Alternative splicing of human prostaglandin G/H synthase mRNA and evidence of differential regulation of the resulting transcripts by transforming growth factor beta 1, interleukin 1 beta, and tumor necrosis factor alpha.

Prostaglandin G/H synthase (PGG/HS) is the rate-limiting enzyme in the conversion of arachidonic acid to prostaglandins and thromboxanes. We screened a human lung fibroblast cDNA library with an ovine PGG/HS cDNA and isolated a 2.3-kilobase clone (HCO-T9). Sequence analysis of this clone showed that (a) it contained the entire translated region of PGG/HS and (b) it displayed an in-frame splicing of the last 111 base pairs encoded by exon 9, which resulted in the elimination of the N-glycosylation site at residue 409. Polymerase chain reaction amplification with specific oligonucleotides of reverse-transcribed mRNA from diverse human tissues and cultured cells yielded 400- and 300-base pair fragments that corresponded, respectively, to the intact and spliced transcripts. The expression of these two transcripts in cultured human lung fibroblasts was differentially regulated by serum, transforming growth factor beta 1, interleukin 1 beta, tumor necrosis factor alpha, and phorbol 12-myristate 13-acetate, as each of these conditions stimulated preferentially the expression of the unspliced transcripts. The elimination of one of the four N-glycosylation sites by the alternative splicing of exon 9 and the differential regulation of this process by relevant cytokines and growth factors may represent a mechanism for the regulation of PGG/HS enzymatic activity under physiological or pathological conditions

A free boundary model for oxygen diffusion in a spherical medium

The goal of this article is to find a correct approximated solution using a polynomial of sixth degree for the free boundary problem corresponding to the diffusion of oxygen in a spherical medium with simultaneous absorption at a constant rate, and to show some mistakes in previously published solutions.Comment: 10 pages, 6 figures and 2 tables. Paper accepted, in press in Journal of Biological Systems (2015

There and back again: molecular phylogenetics of the Brazilian endemic Psyllocarpus (Rubiaceae: Spermacoceae) supports a circumscription of the genus based on its original concept

The Spermacoce clade (tribe Spermacoceae) is one of the most taxonomically complex groups in Rubiaceae due to the unclear delimitation of Borreria and Spermacoce, in which several smaller genera are phylogenetically intermingled. One of these genera is the Brazilian endemic Psyllocarpus, whose circumscription was broadened, thereby including two sections. Psyllocarpus sect. Psyllocarpus, being based on the original genus delineation, includes nine species, distributed in the Cerrado and campo rupestre of eastern Brazil, whereas P. sect. Amazonica comprises three species, occurring in the Amazonian campinas. Furthermore, P. intermedius was not classified in any of these sections when it was later described. In order to test the monophyly of Psyllocarpus and assess its relationships to other genera, we conducted phylogenetic analyses, sampling across the whole Spermacoce clade, including nearly all Psyllocarpus species. A combined nuclear ribosomal (ETS and ITS) and plastid (rps16 and trnLtrnF) dataset was generated, representing 124 species (ca 25% of the species in the clade) in 15 genera (ca 65%). Various methodologies were applied to investigate the degree of incongruence among markers and address the lack of resolution and low support values for some branches. Our results revealed that Psyllocarpus is not monophyletic. Psyllocarpus campinorum (from P . sect. Amazonica) and P intermedius are situated as distinct lineages in the Spermacoce clade, yet do not belong to Psyllocarpus. Members of section Psyllocarpus form a strongly supported clade sister to Staelia and was recovered with high to maximum support across different datasets and inference methods. Therefore, Psyllocarpus has to be circumscribed based on its original concept, excluding P. sect. Amazonica and P. intermedius. This establishes the genus as a monophyletic and easily diagnosable taxon, characterized by terete leaves, homostylous flowers, a bilobate calyx, included stamens and style, and compressed, septifragally dehiscent capsules with a persistent septum

Nutrient sensor O-GlcNAc transferase controls cancer lipid metabolism via SREBP-1 regulation

Elevated O-GlcNAcylation is associated with disease states such as diabetes and cancer. O-GlcNAc transferase (OGT) is elevated in multiple cancers and inhibition of this enzyme genetically or pharmacologically inhibits oncogenesis. Here we show that O-GlcNAcylation modulates lipid metabolism in cancer cells. OGT regulates expression of the master lipid regulator the transcription factor sterol regulatory element binding protein 1 (SREBP-1) and its transcriptional targets both in cancer and lipogenic tissue. OGT regulates SREBP-1 protein expression via AMP-activated protein kinase (AMPK). SREBP-1 is critical for OGT-mediated regulation of cell survival and of lipid synthesis, as overexpression of SREBP-1 rescues lipogenic defects associated with OGT suppression, and tumor growth in vitro and in vivo. These results unravel a previously unidentified link between O-GlcNAcylation, lipid metabolism and the regulation of SREBP-1 in cancer and suggests a crucial role for O-GlcNAc signaling in transducing nutritional state to regulate lipid metabolism

Magnetic core studies at LBNL and LLNL

The objective of this work is to minimize the cost of the materials and maximize the performance of magnetic cores, a major cost component of a Heavy-Ion-Fusion, HIF, induction accelerator driver. This includes selection of the alloy for cost and performance, and maximizing the performance of each alloy evaluated. The two major performance parameters are the magnetic flux swing and the energy loss. The volt seconds of the cores, obtained from the flux swing with Faraday's Law, determines the beam energy and duration. Core losses from forming domains and moving their boundaries are a major factor in determining the efficiency of an induction accelerator

Expansion microscopy of zebrafish for neuroscience and developmental biology studies

Expansion microscopy (ExM) allows scalable imaging of preserved 3D biological specimens with nanoscale resolution on fast diffraction-limited microscopes. Here, we explore the utility of ExM in the larval and embryonic zebrafish, an important model organism for the study of neuroscience and development. Regarding neuroscience, we found that ExM enabled the tracing of fine processes of radial glia, which are not resolvable with diffraction-limited microscopy. ExM further resolved putative synaptic connections, as well as molecular differences between densely packed synapses. Finally, ExM could resolve subsynaptic protein organization, such as ring-like structures composed of glycine receptors. Regarding development, we used ExM to characterize the shapes of nuclear invaginations and channels, and to visualize cytoskeletal proteins nearby. We detected nuclear invagination channels at late prophase and telophase, potentially suggesting roles for such channels in cell division. Thus, ExM of the larval and embryonic zebrafish may enable systematic studies of how molecular components are configured in multiple contexts of interest to neuroscience and developmental biology.National Institutes of Health (U.S.) (Grant 1R01EB024261)National Institutes of Health (U.S.) (Grant 1R01MH110932)National Institutes of Health (U.S.) (Grant 2R01DA029639)National Institutes of Health (U.S.) (Grant 1R01NS087950)National Institutes of Health (U.S.) (Grant 1U01MH106011