Mass of Spiral Galaxies by Means of a Maximum Disc Model / Masa de galaxias espirales por medio de un modelo de disco máximo / Massa de galáxias espirais por meio de um modelo de disco máximo

Abstract Maximum disc mass models for a set of spiral galaxies from the Ursa Major Cluster are presented. We construct the models using the Hunther method and the particular solutions are chosen in such a way that the circular velocities are adjusted very accurately to the observed rotation curves of some specific spiral galaxies. Under the maximum disc hypothesis, we consider that the rotation curves of the analyzed galaxies can be modeled with only the contribution of the disc. This implies that it is not necessary to consider the contribution ot the dark matter halo in the inner part of the spiral. In this way, the models reproduce the global behavior of the rotation curves in the great majority of galaxies. Producing good adjustments to calculate the total mass of these galaxies, and yielding values of the order of 1O10 M ☉. Based on the vertical stability criterion presented by Viera & Ramos-caro (2016), we find that all the galaxies analyzed present a vertically stable behavior. On the other hand, from the analysis of the epicyclic frequency we find that all the models exhibit mainly a radial stable behaviour except at the edge of the disc.

Resumen Presentamos modelos de masa de disco máximo para un conjunto de galaxias espirales del Cluster Ursa Major. Los modelos se obtienen por medio del método de Hunter y las soluciones particulares se eligen de tal manera que las velocidades circulares se ajustan muy exactamente a las curvas de rotación observadas de algunas galaxias espirales específicas. Bajo la hipótesis del disco máximo, suponemos que la masa del disco es lo más grande posible, en consonancia con la curva de rotación de la galaxia. Por lo tanto, la contribución de la masa del halo de la materia oscura se considera insignificante en las partes internas de las espirales. Los modelos reproducen la estructura general de las curvas de rotación en la mayoría de las galaxias, proporcionando buenos ajustes para calcular la masa total de estas galaxias obteniendo valores del orden de 1010 M ☉. Basados en el criterio de estabilidad vertical presentado por Vieira and Ramos-Caro (2016), encontramos que todas las galaxias analizadas presentan un comportamiento verticalmente estable. Por otro lado, a partir del análisis de la frecuencia epicíclica se observa que todos los modelos presentaron mayormente un comportamiento estable radial excepto en el borde del disco.

Resumo Apresentamos modelos de massa de disco máximo para um conjunto de galáxias espirais do Cluster Ursa Major. Os modelos são obtidos por meio do método Hunter e as soluções particulares são escolhidas de tal forma que as velocidades circulares são ajustadas com muita precisão às curvas de rotação observadas de algumas galáxias espirais específicas. Sob a hipótese de disco máximo, supomos que a massa do disco é tão grande quanto possível, consistente com a curva de rotação da galáxia. A contribuição de massa do halo da matéria escura é, portanto, assumida como insignificante nas partes internas das espirais. Os modelos reproduzem a estrutura geral das curvas de rotação na maioria das galáxias, proporcionando bons ajustes para calcular a massa total dessas galáxias obtendo valores da ordem de 1010 M ☉. Com base no critério de estabilidade vertical apresentado por Vieira and Ramos-Caro (2016), descobrimos que todas as galáxias analisadas apresentam um comportamento verticalmente estável. Por outro lado, a partir da análise da frequência epicíclica, descobrimos que todos os modelos apresentaram principalmente um comportamento estável radial, exceto na borda do disco.

Development and testing of AAV-delivered single-chain variable fragments for the treatment of methamphetamine abuse.

Methamphetamine (METH) substance abuse disorders have major impact on society, yet no medications have proven successful at preventing METH relapse or cravings. Anti-METH monoclonal antibodies can reduce METH brain concentrations; however, this therapy has limitations, including the need for repeated dosing throughout the course of addiction recovery. An adeno-associated viral (AAV)-delivered DNA sequence for a single-chain variable fragment could offer long-term, continuous expression of anti-METH antibody fragments. For these studies, we injected mice via tail vein with 1 x 10(12) vector genomes of two AAV8 scFv constructs and measured long-term expression of the antibody fragments. Mice expressed each scFv for at least 212 days, achieving micromolar scFv concentrations in serum. In separate experiments 21 days and 50 days after injecting mice with AAV-scFvs mice were challenged with METH in vivo. The circulating scFvs were capable of decreasing brain METH concentrations by up to 60% and sequestering METH in serum for 2 to 3 hrs. These results suggest that AAV-delivered scFv could be a promising therapy to treat methamphetamine abuse.

Evidence-based treatment for gynoid lipodystrophy: A review of the recent literature.

Gynoid lipodystrophy (GLD) is a structural, inflammatory, and biochemical disorder of the subcutaneous tissue causing alterations in the topography of the skin. Commonly known as "cellulite," GLD affects up to 90% of women, practically in all stages of the life cycle, beginning in puberty. It is a clinical condition that considerably affects the patients' quality of life. It is a frequent reason for consultation, although the patients resort to empirical, improvised, nonevidence-based treatments which discourage and can be a source of frustration not only because of the lack of results but also due to the complications derived from those treatments. In this article, a panel of experts from different specialties involved in the management of this clinical skin disorder presents the results of a systematic literature search and of the consensus discussion of the evidence obtained from different treatments currently available. The analysis was divided into topical, systemic, noninvasive, and minimally invasive treatments.

Libyostrongylus douglassii (Strongylida: Trichostrongylidae) in ostrich (Struthio camelus) farms from Colombia.

Ostrich farming is an important livestock industry in different world regions with a diverse offer of products and services. In Colombia, as in other countries, this market led the importation of animals from countries like Canada, United States of America and South Africa for breeding objectives. With the animals, specific pathogens for these ratites could be introduced. Libyostrongylus spp. is a strongylid nematode with worldwide distribution, which can induce a severe disease and mortality in infected animals. Limited studies in Colombia have identified parasites in ostrich farming systems. The aim of this study was to identify parasites of the genus Libyostrongylus to a species level in faecal samples from ostrich farms in three departments of Colombia. Five ostrich farms from Boyacá, Meta and Tolima were sampled in 2011 and in 2013 to obtain fresh faecal samples which were further processed by flotation tests for egg visualization and faecal culture for infective larvae identification by morphological and morphometric parameters. One from the five farms, located in Meta department, was positive for strongylid eggs in both sampling periods. After faecal culture, infective larvae were identified as Libyostrongylus douglassii. These results corroborate previous records of Libyostrongylus in ostrich farms from Meta and confirms, for the first time, infection by L. douglassii in ratites from this region. Further studies must identify associated determinants for infection and its effects on the flock health and production.

PEGylation of a High-Affinity Anti-(+)Methamphetamine Single Chain Antibody Fragment Extends Functional Half-Life by Reducing Clearance.

PURPOSE: Methamphetamine (METH) abuse is a worldwide drug problem, yet no FDA-approved pharmacological treatments are available for METH abuse. Therefore, we produced an anti-METH single chain antibody fragment (scFv7F9Cys) as a pharmacological treatment for METH abuse. ScFv's have a short half-life due to their small size, limiting their clinical use. Thus, we examined the pharmacokinetic effects of conjugating poly(ethylene) glycol (-PEG) to scFv7F9Cys to extend its functional half-life. METHODS: The affinity of scFv7F9Cys and PEG conjugates to METH was determined in vitro via equilibrium dialysis saturation binding. Pharmacokinetic and parameters of scFv7F9Cys and scFv7F9Cys-PEG20K (30 mg/kg i.v. each) and their ability to bind METH in vivo were determined in male Sprague-Dawley rats receiving a subcutaneous infusion of METH (3.2 mg/kg/day). RESULTS: Of three PEGylated conjugates, scFv7F9Cys-PEG20K was determined the most viable therapeutic candidate. PEGylation of scFv7F9Cys did not alter METH binding functionality in vitro, and produced a 27-fold increase in the in vivo half-life of the antibody fragment. Furthermore, total METH serum concentrations increased following scFv7F9Cys or scFv7F9Cys-PEG20K administration, with scFv7F9Cys-PEG20K producing significantly longer changes in METH distribution than scFv7F9Cys. CONCLUSIONS: PEGylation of scFv7F9Cys significantly increase the functional half-life of scFv7F9Cys, suggesting it may be a long-lasting pharmacological treatment option for METH abuse.

A Nanotechnology-Based Platform for Extending the Pharmacokinetic and Binding Properties of Anti-methamphetamine Antibody Fragments.

To address the need for effective medications to aid in the treatment of methamphetamine (METH) abuse, we used a nanotechnology approach to customize the in vivo behavior of an anti-METH single chain antibody (scFv7F9Cys). Anti-METH scFv7F9Cys was conjugated to dendrimer nanoparticles via a polyethylene glycol (PEG) linker to generate high-order conjugates termed dendribodies. We found that the high affinity (KD = 6.2 nM) and specificity for METH was unchanged after nanoparticle conjugation. The dendribodies were administered in an i.v. bolus to male Sprague Dawley rats after starting a s.c. infusion of METH. The PCKN values for clearance and volume of distribution of scFv7F9Cys after conjugation to dendrimers decreased 45 and 1.6-fold respectively, and the terminal elimination half-life increased 20-fold. Organ distribution of scFv7F9Cys and dendribody in blood and urine agreed well with the PCKN data. Renal clearance appeared to be the major route of elimination for both experimental medications. We have thus successfully developed a novel multivalent METH-binding nanomedicine by conjugating multiple anti-METH scFvs to dendrimer nanoparticles, extending the scFv half-life from 1.3 (± 0.3) to 26 (± 2.6) hr. These data suggest that the dendribody design could be a feasible platform for generating multivalent antibodies with customizable PCKN profiles.

Therapeutic anti-methamphetamine antibody fragment-nanoparticle conjugates: synthesis and in vitro characterization.

Treatments specific to the medical problems caused by methamphetamine (METH) abuse are greatly needed. Toward this goal, we are developing new multivalent anti-METH antibody fragment-nanoparticle conjugates with customizable pharmacokinetic properties. We have designed a novel anti-METH single chain antibody fragment with an engineered terminal cysteine (scFv6H4Cys). Generation 3 (G3) polyamidoamine dendrimer nanoparticles were chosen for conjugation due to their monodisperse properties and multiple amine functional groups. ScFv6H4Cys was conjugated to G3 dendrimers via a heterobifunctional PEG cross-linker that is reactive to a free amine on one end and a thiol group on the other. PEG modified dendrimers were synthesized by reacting the PEG cross-linker with dendrimers in a stoichiometric ratio of 11:1, which were further reacted with 3-fold molar excess of anti-METH scFv6H4Cys. This reaction resulted in a heterogeneous mix of G3-PEG-scFv6H4Cys conjugates (dendribodies) with three to six scFv6H4Cys conjugated to each dendrimer. The dendribodies were separated from the unreacted PEG modified dendrimers and scFv6H4Cys using affinity chromatography. A detailed in vitro characterization of the PEG modified dendrimers and the dendribodies was performed to determine size, purity, and METH binding function. The dendribodies were found to have affinity for METH identical to that of the unconjugated scFv6H4Cys in saturation binding assays, whereas the PEG modified dendrimers had no affinity for METH. These data suggest that an anti-METH scFv can be successfully conjugated to a PEG modified dendrimer nanoparticle with no adverse effects on METH binding properties. This study is a critical step toward preclinical characterization and development of a novel nanomedicine for the treatment of METH abuse.

A mutant ataxin-3 fragment results from processing at a site N-terminal to amino acid 190 in brain of Machado-Joseph disease-like transgenic mice.

Machado-Joseph disease also called spinocerebellar ataxia type 3 (MJD/SCA3) is a hereditary and neurodegenerative movement disorder caused by ataxin-3 with a polyglutamine expansion (mutant ataxin-3). Neuronal loss in MJD/SCA3 is associated with a mutant ataxin-3 toxic fragment. Defining mutant ataxin-3 proteolytic site(s) could facilitate the identification of the corresponding enzyme(s). Previously, we reported a mutant ataxin-3 mjd1a fragment in the brain of transgenic mice (Q71) that contained epitopes C-terminal to amino acid 220. In this study, we generated and characterized neuroblastoma cells and transgenic mice expressing mutant ataxin-3 mjd1a lacking amino acids 190-220 (deltaQ71). Less deltaQ71 than Q71 fragments were detected in the cell but not mouse model. The transgenic mice developed an MJD/SCA3-like phenotype and their brain homogenates had a fragment containing epitopes C-terminal to amino acid 220. Our results support the toxic fragment hypothesis and narrow the mutant ataxin-3 cleavage site to the N-terminus of amino acid 190.

A critical function for the actin cytoskeleton in targeted exocytosis of prefusion vesicles during myoblast fusion.

Myoblast fusion is an essential step during muscle differentiation. Previous studies in Drosophila have revealed a signaling pathway that relays the fusion signal from the plasma membrane to the actin cytoskeleton. However, the function for the actin cytoskeleton in myoblast fusion remains unclear. Here we describe the characterization of solitary (sltr), a component of the myoblast fusion signaling cascade. sltr encodes the Drosophila ortholog of the mammalian WASP-interacting protein. Sltr is recruited to sites of fusion by the fusion-competent cell-specific receptor Sns and acts as a positive regulator for actin polymerization at these sites. Electron microscopy analysis suggests that formation of F-actin-enriched foci at sites of fusion is involved in the proper targeting and coating of prefusion vesicles. These studies reveal a surprising cell-type specificity of Sltr-mediated actin polymerization in myoblast fusion, and demonstrate that targeted exocytosis of prefusion vesicles is a critical step prior to plasma membrane fusion.

Control of myoblast fusion by a guanine nucleotide exchange factor, loner, and its effector ARF6.

Myoblast fusion is essential for the formation and regeneration of skeletal muscle. In a genetic screen for regulators of muscle development in Drosophila, we discovered a gene encoding a guanine nucleotide exchange factor, called loner, which is required for myoblast fusion. Loner localizes to subcellular sites of fusion and acts downstream of cell surface fusion receptors by recruiting the small GTPase ARF6 and stimulating guanine nucleotide exchange. Accordingly, a dominant-negative ARF6 disrupts myoblast fusion in Drosophila embryos and in mammalian myoblasts in culture, mimicking the fusion defects caused by loss of Loner. Loner and ARF6, which also control the proper membrane localization of another small GTPase, Rac, are key components of a cellular apparatus required for myoblast fusion and muscle development. In muscle cells, this fusigenic mechanism is coupled to fusion receptors; in other fusion-competent cell types it may be triggered by different upstream signals.