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COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/complicaciones , Comorbilidad , Masculino , Femenino , SARS-CoV-2 , Persona de Mediana Edad , Tuberculosis/epidemiología , Coinfección , Adulto , AncianoRESUMEN
In 2019, sands in nearby runoff streams from public beach showers were sampled on three islands in the State of Hawaii and tested for over 18 different petrochemical UV filters. Beach sands that are directly in the plume discharge of beach showers on three of the islands of Hawaii (Maui, Oahu, Hawai'i) were found to be contaminated with a wide array of petrochemical-based UV-filters that are found in sunscreens. Sands from beach showers across all three islands had a mean concentration of 5619 ng/g of oxybenzone with the highest concentration of 34,518 ng/g of oxybenzone at a beach shower in the Waikiki area of Honolulu. Octocrylene was detected at a majority of the beach shower locations, with a mean concentration of 296.3 ng/g across 13 sampling sites with the highest concentration of 1075 ng/g at the beach shower in Waikiki. Avobenzone, octinoxate, 4-methylbenzylidene camphor and benzophenone-2 were detected, as well as breakdown products of oxybenzone, including benzophenone-1, 2,2'-dihydroxy-4-methoxybenzophenone, and 4-hydroxybenzophenone. Dioxybenzone (DHMB) presented the highest concentration in water (75.4 ng/mL), whereas octocrylene was detected in all water samples. Some of these same target analytes were detected in water samples on coral reefs that are adjacent to the beach showers. Risk assessments for both sand and water samples at a majority of the sampling sites had a Risk Quotient > 1, indicating that these chemicals could pose a serious threat to beach zones and coral reef habitats. There are almost a dozen mitigation options that could be employed to quickly reduce contaminant loads associated with discharges from these beach showers, like those currently being employed (post-study sampling and analysis) in the State of Hawaii, including banning the use of sunscreens using petrochemical-based UV filters or educating tourists before they arrive on the beach.
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Protectores Solares , Turismo , Hawaii , Arena , Protectores Solares/análisis , Agua/análisisRESUMEN
A preponderance of recent evidence indicates that oxybenzone and other personal-care product chemicals threaten the biota inhabiting various ecological niches. What is understudied is the ecotoxicological impact of oxybenzone, a UV filter in sunscreens and anti-aging products, to terrestrial/soil organisms that are keystone species in these habitats. In the present study, acute exposure (14-day) to oxybenzone resulted in earthworm mortality (LC50 of 364 mg/kg) and growth rate inhibition. Environmentally relevant concentration of oxybenzone (3.64, 7.28 and 36.4 mg/kg) at exposures of 7-day, 14-day, 28-day induced oxidative stress and neurotoxicity followed by perturbations in reproduction processes and changes in vital organs. Decreased levels of superoxide dismutase (SOD) and catalase (CAT) activity were statistically lower than controls (p < 0.05) on day 14 for all three concentrations, while glutathione-s-transferase (GST) activity was significantly elevated from controls on days 7 and 14. On day 28, SOD and CAT activities were either not significantly different from the control or were higher, demonstrating a temporal multiphasic response of anti-oxidant enzymes. GST activity on day 28 was significantly reduced compared to controls. Acetylcholinesterase levels across the three-time points exhibited a complicated behaviour, with every exposure concentration being significantly different from the control. Chronic exposure negatively influences earthworm health status with elevated biomarker values analysed using IBRv2 index. This, in turn, impacted higher levels of hierarchical organization, significantly impairing reproduction and organismal homeostasis at the histological level and manifesting as decreasing cocoon formation and successful hatching events. Thus, the overall findings demonstrate that oxybenzone is toxic to Eisenia fetida at low-level, long-term exposure. Based on the concentration verification analysis and application of the EPA PestDF tool, oxybenzone undergoes single first-order kinetics degradation in OECD soil with DT50 and DT90 as 8.7-28.9 days, respectively.
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Oligoquetos , Contaminantes del Suelo , Acetilcolinesterasa/metabolismo , Animales , Antioxidantes/metabolismo , Benzofenonas , Catalasa/metabolismo , Oligoquetos/metabolismo , Estrés Oxidativo , Suelo/química , Contaminantes del Suelo/metabolismo , Contaminantes del Suelo/toxicidad , Superóxido Dismutasa/metabolismoRESUMEN
Hanauma Bay is a 101-acre bay created by the partial collapse of a volcanic cone and once supported a vibrant coral reef system. It is the most popular swimming area in the Hawaiian Islands and has been reported to have averaged between 2.8 and 3.5 million visitors a year between the 1980s and the 2010s, with visitors averaging between 3000-4000 a day and peaking around 10,000-13,000 per day. Concentrations of oxybenzone and other common UV filters were measured in subsurface water samples and in sands from the beach-shower areas in Hanauma Bay. Results demonstrate that beach showers also can be a source of sunscreen environmental contamination. Hydrodynamic modeling indicates that oxybenzone contamination within Hanauma Bay's waters could be retained between 14 and 50 h from a single release event period. Focusing on only oxybenzone, two different Hazard and Risk Assessment analyses were conducted to determine the danger of oxybenzone to Hanauma Bay's coral reef system. Results indicate that oxybenzone contamination poses a significant threat to the wildlife of Hanauma Bay. To recover Hanauma Bay's natural resources to a healthy condition and to satisfactorily conserve its coral reef and sea grass habitats, effective tourism management policies need to be implemented that mitigate the threat of sunscreen pollution.
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Bahías , Protectores Solares , Benzofenonas , Arrecifes de Coral , Hawaii , Protectores Solares/toxicidadRESUMEN
Most organic ultraviolet filters are very lipophilic and some of them are difficult to quantify in the environment. This article describes an optimization method for the quantification of these compounds in sand samples with diverse compositions. The standard additions method was used. The search for a unique high-performance liquid chromatography method to analyze all these filters along with the search for optimal detection conditions are presented in detail. The best extraction solvent was methanol, and the best conditions for analysis and detection involved the use of a high-performance liquid chromatography system equipped with a biphenyl column (2.6 µm, 150 × 4.6 mm), and an Orbitrap MS detector. We also demonstrated that sample freeze-drying can induce significant loss of some of the ultraviolet filters.
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Benzophenone is a mutagen, carcinogen, and endocrine disruptor. Its presence in food products or food packaging is banned in the United States. Under California Proposition 65, there is no safe harbor for benzophenone in any personal care products, including sunscreens, anti-aging creams, and moisturizers. The purpose of this study was to determine (1) if benzophenone was present in a wide variety of commercial sun protection factor (SPF)/sunscreen products, (2) whether benzophenone concentration in the product increased over time, and (3) if the degradation of octocrylene was the likely source for benzophenone contamination. Benzophenone concentration was assayed in nine commercial sunscreen products from the European Union and eight from the United States (in triplicate), including two single ingredient sources of octocrylene. These same SPF items were subjected to the United States Food and Drug Administration (U.S. FDA)-accelerated stability aging protocol for 6 weeks. Benzophenone was measured in the accelerated-aged products. Sixteen octocrylene-containing product lines that were recently purchased had an average concentration of 39 mg/kg benzophenone, ranging from 6 mg/kg to 186 mg/kg. Benzophenone was not detectable in the product that did not contain octocrylene. After subjecting the 17 products to the U.S. FDA-accelerated stability method, the 16 octocrylene-containing products had an average concentration of 75 mg/kg, ranging from 9.8 mg/kg to 435 mg/kg. Benzophenone was not detectable in the product that did not contain octocrylene. Benzophenone was detected in the pure octocrylene manufactured ingredient. Octocrylene generates benzophenone through a retro-aldol condensation. In vivo, up to 70% of the benzophenone in these sunscreen products may be absorbed through the skin. U.S. FDA has established a zero tolerance for benzophenone as a food additive. In the United States, there were 2999 SPF products containing octocrylene in 2019. The safety of octocrylene as a benzophenone generator in SPF or any consumer products should be expeditiously reviewed by regulatory agencies.
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Acrilatos/metabolismo , Benzofenonas/metabolismo , Protectores Solares/metabolismo , Acrilatos/química , Benzofenonas/química , Contaminación de Alimentos/análisis , Humanos , Estructura Molecular , Protectores Solares/química , Factores de Tiempo , Estados UnidosRESUMEN
Benzophenone-3 (BP-3; oxybenzone) is an ingredient in sunscreen lotions and personal-care products that protects against the damaging effects of ultraviolet light. Oxybenzone is an emerging contaminant of concern in marine environmentsproduced by swimmers and municipal, residential, and boat/ship wastewater discharges. We examined the effects of oxybenzone on the larval form (planula) of the coral Stylophora pistillata, as well as its toxicity in vitro to coral cells from this and six other coral species. Oxybenzone is a photo-toxicant; adverse effects are exacerbated in the light. Whether in darkness or light, oxybenzone transformed planulae from a motile state to a deformed, sessile condition. Planulae exhibited an increasing rate of coral bleaching in response to increasing concentrations of oxybenzone. Oxybenzone is a genotoxicant to corals, exhibiting a positive relationship between DNA-AP lesions and increasing oxybenzone concentrations. Oxybenzone is a skeletal endocrine disruptor; it induced ossification of the planula, encasing the entire planula in its own skeleton. The LC50 of planulae exposed to oxybenzone in the light for an 8- and 24-h exposure was 3.1 mg/L and 139 µg/L, respectively. The LC50s for oxybenzone in darkness for the same time points were 16.8 mg/L and 779 µg/L. Deformity EC20 levels (24 h) of planulae exposed to oxybenzone were 6.5 µg/L in the light and 10 µg/L in darkness. Coral cell LC50s (4 h, in the light) for 7 different coral species ranges from 8 to 340 µg/L, whereas LC20s (4 h, in the light) for the same species ranges from 0.062 to 8 µg/L. Coral reef contamination of oxybenzone in the U.S. Virgin Islands ranged from 75 µg/L to 1.4 mg/L, whereas Hawaiian sites were contaminated between 0.8 and 19.2 µg/L. Oxybenzone poses a hazard to coral reef conservation and threatens the resiliency of coral reefs to climate change.
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Antozoos/efectos de los fármacos , Benzofenonas/toxicidad , Monitoreo del Ambiente , Protectores Solares/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Hawaii , Islas Virgenes de los Estados UnidosRESUMEN
We assessed the state of knowledge regarding the effects of large-scale pollution with neonicotinoid insecticides and fipronil on non-target invertebrate species of terrestrial, freshwater and marine environments. A large section of the assessment is dedicated to the state of knowledge on sublethal effects on honeybees (Apis mellifera) because this important pollinator is the most studied non-target invertebrate species. Lepidoptera (butterflies and moths), Lumbricidae (earthworms), Apoidae sensu lato (bumblebees, solitary bees) and the section "other invertebrates" review available studies on the other terrestrial species. The sections on freshwater and marine species are rather short as little is known so far about the impact of neonicotinoid insecticides and fipronil on the diverse invertebrate fauna of these widely exposed habitats. For terrestrial and aquatic invertebrate species, the known effects of neonicotinoid pesticides and fipronil are described ranging from organismal toxicology and behavioural effects to population-level effects. For earthworms, freshwater and marine species, the relation of findings to regulatory risk assessment is described. Neonicotinoid insecticides exhibit very high toxicity to a wide range of invertebrates, particularly insects, and field-realistic exposure is likely to result in both lethal and a broad range of important sublethal impacts. There is a major knowledge gap regarding impacts on the grand majority of invertebrates, many of which perform essential roles enabling healthy ecosystem functioning. The data on the few non-target species on which field tests have been performed are limited by major flaws in the outdated test protocols. Despite large knowledge gaps and uncertainties, enough knowledge exists to conclude that existing levels of pollution with neonicotinoids and fipronil resulting from presently authorized uses frequently exceed the lowest observed adverse effect concentrations and are thus likely to have large-scale and wide ranging negative biological and ecological impacts on a wide range of non-target invertebrates in terrestrial, aquatic, marine and benthic habitats.
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Contaminantes Ambientales/toxicidad , Insecticidas/toxicidad , Invertebrados/efectos de los fármacos , Agonistas Nicotínicos/toxicidad , Pirazoles/toxicidad , Animales , Ecosistema , Polinización , Medición de RiesgoRESUMEN
Benzophenone-2 (BP-2) is an additive to personal-care products and commercial solutions that protects against the damaging effects of ultraviolet light. BP-2 is an "emerging contaminant of concern" that is often released as a pollutant through municipal and boat/ship wastewater discharges and landfill leachates, as well as through residential septic fields and unmanaged cesspits. Although BP-2 may be a contaminant on coral reefs, its environmental toxicity to reefs is unknown. This poses a potential management issue, since BP-2 is a known endocrine disruptor as well as a weak genotoxicant. We examined the effects of BP-2 on the larval form (planula) of the coral, Stylophora pistillata, as well as its toxicity to in vitro coral cells. BP-2 is a photo-toxicant; adverse effects are exacerbated in the light versus in darkness. Whether in darkness or light, BP-2 induced coral planulae to transform from a motile planktonic state to a deformed, sessile condition. Planulae exhibited an increasing rate of coral bleaching in response to increasing concentrations of BP-2. BP-2 is a genotoxicant to corals, exhibiting a strong positive relationship between DNA-AP lesions and increasing BP-2 concentrations. BP-2 exposure in the light induced extensive necrosis in both the epidermis and gastro dermis. In contrast, BP-2 exposure in darkness induced autophagy and autophagic cell death.The LC50 of BP-2 in the light for an 8 and 24 hour exposure was 120 parts per million (ppm) and 165 parts per billion (ppb), respectively. The LC50s for BP-2 in darkness for the same time points were 144 parts per million and 548 parts per billion [corrected].
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Antozoos/efectos de los fármacos , Benzofenonas/toxicidad , Protectores Solares/toxicidad , Rayos Ultravioleta , Animales , Arrecifes de Coral , Filtración , Larva/efectos de los fármacos , Dosificación Letal Mediana , Microscopía Electrónica de Transmisión , Nivel sin Efectos Adversos Observados , Análisis de Regresión , Pruebas de ToxicidadRESUMEN
Coral bleaching is a significant contributor to the worldwide degradation of coral reefs and is indicative of the termination of symbiosis between the coral host and its symbiotic algae (dinoflagellate; Symbiodinium sp. complex), usually by expulsion or xenophagy (symbiophagy) of its dinoflagellates. Herein, we provide evidence that during the earliest stages of environmentally induced bleaching, heat stress and light stress generate distinctly different pathomorphological changes in the chloroplasts, while a combined heat- and light-stress exposure induces both pathomorphologies; suggesting that these stressors act on the dinoflagellate by different mechanisms. Within the first 48 hours of a heat stress (32°C) under low-light conditions, heat stress induced decomposition of thylakoid structures before observation of extensive oxidative damage; thus it is the disorganization of the thylakoids that creates the conditions allowing photo-oxidative-stress. Conversely, during the first 48 hours of a light stress (2007 µmoles m(-2) s(-1) PAR) at 25°C, condensation or fusion of multiple thylakoid lamellae occurred coincidently with levels of oxidative damage products, implying that photo-oxidative stress causes the structural membrane damage within the chloroplasts. Exposure to combined heat- and light-stresses induced both pathomorphologies, confirming that these stressors acted on the dinoflagellate via different mechanisms. Within 72 hours of exposure to heat and/or light stresses, homeostatic processes (e.g., heat-shock protein and anti-oxidant enzyme response) were evident in the remaining intact dinoflagellates, regardless of the initiating stressor. Understanding the sequence of events during bleaching when triggered by different environmental stressors is important for predicting both severity and consequences of coral bleaching.
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Antozoos/efectos de la radiación , Cloroplastos/efectos de la radiación , Dinoflagelados/efectos de la radiación , Membranas Intracelulares/efectos de la radiación , Animales , Clorofila/metabolismo , Cloroplastos/ultraestructura , Arrecifes de Coral , Dinoflagelados/ultraestructura , Expresión Génica , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Calor , Membranas Intracelulares/ultraestructura , Luz , Microscopía Electrónica de Transmisión , Oxidación-Reducción , Estrés Oxidativo , Fotólisis , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Estrés Fisiológico , Simbiosis , TemperaturaRESUMEN
Biochemical and molecular biomarkers tools are utilized as early warning signatures of contaminant exposure to target and non-target organisms. The objective of this study was to investigate the sublethal effects of iron chloride to the larvae of the lace coral Pocillopora damicornis by measuring a suit of oxidative-stress biomarkers. The larvae were exposed to a range of sublethal concentrations of iron chloride (0.01, 0.1, 1, 10, and 100 ppm) for seven days. With reference to oxidative stress biomarkers, the no-observed effect concentration (NOEC) and the lowest observed effect concentration (LOEC) of iron chloride were observed to be 0.01 and 100 ppm respectively. At the end of the seventh day the antioxidant status of the larvae was evaluated by the levels of glutathione (GSH), glutathione peroxidase (GPX), glutathione reductase (GR), and glutathione-S-transferase (GST), in both experimental and control groups. For the quantification of cellular oxidative damage, lipid peroxidation (LPO) activity was determined in the same and the extent of DNA damage was assessed by the expression of DNA apurinic/apyrimidinic (AP) sites. Iron chloride exhibited a concentration-dependent inhibition of GSH and GPX and induction of GR, GST, LPO, and DNA-AP sites in the P. damicornis larvae when compared to the control group. The oxidative stress biomarkers of the larvae exposed to 0.1, 1, and 10 ppm of iron chloride did not show any significant overall differences when compared to the control group. However the activities of LPO, GSH, GPX, GR, GST and DNA-AP in the larval group exposed to 100 ppm of iron chloride exhibited statistically significant (P=0.002, 0.003, 0.002, 0.002, 0.005 and 0.007) differences when compared to the control group. The research results indicated that iron chloride in concentrations at the 100 ppm level caused oxidative stress in the P. damicornis larvae.
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Antozoos/efectos de los fármacos , Cloruros/toxicidad , Daño del ADN , Compuestos de Hierro/toxicidad , Estrés Oxidativo/efectos de los fármacos , Animales , Antozoos/genética , Antozoos/metabolismo , Antioxidantes/metabolismo , Ácido Apurínico/genética , Relación Dosis-Respuesta a Droga , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Glutatión Transferasa/metabolismo , Larva/efectos de los fármacos , Larva/genética , Larva/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Nivel sin Efectos Adversos Observados , Polinucleótidos/genética , Factores de TiempoRESUMEN
Benthic marine organisms such as mollusks are often exposed to periodic oxygen deficiency (due to the tidal exposure and/or seasonal expansion of the oxygen-deficient dead zones) and pollution by metals [e.g., cadmium, (Cd)]. These stressors can strongly affect mollusks' survival; however, physiological mechanisms of their combined effects are not fully understood. We studied the effects of Cd exposure on metabolic responses to prolonged anoxia and subsequent recovery in anoxia-tolerant intertidal mollusks Crassostrea virginica (eastern oysters). Anoxia led to an onset of anaerobiosis indicated by accumulation of l-alanine, acetate, and succinate. Prolonged anoxia (for 6 days) caused a decline in the maximum activity of electron transport chain and ADP-stimulated (state 3) oxygen uptake by mitochondria (MO(2)), but no change in the resting (state 4) MO(2) of oyster mitochondria, along with a slight but significant reduction of mitochondrial respiratory control ratio. During reoxygenation, there was a significant overshoot of mitochondrial MO(2) (by up to 70% above the normoxic steady-state values) in control oysters. Mild mitochondrial uncoupling during prolonged shutdown in anoxic tissues and a subsequent strong stimulation of mitochondrial flux during recovery may help to rapidly restore redox status and protect against elevated reactive oxygen species formation in oysters. Exposure to Cd inhibits anaerobic metabolism, abolishes reoxygenation-induced stimulation of mitochondrial MO(2), and leads to oxidative stress (indicated by accumulation of DNA lesions) and a loss of mitochondrial capacity during postanoxic recovery. This may result in increased sensitivity to intermittent hypoxia and anoxia in Cd-exposed mollusks and will have implications for their survival in polluted estuaries and coastal zones.
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Cadmio/toxicidad , Crassostrea/efectos de los fármacos , Crassostrea/metabolismo , Oxígeno/metabolismo , Contaminantes del Agua/toxicidad , Aminoácidos/metabolismo , Anaerobiosis/fisiología , Animales , Cadmio/farmacología , Daño del ADN/efectos de los fármacos , Daño del ADN/fisiología , Ácidos Grasos/metabolismo , Hemolinfa/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Consumo de Oxígeno/efectos de los fármacos , Consumo de Oxígeno/fisiología , Contaminantes del Agua/farmacologíaRESUMEN
Coral reefs within the Florida Keys are disappearing at an alarming rate. Coral cover in the Florida Keys National Marine Sanctuary declined by 38% from 1996 to 2000. In 2000, populations of Montastraea annularis at four sites near Molasses Reef within the Florida Keys National Marine Sanctuary and one reef within Biscayne National Park were sampled on a quarterly basis. Anecdotal observations showed corals at Alina's Reef in Biscayne National Park appeared healthy in March, but experienced an acute loss of coral cover by August. Cellular Diagnostic analysis indicated that Alina's Reef corals were in distress: they had been afflicted with a severe oxidative damaging and protein-denaturing stress that affected both the corals and their symbiotic zooxanthellae. This condition was associated with a significant xenobiotic detoxification response in both species, reflecting probable chemical contaminant exposure. These results demonstrate that applying a Cellular Diagnostic approach can be effective in helping to identify stress and its underlying causes, providing diagnostic and prognostic biomarkers of coral health.
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Antozoos/fisiología , Dinoflagelados/fisiología , Exposición a Riesgos Ambientales , Monitoreo del Ambiente/estadística & datos numéricos , Estrés Fisiológico/fisiopatología , Contaminantes Químicos del Agua/toxicidad , Análisis de Varianza , Animales , Antozoos/efectos de los fármacos , Biomarcadores/análisis , Western Blotting , Dinoflagelados/efectos de los fármacos , Electroforesis en Gel de Poliacrilamida , Ensayo de Inmunoadsorción Enzimática , Florida , Dinámica PoblacionalRESUMEN
During the past two decades, coral reefs have experienced extensive degradation worldwide. One etiology for this global degradation is a syndrome known as coral bleaching. Mass coral bleaching events are correlated with increased sea-surface temperatures, however, the cellular mechanism underlying this phenomenon is uncertain. To determine if oxidative stress plays a mechanistic role in the process of sea-surface temperature-related coral bleaching, we examined corals along a depth transect in the Florida Keys over a single season that was characterized by unusually high sea-surface temperatures. We observed strong positive correlations between accumulation of oxidative damage products and bleaching in corals over a year of sampling. High levels of antioxidant enzymes and small heat-shock proteins were negatively correlated with levels of oxidative damage products. Corals that experienced oxidative stress had higher chaperonin levels and protein turnover activity. Our results indicate that coral bleaching is tightly coupled to the antioxidant and cellular stress capacity of the symbiotic coral, supporting the mechanistic model that coral bleaching (zooxanthellae loss) may be a final strategy to defend corals from oxidative stress.
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Antozoos/metabolismo , Estrés Oxidativo , Animales , Océano Atlántico , Chaperoninas/metabolismo , Citosol/metabolismo , Dinoflagelados/metabolismo , Ecología , Glutatión/metabolismo , Proteínas de Choque Térmico/metabolismo , Peróxido de Hidrógeno/metabolismo , Modelos Biológicos , Especies Reactivas de Oxígeno , Agua de Mar , Superóxido Dismutasa/metabolismo , Simbiosis , TemperaturaRESUMEN
BACKGROUND: Hereditary lymphoedema-distichiasis (LD) is an autosomal dominant disorder that classically presents as lymphoedema of the limbs, with variable age of onset, and extra aberrant growth of eyelashes from the Meibomian gland (distichiasis). Other major reported complications include cardiac defects, cleft palate, and extradural cysts. Photophobia, exotropia, ptosis, congenital ectropion, and congenital cataracts are additional eye findings. Recently, we reported that truncating mutations in the forkhead transcription family member FOXC2 resulted in LD in two families. METHODS: The clinical findings in seven additional families with LD, including the original family described by Falls and Kertesz, were determined and mutational analyses were performed. RESULTS: Distichiasis was the most common clinical feature followed by age dependent lymphoedema. There is a wide variation of associated secondary features including tetralogy of Fallot and cleft palate. The mutational analyses identified truncating mutations in all of the families studied (two nonsense, one deletion, three insertion, and one insertion-deletion), which most likely result in haploinsufficiency of FOXC2. CONCLUSIONS: FOXC2 mutations are highly penetrant with variable expressivity which is not explicable by the pattern of mutations.
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Proteínas de Unión al ADN/genética , Pestañas/anomalías , Linfedema/genética , Factores de Transcripción/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , ADN/química , ADN/genética , Análisis Mutacional de ADN , Salud de la Familia , Femenino , Factores de Transcripción Forkhead , Heterogeneidad Genética , Humanos , Linfedema/patología , Masculino , Persona de Mediana Edad , Mutación , FenotipoRESUMEN
We developed a Molecular Biomarker System (MBS) to assess the physiological status of mud snails (Ilyanassa obsoleta) challenged by exposure to high temperature, cadmium, atrazine, endosulfan and the water-accommodating fraction of bunker fuel #2. The MBS is used to assay specific cellular parameters of the gastropod cell that are indicative of a non-stressed or stressed condition. The MBS distinguished among responses to each stressor and to non-stressed control conditions. For example, the biomarkers metallothionein and cytochrome P450 2E1 homologue distinguished between metal and non-metal stresses. MBS data from this study corroborate toxicological studies of organismal responses to endosulfan, atrazine, fuel and cadmium stresses. The MBS technology aids in the accurate diagnosis of the snail's health condition because the physiological significance of the changes of each biomarker is well known. This technology is particularly relevant for environmental monitoring because gastropods are used as key indicator species in many estuarine, marine, freshwater and terrestrial ecosystems. Finally, the Molecular Biomarker System technology is relatively inexpensive, easy to implement, precise and can be quickly adapted to an automated, high-throughput system for large sample analysis.
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We developed a molecular biomarker system (MBS) to assess the physiological status of Palaomenetes pugio (grass shrimp) challenged with exposure to heat stress, cadmium, atrazine, and the water-accommodating fraction of either diesel fuel or bunker fuel No. 2. The MBS assayed 9 specific cellular parameters of shrimp that are indicative of a nonstressed or stressed condition: heat-shock protein 60, heat-shock protein 70, alpha B-crystallin homologue, lipid peroxide, total glutathione level, ubiquitin, mitochondrial manganese superoxide dismutase, metallothionein, and cytochrome P-450 2E homologue. Using these 9 parameters, the MBS can distinguish between the responses to each stressor, and to the nonstressed control conditions. The MBS was able to determine the structural integrity of the cell as defined by protein turnover, protein chaperoning, and lipid composition via lipid peroxide levels, and the status of key metabolic processes such as cytoskeletal integrity and glutathione redox potential. This technology aids in the accurate diagnosis of the health of shrimp because the physiological significance of changes of each parameter is well known. This technology is particularly relevant for environmental monitoring because grass shrimp are used as key indicator species in many estuarine ecosystems. Finally, this system is easy to implement, precise, and can be quickly adapted to an automated high-throughput system for mass sample analysis.
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PURPOSE: To screen a population with primary open-angle glaucoma for mutations in the gene that encodes the trabecular meshwork inducible glucocorticoid response protein (TIGR), also known as myocilin (MYOC). METHODS: Ophthalmologic information was collected for study subjects with primary open-angle glaucoma and their relatives. Mutation screening of 74 primary open-angle glaucoma probands was conducted by sequencing TIGR/MYOC coding sequence and splice sites. RESULTS: In 23 families we detected 13 nonsynonymous sequence changes, nine of which appear to be mutations likely to cause or contribute to primary open-angle glaucoma. Two mutations, Arg272Gly and Ile499Ser, and one nonsynonymous sequence variant, Asn57Asp, are novel. We found mutations in nine of 25 juvenile glaucoma probands (36%) and two of 49 adult-onset glaucoma probands (4%). Age classification of families rather than individual probands revealed mutations in three of nine families with strictly juvenile primary open-angle glaucoma (33%), and no mutations in 39 families with strictly adult-onset primary open-angle glaucoma (0%). In families with mixed-onset primary open-angle glaucoma containing both juvenile primary open-angle glaucoma and adult-onset primary open-angle glaucoma cases, we found mutations in eight of 26 families (31%). CONCLUSIONS: Our data suggest that Gly252Arg, Arg272Gly, Glu323Lys, Gln368STOP, Pro370Leu, Thr377Met, Val426Phe, Ile477Asn, and Ile499Ser are likely to play roles that cause or contribute to the etiology of autosomal dominant primary open-angle glaucoma. Our finding of more TIGR/MYOC mutations in families with mixed-onset primary open-angle glaucoma than in the families with strictly adult-onset primary open-angle glaucoma implies that the presence of relatives with juvenile primary open-angle glaucoma in a family could be used as a basis for identifying a subset of the population with adult-onset primary open-angle glaucoma with higher prevalence of TIGR/MYOC mutations. To address this issue, and to refine estimations of mutation prevalence in these age-defined subpopulations, prospective study of a larger population ascertained entirely through adult-onset primary open-angle glaucoma probands will be needed.