The Contribution of Diet and Genotype to Iron Status in Women: A Classical Twin Study

This is the first published report examining the combined effect of diet and genotype on body iron content using a classical twin study design. The aim of this study was to determine the relative contribution of genetic and environmental factors in determining iron status. The population was comprised of 200 BMI- and age-matched pairs of MZ and DZ healthy twins, characterised for habitual diet and 15 iron-related candidate genetic markers. Variance components analysis demonstrated that the heritability of serum ferritin (SF) and soluble transferrin receptor was 44% and 54% respectively. Measured single nucleotide polymorphisms explained 5% and selected dietary factors 6% of the variance in iron status; there was a negative association between calcium intake and body iron (p = 0.02) and SF (p = 0.04).     

Splenocytes Seed Bone Marrow of Myeloablated Mice: Implication for Atherosclerosis

Extramedullary hematopoiesis has been shown to contribute to the pathogenesis of a variety of diseases including cardiovascular diseases. In this process, the spleen is seeded with mobilized bone marrow cells that augment its hematopoietic ability. It is unclear whether these immigrant cells that are produced/reprogrammed in spleen are similar or different from those found in the bone marrow. To begin to understand this, we investigated the relative potency of adult splenocytes per se to repopulate bone marrow of lethally-irradiated mice and its functional consequences in atherosclerosis. The splenocytes were harvested from GFP donor mice and transplanted into myeloablated wild type recipient mice without the inclusion of any bone marrow helper cells. We found that adult splenocytes repopulated bone marrow of myeloablated mice and the transplanted cells differentiated into a full repertoire of myeloid cell lineages. The level of monocytes/macrophages in the bone marrow of recipient mice was dependent on the cell origin, i.e., the donor splenocytes gave rise to significantly more monocytes/macrophages than the donor bone marrow cells. This occurred despite a significantly lower number of hematopoietic stem cells being present in the donor splenocytes when compared with donor bone marrow cells. Atherosclerosis studies revealed that donor splenocytes displayed a similar level of atherogenic and atheroprotective activities to those of donor bone marrow cells. Cell culture studies showed that the phenotype of macrophages derived from spleen is different from those of bone marrow. Together, these results demonstrate that splenocytes can seed bone marrow of myeloablated mice and modulate atherosclerosis. In addition, our study shows the potential of splenocytes for therapeutic interventions in inflammatory disease.     

Immunology of pregnancy: cellular mechanisms allowing fetal survival within the maternal uterus

Pregnancy success remains a fascinating phenomenon to immunologists as it defies the immunological rules of rejection. Although it was previously thought that the maternal immune system does not see the fetus, it is now well documented that fetal cells reach the maternal body and encounter host immune cells. Natural tolerance mechanisms following this interaction remain to be fully elucidated. This article reviews the current literature on mechanisms of adaptive immunity, with emphasis on regulatory T cells and heme oxygenase 1 (HO-1). We propose a scenario in which regulatory T cells create a tolerant microenvironment at the fetal-maternal interface characterised by the presence of tolerance-associated molecules such as HO-1, which has been shown to be of vital importance for fetal survival.     

Getting the right stuff： controlling neural stem cell state and fate in vivo and in vitro with biomaterials

Stem cell therapy holds great promises in medical treatment by, e.g., replacing lost cells, re-constitute healthy cell populations and also in the use of stem cells as vehicles for factor and gene delivery. Embryonic stem cells have rightfully attracted a large interest due to their proven capacity of differentiating into any cell type in the embryo in vivo. Tissue-specific stem ceils are however already in use in medical practice, and recently the first systematic medical trials involving human neural stem cell （NSC） therapy have been launched. There are yet many obstacles to overcome and procedures to improve. To ensure progress in the medical use of stem cells increased basic knowledge of the molecular mechanisms that govern stem cell characteristics is necessary. Here we provide a review of the literature on NSCs in various aspects of cell therapy, with the main focus on the potential of using biomaterials to control NSC characteristics, differentiation, and delivery. We summarize results from studies on the characteristics of endogenous and transplanted NSCs in rodent models of neurological and cancer diseases, and highlight recent advancements in polymer compatibility and applicability in regulating NSC state and fate. We suggest that the development of specially designed polymers, such as hydrogels, is a crucial issue to improve the outcome of stem cell therapy in the central nervous system.     

Production of xylanase and protease by Penicillium janthinellum CRC 87M-115 from different agricultural wastes

Five agricultural wastes were evaluated in submerged fermentation for xylanolytic enzymes production by Penicillium janthinellum. The wastes were hydrolyzed in acid medium and the liquid fraction was used for cultivation. Corn cob (55.3 U/mL) and oat husk (54.8 U/mL) were the best inducers of xylanase. Sugar cane bagasse (23.0 U/mL) and corn husk (23.8 U/mL) were moderately good, while cassava peel was negligible. Protease production was very low in all agro-industrial residues. The maximum biomass yields were 1.30 and 1.17 g/L for cassava peel and corn husk after 180 h, respectively. Xylanolytic activity showed a cell growth associated profile.     

IgE-dependent activation of sphingosine kinases 1 and 2 and secretion of sphingosine 1-phosphate requires Fyn kinase and contributes to mast cell responses

Engagement of the high affinity receptor for IgE (FcepsilonRI) on mast cells results in the production and secretion of sphingosine 1-phosphate (S1P), a lipid metabolite present in the lungs of allergen-challenged asthmatics. Herein we report that two isoforms of sphingosine kinase (SphK1 and SphK2) are expressed and activated upon FcepsilonRI engagement of bone marrow-derived mast cells (BMMC). Fyn kinase is required for FcepsilonRI coupling to SphK1 and -2 and for subsequent S1P production. Normal activation of SphK1 and -2 was restored by expression of wild type Fyn but only partly with a kinase-defective Fyn, indicating that induction of SphK1 and SphK2 depended on both catalytic and noncatalytic properties of Fyn. Downstream of Fyn, the requirements for SphK1 activation differed from that of SphK2. Whereas SphK1 was considerably dependent on the adapter Grb2-associated binder 2 and phosphatidylinositol 3-OH kinase, SphK2 showed minimal dependence on these molecules. Fyn-deficient BMMC were defective in chemotaxis and, as previously reported, in degranulation. These functional responses were partly reconstituted by the addition of exogenous S1P to FcepsilonRI-stimulated cells. Taken together with our previous study, which demonstrated delayed SphK activation in Lyn-deficient BMMC, we propose a cooperative role between Fyn and Lyn kinases in the activation of SphKs, which contributes to mast cell responses.     

Vanadium derivatives act as growth factor — mimetic compounds upon differentiation and proliferation of osteoblast-like UMR106 cells

The effect of different vanadium compounds on proliferation and differentiation was examined in osteoblast-like UMR106 cells. Vanadate increased the cell growth in a biphasic manner, the higher doses inhibiting cell progression. Vanadyl stimulated cell proliferation in a dose-responsive manner. Similar to vanadate, pervanadate increased osteoblast-like cell proliferation in a biphasic manner but no inhibition of growth was observed. Vanadyl and pervanadate were stronger stimulators of cell growth than vanadate. Only vanadate was able to regulate the cell differentiation as measured by cell alkaline phosphatase activity. These results suggest that vanadium derivatives behave like growth factors on osteoblast-like cells and are potential pharmacological tools in the control of cell growth.     

Dependence of broad-scale geographical variation in fleshy-fruited plant species richness on disperser bird species richness

Aim We analysed the interdependence of avian frugivore‐ and fruited plant‐species richness at the scale of major river basins across Europe, taking into account several environmental factors along different spatial gradients. Location Continental Europe and the British Isles. Methods We focused on wintering birds and autumn/winter fruiting plants, and used major river basins as geographical units and Structural Equation Modelling as the principal analytical tool. Results The statistical influence of disperser species richness on fleshy‐fruited plant species richness is roughly double that of the reverse. Broad‐scale variation in frugivore richness is more dependent on environmental factors than on fruited plant richness. However, the influence of disperser richness on plant richness is four times higher than the influence of environmental factors. Environmental influences on both birds and plants are greater than purely spatial influences. Main conclusions Our results are interpreted as indicating that biotic dispersal of fruits strongly affects broad‐scale geographical trends of fleshy‐fruited plant species richness, whereas richness of fruited plants moderately affects frugivore richness.