RESUMO
Global food demand is rising, and serious questions remain about whether supply can increase sustainably1. Land-based expansion is possible but may exacerbate climate change and biodiversity loss, and compromise the delivery of other ecosystem services2-6. As food from the sea represents only 17% of the current production of edible meat, we ask how much food we can expect the ocean to sustainably produce by 2050. Here we examine the main food-producing sectors in the ocean-wild fisheries, finfish mariculture and bivalve mariculture-to estimate 'sustainable supply curves' that account for ecological, economic, regulatory and technological constraints. We overlay these supply curves with demand scenarios to estimate future seafood production. We find that under our estimated demand shifts and supply scenarios (which account for policy reform and technology improvements), edible food from the sea could increase by 21-44 million tonnes by 2050, a 36-74% increase compared to current yields. This represents 12-25% of the estimated increase in all meat needed to feed 9.8 billion people by 2050. Increases in all three sectors are likely, but are most pronounced for mariculture. Whether these production potentials are realized sustainably will depend on factors such as policy reforms, technological innovation and the extent of future shifts in demand.
Assuntos
Pesqueiros/provisão & distribuição , Abastecimento de Alimentos/estatística & dados numéricos , Oceanos e Mares , Alimentos Marinhos/provisão & distribuição , Desenvolvimento Sustentável/tendências , Animais , Organismos Aquáticos/crescimento & desenvolvimento , Pesqueiros/economia , Peixes/crescimento & desenvolvimento , Abastecimento de Alimentos/economia , Humanos , Moluscos/crescimento & desenvolvimento , Alimentos Marinhos/economia , Desenvolvimento Sustentável/economia , Fatores de TempoRESUMO
Partial replacement of mineral fertilisers (MF) with animal manures is a good alternative to reduce MF use and increase both nutrient cycling in agriculture and soil organic matter. However, the adoption of this practice must not lead to increased environmental impacts. In this two-year study conducted in an apple orchard, MF were partially replaced with various animal manures, including cattle slurry (CS), acidified cattle slurry (ACS), solid cattle manure (CsM), or poultry manure (PM), and their impacts on greenhouse gas emission (GHG: CO2, N2O and CH4) were examined. A control (CTRL) receiving only MF served as the baseline, representing the conventional scenario in orchard fertilisation. Overall, replacing MF with manures increased GHG emissions, with the magnitude of the impacts depending on the specific characteristics of the manures and the amount of nutrients and organic matter applied. Comparing to the CTRL, application of ACS and CS led to higher CH4 and N2O emissions, while PM application increased both N2O and CO2 emissions. In contrast, replacement with PM and CsM decreased CH4 emissions. Nevertheless, results varied between the two years, influenced by several factors, including soil conditions. While acidification showed potential to mitigate CH4 emissions, it also led to increased N2O emissions compared to CS, particularly in 2022, suggesting the need for further investigation to avoid emission trade-offs. Replacement with CS (20.49 t CO2-eq ha-1) and CsM (20.30 t CO2-eq ha-1) showed comparable global warming potential (GWP) to the conventional scenario (CTRL, 19.49 t CO2-eq ha-1), highlighting their potential as viable MF substitutes.
Assuntos
Malus , Esterco , Animais , Bovinos , Fertilizantes , Dióxido de Carbono/análise , Óxido Nitroso/análise , Solo , Agricultura , Minerais , Aves Domésticas , MetanoRESUMO
Aortic coarctation (AoCo) leads to long-term sequelae that may impair heart function. Data regarding new echocardiographic function parameters such as atrial strain, in affected patients, are scarce. This study aims to describe these parameters in AoCo patients and define their association with severity measures. 53 AoCo patients and 31 healthy controls, aged 12-40 years, were evaluated. Effectively corrected AoCo (cAoCo) was defined as aortic trans-isthmic corrected Doppler gradient (Dgrad) ≤ 20 mmHg (n = 36), and recoarctation (rAoCo) as Dgrad > 20 mmHg (n = 17). Dependent variables were: E/E'; atrial reservoir strain (Ares); and atrial conduit strain (Acd). T-tests/Mann-Whitney U tests were used to compare these among groups. Multivariable regression was used to test correlation with systolic blood pressure (SBP), indexed LV mass (ILVM), Dgrad, and the ratio between the narrowest diameter of aortic arch and aorta at diaphragm level (Aoratio). In cAoCo and rAoCo patients, E/E' was higher (p < 0.001), Ares, and Acd were lower (p < 0.001 for both) comparing with controls. Acd was higher in cAoCo than rAoCo (p = 0.045). Higher Ares was associated with higher Aoratio (p = 0.002), and lower Acd with higher Dgrad (0.014). EF and GLS were not different among groups. Young patients with effectively corrected aortic coarctation have persistent changes in diastolic function parameters (E/E' and atrial strain), and these are affected by anatomical sequelae. These patients' physiology is closer to patients with recoarctation, than to healthy individuals. This provides rationale for a stronger prevention, and treatment, of arterial dysfunction and high left ventricular afterload in these patients.
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Coartação Aórtica , Fibrilação Atrial , Disfunção Ventricular Esquerda , Humanos , Fibrilação Atrial/complicações , Aorta , Átrios do Coração , Aorta Torácica , Função Ventricular Esquerda/fisiologiaRESUMO
The Flaviviridae are a family of viruses that cause severe human diseases. For example, dengue virus (DENV) is a rapidly emerging pathogen causing an estimated 100 million symptomatic infections annually worldwide. No approved antivirals are available to date and clinical trials with a tetravalent dengue vaccine showed disappointingly low protection rates. Hepatitis C virus (HCV) also remains a major medical problem, with 160 million chronically infected patients worldwide and only expensive treatments available. Despite distinct differences in their pathogenesis and modes of transmission, the two viruses share common replication strategies. A detailed understanding of the host functions that determine viral infection is lacking. Here we use a pooled CRISPR genetic screening strategy to comprehensively dissect host factors required for these two highly important Flaviviridae members. For DENV, we identified endoplasmic-reticulum (ER)-associated multi-protein complexes involved in signal sequence recognition, N-linked glycosylation and ER-associated degradation. DENV replication was nearly completely abrogated in cells deficient in the oligosaccharyltransferase (OST) complex. Mechanistic studies pinpointed viral RNA replication and not entry or translation as the crucial step requiring the OST complex. Moreover, we show that viral non-structural proteins bind to the OST complex. The identified ER-associated protein complexes were also important for infection by other mosquito-borne flaviviruses including Zika virus, an emerging pathogen causing severe birth defects. By contrast, the most significant genes identified in the HCV screen were distinct and included viral receptors, RNA-binding proteins and enzymes involved in metabolism. We found an unexpected link between intracellular flavin adenine dinucleotide (FAD) levels and HCV replication. This study shows notable divergence in host-depenency factors between DENV and HCV, and illuminates new host targets for antiviral therapy.
Assuntos
Sistemas CRISPR-Cas/genética , Vírus da Dengue/fisiologia , Genoma Humano/genética , Hepacivirus/fisiologia , Fatores Celulares Derivados do Hospedeiro/genética , Interações Hospedeiro-Patógeno/genética , Vírus da Dengue/genética , Vírus da Dengue/crescimento & desenvolvimento , Descoberta de Drogas , Retículo Endoplasmático/metabolismo , Degradação Associada com o Retículo Endoplasmático , Flavina-Adenina Dinucleotídeo/biossíntese , Flavina-Adenina Dinucleotídeo/metabolismo , Infecções por Flavivirus/genética , Infecções por Flavivirus/virologia , Glicosilação , Hexosiltransferases/deficiência , Hexosiltransferases/genética , Hexosiltransferases/metabolismo , Humanos , Proteínas de Membrana/deficiência , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Terapia de Alvo Molecular , Ligação Proteica , Sinais Direcionadores de Proteínas , Proteínas de Ligação a RNA/genética , Receptores Virais/genética , Proteínas não Estruturais Virais/metabolismo , Replicação Viral , Zika virus/metabolismoRESUMO
INTRODUCTION: Pericardial effusions are rare yet potentially fatal conditions in children. Azacitidine is a DNA-hypomethylating agent used in the treatment of myelodysplastic syndrome. Although seldomly described in adults, no cases of azacitidine-induced pericardial effusion have been reported in children. CASE REPORT: A 7-year-old boy with myelodysplastic syndrome presented with a large pericardial effusion with risk for cardiac tamponade after his first azacitidine cycle. MANAGEMENT & OUTCOME: The patient was admitted to a pediatric ICU, antibiotic and steroid therapy were initiated. Pericardiocentesis was done due to hemodynamic instability. Serum and pericardial fluid complementary evaluation excluded infectious and malignant causes. The pericardial effusion did not reappear and additional pleural and ascitic slight effusions responded well to diuretics. Follow-up azacitidine cycles were administered by tapering daily dosages and using adjunctive steroid therapy, with no additional adverse events. DISCUSSION: We report the first pediatric case of large pericardial effusion secondary to azacitidine therapy in a child with MDS. This adverse reaction has not been described in pediatric patients, in which this therapeutic option has been increasingly used. We seek to raise awareness on the potential life-threatening cardiotoxicity of azacitidine in pediatric patients.
Assuntos
Tamponamento Cardíaco , Síndromes Mielodisplásicas , Derrame Pericárdico , Adulto , Azacitidina/efeitos adversos , Tamponamento Cardíaco/induzido quimicamente , Criança , Humanos , Masculino , Síndromes Mielodisplásicas/tratamento farmacológico , Derrame Pericárdico/induzido quimicamente , Pericardiocentese/efeitos adversosRESUMO
An 18-month-old male with pulmonary atresia and ventricular septal defect presented with stridor after neonatal systemic-to-pulmonary artery shunt surgery, that persisted on follow-up. CT angiography revealed a vascular ring with balanced double aortic arch.
Assuntos
Cardiopatias Congênitas , Comunicação Interventricular , Atresia Pulmonar , Anel Vascular , Aorta Torácica/diagnóstico por imagem , Criança , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/diagnóstico por imagem , Comunicação Interventricular/diagnóstico por imagem , Comunicação Interventricular/cirurgia , Humanos , Lactente , Recém-Nascido , Masculino , Anel Vascular/diagnóstico , Anel Vascular/diagnóstico por imagemRESUMO
Accelerated idioventricular rhythm is a rare but benign form of ventricular tachycardia which might be challenging to differentiate from other more worrisome forms. We present the case of a healthy newborn diagnosed with an accelerated idioventricular rhythm which is spontaneously terminated without the need for medical therapy.
Assuntos
Ritmo Idioventricular Acelerado , Taquicardia Ventricular , Ritmo Idioventricular Acelerado/diagnóstico , Ritmo Idioventricular Acelerado/etiologia , Arritmias Cardíacas , Eletrocardiografia , Humanos , Recém-Nascido , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/terapiaRESUMO
Hepatitis C virus (HCV) depends on liver-specific microRNA miR-122 for efficient viral RNA amplification in liver cells. This microRNA interacts with two different conserved sites at the very 5' end of the viral RNA, enhancing miR-122 stability and promoting replication of the viral RNA. Treatment of HCV patients with oligonucleotides that sequester miR-122 resulted in profound loss of viral RNA in phase II clinical trials. However, some patients accumulated in their sera a viral RNA genome that contained a single cytidine to uridine mutation at the third nucleotide from the 5' genomic end. It is shown here that this C3U variant indeed displayed higher rates of replication than that of wild-type HCV when miR-122 abundance is low in liver cells. However, when miR-122 abundance is high, binding of miR-122 to site 1, most proximal to the 5' end in the C3U variant RNA, is impaired without disrupting the binding of miR-122 to site 2. As a result, C3U RNA displays a much lower rate of replication than wild-type mRNA when miR-122 abundance is high in the liver. This phenotype was accompanied by binding of a different set of cellular proteins to the 5' end of the C3U RNA genome. In particular, binding of RNA helicase DDX6 was important for displaying the C3U RNA replication phenotype in liver cells. These findings suggest that sequestration of miR-122 leads to a resistance-associated mutation that has only been observed in treated patients so far, and raises the question about the function of the C3U variant in the peripheral blood.
Assuntos
Nucleotídeos de Citosina/genética , Genoma Viral , Hepacivirus/genética , Hepatite C/virologia , MicroRNAs/metabolismo , Mutação , RNA Viral/genética , Sítios de Ligação , Hepatite C/genética , Hepatite C/metabolismo , Interações Hospedeiro-Patógeno , Humanos , MicroRNAs/genética , Replicação ViralRESUMO
Cardiac involvement in systemic lupus erythematosus (SLE) is well documented. The pericardium, myocardium and endocardium, as well as the coronary arteries, the valves and the conduction system can all be affected. While pericarditis is common, arrythmias are less frequently described.We present a 13-year-old male, who had fatigue, anorexia, weight loss, myalgias and arthralgias for four months. On physical examination, we identified bradycardia (heart rate 31-50 bpm), oral and nasal ulcers and polyarthritis. The laboratory results showed hemolytic anemia, hypocomplementemia, antinuclear and anti-dsDNA antibodies, hematuria and non-nephrotic proteinuria. Renal function was normal. Lupus nephritis class II was diagnosed by kidney biopsy. On the transthoracic echocardiogram we identified a minimal pericardial effusion, suggesting pericarditis, and, on the electrocardiogram, we detected sinus arrest with junctional rhythm, denoting sinus node dysfunction. The patient was diagnosed with juvenile SLE with cardiac, renal, musculoskeletal and hematologic involvement. Disease remission and cardiac rhythm control were obtained with steroids and mycophenolate mofetil. Currently, the patient is asymptomatic, with normal sinus rhythm.We described an adolescent with SLE who had sinus node dysfunction upon diagnosis. Other cases have been reported in adults but none in juvenile SLE. All SLE patients should have a thorough cardiac examination to promptly diagnose and treat the innumerous cardiac manifestations of this disease.
Assuntos
Lúpus Eritematoso Sistêmico/diagnóstico , Síndrome do Nó Sinusal/etiologia , Adolescente , Bradicardia/etiologia , Eletrocardiografia , Hematúria/etiologia , Humanos , Glomérulos Renais/patologia , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica/etiologia , Nefrite Lúpica/patologia , Masculino , Derrame Pericárdico/etiologia , Pericardite/etiologia , Proteinúria/etiologia , Síndrome do Nó Sinusal/diagnósticoRESUMO
The illegal harvest of marine species within exclusive economic zones can have a strong impact on the function of local ecosystems and livelihoods of coastal communities. The complexity of these problems is often overlooked in the development of solutions, leading to ineffective and sometimes harmful social and environmental outcomes. One-dimensional, oversimplified perspectives can lead to conservation prescriptions that exacerbate social stressors. This is particularly critical in the case of international illegal trade of endangered, high-value species, which generate a value chain in which artisanal fishers are the first operational and often the weakest link of an intricate web. We examined 2 illegal fisheries, totoaba (Totoaba macdonaldi) and sea cucumber (Isostichopus badionotus and Holothuria floridana), in Mexico. Although these are 2 separate and independent fisheries, important ecological (resource condition, fishery impacts at the ecosystem level) and social (governance, markets) similarities improve understanding of their complexity. Our findings are relevant globally and show the need for interdisciplinary decision-making groups, community engagement, and the development of demand reduction measures.
Pesquerías Ilegales, Crímenes Ambientales y la Conservación de los Recursos Marinos Resumen La cosecha ilegal de especies marinas dentro de las zonas económicas exclusivas puede tener un impacto serio sobre la función de los ecosistemas locales y el economia de las comunidades costeras. La complejidad de estos problemas generalmente se ignora durante el desarrollo de soluciones, lo que conlleva a resultados ambientales y sociales poco efectivos y algunas veces dañinos. Las perspectivas unidimensionales y sobresimplificadas pueden derivar en prescripciones de conservación que empeoran las condiciones sociales sociales. Lo anterior es particularmente crítico para el caso del mercado ilegal de especies en peligro y de alto valor, lo que genera una cadena de valores en la que los pescadores tradicionales son el primer eslabón operativo y con frecuencia el más débil de una red intrincada. Examinamos dos pesquerías ilegales, la de la totoaba (Totoaba macdonaldi) y la del pepino de mar (Isostichopus badionotus y Holothuria floridana), en México. Aunque estas dos pesquerías son diferentes e independientes, las importantes similitudes ecológicas (estado del recurso, impactos de la pesquería a nivel de ecosistema) y sociales (governancia, mercados) mejoran el conocimiento de su complejidad. Nuestros hallazgos son relevantes a escala global y muestran la necesidad de tener grupos interdisciplinarios para tomar decisiones, la participación de la comunidad y el desarrollo de medidas para reducir la demanda por el producto pesquero.
Assuntos
Ecossistema , Pesqueiros , Conservação dos Recursos Naturais , Crime , MéxicoRESUMO
ciRS-7 is an intensely studied, highly expressed and conserved circRNA. Essentially nothing is known about its biogenesis, including the location of its promoter. A prevailing assumption has been that ciRS-7 is an exceptional circRNA because it is transcribed from a locus lacking any mature linear RNA transcripts of the same sense. To study the biogenesis of ciRS-7, we developed an algorithm to define its promoter and predicted that the human ciRS-7 promoter coincides with that of the long non-coding RNA, LINC00632. We validated this prediction using multiple orthogonal experimental assays. We also used computational approaches and experimental validation to establish that ciRS-7 exonic sequence is embedded in linear transcripts that are flanked by cryptic exons in both human and mouse. Together, this experimental and computational evidence generates a new model for regulation of this locus: (a) ciRS-7 is like other circRNAs, as it is spliced into linear transcripts; (b) expression of ciRS-7 is primarily determined by the chromatin state of LINC00632 promoters; (c) transcription and splicing factors sufficient for ciRS-7 biogenesis are expressed in cells that lack detectable ciRS-7 expression. These findings have significant implications for the study of the regulation and function of ciRS-7, and the analytic framework we developed to jointly analyze RNA-seq and ChIP-seq data reveal the potential for genome-wide discovery of important biological regulation missed in current reference annotations.
Assuntos
RNA/biossíntese , RNA/genética , Algoritmos , Processamento Alternativo , Animais , Química Encefálica , Éxons , Feminino , Células HEK293 , Humanos , Camundongos , Gravidez , Splicing de RNA , RNA Circular , RNA Longo não Codificante/genética , Análise de Sequência de RNA/métodosRESUMO
Influenza A virus usurps host signaling factors to regulate its replication. One example is mTOR, a cellular regulator of protein synthesis, growth and motility. While the role of mTORC1 in viral infection has been studied, the mechanisms that induce mTORC1 activation and the substrates regulated by mTORC1 during influenza virus infection have not been established. In addition, the role of mTORC2 during influenza virus infection remains unknown. Here we show that mTORC2 and PDPK1 differentially phosphorylate AKT upon influenza virus infection. PDPK1-mediated phoshorylation of AKT at a distinct site is required for mTORC1 activation by influenza virus. On the other hand, the viral NS1 protein promotes phosphorylation of AKT at a different site via mTORC2, which is an activity dispensable for mTORC1 stimulation but known to regulate apoptosis. Influenza virus HA protein and down-regulation of the mTORC1 inhibitor REDD1 by the virus M2 protein promote mTORC1 activity. Systematic phosphoproteomics analysis performed in cells lacking the mTORC2 component Rictor in the absence or presence of Torin, an inhibitor of both mTORC1 and mTORC2, revealed mTORC1-dependent substrates regulated during infection. Members of pathways that regulate mTORC1 or are regulated by mTORC1 were identified, including constituents of the translation machinery that once activated can promote translation. mTORC1 activation supports viral protein expression and replication. As mTORC1 activation is optimal midway through the virus life cycle, the observed effects on viral protein expression likely support the late stages of influenza virus replication when infected cells undergo significant stress.
Assuntos
Complexos Multiproteicos/metabolismo , Orthomyxoviridae/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Replicação Viral , Proteínas de Transporte/metabolismo , Movimento Celular/fisiologia , Replicação do DNA , Regulação para Baixo/efeitos dos fármacos , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina , Alvo Mecanístico do Complexo 2 de Rapamicina , Fosforilação/efeitos dos fármacos , Transdução de Sinais/fisiologia , Fatores de Transcrição/metabolismoRESUMO
Trafficking of proteins and RNA into and out of the nucleus occurs through the nuclear pore complex (NPC). Because of its critical function in many cellular processes, the NPC and transport factors are common targets of several viruses that disrupt key constituents of the machinery to facilitate viral replication. Many viruses such as poliovirus and severe acute respiratory syndrome (SARS) virus inhibit protein import into the nucleus, whereas viruses such as influenza A virus target and disrupt host mRNA nuclear export. Current evidence indicates that these viruses may employ such strategies to avert the host immune response. Conversely, many viruses co-opt nucleocytoplasmic trafficking to facilitate transport of viral RNAs. As viral proteins interact with key regulators of the host nuclear transport machinery, viruses have served as invaluable tools of discovery that led to the identification of novel constituents of nuclear transport pathways. This review explores the importance of nucleocytoplasmic trafficking to viral pathogenesis as these studies revealed new antiviral therapeutic strategies and exposed previously unknown cellular mechanisms. Further understanding of nuclear transport pathways will determine whether such therapeutics will be useful treatments for important human pathogens.
Assuntos
Núcleo Celular/metabolismo , Vírus/patogenicidade , Transporte Ativo do Núcleo Celular , Animais , Núcleo Celular/virologia , Citoplasma/metabolismo , Citoplasma/virologia , Humanos , Transporte de RNA , Vírus/metabolismoRESUMO
The brown swimming crab (Callinectes bellicosus) is an economically important species in the Gulf of California, and its fishing activity, held in Sonora from 1986, has been affected by a 20-year declining trend in its biomass. With the aim to understand the possible reasons of this species population changes along time, we estimated population growth rate (r) and sex ratio of C. bellicosus, and combined them with three parameters describing its habitat: sea temperature, wetland extension and habitat size in four areas along the coast of Sonora. For this, monthly mean sex ratio was estimated from crabs samples obtained from commercial catches during 1998-2002 and 2012; mean sea surface temperature for the spawning period (May-August) were derived from remote sensors for the same years; while wetland coverages were obtained from published reports, and habitat size was estimated as the fishing surface. For each area, r was estimated using a method developed for limited data situations using commercial landings (t) from 1986-2013. With data from the four areas, simple and multiple linear regression models were developed to ascertain theoretical sensitivities of r to variations in sex ratio and environmental parameters. A total of 24 556 crabs were sampled; males dominated (68.8 %) over females during the study period and in all areas; a cluster analysis identified two groups according to sex ratio: a Northern group with zones 1 and 2, and a Southern group with zones 3 and 4. r values were different in all zones (P<0.001) as was sex ratio (P=0.037); no differences in temperature were identified within the study years (P>0.995). Both the estimated data and sensitivity analyses suggest the existence of a direct and positive dependence of r on the proportion of female crabs and wetland size. We hypothesize that excess fishing of females caused the declining biomass trend of the brown swimming crab in Sonora, and concluded on the convenience of implementing harvest refugia inside coastal wetlands to protect females during the spawning season.
Assuntos
Decápodes/crescimento & desenvolvimento , Meio Ambiente , Razão de Masculinidade , Animais , Biomassa , Feminino , Modelos Lineares , Masculino , México , Crescimento Demográfico , Estações do Ano , Análise Espacial , Estatísticas não Paramétricas , Fatores de TempoRESUMO
BACKGROUND: Prenatal diagnosis (PND) of aortic coarctation (AoCo) has been associated with a significant improvement in early results, but there is limited information on the long-term cardiovascular outcome. METHODS: We studied 103 patients with simple AoCo, operated in the neonatal period, with a median follow-up of 8,5 years (2 to 23,7 years), with 47% followed for over 10 years. PND was made in 35%. The primary aim was to determine the short and long-term cardiovascular impact of PND of AoCo. RESULTS: Neonates with PND had less preoperative neonatal complications, with only 2,8% incidence of a composite preoperative severe morbidity course, compared to 28% in the postnatal group. PND patients underwent surgery 8 days earlier and had a shorter length of stay in ICU. PND did not impact the incidence of post-operative complications. On the long-term, prevalence of hypertension, left ventricular hypertrophy and rate of recoarctation were not influenced by PND. The PND group had mean 24 h diastolic BP 9 mmHg lower and mean daytime diastolic BP 11 mmHg lower. In the final multivariable model, PND was the single independent variable correlating with daytime diastolic BP. CONCLUSION: PND of AoCo effectively leads to a better pre-operative course with less pre-operative morbidity. We found no significant differences in immediate post-operative cardiovascular outcomes. A better initial course of patients with PND does not have a major long-term impact on cardiovascular outcomes, nevertheless, at late follow-up PND patients had lower diastolic BP values on ambulatory monitoring, which may have an impact on long-term cardiovascular risk.
Assuntos
Coartação Aórtica , Sistema Cardiovascular , Hipertensão , Recém-Nascido , Gravidez , Feminino , Humanos , Coartação Aórtica/diagnóstico por imagem , Coartação Aórtica/epidemiologia , Coartação Aórtica/cirurgia , Diagnóstico Pré-Natal , Hipertensão/epidemiologia , Prevalência , SeguimentosRESUMO
Brugada syndrome is a rare arrhythmogenic syndrome associated mainly with pathogenic variants in the SCN5A gene. Right ventricle outflow tract fibrosis has been reported in some cases of patients diagnosed with Brugada syndrome. Pulmonary atresia with an intact ventricular septum is characterized by the lack of a functional pulmonary valve, due to the underdevelopment of the right ventricle outflow tract. We report, for the first time, a 4-year-old boy with pulmonary atresia with an intact ventricular septum who harbored a pathogenic de novo variant in SCN5A, and the ajmaline test unmasked a type-1 Brugada pattern. We suggest that deleterious variants in the SCN5A gene could be implicated in pulmonary atresia with an intact ventricular septum embryogenesis, leading to overlapping phenotypes.
Assuntos
Síndrome de Brugada , Canal de Sódio Disparado por Voltagem NAV1.5 , Atresia Pulmonar , Humanos , Atresia Pulmonar/genética , Atresia Pulmonar/patologia , Masculino , Síndrome de Brugada/genética , Síndrome de Brugada/patologia , Pré-Escolar , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/patologia , Septo Interventricular/patologiaRESUMO
A chemical genetics approach was taken to identify inhibitors of NS1, a major influenza A virus virulence factor that inhibits host gene expression. A high-throughput screen of 200,000 synthetic compounds identified small molecules that reversed NS1-mediated inhibition of host gene expression. A counterscreen for suppression of influenza virus cytotoxicity identified naphthalimides that inhibited replication of influenza virus and vesicular stomatitis virus (VSV). The mechanism of action occurs through activation of REDD1 expression and concomitant inhibition of mammalian target of rapamycin complex 1 (mTORC1) via TSC1-TSC2 complex. The antiviral activity of naphthalimides was abolished in REDD1(-/-) cells. Inhibition of REDD1 expression by viruses resulted in activation of the mTORC1 pathway. REDD1(-/-) cells prematurely upregulated viral proteins via mTORC1 activation and were permissive to virus replication. In contrast, cells conditionally expressing high concentrations of REDD1 downregulated the amount of viral protein. Thus, REDD1 is a new host defense factor, and chemical activation of REDD1 expression represents a potent antiviral intervention strategy.
Assuntos
Antivirais/farmacologia , Naftalimidas/farmacologia , Orthomyxoviridae/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Vesiculovirus/efeitos dos fármacos , Animais , Antivirais/química , Linhagem Celular , Cães , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Ensaios de Triagem em Larga Escala , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Naftalimidas/química , Orthomyxoviridae/genética , Orthomyxoviridae/metabolismo , Relação Estrutura-Atividade , Fatores de Transcrição/deficiência , Vesiculovirus/genética , Vesiculovirus/metabolismo , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/efeitos dos fármacosRESUMO
Jellyfish are economically important organisms in diverse countries, carnivorous organisms that consume various prey (crustaceans, mollusks, bivalves, etc.) and dissolved carbohydrates in marine waters. This study was focused on detecting and quantifying the activity of digestive glycosidases from the cannonball jellyfish (Stomolophus sp. 2) to understand carbohydrate digestion and its temporal-spatial variation. Twenty-three jellyfish gastric pouches were collected in 2015 and 2016 in the Gulf of California in three localities (Las Guásimas, Hermosillo, and Caborca). Nine samples were in intra-localities from Las Guásimas. Chitinase (Ch), ß-glucosidase (ß-glu), and ß-N-acetylhexosaminidase (ß-NAHA) were detected in the gastric pouches. However, cellulase, exoglucanase, α-amylase, polygalacturonase, xylanase, and κ-carrageenase were undetected. Detected enzymes showed halotolerant glycolytic activity (i = 0-4 M NaCl), optimal pH, and temperature at 5.0 and 30-50 °C, respectively. At least five ß-glucosidase and two ß-N-acetylhexosaminidase were detected using zymograms; however, the number of proteins with chitinase activity is not precise. The annual variation of cannonball jellyfish digestive glycosidases from Las Guásimas between 2015-2016 does not show significant differences despite the difference in phytoplankton measured as chlorophyll α (1.9 and 3.4 mg/m3, respectively). In the inter-localities, the glycosidase activity was statistically different in all localities, except for ß-N-acetylhexosaminidase activity between Caborca and Hermosillo (3,009.08 ± 87.95 and 3,101.81 ± 281.11 mU/g of the gastric pouch, respectively), with chlorophyll α concentrations of 2.6, 3.4 mg/m3, respectively. For intra-localities, the glycosidase activity did not show significant differences, with a mean chlorophyll α of 1.3 ± 0.1 mg/m3. These results suggest that digestive glycosidases from Stomolophus sp. 2 can hydrolyze several carbohydrates that may belong to their prey or carbohydrates dissolved in marine waters, with salinity over ≥ 0.6 M NaCl and diverse temperature (4-80 °C) conditions. Also, chlorophyll α is related to glycosidase activity in both seasons and inter-localities, except for chitinase activity in an intra-locality (Las Guásimas).
Assuntos
Celulases , Quitinases , Cifozoários , Animais , Glicosídeo Hidrolases , Cloreto de Sódio , Cifozoários/química , beta-N-Acetil-Hexosaminidases , Carboidratos , ClorofilaRESUMO
We examined post-eclosion elimination of the Drosophila wing epithelium in vivo where collective "suicide waves" promote sudden, coordinated death of epithelial sheets without a final engulfment step. Like apoptosis in earlier developmental stages, this unique communal form of cell death is controlled through the apoptosome proteins, Dronc and Dark, together with the IAP antagonists, Reaper, Grim, and Hid. Genetic lesions in these pathways caused intervein epithelial cells to persist, prompting a characteristic late-onset blemishing phenotype throughout the wing blade. We leveraged this phenotype in mosaic animals to discover relevant genes and establish here that homeodomain interacting protein kinase (HIPK) is required for collective death of the wing epithelium. Extra cells also persisted in other tissues, establishing a more generalized requirement for HIPK in the regulation of cell death and cell numbers.
Assuntos
Morte Celular , Drosophila/citologia , Animais , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Células Epiteliais , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Asas de Animais/citologia , Asas de Animais/metabolismoRESUMO
Climate change is driving shifts in the abundance and distribution of marine fish and invertebrates and is having direct and indirect impacts on seafood catches and fishing communities, exacerbating the already negative effects of unsustainably high fishing pressure that exist for some stocks. Although the majority of fisheries in the world are managed at the national or local scale, most existing approaches to assessing climate impacts on fisheries have been developed on a global scale. It is often difficult to translate from the global to regional and local settings because of limited relevant data. To address the need for fisheries management entities to identify those fisheries with the greatest potential for climate change impacts, we present an approach for estimating expected climate change-driven impacts on the productivity and spatial range of fisheries at the regional scale in a data-poor context. We use a set of representative Mexican fisheries as test cases. To assess the implications of climate impacts, we compare biomass, harvest, and profit outcomes from a bioeconomic model under contrasting management policies and with and without climate change. Overall results show that climate change is estimated to negatively affect nearly every fishery in our study. However, the results indicate that overfishing is a greater threat than climate change for these fisheries, hence fixing current management challenges has a greater upside than the projected future costs of moderate levels of climate change. Additionally, this study provides meaningful first approximations of potential effects of both climate change and management reform in Mexican fisheries. Using the climate impact estimations and model outputs, we identify high priority stocks, fleets, and regions for policy reform in Mexico in the face of climate change. This approach can be applied in other data-poor circumstances to focus future research and policy reform efforts on stocks now subject to additional stress due to climate change. Considering their growing relevance as a critical source of protein and micronutrients to nourish our growing population, it is urgent for regions to develop sound fishery management policies in the short-term as they are the most important intervention to mitigate the adverse effects of climate change on marine fisheries.