1,275 research outputs found

    Total Syntheses of (+)-Vigulariol and (−)-Sclerophytin A

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    The total synthesis of (+)-vigulariol and (−)-sclerophytin A are reported in 15 steps and 16 steps, respectively, from a known compound. The flexible, readily scalable synthetic strategy allows for rapid construction of a critical tricyclic intermediate and is demonstrated via the synthesis of these two marine natural products. A key reaction in this synthetic protocol is a combination Wittig/intramolecular Diels-Alder cycloaddition

    Distinct TLR- and NLR-Mediated Transcriptional Responses to an Intracellular Pathogen

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    How the innate immune system tailors specific responses to diverse microbial infections is not well understood. Cells use a limited number of host receptors and signaling pathways to both discriminate among extracellular and intracellular microbes, and also to generate responses commensurate to each threat. Here, we have addressed these questions by using DNA microarrays to monitor the macrophage transcriptional response to the intracellular bacterial pathogen Listeria monocytogenes. By utilizing combinations of host and bacterial mutants, we have defined the host transcriptional responses to vacuolar and cytosolic bacteria. These compartment-specific host responses induced significantly different sets of target genes, despite activating similar transcription factors. Vacuolar signaling was entirely MyD88-dependent, and induced the transcription of pro-inflammatory cytokines. The IRF3-dependent cytosolic response induced a distinct set of target genes, including IFNβ. Many of these cytosolic response genes were induced by secreted cytokines, so we further identified those host genes induced independent of secondary signaling. The host response to cytosolic bacteria was reconstituted by the cytosolic delivery of L. monocytogenes genomic DNA, but we observed an amplification of this response by NOD2 signaling in response to MDP. Correspondingly, the induction of IFNβ was reduced in nod2−/− macrophages during infection with either L. monocytogenes or Mycobacterium tuberculosis. Combinatorial control of IFNβ induction by recognition of both DNA and MDP may highlight a mechanism by which the innate immune system integrates the responses to multiple ligands presented in the cytosol by intracellular pathogens

    Total Synthesis of Apoptolidin A

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    A highly convergent, enantioselective total synthesis of the potent antitumor agent apoptolidin A, has been completed. The key transformations include highly selective glycosylations to attach the C27 disaccharide and the C9 6′-deoxy-l-glucose, a cross metathesis to incorporate the C1-C10 trienoate unit, and a Yamaguchi macrolactonization to complete the macrocycle. Twelve stereocenters in the polypropionate segments and sugar units were established through diastereoselective chlorotitanium enolate aldol reactions

    Dried blood spots: Effects of less than optimal collection, shipping time, heat, and humidity

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    ObjectivesThis study investigates how factors related to collection, storage, transport time, and environmental conditions affect the quality and accuracy of analyses of dried blood spot (DBS) samples.MethodsData come from the 2016 Health and Retirement Study (HRS) DBS laboratory reports and the HRS merged with the National Climatic Data Center (NCDC) Global Historical Climate Network Daily (NCDC GHCN‐Daily) and the NCDC Local Climatological Data, by zip code. We ran regression models to examine the associations between assay values based on DBS for five analytes (total cholesterol, high‐density lipoprotein (HDL) cholesterol, glycosylated hemoglobin (HbA1c), C‐reactive protein (CRP), and cystatin C) and the characteristics of DBS cards and drops, shipping time, and temperature, and humidity at the time of collection.ResultsWe found cholesterol measures to be sensitive to many factors including small spots, shipping time, high temperature and humidity. Small spots in DBS cards are related to lower values across all analytes. Longer DBS transit time before freezing is associated with lower values of total and HDL cholesterol and cystatin C. Results were similar whether or not venous blood sample values were included in equations.ConclusionsSmall spots, long shipping time, and exposure to high temperature and humidity need to be avoided if possible. Quality of spots and cards and information on shipping time and conditions should be coded with the data to make adjustments in values when necessary. The different results across analytes indicate that results cannot be generalized to all DBS assays.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162768/2/ajhb23390_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162768/1/ajhb23390.pd

    Are Differences in Disability-Free Life Expectancy by Gender, Race, and Education Widening at Older Ages?

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    To examine change from 1991 to 2001 in disability-free life expectancy in the age range 60-90 by gender, race, and education in the United States. Mortality is estimated over two 10-year follow-up periods for persons in the National Health Interview Surveys of 1986/1987 and 1996/1997. Vital status is ascertained through the National Death Index. Disability prevalence is estimated from the National Health and Nutrition Examination Surveys of 1988-1994 and 1999-2002. Disability is defined as ability to perform four activities of daily living without difficulty. Disability-free life expectancy increased only among white men. Disabled life expectancy increased for all groups-black and white men and women. Racial differences in disability-free life expectancy widened among men; gender differences were reduced among whites. Expansion of socioeconomic differentials in disability-free life at older ages occurred among white men and women and black women. The 1990s was a period where the increased years of life between ages 60 and 90 were concentrated in disabled years for most population groups

    Promotion of self-management in vulnerable older people: a narrative literature review of outcomes of the Chronic Disease Self-Management Program (CDSMP)

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    With ageing, older people can become frail, and this has been shown to be associated with a decrease in well-being. Observational studies provide evidence of a positive effect of coping resources on well-being. The question is: can coping resources be improved in vulnerable older people? The Chronic Disease Self-Management Program (CDSMP) is a target group-specific intervention which aims to promote the self-management of older people who are confronted with deteriorating health. The aim of this study was to review intervention studies focusing on the CDSMP and to draw conclusions on the benefits of the program. A systematic search was conducted in PubMed and PsychINFO to identify randomized controlled trials (RCTs) focusing on the CDSMP. Nine RCTs focusing on relatively young older adults, 75% of whom with an average age between 49 and 65 years, were included. We found that the CDSMP was consistently beneficial for Health behaviour, especially with regard to the variables of exercise and self-care. For Health status, the majority of studies only showed improvement in the domain of health distress. Most of the studies that investigated Self-efficacy showed convincing improvement in self-efficacy, cognitive symptom management and mental stress management. In Health care utilization, there was no significant decrease. On the whole, the studies showed that CDSMP led to an increase in physical exercise, a decrease in health distress, an improvement in self-care, and it had a beneficial effect on self-efficacy

    (R)-2-Phen­oxy-1-(4-phenyl-2-sulfan­ylidene-1,3-oxazolidin-3-yl)ethanone

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    The central 1,3-oxazolidine-2-thione ring in the title compound, C17H15NO3S, is approximately planar with maximum deviations of 0.036 (4) and −0.041 (5) Å for the O and methyl­ene-C atoms, respectively. The dihedral angles formed between this plane and the two benzene rings, which lie to the same side of the central plane, are 86.5 (2) [ring-bound benzene] and 50.6 (3)°. The ethan-1-one residue is also twisted out of the central plane, forming a O—C—N—C torsion angle of 151.5 (5)°. The dihedral angle formed by the benzene rings is 62.8 (2)° so that overall, the mol­ecule has a twisted U-shape. In the crystal, mol­ecules are linked into supra­molecular arrays two mol­ecules thick in the bc plane through C—H⋯O, C—H⋯S and C—H⋯π inter­actions
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