Medium- and short-chain dehydrogenase/reductase gene and protein families: The MDR superfamily

The MDR superfamily with ~350-residue subunits contains the classical liver alcohol dehydrogenase (ADH), quinone reductase, leukotriene B4 dehydrogenase and many more forms. ADH is a dimeric zinc metalloprotein and occurs as five different classes in humans, resulting from gene duplications during vertebrate evolution, the first one traced to ~500 MYA (million years ago) from an ancestral formaldehyde dehydrogenase line. Like many duplications at that time, it correlates with enzymogenesis of new activities, contributing to conditions for emergence of vertebrate land life from osseous fish. The speed of changes correlates with function, as do differential evolutionary patterns in separate segments. Subsequent recognitions now define at least 40 human MDR members in the Uniprot database (corresponding to 25 genes when excluding close homologues), and in all species at least 10888 entries. Overall, variability is large, but like for many dehydrogenases, subdivided into constant and variable forms, corresponding to household and emerging enzyme activities, respectively. This review covers basic facts and describes eight large MDR families and nine smaller families. Combined, they have specific substrates in metabolic pathways, some with wide substrate specificity, and several with little known functions

Tax Expenditure Review Report: Bringing Tax Expenditures into the Budget Process

The term “tax expenditures” refers to tax provisions that are exceptions to a broadly-defined tax base – often referred to as the “reference tax base.” For example, the reference tax base for the income tax would include all forms of income. Tax expenditures include any tax provision that exempts certain forms of income, any tax deduction that favors particular forms or uses of income, and tax credits that reward particular behavior. Each tax expenditure narrows the tax base, resulting in either less revenue or higher tax rates. Tax expenditures are not inherently unsound. In fact, they can be useful tools to support important public policy goals. But there is general agreement that tax expenditures receive less scrutiny than direct expenditures. This report starts by making the case for bringing tax expenditures into the budget process and subjecting them to the same level of review as direct expenditures. It then recommends ways to accomplish that goal. As discussed in Chapter 1, Minnesota’s Tax Expenditure Budget report (TEB) is among the nation’s best. The 2010 report provides useful information on each of 296 tax expenditures, but it makes no attempt to evaluate whether those tax expenditures succeed in achieving their goals. Moreover, the TEB’s cost estimates for these provisions do not appear in any of the state’s biennial budget documents. Defining what is (and is not) a tax expenditure can be controversial. Chapter 2 reviews definitional issues. The definitions proposed in this report generally (though not always) agree with the list of tax expenditures provided in the TEB. Chapter 3 defines criteria to be used when evaluating tax expenditures, and it describes the additional information that would be required. Given the large number of tax expenditures, an evaluation process must determine which of them should be reviewed earliest. Chapter 4 recommends a process for setting those priorities. Chapter 5 proposes an ongoing evaluation process and recommends ways to bring tax expenditures into the normal budget process. A full list of recommendations can be found in Appendix A of this report. They include: Establish an eight-year evaluation cycle during which each tax expenditure would be reviewed. Create a Tax Expenditure Commission to oversee the evaluation process and make recommendations to the Legislature and governor. Prioritize which tax expenditures to evaluate earliest using the six criteria described in Chapter 4. Require the Tax Expenditure Commission to define a clear and measurable purpose for each tax expenditure if one is not stated in law. Require evaluations to list and analyze selected alternatives to the current provision. Provide adequate funding to the Department of Revenue and other state agencies, that would be responsible for completing the evaluations. Set a “revenue-neutral” sunset date at completion of each evaluation. Unless the tax expenditure is extended by that sunset date, it would expire and the tax rate for the affected tax would be adjusted downward to hold revenue constant. Fully integrate tax expenditures into the biennial budget process and include total expenditures for each tax in state budget summaries to show their fiscal impact on gross tax revenu

Efficacy and Safety of 5-Fluorouracil 0.5%/Salicylic Acid 10% in the Field-Directed Treatment of Actinic Keratosis: A Phase III, Randomized, Double-Blind, Vehicle-Controlled Trial

<p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s13555-016-0161-2">https://link.springer.com/article/10.1007/s13555-016-0161-2</a></p><p></p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p

Microscale chemically reactive electronic agents

En este artículo interesa, desde un enfoque globalizador, tratar los escenarios socioculturales y sus dimensiones en la evaluación del proceso educativo. Se presentan aspectos preliminares sobre la evaluación, sus funciones, componentes y valores, profundizando en la dinámica que configura el formato interactivo de la evaluación escrita.This acticle gives an overview of socio-cultural scenarios and their influences on evalution in the educational process. Preliminary observations on evalution, its functions, components and values are followed by a closer examination of the dynamics of the interactive format of written evalution.Cet article veut traiter les scénarios socioculturels et leurs dimensions en ce qui concerne l'évalution du processus éducatif. On présente des aspects préliminaires sur l'évaluation, ses fonctions, ses composantes et ses valeurs tout en analysant la dynamique du cadre interactif de l'évalution écrite

Extracellular ATP-Induced Alterations in Extracellular H+ Fluxes From Cultured Cortical and Hippocampal Astrocytes

Small alterations in the level of extracellular H+ can profoundly alter neuronal activity throughout the nervous system. In this study, self-referencing H+-selective microelectrodes were used to examine extracellular H+ fluxes from individual astrocytes. Activation of astrocytes cultured from mouse hippocampus and rat cortex with extracellular ATP produced a pronounced increase in extracellular H+ flux. The ATP-elicited increase in H+ flux appeared to be independent of bicarbonate transport, as ATP increased H+ flux regardless of whether the primary extracellular pH buffer was 26 mM bicarbonate or 1 mM HEPES, and persisted when atmospheric levels of CO2 were replaced by oxygen. Adenosine failed to elicit any change in extracellular H+ fluxes, and ATP-mediated increases in H+ flux were inhibited by the P2 inhibitors suramin and PPADS suggesting direct activation of ATP receptors. Extracellular ATP also induced an intracellular rise in calcium in cultured astrocytes, and ATP-induced rises in both calcium and H+ efflux were significantly attenuated when calcium re-loading into the endoplasmic reticulum was inhibited by thapsigargin. Replacement of extracellular sodium with choline did not significantly reduce the size of the ATP-induced increases in H+ flux, and the increases in H+ flux were not significantly affected by addition of EIPA, suggesting little involvement of Na+/H+ exchangers in ATP-elicited increases in H+ flux. Given the high sensitivity of voltage-sensitive calcium channels on neurons to small changes in levels of free H+, we hypothesize that the ATP-mediated extrusion of H+ from astrocytes may play a key role in regulating signaling at synapses within the nervous system