Natural Products from the Lithistida: A Review of the Literature since 2000

Lithistid sponges are known to produce a diverse array of compounds ranging from polyketides, cyclic and linear peptides, alkaloids, pigments, lipids, and sterols. A majority of these structurally complex compounds have very potent and interesting biological activities. It has been a decade since a thorough review has been published that summarizes the literature on the natural products reported from this amazing sponge order. This review provides an update on the current taxonomic classification of the Lithistida, describes structures and biological activities of 131 new natural products, and discusses highlights from the total syntheses of 16 compounds from marine sponges of the Order Lithistida providing a compilation of the literature since the last review published in 2002

A rare IL33 loss-of-function mutation reduces blood eosinophil counts and protects from asthma.

Efst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinnIL-33 is a tissue-derived cytokine that induces and amplifies eosinophilic inflammation and has emerged as a promising new drug target for asthma and allergic disease. Common variants at IL33 and IL1RL1, encoding the IL-33 receptor ST2, associate with eosinophil counts and asthma. Through whole-genome sequencing and imputation into the Icelandic population, we found a rare variant in IL33 (NM_001199640:exon7:c.487-1G>C (rs146597587-C), allele frequency = 0.65%) that disrupts a canonical splice acceptor site before the last coding exon. It is also found at low frequency in European populations. rs146597587-C associates with lower eosinophil counts (β = -0.21 SD, P = 2.5×10-16, N = 103,104), and reduced risk of asthma in Europeans (OR = 0.47; 95%CI: 0.32, 0.70, P = 1.8×10-4, N cases = 6,465, N controls = 302,977). Heterozygotes have about 40% lower total IL33 mRNA expression than non-carriers and allele-specific analysis based on RNA sequencing and phased genotypes shows that only 20% of the total expression is from the mutated chromosome. In half of those transcripts the mutation causes retention of the last intron, predicted to result in a premature stop codon that leads to truncation of 66 amino acids. The truncated IL-33 has normal intracellular localization but neither binds IL-33R/ST2 nor activates ST2-expressing cells. Together these data demonstrate that rs146597587-C is a loss of function mutation and support the hypothesis that IL-33 haploinsufficiency protects against asthma.Netherlands Asthma Foundation University Medical Center Groningen Ministry of Health and Environmental Hygiene of Netherlands Netherlands Asthma Stichting Astma Bestrijding BBMRI European Respiratory Society private and public research funds AstraZeneca ALK-Abello, Denmar

National Biomedical Tracer Facility planning and feasibility study. Revision 1

Since its establishment in mid-1989, the DOE Office of Isotope Production and Distribution has examined the recommendations of the Los Alamos Report and the Health and Environmental Research Advisory Committee (HERAC) Report. The main recommendation from these deliberations is for the DOE to establish an accelerator dedicated to biomedical radioisotope production. Representatives of the nuclear medicine community, meeting at a DOE workshop in August 1988, evaluated present and future needs for accelerator-produced radioisotopes. Workshop participants concluded in the Los Alamos Report that approximately 90% of their radioisotope needs could be met by a machine that delivers a 70 million electronic volts (MeV), 500-microamp proton beam. The HERAC Report provides more quantification of radioisotope needs, and included isotopes that can be produced effectively only at higher energies. An accelerator facility with an upper energy limit of 100 MeV and beam current of 750 to 1,000 microamps, could produce all important accelerator- produced radioisotopes in current use, as well as those isotopes judged to have future potential value in medical research and clinical practice. We therefore recommend that the NBTF have a 100-MeV proton beam accelerator with an extracted beam current of 750 to 1,000 microamps

National Biomedical Tracer Facility planning and feasibility study

Since its establishment in mid-1989, the DOE Office of Isotope Production and Distribution has examined the recommendations of the Los Alamos Report and the Health and Environmental Research Advisory Committee (HERAC) Report. The main recommendation from these deliberations is for the DOE to establish an accelerator dedicated to biomedical radioisotope production. Representatives of the nuclear medicine community, meeting at a DOE workshop in August 1988, evaluated present and future needs for accelerator-produced radioisotopes. Workshop participants concluded in the Los Alamos Report that approximately 90% of their radioisotope needs could be met by a machine that delivers a 70 million electronic volts (MeV), 500-microamp proton beam. The HERAC Report provides more quantification of radioisotope needs, and included isotopes that can be produced effectively only at higher energies. An accelerator facility with an upper energy limit of 100 MeV and beam current of 750 to 1,000 microamps, could produce all important accelerator- produced radioisotopes in current use, as well as those isotopes judged to have future potential value in medical research and clinical practice. We therefore recommend that the NBTF have a 100-MeV proton beam accelerator with an extracted beam current of 750 to 1,000 microamps

Loss of NHERF-1 Expression Prevents Dopamine-Mediated Na-K-ATPase Regulation in Renal Proximal Tubule Cells from Rat Models of Hypertension: Aged F344 Rats and Spontaneously Hypertensive Rats.

Dopamine decreases Na-K-ATPase (NKA) activity by PKC-dependent phosphorylation and endocytosis of the NKA α1. Dopamine-mediated regulation of NKA is impaired in aging and some forms of hypertension. Using opossum (OK) proximal tubule cells (PTCs), we demonstrated that sodium-hydrogen exchanger regulatory factor-1 (NHERF-1) associates with NKA α1 and dopamine-1 receptor (D1R). This association is required for the dopamine-mediated regulation of NKA. In OK cells, dopamine decreases NHERF-1 association with NKA α1 but increases its association with D1R. However, it is not known whether NHERF-1 plays a role in dopamine-mediated NKA regulation in animal models of hypertension. We hypothesized that defective dopamine-mediated regulation of NKA results from the decrease in NHERF-1 expression in rat renal PTCs isolated from animal models of hypertension [spontaneously hypertensive rats (SHRs) and aged F344 rats]. To test this hypothesis, we isolated and cultured renal PTCs from 22-mo-old F344 rats and their controls, normotensive 4-mo-old F344 rats, and SHRs and their controls, normotensive Wistar-Kyoto (WKY) rats. The results demonstrate that in both hypertensive models (SHR and aged F344), NHERF-1 expression, dopamine-mediated phosphorylation of NKA, and ouabain-inhibitable K+ transport are reduced. Transfection of NHERF-1 into PTCs from aged F344 and SHRs restored dopamine-mediated inhibition of NKA. These results suggest that decreased renal NHERF-1 expression contributes to the impaired dopamine-mediated inhibition of NKA in PTCs from animal models of hypertension. </jats:p