34 research outputs found
Genetic Rat Models of Parkinson's Disease
Parkinson's disease (PD) is a neurodegenerative disease characterized by a specific loss of dopaminergic neurons. Although the vast majority of PD cases are idiopathic in nature, there is a subset that contains genetic links. Of the genes that have been linked to PD, α-synuclein and leucine-rich repeat kinase 2 have been used to develop transgenic rat models of the disease. In this paper we focused on the various transgenic rat models of PD in terms of their ability to mimic key symptoms of PD in a progressive manner. In general, we found that most of these models provided useful tools for the early stages of PD, but the development of new transgenic rats that present significant neuropathologic and motoric deficits in a progressive manner that more accurately mimics PD is needed
Direct interaction of TrkA/CD44v3 is essential for NGF-promoted aggressiveness of breast cancer cells
Background
CD44 is a multifunctional membrane glycoprotein. Through its heparan sulfate chain, CD44 presents growth factors to their receptors. We have shown that CD44 and Tropomyosin kinase A (TrkA) form a complex following nerve growth factor (NGF) induction. Our study aimed to understand how CD44 and TrkA interact and the consequences of inhibiting this interaction regarding the pro-tumoral effect of NGF in breast cancer.
Methods
After determining which CD44 isoforms (variants) are involved in forming the TrkA/CD44 complex using proximity ligation assays, we investigated the molecular determinants of this interaction. By molecular modeling, we isolated the amino acids involved and confirmed their involvement using mutations. A CD44v3 mimetic peptide was then synthesized to block the TrkA/CD44v3 interaction. The effects of this peptide on the growth, migration and invasion of xenografted triple-negative breast cancer cells were assessed. Finally, we investigated the correlations between the expression of the TrkA/CD44v3 complex in tumors and histo-pronostic parameters.
Results
We demonstrated that isoform v3 (CD44v3), but not v6, binds to TrkA in response to NGF stimulation. The final 10 amino acids of exon v3 and the TrkA H112 residue are necessary for the association of CD44v3 with TrkA. Functionally, the CD44v3 mimetic peptide impairs not only NGF-induced RhoA activation, clonogenicity, and migration/invasion of breast cancer cells in vitro but also tumor growth and metastasis in a xenograft mouse model. We also detected TrkA/CD44v3 only in cancerous cells, not in normal adjacent tissues.
Conclusion
Collectively, our results suggest that blocking the CD44v3/TrkA interaction can be a new therapeutic option for triple-negative breast cancers
JMIR Res Protoc
Background: Breast cancer is the most frequent cancer in women in industrialized countries. Lifestyle and environmental factors, particularly endocrine-disrupting pollutants, have been suggested to play a role in breast cancer risk. Current epidemiological studies, although not fully consistent, suggest a positive association of breast cancer risk with exposure to several International Agency for Research on Cancer Group 1 air-pollutant carcinogens, such as particulate matter, polychlorinated biphenyls (PCB), dioxins, Benzo[a]pyrene (BaP), and cadmium. However, epidemiological studies remain scarce and inconsistent. It has been proposed that the menopausal status could modify the relationship between pollutants and breast cancer and that the association varies with hormone receptor status. Objective: The XENAIR project will investigate the association of breast cancer risk (overall and by hormone receptor status) with chronic exposure to selected air pollutants, including particulate matter, nitrogen dioxide (NO2), ozone (O3), BaP, dioxins, PCB-153, and cadmium. Methods: Our research is based on a case-control study nested within the French national E3N cohort of 5222 invasive breast cancer cases identified during follow-up from 1990 to 2011, and 5222 matched controls. A questionnaire was sent to all participants to collect their lifetime residential addresses and information on indoor pollution. We will assess these exposures using complementary models of land-use regression, atmospheric dispersion, and regional chemistry-transport (CHIMERE) models, via a Geographic Information System. Associations with breast cancer risk will be modeled using conditional logistic regression models. We will also study the impact of exposure on DNA methylation and interactions with genetic polymorphisms. Appropriate statistical methods, including Bayesian modeling, principal component analysis, and cluster analysis, will be used to assess the impact of multipollutant exposure. The fraction of breast cancer cases attributable to air pollution will be estimated. Results: The XENAIR project will contribute to current knowledge on the health effects of air pollution and identify and understand environmental modifiable risk factors related to breast cancer risk. Conclusions: The results will provide relevant evidence to governments and policy-makers to improve effective public health prevention strategies on air pollution. The XENAIR dataset can be used in future efforts to study the effects of exposure to air pollution associated with other chronic conditions
The Southern Hemisphere ascidian Asterocarpa humilis is unrecognised but widely established in NW France and Great Britain
8 pĂĄginas, 1 figura, 1 tabla.Non-native ascidians can be a major
feature of sessile communities, particularly in artificial
habitats, but may be overlooked because of poor
understanding of speciesâ taxonomy and biogeographic
status. The styelid unitary ascidian Asterocarpa
humilis, up to now only reported in the Southern
Hemisphere, has been found on the coast of NW
France from St Malo to Quiberon, on the south coast of
England from Falmouth to Brighton, and also in north
Wales. The first documented occurrence was in 2005
in Brittany, but the species was found to be relatively
widespread at a regional scale and common in many
places during surveys in 2009, 2010 and 2011. It has
possibly been present but overlooked for some time.
The identification based on morphology was confirmed
by comparison with specimens from New
Zealand, within the speciesâ presumed native range,
by molecular barcoding based on mitochondrial (COI)
and nuclear (18S) genes.The collaboration between the Station Biologique de Roscoff
and the Marine Biological Association was supported by the
Interreg IVa Marinexus programme and the AXA Research
Fund Marine Aliens and Climate Change projectPeer reviewe
Enhanced Near-Infrared Photoresponse for Efficient Organic Solar Cells Using Hybrid Plasmonic Nanostructures
SSRN preprint article https://ssrn.com/abstract=4108410Nonfullerene organic solar cells (OSCs) have recently made remarkable progress as one of the most promising next-generation photovoltaic technologies. Still, it is highly desirable to enhance the light harvesting for the sake of photoactive layer with a limited thickness. In this work, we developed efficient nonfullerene OSCs through incorporating hybrid plasmonic metal nanostructures (MNS) consisted of gold nanobipyramids (AuNBPs) and gold nanospheres (AuNSs). The synergistic localized surface plasmon resonance (LSPR) of hybrid MNS has been predesigned to perfectly match with the absorption range of nonfullerene photoactive layer especially in the near-infrared (NIR) region, subsequently delivering enhanced light harvesting and photo-response. The plasmonic enhancement mechanisms were systematically investigated by theoretical simulations and various experimental measurements, showing that hybrid MNS exhibited significant broadband near field enhancement and scattering effect as well as the advantage in electrical aspect to facilitate the charge extraction and transport. As a result, the power conversion efficiency (PCE) was improved from 15.46% to 16.62% for OSCs based on PM6:Y6 due to the synergistic plasmonic effect of hybrid MNS. Overall, this work paves the way for using plasmonic MNS with tunable optical properties as an alternative approach for the development of high-performance OSCs
Expression of Heme Oxygenase-1 in Neural Stem/Progenitor Cells as a Potential Mechanism to Evade Host Immune Response
International audienc