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1.
J Cell Sci ; 134(8)2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33912915

RESUMO

Intercellular bridges are essential for fertility in many organisms. The developing fruit fly egg has become the premier model system to study intercellular bridges. During oogenesis, the oocyte is connected to supporting nurse cells by relatively large intercellular bridges, or ring canals. Once formed, the ring canals undergo a 20-fold increase in diameter to support the movement of materials from the nurse cells to the oocyte. Here, we demonstrate a novel role for the conserved SH2/SH3 adaptor protein Dreadlocks (Dock) in regulating ring canal size and structural stability in the germline. Dock localizes at germline ring canals throughout oogenesis. Loss of Dock leads to a significant reduction in ring canal diameter, and overexpression of Dock causes dramatic defects in ring canal structure and nurse cell multinucleation. The SH2 domain of Dock is required for ring canal localization downstream of Src64 (also known as Src64B), and the function of one or more of the SH3 domains is necessary for the strong overexpression phenotype. Genetic interaction and localization studies suggest that Dock promotes WASp-mediated Arp2/3 activation in order to determine ring canal size and regulate growth. This article has an associated First Person interview with the first author of the paper.


Assuntos
Proteínas de Drosophila , Drosophila , Animais , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Células Germinativas , Oogênese/genética , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas
2.
Pancreatology ; 20(5): 852-859, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32595109

RESUMO

INTRODUCTION: Chronic pancreatitis is a chronic inflammatory disease, which progresses to fibrosis. Currently there are no interventions to delay or stop the progression to irreversible organ damage. In this study, we assessed the tolerability and feasibility of administering soy bread to reduce circulating inflammatory mediators. METHODS: Subjects with chronic pancreatitis diagnosed using the American Pancreatic Association diagnostic guidelines were enrolled. During the dose escalation (DE) phase, subjects received one week of soy bread based using a 3 + 3 dose-escalation design, which was then followed by a maximally tolerated dose (MTD) phase with four weeks of intervention. Dose-limiting toxicities (DLTs) were monitored. Plasma cytokine levels were measured using a Meso Scale Discovery multiplex assay kit. Isoflavonoid excretion in 24-h urine collection was used to measure soy bread compliance. RESULTS: Nine subjects completed the DE phase, and one subject completed the MTD phase without any DLTs at a maximum dosage of three slices (99 mg of isoflavones) per day. Reported compliance to soy bread intervention was 98%, and this was confirmed with urinary isoflavones and their metabolites detected in all subjects. There was a significant decline in the TNF-α level during the DE phase (2.667 vs 2.382 pg/mL, p = 0.039); other levels were similar. CONCLUSIONS: In this feasibility study, there was excellent compliance with a short-term intervention using soy bread in chronic pancreatitis. Reduction was seen in at least one pro-inflammatory cytokine with short-term intervention. Larger cohorts and longer interventions with soy are warranted to assess the efficacy of reducing pro-inflammatory mediators of disease.


Assuntos
Pão , Glycine max , Pancreatite Crônica/dietoterapia , Pancreatite Crônica/patologia , Idoso , Citocinas/sangue , Relação Dose-Resposta a Droga , Estudos de Viabilidade , Feminino , Humanos , Inflamação/dietoterapia , Inflamação/patologia , Mediadores da Inflamação/sangue , Isoflavonas/urina , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Projetos Piloto , Fator de Necrose Tumoral alfa/sangue
4.
Int J Biometeorol ; 58(6): 1237-49, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23975107

RESUMO

Citizen science is proving to be an effective tool in tracking the rapid pace at which our environment is changing over large geographic areas. It is becoming increasingly popular, in places such as North America and some European countries, to engage members of the general public and school pupils in the collection of scientific data to support long-term environmental monitoring. Participants in such schemes are generally volunteers and are referred to as citizen scientists. The Christmas bird count in the US is one of the worlds longest running citizen science projects whereby volunteers have been collecting data on birds on a specific day since 1900. Similar volunteer networks in Ireland have been in existence since the 1960s and were established to monitor the number and diversity of birds throughout the country. More recently, initiatives such as Greenwave (2006) and Nature Watch (2009) invite school children and members of the general public respectively, to record phenology data from a range of common species of plant, insect and bird. In addition, the Irish butterfly and bumblebee monitoring schemes engage volunteers to record data on sightings of these species. The primary purpose of all of these networks is to collect data by which to monitor changes in wildlife development and diversity, and in the case of Greenwave to involve children in hands-on, inquiry-based science. Together these various networks help raise awareness of key environmental issues, such as climate change and loss of biodiversity, while at the same time promote development of scientific skills among the general population. In addition, they provide valuable scientific data by which to track environmental change. Here we examine the role of citizen science in monitoring biodiversity in Ireland and conclude that some of the data collected in these networks can be used to fulfil Ireland's statutory obligations for nature conservation. In addition, a bee thought previously to be extinct has been rediscovered and a range expansion of a different bee has been confirmed. However, it also became apparent that some of the networks play more of an educational than a scientific role. Furthermore, we draw on experience from a range of citizen science projects to make recommendations on how best to establish new citizen science projects in Ireland and strengthen existing ones.


Assuntos
Biodiversidade , Projetos de Pesquisa , Voluntários , Animais , Aves , Mudança Climática , Humanos , Insetos , Irlanda , Plantas , Controle de Qualidade
5.
Pancreas ; 53(5): e416-e423, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38530954

RESUMO

OBJECTIVES: Chronic pancreatitis (CP) is an inflammatory disease affecting the absorption of fat-soluble nutrients. Signaling in pancreatic cells that lead to inflammation may be influenced by fatty acids (FAs) through diet and de novo lipogenesis. Here, we investigated the relationship between plasma FA composition in CP with heterogeneity of etiology and complications of CP. MATERIALS AND METHODS: Blood and clinical parameters were collected from subjects with CP (n = 47) and controls (n = 22). Plasma was analyzed for FA composition using gas chromatography and compared between controls and CP and within CP. RESULTS: Palmitic acid increased, and linoleic acid decreased in CP compared with controls. Correlations between age or body mass index and FAs are altered in CP compared with controls. Diabetes, pancreatic calcifications, and substance usage, but not exocrine pancreatic dysfunction, were associated with differences in oleic acid and linoleic acid relative abundance in CP. De novo lipogenesis index was increased in the plasma of subjects with CP compared with controls and in calcific CP compared with noncalcific CP. CONCLUSIONS: Fatty acids that are markers of de novo lipogenesis and linoleic acid are dysregulated in CP depending on the etiology or complication. These results enhance our understanding of CP and highlight potential pathways targeting FAs for treating CP.


Assuntos
Ácidos Graxos , Ácido Linoleico , Pancreatite Crônica , Humanos , Projetos Piloto , Pancreatite Crônica/sangue , Pancreatite Crônica/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Ácidos Graxos/sangue , Ácido Linoleico/sangue , Estudos de Casos e Controles , Lipogênese , Idoso , Ácido Palmítico/sangue , Ácido Oleico/sangue , Biomarcadores/sangue
6.
bioRxiv ; 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36711757

RESUMO

Objectives: Chronic pancreatitis (CP) is an inflammatory disease that affects the absorption of nutrients like fats. Molecular signaling in pancreatic cells can be influenced by fatty acids (FAs) and changes in FA abundance could impact CP-associated complications. Here, we investigated FA abundance in CP compared to controls and explored how CP-associated complications and risk factors affect FA abundance. Methods: Blood and clinical parameters were collected from subjects with (n=47) and without CP (n=22). Plasma was analyzed for relative FA abundance using gas chromatography and compared between controls and CP. Changes in FA abundance due to clinical parameters were also assessed in both groups. Results: Decreased relative abundance of polyunsaturated fatty acids (PUFAs) and increased monounsaturated fatty acids (MUFAs) were observed in subjects with CP in a sex-dependent manner. The relative abundance of linoleic acid increased, and oleic acid decreased in CP subjects with exocrine pancreatic dysfunction and a history of substance abuse. Conclusions: Plasma FAs like linoleic acid are dysregulated in CP in a sex-dependent manner. Additionally, risk factors and metabolic dysfunction further dysregulate FA abundance in CP. These results enhance our understanding of CP and highlight potential novel targets and metabolism-related pathways for treating CP.

7.
Cells ; 11(5)2022 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-35269531

RESUMO

Cachexia occurs in up to 80% of pancreatic ductal adenocarcinoma (PDAC) patients and is characterized by unintentional weight loss and tissue wasting. To understand the metabolic changes that occur in PDAC-associated cachexia, we compared the abundance of plasma fatty acids (FAs), measured by gas chromatography, of subjects with treatment-naïve metastatic PDAC with or without cachexia, defined as a loss of > 2% weight and evidence of sarcopenia (n = 43). The abundance of saturated, monounsaturated, and polyunsaturated FAs was not different between subjects with cachexia and those without. Oleic acid was significantly higher in subjects with cachexia (p = 0.0007) and diabetes (p = 0.015). Lauric (r = 0.592, p = 0.0096) and eicosapentaenoic (r = 0.564, p = 0.015) acids were positively correlated with age in cachexia patients. Subjects with diabetes (p = 0.021) or both diabetes and cachexia (p = 0.092) had low palmitic:oleic acid ratios. Linoleic acid was lower in subjects with diabetes (p = 0.018) and correlated with hemoglobin (r = 0.519, p = 0.033) and albumin (r = 0.577, p = 0.015) in subjects with cachexia. Oleic or linoleic acid may be useful treatment targets or biomarkers of cachexia in patients with metastatic PDAC, particularly those with diabetes.


Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma/complicações , Caquexia/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Ácidos Graxos/metabolismo , Humanos , Ácidos Linoleicos , Ácido Oleico , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas
8.
Science ; 352(6281): 84-7, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-27034371

RESUMO

Global climate change is a major threat to biodiversity. Large-scale analyses have generally focused on the impacts of climate change on the geographic ranges of species and on phenology, the timing of ecological phenomena. We used long-term monitoring of the abundance of breeding birds across Europe and the United States to produce, for both regions, composite population indices for two groups of species: those for which climate suitability has been either improving or declining since 1980. The ratio of these composite indices, the climate impact indicator (CII), reflects the divergent fates of species favored or disadvantaged by climate change. The trend in CII is positive and similar in the two regions. On both continents, interspecific and spatial variation in population abundance trends are well predicted by climate suitability trends.


Assuntos
Aves , Mudança Climática , Migração Animal , Animais , Biodiversidade , Cruzamento , Monitorização de Parâmetros Ecológicos , Europa (Continente) , Dinâmica Populacional , Estados Unidos
10.
Glob Chang Biol ; 19(7): 2071-81, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23509023

RESUMO

Climate change is predicted to cause changes in species distributions and several studies report margin range shifts in some species. However, the reported changes rarely concern a species' entire distribution and are not always linked to climate change. Here, we demonstrate strong north-eastwards shifts in the centres of gravity of the entire wintering range of three common waterbird species along the North-West Europe flyway during the past three decades. These shifts correlate with an increase of 3.8 °C in early winter temperature in the north-eastern part of the wintering areas, where bird abundance increased exponentially, corresponding with decreases in abundance at the south-western margin of the wintering ranges. This confirms the need to re-evaluate conservation site safeguard networks and associated biodiversity monitoring along the flyway, as new important wintering areas are established further north and east, and highlights the general urgency of conservation planning in a changing world. Range shifts in wintering waterbirds may also affect hunting pressure, which may alter bag sizes and lead to population-level consequences.


Assuntos
Migração Animal/fisiologia , Mudança Climática , Conservação dos Recursos Naturais , Patos/fisiologia , Estações do Ano , Animais , Europa (Continente) , Dinâmica Populacional
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