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1.
Sol Phys ; 299(8): 120, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39220341

RESUMO

The Solar eruptioN Integral Field Spectrograph (SNIFS) is a solar-gazing spectrograph scheduled to fly in the summer of 2025 on a NASA sounding rocket. Its goal is to view the solar chromosphere and transition region at a high cadence (1 s) both spatially ( 0.5 ″ ) and spectrally (33 mÅ) viewing wavelengths around Lyman alpha (1216 Å), Si iii (1206 Å), and O v (1218 Å) to observe spicules, nanoflares, and possibly a solar flare. This time cadence will provide yet-unobserved detail about fast-changing features of the Sun. The instrument is comprised of a Gregorian-style reflecting telescope combined with a spectrograph via a specialized mirrorlet array that focuses the light from each spatial location in the image so that it may be spectrally dispersed without overlap from neighboring locations. This paper discusses the driving science, detailed instrument and subsystem design, and preintegration testing of the SNIFS instrument.

2.
Age Ageing ; 53(5)2024 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-38706391

RESUMO

INTRODUCTION: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly progressive neurodegenerative disease with public health implications. Mean age of onset is 68 years. Age-specific incidence declines after 80 years. This may arise from under-ascertainment or other biological features of the disease. Accurate characterisation of late-onset sCJD is important for early diagnosis, avoiding unnecessary investigations and improving ascertainment for public health purposes. OBJECTIVE: To phenotype the clinical features and investigation profile of sCJD in adults >80 years. METHODS: We analysed all probable and definite sCJD cases identified by the UK National CJD Research & Surveillance Unit over a 10-year period (2011-2021). Individuals were grouped by age of onset. Clinical features and investigation profiles were compared. RESULTS: 10.3% (123/1196) had an age of onset over 80. Median survival was shorter (3.2 vs 4.3 months; P < 0.001). Pyramidal signs (48.3% vs 34.2%; P = 0.008) and akinetic mutism (55.1% vs 33.2%; P < 0.001) were more frequent. Psychiatric symptoms (26.3% vs 39.6%; P = 0.01) and cerebellar signs (65.4% vs 78.6%, P = 0.007) were less frequent. Cognitive impairment and myoclonus were highly prevalent regardless of age. Between age groups, the diagnostic sensitivity of cerebrospinal fluid real-time quaking-induced conversion (CSF RT-QuIC) (92.9% vs 91.9%, P = 0.74) was comparable, electroencephalography was superior (41.5% vs 25.4%; P = 0.006) and MRI was inferior (67.8% vs 91.4%; P < 0.001). CONCLUSIONS: Late-onset sCJD has distinct clinical features, shorter survival and a different profile of investigation sensitivity. CSF RT-QuIC, MRI brain and specialist CJD review is recommended in older adults with a rapidly progressive neurological disorder. Autopsy is valuable when the cause remains elusive.


Assuntos
Idade de Início , Síndrome de Creutzfeldt-Jakob , Humanos , Síndrome de Creutzfeldt-Jakob/epidemiologia , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/mortalidade , Reino Unido/epidemiologia , Masculino , Feminino , Idoso de 80 Anos ou mais , Incidência , Fenótipo , Imageamento por Ressonância Magnética , Eletroencefalografia
3.
J Environ Manage ; 370: 122632, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39357441

RESUMO

The plantation forestry estate in Australia has been in decline for a decade or more. Previous studies attribute observed investment inertia to factors including the long-term nature of forestry investments, high up front establishment cost and more recently water resource constraints. The introduction of plantation forestry methods as part of the Australian Carbon Credit Unit Scheme in 2017 has generated renewed interest in plantation forestry as a carbon abatement option. To assess this opportunity, we performed high spatial resolution bioeconomic modelling of southeastern Australia's Green Triangle forestry region to understand the joint influence of site productivity, species selection and spatially variable costs including agricultural land prices and transport distances on land use change and additional future timber flows. We found that additional plantations may be economically viable at a carbon price of AU$39/t CO2e. New softwood (P. radiata) plantations provide the lowest cost option across the region when compared to hardwood (E. globulus). However, at carbon prices below AU$50/t CO2e comparatively little technically feasible abatement is possible for both plantation species with only 632,000 t CO2e from hardwood and 12.9 Mt CO2e, from softwood under economically optimised conditions which equates to 0.13 and 2.5 percent of Australia's 2023 emissions respectively. We found however that this may translate to significant additional timber flows for the region's processing industry even at lower carbon prices. We estimated an additional 62,600 green metric tonnes of hardwood (1 percent of annual Australian plantation hardwood harvest) and 6.6 million m3 of cumulative softwood (44 percent supply of annual Australian plantation softwood harvest) over a 50-year period at AU$40/t CO2e. However, the results were found to be sensitive to discount rate assumptions. The discussion focuses on the economic and policy factors that may enable/limit the use of carbon markets to expand the Australian plantation forestry estate.

4.
J Sports Sci Med ; 22(3): 549-558, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37711717

RESUMO

Non-local muscle fatigue (NLMF) has been attributed to both physical and mental fatigue. The purpose of this study was to investigate the effects of mental exertion versus unilateral physical fatigue on NLMF. Sixteen recreationally active participants completed a physical task (2-sets of 100-s unilateral knee extension (KE) maximal voluntary isometric contractions (MVIC) with the dominant leg with 40-s recovery between sets, mental task (4-minute Stroop task), and control condition. Before and after each condition, blood lactate was collected, and contralateral 5-s KE, flexion (KF) and bilateral lateral trunk flexors MVIC (measure of trunk stability strength) was performed. Following the post-test 5-s MVICs, participants performed 12 non-dominant KE MVICs with a work-to-rest ratio of 5/10-s. Electromyography was monitored during the MVICs. Neither the 4-minute Stroop test or the unilateral KE physical fatigue intervention adversely affected the non-dominant KE forces or EMG activity with a single MVIC or 12 repetition MVICs. Although the non-dominant KF fatigue index forces and hamstrings EMG were not impaired by the interventions, there was a significant interaction (p = 0.001) small magnitude (d = 0.42) decrease in the non-dominant KF single MVIC force following the contralateral fatigue intervention, albeit with no significant change in hamstrings EMG. This MVIC deficit may be related to the significant decrease in dominant (p = 0.046, d = 2.6) and non-dominant external obliques (p = 0.048, d = 0.57) activation adversely affecting trunk stability. In conclusion, a 4-minute Stroop test or unilateral KE physical fatigue intervention did not impair non-dominant KE single or repeated 12 repetition MVIC forces or EMG activity. The small magnitude deficit in the non-dominant KF single MVIC force following the contralateral fatigue intervention are in accord with the heterogenous findings common in the literature.


Assuntos
Músculos Isquiossurais , Fadiga Muscular , Humanos , Adulto Jovem , Articulação do Joelho , Eletromiografia , Contração Isométrica
5.
Crit Care Med ; 50(3): 398-409, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34612846

RESUMO

OBJECTIVES: To explore candidate prognostic and predictive biomarkers identified in retrospective observational studies (interleukin-6, C-reactive protein, lactate dehydrogenase, ferritin, lymphocytes, monocytes, neutrophils, d-dimer, and platelets) in patients with coronavirus disease 2019 pneumonia after treatment with tocilizumab, an anti-interleukin-6 receptor antibody, using data from the COVACTA trial in patients hospitalized with severe coronavirus disease 2019 pneumonia. DESIGN: Exploratory analysis from a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial. SETTING: Hospitals in North America and Europe. PATIENTS: Adults hospitalized with severe coronavirus disease 2019 pneumonia receiving standard care. INTERVENTION: Randomly assigned 2:1 to IV tocilizumab 8 mg/kg or placebo. MEASUREMENTS AND MAIN RESULTS: Candidate biomarkers were measured in 295 patients in the tocilizumab arm and 142 patients in the placebo arm. Efficacy outcomes assessed were clinical status on a seven-category ordinal scale (1, discharge; 7, death), mortality, time to hospital discharge, and mechanical ventilation (if not receiving it at randomization) through day 28. Prognostic and predictive biomarkers were evaluated continuously with proportional odds, binomial or Fine-Gray models, and additional sensitivity analyses. Modeling in the placebo arm showed all candidate biomarkers except lactate dehydrogenase and d-dimer were strongly prognostic for day 28 clinical outcomes of mortality, mechanical ventilation, clinical status, and time to hospital discharge. Modeling in the tocilizumab arm showed a predictive value of ferritin for day 28 clinical outcomes of mortality (predictive interaction, p = 0.03), mechanical ventilation (predictive interaction, p = 0.01), and clinical status (predictive interaction, p = 0.02) compared with placebo. CONCLUSIONS: Multiple biomarkers prognostic for clinical outcomes were confirmed in COVACTA. Ferritin was identified as a predictive biomarker for the effects of tocilizumab in the COVACTA patient population; high ferritin levels were associated with better clinical outcomes for tocilizumab compared with placebo at day 28.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Tratamento Farmacológico da COVID-19 , COVID-19/epidemiologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Biomarcadores , COVID-19/mortalidade , Método Duplo-Cego , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Tempo de Internação , Masculino , Alta do Paciente , Prognóstico , Respiração Artificial , SARS-CoV-2
6.
Eur J Neurol ; 29(4): 1222-1226, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34941016

RESUMO

BACKGROUND AND PURPOSE: Creutzfeldt-Jakob disease (CJD) is lethal and transmissible. We assessed the impact of the COVID-19 pandemic on UK CJD surveillance. We hypothesized that (i) disruptions prolonged diagnostic latency; (ii) autopsy rates declined; and (iii) COVID-19 infection negatively affected diagnosis, care, and survival. METHODS: We retrospectively investigated the first year of the pandemic, using the preceding year as a comparator, quantifying numbers of individuals assessed by the UK National CJD Research & Surveillance Unit for suspected CJD, time to diagnosis, disease duration, and autopsy rates. We evaluated the impact of COVID-19 status on diagnosis, care, and survival in CJD. RESULTS: A total of 148 individuals were diagnosed with CJD in the pandemic (from a total of 166 individuals assessed) compared to 141 in the comparator (from 145 assessed). No differences were identified in disease duration or time to diagnosis. Autopsy rates were unchanged. Twenty individuals had COVID-19; 60% were symptomatic, and 10% had severe disease. Disruptions in diagnosis and care were frequently identified. Forty percent of COVID-19-positive individuals died; however, COVID-19 status did not significantly alter survival duration in CJD. CONCLUSIONS: The COVID-19 pandemic has not impacted UK CJD case ascertainment or survival, but diagnostic evaluation and clinical care of individuals have been affected.


Assuntos
COVID-19 , Síndrome de Creutzfeldt-Jakob , COVID-19/epidemiologia , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/epidemiologia , Humanos , Pandemias , Assistência ao Paciente , Estudos Retrospectivos , SARS-CoV-2 , Reino Unido/epidemiologia
7.
J Environ Manage ; 302(Pt A): 113964, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34678538

RESUMO

Reforestation is identified as one of the key nature-based solutions to deliver carbon dioxide removal, which will be required to achieve the net zero ambition of the Paris Agreement. However, the potential for sequestration through reforestation is uncertain because climate change is expected to affect the drivers of forest growth. This study used the process-based 3-PG model to investigate the effects of climate change on development of above-ground biomass (AGB), as an indicator of forest growth, in regenerating native forests in southeast Australia. We investigated how changing climate affects AGB, by combining historical data and future climate projections based on 25 global climate models (GCMs) for the Coupled Model Intercomparison Project Phase 6 (CMIP6) under two Shared Socioeconomic Pathways. We found that the ensemble means of 25 GCMs indicated an increase in temperature with large variations in projected rainfall. When these changes were applied in 3-PG, we found an increase in the simulated AGB by as much as 25% under a moderate emission scenario. This estimate rose to 51% under a high emission scenario by the end of the 21st century across nine selected sites in southeast Australia. However, when CO2 response was excluded, we found a large decrease in AGB at the nine sites. Our modelling results showed that the modelled response to elevated atmospheric CO2 (the CO2 fertilization effect) was largely responsible for the simulated increase of AGB (%). We found that the estimates of future changes in the AGB were subject to uncertainties originating from climate projections, future emission scenarios, and the assumed response to CO2 fertilization. Such modelling simulation improves understanding of possible climate change impacts on forest growth and the inherent uncertainties in estimating mitigation potential through reforestation, with implications for climate policy in Australia.


Assuntos
Sequestro de Carbono , Modelos Climáticos , Biomassa , Mudança Climática , Florestas
8.
Clin Infect Dis ; 73(9): e3536-e3544, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33283229

RESUMO

BACKGROUND: Neurological complications of tuberculous meningitis (TBM) often lead to raised intracranial pressure (ICP) resulting in high morbidity and mortality. Measurement of optic nerve sheath diameter (ONSD) by point-of-care ultrasound may aid in the identification of raised ICP in TBM. METHODS: From June 2017 to December 2019, 107 Vietnamese adults with TBM, enrolled in the ACT HIV or LAST ACT trials (NCT03092817, NCT03100786), underwent ONSD ultrasound at ≥1 of days 0, 3, 7, 14, 21, and day ±30 after enrollment. Demographic data, TBM severity grade, HIV coinfection status, and clinical endpoints by 3 months were recorded. ONSD values were correlated with disease severity, baseline brain imaging, cerebrospinal fluid parameters, and clinical endpoints. RESULTS: 267 ONSD ultrasound scans were performed in 107 participants over the first 30 days of treatment, with measurements from 0.38-0.74 cm. Paired baseline ONSD and brain imaging were performed in 63 participants. Higher baseline ONSD was associated with more severe disease and abnormal brain imaging (abnormal imaging 0.55 cm vs 0.50 cm normal imaging, P = .01). Baseline median ONSD was significantly higher in participants who died by 3 months (0.56 cm [15/72]) versus participants who survived by 3 months (0.52 cm [57/72]) (P = .02). Median ONSD was higher at all follow-up times in participants who died by 3 months. CONCLUSIONS: Higher ONSD was associated with increased disease severity, brain imaging abnormalities, and increased death by 3 months. ONSD ultrasound has a potential role as a noninvasive, affordable bedside tool for predicting brain pathology and death in TBM.


Assuntos
Hipertensão Intracraniana , Tuberculose Meníngea , Adulto , Humanos , Hipertensão Intracraniana/diagnóstico por imagem , Pressão Intracraniana , Nervo Óptico/diagnóstico por imagem , Tuberculose Meníngea/diagnóstico por imagem , Ultrassonografia
9.
Glob Chang Biol ; 27(12): 2744-2762, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33759299

RESUMO

Biological sources of carbon sequestration such as revegetation have been highlighted as important avenues to combat climate change and meet global targets by the global community including the Paris Climate Agreement. However, current and projected carbon prices present a considerable barrier to broad-scale adoption of tree planting as a key mitigation strategy. One avenue to provide additional economic and environmental incentives to encourage wider adoption of revegetation is the bundling or stacking of additional co-beneficial ecosystem services that can be realized from tree planting. Using the World's largest land-based carbon credit trading scheme, the Australian Emissions Reduction Scheme (ERF), we examine the potential for three pairs of ecosystem services, where the carbon sequestration value of land use change is paired with an additional co-benefit with strong prospects for local tangible benefits to land owners/providers. Two cases consider agricultural provisioning values that can be realized by the landowners in higher returns: increased pollination services and reduced lamb mortality. The third case examined payments for tree plantings along riparian buffers, with payments to farmers by a water utility who realizes the benefit from reduced treatment cost due to water quality improvements. Economic incentives from these co-benefit case studies were found to be mixed, with avoided treatment costs from water quality paired with carbon payments the most promising, while pollination and reduced lamb mortality paired with carbon payments were unable to bridge the economic gap except under the most optimistic assumptions. We conclude that the economics case for significant land use change are likely to be geographically dispersed and only viable in relatively niche landscape positions in high establishment, high opportunity cost areas even when carbon payments are augmented with the value of co-benefits classified as providing direct and local benefits.


Assuntos
Carbono , Ecossistema , Animais , Austrália , Carbono/análise , Sequestro de Carbono , Conservação dos Recursos Naturais , Ovinos
12.
Plasmid ; 78: 59-64, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25446541

RESUMO

Regulation by non-coding RNAs was found to be widespread among plasmids and other mobile elements of bacteria well before its ubiquity in the eukaryotic world was suspected. As an increasing number of examples was characterised, a common mechanism began to emerge. Non-coding RNAs, such as CopA and Sok from plasmid R1, or RNAI from ColE1, exerted regulation by refolding the secondary structures of their target RNAs or modifying their translation. One regulatory RNA that seemed to swim against the tide was Rcd, encoded within the multimer resolution site of ColE1. Required for high fidelity maintenance of the plasmid in recombination-proficient hosts, Rcd was found to have a protein target, elevating indole production by stimulating tryptophanase. Rcd production is up-regulated in dimer-containing cells and the consequent increase in indole is part of the response to the rapid accumulation of dimers by over-replication (known as the dimer catastrophe). It is proposed that indole simultaneously inhibits cell division and plasmid replication, stopping the catastrophe and allowing time for the resolution of dimers to monomers. The idea of a plasmid-mediated cell division checkpoint, proposed but then discarded in the 1980s, appears to be enjoying a revival.


Assuntos
Escherichia coli/crescimento & desenvolvimento , Escherichia coli/genética , Plasmídeos/genética , Adenosina Trifosfatases/genética , Proteínas de Bactérias/genética , Proteínas de Transporte de Cátions/genética , ATPases Transportadoras de Cobre , Replicação do DNA , Escherichia coli/citologia , Proteínas de Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Indóis/metabolismo , Triptofanase/genética , Triptofanase/metabolismo
13.
Langmuir ; 31(39): 10633-7, 2015 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-26177350

RESUMO

One of the fundamental structures of a cell is the membrane. Self-assembling lipid bilayer vesicles can form the membrane of an artificial cell and could also have plausibly assembled prebiotically for the origin of life. Such cell-like structures, that encapsulate some basic subset of the functions of living cells, are important for research to infer the minimum chemistry necessary for a cell, to help understand the origin of life, and to allow the production of useful species in microscopic containers. We show that the encapsulation of TiO2 particles has the potential to provide the basis for an energy transduction system inside vesicles which can be used to drive subsequent chemistry. TiO2 encapsulated in vesicles can be used to produce biochemical species such as NADH. The NADH is formed from NAD(+) reduction and is produced in a form that is able to drive further enzymatic chemistry. This allows us to link a mineral-based, nonbiological photosystem to biochemical reactions. This is a fundamental step toward being able to use this mineral photosystem in a protocell/artificial cell.


Assuntos
NAD/química , Fotoquímica , Cromatografia em Gel , Cromatografia por Troca Iônica , Espectrofotometria Ultravioleta
14.
Gigascience ; 132024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38442145

RESUMO

BACKGROUND: Spatial information about the location and suitability of areas for native plant and animal species under different climate futures is an important input to land use and conservation planning and management. Australia, renowned for its abundant species diversity and endemism, often relies on modeled data to assess species distributions due to the country's vast size and the challenges associated with conducting on-ground surveys on such a large scale. The objective of this article is to develop habitat suitability maps for Australian flora and fauna under different climate futures. RESULTS: Using MaxEnt, we produced Australia-wide habitat suitability maps under RCP2.6-SSP1, RCP4.5-SSP2, RCP7.0-SSP3, and RCP8.5-SSP5 climate futures for 1,382 terrestrial vertebrates and 9,251 vascular plants vascular plants at 5 km2 for open access. This represents 60% of all Australian mammal species, 77% of amphibian species, 50% of reptile species, 71% of bird species, and 44% of vascular plant species. We also include tabular data, which include summaries of total quality-weighted habitat area of species under different climate scenarios and time periods. CONCLUSIONS: The spatial data supplied can help identify important and sensitive locations for species under various climate futures. Additionally, the supplied tabular data can provide insights into the impacts of climate change on biodiversity in Australia. These habitat suitability maps can be used as input data for landscape and conservation planning or species management, particularly under different climate change scenarios in Australia.


Assuntos
Biodiversidade , Mamíferos , Animais , Austrália
15.
J Neurol ; 271(7): 4216-4226, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38597944

RESUMO

INTRODUCTION: Incorporation of the real-time quaking-induced conversion (RT-QuIC) assays for diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) has transformed diagnosis largely related to its extremely high specificity. However, the test has a c.10% false-negative result and we aim to characterize the clinical features, investigation profile, and molecular subtype in this cohort of patients. METHODS: 250 individuals diagnosed with definite sporadic CJD were identified from the UK National CJD Research and Surveillance Unit from 2012 to 2023. We compared the clinical features and investigation profile in those with a negative CSF RT-QuIC to those with a positive RT-QuIC. RESULTS: 27 individuals (10.8%) were CSF RT-QuIC negative. Median age of onset was younger (62 years vs 68 years, p = 0.002), median disease duration was longer (4.4 months vs 10.5 months, p < 0.001), and these individuals were less likely to present with gait difficulties (73% vs 93%, p = 0.003) or motor symptoms (62% vs 80%, p = 0.04). The sensitivity of electroencephalography and diffusion-weighted MRI were similar in both groups. In those who were RT-QuIC negative, there was an overrepresentation of the VV1 (32% vs 1%) and MM2 molecular subtypes (21% vs 3%). Co-occurring neurodegenerative disease was found in 33% (9/27) of those who were RT-QuIC negative. CONCLUSIONS: Individuals with sporadic CJD and a negative CSF RT-QuIC present with younger age of onset, different clinical features and are over-represented with the VV1 and MM2 subtypes of sporadic CJD. Further work is required to better understand the biochemical properties contributing to RT-QuIC negative results in these cases.


Assuntos
Síndrome de Creutzfeldt-Jakob , Humanos , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Síndrome de Creutzfeldt-Jakob/diagnóstico , Síndrome de Creutzfeldt-Jakob/epidemiologia , Pessoa de Meia-Idade , Masculino , Feminino , Reino Unido/epidemiologia , Idoso , Eletroencefalografia , Idade de Início , Estudos de Coortes
16.
Biochim Biophys Acta ; 1818(7): 1590-4, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22387460

RESUMO

Indole is a bacterial signalling molecule that blocks E. coli cell division at concentrations of 3-5 mM. We have shown that indole is a proton ionophore and that this activity is key to the inhibition of division. By reducing the electrochemical potential across the cytoplasmic membrane of E. coli, indole deactivates MinCD oscillation and prevents formation of the FtsZ ring that is a prerequisite for division. This is the first example of a natural ionophore regulating a key biological process. Our findings have implications for our understanding of membrane biology, bacterial cell cycle control and potentially for the design of antibiotics that target the cell membrane.


Assuntos
Divisão Celular/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Indóis/farmacologia , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Carbonil Cianeto m-Clorofenil Hidrazona/farmacologia , Membrana Celular/metabolismo , Membrana Celular/fisiologia , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Relação Dose-Resposta a Droga , Escherichia coli/citologia , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Citometria de Fluxo , Transporte de Íons/efeitos dos fármacos , Bicamadas Lipídicas/metabolismo , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Microscopia de Fluorescência , Transporte Proteico/efeitos dos fármacos , Ionóforos de Próton/farmacologia
17.
Appl Environ Microbiol ; 79(6): 1948-55, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23335776

RESUMO

The type I polyhydroxyalkanoate synthase from Cupriavidus necator was heterologously expressed in Escherichia coli with simultaneous overexpression of chaperone proteins. Compared to expression of synthase alone (14.55 mg liter(-1)), coexpression with chaperones resulted in the production of larger total quantities of enzyme, including a larger proportion in the soluble fraction. The largest increase was seen when the GroEL/GroES system was coexpressed, resulting in approximately 6-fold-greater enzyme yields (82.37 mg liter(-1)) than in the absence of coexpressed chaperones. The specific activity of the purified enzyme was unaffected by coexpression with chaperones. Therefore, the increase in yield was attributed to an enhanced soluble fraction of synthase. Chaperones were also coexpressed with a polyhydroxyalkanoate production operon, resulting in the production of polymers with generally reduced molecular weights. This suggests a potential use for chaperones to control the physical properties of the polymer.


Assuntos
Aciltransferases/biossíntese , Proteínas de Bactérias/biossíntese , Chaperoninas/biossíntese , Cupriavidus necator/enzimologia , Escherichia coli/genética , Expressão Gênica , Aciltransferases/genética , Proteínas de Bactérias/genética , Chaperoninas/genética , Cupriavidus necator/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo
18.
Chemphyschem ; 14(2): 417-23, 2013 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-23303560

RESUMO

Indole is an important biological signalling molecule produced by many Gram positive and Gram negative bacterial species, including Escherichia coli. Here we study the effect of indole on the electrical properties of lipid membranes. Using electrophysiology, we show that two indole molecules act cooperatively to transport charge across the hydrophobic core of the lipid membrane. To enhance charge transport, induced by indole across the lipid membrane, we use an indole derivative, 4 fluoro-indole. We demonstrate parallels between charge transport through artificial lipid membranes and the function of complex eukaryotic membrane systems by showing that physiological indole concentrations increase the rate of mitochondrial oxygen consumption. Our data provide a biophysical explanation for how indole may link the metabolism of bacterial and eukaryotic cells.


Assuntos
Bactérias Gram-Negativas/química , Bactérias Gram-Positivas/química , Indóis/química , Bicamadas Lipídicas/química , Eletrofisiologia , Bactérias Gram-Negativas/metabolismo , Bactérias Gram-Positivas/metabolismo , Indóis/metabolismo
19.
J Neurol ; 270(2): 1036-1046, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36334135

RESUMO

INTRODUCTION: Sporadic Creutzfeldt-Jakob Disease (sCJD) is the commonest human prion disease, with a median age of onset of 68 years. We characterise the clinical, investigation, and neuropathological features in young individuals with sCJD using data from UK national CJD surveillance. METHODS: Referrals between 2011 and 2021 were examined, with definite (post-mortem confirmed) or probable sCJD cases included. Clinical features, MRI, EEG, CSF RT-QuIC, 14-3-3, PRNP sequencing and neuropathological findings were examined. We compared younger (≤ 50 years age of onset) with older individuals. Records of Non-sCJD referrals were also reviewed. RESULTS: 46 (4%) young individuals were identified (age at onset 25-50) from 1178 cases. 15 (33%) were autopsy confirmed. Psychiatric disturbance (37% vs 22%, p = 0.02) and headache (11% vs 3%, p = 0.01) at presentation, and longer disease duration (by 1.45 months, 95% CI 0.43-2.79, logrank p = 0.007) were commoner. CSF RT-QuIC showed lower sensitivity (82% vs 93%, p = 0.02). There was no difference in sensitivity of MR brain or CSF 14-3-3. There were no significant co-pathologies in autopsy-confirmed cases. For non-sCJD referrals, 41 cases were of other CJD subtypes, and 7 non-prion diagnoses. CONCLUSIONS: Young-onset sCJD is more likely to present with neuropsychiatric symptoms and headache, longer disease duration, and lower sensitivity of RT-QuIC. These findings may be driven by the underlying molecular subtypes. Our results guide the evaluation of younger individuals presenting with rapidly progressive cognitive, neuropsychiatric, and motor decline, and emphasise the need for additional vigilance for atypical features by clinicians and CJD surveillance programmes worldwide.


Assuntos
Síndrome de Creutzfeldt-Jakob , Humanos , Idoso , Síndrome de Creutzfeldt-Jakob/diagnóstico por imagem , Síndrome de Creutzfeldt-Jakob/epidemiologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Reino Unido/epidemiologia
20.
Antimicrob Agents Chemother ; 56(12): 6080-7, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23006760

RESUMO

Despite being genetically monomorphic, the limited genetic diversity within the Mycobacterium tuberculosis complex (MTBC) has practical consequences for molecular methods for drug susceptibility testing and for the use of current antibiotics and those in clinical trials. It renders some representatives of MTBC intrinsically resistant against one or multiple antibiotics and affects the spectrum and consequences of resistance mutations selected for during treatment. Moreover, neutral or silent changes within genes responsible for drug resistance can cause false-positive results with hybridization-based assays, which have been recently introduced to replace slower phenotypic methods. We discuss the consequences of these findings and propose concrete steps to rigorously assess the genetic diversity of MTBC to support ongoing clinical trials.


Assuntos
Antituberculosos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Animais , Interpretação Estatística de Dados , Genótipo , Humanos , Testes de Sensibilidade Microbiana/métodos , Tuberculose/tratamento farmacológico
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