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1.
PLoS Genet ; 16(12): e1009297, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33370287

RESUMO

Dis3L2 is a highly conserved 3'-5' exoribonuclease which is mutated in the human overgrowth disorders Perlman syndrome and Wilms' tumour of the kidney. Using Drosophila melanogaster as a model system, we have generated a new dis3L2 null mutant together with wild-type and nuclease-dead genetic lines in Drosophila to demonstrate that the catalytic activity of Dis3L2 is required to control cell proliferation. To understand the cellular pathways regulated by Dis3L2 to control proliferation, we used RNA-seq on dis3L2 mutant wing discs to show that the imaginal disc growth factor Idgf2 is responsible for driving the wing overgrowth. IDGFs are conserved proteins homologous to human chitinase-like proteins such as CHI3L1/YKL-40 which are implicated in tissue regeneration as well as cancers including colon cancer and non-small cell lung cancer. We also demonstrate that loss of DIS3L2 in human kidney HEK-293T cells results in cell proliferation, illustrating the conservation of this important cell proliferation pathway. Using these human cells, we show that loss of DIS3L2 results in an increase in the PI3-Kinase/AKT signalling pathway, which we subsequently show to contribute towards the proliferation phenotype in Drosophila. Our work therefore provides the first mechanistic explanation for DIS3L2-induced overgrowth in humans and flies and identifies an ancient proliferation pathway controlled by Dis3L2 to regulate cell proliferation and tissue growth.


Assuntos
Proliferação de Células , Discos Imaginais/metabolismo , Animais , Proteína 1 Semelhante à Quitinase-3/química , Proteína 1 Semelhante à Quitinase-3/metabolismo , Sequência Conservada , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Glicoproteínas/metabolismo , Células HEK293 , Humanos , Discos Imaginais/crescimento & desenvolvimento , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
2.
Clin Endocrinol (Oxf) ; 95(3): 369-377, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33650180

RESUMO

The literature on COVID-19-related thyroid complications has accumulated over the past year or so as the pandemic has accelerated throughout the world. In particular, several recent case reports have been published describing a possible correlation between COVID-19 disease and subacute thyroiditis (SAT). In this review, we briefly present one of our own patients and review the current published literature in this area up to January 2021, including analyses of major series of thyroid function tests in patients with significant COVID-19 infection. We conclude that while the great majority of patients with severe COVID-19 infection may show manifestations of the sick euthyroid syndrome, clinicians should be aware of the possibility of SAT, especially in the early weeks and months following even mild COVID-19 infection.


Assuntos
COVID-19 , Tireoidite Subaguda , Tireoidite , COVID-19/complicações , Humanos , Testes de Função Tireóidea , Tireoidite/virologia , Tireoidite Subaguda/virologia
3.
NMR Biomed ; 34(11): e4587, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34240782

RESUMO

Diffusion MRI characteristics assessed by apparent diffusion coefficient (ADC) histogram analysis in head and neck squamous cell carcinoma (HNSCC) have been reported as helpful in classifying tumours based on diffusion characteristics. There is little reported on HNSCC lymph nodes classification by diffusion characteristics. The aim of this study was to determine whether pretreatment nodal microstructural diffusion MRI characteristics can classify diseased nodes of patients with HNSCC from normal nodes of healthy volunteers. Seventy-nine patients with histologically confirmed HNSCC prior to chemoradiotherapy, and eight healthy volunteers, underwent diffusion-weighted (DW) MRI at a 1.5-T MR scanner. Two radiologists contoured lymph nodes on DW (b = 300 s/m2 ) images. ADC, distributed diffusion coefficient (DDC) and alpha (α) values were calculated by monoexponential and stretched exponential models. Histogram analysis metrics of drawn volume were compared between patients and volunteers using a Mann-Whitney test. The classification performance of each metric between the normal and diseased nodes was determined by receiver operating characteristic (ROC) analysis. Intraclass correlation coefficients determined interobserver reproducibility of each metric based on differently drawn ROIs by two radiologists. Sixty cancerous and 40 normal nodes were analysed. ADC histogram analysis revealed significant differences between patients and volunteers (p ≤0.0001 to 0.0046), presenting ADC distributions that were more skewed (1.49 for patients, 1.03 for volunteers; p = 0.0114) and 'peaked' (6.82 for patients, 4.20 for volunteers; p = 0.0021) in patients. Maximum ADC values exhibited the highest area under the curve ([AUC] 0.892). Significant differences were revealed between patients and volunteers for DDC and α value histogram metrics (p ≤0.0001 to 0.0044); the highest AUC were exhibited by maximum DDC (0.772) and the 25th percentile α value (0.761). Interobserver repeatability was excellent for mean ADC (ICC = 0.88) and the 25th percentile α value (ICC = 0.78), but poor for all other metrics. These results suggest that pretreatment microstructural diffusion MRI characteristics in lymph nodes, assessed by ADC and α value histogram analysis, can identify nodal disease.


Assuntos
Imagem de Difusão por Ressonância Magnética , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Voluntários Saudáveis , Linfonodos/diagnóstico por imagem , Pescoço/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Curva ROC
4.
Glob Chang Biol ; 27(13): 3157-3165, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33861505

RESUMO

All coastal systems experience disturbances and many across the planet are under unprecedented threat from an intensification of a variety of stressors. The West Antarctic Peninsula is a hotspot of physical climate change and has experienced a dramatic loss of sea-ice and glaciers in recent years. Among other things, sea-ice immobilizes icebergs, reducing collisions between icebergs and the seabed, thus decreasing ice-scouring. Ice disturbance drives patchiness in successional stages across seabed assemblages in Antarctica's shallows, making this an ideal system to understand the ecosystem resilience to increasing disturbance with climate change. We monitored a shallow benthic ecosystem before, during and after a 3-year pulse of catastrophic ice-scouring events and show that such systems can return, or bounce back, to previous states within 10 years. Our long-term data series show that recovery can happen more rapidly than expected, when disturbances abate, even in highly sensitive cold, polar environments.


Assuntos
Mudança Climática , Ecossistema , Regiões Antárticas , Camada de Gelo
5.
Eur J Haematol ; 106(2): 267-272, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33159689

RESUMO

INTRODUCTION: Whilst excision biopsy is traditionally preferred, advances in radiological and histological techniques warrant a re-look at core biopsy as a viable primary diagnostic method. METHOD: Over a 3-year period, all patients who underwent core biopsy to investigate lymphoma at our centre were included. RESULTS: 554 consecutive patients were included (40.1% prior lymphoma and 59.4% new presentations). Three or more cores were taken in 420 (75.8%) cases. Median time from request to biopsy and biopsy to histology report was 2 (0-40) days and 7 (1-24) days, respectively. 510/544 (93.8%) biopsies were diagnostic. There was no difference in whether the biopsy was diagnostic based on indication (new vs. relapsed lymphoma) (P = .445), whether biopsy was PET-directed (P = .507), for T-cell lymphoma (P = .468) or nodal vs. extra-nodal (P = .693). Thirty-eight patients (6.9%) required a second biopsy due to inadequate tissue. In a patient experience survey, only 13.9% reported any complications (1 self-limiting minor bleeding, 4 bruising) whilst 16.7% reported any discomfort beyond 12 hours. CONCLUSION: Core biopsy performed by experienced radiologists and analysed by expert haemato-pathologists is a reliable, well-tolerated method for diagnosing lymphoma and confirming relapse. Multiple cores can be obtained under local anaesthetic yielding sufficient material in the majority of cases.


Assuntos
Biópsia com Agulha de Grande Calibre , Linfonodos/patologia , Transtornos Linfoproliferativos/diagnóstico , Biópsia , Biópsia com Agulha de Grande Calibre/métodos , Biópsia com Agulha de Grande Calibre/normas , Humanos , Biópsia Guiada por Imagem , Excisão de Linfonodo , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
6.
Glob Chang Biol ; 26(4): 2702-2716, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31930639

RESUMO

The Antarctic is considered to be a pristine environment relative to other regions of the Earth, but it is increasingly vulnerable to invasions by marine, freshwater and terrestrial non-native species. The Antarctic Peninsula region (APR), which encompasses the Antarctic Peninsula, South Shetland Islands and South Orkney Islands, is by far the most invaded part of the Antarctica continent. The risk of introduction of invasive non-native species to the APR is likely to increase with predicted increases in the intensity, diversity and distribution of human activities. Parties that are signatories to the Antarctic Treaty have called for regional assessments of non-native species risk. In response, taxonomic and Antarctic experts undertook a horizon scanning exercise using expert opinion and consensus approaches to identify the species that are likely to present the highest risk to biodiversity and ecosystems within the APR over the next 10 years. One hundred and three species, currently absent in the APR, were identified as relevant for review, with 13 species identified as presenting a high risk of invading the APR. Marine invertebrates dominated the list of highest risk species, with flowering plants and terrestrial invertebrates also represented; however, vertebrate species were thought unlikely to establish in the APR within the 10 year timeframe. We recommend (a) the further development and application of biosecurity measures by all stakeholders active in the APR, including surveillance for species such as those identified during this horizon scanning exercise, and (b) use of this methodology across the other regions of Antarctica. Without the application of appropriate biosecurity measures, rates of introductions and invasions within the APR are likely to increase, resulting in negative consequences for the biodiversity of the whole continent, as introduced species establish and spread further due to climate change and increasing human activity.

7.
Environ Sci Technol ; 54(5): 2763-2771, 2020 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-31950826

RESUMO

Pollutant levels in polar regions are gaining progressively more attention from the scientific community. This is especially so for pollutants that persist in the environment and can reach polar latitudes via a wide range of routes, such as some persistent organic pollutants (POPs). In this study, samples of Antarctic marine benthic organisms were analyzed for legacy and emerging POPs (polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides) to comprehensively assess their current POP concentrations and infer the potential sources of the pollutants. Specimens of five benthic invertebrate species were collected at two distinct locations near Rothera research station on the Antarctic Peninsula (67°35'8 ̋ S and 68°7'59 ̋ W). Any impact of the nearby Rothera station as a local source of pollution appeared to be negligible. The most abundant chemicals detected were hexachlorobenzene (HCB) and BDE-209. The highest concentrations detected were in limpets and sea urchins, followed by sea stars, ascidians, and sea cucumbers. The relative congener patterns of PCBs and PBDEs were similar in all of the species. Some chemicals (e.g., heptachlor, oxychlordane, and mirex) were detected in the Antarctic invertebrates for the first time. Statistical analyses revealed that the distribution of the POPs was not only driven by the feeding traits of the species but also by the physicochemical properties of the specific compounds.


Assuntos
Poluentes Ambientais , Hidrocarbonetos Clorados , Bifenilos Policlorados , Poluentes Químicos da Água , Animais , Regiões Antárticas , Monitoramento Ambiental , Éteres Difenil Halogenados , Invertebrados
8.
Radiographics ; 40(3): 775-790, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32364882

RESUMO

Although US is one of the most used modalities for head and neck imaging, its use in the diagnosis of laryngeal abnormalities is much less widespread. The standard assessment of laryngeal abnormalities currently involves direct laryngoscopy and cross-sectional imaging (either CT or MRI) but rarely US. US is readily available, noninvasive, and radiation free, and it allows real-time imaging (with video for dynamic assessment), higher resolution than that of cross-sectional imaging, and the performance of targeted fine needle aspiration cytology or biopsy. This modality, particularly with the advent of high-resolution US, has been found to be at least comparable to CT or MRI for diagnosis of malignant lesions and benign abnormalities such as vocal nodules, polyps, cysts, and Reinke edema. Furthermore, it has been found to be more sensitive for diagnosis of abnormalities such as small glottic tumors, and its dynamic capability can be used to identify functional abnormalities such as vocal cord palsy. The authors outline the technique of laryngeal US, which includes strategies to avoid calcified laryngeal cartilage by imaging through the thyrohyoid and cricothyroid membranes with a five-sweep strategy supplemented by cine film of the technique. They also provide US images of common laryngeal abnormalities such as tumors with and without extralaryngeal extension; vallecular, thyroglossal, and vocal cord cysts; laryngeal mucoceles; and vocal cord palsy. Online supplemental material is available for this article. ©RSNA, 2020.


Assuntos
Doenças da Laringe/diagnóstico por imagem , Laringe/anatomia & histologia , Ultrassonografia/métodos , Diagnóstico Diferencial , Humanos
9.
Clin Endocrinol (Oxf) ; 90(2): 277-284, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30346646

RESUMO

BACKGROUND/OBJECTIVE: Intraoperative parathyroid hormone (IOPTH) monitoring during surgery for primary hyperparathyroidism (PHPT) could improve cure rate and simplify current care pathways. This study assesses the performance of US, MIBI and IOPTH monitoring and their impact on outcomes and perioperative strategy. DESIGN: This is a retrospective study of a prospectively maintained database of patients who underwent parathyroidectomy guided by preoperative US, MIBI and IOPTH monitoring. Test performance (sensitivity, specificity, PPV, NPV, accuracy) and IOPTH added value (percentage of patients in whom test contributed to achieving cure) were calculated. RESULTS: A total of 617 patients (median age 59 years, 75% females), 603 (97.7%) of them cured, were included in analysis. Sensitivity of US was higher than MIBI (78.2% vs 70%, P < 0.05), but both were inferior to IOPTH (98.6%, P < 0.05). US and MIBI were more sensitive at detecting single gland disease (SGD) than multigland disease (MGD) (85% vs 55% and 77.5% vs 45.5%, respectively, P < 0.05), while IOPTH performed well in both situations (98.8% vs 96.7%, P > 0.05). In 41 patients with incorrect US predictions, MIBI gave correct result only in 12 (29.3%) cases, while IOPTH gave correct predictions in all but one patient (97.6%). Minimally invasive parathyroidectomy (MIP) was completed in 409 patients, with a similar completion rate regardless whether both or one scan was positive. IOPTH added value was significant in whole cohort (14%) and in subgroups of patients with concordant vs discordant scans, minimally invasive vs conventional surgery, and initial vs reoperative surgery. CONCLUSIONS: Intraoperative parathyroid hormone monitoring is more accurate at predicting cure than US and MIBI are at identifying abnormal glands in patients undergoing parathyroidectomy for PHPT and significantly contributes to cure rate in range of clinical scenarios. This implies that its routine use could facilitate successful surgery in patients with single positive imaging and increase number of MIPs while maintaining high cure rate.


Assuntos
Hiperparatireoidismo Primário/cirurgia , Monitorização Intraoperatória/métodos , Hormônio Paratireóideo/sangue , Paratireoidectomia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/normas , Monitorização Intraoperatória/normas , Estudos Retrospectivos , Sensibilidade e Especificidade
10.
BMC Ecol ; 19(1): 27, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31262299

RESUMO

BACKGROUND: Marine soft sediments are some of the most widespread habitats in the ocean, playing a vital role in global carbon cycling, but are amongst the least studied with regard to species composition and ecosystem functioning. This is particularly true of the Polar Regions, which are currently undergoing rapid climate change, the impacts of which are poorly understood. Compared to other latitudes, Polar sediment habitats also experience additional environmental drivers of strong seasonality and intense disturbance from iceberg scouring, which are major structural forces for hard substratum communities. This study compared sediment assemblages from two coves, near Rothera Point, Antarctic Peninsula, 67°S in order to understand the principal drivers of community structure, for the first time, evaluating composition across all size classes from mega- to micro-fauna. RESULTS: Morpho-taxonomy identified 77 macrofaunal species with densities of 464-16,084 individuals m-2. eDNA metabarcoding of microfauna, in summer only, identified a higher diversity, 189 metazoan amplicon sequence variants (ASVs) using the 18S ribosomal RNA and 249 metazoan ASVs using the mitochondrial COI gene. Both techniques recorded a greater taxonomic diversity in South Cove than Hangar Cove, with differences in communities between the coves, although the main taxonomic drivers varied between techniques. Morphotaxonomy identified the main differences between coves as the mollusc, Altenaeum charcoti, the cnidarian Edwardsia sp. and the polychaetes from the family cirratulidae. Metabarcoding identified greater numbers of species of nematodes, crustaceans and Platyhelminthes in South Cove, but more bivalve species in Hangar Cove. There were no detectable differences in community composition, measured through morphotaxonomy, between seasons, years or due to iceberg disturbance. CONCLUSIONS: This study found that unlike hard substratum communities the diversity of Antarctic soft sediment communities is correlated with the same factors as other latitudes. Diversity was significantly correlated with grain size and organic content, not iceberg scour. The increase in glacial sediment input as glaciers melt, may therefore be more important than increased iceberg disturbance.


Assuntos
Mudança Climática , Ecossistema , Animais , Regiões Antárticas , Ecologia , Camada de Gelo
11.
J Cell Sci ; 129(12): 2407-15, 2016 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-27160682

RESUMO

Regulation of protein synthesis is crucial for cells to maintain viability and to prevent unscheduled proliferation that could lead to tumorigenesis. Exposure to stress results in stalling of translation, with many translation initiation factors, ribosomal subunits and mRNAs being sequestered into stress granules or P bodies. This allows the re-programming of the translation machinery. Many aspects of translation are regulated by post-translational modification. Several proteomic screens have identified translation initiation factors as targets for sumoylation, although in many cases the role of this modification has not been determined. We show here that eIF4A2 is modified by SUMO, with sumoylation occurring on a single residue (K226). We demonstrate that sumoylation of eIF4A2 is modestly increased in response to arsenite and ionising radiation, but decreases in response to heat shock or hippuristanol. In arsenite-treated cells, but not in hippuristanol-treated cells, eIF4A2 is recruited to stress granules, suggesting sumoylation of eIF4A2 correlates with its recruitment to stress granules. Furthermore, we demonstrate that the inability to sumoylate eIF4A2 results in impaired stress granule formation, indicating a new role for sumoylation in the stress response.


Assuntos
Grânulos Citoplasmáticos/metabolismo , Fator de Iniciação 4A em Eucariotos/metabolismo , Estresse Fisiológico , Sumoilação , Sequência de Aminoácidos , Arsenitos/farmacologia , Grânulos Citoplasmáticos/efeitos dos fármacos , Grânulos Citoplasmáticos/efeitos da radiação , Fator de Iniciação 4A em Eucariotos/química , Células HeLa , Resposta ao Choque Térmico/efeitos dos fármacos , Humanos , Mutação/genética , Radiação Ionizante , Esteróis/farmacologia , Estresse Fisiológico/efeitos dos fármacos , Estresse Fisiológico/efeitos da radiação , Sumoilação/efeitos dos fármacos , Sumoilação/efeitos da radiação
12.
Biochem J ; 474(18): 3109-3120, 2017 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-28733330

RESUMO

DDX3X, a helicase, can interact directly with mRNA and translation initiation factors, regulating the selective translation of mRNAs that contain a structured 5' untranslated region. This activity modulates the expression of mRNAs controlling cell cycle progression and mRNAs regulating actin dynamics, contributing to cell adhesion and motility. Previously, we have shown that ribosomes and translation initiation factors localise to the leading edge of migrating fibroblasts in loci enriched with actively translating ribosomes, thereby promoting steady-state levels of ArpC2 and Rac1 proteins at the leading edge of cells during spreading. As DDX3X can regulate Rac1 levels, cell motility and metastasis, we have examined DDX3X protein interactions and localisation using many complementary approaches. We now show that DDX3X can physically interact and co-localise with poly(A)-binding protein 1 and caprin-1 at the leading edge of spreading cells. Furthermore, as depletion of DDX3X leads to decreased cell motility, this provides a functional link between DDX3X, caprin-1 and initiation factors at the leading edge of migrating cells to promote cell migration and spreading.


Assuntos
Proteínas de Ciclo Celular/metabolismo , RNA Helicases DEAD-box/metabolismo , Pulmão/metabolismo , Proteína I de Ligação a Poli(A)/metabolismo , Pseudópodes/metabolismo , RNA Mensageiro/metabolismo , Mucosa Respiratória/metabolismo , Western Blotting , Sistemas CRISPR-Cas , Linhagem Celular , Movimento Celular , Cromatografia de Afinidade , RNA Helicases DEAD-box/genética , Corantes Fluorescentes/química , Humanos , Imunoprecipitação , Pulmão/citologia , Pulmão/enzimologia , Microscopia Confocal , Microscopia de Fluorescência , Mapeamento de Peptídeos , Transporte Proteico , Proteômica/métodos , Pseudópodes/enzimologia , Mucosa Respiratória/citologia , Mucosa Respiratória/enzimologia
13.
Molecules ; 23(9)2018 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-30142961

RESUMO

Two novel ferrocene-containing compounds based upon a known MNK1/2 kinase (MAPK-interacting kinase) inhibitor have been synthesized. The compounds were designed to use the unique shape of ferrocene to exploit a large hydrophobic pocket in MNK1/2 that is only partially occupied by the original compound. Screening of the ferrocene analogues showed that both exhibited potent anticancer effects in several breast cancer and AML (acute myeloid leukemia) cell lines, despite a loss of MNK potency. The most potent ferrocene-based compound 5 was further analysed in vitro in MDA-MB-231 (triple negative breast cancer cells). Dose⁻response curves of compound 5 for 2D assay and 3D assay generated IC50 values (half maximal inhibitory concentration) of 0.55 µM and 1.25 µM, respectively.


Assuntos
Antineoplásicos/farmacologia , Compostos Ferrosos/química , Metalocenos/química , Antineoplásicos/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Leucemia Mieloide Aguda/metabolismo , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Tamoxifeno/química , Tamoxifeno/farmacologia , Neoplasias de Mama Triplo Negativas/metabolismo
14.
Glob Chang Biol ; 23(1): 318-330, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27312151

RESUMO

Understanding species' responses to environmental change underpins our abilities to make predictions on future biodiversity under any range of scenarios. In spite of the huge biodiversity in most ecosystems, a model species approach is often taken in environmental studies. To date, we still do not know how many species we need to study to input into models and inform on ecosystem-level responses to change. In this study, we tested current paradigms on factors setting thermal limits by investigating the acute warming response of six Antarctic marine invertebrates: a crustacean Paraceradocus miersi, a brachiopod Liothyrella uva, two bivalve molluscs, Laternula elliptica, Aequiyoldia eightsii, a gastropod mollusc Marseniopsis mollis and an echinoderm Cucumaria georgiana. Each species was warmed at the rate of 1 °C h-1 and taken to the same physiological end point (just prior to heat coma). Their molecular responses were evaluated using complementary metabolomics and transcriptomics approaches with the aim of discovering the underlying mechanisms of their resilience or sensitivity to warming. The responses were species-specific; only two showed accumulation of anaerobic end products and three exhibited the classical heat shock response with expression of HSP70 transcripts. These diverse cellular measures did not directly correlate with resilience to heat stress and suggested that each species may have a different critical point of failure. Thus, one unifying molecular mechanism underpinning response to warming could not be assigned, and no overarching paradigm was supported. This biodiversity in response makes future ecosystems predictions extremely challenging, as we clearly need to develop a macrophysiology-type approach to cellular evaluations of the environmental stress response, studying a range of well-rationalized members from different community levels and of different phylogenetic origins rather than extrapolating from one or two arbitrary model species.


Assuntos
Biodiversidade , Invertebrados , Animais , Regiões Antárticas , Organismos Aquáticos , Previsões , Filogenia , Temperatura
15.
Eur Radiol ; 27(2): 598-606, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27085701

RESUMO

OBJECTIVE: Determine feasibility of vocal fold (VF) abduction and adduction assessment by cine magnetic resonance imaging (cine-MRI) METHODS: Cine-MRI of the VF was performed on five healthy and nine unilateral VF paralysis (UVFP) participants using an axial gradient echo acquisition with temporal resolution of 0.7 s. VFs were continuously imaged with cine-MRI during a 10-s period of quiet respiration and phonation. Scanning was repeated twice within an individual session and then once again at a 1-week interval. Asymmetry of VF position during phonation (VF phonation asymmetry, VFPa) and respiration (VF respiration asymmetry, VFRa) was determined. Percentage reduction in total glottal area between respiration and phonation (VF abduction potential, VFAP) was derived to measure overall mobility. An un-paired t-test was used to compare differences between groups. Intra-session, inter-session and inter-reader repeatability of the quantitative metrics was evaluated using intraclass correlation coefficient (ICC). RESULTS: VF position asymmetry (VFPa and VFRa) was greater (p=0.012; p=0.001) and overall mobility (VFAP) was lower (p=0.008) in UVFP patients compared with healthy participants. ICC of repeatability of all metrics was good, ranged from 0.82 to 0.95 except for the inter-session VFPa (0.44). CONCLUSION: Cine-MRI is feasible for assessing VF abduction and adduction. Derived quantitative metrics have good repeatability. KEY POINTS: • Cine-MRI is used to assess vocal folds (VFs) mobility: abduction and adduction. • New quantitative metrics are derived from VF position and abduction potential. • Cine-MRI able to depict the difference between normal and abnormal VF mobility. • Cine-MRI derived quantitative metrics have good repeatability.


Assuntos
Imagem Cinética por Ressonância Magnética/métodos , Paralisia das Pregas Vocais/diagnóstico por imagem , Prega Vocal/diagnóstico por imagem , Adulto , Estudos de Viabilidade , Feminino , Humanos , Masculino , Fonação , Reprodutibilidade dos Testes
17.
J Biol Chem ; 290(8): 4748-4758, 2015 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-25561727

RESUMO

Protein synthesis is a tightly controlled process responding to several stimuli, including viral infection. As obligate intracellular parasites, viruses depend on the translation machinery of the host and can manipulate it by affecting the availability and function of specific eukaryotic initiation factors (eIFs). Human norovirus is a member of the Caliciviridae family and is responsible for gastroenteritis outbreaks. Previous studies on feline calicivirus and murine norovirus 1 (MNV1) demonstrated that the viral protein, genome-linked (VPg), acts to direct translation by hijacking the host protein synthesis machinery. Here we report that MNV1 infection modulates the MAPK pathway to activate eIF4E phosphorylation. Our results show that the activation of p38 and Mnk during MNV1 infection is important for MNV1 replication. Furthermore, phosphorylated eIF4E relocates to the polysomes, and this contributes to changes in the translational state of specific host mRNAs. We propose that global translational control of the host by eIF4E phosphorylation is a key component of the host-pathogen interaction.


Assuntos
Infecções por Caliciviridae/metabolismo , Fator de Iniciação 4E em Eucariotos/metabolismo , Interações Hospedeiro-Patógeno , Norovirus/fisiologia , Biossíntese de Proteínas , Proteínas Virais/biossíntese , Replicação Viral/fisiologia , Animais , Infecções por Caliciviridae/genética , Gatos , Linhagem Celular , Fator de Iniciação 4E em Eucariotos/genética , Humanos , Camundongos , Fosforilação/genética , Polirribossomos/genética , Polirribossomos/metabolismo , Transporte Proteico/genética , Proteínas Virais/genética
18.
Glob Chang Biol ; 22(3): 1110-20, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26682944

RESUMO

The Southern Ocean archipelago, the South Orkney Islands (SOI), became the world's first entirely high seas marine protected area (MPA) in 2010. The SOI continental shelf (~44 000 km(2) ), was less than half covered by grounded ice sheet during glaciations, is biologically rich and a key area of both sea surface warming and sea-ice losses. Little was known of the carbon cycle there, but recent work showed it was a very important site of carbon immobilization (net annual carbon accumulation) by benthos, one of the few demonstrable negative feedbacks to climate change. Carbon immobilization by SOI bryozoans was higher, per species, unit area and ice-free day, than anywhere-else polar. Here, we investigate why carbon immobilization has been so high at SOI, and whether this is due to high density, longevity or high annual production in six study species of bryozoans (benthic suspension feeders). We compared benthic carbon immobilization across major regions around West Antarctica with sea-ice and primary production, from remotely sensed and directly sampled sources. Lowest carbon immobilization was at the northernmost study regions (South Georgia) and southernmost Amundsen Sea. However, data standardized for age and density showed that only SOI was anomalous (high). High immobilization at SOI was due to very high annual production of bryozoans (rather than high densities or longevity), which were 2x, 3x and 5x higher than on the Bellingshausen, South Georgia and Amundsen shelves, respectively. We found that carbon immobilization correlated to the duration (but not peak or integrated biomass) of phytoplankton blooms, both in directly sampled, local scale data and across regions using remote-sensed data. The long bloom at SOI seems to drive considerable carbon immobilization, but sea-ice losses across West Antarctica mean that significant carbon sinks and negative feedbacks to climate change could also develop in the Bellingshausen and Amundsen seas.


Assuntos
Briozoários/fisiologia , Sequestro de Carbono , Animais , Regiões Antárticas , Briozoários/crescimento & desenvolvimento , Ilhas , Longevidade , Oceanos e Mares , Densidade Demográfica
19.
Ecology ; 96(7): 2004-14, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26378322

RESUMO

Selection acts on individuals, specifically on their differences. To understand adaptation and responses to change therefore requires knowledge of how variation is generated and distributed across traits. Variation occurs on different biological scales, from genetic through physiological to morphological, yet it is unclear which of these carries the most variability. For example, if individual variation is mainly generated by differences in gene expression, variability should decrease progressively from coding genes to morphological traits, whereas if post-translational and epigenetic effects increase variation, the opposite should occur. To test these predictions, we compared levels of variation among individuals in various measures of gene expression, physiology (including activity), and morphology in two abundant and geographically widespread Antarctic molluscs, the clam Laternula elliptica and the limpet Nacella concinna. Direct comparisons among traits as diverse as heat shock protein QPCR assays, whole transcription profiles, respiration rates, burying rate, shell length, and ash-free dry mass were made possible through the novel application of an established metric, the Wentworth Scale. In principle, this approach could be extended to analyses of populations, communities, or even entire ecosystems. We found consistently greater variation in gene expression than morphology, with physiological measures falling in between. This suggests that variability is generated at the gene expression level. These findings have important implications for refining current biological models and predictions of how biodiversity may respond to climate change.


Assuntos
Regulação da Expressão Gênica/fisiologia , Moluscos/genética , Moluscos/fisiologia , Animais , Regiões Antárticas , Mudança Climática , Ecossistema
20.
J Anim Ecol ; 84(3): 773-784, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25491898

RESUMO

This study examined the effects of long-term culture under altered conditions on the Antarctic sea urchin, Sterechinus neumayeri. Sterechinus neumayeri was cultured under the combined environmental stressors of lowered pH (-0.3 and -0.5 pH units) and increased temperature (+2 °C) for 2 years. This time-scale covered two full reproductive cycles in this species and analyses included studies on both adult metabolism and larval development. Adults took at least 6-8 months to acclimate to the altered conditions, but beyond this, there was no detectable effect of temperature or pH. Animals were spawned after 6 and 17 months exposure to altered conditions, with markedly different outcomes. At 6 months, the percentage hatching and larval survival rates were greatest in the animals kept at 0 °C under current pH conditions, whilst those under lowered pH and +2 °C performed significantly less well. After 17 months, performance was not significantly different across treatments, including controls. However, under the altered conditions urchins produced larger eggs compared with control animals. These data show that under long-term culture adult S. neumayeri appear to acclimate their metabolic and reproductive physiology to the combined stressors of altered pH and increased temperature, with relatively little measureable effect. They also emphasize the importance of long-term studies in evaluating effects of altered pH, particularly in slow developing marine species with long gonad maturation times, as the effects of altered conditions cannot be accurately evaluated unless gonads have fully matured under the new conditions.


Assuntos
Ouriços-do-Mar/fisiologia , Temperatura , Aclimatação , Animais , Regiões Antárticas , Mudança Climática , Concentração de Íons de Hidrogênio , Larva/fisiologia , Consumo de Oxigênio , Reprodução , Ouriços-do-Mar/crescimento & desenvolvimento , Água do Mar/química , Fatores de Tempo
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