Natural Voltage-Gated Sodium Channel Ligands: Biosynthesis and Biology

Natural product biosynthetic pathways are composed of enzymes that use powerful chemistry to assemble complex molecules. Small molecule neurotoxins are examples of natural products with intricate scaffolds which often have high affinities for their biological targets. The focus of this Minireview is small molecule neurotoxins targeting voltage-gated sodium channels (VGSCs) and the state of knowledge on their associated biosynthetic pathways. There are three small molecule neurotoxin receptor sites on VGSCs associated with three different classes of molecules: guanidinium toxins, alkaloid toxins, and ladder polyethers. Each of these types of toxins have unique structural features which are assembled by biosynthetic enzymes and the extent of information known about these enzymes varies among each class. The biosynthetic enzymes involved in the formation of these toxins have the potential to become useful tools in the efficient synthesis of VGSC probes.     

Growth factors in subglottic stenosis

We sought to define the role of fibrogenic peptides in subglottic stenosis (SGS). Biopsy specimens were obtained from patients with stenosis following endotracheal intubation (group 1, n = 5, mean age 5), patients without a history of any precedent trauma, ie. idiopathic stenosis (group 2, n = 3, mean age 40), and those without stenosis (group 3, n = 3, mean age 70). Formalin-fixed biopsy specimens were analyzed following immunohistochemical staining to determine if epidermal growth factor (EGF), platelet-derived growth factor-AA and -BB (PDGF-AA/BB), transforming growth factor-beta 1 and -beta 2 (TGF-beta 1, beta 2), or basic fibroblast growth factor (bFGF) was deposited in these tissues. Blinded analysis revealed TGF-beta 2 and PDGF-AA to be present in seven of eight biopsy specimens from SGS and absent in controls. Staining for PDGF-BB was observed in the mucosa and submucosa and occasionally within vessel walls. Staining of individual growth factors appeared to correlate closely with the presence of granulation tissue. Essentially no bFGF or TGF-beta 1 was observed. Differences were found between patients in groups 1 and 2; tissue from group 1 revealed deposition of EGF and PDGF-BB in submucosa, epithelium, and vasculature. In summary, our experimental findings implicate PDGF and TGF-beta 2, perhaps acting in concert, in mediating the pathologic fibrotic process observed in subglottic stenosis. Epidermal growth factor, in conjunction with TGF-beta and PDGF, may also have a role, but further investigation is needed to more precisely define it.     

ETHANOL FROM SOUTHERN HARDWOODS: THE ROLE OF PRESULFONATION IN THE ACID HYDROLYSIS PROCESS

A two-stage acid hydrolysis process is currently used in the production of ethanol from hardwoods. In this process, dilute sulfuric acid in water at high pressure and short residence times hydrolyzes the wood and first stage substrate. The chemical action is particularly impeded in the second stage by the presence of acid condensed lignin.

Presulfonation followed by delignification is proposed using a sulfur dioxide/water sulfuric acid/ethanol treatment step in place of the first stage acid hydrolysis step to alleviate this problem.

Results presented include the effects caused by varying treatment time, sulfur dioxide concentration, temperature and ethanol concentration on the degree of delignification, and, on the recovery of C₅ and C₆ sugars in the hydrolysates. A preliminary economic feasibility analysis is made to determine the impact of improved ethanol yields and lignin by-product values in the production of ethanol from hardwoods.     

Body image, attitudes to weight, and misperceptions of figure preferences of the opposite sex: A comparison of men and women in two generations.

This study explores some possible causes of the recent increase in dieting and eating disorders among American women. Measures on body image, attitudes to eating and weight, and eating behaviors were collected from male (sons) and female (daughters) college students and their biological parents. All groups but the sons considered their current body shape to be heavier than their ideal. Mothers and daughters believed that men (of their own generation) prefer much thinner women than these men actually prefer. Mothers and daughters both showed great concern about weight and eating. Although fathers resembled mothers and daughters in their perception of being overweight, they were more similar to their sons in being relatively unconcerned about weight and eating. Hence, the major factor in concern about weight is sex rather than generation or discrepancy between perception of current and ideal body shape. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

DC harmonic distortion minimization of thyristor converters underunbalanced voltage supply using asymmetrical firing angle

Noncharacteristic harmonics of significant magnitude are produced at the output and input terminals of phase-controlled power converters under unbalanced voltage supply conditions. The concept of switching functions has been proposed before to evaluate the harmonics produced by a phase-controlled six-pulse power converter under both balanced and unbalanced power supply conditions. This paper extends the switching-functions approach to establish analytical equations for the DC output voltage harmonics produced by 12-, 18-, and 24-pulse power converters. The problem is approached from the standpoint of symmetrical voltage components. The increase in distortion under unbalance is caused by the appearance of a second harmonic component. A method, based on an asymmetrical firing angle, to cancel the second harmonic at the power converter output under unbalanced voltage supply is also presented. Cancellation of the second harmonic improves power converter DC output voltage quality     

Improving the usability of standard schemas

Due to the development of XML and other data models such as OWL and RDF, sharing data is an increasingly common task since these data models allow simple syntactic translation of data between applications. However, in order for data to be shared semantically, there must be a way to ensure that concepts are the same. One approach is to employ commonly usedschemas—called standard schemas —which help guarantee that syntactically identical objects have semantically similar meanings. As a result of the spread of data sharing, there has been widespread adoption of standard schemas in a broad range of disciplines and for a wide variety of applications within a very short period of time. However, standard schemas are still in their infancy and have not yet matured or been thoroughly evaluated. It is imperative that the data management research community takes a closer look at how well these standard schemas have fared in real-world applications to identify not only their advantages, but also the operational challenges that real users face.     

Neuroendocrine Tumor‐Targeted Upconversion Nanoparticle‐Based Micelles for Simultaneous NIR‐Controlled Combination Chemotherapy and Photodynamic Therapy,and Fluorescence Imaging

Although neuroendocrine tumors (NETs) are slow growing, they are frequently metastatic at the time of discovery and no longer amenable to curative surgery, emphasizing the need for the development of other treatments. In this study, multifunctional upconversion nanoparticle (UCNP)‐based theranostic micelles are developed for NET‐targeted and near‐infrared (NIR)‐controlled combination chemotherapy and photodynamic therapy (PDT), and bioimaging. The theranostic micelle is formed by individual UCNP functionalized with light‐sensitive amphiphilic block copolymers poly(4,5‐dimethoxy‐2‐nitrobenzyl methacrylate)‐polyethylene glycol (PNBMA‐PEG) and Rose Bengal (RB) photosensitizers. A hydrophobic anticancer drug, AB3, is loaded into the micelles. The NIR‐activated UCNPs emit multiple luminescence bands, including UV, 540 nm, and 650 nm. The UV peaks overlap with the absorption peak of photocleavable hydrophobic PNBMA segments, triggering a rapid drug release due to the NIR‐induced hydrophobic‐to‐hydrophilic transition of the micelle core and thus enabling NIR‐controlled chemotherapy. RB molecules are activated via luminescence resonance energy transfer to generate ¹O₂ for NIR‐induced PDT. Meanwhile, the 650 nm emission allows for efficient fluorescence imaging. KE108, a true pansomatostatin nonapeptide, as an NET‐targeting ligand, drastically increases the tumoral uptake of the micelles. Intravenously injected AB3‐loaded UCNP‐based micelles conjugated with RB and KE108—enabling NET‐targeted combination chemotherapy and PDT—induce the best antitumor efficacy.     

The detection of fake-bad and fake-good responding on the Millon Clinical Multiaxial Inventory III.

The purpose of this study was to examine the effectiveness of the 3 Modifying Indices of the Millon Clinical Multiaxial Inventory III (MCMI—III) in the detection of fake-bad and fake-good responding. The sample consisted of 160 psychiatric outpatients. Paired t tests were performed to examine the effects of instructional set (faking vs standard instructions). As hypothesized, instructional set produced significant differences on Scale X, Scale Y, and Scale Z in both fake-bad and fake-good analyses. Single-scale cutoff scores were as effective as multiple-scale cutoffs. The overall rates of successful classification indicated moderate effectiveness and utility of the MCMI—III Modifying Indices in the detection of dissimulated responding. When base rates were varied to more closely approximate a general clinical population, overall classification accuracy increased, but identification of faking (positive predictive power) gradually eroded with declining base-rate estimates. At lower base rates of faking, MCMI—III standard cutoff points yielded a high number of false positives. (PsycINFO Database Record (c) 2010 APA, all rights reserved)