124 research outputs found
Collagen II antibody-induced arthritis in Tg1278TNFko mice: optimization of a novel model to assess treatments targeting human TNFα in rheumatoid arthritis
Expectations and perceptions of primary healthcare professionals regarding their own continuous education in Catalonia (Spain): a qualitative study
Use of 1H and 31P HRMAS to evaluate the relationship between quantitative alterations in metabolite concentrations and tissue features in human brain tumour biopsies
[EN] Quantitative multinuclear high-resolution magic angle
spinning (HRMAS) was performed in order to determine
the tissue pH values of and the absolute metabolite concentrations
in 33 samples of human brain tumour tissue. Metabolite
concentrations were quantified by 1D 1
H and 31P HRMAS
using the electronic reference to in vivo concentrations
(ERETIC) synthetic signal. 1
H–1
H homonuclear and 1
H–31P
heteronuclear correlation experiments enabled the direct assessment
of the 1
H–31P spin systems for signals that suffered from
overlapping in the 1D 1
H spectra, and linked the information
present in the 1D 1
H and 31P spectra. Afterwards, the main
histological features were determined, and high heterogeneity
in the tumour content, necrotic content and nonaffected tissue
content was observed. The metabolite profiles obtained by
HRMAS showed characteristics typical of tumour tissues: rather
low levels of energetic molecules and increased concentrations
of protective metabolites. Nevertheless, these
characteristics were more strongly correlated with the total
amount of living tissue than with the tumour cell contents of
the samples alone, which could indicate that the sampling
conditions make a significant contribution aside from the effect
of tumour development in vivo. The use of methylene diphosphonic
acid as a chemical shift and concentration reference for
the 31P HRMAS spectra of tissues presented important drawbacks
due to its interaction with the tissue. Moreover, the pH
data obtained from 31P HRMAS enabled us to establish a
correlation between the pH and the distance between the
N(CH3)3 signals of phosphocholine and choline in 1
H spectra
of the tissue in these tumour samples.The authors acknowledge the SCSIE-University of Valencia Microscopy Service for the histological preparations. They also acknowledge Martial Piotto (Bruker BioSpin, France) for providing the ERETIC synthetic signal. Furthermore, they acknowledge financial support from the Spanish Government project SAF2007-6547, the Generalitat Valenciana project GVACOMP2009-303, and the E.U.'s VI Framework Programme via the project "Web accessible MR decision support system for brain tumor diagnosis and prognosis, incorporating in vivo and ex vivo genomic and metabolomic data" (FP6-2002-LSH 503094). CIBER-BBN is an initiative funded by the VI National R&D&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund.Esteve Moya, V.; Celda, B.; Martínez Bisbal, MC. (2012). Use of 1H and 31P HRMAS to evaluate the relationship between quantitative alterations in metabolite concentrations and tissue features in human brain tumour biopsies. 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Clamp loader ATPases and the evolution of DNA replication machinery
Clamp loaders are pentameric ATPases of the AAA+ family that operate to ensure processive DNA replication. They do so by loading onto DNA the ring-shaped sliding clamps that tether the polymerase to the DNA. Structural and biochemical analysis of clamp loaders has shown how, despite differences in composition across different branches of life, all clamp loaders undergo the same concerted conformational transformations, which generate a binding surface for the open clamp and an internal spiral chamber into which the DNA at the replication fork can slide, triggering ATP hydrolysis, release of the clamp loader, and closure of the clamp round the DNA. We review here the current understanding of the clamp loader mechanism and discuss the implications of the differences between clamp loaders from the different branches of life
Transmembrane signalling in eukaryotes: a comparison between higher and lower eukaryotes
Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019
Five insights from the Global Burden of Disease Study 2019
The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.Peer reviewe
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
Transmembrane signalling in eukaryotes: a comparison between higher and lower eukaryotes
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