(6R)-2-tert-Butyl-6-[(4R,5S)-3-isopropyl-4-methyl-5-phenyl­oxazolidin-2-yl]phenol

In the title compound, C23H31NO2, the lone pair on the nitro­gen atom is oriented to facilitate intra­molecular hydrogen bonding with the hydr­oxy group residing on the phenyl substituent. The five-membered ring adopts an envelope confornmation with the O atom at the flap. The absolute stereochemistry was verified by measurement of optical activity using a digital polarimeter

Entomophagy: a key to space agriculture

Abstract The intentional inclusion of insects in space-based agricultural schemes and their use as human food (entomophagy) were examined. Insects could be useful both from an ecosystem design point of view, as well as serving as a protein-rich food for human occupants. Some candidate species are the silkworm, the hawkmoth, the drugstore beetle, and the termite. Plants in the ecosystem would include rice, soybean, sweet potato, and green-yellow vegetable but in combination they still lead to a diet that is deficient (for humans) in several nutrients. Normally these are supplied with animal-derived foods such as meat, poultry, fish, eggs, dairy products, etc. However, they can also be derived from insects which may be much easier to produce than any of the foregoing, and can also fulfill other useful ecological roles. Spinoff from this research could include some solutions to terrestrial problems such as supplying critical amino acids to people who suffer from a shortage of more conventional animal-derived proteins

Vaccination Targeting a Surface Sialidase of P. acnes: Implication for New Treatment of Acne Vulgaris

BACKGROUND: Acne vulgaris afflicts more than fifty million people in the United State and the severity of this disorder is associated with the immune response to Propionibacterium acnes (P. acnes). Systemic therapies for acne target P. acnes using antibiotics, or target the follicle with retinoids such as isotretinoin. The latter systemic treatment is highly effective but also carries a risk of side effects including immune imbalance, hyperlipidemia, and teratogenicity. Despite substantial research into potential new therapies for this common disease, vaccines against acne vulgaris are not yet available. METHODS AND FINDINGS: Here we create an acne vaccine targeting a cell wall-anchored sialidase of P. acnes. The importance of sialidase to disease pathogenesis is shown by treatment of a human sebocyte cell line with recombinant sialidase that increased susceptibility to P. acnes cytotoxicity and adhesion. Mice immunized with sialidase elicit a detectable antibody; the anti-sialidase serum effectively neutralized the cytotoxicity of P. acnes in vitro and P. acnes-induced interleukin-8 (IL-8) production in human sebocytes. Furthermore, the sialidase-immunized mice provided protective immunity against P. acnes in vivo as this treatment blocked an increase in ear thickness and release of pro-inflammatory macrophage inflammatory protein (MIP-2) cytokine. CONCLUSIONS: Results indicated that acne vaccines open novel therapeutic avenues for acne vulgaris and other P. acnes-associated diseases

Insertional mutation of the hairless locus on mouse Chromosome 14

Crosses between heterozygous transgenic mice from line 5053 produced offspring with progressive irreversible hair loss beginning at day 10. With increasing age, the skin of these animals became thicker and plicated in appearance. Histological analysis revealed the complete absence of normal hair follicles and numerous intradermic cystic structures, which enlarged with time and became filled with keratinaceous material. Test crosses demonstrated that the affected animals are homozygous for the transgene insertion. The clinicla and histological phenotype of the new mutant closely resembles that of the rhino allele at the hairless locus on Chromosome (Chr) 14. Complementation tests and linkage analysis indicate that the transgene has interrupted the hairless locus. It has been demonstrated previously that mutation at the hr locus is accompanied by a variety of immune deficiencies. Many of the older affected transgenic mice developed an impetigo-like skin eruption which responded to antibiotic ointment and which may reflect impaired immune function. The transgenic allele, hr TgN5053Mm , will be useful for identification of the transcription unit of the hairless locus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47000/1/335_2004_Article_BF00360900.pd

Acetaminophen Modulates the Transcriptional Response to Recombinant Interferon-β

BACKGROUND: Recombinant interferon treatment can result in several common side effects including fever and injection-site pain. Patients are often advised to use acetaminophen or other over-the-counter pain medications as needed. Little is known regarding the transcriptional changes induced by such co-administration. METHODOLOGY/PRINCIPAL FINDINGS: We tested whether the administration of acetaminophen causes a change in the response normally induced by interferon-beta treatment. CD-1 mice were administered acetaminophen (APAP), interferon-beta (IFN-beta) or a combination of IFN-beta+APAP and liver and serum samples were collected for analysis. Differential gene expression was determined using an Agilent 22 k whole mouse genome microarray. Data were analyzed by several methods including Gene Ontology term clustering and Gene Set Enrichment Analysis. We observed a significant change in the transcription profile of hepatic cells when APAP was co-administered with IFN-beta. These transcriptional changes included a marked up-regulation of genes involved in signal transduction and cell differentiation and down-regulation of genes involved in cellular metabolism, trafficking and the IkappaBK/NF-kappaB cascade. Additionally, we observed a large decrease in the expression of several IFN-induced genes including Ifit-3, Isg-15, Oasl1, Zbp1 and predicted gene EG634650 at both early and late time points. CONCLUSIONS/SIGNIFICANCE: A significant change in the transcriptional response was observed following co-administration of IFN-beta+APAP relative to IFN-beta treatment alone. These results suggest that administration of acetaminophen has the potential to modify the efficacy of IFN-beta treatment

Impaired antibody response against T-dependent antigens in rhino mice.

The antibody response in rhino mice, which carry a mutant gene hrrh, to thymus-dependent (TD) or thymus-independent (TI) antigens was compared with that of phenotypically normal littermates. The magnitude of antibody response to TD antigens in rhino mice decreased as they grew up, whereas the antibody response to TI antigens in rhino mice was indistinguishable from that of littermates. A transfer of thymus cells from littermates to rhino mice resulted in the partial restoration of the responsiveness to TD antigens. The experiments employing adoptive transfer of spleen cells from rhino mice to the irradiated normal mice suggested that the hyporesponsiveness of TD antigens of adult rhino mice was mainly due to the defect in the T helper cell activities rather than either the increase of the suppressor cells or defects in other cell types

Cell-mediated and humoral immune responses in mice. IV. Difference of the functional cell population between helper activity and delayed-type hypersensitivity.

Helper activity in the anti-hapten antibody response was studied in mice in reference to the induction of delayed-type hypersensitivity (DTH) to the carrier protein. Mice were immunized either by an i.v. injection of alum-precipitated bovine serum albumin (AP-BSA) plus bacterial endotoxin or by a s.c. injection of BSA in Freund's complete adjuvant, the latter being effective in inducing DTH. The helper activity was estimated by the antibody response to the challenge with dinitrophenylated BSA (DNP-BSA) given at varying intervals after the injection of BSA. The results indicated that the helper activity was independent of DTH to the carrier protein, suggesting that these two activities, are mediated by different populations of functional cells. A low dose of tolerogenic soluble BSA (sBSA) was sufficient to abrogate the helper activity in the response to DNP-BSA. In contrast, DTH to BSA was only partially depressed by the pretreatment with a low dose of sBSA and was completely depressed by a high dose. DTH reactivity in mice pretreated with a low dose of tolerogen and followed by the immunization with BSA in Freund's complete adjuvant was substantiated by the microscopic observation of mononuclear cell infiltration at the site of the test antigen injection. These results suggest that cells involved in the helper function and DTH may be derived from different precursors