Nanomaterials for reversion of multidrug resistance in cancer: a new hope for an old idea?

publishersversionpublishe

Variable threshold of trigeminal cold-thermosensitive neurons is determined by a balance between TRPM8 and Kv1 potassium channels

Molecular determinants of threshold differences among cold thermoreceptors are unknown. Here we show that such differences correlate with the relative expression of IKD, a current dependent on Shaker-like Kv1 channels that acts as an excitability brake, and ITRPM8, a cold-activated excitatory current. Neurons responding to small temperature changes have high functional expression of TRPM8 (transient receptor potential cation channel, subfamily M, member 8) and low expression of IKD. In contrast, neurons activated by lower temperatures have a lower expression of TRPM8 and a prominent IKD. Otherwise, both subpopulations have nearly identical membrane and firing properties, suggesting that they belong to the same neuronal pool. Blockade of IKD shins the threshold of cold-sensitive neurons to higher temperatures and augments cold-evoked nocifensive responses in mice. Similar behavioral effects of IKD blockade were observed in TRPA1-/- mice. Moreover, only a small percentage of trigeminal cold-sensitive neurons were activated by TRPA1 agonists, suggesting that TRPA1 does not play a major role in the detection of low temperatures by uninjured somatic cold-specific thermosensory neurons under physiological conditions. Collectively, these findings suggest that innocuous cooling sensations and cold discomfort are signaled by specific low- and high-threshold cold thermoreceptor neurons, differing primarily in their relative expression of two ion channels having antagonistic effects on neuronal excitability. Thus, although TRPM8 appears to function as a critical cold sensor in the majority of peripheral sensory neurons, the expression of Kv1 channels in the same terminals seem to play an important role in the peripheral gating of cold-evoked discomfort and pain. Copyright © 2009 Society for Neuroscience.This work was supported by funds from the Spanish Ministry of Education and Science: Projects BFU2007-61855 to F.V., and BFU2005-08741 and CONSOLIDER-INGENIO 2010 CSD2007-00023 to C.B., and the Spanish Fundación Marcelino BotínPeer Reviewe

Novas atividades experimentais para o ensino básico - secundário

Dissertação de mestrado em Química – Formação Contínua de ProfessoresO objetivo primordial deste trabalho consistiu no desenvolvimento de técnicas simples, com impacto visual e em que os materiais utilizados, para além de acessíveis e de baixa toxicidade, fossem produtos do quotidiano. A separação dos pigmentos vegetais carotenoides, clorofilas a e b e flavonoides por cromatografia em coluna e em papel foi o tema central da investigação apresentada. Foram realizados vários estudos em que se investigou vários adsorventes não tóxicos do quotidiano, solventes de fácil acesso e procurou-se contornar os problemas encontrados recorrendo sempre a procedimentos experimentais simples de modo a evitar técnicas e equipamentos tipicamente laboratoriais. Os resultados obtidos permitiram desenvolver técnicas de cromatografia em coluna e em papel muito simples e eficazes na separação das bandas coloridas típicas destes pigmentos, que obedecem estritamente aos requisitos estabelecidos. Prosseguiu-se o estudo com a cromatografia dos pigmentos carotenoides existentes no pimento vermelho, na cenoura e na polpa de tomate. Realizou-se um estudo comparativo entre a maceração dos alimentos em acetona e a sua desidratação prévia em etanol. Realizou-se ainda algumas atividades com pigmentos flavonoides, nomeadamente a preparação de “bolas camaleão” para determinar o caráter ácidobase de soluções e o tingimento de tecidos com pétalas de rosa. No Ensino Básico e Secundário é fundamental motivar os alunos para o ensino das ciências. A realização de atividades laboratoriais é um dos meios mais eficazes para atingir esses objetivos. Assim e tendo por base o estudo realizado elaborou-se propostas de atividades laboratoriais para o Ensino Básico e Secundário, que pudessem ser realizadas em laboratórios com pouco equipamento e mesmo em salas de aulas normais.The primary objetive of this work was the development of simple techniques, with attractive visual impact, by the use of materials, not only accessible and with a low-toxicity, but also easily found in our everyday lives The separation of plant pigments carotenoids, chlorophylls a and b and flavonoids by column and paper chromatography was the central theme of this research project.A series of studies were carried out, where several everyday adsorbents, nontoxic and easily accessible solvents were investigated and in order to circumvent research problems, simple experimental procedures were always carried out in order to avoid typically laboratory techniques and equipment. The obtained results allowed the development of very simple column chromatography techniques that demonstrated to be very effective in the separation of the typical colored bands of these pigments and that strictly matched the primary objetives of the proposed work. The study proceeded with the chromatography of carotenoid pigments existing in red pepper, carrot and tomato paste. A comparative study was performed involving methods of food maceration in acetone and methods that used a previous food dehydration step with ethanol. A few activities using the flavonoid pigments were also done, particularly the preparation of "chameleon balls" to determine the acid-base character of solutions, and the dyeing of fabrics with rose petals. In primary and secondary school it is crucial to motivate students for the teaching of science. Carrying out laboratory activities is one of the most effective ways to achieve those goals. Thus, based on the research studies, proposals for laboratory activities for primary and secondary school were elaborated, so that they could be performed in laboratories without much equipment and even in normal classrooms

Validation of Six Commercial Antibodies for the Detection of Heterologous and Endogenous TRPM8 Ion Channel Expression

TRPM8 is a non-selective cation channel expressed in primary sensory neurons and other tissues, including the prostate and urothelium. Its participation in different physiological and pathological processes such as thermoregulation, pain, itch, inflammation and cancer has been widely described, making it a promising target for therapeutic approaches. The detection and quantification of TRPM8 seems crucial for advancing the knowledge of the mechanisms underlying its role in these pathophysiological conditions. Antibody-based techniques are commonly used for protein detection and quantification, although their performance with many ion channels, including TRPM8, is suboptimal. Thus, the search for reliable antibodies is of utmost importance. In this study, we characterized the performance of six TRPM8 commercial antibodies in three immunodetection techniques: Western blot, immunocytochemistry and immunohistochemistry. Different outcomes were obtained for the tested antibodies; two of them proved to be successful in detecting TRPM8 in the three approaches while, in the conditions tested, the other four were acceptable only for specific techniques. Considering our results, we offer some insight into the usefulness of these antibodies for the detection of TRPM8 depending on the methodology of choice

Ultrafine and nanoparticle formation and emission mechanisms during laser processing of ceramic materials

The use of laser technology in the ceramic industry is undergoing an increasing trend, as it improves surface properties. The present work aimed to assess ultrafine and nanoparticle emissions from two different types of laser treatments (tile sintering and ablation) applied to two types of tiles. New particle formation mechanisms were identified, as well as primary nanoparticle emissions, with concentrations reaching up to 6.7 x 10(6) particles Cm-3 and a mean diameter of 18 nm. Nanoparticle emission patterns were strongly dependent on temperature and raw tile chemical composition. Nucleation events were detected during the thermal treatment independently of the laser application. TOM images evidenced spherical ultrafine particles, originating from the tile melting processes. When transported across the indoor environment, particles increased in size (up to 38 nm) with concentrations remaining high (2.3 x 10(6) particles cm(-3)), Concentrations of metals such as Zn, Pb, Cu, Cr, As and al were found in particles < 250 nm

Ultrafine particle formation in the inland sea breeze airflow in Southwest Europe

Studies on ultrafine particles (diameter < 100nm) and air quality have mostly focused on vehicle exhaust emissions and on new particle formation in "clean" ambient air. Here we present a study focused on the processes contributing to ultrafine particle concentrations in a city (Huelva, SW Spain) placed close to a coastal area where significant anthropogenic emissions of aerosol precursors occur. The overall data analysis shows that two processes predominantly contribute to the number of particles coarser than 2.5 nm: vehicle exhaust emissions and new particle formation due to photo-chemical activity. As typically occurs in urban areas, vehicle exhaust emissions result in high concentrations of black carbon (BC) and particles coarser than 2.5 nm (N) during the morning rush hours. The highest N concentrations were recorded during the 11:00–17:00 h period, under the sea breeze regime, when low BC concentrations were registered and photochemical activity resulted in high O3 levels and in new particle formation in the aerosol precursors' rich inland airflow. In this period, it is estimated that about 80% of the number of particles are linked to sulfur dioxide emissions. The contributions to N of "carbonaceous material and those compounds nucleating/condensing immediately after emission" and of the "new particle formation processes in air masses rich gaseous precursors (e.g. SO2)" were estimated by means of a relatively novel method based on simultaneous measurements of BC and N. A comparison with two recent studies suggests that the daily cycles of "new particle formation" during the inland sea breeze is blowing period seem to be a feature of ultrafine particles in coastal areas of South-west Europe.This study has been carried out within the framework of several research projects: AER-REG (P07-RNM- 03125; Department of Innovation, Science and Enterprise of the Andalusian Autonomous Government), GRACCIE (CSD2007- 00067; Ministry of Science and Innovation of Spain), SIMAND (P07- RNM-02729; Department of Innovation, Science and Enterprise of the Andalusian Autonomous Government) and EPAU (B026/2007/3-10.1; Ministry of Environment of Spain)

Respuesta del Maíz ( Zea Mayz,) a Dos fuentes Nitrogenadas ( Urea y Sulfato de Amonio ) utilizando diferentes Dosis en Suelos de la Granja San pedro Alejandrino de Santa Marta

El presente ensayo, se realizó en la granja "San Pedro Alejandrino", propiedad de la Secretaria de fomento del Departamento del Magdalena. Este, tuvo como finalidad, determinar la capacidad de producción de Maíz con dos fuentes nitrogenadas a diferentes dosis. Las fuentes fueron: Urea del 46 % y Sulfato de Amonio. Se utilizaron Cinco niveles de Nitrógeno en cada una de las fuentes con refuerzo del elemento menor: Boro; Azufre. Los tratamientos fueron: para Sulfato de Amonio y para Urea: O kg/ha. - 50 kg/ha. - 100 kg/ha. - 150 kg/ha. - 200 kg/ha. Se empleó semillas certificada del híbrido I.C.A. 11-207. En la Costa Atlántica, el híbrido I.C.A. 11-207, tiene buen comportamiento, según los ensayos de Maíces. y Sorgo hechos por el I.C. A. La precipitación pluvial en los primeros días de iniciado el trabajo, fue bastante escasa, lo que dio lugar a emplear riegos por gravedad; a diferencia de los meses de Octubre (a fines) y noviembre. Se observaron ataques de gusano cogollero, de la mazorca, los cuales fueron fuertes, por lo cual hubo que hacer aplicaciones de los insecticidas correspondientes al ataque de los insectos respectivos, se hicieron en total cinco aplicaciones. También se presentó ataque de DIATRAEA Sp, pero no fue un ataque fuerte, por lo cual no tuvimos necesidad de recurrir a ningún insecticida. Respecto a la producción de biomasa, el análisis estadístico pudo mostrar que no hubo diferencia significativa en ninguno de los tratamientos: O kg/ha. - 50 kg/ha. - 100 kg/ha. 150 y 200. kg/ha

The abundance and clustering of dark haloes in the standard Lambda CDM cosmogony

Much evidence suggests that we live in a flat Cold Dark Matter universe with a cosmological constant. Accurate analytic formulae are now available for many properties of the dark halo population in such a Universe. Assuming current ``concordance'' values for the cosmological parameters, we plot halo abundance against redshift as a function of halo mass, of halo temperature, of the fraction of cosmic matter in haloes, of halo clustering strength, and of the clustering strength of the z=0 descendants of high redshift haloes. These plots are useful for understanding how nonlinear structure grows in the model. They demonstrate a number of properties which may seem surprising, for example: 10^9 solar mass haloes are as abundant at z=20 as L_* galaxies are today; 10^6K haloes are equally abundant at z=8 and at z=0; 10% of all matter is currently in haloes hotter than 1 keV, while more than half is in haloes too cool to trap photo-ionized gas; 1% of all matter at z=15 is in haloes hot enough to ionise hydrogen; haloes of given mass or temperature are more clustered at higher redshift; haloes with the abundance of present-day L_* galaxies are equally clustered at all z10 are more clustered at z=0 than are L_* galaxies.Comment: 10 pages, 2 ps figures, version to be published in MNRA

Process-generated nanoparticles from ceramic tile sintering: Emissions, exposure and environmental release

Under a Creative Commons license.-- et al.The ceramic industry is an industrial sector in need of significant process changes, which may benefit from innovative technologies such as laser sintering of ceramic tiles. Such innovations result in a considerable research gap within exposure assessment studies for process-generated ultrafine and nanoparticles. This study addresses this issue aiming to characterise particle formation, release mechanisms and their impact on personal exposure during a tile sintering activity in an industrial-scale pilot plant, as a follow-up of a previous study in a laboratory-scale plant. In addition, possible particle transformations in the exhaust system, the potential for particle release to the outdoor environment, and the effectiveness of the filtration system were also assessed. For this purpose, a tiered measurement strategy was conducted. The main findings evidence that nanoparticle emission patterns were strongly linked to temperature and tile chemical composition, and mainly independent of the laser treatment. Also, new particle formation (from gaseous precursors) events were detected, with nanoparticles  87% efficiency in particle number concentrations removal.This work was supported by the European Commission FP7 (FP7-PEOPLE-2012-ITN) Marie Curie ITN project no. 315760 (HEXACOMM) and by the Spanish MINECO (PCIN-2015-173-C02-01) under the frame of SIINN, the ERA-NET for a Safe Implementation of Innovative Nanoscience and Nanotechnology, through SIINN-ERANET project CERASAFE (id.:16). Additional support was provided by LIFE projects AIRUSE (LIFE11 ENV/ES/584), CERAMGLASS (LIFE11 ENV/ES/560) and LASERFIRING (LIFE09 ENV/ES/435).Peer Reviewe