Microarray analysis of E9.5 reduced folate carrier (RFC1; Slc19a1) knockout embryos reveals altered expression of genes in the cubilin-megalin multiligand endocytic receptor complex

<p>Abstract</p> <p>Background</p> <p>The reduced folate carrier (<it>RFC1</it>) is an integral membrane protein and facilitative anion exchanger that mediates delivery of 5-methyltetrahydrofolate into mammalian cells. Adequate maternal-fetal transport of folate is necessary for normal embryogenesis. Targeted inactivation of the murine <it>RFC1 </it>gene results in post-implantation embryolethality, but daily folic acid supplementation of pregnant dams prolongs survival of homozygous embryos until mid-gestation. At E10.5 <it>RFC1</it>^-/-embryos are developmentally delayed relative to wildtype littermates, have multiple malformations, including neural tube defects, and die due to failure of chorioallantoic fusion. The mesoderm is sparse and disorganized, and there is a marked absence of erythrocytes in yolk sac blood islands. The identification of alterations in gene expression and signaling pathways involved in the observed dysmorphology following inactivation of RFC1-mediated folate transport are the focus of this investigation.</p> <p>Results</p> <p>Affymetrix microarray analysis of the relative gene expression profiles in whole E9.5 <it>RFC1</it>^-/-vs. <it>RFC1</it>^+/+embryos identified 200 known genes that were differentially expressed. Major ontology groups included transcription factors (13.04%), and genes involved in transport functions (ion, lipid, carbohydrate) (11.37%). Genes that code for receptors, ligands and interacting proteins in the cubilin-megalin multiligand endocytic receptor complex accounted for 9.36% of the total, followed closely by several genes involved in hematopoiesis (8.03%). The most highly significant gene network identified by Ingenuity™ Pathway analysis included 12 genes in the cubilin-megalin multiligand endocytic receptor complex. Altered expression of these genes was validated by quantitative RT-PCR, and immunohistochemical analysis demonstrated that megalin protein expression disappeared from the visceral yolk sac of <it>RFC1</it>^-/-embryos, while cubilin protein was widely misexpressed.</p> <p>Conclusion</p> <p>Inactivation of <it>RFC1 </it>impacts the expression of several ligands and interacting proteins in the cubilin-amnionless-megalin complex that are involved in the maternal-fetal transport of folate and other nutrients, lipids and morphogens such as sonic hedgehog (Shh) and retinoids that play critical roles in normal embryogenesis.</p

Optimization of Concurrent Deployments of the Juvenile Salmon Acoustic Telemetry System and Other Hydroacoustic Equipment at John Day Dam

The purpose of this report is to document the results of the acoustic optimization study conducted at John Day Dam during January and February 2008. The goal of the study was to optimize performance of the Juvenile Salmon Acoustic Telemetry System (JSATS) by determining deployment and data acquisition methods to minimize electrical and acoustic interference from various other acoustic sampling devices. Thereby, this would allow concurrent sampling by active and passive acoustic methods during the formal evaluations of the prototype surface flow outlets at the dam during spring and summer outmigration seasons for juvenile salmonids. The objectives for the optimization study at John Day Dam were to: 1. Design and test prototypes and provide a total needs list of pipes and trolleys to deploy JSATS hydrophones on the forebay face of the powerhouse and spillway. 2. Assess the effect on mean percentage decoded of JSATS transmissions from tags arrayed in the forebay and detected on the hydrophones by comparing: turbine unit OFF vs. ON; spill bay OPEN vs. CLOSED; dual frequency identification sonar (DIDSON) and acoustic Doppler current profiler (ADCP) both OFF vs. ON at a spill bay; and, fixed-aspect hydroacoustic system OFF vs. ON at a turbine unit and a spill bay. 3. Determine the relationship between fixed-aspect hydroacoustic transmit level and mean percentage of JSATS transmissions decoded. The general approach was to use hydrophones to listen for transmissions from JSATS tags deployed in vertical arrays in a series perpendicular to the face of the dam. We used acoustic telemetry equipment manufactured by Technologic and Sonic Concepts. In addition, we assessed old and new JSATS signal detectors and decoders and two different types of hydrophone baffling. The optimization study consisted of a suite of off/on tests. The primary response variable was mean percentage of tag transmissions decoded. We found that there was no appreciable adverse effect on mean percentage decoded for JSATS transmitters from: turbine operations; spillway operations; DIDSON/ADCP acoustic energy; and PAS hydroacoustic systems at transmit level of -12 dB, although there was a significant impact at all higher transmit levels (-11 to -6 dB). The main conclusion from this optimization study is that valid JSATS telemetry data can be collected simultaneously with a DIDSON/ADCP and a PAS hydroacoustic system at transmit level -12 dB. Multiple evaluation tools should be considered to increase the robustness and thoroughness of future fish passage evaluations at John Day and other dams

Intelligible Kinds and Natural Kinds in Plotinus

Plotinus repeatedly emphasizes that the sensible world is the best possible world. This is supposed to follow from his etiological account of the world’s perpetual generation: As the automatic product of higher principles, the sensible world is simply another instantiation of intelligible principles, albeit embedded at a lower level in matter. This is meant to apply above all to the biological activity of nature, as each kind of living thing in the sensible world is supposed by Plotinus to co..

Funk from a Legal Prism

For more than 25 years, James Diamond Williams has had the opportunity to see the Funk world from a legal prism, engaging in a wide spectrum of experiences with the Ohio Players. He discusses his meeting with the music icon Clive Davis, the president of Arista Records, and the potential legal pitfalls, including issues with (and between) record companies, booking agents, competing and infringing groups, promoters with their own agendas, and, of course, the Internal Revenue Service.https://ecommons.udayton.edu/dayton_funk_content/1021/thumbnail.jp

From Plotinus to Proclus

Ancient Platonists after Plotinus maintain some central Plotinian tenets regarding the One as first cause, followed by Intellect and Soul, and the metaphysical processes of emanation and reversion, but are also critical of some of his views, and elaborate on them in crucial ways, often to solve perceived problems therein, or to incorporate other sources of wisdom. This chapter discusses three pagan Platonists, Porphyry, Iamblichus and Proclus, starting from their criticism, and subsequent development, of Plotinus' Platonism. The main changes they introduce concern the harmonization of Aristotle and Plato, an increased attention for logic and mathematics, a resort to a more religious approach (esp. theurgy), and the addition of numerous metaphysical distinctions. For the latter, most influential are a revision of the causal role of the One, and the introduction of a layer right below the One, of henads or 'ones'; the incorporation of the principle that everything is present in everything, in some relevant mode ("all in all"); a revision of the principles of causation, and an accompanying revaluation of matter; the more emphatic elaboration of intellect into a triad; the separation of universal and individual soul, and the view of the individual soul as completely descended; and the rejection of substantial evil

Plotinus and the Theory of Forms

Plotinus’ interpretation of the Forms is one of the most interesting aspects of his philosophical thought. The traditional interpretation of the Forms as the Demiurge’s Thoughts put at risk their ontological autonomy. With his theory Plotinus developed a brilliant solution to the problem. Firstly, by taking the cue from his view that the Intelligibles are not outside the Intellect, Plotinus argues that Forms are active thinking thoughts and not merely objects of thought. The Intellect, then, amounts to the systematic interrelation between the different Forms simultaneously thinking themselves and reflecting all the others from their own perspective. A second issue concerns the Forms’ causal role, which Plotinus explains with his theory of the double activity. Thirdly, this theory plays an important epistemological role. The identification between the Forms and the Intellect is the only possible solution to scepticism (to which are virtually doomed all previous Platonists, according to Plotinus). How important this problem was for Plotinus will be further clarified by the reference to another controversial theory, that of the undescended soul, whose main aim was precisely to show that (and how) human beings have access to real knowledge