70 research outputs found
Cell Host Microbe
No full textAltered commensal communities are associated with human disease. IgA mediates intestinal homeostasis and regulates microbiota composition. Intestinal IgA is produced at high levels as a result of T follicular helper cell (TFH) and B cell interactions in germinal centers. However, the pathways directing host IgA responses toward the microbiota remain unknown. Here, we report that signaling through the innate adaptor MyD88 in gut T\ua0cells coordinates germinal center responses, including TFH and IgA+ B cell development. TFH development is deficient in germ-free mice and can be restored by feeding TLR2 agonists that activate T\ua0cell-intrinsic MyD88 signaling. Loss of this pathway diminishes high-affinity IgA targeting of the microbiota and fails to control the bacterial community, leading to worsened disease. Our findings identify that T\ua0cells converge innate and adaptive immune signals to coordinate IgA against the microbiota, constraining microbial community membership to promote symbiosis.1S10RR026802-01/RR/NCRR NIH HHS/United States5-P39-DK034987/DK/NIDDK NIH HHS/United States5-P40-OD010995/OD/NIH HHS/United StatesAI107090/AI/NIAID NIH HHS/United StatesAI109122/AI/NIAID NIH HHS/United StatesDP2 AT008746/AT/NCCIH NIH HHS/United StatesDP2AT008746-01/AT/NCCIH NIH HHS/United StatesDP2GM111099-01/DP/NCCDPHP CDC HHS/United StatesK22 AI095375/AI/NIAID NIH HHS/United StatesK22 AI95375/AI/NIAID NIH HHS/United StatesP30 DK034987/DK/NIDDK NIH HHS/United StatesP40 OD010995/OD/NIH HHS/United StatesR00HL102228-05/HL/NHLBI NIH HHS/United StatesR21 AI109122/AI/NIAID NIH HHS/United StatesT32 AI-055434/AI/NIAID NIH HHS/United StatesT32 GM007464/GM/NIGMS NIH HHS/United State
IgA Targets the Troublemakers
No full textResident microbes within the gastrointestinal tract are known to influence the progression of inflammatory bowel diseases (IBD); however, the identity of the bacteria that exacerbate inflammation remains unknown. In the most recent issue of Cell, Palm et al. (2014) utilize the host immune response as a way to identify colitogenic bacteria
PLoS One
No full textMammalian microRNA expression is dysregulated in human cancer. However, the functional relevance of many microRNAs in the context of tumor biology remains unclear. Using CRISPR-Cas9 technology, we performed a global loss-of-function screen to simultaneously test the functions of individual microRNAs and protein-coding genes during the growth of a myeloid leukemia cell line. This approach identified evolutionarily conserved human microRNAs that suppress or promote cell growth, revealing that microRNAs are extensively integrated into the molecular networks that control tumor cell physiology. miR-155 was identified as a top microRNA candidate promoting cellular fitness, which we confirmed with two distinct miR-155-targeting CRISPR-Cas9 lentiviral constructs. Further, we performed anti-correlation functional profiling to predict relevant microRNA-tumor suppressor gene or microRNA-oncogene interactions in these cells. This analysis identified miR-150 targeting of p53, a connection that was experimentally validated. Taken together, our study describes a powerful genetic approach by which the function of individual microRNAs can be assessed on a global level, and its use will rapidly advance our understanding of how microRNAs contribute to human disease.20165P30CA042014-24/CA/NCI NIH HHS/United StatesDP2GM111099-01/DP/NCCDPHP CDC HHS/United States27081855PMC48334281018
ANOMALOUS BEHAVIOUR OF THE ANTICROSSING DENSITY AS A FUNCTION OF EXCITATION ENERGY IN THE C2H2 MOLECULE
No full text P. Dupre, R. Jost, M. Lombardi, P. G. Green, E. Abramson and R. W. Field, in preparation. P.P. G. Green, PhD Thesis, MIT (1989). CAMBRIDGE MA (U.S.A.).Author Institution: Service National des Champs Intenses.; Service National des Champs Intenses.; Mail Stop 170-25, California Institute of Technology; Mail Stop 170-25, Service National des Champs Intenses.; Department of Chemistry, MITWe have recorded Zeenan Anticrossing (ZAC) spectra of gas phase acetylene in the is the trans-bending normal mode of the trans-bent excited electronic state). . levels. The energy range thus sampled was from 42,200 to 45,300 cm1 above the state. The eugnetic field scanned from 0 to 8 Tesin and the ZAC spectre were recorded as variations (decreases) in the intensity of the fluorescence excited by a pulsed, frequency doubled dye laser. The ZAC spectra wore unassignably complex. We report a surprisingly rapid increase in the density of anticrossing (AC) over a (only 7\% of the total excitation energy) energy interval, In the level the ZAC spectra are unassignably complex and the anticrossing density is Limes larger than the maximum computed density of triplet vibrational states and quite comparable to the computed density of vibrational states. This constrasts with the AC level density observed in the vibrational level where the agreement with the calculated level density is good enough. We suggest three plausible mechanisms to explain this behaviour : the existence of a dissociation limit, the potential curve crossing or the vicinity of a triplet trans- cia-bent isomerization barrier. We prefer this last explanation because this barrier should increase the and the couplings, Indeed, we suggest that the large level densities are due to tran-sitions induced by a triplet . Moreover, the existence of the isomerization barrier is suggested by recent work using the Stark quantus beat
An overview of group work and implications for school counselors
No full textIncludes bibliographical references
Nat Commun
No full textThe presentation of protein antigens on the cell surface by major histocompatibility complex (MHC) molecules coordinates vertebrate adaptive immune responses, thereby mediating susceptibility to a variety of autoimmune and infectious diseases. The composition of symbiotic microbial communities (the microbiota) is influenced by host immunity and can have a profound impact on host physiology. Here we use an MHC congenic mouse model to test the hypothesis that genetic variation at MHC genes among individuals mediates susceptibility to disease by controlling microbiota composition. We find that MHC genotype significantly influences antibody responses against commensals in the gut, and that these responses are correlated with the establishment of unique microbial communities. Transplantation experiments in germfree mice indicate that MHC-mediated differences in microbiota composition are sufficient to explain susceptibility to enteric infection. Our findings indicate that MHC polymorphisms contribute to defining an individual's unique microbial fingerprint that influences health.DP2 AT008746/AT/NCCIH NIH HHSUnited States/P40 OD010995/OD/NIH HHSUnited States/K22 AI95375/AI/NIAID NIH HHSUnited States/DP2 GM111099/GM/NIGMS NIH HHSUnited States/N01AI95375/AI/NIAID NIH HHSUnited States/R00 HL102228/HL/NHLBI NIH HHSUnited States/P30 DK034987/DK/NIDDK NIH HHSUnited States/DP2AT008746-01/AT/NCCIH NIH HHSUnited States/T32 AI-055434/AI/NIAID NIH HHSUnited States/1S10RR026802-01/RR/NCRR NIH HHSUnited States/S10 RR026802/RR/NCRR NIH HHSUnited States/5-P39-DK034987/DK/NIDDK NIH HHSUnited States/T32 AI055434/AI/NIAID NIH HHSUnited States/AI109122/AI/NIAID NIH HHSUnited States/K22 AI095375/AI/NIAID NIH HHSUnited States/DP2GM111099-01/DP/NCCDPHP CDC HHSUnited States/R56 AI107090/AI/NIAID NIH HHSUnited States/AI107090/AI/NIAID NIH HHSUnited States/T32 GM007464/GM/NIGMS NIH HHSUnited States/R21 AI109122/AI/NIAID NIH HHSUnited States/5-P40-OD010995/OD/NIH HHSUnited States/R00HL102228-05/HL/NHLBI NIH HHSUnited States
Retinoic acid is required for endodermal pouch morphogenesis and not for pharyngeal endoderm specification
No full text
Neuronal Neuregulin 1 type III directs Schwann cell migration
No full textDuring peripheral nerve development, each segment of a myelinated axon is matched with a single Schwann cell. Tight regulation of Schwann cell movement, proliferation and differentiation is essential to ensure that these glial cells properly associate with axons. ErbB receptors are required for Schwann cell migration, but the operative ligand and its mechanism of action have remained unknown. We demonstrate that zebrafish Neuregulin 1 (Nrg1) type III, which signals through ErbB receptors, controls Schwann cell migration in addition to its previously known roles in proliferation and myelination. Chimera analyses indicate that ErbB receptors are required in all migrating Schwann cells, and that Nrg1 type III is required in neurons for migration. Surprisingly, expression of the ligand in a few axons is sufficient to induce migration along a chimeric nerve constituted largely of nrg1 type III mutant axons. These studies also reveal a mechanism that allows Schwann cells to fasciculate axons regardless of nrg1 type III expression. Time-lapse imaging of transgenic embryos demonstrated that misexpression of human NRG1 type III results in ectopic Schwann cell migration, allowing them to aberrantly enter the central nervous system. These results demonstrate that Nrg1 type III is an essential signal that controls Schwann cell migration to ensure that these glia are present in the correct numbers and positions in developing nerves.</jats:p
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