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2.
Nat Commun ; 9(1): 1132, 2018 03 19.
Artículo en Inglés | MEDLINE | ID: mdl-29556067

RESUMEN

Many epithelial stem cell populations follow a pattern of stochastic stem cell divisions called 'neutral drift'. It is hypothesised that neutral competition between stem cells protects against the acquisition of deleterious mutations. Here we use a Porcupine inhibitor to reduce Wnt secretion at a dose where intestinal homoeostasis is maintained despite a reduction of Lgr5+ stem cells. Functionally, there is a marked acceleration in monoclonal conversion, so that crypts become rapidly derived from a single stem cell. Stem cells located further from the base are lost and the pool of competing stem cells is reduced. We tested whether this loss of stem cell competition would modify tumorigenesis. Reduction of Wnt ligand secretion accelerates fixation of Apc-deficient cells within the crypt leading to accelerated tumorigenesis. Therefore, ligand-based Wnt signalling influences the number of stem cells, fixation speed of Apc mutations and the speed and likelihood of adenoma formation.


Asunto(s)
Carcinogénesis/metabolismo , Transformación Celular Neoplásica/metabolismo , Mucosa Intestinal/citología , Mucosa Intestinal/metabolismo , Células Madre/citología , Células Madre/metabolismo , Vía de Señalización Wnt , Aciltransferasas/antagonistas & inhibidores , Adenoma/etiología , Adenoma/metabolismo , Adenoma/patología , Proteína de la Poliposis Adenomatosa del Colon/deficiencia , Proteína de la Poliposis Adenomatosa del Colon/genética , Proteína de la Poliposis Adenomatosa del Colon/metabolismo , Animales , Carcinogénesis/efectos de los fármacos , Transformación Celular Neoplásica/efectos de los fármacos , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Inhibidores Enzimáticos/farmacología , Mucosa Intestinal/efectos de los fármacos , Ligandos , Proteínas de la Membrana/antagonistas & inhibidores , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Pirazinas/farmacología , Piridinas/farmacología , Células Madre/efectos de los fármacos , Vía de Señalización Wnt/efectos de los fármacos
3.
Clin Transl Oncol ; 13(12): 848-54, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22126727

RESUMEN

High-resolution intravital imaging (IVM) has proven to be a powerful technique to visualise dynamic processes that are important for tumour progression, such as the interplay between tumour cells and cellular components of the tumour microenvironment. The development of IVM tools, including imaging windows and photo-marking of individual cells, has led to the visualisation of dynamic processes and tracking of individual cells over a time span of days. In order to visualise these dynamic processes, several strategies have been described to develop fluorescent IVM tumour models. Genetic tools to engineer fluorescent tumour cell lines have advanced the applications of cell line-based tumour models to study, for example, changes in behaviour or transcriptional and differentiation state of individual cells in a tumour. In order to study tumour progression, fluorescent genetic mouse models have been engineered that better recapitulate human tumours. These technically challenging tumour models are key in visualising dynamic processes during cancer progression and in the translational aspects of IVM experiments.


Asunto(s)
Modelos Animales de Enfermedad , Imagen Molecular , Neoplasias Experimentales/patología , Animales , Humanos , Procesamiento de Imagen Asistido por Computador , Ratones , Microscopía de Fluorescencia por Excitación Multifotónica
4.
Oecologia ; 111(4): 460-469, 1997 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28308106

RESUMEN

This study aimed to identify functional correlates of seedling leaf nutrient content among woody species and to characterise functional species groups with respect to leaf nutrient attributes. Seedlings of 81 woody species from the temperate zone of western Europe were grown in a standard laboratory environment with standard, near-optimal nutrient availability. Weight-based leaf N content (Nwght) was positively correlated with mean relative growth rate (RGR), but the correlation with mean RGR was tighter when leaf N was expressed on a whole-plant weight basis: leaf nitrogen weight ratio (LNWR). Area-based leaf N content (Narea) was not associated with mean RGR, but was closely correlated with the quotient of saturated leaf weight and leaf area. Weight-based leaf K content (Kwght) was a close correlate of the saturated/dry weight ratio of the foliage. Within the lower range, Kwght corresponded with growth-related nutrient attributes, but higher values appeared to indicate succulence or remobilisable stored water. Functional groups of species and genera could be distinguished with respect to seedling leaf nutrient attributes. Deciduous woody climbers and scramblers had consistently higher leaf Nwght, LNWR and (apparently) leaf Kwght than other deciduous species or genera, and shrubs had higher values than trees. These differences seemed due partly to variation in specific leaf area. Evergreens had consistently higher leaf Narea than deciduous plants, but there were no significant differences in weight-based leaf nutrient attributes between these two groups, possibly because of `luxury nutrient consumption' by the slow-growing evergreens. Another functional group was that of the nitrogen-fixing species, which had consistently high innate leaf Nwght compared to non-N-fixers. The ecological significance of the leaf nutrient attributes in this study is discussed by comparing the seedling data with those from field-collected material, and by brief reference to the natural habitats of the species.

5.
Oecologia ; 77(2): 145-150, 1988 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28310366

RESUMEN

A hypothesis that a dense stand should develop a less uniform distribution of leaf nitrogen through the canopy than an open stand to increase total canopy photosynthesis was tested with experimentally established stands of Lysimachia vulgaris L. The effect of stand density on spatial variation of photon flux density, leaf nitrogen and specific leaf weight within the canopy was examined. Stand density had little effect on the value of the light extinction coefficient, but strongly affected the distribution of leaf nitrogen per unit area within a canopy. The open stand had more uniform distribution of leaf nitrogen than the dense stand. However, different light climates between stands explained only part of the variation of leaf nitrogen in the canopy. The specific leaf weight in the canopy increased with increasing relative photon flux density and with decreasing nitrogen concentration.

8.
Arch Int Physiol Biochim ; 83(3): 563-72, 1975 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-54135

RESUMEN

The lipid content of sea squirts is low, namely less than a half percent of the fresh weight. Lipids consist of about seventy percent of saponifiable lipids and of about twenty percent of non-saponifiable lipids. Both types of these lipids, including sterols, can be synthesized from acetate by these animals. Small amounts of C30 sterols were observed only in Microcosmus sulcatus and Halocynthia papillosa, the species with a low content of C27 sterols and a high content of C28 sterols. In addition these species contained considerable higher amounts of sterols with a double bond at the C22 position than Ciona intestinalis and Styela plicata did.


Asunto(s)
Esteroles/metabolismo , Urocordados/metabolismo , Acetatos/metabolismo , Animales , Colestadienoles/metabolismo , Colestenos/metabolismo , Ciona intestinalis/metabolismo , Lípidos/aislamiento & purificación , Especificidad de la Especie
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