RESUMO
The integration of monitoring technologies in the last decades has been a key factor in the development of new ways to track air pollutants and supplementing the network of traditional monitoring systems. In this regard, the appearance of affordable and accurate sensor devices to monitor air quality has made possible to obtain relevant data about the state of the air, and moreover, eminent institutions are interested in promoting the use of novel and more affordable tools for air pollution, such as the United States Environmental Protection Agency and European institutions, within a new approach to environmental surveillance, known as Next Generation Compliance and Enforcement technologies. On other hand, in order to get more reliable measurements, the use of machine learning to support adjustment or calibration process has been used in some studies to improve the performance of monitoring devices. On this paper, led by a group of specialists of the Chilean Superintendence of Environment (henceforth, SMA from its Spanish initials), a first approach case study related to the convenience of the usage of low-cost devices in environmental enforcement will be presented. The study was made in the Metropolitan Region of Santiago and considers the spatial distribution of different particulate matter sensors in the region. Some aspects regarding communication and technical issues are presented as well as the main findings about their performance. Results illustrate that low-cost sensors, aided by machine learning algorithms, could provide a reliable enough general screening of particulate matter within a large city, constituting a valuable decision-making tool for environmental oversight, as well as a powerful preventive and deterrent approach for compliance.
Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/análise , Monitoramento Ambiental/métodos , Material Particulado/análise , Algoritmos , Chile , Cidades , Tomada de Decisões , Aprendizado de Máquina , Estados Unidos , United States Environmental Protection AgencyRESUMO
Transmembrane BAX inhibitor motif-containing (TMBIM)-6, also known as BAX-inhibitor 1 (BI-1), is an anti-apoptotic protein that belongs to a putative family of highly conserved and poorly characterized genes. Here we report the function of TMBIM3/GRINA in the control of cell death by endoplasmic reticulum (ER) stress. Tmbim3 mRNA levels are strongly upregulated in cellular and animal models of ER stress, controlled by the PERK signaling branch of the unfolded protein response. TMBIM3/GRINA synergies with TMBIM6/BI-1 in the modulation of ER calcium homeostasis and apoptosis, associated with physical interactions with inositol trisphosphate receptors. Loss-of-function studies in D. melanogaster demonstrated that TMBIM3/GRINA and TMBIM6/BI-1 have synergistic activities against ER stress in vivo. Similarly, manipulation of TMBIM3/GRINA levels in zebrafish embryos revealed an essential role in the control of apoptosis during neuronal development and in experimental models of ER stress. These findings suggest the existence of a conserved group of functionally related cell death regulators across species beyond the BCL-2 family of proteins operating at the ER membrane.
Assuntos
Cálcio/metabolismo , Retículo Endoplasmático/metabolismo , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Resposta a Proteínas não Dobradas/genética , Fator 4 Ativador da Transcrição/metabolismo , Animais , Apoptose , Drosophila melanogaster , Estresse do Retículo Endoplasmático , Fibroblastos/metabolismo , Células HEK293 , Células HeLa , Homeostase , Humanos , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Camundongos , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Peixe-Zebra , eIF-2 Quinase/metabolismoRESUMO
Saxitoxin (STX) and its derivatives are highly toxic natural compounds produced by dinoflagellates commonly present in marine phytoplankton. During algal blooms ("red tides"), shellfish accumulate saxitoxins leading to paralytic shellfish poisoning (PSP) in human consumers. PSP is a consequence of the high-affinity block of voltage-dependent Na channels in neuronal and muscle cells. PSP poses a significant public health threat and an enormous economic challenge to the shellfish industry worldwide. The standard screening method for marine toxins is the mouse mortality bioassay that is ethically problematic, costly and time-consuming. We report here an alternative, functional assay based on electrical recordings in cultured cells stably expressing a PSP target molecule, the STX-sensitive skeletal muscle Na channel. STX-equivalent concentration in the extracts was calibrated by comparison with purified STX, yielding a highly significant correlation (R=0.95; N=30) between electrophysiological determinations and the values obtained by conventional methods. This simple, economical, and reproducible assay obviates the need to sacrifice millions of animals in mandatory paralytic shellfish toxin screening programs.
Assuntos
Toxinas Marinhas/toxicidade , Paralisia/induzido quimicamente , Saxitoxina/toxicidade , Frutos do Mar/análise , Bloqueadores dos Canais de Sódio , Animais , Ligação Competitiva/efeitos dos fármacos , Linhagem Celular , Eletrofisiologia , Humanos , Camundongos , Técnicas de Patch-Clamp , Proteínas Recombinantes , Reprodutibilidade dos Testes , Canais de Sódio/genéticaRESUMO
The functional heterogeneity of the ryanodine receptor (RyR) channels in avian cerebellum was defined. Heavy endoplasmic reticulum microsomes had significant levels of ryanodine and inositol 1,4,5-trisphosphate binding. Scatchard analysis and kinetic studies indicated the existence of at least two distinct ryanodine binding sites. Ryanodine binding was calcium-dependent but was not significantly enhanced by caffeine. Incorporation of microsomes into planar lipid bilayers revealed ion channels with pharmacological features (calcium, magnesium, ATP, and caffeine sensitivity) similar to the RyR channels found in mammalian striated muscle. Despite a wide range of unitary conductances (220-500 picosiemens, symmetrical cesium methanesulfonate), ryanodine locked both channels into a characteristic slow gating subconductance state, positively identifying them as RyR channels. Two populations of avian RyR channels were functionally distinguished by single channel calcium sensitivity. One population was defined by a bell-shaped calcium sensitivity analogous to the skeletal muscle RyR isoform (type I). The calcium sensitivity of the second RyR population was sigmoidal and analogous to the cardiac muscle RyR isoform (type II). These data show that there are at least two functionally distinct RyR channel populations in avian cerebellum. This leads to the possibility that these functionally distinct RyR channels are involved in different intracellular calcium signaling pathways.
Assuntos
Canais de Cálcio/fisiologia , Cerebelo/fisiologia , Retículo Endoplasmático Liso/fisiologia , Inositol 1,4,5-Trifosfato/metabolismo , Microssomos/fisiologia , Proteínas Musculares/fisiologia , Rianodina/metabolismo , Trifosfato de Adenosina/farmacologia , Animais , Ligação Competitiva , Cafeína/farmacologia , Cálcio/metabolismo , Cálcio/farmacologia , Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio/isolamento & purificação , Galinhas , Membranas Intracelulares/fisiologia , Cinética , Bicamadas Lipídicas , Mamíferos , Potenciais da Membrana/efeitos dos fármacos , Proteínas Musculares/efeitos dos fármacos , Proteínas Musculares/isolamento & purificação , Canal de Liberação de Cálcio do Receptor de RianodinaRESUMO
The bursting behavior of ryanodine-sensitive single Ca2+ release channels present in chicken cerebellum endoplasmic reticulum (ER), rat hippocampus ER, and frog and rabbit skeletal muscle sarcoplasmic reticulum was established. Unconditional dwell time distributions fitted by the maximum likelihood method reveal at least three open and closed exponential components. Trains of low open probability (P(o)) bursts were interspersed with trains of high P(o) bursts (> or = 0.8) in all the ryanodine receptor isotypes tested. The gating kinetics of the Ca2+ release channels were defined in long recordings by analyzing burst sequences and gamma distributions of average intraburst open (T(o)) and closed times (Tc). The gamma distributions of T(o) had two gamma components, suggesting the existence of two distinct burst types. In contrast, the gamma distributions of Tc had only one component. The correlation between consecutive burst pairs was defined in terms of T(o) and then statistically tested by 2 x 2 matrix contingency analysis. The probability that the ubiquitous sequential burst pattern was generated by random occurrence was < 0.01 (two-tailed Fisher's exact test). Temporal correlations were observed in all ryanodine receptor isotypes under a variety of experimental conditions. These data strongly suggest that single Ca2+ release channels switch slowly between modes of gating. We propose that the effects of agonists of Ca2+ release channels such as Ca2+ itself can be explained as concentration-dependent changes in the availability of each mode.
Assuntos
Canais de Cálcio/efeitos dos fármacos , Canais de Cálcio/metabolismo , Ativação do Canal Iônico , Músculo Esquelético/metabolismo , Neurônios/metabolismo , Rianodina/farmacologia , Animais , Anuros , Cálcio/farmacologia , Galinhas , Homeostase , Cinética , Modelos Biológicos , Coelhos , Ratos , Fatores de TempoRESUMO
The effect of a lack of dopamine (DA) in the striatum upon the K(+)-evoked release of cholecystokinin (CCK) from superfused rat striatal slices has been studied. Two pharmacological tools were used to deplete the nigrostriatal DA system: administration of alpha-methyl-p-tyrosine which competitively inhibits DA synthesis and lesions with 6-hydroxydopamine of the medial forebrain bundle. In both cases there was a significant inhibition of the K(+)-evoked release of CCK. The observed effects might be relevant on pathological conditions implying depletion of the DA system.