ABSTRACT
Organic cages can possess complex, functionalised cavities that make them promising candidates for synthetic enzyme mimics. Conformationally flexible, chemically robust structures are needed for adaptable guest binding and catalysis, but rapidly exchanging systems are difficult to resolve in solution. Here, we use low-cost calculations and high-throughput crystallisation to identify accessible conformers of a recently reported organic cage by 'locking' them in the solid state. The conformers exhibit varying distances between the internal carboxylic acid groups, suggesting adaptability for binding a wide array of target guest molecules.
ABSTRACT
Enterotoxigenic Bacteroides fragilis (ETBF), a human commensal and candidate pathogen in colorectal cancer (CRC), is a potent initiator of interleukin-17 (IL-17)-dependent colon tumorigenesis in MinApc+/- mice. We examined the role of IL-17 and ETBF on the differentiation of myeloid cells into myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages, which are known to promote tumorigenesis. The myeloid compartment associated with ETBF-induced colon tumorigenesis in Min mice was defined using flow cytometry and gene expression profiling. Cell-sorted immature myeloid cells were functionally assayed for inhibition of T-cell proliferation and inducible nitric oxide synthase expression to delineate MDSC populations. A comparison of ETBF infection with that of other oncogenic bacteria (Fusobacterium nucleatum or pks+Escherichia coli) revealed a specific, ETBF-associated colonic immune infiltrate. ETBF-triggered colon tumorigenesis is associated with an IL-17-driven myeloid signature characterized by subversion of steady-state myelopoiesis in favor of the generation of protumoral monocytic-MDSCs (MO-MDSCs). Combined action of the B. fragilis enterotoxin BFT and IL-17 on colonic epithelial cells promoted the differentiation of MO-MDSCs, which selectively upregulated Arg1 and Nos2, produced NO, and suppressed T-cell proliferation. Evidence of a pathogenic inflammatory signature in humans colonized with ETBF may allow for the identification of populations at risk for developing colon cancer.
Subject(s)
Bacteroides Infections/immunology , Bacteroides fragilis/immunology , Colon/microbiology , Colorectal Neoplasms/immunology , Epithelial Cells/immunology , Myeloid-Derived Suppressor Cells/immunology , T-Lymphocytes/immunology , Animals , Arginase/genetics , Arginase/metabolism , Bacterial Toxins/immunology , Carcinogenesis , Cell Differentiation , Cell Proliferation , Cells, Cultured , Colon/immunology , Colon/pathology , Colorectal Neoplasms/genetics , Disease Models, Animal , Genes, APC , Humans , Immune Tolerance , Interleukin-17/metabolism , Metalloendopeptidases/immunology , Mice , Mice, Inbred C57BL , Mice, Mutant Strains , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , TranscriptomeABSTRACT
Giving patients bad news involves the physician discussing the situation with the recipient and selected family members. Interview factors include knowledge of the medical facts and awareness of the patient and family dynamics. These can be altered as medical information is gained during the course of the illness, as well as a better understanding of the patient and the socio-cultural expectations. Despite the inevitability of death, no satisfactory uniform approach has been developed, because the interaction must be modulated into a sympathetic and humane interaction between medical provider and recipient.
Subject(s)
Neoplasms/diagnosis , Physician-Patient Relations , Truth Disclosure , Adolescent , Adult , Age Factors , Child , Family/psychology , Humans , Infant, Newborn , Informed Consent , Interviews as Topic/methods , Neoplasms/prevention & control , Patient Education as Topic , Terminal Care/psychologySubject(s)
Hispanic or Latino , Medicine, Traditional , Physician-Patient Relations , Humans , Mexico/ethnology , TexasSubject(s)
Blood Pressure , Outpatients , Patients , Adolescent , Adult , Age Factors , Diastole , Female , Humans , Male , Middle Aged , SystoleABSTRACT
Appropriately chosen and supervised physical activity promotes normal growth and is beneficial in treating some diseases; it can also help a child adjust to a physical handicap. Participation in general or team sports is not only enjoyable but also important to normal physical, mental and emotional development. A child's activity level can indicate both normal variations in growth and possible medical problems.
Subject(s)
Physical Exertion , Adolescent , Amenorrhea/etiology , Body Weight , Child , Child, Preschool , Female , Growth , Humans , Infant , Infant, Newborn , Male , Menarche , Physician's Role , Physicians, Family , Play and Playthings , Running , SportsSubject(s)
Blood Pressure , Body Weight , Military Medicine , Adolescent , Adult , Age Factors , Humans , Hypertension/etiology , Male , Obesity/complications , United StatesSubject(s)
Ambulatory Care/standards , Medical Audit/methods , Pharynx/microbiology , Adolescent , Age Factors , Child , Female , Humans , Male , Streptococcal Infections/therapyABSTRACT
A large dose of 2, 8-dioxyadenine-14C was injected intravenously into rats and its fate followed at several intervals during the first 24 hours after administration. The distribution of the radioactive material throughout the various tissues or organs was calculated and expressed as a percentage of the injected dose as well as a specific activity per unit organ weight. It appears that dioxyadenine is rapidly distributed throughout the organs and tissues of the rats and that specific concentration occurs in a few organs. High retention of the radioactive material and a very high specific activity are observed in the kidney. Smaller but significant concentrations of the 14C-compound are also observed in muscle and skin, and cannot be attributed to the presence of residual blood. The radioactive material is gradually released from these tissues and, by 24 hours after injection, 92 per cent of the injected dose is found in the urine. Microscopic observation shows deposition of crystals in the kidney. Crystals are also present in the urine and appear as small slightly yellow spheres.
