Dataset Information

Biological profile of the less lipophilic and synthetically more accessible bryostatin 7 closely resembles that of bryostatin 1.

ABSTRACT: The bryostatins are a group of 20 macrolides isolated by Pettit and co-workers from the marine organism Bugula neritina. Bryostatin 1, the flagship member of the family, has been the subject of intense chemical and biological investigations due to its remarkably diverse biological activities, including promising indications as therapy for cancer, Alzheimer's disease, and HIV. Other bryostatins, however, have attracted far less attention, most probably due to their relatively low natural abundance and associated scarcity of supply. Among all macrolides in this family, bryostatin 7 is biologically the most potent protein kinase C (PKC) ligand (in terms of binding affinity) and also the first bryostatin to be synthesized in the laboratory. Nonetheless, almost no biological studies have been carried out on this agent. We describe herein the total synthesis of bryostatin 7 based on our pyran annulation technology, which allows for the first detailed biological characterizations of bryostatin 7 with side-by-side comparisons to bryostatin 1. The results suggest that the more easily synthesized and less lipophilic bryostatin 7 may be an effective surrogate for bryostatin 1.

SUBMITTER: Kedei N

PROVIDER: S-EPMC3631439 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Biological profile of the less lipophilic and synthetically more accessible bryostatin 7 closely resembles that of bryostatin 1.

Kedei Noemi N Lewin Nancy E NE Géczy Tamás T Selezneva Julia J Braun Derek C DC Chen Jinqiu J Herrmann Michelle A MA Heldman Madeleine R MR Lim Langston L Mannan Poonam P Garfield Susan H SH Poudel Yam B YB Cummins Thomas J TJ Rudra Arnab A Blumberg Peter M PM Keck Gary E GE

ACS chemical biology 20130201 4

The bryostatins are a group of 20 macrolides isolated by Pettit and co-workers from the marine organism Bugula neritina. Bryostatin 1, the flagship member of the family, has been the subject of intense chemical and biological investigations due to its remarkably diverse biological activities, including promising indications as therapy for cancer, Alzheimer's disease, and HIV. Other bryostatins, however, have attracted far less attention, most probably due to their relatively low natural abundanc ...[more]

PMID: 23369356

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Project description:BackgroundLittle is known about the initial, symptomless (latent) phase of the devastating wheat disease Septoria tritici blotch. However, speculations as to its impact on fungal success and disease severity in the field have suggested that a long latent phase is beneficial to the host and can reduce inoculum build up in the field over a growing season. The winter wheat cultivar Stigg is derived from a synthetic hexaploid wheat and contains introgressions from wild tetraploid wheat Triticum turgidum subsp. dicoccoides, which contribute to cv. Stigg's exceptional STB resistance, hallmarked by a long latent phase. We compared the early transcriptomic response to Zymoseptoria tritici of cv. Stigg to a susceptible wheat cultivar, to elucidate the mechanisms of and differences in pathogen recognition and disease response in these two hosts.ResultsThe STB-susceptible cultivar Longbow responds to Z. tritici infection with a stress response, including activation of hormone-responsive transcription factors, post translational modifications, and response to oxidative stress. The activation of key genes associated with these pathways in cv. Longbow was independently observed in a second susceptible wheat cultivar based on an independent gene expression study. By comparison, cv. Stigg is apathetic in response to STB, and appears to fail to activate a range of defence pathways that cv. Longbow employs. Stigg also displays some evidence of sub-genome bias in its response to Z. tritici infection, whereas the susceptible cv. Longbow shows even distribution of Z. tritici responsive genes across the three wheat sub-genomes.ConclusionsWe identify a suite of disease response genes that are involved in early pathogen response in susceptible wheat cultivars that may ultimately lead to susceptibility. In comparison, we hypothesise that rather than an active defence response to stave off disease progression, cv. Stigg's defence strategy is molecular lethargy, or a lower-amplitude of pathogen recognition that may stem from cv. Stigg's wild wheat-derived ancestry. Overall, we present insights into cv. Stigg's exceptional resistance to STB, and present key biological processes for further characterisation in this pathosystem.

Project description:BACKGROUND:Sleep and physical activity are modifiable behaviors that play an important role in preventing overweight, obesity, and metabolic health problems. Studies of the association between concurrent objective measures of sleep, physical activity, and metabolic risk factors among adolescents are limited. OBJECTIVE:The aim of the study was to examine the association between metabolic risk factors and objectively measured school day physical activity and sleep duration, quality, onset, and variability in adolescents. MATERIALS AND METHODS:We measured one school week of free-living sleep and physical activity with wrist actigraphy in 252 adolescents (146 girls), aged 15.8±0.3 years. Metabolic risk factors included body mass index, waist circumference, total body and trunk fat percentage, resting blood pressure, and fasting glucose and insulin levels. Multiple linear regression adjusted for sex, parental education, and day length was used to assess associations between metabolic risk factors and sleep and activity parameters. RESULTS:On average, participants went to bed at 00:22±0.88 hours and slept 6.2±0.7 hours/night, with 0.83±0.36 hours of awakenings/night. However, night-to-night variability in sleep duration was considerable (mean ± interquartile range) 0.75±0.55 hours) and bedtime (0.64±0.53 hours) respectively. Neither average sleep duration nor mean bedtime was associated with any metabolic risk factors. However, greater night-to-night variability in sleep duration and bedtime was associated with higher total body and trunk fat percentage, and less physical activity was associated with higher trunk fat percentage and insulin levels. CONCLUSION:Greater nightly variation in sleep duration and in bedtime and less physical activity were associated with a less favorable metabolic profile in adolescents. These findings support the idea that, along with an adequate amount of physical activity, a regular sleep schedule is important for the metabolic health of adolescents.

Dataset Information

Biological profile of the less lipophilic and synthetically more accessible bryostatin 7 closely resembles that of bryostatin 1.

Publications

Biological profile of the less lipophilic and synthetically more accessible bryostatin 7 closely resembles that of bryostatin 1.

Similar Datasets

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