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2.
Mol Psychiatry ; 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33859359

RESUMO

Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups in two stages using 2 degree of freedom (df) joint test followed by 1df test of interaction effects. Primary multi-ancestry analysis in 62,969 individuals in stage 1 identified three novel gene by sleep interactions that were replicated in an additional 59,296 individuals in stage 2 (stage 1 + 2 Pjoint < 5 × 10-8), including rs7955964 (FIGNL2/ANKRD33) that increases BP among long sleepers, and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) that increase BP among short sleepers (Pint < 5 × 10-8). Secondary ancestry-specific analysis identified another novel gene by long sleep interaction at rs111887471 (TRPC3/KIAA1109) in individuals of African ancestry (Pint = 2 × 10-6). Combined stage 1 and 2 analyses additionally identified significant gene by long sleep interactions at 10 loci including MKLN1 and RGL3/ELAVL3 previously associated with BP, and significant gene by short sleep interactions at 10 loci including C2orf43 previously associated with BP (Pint < 10-3). 2df test also identified novel loci for BP after modeling sleep that has known functions in sleep-wake regulation, nervous and cardiometabolic systems. This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.

3.
Nat Commun ; 12(1): 900, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568662

RESUMO

Daytime napping is a common, heritable behavior, but its genetic basis and causal relationship with cardiometabolic health remain unclear. Here, we perform a genome-wide association study of self-reported daytime napping in the UK Biobank (n = 452,633) and identify 123 loci of which 61 replicate in the 23andMe research cohort (n = 541,333). Findings include missense variants in established drug targets for sleep disorders (HCRTR1, HCRTR2), genes with roles in arousal (TRPC6, PNOC), and genes suggesting an obesity-hypersomnolence pathway (PNOC, PATJ). Association signals are concordant with accelerometer-measured daytime inactivity duration and 33 loci colocalize with loci for other sleep phenotypes. Cluster analysis identifies three distinct clusters of nap-promoting mechanisms with heterogeneous associations with cardiometabolic outcomes. Mendelian randomization shows potential causal links between more frequent daytime napping and higher blood pressure and waist circumference.


Assuntos
Miócitos Cardíacos/metabolismo , Sono , Adulto , Idoso , Pressão Sanguínea , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Canal de Cátion TRPC6/genética , Reino Unido , Circunferência da Cintura
4.
Neuroreport ; 32(3): 177-187, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33323840

RESUMO

OBJECTIVE: The traditional Chinese medicine, Dendrobium nobile Lindl. polysaccharides (DNLP), reportedly has neuroprotective effects. However, its effects following ischemic stroke remain unclear. This study aimed to explore the role and mechanism of DNLP in experimental models of inflammation and apoptosis. METHODS: Inflammation and apoptosis were induced by in vivo ischemia/reperfusion and by in vitro oxygen glucose deprivation/reperfusion (OGD/R). In the in vivo model, immediately after the induction of cerebral ischemia, 50, 100, and 200 mg/kg DNLP were injected intraperitoneally. We subsequently detected indicators of neuronal damage. RESULTS: Treatment with Dendrobium nobile Lindl. polysaccharide significantly reduced cerebral ischemic injury. After in vivo and in vitro middle cerebral artery occlusion/reperfusion or OGD/R-induced hypoxia injury, miR-134 expression in neurons was significantly increased. Altering the expression of miR-134 induced changes in myeloid cell leukemia 1 (MCL-1), one of its target proteins. In addition, DNLP significantly downregulated the in vivo and in vitro expression of miR-134 after ischemic injury, and influenced inflammation and apoptotic proteins by altering the level of MCL-1 protein. DNLP also had a protective effect on neurons damaged by OGD/R, which could improve cell survival rates and inhibit lactate dehydrogenase release as well as apoptosis. CONCLUSIONS: DNLP may protect the brain and neurons from hypoxic damage in mice with ischemic stroke by activating MCL-1 and downregulating miR-134, providing a new therapeutic target for ischemic stroke.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33285084

RESUMO

RATIONALE: Symptoms and morbidities associated with obstructive sleep apnea (OSA) vary across individuals and are not predicted by the apnea-hypopnea index (AHI). Respiratory event duration is a heritable trait associated with mortality that may further characterize OSA. OBJECTIVE: We evaluated how hypopnea and apnea durations in non-rapid eye movement (NREM) sleep vary across demographic groups and quantified their associations with physiological traits (loop gain, arousal threshold, circulatory delay, pharyngeal collapsibility). METHODS: Data were analyzed from 1546 participants from the Multi-Ethnic Study of Atherosclerosis with an AHI ≥5. Physiological traits were derived using a validated model fit to the polysomnographic airflow signal. Multiple linear regression models were used to evaluate associations of event duration with demographic and physiological factors. MAIN RESULTS: Participants had a mean age ±SD of 68.9 ±9.2 years, mean NREM hypopnea duration of 21.73 ±5.60 and mean NREM apnea duration of 23.87 ±7.44 seconds. In adjusted analyses, shorter events were associated with younger age, female sex, higher body mass index (p <0.01, all) and Black race (p <0.05). Longer events were associated with Asian race (p<0.01). Shorter event durations were associated with lower circulatory delay (2.53 ±0.13s, p<0.01), lower arousal threshold (1.39 ±0.15s, p<0.01), reduced collapsibility (-0.71 ±0.16s, p<0.01), and higher loop gain (-0.27 ±0.11s, p<0.05) per SD change. Adjustment for physiological traits attenuated age, sex, and obesity associations and eliminated racial differences in event duration. CONCLUSIONS: Average event duration varies across population groups and provides information on ventilatory features and airway collapsibility not captured by the AHI.

6.
Int J Epidemiol ; 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33150399

RESUMO

BACKGROUND: It is established that Alzheimer's disease (AD) patients experience sleep disruption. However, it remains unknown whether disruption in the quantity, quality or timing of sleep is a risk factor for the onset of AD. METHODS: We used the largest published genome-wide association studies of self-reported and accelerometer-measured sleep traits (chronotype, duration, fragmentation, insomnia, daytime napping and daytime sleepiness), and AD. Mendelian randomization (MR) was used to estimate the causal effect of self-reported and accelerometer-measured sleep parameters on AD risk. RESULTS: Overall, there was little evidence to support a causal effect of sleep traits on AD risk. There was some suggestive evidence that self-reported daytime napping was associated with lower AD risk [odds ratio (OR): 0.70, 95% confidence interval (CI): 0.50-0.99). Some other sleep traits (accelerometer-measured 'eveningness' and sleep duration, and self-reported daytime sleepiness) had ORs of a similar magnitude to daytime napping, but were less precisely estimated. CONCLUSIONS: Overall, we found very limited evidence to support a causal effect of sleep traits on AD risk. Our findings provide tentative evidence that daytime napping may reduce AD risk. Given that this is the first MR study of multiple self-report and objective sleep traits on AD risk, findings should be replicated using independent samples when such data become available.

7.
Opt Lett ; 45(18): 5129-5131, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32932469

RESUMO

High optical quality (Q) factors are critically important in optical microcavities, where performance in applications spanning nonlinear optics to cavity quantum electrodynamics is determined. Here, a record Q factor of over 1.1 billion is demonstrated for on-chip optical resonators. Using silica whispering-gallery resonators on silicon, Q-factor data is measured over wavelengths spanning the C/L bands (100 nm) and for a range of resonator sizes and mode families. A record low sub-milliwatt parametric oscillation threshold is also measured in 9 GHz free-spectral-range devices. The results show the potential for thermal silica on silicon as a resonator material.

8.
J Environ Manage ; 274: 111220, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32823086

RESUMO

China is experiencing unprecedented industrialization and urbanization which promotes the rapid growth of iron resource consumption and in-use stock. The material flow analysis (MFA) model and the average use life method were applied to analyze China's iron in-use stock (IIUS), and the IIUS reached 7.07 billion tons in 2016 in the reference scenario. Three driving factors of the intensity of IIUS were analyzed. Among them, the per capita IIUS was rising, and it was 5.11 t/cap in 2016 in the reference scenario. In addition, the per capita crude steel output has stabilized, which was 0.58 t/cap in 2016. The intensity of crude steel use was declining and showed the inverted U-shape. The decoupling indicator was applied to analyze the relationship between IIUS and economic growth. The decoupling of IIUS from economic growth was later than that of actual iron consumption, and the IIUS did not decoupling from economic growth in recent years. The actual iron consumption has continued to decoupling from economic growth since 2010, and the decoupling indicator peaked at 1.76 in 2015. The future per capita IIUS was predicted in different scenario and the relationship between future IIUS and GDP was analyzed. The per capita IIUS will reach saturation in 2030-2040, and the intensity of IIUS also conforms to the inverted U-shape.


Assuntos
Desenvolvimento Econômico , Ferro , China , Aço , Urbanização
9.
BMC Genomics ; 21(1): 476, 2020 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-32652930

RESUMO

BACKGROUND: Fitness epistasis, the interaction effect of genes at different loci on fitness, makes an important contribution to adaptive evolution. Although fitness interaction evidence has been observed in model organisms, it is more difficult to detect and remains poorly understood in human populations as a result of limited statistical power and experimental constraints. Fitness epistasis is inferred from non-independence between unlinked loci. We previously observed ancestral block correlation between chromosomes 4 and 6 in African Americans. The same approach fails when examining ancestral blocks on the same chromosome due to the strong confounding effect observed in a recently admixed population. RESULTS: We developed a novel approach to eliminate the bias caused by admixture linkage disequilibrium when searching for fitness epistasis on the same chromosome. We applied this approach in 16,252 unrelated African Americans and identified significant ancestral correlations in two pairs of genomic regions (P-value< 8.11 × 10- 7) on chromosomes 1 and 10. The ancestral correlations were not explained by population admixture. Historical African-European crossover events are reduced between pairs of epistatic regions. We observed multiple pairs of co-expressed genes shared by the two regions on each chromosome, including ADAR being co-expressed with IFI44 in almost all tissues and DARC being co-expressed with VCAM1, S1PR1 and ELTD1 in multiple tissues in the Genotype-Tissue Expression (GTEx) data. Moreover, the co-expressed gene pairs are associated with the same diseases/traits in the GWAS Catalog, such as white blood cell count, blood pressure, lung function, inflammatory bowel disease and educational attainment. CONCLUSIONS: Our analyses revealed two instances of fitness epistasis on chromosomes 1 and 10, and the findings suggest a potential approach to improving our understanding of adaptive evolution.

10.
EBioMedicine ; 56: 102803, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32512511

RESUMO

BACKGROUND: Sleep Disordered Breathing (SDB) is associated with a wide range of pathophysiological changes due, in part, to hypoxemia during sleep. We sought to identify gene transcription associations with measures of SDB and hypoxemia during sleep, and study their response to treatment. METHODS: In two discovery cohorts, Framingham Offspring Study (FOS; N = 571) and the Multi-Ethnic Study of Atherosclerosis (MESA; N = 580), we studied gene expression in peripheral blood mononuclear cells in association with three measures of SDB: Apnea Hypopnea Index (AHI); average oxyhemoglobin saturation (avgO2) during sleep; and minimum oxyhemoglobin saturation (minO2) during sleep. Associated genes were used for analysis of gene expression in the blood of 15 participants with moderate or severe obstructive sleep apnea (OSA) from the Heart Biomarkers In Apnea Treatment (HeartBEAT) trial. These genes were studied pre- and post-treatment (three months) with continuous positive airway pressure (CPAP). We also performed Gene Set Enrichment Analysis (GSEA) on all traits and cohort analyses. FINDINGS: Twenty-two genes were associated with SDB traits in both MESA and FOS. Of these, lower expression of CD1D and RAB20 was associated with lower avgO2 in MESA and FOS. CPAP treatment increased the expression of these genes in HeartBEAT participants. Immunity and inflammation pathways were up-regulated in subjects with lower avgO2; i.e., in those with a more severe SDB phenotype (MESA), whereas immuno-inflammatory processes were down-regulated following CPAP treatment (HeartBEAT). INTERPRETATION: Low oxygen saturation during sleep is associated with alterations in gene expression and transcriptional programs that are partially reversed by CPAP treatment.

11.
Circ Genom Precis Med ; 13(4): e002772, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32510982

RESUMO

BACKGROUND: Alcohol intake influences plasma lipid levels, and such effects may be moderated by genetic variants. We aimed to characterize the role of aggregated rare and low-frequency protein-coding variants in gene by alcohol consumption interactions associated with fasting plasma lipid levels. METHODS: In the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, fasting plasma triglycerides and high- and low-density lipoprotein cholesterol were measured in 34 153 individuals with European ancestry from 5 discovery studies and 32 277 individuals from 6 replication studies. Rare and low-frequency functional protein-coding variants (minor allele frequency, ≤5%) measured by an exome array were aggregated by genes and evaluated by a gene-environment interaction test and a joint test of genetic main and gene-environment interaction effects. Two dichotomous self-reported alcohol consumption variables, current drinker, defined as any recurrent drinking behavior, and regular drinker, defined as the subset of current drinkers who consume at least 2 drinks per week, were considered. RESULTS: We discovered and replicated 21 gene-lipid associations at 13 known lipid loci through the joint test. Eight loci (PCSK9, LPA, LPL, LIPG, ANGPTL4, APOB, APOC3, and CD300LG) remained significant after conditioning on the common index single-nucleotide polymorphism identified by previous genome-wide association studies, suggesting an independent role for rare and low-frequency variants at these loci. One significant gene-alcohol interaction on triglycerides in a novel locus was significantly discovered (P=6.65×10-6 for the interaction test) and replicated at nominal significance level (P=0.013) in SMC5. CONCLUSIONS: In conclusion, this study applied new gene-based statistical approaches and suggested that rare and low-frequency genetic variants interacted with alcohol consumption on lipid levels.

12.
Nature ; 582(7812): 365-369, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32555486

RESUMO

Optical frequency combs have a wide range of applications in science and technology1. An important development for miniature and integrated comb systems is the formation of dissipative Kerr solitons in coherently pumped high-quality-factor optical microresonators2-9. Such soliton microcombs10 have been applied to spectroscopy11-13, the search for exoplanets14,15, optical frequency synthesis16, time keeping17 and other areas10. In addition, the recent integration of microresonators with lasers has revealed the viability of fully chip-based soliton microcombs18,19. However, the operation of microcombs requires complex startup and feedback protocols that necessitate difficult-to-integrate optical and electrical components, and microcombs operating at rates that are compatible with electronic circuits-as is required in nearly all comb systems-have not yet been integrated with pump lasers because of their high power requirements. Here we experimentally demonstrate and theoretically describe a turnkey operation regime for soliton microcombs co-integrated with a pump laser. We show the appearance of an operating point at which solitons are immediately generated by turning the pump laser on, thereby eliminating the need for photonic and electronic control circuitry. These features are combined with high-quality-factor Si3N4 resonators to provide microcombs with repetition frequencies as low as 15 gigahertz that are fully integrated into an industry standard (butterfly) package, thereby offering compelling advantages for high-volume production.

13.
Nat Commun ; 11(1): 2336, 2020 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393765

RESUMO

Since its invention, optical frequency comb has revolutionized a broad range of subjects from metrology to spectroscopy. The recent development of microresonator-based frequency combs (microcombs) provides a unique pathway to create frequency comb systems on a chip. Indeed, microcomb-based spectroscopy, ranging, optical synthesizer, telecommunications and astronomical calibrations have been reported recently. Critical to many of the integrated comb systems is the broad coverage of comb spectra. Here, microcombs of more than two-octave span (450 nm to 2,008 nm) is demonstrated through χ(2) and χ(3) nonlinearities in a deformed silica microcavity. The deformation lifts the circular symmetry and creates chaotic tunneling channels that enable broadband collection of intracavity emission with a single waveguide. Our demonstration introduces a new degree of freedom, cavity deformation, to the microcomb studies, and our microcomb spectral range is useful for applications in optical clock, astronomical calibration and biological imaging.

14.
Environ Res ; 186: 109582, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32361081

RESUMO

Heavy-metal contaminated soils post great environmental and health concerns. In this study, Cr and Cd which are frequently observed in contaminated soils, were selected as representatives of hazardous heavy metals because of their different redox potentials and electric charges. Cr(VI)-, Cd(II)-, Cr(VI)/Cd(II)-contaminated soils were remediated in two-chamber air-cathode MFCs, in order to investigate the remediation of soil contaminated by single heavy metal and mixed heavy metals. Four ion exchange membranes (IEMs) were first evaluated to find out that bipolar membrane (BPM) was able to well maintain pH in both anolyte and catholyte, which was beneficial to support biological metabolism and heavy metal removal. It was also found that heavy metal ions (Cr, Cd or Cr/Cd) could migrate toward the cathode forming a concentration gradient under the weak electric field. The interaction between negatively charged Cr and positively charged Cd had no major effect to hinder each other on the migration, suggesting that the reduction reaction and electric field should be the main motivation for metal ion migration. The remediation performance of mixed heavy metal contaminated soil was superior to that of single heavy metal contaminated soil, for the possible reason of smaller internal resistance under mixed heavy metal condition.


Assuntos
Fontes de Energia Bioelétrica , Recuperação e Remediação Ambiental , Metais Pesados , Poluentes do Solo , Cádmio/análise , Cromo , Metais Pesados/análise , Solo , Poluentes do Solo/análise
15.
Nat Commun ; 11(1): 1610, 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32235844

RESUMO

Exceptional points are singularities of open systems, and among their many remarkable properties, they provide a way to enhance the responsivity of sensors. Here we show that the improved responsivity of a laser gyroscope caused by operation near an exceptional point is precisely compensated by increasing laser noise. The noise, of fundamental origin, is enhanced because the laser mode spectrum loses the oft-assumed property of orthogonality. This occurs as system eigenvectors coalesce near the exceptional point and a bi-orthogonal analysis confirms experimental observations. While the results do not preclude other possible advantages of the exceptional-point-enhanced responsivity, they do show that the fundamental sensitivity limit of the gyroscope is not improved through this form of operation. Besides being important to the physics of microcavities and non-Hermitian photonics, these results help clarify fundamental sensitivity limits in a specific class of exceptional-point sensor.

16.
Nat Commun ; 11(1): 1136, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111834

RESUMO

The coherent light source is one of the most important foundations in both optical physics studies and applied photonic devices. However, the whispering gallery microcavity, as a prime platform for novel light sources, has the intrinsically chiral symmetry and severely rules out access to directional light output, all-optical flip-flops, efficient light extraction, etc. Here, we demonstrate a reconfigurable symmetry-broken microlaser in an ultrahigh-Q whispering gallery microcavity with the symmetric structure, in which a chirality of lasing field is empowered spontaneously by the optical nonlinear effect. Experimentally, the ratio of counter-propagating lasing intensities is found to exceed 160:1, and the chirality can be controlled dynamically and all-optically by the bias in the pump direction. This work not only presents a distinct recipe for coherent light sources with robust and reconfigurable performance, but also opens up an unexplored avenue to symmetry-broken physics in optical micro-structures.

17.
Sci Rep ; 10(1): 189, 2020 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932708

RESUMO

Local ancestry, defined as the genetic ancestry at a genomic location of an admixed individual, is widely used as a genetic marker in genetic association and evolutionary genetics studies. Many methods have been developed to infer the local ancestries in a set of unrelated individuals, a few of them have been extended to small nuclear families, but none can be applied to large (e.g. three-generation) pedigrees. In this study, we developed a method, FamANC, that can improve the accuracy of local ancestry inference in large pedigrees by: (1) using an existing algorithm to infer local ancestries for all individuals in a family, assuming (contrary to fact) they are unrelated, and (2) improving its accuracy by correcting inference errors using pedigree structure. Applied on African-American pedigrees from the Cleveland Family Study, FamANC was able to correct all identified Mendelian errors and most of double crossovers.


Assuntos
Algoritmos , Grupos Étnicos/genética , Genética Populacional , Modelos Genéticos , Modelos Estatísticos , Polimorfismo de Nucleotídeo Único , Simulação por Computador , Genótipo , Haplótipos , Humanos , Linhagem
18.
Proc Natl Acad Sci U S A ; 117(5): 2560-2569, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-31964835

RESUMO

De novo mutations (DNMs), or mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease. Utilizing high-coverage whole-genome sequencing data as part of the Trans-Omics for Precision Medicine (TOPMed) Program, we called 93,325 single-nucleotide DNMs across 1,465 trios from an array of diverse human populations, and used them to directly estimate and analyze DNM counts, rates, and spectra. We find a significant positive correlation between local recombination rate and local DNM rate, and that DNM rate explains a substantial portion (8.98 to 34.92%, depending on the model) of the genome-wide variation in population-level genetic variation from 41K unrelated TOPMed samples. Genome-wide heterozygosity does correlate with DNM rate, but only explains <1% of variation. While we are underpowered to see small differences, we do not find significant differences in DNM rate between individuals of European, African, and Latino ancestry, nor across ancestrally distinct segments within admixed individuals. However, we did find significantly fewer DNMs in Amish individuals, even when compared with other Europeans, and even after accounting for parental age and sequencing center. Specifically, we found significant reductions in the number of C→A and T→C mutations in the Amish, which seem to underpin their overall reduction in DNMs. Finally, we calculated near-zero estimates of narrow sense heritability (h 2), which suggest that variation in DNM rate is significantly shaped by nonadditive genetic effects and the environment.


Assuntos
Amish/genética , Genoma Humano , Adulto , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Genética Populacional , Heterozigoto , Humanos , Masculino , Mutação , Linhagem , Sequenciamento Completo do Genoma , Adulto Jovem
19.
J Hazard Mater ; 384: 121459, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31732350

RESUMO

An ion exchange membrane (IEM) is an important component in dual-chamber microbial fuel cells (MFCs) to separate cathodic chromium from anode bacteria to avoid toxicity. Common used IEMs (e.g., BPM, CEM, PEM, AEM) have different ionic transfer abilities which could influence MFC performance and chromium removal. Additionally, to distinguish chromium "removal" or "reduction" by MFCs, the chromium removal in this study was further analyzed into cathodic reduction, adsorption on the membrane and permeation through membrane to the anode chamber. It was found that BPM achieved the best performance in removing hexavalent chromium (99.4 ± 0.2 %) and balancing pH and conductivity in both chambers, followed by AEM (97.9 ± 0.8 %) and CEM (95.6 ± 0.8 %), while PEM can not well maintain pH and conductivity leading to the worst anode performance and lowest chromium removal efficiency. However, the adsorption of chromium on the AEM accounts for 91.1 ± 0.7 %, which was much higher than the other three membranes. The permeation of chromium through the membrane were all lower than 0.2% which can be ignored. SEM and EDS results showed that chromium deposits and bacteria were detected on the membrane facing cahtode and anode, respectively, indicating that membrane scaling and fouling were inevitable and happened within 24 h operation.

20.
Sci Adv ; 5(11): eaax4249, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31763451

RESUMO

The genetic bases for most human sleep disorders and for variation in human sleep quantity and quality are largely unknown. Using the zebrafish, a diurnal vertebrate, to investigate the genetic regulation of sleep, we found that epidermal growth factor receptor (EGFR) signaling is necessary and sufficient for normal sleep levels and is required for the normal homeostatic response to sleep deprivation. We observed that EGFR signaling promotes sleep via mitogen-activated protein kinase/extracellular signal-regulated kinase and RFamide neuropeptide signaling and that it regulates RFamide neuropeptide expression and neuronal activity. Consistent with these findings, analysis of a large cohort of human genetic data from participants of European ancestry revealed that common variants in genes within the EGFR signaling pathway are associated with variation in human sleep quantity and quality. These results indicate that EGFR signaling and its downstream pathways play a central and ancient role in regulating sleep and provide new therapeutic targets for sleep disorders.


Assuntos
Receptores ErbB/genética , Regulação da Expressão Gênica , Neuropeptídeos/genética , Transdução de Sinais/genética , Sono/genética , Peixe-Zebra/genética , Animais , Animais Geneticamente Modificados , Evolução Molecular , MAP Quinases Reguladas por Sinal Extracelular/genética , Humanos , Proteínas Quinases Ativadas por Mitógeno/genética
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