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1.
iScience ; 24(10): 103151, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34646989

RESUMO

Control of mRNA stability and degradation is essential for appropriate gene expression, and its dysregulation causes various disorders, including cancer, neurodegenerative diseases, diabetes, and obesity. The 5'-3' exoribonuclease XRN1 executes the last step of RNA decay, but its physiological impact is not well understood. To address this, forebrain-specific Xrn1 conditional knockout mice (Xrn1-cKO) were generated, as Xrn1 null mice were embryonic lethal. Xrn1-cKO mice exhibited obesity with leptin resistance, hyperglycemia, hyperphagia, and decreased energy expenditure. Obesity resulted from dysregulated communication between the central nervous system and peripheral tissues. Moreover, expression of mRNAs encoding proteins that regulate appetite and energy expenditure was dysregulated in the hypothalamus of Xrn1-cKO mice. Therefore, we propose that XRN1 function in the hypothalamus is critical for maintenance of metabolic homeostasis.

2.
BMC Nephrol ; 22(1): 240, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193064

RESUMO

BACKGROUND: Hypokalemia and acute kidney injury (AKI) occur in patients administered liposomal amphotericin B (L-AMB), a wide-spectrum anti-fungicidal drug. However, the association between potassium supplementation and the occurrence of AKI in patients with hypokalemia who were administered L-AMB is not well understood. METHODS: Using nationwide claims data and laboratory data, the occurrence of AKI during L-AMB treatment was retrospectively compared between patients with hypokalemia who were or were not supplemented with potassium and between those adequately or inadequately supplemented with potassium (serum potassium levels corrected to ≥3.5 mEq/L or remained < 3.5 mEq/L, respectively) before or after L-AMB treatment initiation. RESULTS: We identified 118 patients who developed hypokalemia before L-AMB treatment initiation (43 received potassium supplementation [25 adequate and 18 inadequate supplementation] and 75 did not receive potassium supplementation), and 117 patients who developed hypokalemia after L-AMB initiation (79 received potassium supplementation [including 23 adequate and 15 inadequate supplementation] and 38 did not receive potassium supplementation). The occurrence of any stage of AKI was similar between patients with hypokalemia, regardless of potassium supplementation (i.e., before L-AMB treatment initiation [supplementation, 51%; non-supplementation, 45%; P = 0.570] or after L-AMB initiation [supplementation, 28%; non-supplementation, 32%; P = 0.671]). After adjusting for confounding factors, we found that the occurrence of any stage of AKI was not associated with potassium supplementation before L-AMB initiation (odds ratio [OR]: 1.291, 95% confidence interval [CI]: 0.584-2.852, P = 0.528) or after L-AMB initiation (OR: 0.954, 95% CI: 0.400-2.275, P = 0.915). The occurrence of any stage of AKI tended to decline in patients with hypokalemia who were adequately supplemented with potassium (44%) before, but not after, L-AMB initiation relative to that in patients inadequately supplemented with potassium (61%), however this result was not significant (P = 0.358). CONCLUSION: Potassium supplementation was not associated with any stage of AKI in patients with hypokalemia who were administered L-AMB.

3.
J Infect Chemother ; 27(10): 1471-1476, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34183236

RESUMO

INTRODUCTION: Liposomal amphotericin B (L-AMB), a broad spectrum anti-fungicidal drug, is often administered to treat invasive fungal infections (IFIs). However, the most suitable time to initiate treatment in septic shock patients with IFI is unknown. METHODS: Patients with septic shock treated with L-AMB were identified from the Japanese Diagnosis Procedure Combination national database and were stratified according to L-AMB treatment initiation either at septic shock onset (early L-AMB group) or after the onset (delayed L-AMB group) to determine their survival rates following septic shock onset and the shock cessation period. RESULTS: We identified 141 patients administered L-AMB on the day of or after septic shock onset: 60 patients received early treatment, whereas 81 patients received delayed treatment. Survival rates after septic shock onset were higher in the early L-AMB group than in the delayed L-AMB group (4 weeks: 68.4% vs 57.9%, P = 0.197; 6 weeks: 62.2% vs 44.5%, P = 0.061; 12 weeks: 43.4% vs 35.0%, P = 0.168, respectively). The septic shock cessation period was shorter in the early L-AMB group than in the delayed L-AMB group (7.0 ± 7.0 days vs 16.5 ± 15.4 days, P < 0.001), with a significant difference confirmed after adjusting for confounding factors with propensity score matching (7.1 ± 7.2 days vs 16.7 ± 14.0 days, P = 0.001). CONCLUSION: Early L-AMB administration at septic shock onset may be associated with early shock cessation.


Assuntos
Choque Séptico , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Humanos , Choque Séptico/tratamento farmacológico
4.
Sci Adv ; 7(20)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33980496

RESUMO

Small mesopelagic fishes dominate the world's total fish biomass, yet their ecological importance as prey for large marine animals is poorly understood. To reveal the little-known ecosystem dynamics, we identified prey, measured feeding events, and quantified the daily energy balance of 48 deep-diving elephant seals throughout their oceanic migrations by leveraging innovative technologies: animal-borne smart accelerometers and video cameras. Seals only attained positive energy balance after feeding 1000 to 2000 times per day on small fishes, which required continuous deep diving (80 to 100% of each day). Interspecies allometry suggests that female elephant seals have exceptional diving abilities relative to their body size, enabling them to exploit a unique foraging niche on small but abundant mesopelagic fish. This unique foraging niche requires extreme round-the-clock deep diving, limiting the behavioral plasticity of elephant seals to a changing mesopelagic ecosystem.

5.
Sci Adv ; 7(12)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33731347

RESUMO

Like landscapes of fear, animals are hypothesized to strategically use lightscapes based on intrinsic motivations. However, longitudinal evidence of state-dependent risk aversion has been difficult to obtain in wild animals. Using high-resolution biologgers, we continuously measured body condition, time partitioning, three-dimensional movement, and risk exposure of 71 elephant seals throughout their 7-month foraging migrations (N = 16,000 seal days). As body condition improved from 21 to 32% fat and daylength declined from 16 to 10 hours, seals rested progressively earlier with respect to sunrise, sacrificing valuable nocturnal foraging hours to rest in the safety of darkness. Seals in superior body condition prioritized safety over energy conservation by resting >100 meters deeper where it was 300× darker. Together, these results provide empirical evidence that marine mammals actively use the three-dimensional lightscape to optimize risk-reward trade-offs based on ecological and physiological factors.

6.
Proc Biol Sci ; 288(1947): 20202817, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33726591

RESUMO

Seasonal resource pulses can have enormous impacts on species interactions. In marine ecosystems, air-breathing predators often drive their prey to deeper waters. However, it is unclear how ephemeral resource pulses such as near-surface phytoplankton blooms alter the vertical trade-off between predation avoidance and resource availability in consumers, and how these changes cascade to the diving behaviour of top predators. We integrated data on Weddell seal diving behaviour, diet stable isotopes, feeding success and mass gain to examine shifts in vertical foraging throughout ice break-out and the resulting phytoplankton bloom each year. We also tested hypotheses about the likely location of phytoplankton bloom origination (advected or produced in situ where seals foraged) based on sea ice break-out phenology and advection rates from several locations within 150 km of the seal colony. In early summer, seals foraged at deeper depths resulting in lower feeding rates and mass gain. As sea ice extent decreased throughout the summer, seals foraged at shallower depths and benefited from more efficient energy intake. Changes in diving depth were not due to seasonal shifts in seal diets or horizontal space use and instead may reflect a change in the vertical distribution of prey. Correspondence between the timing of seal shallowing and the resource pulse was variable from year to year and could not be readily explained by our existing understanding of the ocean and ice dynamics. Phytoplankton advection occurred faster than ice break-out, and seal dive shallowing occurred substantially earlier than local break-out. While there remains much to be learned about the marine ecosystem, it appears that an increase in prey abundance and accessibility via shallower distributions during the resource pulse could synchronize life-history phenology across trophic levels in this high-latitude ecosystem.


Assuntos
Ecossistema , Focas Verdadeiras , Animais , Comportamento Alimentar , Oceanos e Mares , Comportamento Predatório , Estações do Ano
8.
Clin Exp Nephrol ; 25(3): 279-287, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33179180

RESUMO

BACKGROUND: Liposomal amphotericin B (L-AMB), a broad-spectrum antifungicidal drug, is often used to treat fungal infections. However, clinical evidence of its use in patients with renal dysfunction, especially those receiving renal replacement therapy (RRT), is limited. Therefore, we evaluated the usage and occurrence of adverse reactions during L-AMB therapy in patients undergoing RRT. METHODS: Using claims data and laboratory data, we retrospectively evaluated patients who were administered L-AMB. The presence of comorbidities, mortality rate, treatment with L-AMB and other anti-infective agents, and the incidence of adverse reactions were compared between patients receiving RRT, including continuous renal replacement therapy (CRRT) and maintenance hemodialysis (HD), and those that did not receive RRT. RESULTS: In total, 900 cases met the eligibility criteria: 24, 19, and 842 cases in the maintenance HD, CRRT, and non-RRT groups, respectively. Of the patients administered L-AMB, mortality at discharge was higher for those undergoing either CRRT (15/19; 79%) or maintenance HD (16/24; 67%) than for those not receiving RRT (353/842; 42%). After propensity score matching, the average daily and cumulative dose, treatment duration, and dosing interval for L-AMB were not significantly different between patients receiving and not receiving RRT. L-AMB was used as the first-line antifungal agent for patients undergoing CRRT in most cases (12/19; 63%). Although the number of subjects was limited, the incidence of adverse events did not markedly differ among the groups. CONCLUSION: L-AMB may be used for patients undergoing maintenance HD or CRRT without any dosing, duration, or interval adjustments.

9.
Sci Total Environ ; 750: 142201, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33182207

RESUMO

Mercury (Hg) is a natural trace element found in high concentrations in top predators, including Arctic seabirds. Most current knowledge about Hg concentrations in Arctic seabirds relates to exposure during the summer breeding period when researchers can easily access seabirds at colonies. However, the few studies focused on winter have shown higher Hg concentrations during the non-breeding period than breeding period in several tissues. Hence, improving knowledge about Hg exposure during the non-breeding period is crucial to understanding the threats and risks encountered by these species year-round. We used feathers of nine migratory alcid species occurring at high latitudes to study bird Hg exposure during both the breeding and non-breeding periods. Overall, Hg concentrations during the non-breeding period were ~3 times higher than during the breeding period. In addition, spatial differences were apparent within and between the Atlantic and Pacific regions. While Hg concentrations during the non-breeding period were ~9 times and ~3 times higher than during the breeding period for the West and East Atlantic respectively, Hg concentrations in the Pacific during the non-breeding period were only ~1.7 times higher than during the breeding period. In addition, individual Hg concentrations during the non-breeding period for most of the seabird colonies were above 5 µg g-1 dry weight (dw), which is considered to be the threshold at which deleterious effects are observed, suggesting that some breeding populations might be vulnerable to non-breeding Hg exposure. Since wintering area locations, and migration routes may influence seasonal Hg concentrations, it is crucial to improve our knowledge about spatial ecotoxicology to fully understand the risks associated with Hg contamination in Arctic seabirds.


Assuntos
Mercúrio , Animais , Regiões Árticas , Aves , Monitoramento Ambiental , Plumas/química , Mercúrio/análise , Estações do Ano
10.
Nat Commun ; 11(1): 6169, 2020 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-33268794

RESUMO

A repertoire of T cells with diverse antigen receptors is selected in the thymus. However, detailed mechanisms underlying this thymic positive selection are not clear. Here we show that the CCR4-NOT complex limits expression of specific genes through deadenylation of mRNA poly(A) tails, enabling positive selection. Specifically, the CCR4-NOT complex is up-regulated in thymocytes before initiation of positive selection, where in turn, it inhibits up-regulation of pro-apoptotic Bbc3 and Dab2ip. Elimination of the CCR4-NOT complex permits up-regulation of Bbc3 during a later stage of positive selection, inducing thymocyte apoptosis. In addition, CCR4-NOT elimination up-regulates Dab2ip at an early stage of positive selection. Thus, CCR4-NOT might control thymocyte survival during two-distinct stages of positive selection by suppressing expression levels of pro-apoptotic molecules. Taken together, we propose a link between CCR4-NOT-mediated mRNA decay and T cell selection in the thymus.


Assuntos
Apoptose/genética , Exorribonucleases/genética , Proteínas Repressoras/genética , Timócitos/imunologia , Timo/imunologia , Animais , Apoptose/imunologia , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/imunologia , Diferenciação Celular , Linhagem da Célula/genética , Linhagem da Célula/imunologia , Exorribonucleases/imunologia , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Poli A/genética , Poli A/imunologia , Estabilidade de RNA , RNA Mensageiro/genética , RNA Mensageiro/imunologia , Proteínas Repressoras/imunologia , Transdução de Sinais , Timócitos/citologia , Timo/citologia , Timo/crescimento & desenvolvimento , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/imunologia , Proteínas Ativadoras de ras GTPase/genética , Proteínas Ativadoras de ras GTPase/imunologia
11.
Sci Adv ; 6(26): eaba4828, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32637612

RESUMO

Population trends and breeding success variability of Adélie penguins, a bioindicator of Antarctic environments, have been attributed to changing sea-ice extents; however, causative mechanisms remain unclear. By electronically tagging 175 penguins in four seasons with contrasting sea-ice conditions, we show that ice-free environments enhance, not deteriorate, foraging efficiencies and breeding success. In an ice-free season, penguins traveled by swimming rather than walking, leading to larger foraging areas, shorter trip durations, and lower energy expenditure than three ice-covered seasons. Freed from the need to find cracks for breathing, dive durations decreased, and more krill were captured per unit dive time, which may also be associated with phytoplankton blooms and increased krill density in the sunlit ice-free water. Consequently, adult body mass, chick growth rates, and breeding success increased. Our findings explain the regional population trends and demonstrate a key link among sea ice, foraging behavior, and reproductive success in this iconic species.

12.
Life Sci Alliance ; 3(5)2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32238456

RESUMO

The biological significance of deadenylation in global gene expression is not fully understood. Here, we show that the CCR4-NOT deadenylase complex maintains expression of mRNAs, such as those encoding transcription factors, cell cycle regulators, DNA damage response-related proteins, and metabolic enzymes, at appropriate levels in the liver. Liver-specific disruption of Cnot1, encoding a scaffold subunit of the CCR4-NOT complex, leads to increased levels of mRNAs for transcription factors, cell cycle regulators, and DNA damage response-related proteins because of reduced deadenylation and stabilization of these mRNAs. CNOT1 suppression also results in an increase of immature, unspliced mRNAs (pre-mRNAs) for apoptosis-related and inflammation-related genes and promotes RNA polymerase II loading on their promoter regions. In contrast, mRNAs encoding metabolic enzymes become less abundant, concomitant with decreased levels of these pre-mRNAs. Lethal hepatitis develops concomitantly with abnormal mRNA expression. Mechanistically, the CCR4-NOT complex targets and destabilizes mRNAs mainly through its association with Argonaute 2 (AGO2) and butyrate response factor 1 (BRF1) in the liver. Therefore, the CCR4-NOT complex contributes to liver homeostasis by modulating the liver transcriptome through mRNA deadenylation.


Assuntos
Proteínas de Homeodomínio/metabolismo , Fígado/metabolismo , Receptores CCR4/metabolismo , Animais , Citoplasma/metabolismo , Feminino , Proteínas de Homeodomínio/genética , Homeostase , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Poli A/genética , Estabilidade de RNA , RNA Mensageiro/genética , Receptores CCR4/genética , Ribonucleases/genética , Fatores Associados à Proteína de Ligação a TATA/metabolismo , Fatores de Transcrição/genética
13.
Biochimie ; 174: 49-56, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32311426

RESUMO

Eukaryotic gene expression can be spatiotemporally tuned at the post-transcriptional level by cis-regulatory elements in mRNA sequences. An important example is the AU-rich element (ARE), which induces mRNA destabilization in a variety of biological contexts in mammals and can also mediate translational control. Regulation is mediated by trans-acting factors that recognize the ARE, such as Tristetraprolin (TTP) and BRF1/ZFP36L1. Although both proteins can destabilize their target mRNAs through the recruitment of the CCR4-NOT deadenylation complex, TTP also directly regulates translation. Whether ZFP36L1 can directly repress translation remains unknown. Here, we used an in vitro translation system derived from mammalian cell lines to address this key mechanistic issue in ARE regulation by ZFP36L1. Functional assays with mutant proteins reveal that ZFP36L1 can repress translation via AU-Rich elements independent of deadenylation. ZFP36L1-mediated translation repression requires interaction between ZFP36L1 and CNOT1, suggesting that it might use a repression mechanism similar to either TPP or miRISC. However, several lines of evidence suggest that the similarity ends there. Unlike, TTP, it does not efficiently interact with either 4E-HP or GIGYF2, suggesting it does not repress translation by recruiting these proteins to the mRNA cap. Moreover, ZFP36L1 could not repress ECMV-IRES driven translation and was resistant to pharmacological eIF4A inhibitor silvestrol, suggesting fundamental differences with miRISC repression via eIF4A. Collectively, our results reveal that ZFP36L1 represses translation directly and suggest that it does so via a novel mechanism distinct from other translational regulators that interact with the CCR4-NOT deadenylase complex.


Assuntos
Fator 1 de Resposta a Butirato/metabolismo , Regulação da Expressão Gênica , Biossíntese de Proteínas , Fatores de Transcrição/metabolismo , Elementos Ricos em Adenilato e Uridilato , Células HEK293 , Humanos , Ligação Proteica
14.
J Biol Chem ; 295(17): 5588-5601, 2020 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-32144202

RESUMO

Accumulating evidence suggests that brown adipose tissue (BAT) is a potential therapeutic target for managing obesity and related diseases. PGAM family member 5, mitochondrial serine/threonine protein phosphatase (PGAM5), is a protein phosphatase that resides in the mitochondria and regulates many biological processes, including cell death, mitophagy, and immune responses. Because BAT is a mitochondria-rich tissue, we have hypothesized that PGAM5 has a physiological function in BAT. We previously reported that PGAM5-knockout (KO) mice are resistant to severe metabolic stress. Importantly, lipid accumulation is suppressed in PGAM5-KO BAT, even under unstressed conditions, raising the possibility that PGAM5 deficiency stimulates lipid consumption. However, the mechanism underlying this observation is undetermined. Here, using an array of biochemical approaches, including quantitative RT-PCR, immunoblotting, and oxygen consumption assays, we show that PGAM5 negatively regulates energy expenditure in brown adipocytes. We found that PGAM5-KO brown adipocytes have an enhanced oxygen consumption rate and increased expression of uncoupling protein 1 (UCP1), a protein that increases energy consumption in the mitochondria. Mechanistically, we found that PGAM5 phosphatase activity and intramembrane cleavage are required for suppression of UCP1 activity. Furthermore, utilizing a genome-wide siRNA screen in HeLa cells to search for regulators of PGAM5 cleavage, we identified a set of candidate genes, including phosphatidylserine decarboxylase (PISD), which catalyzes the formation of phosphatidylethanolamine at the mitochondrial membrane. Taken together, these results indicate that PGAM5 suppresses mitochondrial energy expenditure by down-regulating UCP1 expression in brown adipocytes and that its phosphatase activity and intramembrane cleavage are required for UCP1 suppression.


Assuntos
Adipócitos Marrons/metabolismo , Regulação para Baixo , Metabolismo Energético , Proteínas Mitocondriais/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Proteína Desacopladora 1/genética , Animais , Células Cultivadas , Células HeLa , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Mitocondriais/genética , Consumo de Oxigênio , Fosfoproteínas Fosfatases/genética , Proteína Desacopladora 1/metabolismo
15.
J Exp Biol ; 223(Pt 5)2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32041802

RESUMO

Knowledge of the diet of marine mammals is fundamental to understanding their role in marine ecosystems and response to environmental change. Recently, animal-borne video cameras have revealed the diet of marine mammals that make short foraging trips. However, novel approaches that allocate video time to target prey capture events is required to obtain diet information for species that make long foraging trips over great distances. We combined satellite telemetry and depth recorders with newly developed date-/time-, depth- and acceleration-triggered animal-borne video cameras to examine the diet of female northern elephant seals during their foraging migrations across the eastern North Pacific. We obtained 48.2 h of underwater video, from cameras mounted on the head (n=12) and jaw (n=3) of seals. Fish dominated the diet (78% of 697 prey items recorded) across all foraging locations (range: 37-55°N, 122-152°W), diving depths (range: 238-1167 m) and water temperatures (range: 3.2-7.4°C), while squid comprised only 7% of the diet. Identified prey included fish such as myctophids, Merluccius sp. and Icosteus aenigmaticus, and squid such as Histioteuthis sp., Octopoteuthis sp. and Taningia danae Our results corroborate fatty acid analysis, which also found that fish are more important in the diet, and are in contrast to stomach content analyses that found cephalopods to be the most important component of the diet. Our work shows that in situ video observation is a useful method for studying the at-sea diet of long-ranging marine predators.


Assuntos
Dieta/veterinária , Comportamento Alimentar , Focas Verdadeiras/fisiologia , Gravação em Vídeo , Aceleração , Animais , Feminino
16.
RNA Biol ; 17(3): 403-416, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31924127

RESUMO

Shortening of mRNA poly(A) tails (deadenylation) to trigger their decay is mediated mainly by the CCR4-NOT deadenylase complex. While four catalytic subunits (CNOT6, 6L 7, and 8) have been identified in the mammalian CCR4-NOT complex, their individual biological roles are not fully understood. In this study, we addressed the contribution of CNOT7/8 to viability of primary mouse embryonic fibroblasts (MEFs). We found that MEFs lacking CNOT7/8 expression [Cnot7/8-double knockout (dKO) MEFs] undergo cell death, whereas MEFs lacking CNOT6/6L expression (Cnot6/6l-dKO MEFs) remain viable. Co-immunoprecipitation analyses showed that CNOT6/6L are also absent from the CCR4-NOT complex in Cnot7/8-dKO MEFs. In contrast, either CNOT7 or CNOT8 still interacts with other subunits in the CCR4-NOT complex in Cnot6/6l-dKO MEFs. Exogenous expression of a CNOT7 mutant lacking catalytic activity in Cnot7/8-dKO MEFs cannot recover cell viability, even though CNOT6/6L exists to some extent in the CCR4-NOT complex, confirming that CNOT7/8 is essential for viability. Bulk poly(A) tail analysis revealed that mRNAs with longer poly(A) tails are more numerous in Cnot7/8-dKO MEFs than in Cnot6/6l-dKO MEFs. Consistent with elongated poly(A) tails, more mRNAs are upregulated and stabilized in Cnot7/8-dKO MEFs than in Cnot6/6l-dKO MEFs. Importantly, Cnot6/6l-dKO mice are viable and grow normally to adulthood. Taken together, the CNOT7/8 catalytic subunits are essential for deadenylation, which is necessary to maintain cell viability, whereas CNOT6/6L are not.


Assuntos
Exorribonucleases/metabolismo , RNA Mensageiro/metabolismo , Receptores CCR4/metabolismo , Proteínas Repressoras/metabolismo , Animais , Sobrevivência Celular/genética , Exorribonucleases/genética , Feminino , Fibroblastos/citologia , Fibroblastos/fisiologia , Masculino , Camundongos Knockout , Complexos Multiproteicos/genética , Complexos Multiproteicos/metabolismo , Poli A/genética , Poli A/metabolismo , Subunidades Proteicas , Estabilidade de RNA , RNA Mensageiro/genética , Receptores CCR4/genética , Proteínas Repressoras/genética
17.
Artigo em Inglês | MEDLINE | ID: mdl-33716412

RESUMO

Die-offs of seabirds in Alaska have occurred with increased frequency since 2015. In 2018, on St. Lawrence Island, seabirds were reported washing up dead on beaches starting in late May, peaking in June, and continuing until early August. The cause of death was documented to be starvation, leading to the conclusion that a severe food shortage was to blame. We use physiology and colony-based observations to examine whether food shortage is a sufficient explanation for the die-off, or if evidence indicates an alternative cause of starvation such as disease. Specifically, we address what species were most affected, the timing of possible food shortages, and food shortage severity in a historical context. We found that thick-billed murres (Uria lomvia) were most affected by the die-off, making up 61% of all bird carcasses encountered during beach surveys. Thick-billed murre carcasses were proportionately more numerous (26:1) than would be expected based on ratios of thick-billed murres to co-occurring common murres (U. aalge) observed on breeding study plots (7:1). Concentrations of the stress hormone corticosterone, a reliable physiological indicator of nutritional stress, in thick-billed murre feathers grown in the fall indicate that foraging conditions in the northern Bering Sea were poor in the fall of 2017 and comparable in severity to those experienced by murres during the 1976-1977 Bering Sea regime shift. Concentrations of corticosterone in feathers grown during the pre-breeding molt indicate that foraging conditions in late winter 2018 were similar to previous years. The 2018 murre egg harvest in the village of Savoonga (on St. Lawrence Is.) was one-fifth the 1993-2012 average, and residents observed that fewer birds laid eggs in 2018. Exposure of thick-billed murres to nutritional stress in August, however, was no different in 2018 compared to 2016, 2017, and 2019, and was comparable to levels observed on St. George Island in 2003-2017. Prey abundance, measured by the National Oceanic and Atmospheric Administration in bottom-trawl surveys, was also similar in 2018 to 2017 and 2019, supporting the evidence that food was not scarce in the summer of 2018 in the vicinity of St. Lawrence Island. Of two moribund thick-billed murres collected at the end of the mortality event, one tested positive for a novel re-assortment H10 strain of avian influenza with Eurasian components, likely contracted during the non-breeding season. It is not currently known how widely spread infection of murres with the novel virus was, thus insufficient evidence exists to attribute the die-off to an outbreak of avian influenza. We conclude that food shortage alone is not an adequate explanation for the mortality of thick-billed murres in 2018, and highlight the importance of rapid response to mortality events in order to document alternative or confounding causes of mortality.

18.
Environ Sci Technol ; 53(22): 13398-13407, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31693348

RESUMO

Marine methylmercury concentrations vary geographically and with depth, exposing organisms to different mercury levels in different habitats. Red-legged kittiwakes (Rissa brevirostris), a specialist predator, forage on fish and invertebrates from the mesopelagic zone, a part of the ocean with elevated methylmercury concentrations. We used kittiwakes as bioindicators of MeHg concentrations in remote mesopelagic systems by examining how wintering distribution and habitat affected kittiwakes' mercury exposure. In 2011-2017, we sampled winter-grown feathers on St. George Island, Alaska, from birds equipped with geolocation loggers. We measured total mercury (THg) and nitrogen stable isotopes in nape and head feathers grown during winter, respectively. THg concentration of kittiwake nape feathers averaged 4.61 ± 0.97 µg/g dry weight. Hierarchical cluster analysis was used to classify winter habitats with remotely sensed environmental variables along each bird's track. Five habitat clusters were identified. Birds that spent more time in the Western Subarctic Gyre and those that wintered further south had elevated THg concentrations. In contrast to THg, trophic level varied annually but did not show strong spatial patterns. Our results documented spatial variability in THg exposure based on the oceanic wintering locations of red-legged kittiwakes and highlight their use as a bioindicator of MeHg across ocean basins.


Assuntos
Mercúrio , Compostos de Metilmercúrio , Poluentes Químicos da Água , Alaska , Animais , Monitoramento Ambiental , Ilhas , Oceanos e Mares
19.
Int J Mol Sci ; 20(21)2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31652943

RESUMO

Shortening of poly(A) tails triggers mRNA degradation; hence, mRNA deadenylation regulates many biological events. In the present study, we generated mice lacking the Cnot1 gene, which encodes an essential scaffold subunit of the CCR4-NOT deadenylase complex in adipose tissues (Cnot1-AKO mice) and we examined the role of CCR4-NOT in adipocyte function. Cnot1-AKO mice showed reduced masses of white adipose tissue (WAT) and brown adipose tissue (BAT), indicating abnormal organization and function of those tissues. Indeed, Cnot1-AKO mice showed hyperinsulinemia, hyperglycemia, insulin resistance, and glucose intolerance and they could not maintain a normal body temperature during cold exposure. Muscle-like fibrous material appeared in both WAT and BAT of Cnot1-AKO mice, suggesting the acquisition of non-adipose tissue characteristics. Gene expression analysis using RNA-sequencing (RNA-seq) showed that the levels of adipose tissue-related mRNAs, including those of metabolic genes, decreased, whereas the levels of inflammatory response-related mRNAs increased. These data suggest that the CCR4-NOT complex ensures proper adipose tissue function by maintaining adipocyte-specific mRNAs at appropriate levels and by simultaneously suppressing mRNAs that would impair adipocyte function if overexpressed.


Assuntos
Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/metabolismo , Fatores de Transcrição/genética , Adipócitos/citologia , Adipócitos/metabolismo , Tecido Adiposo Marrom/patologia , Tecido Adiposo Branco/patologia , Animais , Temperatura Corporal , Células Cultivadas , Regulação da Expressão Gênica , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Hiperinsulinismo/etiologia , Hiperinsulinismo/metabolismo , Metabolismo dos Lipídeos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , RNA Mensageiro/metabolismo , Fatores de Transcrição/deficiência
20.
Front Neurosci ; 13: 626, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31316332

RESUMO

Animal behavior is the final and integrated output of brain activity. Thus, recording and analyzing behavior is critical to understand the underlying brain function. While recording animal behavior has become easier than ever with the development of compact and inexpensive devices, detailed behavioral data analysis requires sufficient prior knowledge and/or high content data such as video images of animal postures, which makes it difficult for most of the animal behavioral data to be efficiently analyzed. Here, we report a versatile method using a hybrid supervised/unsupervised machine learning approach for behavioral state estimation and feature extraction (STEFTR) only from low-content animal trajectory data. To demonstrate the effectiveness of the proposed method, we analyzed trajectory data of worms, fruit flies, rats, and bats in the laboratories, and penguins and flying seabirds in the wild, which were recorded with various methods and span a wide range of spatiotemporal scales-from mm to 1,000 km in space and from sub-seconds to days in time. We successfully estimated several states during behavior and comprehensively extracted characteristic features from a behavioral state and/or a specific experimental condition. Physiological and genetic experiments in worms revealed that the extracted behavioral features reflected specific neural or gene activities. Thus, our method provides a versatile and unbiased way to extract behavioral features from simple trajectory data to understand brain function.

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