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1.
Nature ; 628(8006): 195-203, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38480879

ABSTRACT

Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis1. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells2. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species. Mechanistically, blocking complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in an animal disease model in vivo. Complex I activity in microglia is a potential therapeutic target to foster neuroprotection in chronic inflammatory disorders of the central nervous system3.


Subject(s)
Electron Transport Complex I , Inflammation , Microglia , Neuroinflammatory Diseases , Animals , Female , Humans , Male , Mice , Central Nervous System/drug effects , Central Nervous System/metabolism , Central Nervous System/pathology , Disease Models, Animal , Electron Transport/drug effects , Electron Transport Complex I/antagonists & inhibitors , Electron Transport Complex I/metabolism , Inflammation/drug therapy , Inflammation/metabolism , Inflammation/pathology , Microglia/drug effects , Microglia/metabolism , Microglia/pathology , Mitochondria/drug effects , Mitochondria/metabolism , Mitochondria/pathology , Multiomics , Myeloid Cells/metabolism , Myeloid Cells/pathology , Neuroinflammatory Diseases/drug therapy , Neuroinflammatory Diseases/metabolism , Neuroinflammatory Diseases/pathology , Reactive Oxygen Species/metabolism
2.
Appl Opt ; 56(18): 5274-5294, 2017 Jun 20.
Article in English | MEDLINE | ID: mdl-29047582

ABSTRACT

The Cassini spacecraft orbiting Saturn carries the composite infrared spectrometer (CIRS) designed to study thermal emission from Saturn and its rings and moons. CIRS, a Fourier transform spectrometer, is an indispensable part of the payload providing unique measurements and important synergies with the other instruments. It takes full advantage of Cassini's 13-year-long mission and surpasses the capabilities of previous spectrometers on Voyager 1 and 2. The instrument, consisting of two interferometers sharing a telescope and a scan mechanism, covers over a factor of 100 in wavelength in the mid and far infrared. It is used to study temperature, composition, structure, and dynamics of the atmospheres of Jupiter, Saturn, and Titan, the rings of Saturn, and surfaces of the icy moons. CIRS has returned a large volume of scientific results, the culmination of over 30 years of instrument development, operation, data calibration, and analysis. As Cassini and CIRS reach the end of their mission in 2017, we expect that archived spectra will be used by scientists for many years to come.

4.
Environ Sci Pollut Res Int ; 24(3): 2412-2420, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27815855

ABSTRACT

The use of pesticides in agricultural production originates residues in the environment where they are applied. Pesticide aerial application is a frequent source of exposure to pesticides by persons dedicated to agricultural practices and those living in neighboring communities of sprayed fields. The aim of the study was to assess the genotoxic effects of pesticides in workers occupationally exposed to these chemicals during their aerial application to agricultural fields of Sinaloa, Mexico. The study involved 30 pilots of airplanes used to apply pesticides via aerial application and 30 unexposed controls. Damage was evaluated through the micronucleus assay and by other nuclear abnormalities in epithelial cells of oral mucosa. The highest frequency ratios (FR) equal to 269.5 corresponded to binucleated cells followed by 54.2, corresponding to cells with pyknotic nuclei, 45.2 of cells with chromatin condensation, 3.7 of cells with broken-egg, 3.6 of cells with micronucleus, and 2.0 of karyolytic cells. Age, worked time, smoking, and alcohol consumption did not have significant influence on nuclear abnormalities in the pilots studied. Pesticide exposure was the main factor for nuclear abnormality results and DNA damage. Marked genotoxic damage was developed even in younger pilots with 2 years of short working period, caused by their daily occupational exposure to pesticides.


Subject(s)
DNA Damage , Occupational Exposure , Pesticides/toxicity , Pilots , Adult , Agriculture , Alcohol Drinking , Cell Nucleus , Cohort Studies , Humans , Male , Mexico , Micronucleus Tests , Middle Aged , Mouth Mucosa/drug effects , Occupational Exposure/analysis , Smoking , Young Adult
5.
Pediatr. aten. prim ; 10(supl.14): 65-79, abr.-jun. 2008.
Article in Es | IBECS | ID: ibc-68664

ABSTRACT

El cuidado integral del niño con patología endocrina corresponde al pediatra de Atención Primaria (AP). Vamos a hacer un repaso del seguimiento que realizamos en los centros de AP de las patologías endocrinas más frecuentes y repasaremos, también, qué novedades nos encontramos. La misión del pediatra de AP respecto al control de este tipo de niños es armonizar y coordinar la atención interniveles para asegurar la consecución de la mejor calidad de vida posible


The global care of a child with endocrine pathology is handled by the Primary Care Paediatrician. We will review the follow-up made in the Primary Care Centres (PC) of the more frequent endocrine pathologies, and also the novelties we found. The task of the PC Paediatrician with regard to the control of this kind of child is to harmonise and coordinate the care at different levels in order to ensure the best quality of life possible


Subject(s)
Humans , Male , Female , Child , Endocrine System Diseases/diagnosis , Endocrine System Diseases/therapy , Endocrine System Diseases/epidemiology , Comprehensive Health Care/methods , Quality of Life , Metabolic Syndrome , Diabetes Mellitus , Insulin Resistance , Obesity , Growth Disorders
6.
Hum Exp Toxicol ; 26(9): 715-22, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17984142

ABSTRACT

Genotoxicity caused by tobacco smoke was assessed in peripheral blood lymphocytes of smokers living in Mexico City by determining sister chromatid exchange (SCE), cell proliferation kinetics (CPK), replication index (RI) and mitotic index (MI). Nicotine levels, and its major metabolite cotinine, were also estimated in urine samples using gas-chromatography-mass spectrometry to quantify smoking intensity. The outcome of the analysis and the comparison of the 77-smoker group with a non-smoking control group showed that moderate and heavy smokers exhibited significant differences (P < 0.001 and P < 0.05, respectively) in CPK, with an underlying delay in the cellular cycle; similarly, RI was significantly different in these groups (P < 0.001 and P < 0.0001, respectively). There were significant correlations (P < 0.05) between age and number of years the subject had been smoking, as well as between RI and nicotine and cotinine levels and between CPK (M1, M2 and M3) and nicotine and cotinine levels. Smokers were classified for the analysis according to the nicotine levels (it is in relation to number of cigarettes smoked per day) found in urine (ng/mL) as: light (10-250), moderate (251-850) and heavy (851-4110). Significant differences in CPK were found (P < 0.05) between moderate and heavy smokers and non-smokers. Significant differences in RI were found between moderate (P < 0.001) and heavy smokers (P < 0.0001) and non-smokers, but not for the light smoking group. MI was determined in 57 of the smokers, whereas SCE frequency was only recorded in 34 smokers. Both parameters yielded no significant differences, nor correlations with any of the assessed variables. In conclusion, cytokinetic and cytostatic effects were mainly detected in heavy and moderate smokers. Cell cycle delay and RI decrease were found in all ;healthy' smokers. The nicotine and cotinine exposure (causing oxidative damage to DNA) may have implications in the decrease in cell replication due to direct damage to DNA and/or a decrease in the DNA repair mechanisms. Alternatively, nicotine and cotinine may possibly induce apoptosis.


Subject(s)
Cell Proliferation/drug effects , Cotinine/toxicity , Lymphocytes/drug effects , Mutagens/toxicity , Nicotine/toxicity , Nicotinic Agonists/toxicity , Sister Chromatid Exchange/drug effects , Smoking/adverse effects , Adult , Case-Control Studies , Cell Cycle/drug effects , Cells, Cultured , Cotinine/urine , DNA Damage , Female , Gas Chromatography-Mass Spectrometry , Humans , Kinetics , Lymphocytes/pathology , Male , Mexico , Middle Aged , Mitotic Index , Nicotine/urine , Nicotinic Agonists/urine , Oxidative Stress/drug effects , Smoking/urine
9.
Science ; 308(5724): 975-8, 2005 May 13.
Article in English | MEDLINE | ID: mdl-15894528

ABSTRACT

Temperatures obtained from early Cassini infrared observations of Titan show a stratopause at an altitude of 310 kilometers (and 186 kelvin at 15 degrees S). Stratospheric temperatures are coldest in the winter northern hemisphere, with zonal winds reaching 160 meters per second. The concentrations of several stratospheric organic compounds are enhanced at mid- and high northern latitudes, and the strong zonal winds may inhibit mixing between these latitudes and the rest of Titan. Above the south pole, temperatures in the stratosphere are 4 to 5 kelvin cooler than at the equator. The stratospheric mole fractions of methane and carbon monoxide are (1.6 +/- 0.5) x 10(-2) and (4.5 +/- 1.5) x 10(-5), respectively.


Subject(s)
Hydrocarbons , Methane , Nitriles , Saturn , Atmosphere , Carbon Monoxide , Extraterrestrial Environment , Spacecraft , Temperature , Wind
10.
Science ; 307(5713): 1247-51, 2005 Feb 25.
Article in English | MEDLINE | ID: mdl-15618486

ABSTRACT

Stratospheric temperatures on Saturn imply a strong decay of the equatorial winds with altitude. If the decrease in winds reported from recent Hubble Space Telescope images is not a temporal change, then the features tracked must have been at least 130 kilometers higher than in earlier studies. Saturn's south polar stratosphere is warmer than predicted from simple radiative models. The C/H ratio on Saturn is seven times solar, twice Jupiter's. Saturn's ring temperatures have radial variations down to the smallest scale resolved (100 kilometers). Diurnal surface temperature variations on Phoebe suggest a more porous regolith than on the jovian satellites.


Subject(s)
Saturn , Atmosphere , Carbon , Extraterrestrial Environment , Hydrogen , Methane , Spacecraft , Spectrum Analysis , Temperature , Wind
12.
Mutat Res ; 438(2): 81-8, 1999 Jan 13.
Article in English | MEDLINE | ID: mdl-10036329

ABSTRACT

Molinate and butylate treatments for 4 h of Vicia faba root tip meristems, showed that both thiocarbamate herbicides increased significantly SCE frequency. Direct treatments of molinate and butylate on human lymphocytes applied 24 h after the beginning of culture did not induce SCE. When S10 extracts of the Vicia roots, treated for 4 h with molinate and butylate (in vivo activation) were added to lymphocytes (24 h after of the beginning of culture), SCE were induced in a concentration-response manner. The in vitro assays, in which molinate and butylate was added at 48 h lymphocyte cultures for 4 h, showed a negative response, however, in the treatment where the S10 metabolic mix was added the SCE frequencies were significantly different to the control, and the concentration-response relationship was not observed with molinate, but it was obtained with butylate. The results showed that both herbicides needed the V. faba metabolism to produce SCE in human lymphocyte culture.


Subject(s)
Azepines/metabolism , Herbicides/metabolism , Mutagens/metabolism , Plants/metabolism , Sister Chromatid Exchange/drug effects , Thiocarbamates/metabolism , Biotransformation , Cells, Cultured , Humans , Lymphocytes/drug effects , Lymphocytes/ultrastructure
14.
Environ Mol Mutagen ; 26(4): 324-30, 1995.
Article in English | MEDLINE | ID: mdl-8575421

ABSTRACT

Because the carbamate insecticide propoxur induced sister chromatid exchanges (SCE) in Vicia faba but was ineffective in producing SCE in lymphocytes in culture, it was hardly suspected that plant metabolism was involved. Experiments were conducted in which metabolic activation was afforded by Vicia faba roots, and SCE in human lymphocytes in vitro was used to assess cytogenetic damage. Several concentrations of propoxur (250, 500, 1,000, 1,500, and 2,000 ppm) were applied for 4 hr to the roots of Vicia faba. Extracts prepared from these treatments were added to the lymphocyte cultures and a significant increase of SCE frequencies with a concentration-response relationship could be detected. The lymphocyte proliferation kinetics and the proliferation rate index (PRI) were not affected (except in the highest concentration, of 2,000 ppm). This general behavior was in agreement with the presence of an enzymatic system (S10 fraction) in Vicia roots capable of metabolizing or activating the propoxur. With 2,000 ppm, cell necrosis was produced in Vicia; therefore, this extract did not induce SCE in lymphocytes. However, lymphocyte proliferation kinetics were delayed and PRI was significantly decreased. Ethanol, a promutagen activated by this plant, was applied directly to the lymphocyte cultures as a positive control, and the response was negative. On the other hand, the extracts of roots treated with ethanol increased the SCE to more than twice that of the negative control, but the lymphocyte proliferation kinetics and PRI were not affected.


Subject(s)
Fabaceae/metabolism , Insecticides/toxicity , Lymphocytes/physiology , Mutagens/toxicity , Plants, Medicinal , Propoxur/toxicity , Sister Chromatid Exchange , Biotransformation , Humans , Insecticides/metabolism , Lymphocytes/cytology , Lymphocytes/drug effects , Mutagens/metabolism , Plant Roots , Propoxur/metabolism , Tissue Extracts/pharmacology
15.
Pract Odontol ; 11(8): 54-6, 1990 Aug.
Article in Spanish | MEDLINE | ID: mdl-2132282

ABSTRACT

Electromyographic records from the temporal and masseter muscles of 19 edentulous patients were made, before and 30 days after wearing complete dentures. The purpose of this study was to determine the electromyographic changes: The amplitude of electromyographic records from de temporal muscles decreased, while those from the masseter muscles increased. These results suggest that the use of complete denture provokes electromyographic changes by increasing the occlusal vertical dimension and, thus, periodical electromyographic records from temporal and masseter muscles could be useful for determining the time for complete denture change.


Subject(s)
Denture, Complete , Masseter Muscle/physiology , Mouth, Edentulous/physiopathology , Temporal Muscle/physiology , Electromyography , Female , Humans , Male , Vertical Dimension
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