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Detection and precise mapping of germline rearrangements in BRCA1, BRCA2, MSH2, and MLH1 using zoom-in array comparative genomic hybridization (aCGH).

Disease-predisposing germline mutations in cancer susceptibility genes may consist of large genomic rearrangements that are challenging to detect and characterize using standard PCR-based mutation screening methods. Here, we describe a custom-made zoom-in microarray comparative genomic hybridization (CGH) platform of 60mer oligonucleotides. The 4 x 44 K array format provides high-resolution covera

Impact of grafted serotonin and dopamine neurons on development of L-DOPA-induced dyskinesias in parkinsonian rats is determined by the extent of dopamine neuron degeneration.

Previous studies have shown that serotonin neurons play an important role in the induction and maintenance of l-DOPA-induced dyskinesia in animals with lesion of the nigrostriatal dopamine system. Patients with Parkinson's disease that receive transplants of foetal ventral mesencephalic tissue, the graft cell preparation is likely to contain, in addition to dopamine neurons, serotonin neurons that

Perimetry, tonometry and epidemiology: the fate of glaucoma management.

This is the lecture that I gave when I was awarded Acta Ophthalmologica's gold medal and honorary award at the Nordic Ophthalmological Congress in Reykjavik in August 2010. I was inspired by Jared Diamond's famous book: Guns, Germs, and Steel, The Fates of Human Societies. Diamond is professor of geography and physiology at the University of California, Los Angeles. In this book, which won the Pul

Glucose Generates Coincident Insulin and Somatostatin Pulses and Antisynchronous Glucagon Pulses from Human Pancreatic Islets.

The kinetics of insulin, glucagon and somatostatin release was studied in human pancreatic islets. Batches of 10-15 islets were perifused and the hormones measured with RIA in 30-sec fractions. Increase of glucose from 3 to 20 mM resulted in a brief pulse of glucagon coinciding with suppression of basal insulin and somatostatin release. There was a subsequent drop of glucagon release concomitant w

High-precision mapping of protein protein interfaces: an integrated genetic strategy combining en masse mutagenesis and DNA-level parallel analysis on a yeast two-hybrid platform.

Understanding networks of protein-protein interactions constitutes an essential component on a path towards comprehensive description of cell function. Whereas efficient techniques are readily available for the initial identification of interacting protein partners, practical strategies are lacking for the subsequent high-resolution mapping of regions involved in protein-protein interfaces. We pre

Intramolecular dynamics of low molecular weight protein tyrosine phosphatase in monomer-dimer equilibrium studied by NMR: A model for changes in dynamics upon target binding

Low molecular weight protein tyrosine phosphatase (LMW-PTP) dimerizes in the phosphate-bound state in solution with a dissociation constant of K-d = 1.5(+/-0.1) mM and an off-rate on the order of 10(4) s(-1).H-1 and N-15 NMR chemical shifts identify the dimer interface, which is in excellent agreement with that observed in the crystal structure of the dimeric S19A mutant. Two tyrosine residues of

A combination of magnetic permeability detection with nanometer-scaled superparamagnetic tracer and its application for one-step detection of human urinary albumin in undiluted urine

A rapid (6.5 min) and simple one-step magnetic immunoassay (MIA) has been developed for analysis of human urinary albumin in near patient settings. Polyclonal rabbit anti-human albumin was used as a capture antibody and monoclonal mouse anti-human albumin as a detection antibody in a two-site immunometric assay requiring no additional washing procedures. The polyclonal anti-human albumin was conju

Expression pattern analysis of transcribed HERV sequences is complicated by ex vivo recombination

Background: The human genome comprises numerous human endogenous retroviruses ( HERVs) that formed millions of years ago in ancestral species. A number of loci of the HERV-K(HML-2) family are evolutionarily much younger. A recent study suggested an infectious HERV-K(HML-2) variant in humans and other primates. Isolating such a varian t from human individuals would be a significant finding for huma

Logarithmic norms and nonlinear DAE stability

Logarithmic norms are often used to estimate stability and perturbation bounds in linear ODEs. Extensions to other classes of problems such as nonlinear dynamics, DAEs and PDEs require careful modifications of the logarithmic norm. With a conceptual focus, we combine the extension to nonlinear ODEs [15] with that of matrix pencils [10] in order to treat nonlinear DAEs with a view to cover certain

On geodesic exponential maps of the Virasoro group

We study the geodesic exponential maps corresponding to Sobolev type right-invariant (weak) Riemannian metrics mu((k)) (k >= 0) on the Virasoro group Vir and show that for k >= 2, but not for k = 0, 1, each of them defines a smooth Frechet chart of the unital element e is an element of Vir. In particular, the geodesic exponential map corresponding to the Korteweg - de Vries (KdV) equation ( k = 0)

Patients consulting with students in general practice: Survey of patients' satisfaction and their role in teaching.

Background: General practice is a common setting for medical students' clinical training. However, little is known about patients' views on consulting with senior students. Aims: To investigate patients' attitudes to consultations conducted by senior students alone, before patients saw their GP; and to enquire into patients' perception of their teaching role. Method: Adult patients attending 50 he

Pattern of somatic androgen receptor gene mutations in patients with hormone-refractory prostate cancer.

Progression to hormone-refractory growth of prostate cancer has been suggested to be mediated by androgen receptor (AR) gene alterations. We analyzed AR for mutations and amplifications in 21 locally recurrent prostate carcinomas treated with orchiectomy, estrogens, or a combination of orchiectomy and estramustine phosphate using fluorescence in situ hybridization, single-strand conformation polym

Demonstration of functionally different interactions between phospholipase C-gamma and the two types of platelet-derived growth factor receptors

Phosphorylated tyrosine residues in receptor tyrosine kinases serve as binding sites for signal transduction molecules. We have identified two autophosphorylation sites, Tyr-988 and Tyr-1018, in the platelet-derived growth factor (PDGF) alpha-receptor carboxyl-terminal tail, which are involved in binding of phospholipase C-gamma (PLC-gamma). The capacities of the Y988F and Y1018F mutant PDGF alpha