350 research outputs found
Presence of exon 5-deleted oestrogen receptor in human breast cancer: functional analysis and clinical significance.
A variant form of the human oestrogen receptor (ER) mRNA lacking sequences encoded within exon 5 has been described (Fuqua SAW, Fitzgerald SD, Chamness GC, Tandon AK, McDonnell DP, Nawaz Z, O'Malloy BW, McGuire WL 1991, Cancer Res 51: 105-109). We have examined the expression of the exon 5-deleted ER (HE delta5) mRNA variant in breast biopsies using reverse transcriptase polymerase chain reaction (RT - PCR). HE delta5 mRNA was present in only 13% of non-malignant breast tissues compared with 32% of carcinomas (95% CI, P=0.05). Presence of the HE delta5 mRNA was associated with the presence of immunohistochemically detected ER (P=0.015) and progesterone receptor (PR) (P=0.02). There was a positive correlation between the presence of HE delta5 and disease-free survival (P=0.05), suggesting that the presence of HE delta5 may be an indicator of better prognosis. We have raised a monoclonal antibody specific to the C-terminal amino acids of HE delta5. This antibody recognized the variant but not the wild-type ER protein. We show that HE delta5 protein is present in breast cancer using immunohistochemical techniques. We also analysed trans-activation by HE delta5 in mammalian cells and showed that, in MCF-7 cells, HE delta5 competes with wild-type ER to inhibit ERE-dependent trans-activation. Our results indicate that this variant is unlikely to be responsible for endocrine resistance of breast cancer, but its presence at both the mRNA and protein level suggest that it may, nevertheless, be involved in regulating the expression of oestrogen-responsive genes in breast cancer
Preliminary archaeoentomological analyses of permafrost-preserved cultural layers from the pre-contact Yupâik Eskimo site of Nunalleq, Alaska : implications, potential and methodological considerations
Acknowledgements Site excavation and samples collection were conducted by archaeologists from the University of Aberdeen, with the help of archaeologists and student excavators from the University of Aberdeen University of Alaska Fairbanks and Bryn Mawr College, Kuskokwim Campus, College of Rural Alaska and residents of Quinhagak and Mekoryuk. This study is funded through AHRC grant to the project âUnderstanding Cultural Resilience and Climate Change on the Bering Sea through Yupâik Ecological Knowledge, Lifeways, Learning and Archaeologyâ to Rick Knecht, Kate Britton and Charlotta Hillderal (University of Aberdeen; AH/K006029/1). Thanks are due to Qanirtuuq Inc. and Quinhagak, Alaska for sampling permissions and to entomologists working at the CNC in Ottawa for allowing access to reference collections of beetles, lice and fleas. Yves Bousquet, Ales Smetana and Anthony E. Davies are specially acknowledged for their help with the identification of coleopteran specimens. Finally, we would also like to thank Scott Elias for useful comments on the original manuscript.Peer reviewedPublisher PD
The impacts of environmental warming on Odonata: a review
Climate change brings with it unprecedented rates of increase in environmental temperature, which will have major consequences for the earth's flora and fauna. The Odonata represent a taxon that has many strong links to this abiotic factor due to its tropical evolutionary history and adaptations to temperate climates. Temperature is known to affect odonate physiology including life-history traits such as developmental rate, phenology and seasonal regulation as well as immune function and the production of pigment for thermoregulation. A range of behaviours are likely to be affected which will, in turn, influence other parts of the aquatic ecosystem, primarily through trophic interactions. Temperature may influence changes in geographical distributions, through a shifting of species' fundamental niches, changes in the distribution of suitable habitat and variation in the dispersal ability of species. Finally, such a rapid change in the environment results in a strong selective pressure towards adaptation to cope and the inevitable loss of some populations and, potentially, species. Where data are lacking for odonates, studies on other invertebrate groups will be considered. Finally, directions for research are suggested, particularly laboratory studies that investigate underlying causes of climate-driven macroecological patterns
Astrometric and Timing Effects of Gravitational Waves from Localized Sources
A consistent approach for an exhaustive solution of the problem of
propagation of light rays in the field of gravitational waves emitted by a
localized source of gravitational radiation is developed in the first
post-Minkowskian and quadrupole approximation of General Relativity. We
demonstrate that the equations of light propagation in the retarded
gravitational field of an arbitrary localized source emitting quadrupolar
gravitational waves can be integrated exactly. The influence of the
gravitational field on the light propagation is examined not only in the wave
zone but also in cases when light passes through the intermediate and near
zones of the source. Explicit analytic expressions for light deflection and
integrated time delay (Shapiro effect) are obtained accounting for all possible
retardation effects and arbitrary relative locations of the source of
gravitational waves, that of light rays, and the observer. It is shown that the
ADM and harmonic gauge conditions can both be satisfied simultaneously outside
the source of gravitational waves. Their use drastically simplifies the
integration of light propagation equations and those for the motion of light
source and observer in the field of the source of gravitational waves, leading
to the unique interpretation of observable effects. The two limiting cases of
small and large values of impact parameter are elaborated in more detail.
Explicit expressions for Shapiro effect and deflection angle are obtained in
terms of the transverse-traceless part of the space-space components of the
metric tensor. We also discuss the relevance of the developed formalism for
interpretation of radio interferometric and timing observations, as well as for
data processing algorithms for future gravitational wave detectors.Comment: 43 pages, 4 Postscript figures, uses revtex.sty, accepted to Phys.
Rev. D, minor corrections in formulae regarding algebraic sign
Toll-like Receptor 4, F4/80 And Pro-inflammatory Cytokines In Intestinal And Mesenteric Fat Tissue Of Crohn's Disease.
Crohn's disease (CD) is a chronic intestinal ailment with a multifactorial etiology, whose incidence has increased during the last three decades. Recently, a role for mesenteric fat has been proposed in CD pathophysiology, since fat hypertrophy is detected nearby the affected intestinal area; however, there are few studies on this aspect. To evaluate inflammatory activity in intestinal mucosa and mesenteric fat tissue of patients with CD and controls. Ten patients with ileocecal CD and 16 patients with non-inflammatory disease (control groups) were studied. The specimens were snap-frozen and the expression of TLR-4, F4/80, IL1-ÎČ and IL-6 were determined by immunoblot of protein extracts. TLR4 RNA level were measured using RT-PCR. The t Test was applied (p<0.05). The local ethical committee approved the study. The intestinal mucosa of CD group had significantly higher protein levels of TLR-4, F4/80, IL-1ÎČ and IL-6 than the controls. The gene expression of TLR4 was lower in the intestinal mucosa of CD compared to the control group. Regard the mesenteric fat tissue, there was no statistical difference related to TLR-4, F4/80, IL-1ÎČ and IL-6 proteins expression. These findings may result from an up-regulation of macrophage activation and intracellular pathways activated by bacterial antigens, which are more important in intestinal mucosa than fat tissue in CD patients. This may represent an anomalous regulation of innate immunity and could contribute to the production of proinflammatory mediators and disease development.698-10
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