expressed by monocytopoietic, eosinopoietic and neutropoietic foci, with isolated megakaryocytes and small foci of late normoblasts and mast cells. Nevertheless, pleural or thoracic MS of infected mice were monotonous, consisting of small and medium lymphocytes with few mast and plasma cells and no myeloid component. Our data indicate that compartmentalisation of the MS response is dependent on the lymphatic vascularisation of each coelomic cavity, limiting the effects or consequences of any stimulating or aggressive agents, as is the case with S. mansoni infection

Working conditions as predictors of retirement intentions and exit from paid employment: a 10-year follow-up of the English Longitudinal Study of Ageing

This work was funded by the Economic and Social Research Council and the Medical Research Council as part of the Lifelong Health and Well-Being (LLHW) initiative (grant number ES/L002892/1)

Visual guidance of landing behaviour when stepping down to a new level

When stepping down from one level to another, the leading limb has to arrest downward momentum of the body and subsequently receive and safely support bodyweight before level walking can begin. Such step downs are performed over a wide range of heights and predicting when and where contact between the landing limb and the lower level will be made is likely a critical factor. To determine if visual feedback obtained after movement initiation is habitually used in guiding landing behaviour, the present study determined whether pre-landing kinematics and the mechanics of landing would be modulated according to the type of visual feedback available during the stepping down phase. Ten healthy participants (32.3 ± 7.9 years) stepped, from a standing position, down from three different heights onto a forceplatform, either coming immediately to rest or proceeding directly to walking across the laboratory. Repeated trials were undertaken under habitual vision conditions or with vision blurred or occluded 2¿3 s prior to movement initiation. Pre-landing kinematics were assessed by determining, for the instant of landing, lead-limb knee and ankle angle, stepping distance, forwards positioning of the body CM within the base of support and the forwards and downwards body CM velocity. Landing mechanics for the initial contact period were characterized using lead limb vertical loading and stiffness, and trail limb un-weighting. When vision was occluded movement time, ankle plantarflexion and knee flexion were significantly increased compared to that determined for habitual vision, whereas forwards body CM positioning and velocity, vertical loading and stiffness, and trail limb un-weighting, were significantly reduced (p < 0.05). Similar adaptations were observed under blurred conditions, although to a lesser extent. Most variables were significantly affected by stepping task and step height. Subjects likely reduced forwards CM position and velocity at instant of landing, in order to keep the CM well away from the anterior border of the base of support, presumably to ensure boundary margins of safety were high should landing occur sooner or later than expected. The accompanying increase in ankle plantarflexion at instant of landing, and increase in single limb support time, suggests that subjects tended to probe for the ground with their lead limb under modified vision conditions. They also had more bodyweight on the trail limb at the end of the initial contact period and as a consequence had a prolonged weight transfer time. These findings indicate that under blurred or occluded vision conditions subjects adopted a cautious strategy where by they ¿sat back¿ on their trail limb and used their lead limb to probe for the ground. Hence, they did not fully commit to weight transfer until somatosensory feedback from the lead limb confirmed they had safely made contact. The effect of blurring vision was not identical to occluding vision, and led to several important differences between these conditions consistent with the use of impoverished visual information on depth. These findings indicate that online vision is customarily used to regulate landing behaviour when stepping down

The Nrf2 transcription factor is a positive regulator of myeloid differentiation of acute myeloid leukemia cells

1α,25-dihydroxyvitamin D3 (1,25D) is a powerful differentiation agent, which has potential for treatment of acute myeloid leukemia (AML), but induces severe hypercalcemia at pharmacologically active doses. We have previously shown that carnosic acid (CA), the polyphenolic antioxidant from rosemary plant, markedly potentiates differentiation induced by low concentrations of 1,25D in human AML cell lines. Here, we demonstrated similar enhanced differentiation responses to the 1,25D/CA combination in primary leukemic cells derived from patients with AML, and determined the role of the Nrf2/antioxidant response element (Nrf2/ARE) pathway in these effects using U937 human monoblastic leukemia cells as the model. CA strongly transactivated the ARE-luciferase reporter gene, induced the ARE-responsive genes, NADP(H)-quinone oxidoreductase and the γ-glutamylcysteine synthetase heavy subunit, and elevated cellular glutathione levels. Interestingly, 1,25D potentiated the effects of CA on these activities. Stable transfection of wild-type (wt) Nrf2 resulted in the enhancement, while transfection of dominant-negative (dn) Nrf2 produced suppression of differentiation induced by the 1,25D/CA combination and, surprisingly, by 1,25D alone. These opposite effects were associated with a corresponding increase or decrease in vitamin D receptor and retinoid X receptor-α protein levels, and in vitamin D responsive element transactivation. Cells transfected with wtNrf2 and dnNrf2 also displayed opposing changes in the levels of the AP-1 family proteins (c-Jun and ATF2) and AP-1 transcriptional activity. Pretreatment with AP-1 decoy oligodeoxynucleotide markedly attenuated the differentiation in wtNrf2-transfected cells, suggesting that the pro-differentiation action of Nrf2 is mediated by functional AP-1. Our findings suggest that the Nrf2/ARE pathway plays an important part in the cooperative induction of myeloid leukemia cell differentiation by 1,25D and a plant polyphenol