The light-activated signaling pathway in SCN-projecting rat retinal ganglion cells.

In mammals, the master circadian clock resides in the suprachiasmatic nuclei (SCN) of the hypothalamus. The period and phase of the circadian pacemaker are calibrated by direct photic input from retinal ganglion cells (RGCs). SCN-projecting RGCs respond to light in the absence of rod- and cone-driven synaptic input, a property for which they are termed intrinsically photosensitive.

Trends in the treatment of breast cancer in Southeast England following the introduction of national guidelines.

There is little published evidence on trends in the treatment of breast cancer in England following the publication of the Calman-Hine report in 1995. Reliable national data are available for women with screen-detected breast cancer, but data on women presenting symptomatically have been difficult to collect. Using data from both a clinical audit database and a population-based cancer register, we show that between 1996 and 2003 the rates of mastectomy and chemotherapy treatment for women with breast cancer in Southeast England have increased marginally, whereas there has been a steady decline in the use of hormone therapy and radiotherapy recorded within 6 months of diagnosis.

Substrate specificity in enzymatic fluorination. The fluorinase from Streptomyces cattleya accepts 2'-deoxyadenosine substrates.

The fluorinase enzyme from Streptomyces cattleya displays an unusual ability in biocatalysis in that it forms a C-F bond. We now report that the enzyme will accept 2'-deoxyadenosine in place of adenosine substrates, and structural evidence reveals a reorganisation in hydrogen bonding to accommodate this substrate series. It emerges from this study that the enzyme does not require a planar ribose conformation of the substrate to catalyse C-F bond formation.

Plant retromer, localized to the prevacuolar compartment and microvesicles in Arabidopsis, may interact with vacuolar sorting receptors.

Receptors for acid hydrolases destined for the lytic compartment in yeast and mammalian cells are retrieved from intermediate, endosomal organelles with the help of a pentameric protein complex called the retromer. We cloned the Arabidopsis thaliana homologs of the three yeast proteins (Vps35, Vps29, and Vps26) constituting the larger subunit of retromer and prepared antisera against them. With these antibodies, we demonstrated the presence of a retromer-like protein complex in salt extracts prepared from Arabidopsis microsomes.

Influence of the MDM2 single nucleotide polymorphism SNP309 on tumour development in BRCA1 mutation carriers.

Background: The MDM2 gene encodes a negative regulator of the p53 tumour suppressor protein. A single nucleotide polymorphism (SNP) in the MDM2 promoter (a T to G exchange at nucleotide 309) has been reported to produce accelerated tumour formation in individuals with inherited p53 mutations. We have investigated the effect of the MDM2 SNP309 on clinical outcome in a cohort of patients with germline mutations of BRCA1.

Evaluation of corneal sensitivity to mechanical and chemical stimuli after LASIK: a pilot study.

Purpose: To evaluate the effect of laser in situ keratomileusis (LASIK) on corneal sensitivity, nerve morphology, and tear film characteristics.

Methods: A cross-sectional study design was used. Eighteen patients (eight men and 10 women with a mean age of 36.

Transcriptional analysis of protective antigen-stimulated PBMC from non-human primates vaccinated with the anthrax vaccine absorbed.

The transcriptional responses in recombinant protective antigen (PA)-stimulated peripheral blood mononuclear cells (PBMCs) from Anthrax Vaccine Absorbed (AVA)-vaccinated rhesus macaques were evaluated using Affymetrix HGU133 Plus 2.0 GeneChips. PBMCs from animals vaccinated at 0, 4, and 26 weeks were harvested at week 30, stimulated with PA, and RNA isolated.

Microfluidic electroporation of robust 10-microm vesicles for manipulation of picoliter volumes.

We present a new way to transport and handle picoliter volumes of analytes in a microfluidic context through electrically monitored electroporation of 10-25 microm vesicles. In this method, giant vesicles are used to isolate analytes in a microfluidic environment. Once encapsulated inside a vesicle, contents will not diffuse and become diluted when exposed to pressure-driven flow.

Crystal structures of Helicobacter pylori type II dehydroquinase inhibitor complexes: new directions for inhibitor design.

The crystal structures of the type II dehydroquinase (DHQase) from Helicobacter pylori in complex with three competitive inhibitors have been determined. The inhibitors are the substrate analogue 2,3-anhydroquinate (FA1), citrate, and an oxoxanthene sulfonamide derivative (AH9095). Despite the very different chemical nature of the inhibitors, in each case the primary point of interaction with the enzyme is via the residues that bind the C1 functionalities of the substrate, 3-dehydroquinate, i.

A dynamic model of Rubisco turnover in cereal leaves.

A simple, improved model of Rubisco synthesis and degradation in cereal leaves is developed using data obtained over the leaf lifespan to return maximum likelihood values for Rubisco proteolysis and biosynthesis. It assumes that the time course of leaf Rubisco content can be described using a log-normal curve, and degradation of the Rubisco pool occurs exponentially. Curve parameters give an insight into how Rubisco dynamics differ among treatments or genotypes; also, statistical analyses can be performed more easily, requiring fewer data and allowing more flexibility in sampling than previous studies.

Operation for adult patent ductus arteriosus using an aortic stent-graft technique.

Patent ductus arteriosus is a condition usually diagnosed and treated in childhood but in some instances is not detected until adult life. Although surgical closure remains the accepted treatment in most cases, stent-grafting has emerged as a possible alternative treatment for persistent ductus arteriosus in the adult. We describe a case of elective repair of a patent ductus arteriosus using an aortic stent-graft technique in a young man.

Golgi-mediated vacuolar sorting of the endoplasmic reticulum chaperone BiP may play an active role in quality control within the secretory pathway.

Quality control in the endoplasmic reticulum (ER) prevents the arrival of incorrectly or incompletely folded proteins at their final destinations and targets permanently misfolded proteins for degradation. Such proteins have a high affinity for the ER chaperone BiP and are finally degraded via retrograde translocation from the ER lumen back to the cytosol. This ER-associated protein degradation (ERAD) is currently thought to constitute the main disposal route, but there is growing evidence for a vacuolar role in quality control.

A 13-year follow-up of patients with breast cancer presenting to a District General Hospital breast unit in southeast England.

The purpose of this clinical cohort study was to examine long-term survival in groups of screen-detected and symptomatic breast cancer patients attending a specialist breast unit, and to determine the factors affecting this survival. A total of 3239 breast cancer cases (1252 screen-detected and 1987 symptomatic) diagnosed between 1989 and 2002 were followed up until the end of 2002, and breast cancer-specific survival was examined in the screened and symptomatic groups, in relation to patient age, tumour size, nodal status and histological grade. Long-term survival in this clinical cohort was high.

A genetic and epidemiologic study of cardiovascular disease in Alaska natives (GOCADAN): design and methods.

This article is a report of the design and methods of the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) Study. This longitudinal, population-based study was initiated to investigate the genetic determinants of cardiovascular disease and its risk factors. Between October 2000 and April 2004, this family study enrolled 1,214 Eskimos from several coastal villages in the Norton Sound region of Western Alaska.

The 50 ml syringe training aid should be utilized immediately before cricoid pressure application.

Objective: Cricoid pressure, applied during rapid sequence induction of anaesthesia, should be performed only by trained staff. Recommended training intervals vary from weekly to every 3 months, but this is unrealistic in day-to-day practice. Performance, when assessed, is often shown to be unacceptable before training.

Vascular lesions of the skull base: endovascular prospective for the otolaryngologist.

With continual advances being made in endovascular equipment and techniques, the role that these image-guided, minimally invasive therapies play in the multidisciplinary management of vascular lesions of the skull base will probably continue to expand. The introduction of emerging technologies, including the development and implementation of implantable bioactive devices such as drug-eluting stents, bioactive embolic coils, and bioactive particulate embolic materials, will provide an increasing array of options for these patients. This article has reviewed the basic concepts of embolization and revascularization for vascular lesions of the skull base encountered by the practicing otolaryngologist.

Protein sorting to the storage vacuoles of plants: a critical appraisal.

The vacuole of plant cells is no longer considered to be a single compartment with multifunctional properties. A lot of evidence now points to the presence of multiple functionally distinct vacuolar compartments, some existing side by side in the same cell. As a consequence, the plant Golgi apparatus is faced with the problem of recognizing proteins destined for lytic and storage vacuoles and segregating them individually from the flow of secretory proteins to the cell surface.

Differential chemosensory function and receptor expression of splanchnic and pelvic colonic afferents in mice.

Lumbar splanchnic (LSN) and sacral pelvic (PN) nerves convey different mechanosensory information from the colon to the spinal cord. Here we determined whether these pathways also differ in their chemosensitivity and receptor expression. Using an in vitro mouse colon preparation, individual primary afferents were tested with selective P2X and transient receptor potential vanilloid receptor 1 (TRPV1) receptor ligands.

Familial seropositive rheumatoid arthritis in North American Native families: effects of shared epitope and cytokine genotypes.

Objective: A number of North American native (NAN) populations have high prevalence rates of both rheumatoid arthritis (RA) and the shared epitope (SE). We examined the phenotype and familial incidence of RA in a NAN population, and investigated how the SE and cytokine genes may affect disease risk within affected families.

Methods: NAN patients with seropositive RA or polyarthritis rheumatoid factor (RF) positive juvenile idiopathic arthritis (JIA) were identified from clinical databases.

Rupture process of the 2004 Sumatra-Andaman earthquake.

The 26 December 2004 Sumatra-Andaman earthquake initiated slowly, with small slip and a slow rupture speed for the first 40 to 60 seconds. Then the rupture expanded at a speed of about 2.5 kilometers per second toward the north northwest, extending 1200 to 1300 kilometers along the Andaman trough.

Glucosamine sulfate and cartilage type II collagen degradation in patients with knee osteoarthritis: randomized discontinuation trial results employing biomarkers.

Objective: To determine whether glucosamine sulfate has an effect on cartilage type II collagen degradation in patients with knee osteoarthritis (OA).

Methods: A randomized, double blind, placebo controlled glucosamine discontinuation trial was conducted in 137 subjects with knee OA, who had had at least moderate relief of knee pain after starting glucosamine. Subjects were randomized to glucosamine at prestudy dose or placebo at an equivalent dose.

Ablation with an internally irrigated radiofrequency catheter: learning how to avoid steam pops.

Objectives: The aim of this study was to assess the feasibility of using electrode temperature, impedance, and power to predict and thereby potentially prevent steam pops during cooled radiofrequency (RF) ablation.

Background: When myocardial temperature reaches 100 degrees C during RF catheter ablation, steam explosions are seen. Saline-cooled RF ablation reduces temperatures at the electrode-tissue interface, but excessive intramyocardial heating still may occur.