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1.
Genome Res ; 31(7): 1269-1279, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34162698

RESUMO

Telomeres are regions of repetitive nucleotide sequences capping the ends of eukaryotic chromosomes that protect against deterioration, and whose lengths can be correlated with age and adverse health risk factors. Yet, given their length and repetitive nature, telomeric regions are not easily reconstructed from short-read sequencing, thus making telomere sequencing, mapping, and variant resolution challenging problems. Recently, long-read sequencing, with read lengths measuring in hundreds of kilobase pairs, has made it possible to routinely read into telomeric regions and inspect their sequence structure. Here, we describe a framework for extracting telomeric reads from whole-genome single-molecule sequencing experiments, including de novo identification of telomere repeat motifs and repeat types, and also describe their sequence variation. We find that long, complex telomeric stretches and repeats can be accurately captured with long-read sequencing, observe extensive sequence heterogeneity of human telomeres, discover and localize noncanonical telomere sequence motifs (both previously reported, as well as novel), and validate them in short-read sequence data. These data reveal extensive intra- and inter-population diversity of repeats in telomeric haplotypes, reveal higher paternal inheritance of telomeric variants, and represent the first motif composition maps of multi-kilobase-pair human telomeric haplotypes across three distinct ancestries (Ashkenazi, Chinese, and Utah), which can aid in future studies of genetic variation, aging, and genome biology.

2.
J Neurophysiol ; 123(5): 2037-2063, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32292116

RESUMO

Space travel presents a number of environmental challenges to the central nervous system, including changes in gravitational acceleration that alter the terrestrial synergies between perception and action, galactic cosmic radiation that can damage sensitive neurons and structures, and multiple factors (isolation, confinement, altered atmosphere, and mission parameters, including distance from Earth) that can affect cognition and behavior. Travelers to Mars will be exposed to these environmental challenges for up to 3 years, and space-faring nations continue to direct vigorous research investments to help elucidate and mitigate the consequences of these long-duration exposures. This article reviews the findings of more than 50 years of space-related neuroscience research on humans and animals exposed to spaceflight or analogs of spaceflight environments, and projects the implications and the forward work necessary to ensure successful Mars missions. It also reviews fundamental neurophysiology responses that will help us understand and maintain human health and performance on Earth.


Assuntos
Astronautas , Sistema Nervoso Central/fisiologia , Emoções/fisiologia , Marte , Desempenho Psicomotor/fisiologia , Voo Espacial , Vestíbulo do Labirinto/fisiologia , Ausência de Peso , Animais , Humanos , Ausência de Peso/efeitos adversos
3.
Radiat Environ Biophys ; 53(2): 255-63, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24477407

RESUMO

Chromosome aberrations in blood lymphocytes provide a useful measure of past exposure to ionizing radiation. Despite the widespread and successful use of the dicentric assay for retrospective biodosimetry, the approach suffers substantial drawbacks, including the fact that dicentrics in circulating blood have a rather short half-life (roughly 1-2 years by most estimates). So-called symmetrical aberrations such as translocations are far more stable in that regard, but their high background frequency, which increases with age, also makes them less than ideal for biodosimetry. We developed a cytogenetic assay for potential use in retrospective biodosimetry that is based on the detection of chromosomal inversions, another symmetrical aberration whose transmissibility (stability) is also ostensibly high. Many of the well-known difficulties associated with inversion detection were circumvented through the use of directional genomic hybridization, a method of molecular cytogenetics that is less labor intensive and better able to detect small chromosomal inversions than other currently available approaches. Here, we report the dose-dependent induction of inversions following exposure to radiations with vastly different ionization densities [i.e., linear energy transfer (LET)]. Our results show a dramatic dose-dependent difference in the yields of inversions induced by low-LET gamma rays, as compared to more damaging high-LET charged particles similar to those encountered in deep space.


Assuntos
Inversão Cromossômica/efeitos da radiação , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Radiometria/métodos , Quebra Cromossômica/efeitos da radiação , Cromossomos Humanos Par 3/genética , Cromossomos Humanos Par 3/efeitos da radiação , Relação Dose-Resposta à Radiação , Raios gama/efeitos adversos , Humanos , Transferência Linear de Energia , Hibridização de Ácido Nucleico , Estudos Retrospectivos
4.
Mutat Res ; 756(1-2): 101-7, 2013 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-23688614

RESUMO

We have studied the induction of chromosome aberrations in human fibroblasts exposed in G0/G1 to X-rays or heavy ions to study the influence of G1 cell cycle arrest. Confluent normal fibroblasts were exposed to X-rays or accelerated particles with different LET values and chromosome aberrations were investigated in the first G0/G1 and G2//M phase. The particles used here were 490MeV/nucleon Si, 500MeV/nucleon Fe, and 200MeV/nucleon Fe ions. Cells were subcultured 24h after exposure and premature chromosome condensation (PCC) was performed by fusion-induced method for analysis of G0/G1 cells, and chemically-induced method for analysis of G2 and metaphase cells. Chromosome damage was assessed in chromosomes 1 and 3 using whole chromosome fluorescence in situ hybridization (FISH). Cell cycle was analyzed by flow cytometry at different incubation times following subculture. After irradiation with 2Gy of high-LET particles, the yields of chromosome aberrations and fragments were significantly higher in G0/G1 phase than in G2/M phase, whereas similar yields of damage were measured in both phases after exposure to X-rays. In contrast, the yield of misrepair, assessed by the number of color junctions, was similar in the G0/G1 and G2/M phases after exposure to either X-rays or high-LET particles. The yields of chromosome aberrations, fragments, and color junctions in both the G0/G1 and the G2/M phases, increased with LET up to 200keV/µm, then decreased for 440keV/µm Fe particles. A good correlation was found between chromosome aberrations in both G0/G1 and G2/M cells and survival fractions after 2Gy of different LET radiations, although the slopes were steeper for the G0/G1 cells. Flow cytometry analysis indicated that high-LET particles induce more non cycling G0/G1 cells within 48h of subculture than X-rays, suggesting that chromosome aberrations scored at the G2/M phase may not accurately describe the true radiation effect.


Assuntos
Ciclo Celular/genética , Ciclo Celular/efeitos da radiação , Aberrações Cromossômicas/efeitos da radiação , Fibroblastos/efeitos da radiação , Pele/efeitos da radiação , Células Cultivadas , Fibroblastos/citologia , Fibroblastos/metabolismo , Citometria de Fluxo , Humanos , Processamento de Imagem Assistida por Computador , Hibridização in Situ Fluorescente , Transferência Linear de Energia , Pele/citologia , Pele/metabolismo , Raios X
5.
Cochrane Database Syst Rev ; (3): CD005106, 2012 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-22419306

RESUMO

BACKGROUND: Neck disorders are common, disabling, and costly. The effectiveness of patient education strategies is unclear. OBJECTIVES: To assess the short- to long-term effects of therapeutic patient education (TPE) strategies on pain, function, disability, quality of life, global perceived effect, patient satisfaction, knowledge transfer, or behaviour change in adults with neck pain associated with whiplash or non-specific and specific mechanical neck pain with or without radiculopathy or cervicogenic headache. SEARCH METHODS: We searched computerised bibliographic databases (inception to 11 July 2010). SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCT) investigating the effectiveness of TPE for acute to chronic neck pain. DATA COLLECTION AND ANALYSIS: Paired independent review authors conducted selection, data abstraction, and 'Risk of bias' assessment. We calculated risk ratio (RR) and standardised mean differences (SMD). Heterogeneity was assessed; no studies were pooled. MAIN RESULTS: Of the 15 selected trials, three were rated low risk of bias. Three TPE themes emerged.Advice focusing on activation: There is moderate quality evidence (one trial, 348 participants) that an educational video of advice focusing on activation was more beneficial for acute whiplash-related pain when compared with no treatment at intermediate-term [RR 0.79 (95% confidence interval (CI) 0.59 to 1.06)] but not long-term follow-up [0.89 (95% CI, 0.65 to 1.21)]. There is low quality evidence (one trial, 102 participants) that a whiplash pamphlet on advice focusing on activation is less beneficial for pain reduction, or no different in improving function and global perceived improvement from generic information given out in emergency care (control) for acute whiplash at short- or intermediate-term follow-up. Low to very low quality evidence (nine trials using diverse educational approaches) showed either no evidence of benefit or difference for varied outcomes. Advice focusing on pain & stress coping skills and workplace ergonomics: Very low quality evidence (three trials, 243 participants) favoured other treatment or showed no difference spanning numerous follow-up periods and disorder subtypes.  Low quality evidence (one trial, 192 participants) favoured specific exercise training for chronic neck pain at short-term follow-up.Self-care strategies: Very low quality evidence (one trial, 58 participants) indicated that self-care strategies did not relieve pain for acute to chronic neck pain at short-term follow-up. AUTHORS' CONCLUSIONS: With the exception of one trial, this review has not shown effectiveness for educational interventions, including advice to activate, advice on stress-coping skills, workplace ergonomics and self-care strategies. Future research should be founded on sound adult learning theory and learning skill acquisition.


Assuntos
Cervicalgia/terapia , Educação de Pacientes como Assunto/métodos , Traumatismos em Chicotada/complicações , Adaptação Psicológica , Adulto , Terapia Combinada , Humanos , Cervicalgia/etiologia , Radiculopatia/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Descanso , Autocuidado/métodos , Resultado do Tratamento , Traumatismos em Chicotada/terapia
6.
Int J Radiat Biol ; 98(3): 395-403, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34270368

RESUMO

PURPOSE: My journey to the stars began as I - along with the whole world - stood still and watched Neil Armstrong take those first small steps on the Moon. Fast forward 50 years and NASA astronauts Scott Kelly and Christina Koch each spend nearly a year in space aboard the International Space Station (ISS), a remarkable multinational collaborative project and floating U.S. National Laboratory that has supported continuous human presence in low Earth orbit for the past 20 years. Marking a new era of human space exploration, the first commercial rocket, SpaceX Falcon 9, recently launched NASA astronauts Doug Hurley and Bob Behnken in the Crew Dragon spacecraft Endeavor to the ISS and returned safely to Earth. NASA and its commercial partners are rapidly advancing innovative space technologies, and with the recently announced Artemis team of astronauts, plans to send the first woman and next man back to the moon and establish sustainable exploration by the end of the decade. Humankind will then be poised to take the next giant leap - pioneering human exploration of Mars. CONCLUSIONS: Historically, fewer than 600 individuals have participated in spaceflight, the vast majority of whom have been middle aged males (35-55 years) on short duration missions (less than 20 days). Thus, as the number and diversity of space travelers increase, a better understanding of how long-duration spaceflight affects human health is essential to maintaining individual astronaut performance during, and improving disease and aging trajectories following, future exploration missions. Here, I review findings from our NASA Twins Study and Telomeres investigations, highlighting potential mechanistic roles of chronic space radiation exposure in changes in telomere length and persistent DNA damage responses associated with long-duration spaceflight. Importantly, similar trends were observed in prostate cancer patients undergoing intensity-modulated radiation therapy (IMRT), additional support specifically for the role of radiation exposure. Individual differences in response were also observed in both cohorts, underscoring the importance of developing personalized approaches for evaluating human health effects and long-term outcomes associated with radiation exposures, whether on Earth or living in the extreme environment of space.


Assuntos
Envelhecimento , Voo Espacial , Feminino , Humanos , Laboratórios , Masculino , Pessoa de Meia-Idade , Telômero
7.
Mutat Res ; 716(1-2): 76-83, 2011 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-21889946

RESUMO

Cells deficient in ATM (product of the gene that is mutated in ataxia telangiectasia patients) or NBS (product of the gene mutated in the Nijmegen breakage syndrome) show increased yields of both simple and complex chromosomal aberrations after high doses (>0.5Gy) of ionizing radiation (X-rays or γ-rays), however less is known on how these cells respond at low dose. Previously we had shown that the increased chromosome aberrations in ATM and NBS defective lines was due to a significantly larger quadratic dose-response term compared to normal fibroblasts for both simple and complex exchanges. The linear dose-response term for simple exchanges was significantly higher in NBS cells compared to wild type cells, but not for AT cells. However, AT cells have a high background level of exchanges compared to wild type or NBS cells that confounds the understanding of low dose responses. To understand the sensitivity differences for high to low doses, chromosomal aberration analysis was first performed at low dose-rates (0.5Gy/d), and results provided further evidence for the lack of sensitivity for exchanges in AT cells below doses of 1Gy. Normal lung fibroblast cells treated with KU-55933, a specific ATM kinase inhibitor, showed increased numbers of exchanges at a dose of 1Gy and higher, but were similar to wild type cells at 0.5Gy or below. These results were confirmed using siRNA knockdown of ATM. The present study provides evidence that the increased radiation sensitivity of AT cells for chromosomal exchanges found at high dose does not occur at low dose.


Assuntos
Ataxia Telangiectasia/genética , Aberrações Cromossômicas/efeitos da radiação , Tolerância a Radiação/genética , Proteínas Mutadas de Ataxia Telangiectasia , Proteínas de Ciclo Celular/genética , Linhagem Celular , Dano ao DNA , Proteínas de Ligação a DNA/genética , Relação Dose-Resposta à Radiação , Fibroblastos , Raios gama , Técnicas de Silenciamento de Genes , Humanos , Morfolinas/farmacologia , Proteínas Nucleares/genética , Proteínas Serina-Treonina Quinases/genética , Pironas/farmacologia , Proteínas Supressoras de Tumor/genética
8.
Neurosci Biobehav Rev ; 127: 307-331, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33915203

RESUMO

Multi-year crewed space exploration missions are now on the horizon; therefore, it is important that we understand and mitigate the physiological effects of spaceflight. The spaceflight hazards-radiation, isolation, confinement, and altered gravity-have the potential to contribute to neuroinflammation and produce long-term cognitive and behavioral effects-while the fifth hazard, distance from earth, limits capabilities to mitigate these risks. Accumulated evidence suggests that nutrition has an important role in optimizing cognition and reducing the risk of neurodegenerative diseases caused by neuroinflammation. Here we review the nutritional perspective of how these spaceflight hazards affect the astronaut's brain, behavior, performance, and sensorimotor function. We also assess potential nutrient/nutritional countermeasures that could prevent or mitigate spaceflight risks and ensure that crewmembers remain healthy and perform well during their missions. Just as history has taught us the importance of nutrition in terrestrial exploration, we must understand the role of nutrition in the development and mitigation of spaceflight risks before humans can successfully explore beyond low-Earth orbit.


Assuntos
Astronautas , Voo Espacial , Encéfalo , Cognição , Humanos
9.
Sci Rep ; 11(1): 5293, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33674665

RESUMO

Space radiation consists of energetic protons and other heavier ions. During the International Space Station program, chromosome aberrations in lymphocytes of astronauts have been analyzed to estimate received biological doses of space radiation. More specifically, pre-flight blood samples were exposed ex vivo to varying doses of gamma rays, while post-flight blood samples were collected shortly and several months after landing. Here, in a study of 43 crew-missions, we investigated whether individual radiosensitivity, as determined by the ex vivo dose-response of the pre-flight chromosome aberration rate (CAR), contributes to the prediction of the post-flight CAR incurred from the radiation exposure during missions. Random-effects Poisson regression was used to estimate subject-specific radiosensitivities from the preflight dose-response data, which were in turn used to predict post-flight CAR and subject-specific relative biological effectiveness (RBEs) between space radiation and gamma radiation. Covariates age, gender were also considered. Results indicate that there is predictive value in background CAR as well as radiosensitivity determined preflight for explaining individual differences in post-flight CAR over and above that which could be explained by BFO dose alone. The in vivo RBE for space radiation was estimated to be approximately 3 relative to the ex vivo dose response to gamma irradiation. In addition, pre-flight radiosensitivity tended to be higher for individuals having a higher background CAR, suggesting that individuals with greater radiosensitivity can be more sensitive to other environmental stressors encountered in daily life. We also noted that both background CAR and radiosensitivity tend to increase with age, although both are highly variable. Finally, we observed no significant difference between the observed CAR shortly after mission and at > 6 months post-mission.

10.
Biomater Sci ; 9(10): 3576-3602, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34008586

RESUMO

The outstretched applications of biosensors in diverse domains has become the reason for their attraction for scientific communities. Because they are analytical devices, they can detect both quantitative and qualitative biological components through the generation of detectable signals. In the recent past, biosensors witnessed significant changes and developments in their design as well as features. Nanotechnology has revolutionized sensing phenomena by increasing biodiagnostic capacity in terms of specificity, size, and cost, resulting in exceptional sensitivity and flexibility. The steep increase of non-communicable diseases across the world has emerged as a matter of concern. In parallel, the abrupt outbreak of communicable diseases poses a serious threat to mankind. For decreasing the morbidity and mortality associated with various communicable and non-communicable diseases, early detection and subsequent treatment are indispensable. Detection of different biological markers generates quantifiable signals that can be electrochemical, mass-based, optical, thermal, or piezoelectric. Speculating on the incumbent applicability and versatility of nano-biosensors in large disciplines, this review highlights different types of biosensors along with their components and detection mechanisms. Moreover, it deals with the current advancements made in biosensors and the applications of nano-biosensors in detection of various non-communicable and communicable diseases, as well as future prospects of nano-biosensors for diagnostics.


Assuntos
Técnicas Biossensoriais , Doenças Transmissíveis , Biomarcadores , Doenças Transmissíveis/diagnóstico , Humanos , Nanotecnologia
11.
Cell Rep ; 33(10): 108457, 2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33242406

RESUMO

Telomere length dynamics and DNA damage responses were assessed before, during, and after one-year or shorter duration missions aboard the International Space Station (ISS) in a comparatively large cohort of astronauts (n = 11). Although generally healthy individuals, astronauts tended to have significantly shorter telomeres and lower telomerase activity than age- and sex-matched ground controls before and after spaceflight. Although telomeres were longer during spaceflight irrespective of mission duration, telomere length shortened rapidly upon return to Earth, and overall astronauts had shorter telomeres after spaceflight than they did before; inter-individual differences were identified. During spaceflight, all crewmembers experienced oxidative stress, which positively correlated with telomere length dynamics. Significantly increased frequencies of chromosomal inversions were observed during and after spaceflight; changes in cell populations were also detected. We propose a telomeric adaptive response to chronic oxidative damage in extreme environments, whereby the telomerase-independent Alternative Lengthening of Telomeres (ALT) pathway is transiently activated in normal somatic cells.


Assuntos
Reparo do DNA/fisiologia , Homeostase do Telômero/fisiologia , Ausência de Peso/efeitos adversos , Adulto , Astronautas , DNA/química , DNA/efeitos da radiação , Dano ao DNA/fisiologia , Reparo do DNA/efeitos da radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Voo Espacial , Telomerase/metabolismo , Telômero/metabolismo , Telômero/fisiologia , Homeostase do Telômero/efeitos da radiação , Fatores de Tempo
12.
Cell Rep ; 33(10): 108435, 2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33242411

RESUMO

Telomeres, repetitive terminal features of chromosomes essential for maintaining genome integrity, shorten with cell division, lifestyle factors and stresses, and environmental exposures, and so they provide a robust biomarker of health, aging, and age-related diseases. We assessed telomere length dynamics (changes over time) in three unrelated astronauts before, during, and after 1-year or 6-month missions aboard the International Space Station (ISS). Similar to our results for National Aeronautics and Space Administration's (NASA's) One-Year Mission twin astronaut (Garrett-Bakelman et al., 2019), significantly longer telomeres were observed during spaceflight for two 6-month mission astronauts. Furthermore, telomere length shortened rapidly after return to Earth for all three crewmembers and, overall, telomere length tended to be shorter after spaceflight than before spaceflight. Consistent with chronic exposure to the space radiation environment, signatures of persistent DNA damage responses were also detected, including mitochondrial and oxidative stress, inflammation, and telomeric and chromosomal aberrations, which together provide potential mechanistic insight into spaceflight-specific telomere elongation.


Assuntos
Dano ao DNA/genética , Reparo do DNA/fisiologia , Telômero/genética , Adulto , Astronautas , DNA/genética , DNA/efeitos da radiação , Quebras de DNA de Cadeia Dupla , Dano ao DNA/efeitos da radiação , Reparo do DNA/genética , Reparo do DNA/efeitos da radiação , Relação Dose-Resposta à Radiação , Meio Ambiente Extraterreno , Feminino , Humanos , Masculino , Voo Espacial , Telômero/metabolismo , Telômero/efeitos da radiação , Fatores de Tempo , Ausência de Peso/efeitos adversos
13.
Radiat Res ; 171(6): 752-63, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19580482

RESUMO

We studied the effects of DNA double-strand break (DSB) repair deficiencies on chromosomal aberration frequency using low doses (<1 Gy) of gamma rays and high-energy iron ions (LET = 151 keV/microm). Chromosomal aberrations were measured using the fluorescence whole-chromosome painting technique. The cell lines included fibroblasts deficient in ATM (product of the gene that is mutated in ataxia telangiectasia patients) or NBS (product of the gene mutated in the Nijmegen breakage syndrome) and gliomablastoma cells proficient in or lacking DNA-dependent protein kinase (DNA-PK) activity. The yields of both simple and complex chromosomal aberrations were increased in DSB repair-defective cells compared to normal cells; the increase was more than twofold higher for gamma rays compared to iron nuclei. For gamma-ray-induced aberrations, the ATM- and NBS-defective lines were found to have significantly larger quadratic components compared to normal fibroblasts for both simple and complex aberrations, while the linear dose-response term was significantly higher only for the NBS cells. For simple and complex aberrations induced by iron nuclei, regression models preferred purely linear and quadratic dose responses, respectively, for each cell line studied. RBEs were reduced relative to normal cells for all of the DSB repair-defective lines, with the DNA-PK-deficient cells found to have RBEs near unity. The large increase in the quadratic dose-response terms in the DSB repair-deficient cell lines points to the importance of the functions of ATM and NBS in chromatin modifications to facilitate correct DSB repair and to minimize aberration formation. The differences found between AT and NBS cells at lower doses suggest important questions about the applicability of observations of radiation sensitivity at high doses to low-dose exposures.


Assuntos
Aberrações Cromossômicas/efeitos da radiação , Distúrbios no Reparo do DNA , Raios gama/efeitos adversos , Ferro , Doses de Radiação , Ataxia Telangiectasia/genética , Linhagem Celular , Linhagem Celular Tumoral , Quebras de DNA de Cadeia Dupla , Distúrbios no Reparo do DNA/genética , Proteína Quinase Ativada por DNA/deficiência , Relação Dose-Resposta à Radiação , Feminino , Humanos , Transferência Linear de Energia , Modelos Lineares , Síndrome de Quebra de Nijmegen/genética , Análise de Regressão
14.
Science ; 364(6436)2019 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-30975860

RESUMO

To understand the health impact of long-duration spaceflight, one identical twin astronaut was monitored before, during, and after a 1-year mission onboard the International Space Station; his twin served as a genetically matched ground control. Longitudinal assessments identified spaceflight-specific changes, including decreased body mass, telomere elongation, genome instability, carotid artery distension and increased intima-media thickness, altered ocular structure, transcriptional and metabolic changes, DNA methylation changes in immune and oxidative stress-related pathways, gastrointestinal microbiota alterations, and some cognitive decline postflight. Although average telomere length, global gene expression, and microbiome changes returned to near preflight levels within 6 months after return to Earth, increased numbers of short telomeres were observed and expression of some genes was still disrupted. These multiomic, molecular, physiological, and behavioral datasets provide a valuable roadmap of the putative health risks for future human spaceflight.


Assuntos
Adaptação Fisiológica , Astronautas , Voo Espacial , Imunidade Adaptativa , Peso Corporal , Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Dano ao DNA , Metilação de DNA , Microbioma Gastrointestinal , Instabilidade Genômica , Humanos , Masculino , Homeostase do Telômero , Fatores de Tempo , Estados Unidos , United States National Aeronautics and Space Administration
15.
Radiat Res ; 170(1): 127-38, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18582161

RESUMO

In this study, we analyzed the biological and physical organ dose equivalents for International Space Station (ISS) astronauts. Individual physical dosimetry is difficult in space due to the complexity of the space radiation environment, which consists of protons, heavy ions and secondary neutrons, and the modification of these radiation types in tissue as well as limitations in dosimeter devices that can be worn for several months in outer space. Astronauts returning from missions to the ISS undergo biodosimetry assessment of chromosomal damage in lymphocyte cells using the multicolor fluorescence in situ hybridization (FISH) technique. Individual-based pre-flight dose responses for lymphocyte exposure in vitro to gamma rays were compared to those exposed to space radiation in vivo to determine an equivalent biological dose. We compared the ISS biodosimetry results, NASA's space radiation transport models of organ dose equivalents, and results from ISS and space shuttle phantom torso experiments. Physical and biological doses for 19 ISS astronauts yielded average effective doses and individual or population-based biological doses for the approximately 6-month missions of 72 mSv and 85 or 81 mGy-Eq, respectively. Analyses showed that 80% or more of organ dose equivalents on the ISS are from galactic cosmic rays and only a small contribution is from trapped protons and that GCR doses were decreased by the high level of solar activity in recent years. Comparisons of models to data showed that space radiation effective doses can be predicted to within about a +/-10% accuracy by space radiation transport models. Finally, effective dose estimates for all previous NASA missions are summarized.


Assuntos
Astronautas , Astronave , Células Cultivadas , Humanos , Hibridização in Situ Fluorescente , Internacionalidade , Modelos Biológicos , Radiometria , Irradiação Corporal Total
16.
Artif Cells Nanomed Biotechnol ; 46(sup2): 1053-1062, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29879850

RESUMO

Nanodrug delivery systems sometimes referred to as nanocarriers (NCs) are nanoengineered biocompatible materials or devices, which in conjugation with desired bioactive compounds plays an indispensable functional role in the field of pharmaceutical and allied sciences. The diversified ability of this bioengineered colloidal or noncolloidal molecule to breach the biological barriers to reach the targeted location in the biological system uplifts its other versatile natures of mono- or polydispersity in biodistribution. Furthermore, its nontoxicity and biodegradability result in making it a unique candidate for its purpose as drug delivery system. A number of different conjugations of chemical and biological substances are currently implemented for the synthesis of this biofunctional hybrid nanomaterial by simple methods. The use of these bioconjugated as a nanoparticulated system is currently being used for the treatment of various deadly incurable infectious diseases such as tuberculosis and disorders such as diabetes and cancers of various forms. Henceforth, the objective of the present review article is to provide overviews of the diversified and types of nanoparticulated systems, their beneficial as well as deleterious impacts along with the future prospect of nanodrug delivery system based on present status.


Assuntos
Portadores de Fármacos/química , Nanoestruturas/química , Humanos
17.
J Radiat Res ; 48(1): 31-8, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17132914

RESUMO

When cell lines are held in a quiescent state after irradiation, survival rates are greater than those from cells that are stimulated to grow immediately after irradiation. These differences in survival rates correspond to rates of potentially lethal damage repair. The effects of confluent holding recovery after gamma-irradiation were investigated using normal human fibroblasts (AG1522) and ataxia telangiectasia fibroblasts (GM02052). Calyculin-A-induced premature chromosome condensation and fluorescent in situ hybridization were applied to study G2/M chromosomal aberrations. Survival results indicated normal capacity for PLDR in AG1522 cells but that PLDR was extremely compromised in GM02052 cells. The chromosomal aberration frequency decreased when AG1522 cells were allowed to repair for 24-h, whereas 24-hour incubation had little effect on the aberration frequency in GM02052 cells. Since the main mechanism for dsbs repair during G0/G1 phases of the cells cycle involve the non-homologous end-joining (NHEJ) process, our study indicates that for AG1522 cells the NHEJ repair process is more likely to induce accurate chromosome repair under quiescent G0 conditions than proliferating G1 phase, while in GM02052 cells the fidelity of NHEJ is similarly defective at either cell cycle phase. Reduced fidelity of NHEJ may be responsible for PLDR defect and its hyper-radiosensitivity in A-T cells.


Assuntos
Ataxia Telangiectasia/patologia , Ataxia Telangiectasia/fisiopatologia , Sobrevivência Celular/efeitos da radiação , Quebra Cromossômica/efeitos da radiação , Dano ao DNA , Reparo do DNA/efeitos da radiação , Fibroblastos/efeitos da radiação , Células Cultivadas , Humanos
18.
PLoS One ; 11(4): e0153998, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27111667

RESUMO

The biological effects of high charge and energy (HZE) particle exposures are of interest in space radiation protection of astronauts and cosmonauts, and estimating secondary cancer risks for patients undergoing Hadron therapy for primary cancers. The large number of particles types and energies that makeup primary or secondary radiation in HZE particle exposures precludes tumor induction studies in animal models for all but a few particle types and energies, thus leading to the use of surrogate endpoints to investigate the details of the radiation quality dependence of relative biological effectiveness (RBE) factors. In this report we make detailed RBE predictions of the charge number and energy dependence of RBE's using a parametric track structure model to represent experimental results for the low dose response for chromosomal exchanges in normal human lymphocyte and fibroblast cells with comparison to published data for neoplastic transformation and gene mutation. RBE's are evaluated against acute doses of γ-rays for doses near 1 Gy. Models that assume linear or non-targeted effects at low dose are considered. Modest values of RBE (<10) are found for simple exchanges using a linear dose response model, however in the non-targeted effects model for fibroblast cells large RBE values (>10) are predicted at low doses <0.1 Gy. The radiation quality dependence of RBE's against the effects of acute doses γ-rays found for neoplastic transformation and gene mutation studies are similar to those found for simple exchanges if a linear response is assumed at low HZE particle doses. Comparisons of the resulting model parameters to those used in the NASA radiation quality factor function are discussed.


Assuntos
Cromossomos , Radiação Cósmica , Neoplasias/fisiopatologia , Relação Dose-Resposta à Radiação , Humanos , Neoplasias/genética , Eficiência Biológica Relativa
19.
Radiat Res ; 164(4 Pt 2): 509-13, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16187758

RESUMO

Caffeine sensitizes cells to ionizing radiation, and this effect is believed to be associated with the disruption of DNA damage-responsive cell cycle checkpoints, which is controlled by ATM. Recent studies suggest that misrejoining of DSBs is one of the underlying mechanisms of AT cell hyper-radiosensitivity. In this study, we investigated the effects of caffeine and radiation on nongrowing G0 normal human fibroblast cells by determining cell survival and scoring aberrations in calyculin A-induced G2 chromosomes. Results from the cell survival study indicate that after X-ray exposure G0 cells were sensitized by 24 h treatment with caffeine. Analysis of chromosome aberrations using FISH (fluorescence in situ hybridization) revealed a high frequency of aberrant cells and color junctions in the caffeine-treated cells. Since most DNA repair in nongrowing G0 cells is believed to result from nonhomologous end joining (NHEJ), caffeine may influence the fidelity of the NHEJ pathway in irradiated G0 cells.


Assuntos
Cafeína/farmacologia , Reparo do DNA/efeitos dos fármacos , Fibroblastos/efeitos da radiação , Radiossensibilizantes/farmacologia , Linhagem Celular , Aberrações Cromossômicas , Fibroblastos/efeitos dos fármacos , Humanos , Recombinação Genética/efeitos dos fármacos , Raios X
20.
Front Oncol ; 5: 226, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26539409

RESUMO

We have investigated chromosome exchanges induced in human cells by seven different energies of protons (5-2500 MeV) with LET values ranging from 0.2 to 8 keV/µm. Human lymphocytes were irradiated in vitro and chromosome damage was assessed using three-color fluorescence in situ hybridization chromosome painting in chemically condensed chromosomes collected during the first cell division post irradiation. The relative biological effectiveness (RBE) was calculated from the initial slope of the dose-response curve for chromosome exchanges with respect to low dose and low dose-rate γ-rays (denoted as RBEmax), and relative to acute doses of γ-rays (denoted as RBEγAcute). The linear dose-response term was similar for all energies of protons, suggesting that the decrease in LET with increasing proton energy was balanced by the increase in dose from the production of nuclear secondaries. Secondary particles increase slowly above energies of a few hundred megaelectronvolts. Additional studies of 50 g/cm(2) aluminum shielded high-energy proton beams showed minor differences compared to the unshielded protons and lower RBE values found for shielded in comparison to unshielded beams of 2 or 2.5 GeV. All energies of protons produced a much higher percentage of complex-type chromosome exchanges when compared to acute doses of γ-rays. The implications of these results for space radiation protection and proton therapy are discussed.

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