Citations

Acetyl‐CoA carboxylase 2 (ACC2) is an isoform of ACC functioning as a negative regulator of fatty acid β‐oxidation. Spot14, a thyroid hormone responsive protein, and Mig12, a Spot14 paralog, have recently been identified as regulators of fatty acid synthesis targeting ACC1, a distinctive subtype of ACC. Here, we examined whether Spot14/Mig12 modulates ACC2. Nanoscale protein topography mapped putative protein–protein interactions between purified human Spot14/Mig12 and ACC2, validated by functional assays. Human ACC2 displayed consistent enzymatic activity, and homogeneous particle distribution was probed by atomic force microscopy. Citrate‐induced polymerization and enzymatic activity of ACC2 were restrained by the addition of the recombinant Spot14/Mig12 heterocomplex but only partially by the oligo‐heterocomplex, demonstrating that the heterocomplex is a designated metabolic inhibitor of human ACC2. Moreover, Spot14/Mig12 demonstrated a sequestering role preventing an initial ACC2 nucleation step during filamentous polymer formation. Thus, the Spot14/Mig12 heterocomplex controls human ACC2 polymerization and catalytic function, emerging as a previously unrecognized molecular regulator in catalytic lipid metabolism. © 2013 The Authors. Journal of Molecular Recognition published by John Wiley & Sons, Ltd.

In order to develop novel, effective therapies for central nervous system regeneration, it is essential to better understand the role of neurotrophic factors and to design, accordingly, better artificial scaffolds to support both neurite outgrowth and synapse formation. Both nerve growth factor and brain-derived neurotrophic factor are major factors in neural survival, development, synaptogenesis, and synaptic connectivity of primary cultured neurons. As a prime candidate coating material for such neural cultures, carbon nanotubes offer unique structural, mechanical, and electrical properties. In this study, carbon nanotubes coated glass-coverslips were used as the matrix of a primary neural culture system used to investigate the effects of carbon nanotubes on neurite outgrowth and nerve growth factor/brain-derived neurotrophic factor release and expression. For these purposes, we performed comparative analyses of primary cultured neurons on carbon nanotubes coated, non-coated, and Matrigel-coated coverslips. The morphological findings showed definite carbon nanotubes effects on the neurite outgrowths and synaptogenic figures in both cortical and hippocampal neurons when compared with the non-coated negative control. Although the carbon nanotubes did not change neurotrophin expression levels, it stimulated brain-derived neurotrophic factor release into the media from both types of neurons. Accordingly, we suggest a different mechanism of action between carbon nanotubes and Matrigel in relation to the specific neurotrophic factors. Since carbon nanotubes supply long-term extracellular molecular cues for the survival and neurite outgrowths of cultured neurons, the results from this study will contribute to an understanding of carbon nanotubes biological effects and provide new insight into their role in the secretion of neurotrophic factors.

Secretion of HCO3− at the apical side of the epithelial cells of the choroid plexus is an essential step in the formation of cerebrospinal fluid. Anion conductance with a high degree of HCO3− permeability has been observed and suggested to be the major pathway for HCO3− transport across the apical membrane. Recently, it was found that NBC (Na+/HCO3− co-transporter) 4, an electrogenic member of the NBC family, was expressed in the choroid plexus. We found that a novel variant of the NBC4 [NBC4g/Slc4a5 (solute carrier family 4, sodium bicarbonate co-transporter, member 5)] is almost exclusively expressed in the apical membrane of rat choroid plexus epithelium at exceptionally high levels. RNA interference-mediated knockdown allowed the functional demonstration that NBC4g is the major player in the HCO3− transport across the apical membrane of the choroid plexus epithelium. When combined with a recent observation that in choroid plexus epithelial cells electrogenic NBC operates with a stoichiometry of 3:1, the results of the present study suggest that NBC4g mediates the efflux of HCO3− and contributes to cerebrospinal fluid production.

Background Oral steroids are commonly used in the management of chronic rhinosinusitis (CRS) with and without nasal polyps (CRSwNP and CRSsNP, respectively). Past reports have included evaluation of the evidence for the use of oral steroids in CRS subtypes. However, a review with evidence‐based recommendations for all CRS subtypes has never been performed. The purpose of this article is to provide a comprehensive, evidence‐based approach for the utilization of oral steroids in the management of CRS. A systematic review of the literature was performed following recommendations of the Clinical Practice Guideline Manual, Conference on Guideline Standardization, and Appraisal of Guidelines and Research Evaluation. Inclusion criteria were: adult population ≥18 years old; CRS; oral steroids as the treatment group; and clearly defined primary clinical end‐point. This review identified and evaluated the literature on the use of oral steroids for CRSwNP, CRSsNP, allergic fungal sinusitis (AFS), and the use of oral steroids in the perioperative period in these patients. Recommendations based on evidence, benefit/harm assessment, and value judgments are made. Oral steroids are strongly recommended for short‐term management of CRSwNP. Oral steroids are also recommended for management of AFS. Oral steroid use in CRSsNP is optional due to insufficient strong evidence. Oral steroids are also strongly recommended in the perioperative period for CRSwNP and AFS. There is no recommendation for oral steroids use in the perioperative period in patients with CRSsNP. The risks of oral steroids are rare, but significant adverse effects must be considered. © 2012 ARS–AAOA, LLC. Methods A systematic review of the literature was performed following recommendations of the Clinical Practice Guideline Manual, Conference on Guideline Standardization, and Appraisal of Guidelines and Research Evaluation. Inclusion criteria were: adult population ≥18 years old; CRS; oral steroids as the treatment group; and clearly defined primary clinical end‐point. This review identified and evaluated the literature on the use of oral steroids for CRSwNP, CRSsNP, allergic fungal sinusitis (AFS), and the use of oral steroids in the perioperative period in these patients. Recommendations based on evidence, benefit/harm assessment, and value judgments are made. Oral steroids are strongly recommended for short‐term management of CRSwNP. Oral steroids are also recommended for management of AFS. Oral steroid use in CRSsNP is optional due to insufficient strong evidence. Oral steroids are also strongly recommended in the perioperative period for CRSwNP and AFS. There is no recommendation for oral steroids use in the perioperative period in patients with CRSsNP. The risks of oral steroids are rare, but significant adverse effects must be considered. © 2012 ARS–AAOA, LLC. Results This review identified and evaluated the literature on the use of oral steroids for CRSwNP, CRSsNP, allergic fungal sinusitis (AFS), and the use of oral steroids in the perioperative period in these patients. Recommendations based on evidence, benefit/harm assessment, and value judgments are made. Oral steroids are strongly recommended for short‐term management of CRSwNP. Oral steroids are also recommended for management of AFS. Oral steroid use in CRSsNP is optional due to insufficient strong evidence. Oral steroids are also strongly recommended in the perioperative period for CRSwNP and AFS. There is no recommendation for oral steroids use in the perioperative period in patients with CRSsNP. The risks of oral steroids are rare, but significant adverse effects must be considered. © 2012 ARS–AAOA, LLC. Conclusion Oral steroids are strongly recommended for short‐term management of CRSwNP. Oral steroids are also recommended for management of AFS. Oral steroid use in CRSsNP is optional due to insufficient strong evidence. Oral steroids are also strongly recommended in the perioperative period for CRSwNP and AFS. There is no recommendation for oral steroids use in the perioperative period in patients with CRSsNP. The risks of oral steroids are rare, but significant adverse effects must be considered. © 2012 ARS–AAOA, LLC.