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1.
Artigo em Inglês | MEDLINE | ID: mdl-38541258

RESUMO

African American women in the United States have a high risk of adverse pregnancy outcomes. DNA methylation is a potential mechanism by which exposure to BTEX (benzene, toluene, ethylbenzene, and xylenes) may cause adverse pregnancy outcomes. Data are from the Maternal Stress Study, which recruited African American women in the second trimester of pregnancy from February 2009 to June 2010. DNA methylation was measured in archived DNA from venous blood collected in the second trimester. Trimester-specific exposure to airshed BTEX was estimated using maternal self-reported addresses and geospatial models of ambient air pollution developed as part of the Geospatial Determinants of Health Outcomes Consortium. Among the 64 women with exposure and outcome data available, 46 differentially methylated regions (DMRs) were associated with BTEX exposure (FDR adjusted p-value < 0.05) using a DMR-based epigenome-wide association study approach. Overall, 89% of DMRs consistently exhibited hypomethylation with increasing BTEX exposure. Biological pathway analysis identified 11 enriched pathways, with the top 3 involving gamma-aminobutyric acid receptor signaling, oxytocin in brain signaling, and the gustation pathway. These findings highlight the potential impact of BTEX on DNA methylation in pregnant women.


Assuntos
Poluentes Atmosféricos , Benzeno , Negro ou Afro-Americano , Metilação de DNA , Feminino , Humanos , Gravidez , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Benzeno/análise , Benzeno/toxicidade , Derivados de Benzeno/análise , Derivados de Benzeno/toxicidade , Negro ou Afro-Americano/genética , Monitoramento Ambiental , Tolueno/toxicidade , Tolueno/análise , Xilenos/toxicidade , Xilenos/análise
2.
Eur J Orthop Surg Traumatol ; 34(1): 237-242, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37433971

RESUMO

PURPOSE: Pilon fractures are often complex injuries involving severe soft tissue injury. Studies have shown pilon fractures may entrap soft tissue structures between fracture fragments. Staged fixation of pilon fractures with spanning external fixation (SEF) is important for soft tissue rest and plays an important role in the management of these injuries. While SEF has been shown to promote soft tissue rest prior to definitive fixation, no studies have shown the effect SEF has on entrapped structures (ES). The purpose of this study was to evaluate how SEF effects ES in pilon fractures. METHODS: A retrospective review of 212 pilon fractures treated at our institution between 2010 and 2022 was performed. Patients with a CT scan pre-SEF and post-SEF met inclusion criteria. CTs were reviewed to characterize ES in pre- and post-SEF imaging. RESULTS: Of the 19 patients with ES identified on CT pre-SEF, seven (36.8%) had full release of ES post-SEF and 12 (63.2%) had no release of ES. The posterior tibial tendon was the most commonly ES and remained entrapped in 62.5% of cases. Only 25% of 43-C3 fractures had release of ES post-SEF, while 100% of 43-C1 and 43-C2 fractures demonstrated complete release of ES post-SEF. CONCLUSION: Entrapped structures in pilon fractures are likely to remain entrapped post-SEF, with only one-third of our cohort demonstrating release. In 43-C3 patterns, if ES are identified on CT pre-SEF, surgeons should consider addressing these either through mini open versus open approaches at the time of SEF as they are likely to remain entrapped post-SEF.


Assuntos
Fraturas do Tornozelo , Traumatismos do Tornozelo , Fraturas da Tíbia , Humanos , Fixação Interna de Fraturas , Fixação de Fratura , Fixadores Externos , Resultado do Tratamento , Traumatismos do Tornozelo/cirurgia , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/cirurgia , Fraturas do Tornozelo/diagnóstico por imagem , Fraturas do Tornozelo/cirurgia , Estudos Retrospectivos
3.
J Orthop Trauma ; 38(1): e15-e19, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37876218

RESUMO

OBJECTIVES: The objective of this study was to define the danger zone at which the anterior tibial artery (ATA) is at risk during anterolateral plating of the distal tibia using a novel 3D computed tomography angiography (CTA) modeling technique. METHODS: 116 patients (232 lower extremities) who underwent lower extremity CTAs between April 2020 and April 2022 were identified. Those with lower extremity trauma, evidence of a previously healed tibial fracture, or poor visualization of the ATA were excluded. The remaining 150 lower extremities (92 patients) were modeled with an anterolateral distal tibia plate using Sectra IDS7 software. The distance of the ATA from bony landmarks was measured perpendicular to the level at which the vessel intersected the plate. RESULTS: The ATA intersected the plate proximally at a mean distance of 10.5 cm (95% confidence intervals, 10.2-10.9) and at a mean distance of 4.6 cm (95% confidence intervals, 4.4-4.9) distally from the central tibial plafond. The ATA intersected with the plate as far distal as hole number 1 and as proximal as hole 14 of the plate. The greatest injury risk was associated with plate holes 3-8. In this region, the artery was at risk in 46-99 percent of specimens. CONCLUSIONS: The ATA is at risk when screws are placed percutaneously in an anterolateral distal tibia plate. The artery can be as close as 4.4 cm and as far as 10.9 cm proximal to the tibial plafond when crossing the plate, correlating to a risk of injury to the ATA at plate holes 1 through 14.


Assuntos
Tíbia , Fraturas da Tíbia , Humanos , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Tíbia/irrigação sanguínea , Artérias da Tíbia/diagnóstico por imagem , Artérias da Tíbia/cirurgia , Artérias da Tíbia/lesões , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/cirurgia , Fixação Interna de Fraturas/métodos , Tomografia Computadorizada por Raios X , Angiografia , Placas Ósseas
4.
Cell Rep ; 42(11): 113282, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-38007688

RESUMO

Schwann cells respond to acute axon damage by transiently transdifferentiating into specialized repair cells that restore sensorimotor function. However, the molecular systems controlling repair cell formation and function are not well defined, and consequently, it is unclear whether this form of cellular plasticity has a role in peripheral neuropathies. Here, we identify Mitf as a transcriptional sensor of axon damage under the control of Nrg-ErbB-PI3K-PI5K-mTorc2 signaling. Mitf regulates a core transcriptional program for generating functional repair Schwann cells following injury and during peripheral neuropathies caused by CMT4J and CMT4D. In the absence of Mitf, core genes for epithelial-to-mesenchymal transition, metabolism, and dedifferentiation are misexpressed, and nerve repair is disrupted. Our findings demonstrate that Schwann cells monitor axonal health using a phosphoinositide signaling system that controls Mitf nuclear localization, which is critical for activating cellular plasticity and counteracting neural disease.


Assuntos
Traumatismos dos Nervos Periféricos , Doenças do Sistema Nervoso Periférico , Humanos , Doenças do Sistema Nervoso Periférico/metabolismo , Células de Schwann/metabolismo , Axônios/metabolismo , Transdução de Sinais/fisiologia , Plasticidade Celular , Regeneração Nervosa/fisiologia , Traumatismos dos Nervos Periféricos/genética , Traumatismos dos Nervos Periféricos/metabolismo , Nervo Isquiático/metabolismo
5.
Plant Physiol ; 192(4): 2958-2970, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37128995

RESUMO

Ala is a central metabolite in leaf cells whose abundance is related to pyruvate (Pyr) metabolism and nocturnal respiration rates. Exposure of Arabidopsis (Arabidopsis thaliana) leaf disks to certain exogenous amino acids including Ala led to substantial increases in nighttime respiration rates as well as increases in alternative oxidase (AOX) 1d transcript and protein levels. During Ala treatment, AOX1d accumulation, but not AOX1a accumulation, was dependent upon the catabolism of Ala. Complete loss of AOX expression in aox1a aox1d leaf disks did not significantly affect oxygen consumption rates (OCR) under Ala treatment, indicating that AOX capacity per se was not essential for respiratory stimulation by Ala. Rather, Ala treatments caused induction of select antioxidant mechanisms in leaf disks, including a large increase of the ascorbate pool, which was substantially more oxidized in aox1a aox1d leaf disks. Furthermore, we observed differences in the accumulation of a sequence of TCA cycle intermediates from Pyr to 2-oxoglutarate (2-OG) in wild type (WT) upon Ala treatment that did not occur in aox1a aox1d leaf disks. The results indicate that AOX induction during enhanced Ala catabolism in leaves mediates mitochondrial redox status, allowing greater metabolic flexibility in mitochondrial organic acid metabolism.


Assuntos
Arabidopsis , Arabidopsis/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Oxirredutases/genética , Oxirredutases/metabolismo , Oxirredução , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo
6.
Environ Sci Pollut Res Int ; 30(21): 60768-60776, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37039917

RESUMO

Urban neighborhoods with locations of environmental contamination, known as brownfields, impact entire neighborhoods, but corrective environmental remedial action on brownfields is often tracked on an individual property basis, neglecting the larger neighborhood-level impact. This study addresses this impact by examining spatial differences between brownfields with unmitigated environmental concerns (open site) and sites that are considered fully mitigated or closed in urban neighborhoods (closed site) on the US census tract scale in Wayne County, MI. Michigan's Department of Environment, Great Lakes, and Energy's leaking underground storage tank (LUST) database provided brownfield information for Wayne County. Local indicators of spatial association (LISA) produced maps of spatial clustering and outliers. A McNemar's test demonstrated significant discordances in LISA categories between LUST open and closed sites (p < 0.001). Geographically weighted regressions (GWR) evaluated the association between open and closed site spatial density (open-closed) with socioeconomic variables (population density, proportion of White or Black residents, proportion of college educated populations, the percentage of owner-occupied units, vacant units, rented units, and median household value). Final multivariate GWR showed that population density, being Black, college education, vacant units, and renter occupied units were significantly associated (p < 0.05) with open-closed, and that those associations varied across Wayne County. Increases in Black population was associated with increased open-closed. Increases in vacant units, renter-occupied units, and college education were associated with decreased open-closed. These results provide input for environmental justice research to identify inequalities and discover the distribution of environmental hazards among urban neighborhoods.


Assuntos
Poluição Ambiental , Características de Residência , Humanos , Michigan , Análise Espacial , Características da Família , Fatores Socioeconômicos
7.
Plant Physiol ; 191(4): 2070-2083, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-36638140

RESUMO

A recent burst of technological innovation and adaptation has greatly improved our ability to capture respiration rate data from plant sources. At the tissue level, several independent respiration measurement options are now available, each with distinct advantages and suitability, including high-throughput sampling capacity. These advancements facilitate the inclusion of respiration rate data into large-scale biological studies such as genetic screens, ecological surveys, crop breeding trials, and multi-omics molecular studies. As a result, our understanding of the correlations of respiration with other biological and biochemical measurements is rapidly increasing. Difficult questions persist concerning the interpretation and utilization of respiration data; concepts such as allocation of respiration to growth versus maintenance, the unnecessary or inefficient use of carbon and energy by respiration, and predictions of future respiration rates in response to environmental change are all insufficiently grounded in empirical data. However, we emphasize that new experimental designs involving novel combinations of respiration rate data with other measurements will flesh-out our current theories of respiration. Furthermore, dynamic recordings of respiration rate, which have long been used at the scale of mitochondria, are increasingly being used at larger scales of size and time to reflect processes of cellular signal transduction and physiological response to the environment. We also highlight how respiratory methods are being better adapted to different plant tissues including roots and seeds, which have been somewhat neglected historically.


Assuntos
Melhoramento Vegetal , Plantas , Plantas/genética , Mitocôndrias/metabolismo , Sementes , Respiração , Respiração Celular
8.
Phys Sportsmed ; 51(6): 582-589, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36373404

RESUMO

OBJECTIVES: Superior labrum anterior posterior (SLAP) tears can cause shoulder pain, disability, instability, and humeral head translation. YouTube has become an increasingly popular source of medical information, but little is currently known in terms of quality control of the uploaded content. The purpose of this study was to assess the quality of YouTube videos related to the diagnosis and treatment of Superior Labrum Anterior Posterior (SLAP) tears. METHODS: YouTube was queried in August 2021 using the two predetermined keywords: 'SLAP tear' and 'superior labral tear.' The first 50 videos were analyzed by two independent reviewers and scored using 3 scoring systems: Global Quality Scale (GQS), the Journal of the American Medical Association (JAMA), and the Shoulder-Specific Score (SSS) to determine video accuracy and reliability. Title, number of views, video duration, video source, content type, views/day, number of likes, number of dislikes, days since upload, like ratio (Like × 100/ [Like + Dislike]) and Video Power Index (VPI) (Like ratio × View ratio/100) were all recorded and analyzed. RESULTS: The scores of most videos were low, with a mean JAMA score of 2.5 (1-4, SD 0.73), a mean GQS of 2.66 (0.5-4.5, SD 0.99) and a mean SSS of 7.13 (0-18, SD 4.39). There were significantly higher mean scores for JAMA, GQS, and SSS in the academic and independent physician categories, with a mean JAMA score of 3.11, GQS score of 3.39, and SSS score of 11 for academic sources and a mean JAMA score of 2.83, GQS score of 3.23, and SSS score of 9.23 for independent physician sources. JAMA score was significantly and positively correlated with video duration (r = 0.405, p = 0.006). Views, likes, dislikes, publication dates, and VPI were not significantly correlated with any scoring scale. CONCLUSION: YouTube videos on the diagnosis and management of SLAP tears have low overall quality and reliability scores. Independent physician and academic institution sources received higher mean scores for JAMA, GQS, and SSS. Video quality was not correlated with number of views.


Assuntos
Lesões do Ombro , Mídias Sociais , Estados Unidos , Humanos , Reprodutibilidade dos Testes , Emoções , Pessoal de Saúde
9.
New Phytol ; 236(3): 943-957, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35872573

RESUMO

Haberlea rhodopensis is a resurrection plant that can tolerate extreme and prolonged periods of desiccation with a rapid restoration of physiological function upon rehydration. Specialized mechanisms are required to minimize cellular damage during desiccation and to maintain integrity for rapid recovery following rehydration. In this study we used respiratory activity measurements, electron microscopy, transcript, protein and blue native-PAGE analysis to investigate mitochondrial activity and biogenesis in fresh, desiccated and rehydrated detached H. rhodopensis leaves. We demonstrate that unlike photosynthesis, mitochondrial respiration was almost immediately activated to levels of fresh tissue upon rehydration. The abundance of transcripts and proteins involved in mitochondrial respiration and biogenesis were at comparable levels in fresh, desiccated and rehydrated tissues. Blue native-PAGE analysis revealed fully assembled and equally abundant OXPHOS complexes in mitochondria isolated from fresh, desiccated and rehydrated detached leaves. We observed a high abundance of alternative respiratory components which correlates with the observed high uncoupled respiration capacity in desiccated tissue. Our study reveals that during desiccation of vascular H. rhodopensis tissue, mitochondrial composition is conserved and maintained at a functional state allowing for an almost immediate activation to full capacity upon rehydration. Mitochondria-specific mechanisms were activated during desiccation which probably play a role in maintaining tolerance.


Assuntos
Craterostigma , Proteínas de Plantas , Craterostigma/metabolismo , Dessecação , Mitocôndrias/metabolismo , Fotossíntese , Folhas de Planta/fisiologia , Proteínas de Plantas/metabolismo
10.
Arthrosc Sports Med Rehabil ; 4(3): e1111-e1118, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35747647

RESUMO

Purpose: To investigate the efficacy of YouTube videos as a patient education resource related to rehabilitation and return to play following medial patellofemoral ligament (MPFL) reconstruction. Methods: YouTube was queried using 6 predetermined search terms. Videos were included if they met the following criteria: (1) written in the English language; and (2) within the first 100 videos for each search term. Videos were excluded if they met any of the following criteria: (1) not written in the English language; (2) did not include medial patellofemoral ligament/MPFL in the title; (3) duplicate videos; (4) part of a multivideo series such a vlogs; (5) advertisements; and (6) videos <1 minute. The remaining videos were evaluated by 2 independent viewers and scored using 4 distinct scoring systems: Global Quality Scale, The Patient Education Materials Assessment Tool for Audiovisual Materials (PEMAT), MPFL Rehabilitation and Return to Play Score, and the Journal of the American Medical Association benchmark criteria. The data was analyzed with IBM SPSS Statistics, version 27). The Kruskal-Wallis test was used to compare quality scores and video analytics to their assigned categories. Results where P < .05 were considered statistically significant and pairwise comparison analysis was completed to determine the video categories with statistically significant differences. Correlation of categorical variables with video analytics (views, video power index, duration, and days since publication) and quality scores was determined using the Pearson Correlation coefficient. Results: Of the initial 600 videos, 58 met inclusion criteria, which were subsequently reviewed and scored. Most videos scored on the low-end of the possible scoring ranges with a mean Global Quality Scale score of 1.61 (standard deviation [SD] 0.81), PEMAT Understandability score of 59.40 (SD 17.54), PEMAT Actionability score of 18.20 (SD 29.92), MPFL Rehabilitation and Return to Play Score of 1.64 (SD 2.13), and Journal of the American Medical Association benchmark score of 2.08 (SD 0.75). Conclusions: The videos in YouTube's library received low scores in quality, reliability, understandability and actionability. Therefore, YouTube is currently a poor source of information for patients regarding postoperative rehabilitation and return to play following MPFL reconstruction. Clinical Relevance: Patients increasingly view medical information online. YouTube is second only to Google as the most used search engine. It is important to understand the quality of information patients receive on YouTube following MPFL reconstruction so orthopaedic surgeons know to guide patients to higher-quality alternatives.

13.
Microbiol Spectr ; 10(1): e0156421, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-35019677

RESUMO

The emergence of SARS-CoV-2 created a crucial need for serology assays to detect anti-SARS-CoV-2 antibodies, which led to many serology assays entering the market. A trans-government collaboration was created in April 2020 to independently evaluate the performance of commercial SARS-CoV-2 serology assays and help inform U.S. Food and Drug Administration (FDA) regulatory decisions. To assess assay performance, three evaluation panels with similar antibody titer distributions were assembled. Each panel consisted of 110 samples with positive (n = 30) serum samples with a wide range of anti-SARS-CoV-2 antibody titers and negative (n = 80) plasma and/or serum samples that were collected before the start of the COVID-19 pandemic. Each sample was characterized for anti-SARS-CoV-2 antibodies against the spike protein using enzyme-linked immunosorbent assays (ELISA). Samples were selected for the panel when there was agreement on seropositivity by laboratories at National Cancer Institute's Frederick National Laboratory for Cancer Research (NCI-FNLCR) and Centers for Disease Control and Prevention (CDC). The sensitivity and specificity of each assay were assessed to determine Emergency Use Authorization (EUA) suitability. As of January 8, 2021, results from 91 evaluations were made publicly available (https://open.fda.gov/apis/device/covid19serology/, and https://www.cdc.gov/coronavirus/2019-ncov/covid-data/serology-surveillance/serology-test-evaluation.html). Sensitivity ranged from 27% to 100% for IgG (n = 81), from 10% to 100% for IgM (n = 74), and from 73% to 100% for total or pan-immunoglobulins (n = 5). The combined specificity ranged from 58% to 100% (n = 91). Approximately one-third (n = 27) of the assays evaluated are now authorized by FDA for emergency use. This collaboration established a framework for assay performance evaluation that could be used for future outbreaks and could serve as a model for other technologies. IMPORTANCE The SARS-CoV-2 pandemic created a crucial need for accurate serology assays to evaluate seroprevalence and antiviral immune responses. The initial flood of serology assays entering the market with inadequate performance emphasized the need for independent evaluation of commercial SARS-CoV-2 antibody assays using performance evaluation panels to determine suitability for use under EUA. Through a government-wide collaborative network, 91 commercial SARS-CoV-2 serology assay evaluations were performed. Three evaluation panels with similar overall antibody titer distributions were assembled to evaluate performance. Nearly one-third of the assays evaluated met acceptable performance recommendations, and two assays had EUAs revoked and were removed from the U.S. market based on inadequate performance. Data for all serology assays evaluated are available at the FDA and CDC websites (https://open.fda.gov/apis/device/covid19serology/, and https://www.cdc.gov/coronavirus/2019-ncov/covid-data/serology-surveillance/serology-test-evaluation.html).


Assuntos
Anticorpos Antivirais/sangue , Teste Sorológico para COVID-19/métodos , COVID-19/sangue , Ensaio de Imunoadsorção Enzimática/métodos , SARS-CoV-2/imunologia , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/virologia , Aprovação de Teste para Diagnóstico , Humanos , Laboratórios , Pandemias , SARS-CoV-2/genética , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus/análise , Glicoproteína da Espícula de Coronavírus/imunologia , Estados Unidos/epidemiologia , United States Food and Drug Administration
14.
Methods Mol Biol ; 2363: 63-75, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34545486

RESUMO

Respiratory rate measurements are crucial assays to understand mitochondrial biochemistry as well as metabolic regulation within tissues. Several technologies currently exist that can measure plant respiratory oxygen consumption or carbon dioxide evolution rates over short durations by either isolated mitochondria or plant tissues. Here we describe recently developed alternative methods for measuring tissue oxygen consumption rates (OCRs) using systems reliant on oxygen sensitive fluorophores. The methods described have distinct experimental advantages: they can allow high-throughput and long-duration measurements; and they are particularly suited to investigating the metabolic regulation of respiration by comparing OCRs among treatments or genotypes.


Assuntos
Consumo de Oxigênio , Dióxido de Carbono/metabolismo , Corantes Fluorescentes/metabolismo , Ionóforos , Mitocôndrias/metabolismo , Oxigênio/metabolismo , Folhas de Planta
15.
Sci Total Environ ; 809: 152120, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-34871691

RESUMO

With urban air quality being a pressing public health concern, community members are becoming increasingly engaged in determining the links between air quality and human health. Although new measurement tools such as low-cost sensors make local data more accessible, a better understanding of gaps in regional datasets is needed to develop effective metropolitan-scale solutions. Using scoping review methodology, we compiled 214 published journal articles and grey literature reports of air quality data from the Detroit, Michigan area from 1952 through 2020. This critical scoping review focuses on air quality datasets, but related topics such as health studies and community-based participatory science studies were examined from the included articles. Most of these publications were peer-reviewed journal articles published after 2001. Particulate matter, nitrous oxides, and sulfur dioxide were the most commonly studied air pollutants, and asthma was the most frequently associated health outcome paired with air pollution datasets. Few publications reported methods for community-based participatory science. This critical scoping review establishes a foundation of historical air quality data for the Detroit metropolitan area and a set of evaluation criteria that can be replicated in other urban centers. This foundation enables future detailed analysis of air quality datasets and showcases strategies for implementing effective community science programs and monitoring efforts.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Monitoramento Ambiental , Humanos , Michigan , Material Particulado/análise , Dióxido de Enxofre/análise
16.
Plant Physiol ; 188(3): 1521-1536, 2022 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-34919733

RESUMO

Proline (Pro) catabolism and reactive oxygen species production have been linked in mammals and Caenorhabditis elegans, while increases in leaf respiration rate follow Pro exposure in plants. Here, we investigated how alternative oxidases (AOXs) of the mitochondrial electron transport chain accommodate the large, atypical flux resulting from Pro catabolism and limit oxidative stress during Pro breakdown in mature Arabidopsis (Arabidopsis thaliana) leaves. Following Pro treatment, AOX1a and AOX1d accumulate at transcript and protein levels, with AOX1d approaching the level of the typically dominant AOX1a isoform. We therefore sought to determine the function of both AOX isoforms under Pro respiring conditions. Oxygen consumption rate measurements in aox1a and aox1d leaves suggested these AOXs can functionally compensate for each other to establish enhanced AOX catalytic capacity in response to Pro. Generation of aox1a.aox1d lines showed complete loss of AOX proteins and activity upon Pro treatment, yet full respiratory induction in response to Pro remained possible via the cytochrome pathway. However, aox1a.aox1d leaves displayed symptoms of elevated oxidative stress and suffered increased oxidative damage during Pro metabolism compared to the wild-type (WT) or the single mutants. During recovery from salt stress, when relatively high rates of Pro catabolism occur naturally, photosynthetic rates in aox1a.aox1d recovered slower than in the WT or the single aox lines, showing that both AOX1a and AOX1d are beneficial for cellular metabolism during Pro drawdown following osmotic stress. This work provides physiological evidence of a beneficial role for AOX1a but also the less studied AOX1d isoform in allowing safe catabolism of alternative respiratory substrates like Pro.


Assuntos
Arabidopsis/genética , Arabidopsis/metabolismo , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oxirredutases/metabolismo , Prolina/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo , Estresse Salino/efeitos dos fármacos , Adaptação Fisiológica/genética , Adaptação Fisiológica/fisiologia , Complexo de Proteínas da Cadeia de Transporte de Elétrons/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Genótipo , Mitocôndrias/metabolismo , Mutação , Oxirredutases/genética , Variantes Farmacogenômicos , Estresse Salino/genética
17.
Neuron ; 109(20): 3252-3267.e6, 2021 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-34450025

RESUMO

Disruption of homeostatic microRNA (miRNA) expression levels is known to cause human neuropathology. However, the gene regulatory and phenotypic effects of altering a miRNA's in vivo abundance (rather than its binary gain or loss) are not well understood. By genetic combination, we generated an allelic series of mice expressing varying levels of miR-218, a motor neuron-selective gene regulator associated with motor neuron disease. Titration of miR-218 cellular dose unexpectedly revealed complex, non-ratiometric target mRNA dose responses and distinct gene network outputs. A non-linearly responsive regulon exhibited a steep miR-218 dose-dependent threshold in repression that, when crossed, resulted in severe motor neuron synaptic failure and death. This work demonstrates that a miRNA can govern distinct gene network outputs at different expression levels and that miRNA-dependent phenotypes emerge at particular dose ranges because of hidden regulatory inflection points of their underlying gene networks.


Assuntos
Dosagem de Genes , Redes Reguladoras de Genes/genética , MicroRNAs/genética , Doença dos Neurônios Motores/genética , Neurônios Motores/metabolismo , Animais , Camundongos , Camundongos Knockout , Análise de Sequência de RNA , Análise de Célula Única
18.
Plant Physiol ; 186(4): 2205-2221, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-33914871

RESUMO

Recent studies in Arabidopsis (Arabidopsis thaliana) have reported conflicting roles for NAC DOMAIN CONTAINING PROTEIN 17 (ANAC017), a transcription factor regulating mitochondria-to-nuclear signaling, and its closest paralog NAC DOMAIN CONTAINING PROTEIN 16 (ANAC016), in leaf senescence. By synchronizing senescence in individually darkened leaves of knockout and overexpressing mutants from these contrasting studies, we demonstrate that elevated ANAC017 expression consistently causes accelerated senescence and cell death. A time-resolved transcriptome analysis revealed that senescence-associated pathways such as autophagy are not constitutively activated in ANAC017 overexpression lines, but require a senescence-stimulus to trigger accelerated induction. ANAC017 transcript and ANAC017-target genes are constitutively upregulated in ANAC017 overexpression lines, but surprisingly show a transient "super-induction" 1 d after senescence induction. This induction of ANAC017 and its target genes is observed during the later stages of age-related and dark-induced senescence, indicating the ANAC017 pathway is also activated in natural senescence. In contrast, knockout mutants of ANAC017 showed lowered senescence-induced induction of ANAC017 target genes during the late stages of dark-induced senescence. Finally, promoter binding analyses show that the ANAC016 promoter sequence is directly bound by ANAC017, so ANAC016 likely acts downstream of ANAC017 and is directly transcriptionally controlled by ANAC017 in a feed-forward loop during late senescence.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/fisiologia , Regulação da Expressão Gênica de Plantas , Senescência Vegetal/genética , Fatores de Transcrição/genética , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Perfilação da Expressão Gênica , Fatores de Transcrição/metabolismo
19.
J Reprod Immunol ; 145: 103305, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33725526

RESUMO

Air pollution is associated with preterm birth (PTB), potentially via inflammation. We recently showed the mixture benzene, toluene, ethylbenzene, and xylene (BTEX) is associated with PTB. We examined if ambient BTEX exposure is associated with mid-pregnancy inflammation in a sample of 140 African-American women residing in Detroit, Michigan. The Geospatial Determinants of Health Outcomes Consortium study collected outdoor air pollution measurements in Detroit; these data were coupled with Michigan Air Sampling Network measurements to develop monthly BTEX concentration estimates at a spatial density of 300 m2. First trimester and mid-pregnancy BTEX exposure estimates were assigned to maternal address. Mid-pregnancy (mean 21.3 ± 3.7 weeks gestation) inflammatory biomarkers (high-sensitivity C-reactive protein, interleukin [IL]-6, IL-10, IL-1ß, and tumor necrosis factor-α) were measured with enzyme immunoassays. After covariate adjustment, for every 1-unit increase in first trimester BTEX, there was an expected mean increase in log-transformed IL-1ß of 0.05 ± 0.02 units (P = 0.014) and an expected mean increase in log-transformed tumor necrosis factor-α of 0.07 ± 0.02 units (P = 0.006). Similarly, for every 1-unit increase in mid-pregnancy BTEX, there was a mean increase in log IL-1ß of 0.06 ± 0.03 units (P = 0.027). There was no association of either first trimester or mid-pregnancy BTEX with high-sensitivity C-reactive protein, IL-10, or IL-6 (all P > 0.05). Ambient BTEX exposure is associated with inflammation in mid-pregnancy in African-American women. Future studies examining if inflammation mediates associations between BTEX exposure and PTB are needed.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Negro ou Afro-Americano/estatística & dados numéricos , Interleucina-1beta/sangue , Nascimento Prematuro/imunologia , Fator de Necrose Tumoral alfa/sangue , Adolescente , Adulto , Benzeno/efeitos adversos , Derivados de Benzeno/efeitos adversos , Biomarcadores/sangue , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Interleucina-1beta/imunologia , Exposição Materna/estatística & dados numéricos , Gravidez , Nascimento Prematuro/sangue , Tolueno/efeitos adversos , Fator de Necrose Tumoral alfa/imunologia , Xilenos/efeitos adversos , Adulto Jovem
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