279 research outputs found
Mass-Deformed BLG Theory in Light-Cone Superspace
Maximally supersymmetric mass deformation of the Bagger-Lambert-Gustavsson
(BLG) theory corresponds to a {non-central} extension of the d=3 N=8 Poincare
superalgebra (allowed in three dimensions). We obtain its light-cone superspace
formulation which has a novel feature of the dynamical supersymmetry generators
being {cubic} in the kinematical ones. The mass deformation picks a
quaternionic direction, which breaks the SO(8) R-symmetry down to SO(4)xSO(4).
The Hamiltonian of the theory is shown to be a quadratic form of the dynamical
supersymmetry transformations, to all orders in the mass parameter, M, and the
structure constants, f^{a b c d}.Comment: 23 page
Time to full enteral feeding after necrotizing enterocolitis in preterm-born children is related to neurodevelopment at 2-3Â years of age
BACKGROUND: Necrotizing enterocolitis (NEC) is associated with poorer neurodevelopment. It is, however, unclear which factors besides surgery affect neurodevelopment in preterm-born children surviving NEC. AIMS: We determined whether time to full enteral feeding (FEFt) and post-NEC complications after NEC were associated with neurodevelopment. STUDY DESIGN: Prospective observational cohort study. SUBJECTS: Two to three year old preterm-born children who survived NEC (Bells stage â„ 2). We categorized children in two groups, one group shorter and equal and one group longer than the group's median FEFt. Post-NEC complications included recurrent NEC and/or post-NEC stricture. OUTCOME MEASURES: Bayley Scales of Infants and Toddler Development III (Bayley-III) and Child Behavior Checklist (CBCL). Associations between Bayley-III and CBCL scores with FEFt and Post-NEC complications were determined using linear regression analyses, adjusted for severity of illness and potential confounders. RESULTS: We included 44 children, median gestational age of 27.9 [IQR: 26.7-29.3] weeks, birth weight 1148 [IQR: 810-1461] grams. Median FEFt after NEC was 20 [IQR: 16-30] days. Median follow-up age was 25.7 [IQR: 24.8-33.5] months. FEFt > 20 days was associated with lower cognitive and lower motor composite scores of the Bayley-III (B: -8.6, 95% CI -16.7 to -0.4, and B: -9.0, 95% CI, -16.7 to -1.4). FEFt was not associated with CBCL scores. Post-NEC complications (n = 11) were not associated with Bayley-III scores nor with CBCL scores. CONCLUSIONS: Prolonged FEFt after NEC in preterm-born children surviving NEC is associated with lower cognitive and lower motor composite scores at the age of 2-3 years. These results show the importance of limiting the duration of the nil per mouth regimen if and when possible
Dietary Fiber and Bacterial SCFA Enhance Oral Tolerance and Protect against Food Allergy through Diverse Cellular Pathways
The incidence of food allergies in western countries has increased dramatically in recent decades. Tolerance to food antigens relies on mucosal CD103+ dendritic cells (DCs), which promote differentiation of regulatory T (Treg) cells. We show that high-fiber feeding in mice improved oral tolerance and protected from food allergy. High-fiber feeding reshaped gut microbial ecology and increased the release of short-chain fatty acids (SCFAs), particularly acetate and butyrate. High-fiber feeding enhanced oral tolerance and protected against food allergy by enhancing retinal dehydrogenase activity in CD103+ DC. This protection depended on vitamin A in the diet. This feeding regimen also boosted IgA production and enhanced T follicular helper and mucosal germinal center responses. Mice lacking GPR43 or GPR109A, receptors for SCFAs, showed exacerbated food allergy and fewer CD103+ DCs. Dietary elements, including fiber and vitamin A, therefore regulate numerous protective pathways in the gastrointestinal tract, necessary for immune non-responsiveness to food antigens
Involutory reflection groups and their models
AbstractA finite subgroup G of GL(n,C) is involutory if the sum of the dimensions of its irreducible complex representations is given by the number of absolute involutions in the group, i.e. elements gâG such that ggÂŻ=1, where the bar denotes complex conjugation. A uniform combinatorial model is constructed for all non-exceptional irreducible complex reflection groups which are involutory including, in particular, all infinite families of finite irreducible Coxeter groups
Determinants of postnatal spleen tissue regeneration and organogenesis
Abstract The spleen is an organ that filters the blood and is responsible for generating blood-borne immune responses. It is also an organ with a remarkable capacity to regenerate. Techniques for splenic auto-transplantation have emerged to take advantage of this characteristic and rebuild spleen tissue in individuals undergoing splenectomy. While this procedure has been performed for decades, the underlying mechanisms controlling spleen regeneration have remained elusive. Insights into secondary lymphoid organogenesis and the roles of stromal organiser cells and lymphotoxin signalling in lymph node development have helped reveal similar requirements for spleen regeneration. These factors are now considered in the regulation of embryonic and postnatal spleen formation, and in the establishment of mature white pulp and marginal zone compartments which are essential for spleen-mediated immunity. A greater understanding of the cellular and molecular mechanisms which control spleen development will assist in the design of more precise and efficient tissue grafting methods for spleen regeneration on demand. Regeneration of organs which harbour functional white pulp tissue will also offer novel opportunities for effective immunotherapy against cancer as well as infectious diseases
Unbiased method for spectral analysis of cells with great diversity of autofluorescence spectra
Autofluorescence is an intrinsic feature of cells, caused by the natural emission of light by photo-excitatory molecular content, which can complicate analysis of flow cytometry data. Different cell types have different autofluorescence spectra and, even within one cell type, heterogeneity of autofluorescence spectra can be present, for example, as a consequence of activation status or metabolic changes. By using full spectrum flow cytometry, the emission spectrum of a fluorochrome is captured by a set of photo detectors across a range of wavelengths, creating an unique signature for that fluorochrome. This signature is then used to identify, or unmix, that fluorochrome's unique spectrum from a multicolor sample containing different fluorescent molecules. Importantly, this means that this technology can also be used to identify intrinsic autofluorescence signal of an unstained sample, which can be used for unmixing purposes and to separate the autofluorescence signal from the fluorophore signals. However, this only works if the sample has a singular, relatively homogeneous and bright autofluorescence spectrum. To analyze samples with heterogeneous autofluorescence spectral profiles, we setup an unbiased workflow to more quickly identify differing autofluorescence spectra present in a sample to include as âautofluorescence signaturesâ during the unmixing of the full stained samples. First, clusters of cells with similar autofluorescence spectra are identified by unbiased dimensional reduction and clustering of unstained cells. Then, unique autofluorescence clusters are determined and are used to improve the unmixing accuracy of the full stained sample. Independent of the intensity of the autofluorescence and immunophenotyping of cell subsets, this unbiased method allows for the identification of most of the distinct autofluorescence spectra present in a sample, leading to less confounding autofluorescence spillover and spread into extrinsic phenotyping markers. Furthermore, this method is equally useful for spectral analysis of different biological samples, including tissue cell suspensions, peripheral blood mononuclear cells, and in vitro cultures of (primary) cells.</p
A molecular map of murine lymph node blood vascular endothelium at single cell resolution
Blood vascular endothelial cells (BECs) control the immune response by regulating blood flow and immune cell recruitment in lymphoid tissues. However, the diversity of BEC and their origins during immune angiogenesis remain unclear. Here we profile transcriptomes of BEC from peripheral lymph nodes and map phenotypes to the vasculature. We identify multiple subsets, including a medullary venous population whose gene signature predicts a selective role in myeloid cell (vs lymphocyte) recruitment to the medulla, confirmed by videomicroscopy. We define five capillary subsets, including a capillary resident precursor (CRP) that displays stem cell and migratory gene signatures, and contributes to homeostatic BEC turnover and to neogenesis of high endothelium after immunization. Cell alignments show retention of developmental programs along trajectories from CRP to mature venous and arterial populations. Our single cell atlas provides a molecular roadmap of the lymph node blood vasculature and defines subset specialization for leukocyte recruitment and vascular homeostasis
Enhanced IgA coating of bacteria in women with Lactobacillus crispatus-dominated vaginal microbiota.
BackgroundImmunoglobulin A (IgA) plays an important role in maintaining a healthy intestinal microbiome, but little is known about the interaction between local immunoglobulins and the vaginal microbiome. We assessed immunoglobulins (unbound and bound to bacteria), their association with vaginal microbiota composition and the changes over time in 25 healthy women of reproductive age.ResultsIn both Lactobacillus crispatus-dominated and non-L. crispatus-dominated microbiota, IgA and IgG (unbound and bound to bacteria) were higher during menses (T = 1) compared to day 7â11 (T = 2) and day 17â25 (T = 3) after menses onset. The majority of vaginal bacteria are coated with IgA and/or IgG. Women with L. crispatus-dominated microbiota have increased IgA coating of vaginal bacteria compared to women with other microbiota compositions, but contained less IgA per bacterium. Presence of a dominantly IgA-coated population at T = 2 and/or T = 3 was also strongly associated with L. crispatus-dominated microbiota. In women with non-L. crispatus-dominated microbiota, more bacteria were uncoated. Unbound IgA, unbound IgG, and bound IgG levels were not associated with microbiota composition.ConclusionsIn conclusion, L. crispatus-dominated vaginal microbiota have higher levels of bacterial IgA coating compared to non-L. crispatus-dominated vaginal microbiota. Similar to its regulating function in the intestinal tract, we hypothesize that IgA is involved in maintaining L. crispatus-dominated microbiota in the female genital tract. This may play a role in L. crispatus-associated health benefits. Video abstract
Wnt3a deficiency irreversibly impairs hematopoietic stem cell self-renewal and leads to defects in progenitor cell differentiation
Canonical Wnt signaling has been implicated in various aspects of hematopoiesis. Its role is controversial due to different outcomes between various inducible Wnt-signaling loss-of-function models and also compared with gain-of-function systems. We therefore studied a mouse deficient for a Wnt gene that seemed to play a nonredundant role in hematopoiesis. Mice lacking Wnt3a die prenatally around embryonic day (E) 12.5, allowing fetal hematopoiesis to be studied using in vitro assays and transplantation into irradiated recipient mice. Here we show that Wnt3a deficiency leads to a reduction in the numbers of hematopoietic stem cells (HSCs) and progenitor cells in the fetal liver (FL) and to severely reduced reconstitution capacity as measured in secondary transplantation assays. This deficiency is irreversible and cannot be restored by transplantation into Wnt3a competent mice. The impaired long-term repopulation capacity of Wnt3a-/- HSCs could not be explained by altered cell cycle or survival of primitive progenitors. Moreover, Wnt3a deficiency affected myeloid but not B-lymphoid development at the progenitor level, and affected immature thymocyte differentiation. Our results show that Wnt3a signaling not only provides proliferative stimuli, such as for immature thymocytes, but also regulates cell fate decisions of HSC during hematopoiesis
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