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Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer r

Multiple stressors on biotic interactions: how climate change and alien species interact to affect pollination

Global change may substantially affect biodiversity and ecosystem functioning but little is known about its effects on essential biotic interactions. Since different environmental drivers rarely act in isolation it is important to consider interactive effects. Here, we focus on how two key drivers of anthropogenic environmental change, climate change and the introduction of alien species, affect p

Dual endothelin receptor blockade with tezosentan markedly attenuates hypoxia induced pulmonary vasoconstriction in a porcine model.

Aim: Our aim was to test the hypothesis that dual endothelin receptor blockade with tezosentan attenuates hypoxia induced pulmonary vasoconstriction. Methods: 14 anaesthetised, ventilated pigs, with a mean±SEM weight of 30,5±0,6 kg, were studied, in normoxia (FiO(2) â0,21) and with tezosentan (5mg·kg(-1) ) infusion during (n=7) or before (n=7) hypoxia (FiO(2) ∼0,10). Results: Compared to normoxia,

Tungsten spectroscopy in the EUV range observed at a high-temperature superconducting electron-beam ion trap

We have recorded extreme ultraviolet spectra from W11+ to W15+ ions using a flat-field spectrometer installed at the Shanghai high-temperature superconducting electron-beam ion trap. The spectra were recorded at beam energies ranging between 200 and 400 eV and showed spectral lines and transition arrays in the 170-260 angstrom region. The charge states and spectra transitions were identified by co

S100A9 expressed in ER(-)PgR(-) breast cancers induces inflammatory cytokines and is associated with an impaired overall survival.

Breast cancer is the most common cancer form among women today. Depending on hormone receptor status, breast cancers are divided into different subtypes with vastly varying prognosis. S100A9 is a calcium-binding protein that is associated with inflammation and expressed not only in myeloid cells but also in some tumours. The role for S100A9 in the malignant cells is not well characterised; however

Polyethyleneimine-protein interactions and implications on protein stability

Protein stability assessment of seven model proteins in the presence of low molecular weight polyethyleneimine (PEI, MW 2000 Da) was performed. Thermodynamic stability, monitored by circular dichroism (CD) spectroscopy, showed that the polymer did not have a major effect on the melting temperature (T-m) of the basic proteins - muscle lactate dehydrogenase (LDH), ribonuclease A, lysozyme and cutina

Genetic differentiation and admixture between sibling allopolyploids in the Dactylorhiza majalis complex.

Allopolyploidization often happens recurrently, but the evolutionary significance of its iterative nature is not yet fully understood. Of particular interest are the gene flow dynamics and the mechanisms that allow young sibling polyploids to remain distinct while sharing the same ploidy, heritage and overlapping distribution areas. By using eight highly variable nuclear microsatellites, newly rep

Analytical solutions to two- and three-dimensional periodic flows for numerical model testing

Analytical solutions to 2D depth-averaged (external mode) and fully 3D (internal mode) periodic flows for numerical model testing are presented in this paper. These solutions take into account the effects of the bottom friction, the horizontal turbulent viscosity, and the vertical turbulent viscosity for the case of 3D flow. The key linkage for the modes is the relationship between the bottom fric

Surface Properties of Nanocrystalline PbS Films Deposited at the Water-Oil Interface: A Study of Atmospheric Aging

Nanocrystalline thin films of PbS are obtained in a straightforward reaction by precipitation at the interface between toluene (containing a Pb precursor) and water (containing Na2S). Lead thiobiuret [Pb(SON(CN(i)Pr-2)(2))(2)] and lead diethyldithiocarbamate [Pb(S2CNEt2)(2)] precursors are used. The films are characterized by X-ray diffraction and electron microscopy, revealing typical particle si

Proteasome Inhibition Improves the Muscle of Laminin {alpha}2 Chain Deficient Mice.

Muscle atrophy, a significant characteristic of congenital muscular dystrophy with laminin α2 chain deficiency (also known as MDC1A), occurs by a change in the normal balance between protein synthesis and protein degradation. The ubiquitin-proteasome system plays a key role in protein degradation in skeletal muscle cells. In order to identify new targets for drug therapy against MDC1A, we have inv

Molecular and pathological studies in the posterior interosseous nerve of diabetic and non-diabetic patients with carpal tunnel syndrome

Aims/hypothesis We sought to establish the molecular and pathological changes predisposing diabetic and non-diabetic patients to the development of carpal tunnel syndrome (CTS). Methods The posterior interosseous nerve (PIN) was biopsied in 25 diabetic and 19 non-diabetic patients undergoing carpal tunnel decompression for CTS. Detailed morphometric and immunohistological analyses were performed i

Human TRPA1 is intrinsically cold- and chemosensitive with and without its N-terminal ankyrin repeat domain.

We have purified and reconstituted human transient receptor potential (TRP) subtype A1 (hTRPA1) into lipid bilayers and recorded single-channel currents to understand its inherent thermo- and chemosensory properties as well as the role of the ankyrin repeat domain (ARD) of the N terminus in channel behavior. We report that hTRPA1 with and without its N-terminal ARD (Δ1-688 hTRPA1) is intrinsically

Novel FOXF1 Mutations in Sporadic and Familial Cases of Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins Imply a Role for its DNA Binding Domain

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA an

Linking chlorophyll biosynthesis to a dynamic plastoquinone pool.

Chlorophylls are essential cofactors in photosynthesis. All steps in the chlorophyll pathway are well characterized except for the cyclase reaction in which the fifth ring of the chlorophyll molecule is formed during conversion of Mg-protoporphyrin IX monomethyl ester into Protochlorophyllide. The only subunit of the cyclase identified so far, is AcsF (Xantha-l in barley and Chl27 in Arabidopsis).