The absolute configuration for inthomycin C: revision of previously published work with a reinstatement of the (3R)-configuration for (-)-inthomycin C.

Stereochemical evidence is presented to demonstrate that (-)-inthomycin C has (3R)- and not (3S)-stereochemistry. Careful reappraisal of the previously published work2-5 now indicates that the Hatakeyama, Hale, Ryu, and Taylor teams all have synthesized (-)-(3R)-inthomycin C. The newly measured [α]D of pure (-)-(3R)-inthomycin C (98% ee) is -7.

Regulation of TGF-β1-driven differentiation of human lung fibroblasts: emerging roles of cathepsin B and cystatin C.

Lung matrix homeostasis partly depends on the fine regulation of proteolytic activities. We examined the expression of human cysteine cathepsins (Cats) and their relative contribution to TGF-β1-induced fibroblast differentiation into myofibroblasts. Assays were conducted using both primary fibroblasts obtained from patients with idiopathic pulmonary fibrosis and human lung CCD-19Lu fibroblasts.

Asymmetric total synthesis of (+)-inthomycin C via O-directed free radical alkyne hydrostannation with Ph3SnH and catalytic Et3B: reinstatement of the Zeeck-Taylor (3R)-structure for (+)-inthomycin C.

A new pathway to (+)-inthomycin C is reported that exploits an O-directed free radical hydrostannation reaction on (-)-12 and a Stille cross-coupling as key steps. Significantly, the latter process was effected on 19 where a gauche-pentane repulsive interaction could interfere. Our stereochemical studies on the alkynol (-)-12 and the enyne (+)-7 confirm that Ryu and Hatakeyama's (3S)-stereochemical revision of (+)-inthomycin C is invalid and that Zeeck and Taylor's original (3R)-stereostructure for (+)-inthomycin C is correct.

Synthesis of the C(7)-C(22) sector of (+)-acutiphycin via O-directed double free radical alkyne hydrostannation with Ph3SnH/Et3B, double I-Sn exchange, and double Stille coupling.

Herein a new double O-directed free radical hydrostannation reaction is reported on the structurally complex dialkyldiyne 11. Through our use of a conformation-restraining acetal to help prevent stereocenter-compromising 1,5-H-atom abstraction reactions by vinyl radical intermediates, the two vinylstannanes of 10 were concurrently constructed with high stereocontrol using Ph3SnH/Et3B/O2. Distannane 10 was thereafter elaborated into the bis-vinyl iodide 9 via O-silylation and double I-Sn exchange; double Stille coupling of 9, O-desilylation, and oxidation thereafter furnished 8.

Androgens and estrogens stimulate ribosome biogenesis in prostate and breast cancer cells in receptor dependent manner.

Ribosome biogenesis is a fundamental cellular process intimately linked to cell growth and proliferation, which is upregulated in most of cancers especially in aggressive cancers. In breast and prostate cancers steroid hormone receptor signalling is the principal stimulus for cancer growth and progression. Here we investigated the link between estrogen and androgen receptor signalling and the initial stage of ribosome biogenesis - transcription of rRNA genes.

Old drug, new target: ellipticines selectively inhibit RNA polymerase I transcription.

Transcription by RNA polymerase I (Pol-I) is the main driving force behind ribosome biogenesis, a fundamental cellular process that requires the coordinated transcription of all three nuclear polymerases. Increased Pol-I transcription and the concurrent increase in ribosome biogenesis has been linked to the high rates of proliferation in cancers. The ellipticine family contains a number of potent anticancer therapeutic agents, some having progressed to stage I and II clinical trials; however, the mechanism by which many of the compounds work remains unclear.

Assessing and training standing balance in older adults: a novel approach using the 'Nintendo Wii' Balance Board.

Older adults, deemed to be at a high risk of falling, are often unable to participate in dynamic exercises due to physical constraints and/or a fear of falling. Using the Nintendo 'Wii Balance Board' (WBB) (Nintendo, Kyoto, Japan), we have developed an interface that allows a user to accurately calculate a participant's centre of pressure (COP) and incorporate it into a virtual environment to create bespoke diagnostic or training programmes that exploit real-time visual feedback of current COP position. This platform allows researchers to design, control and validate tasks that both train and test balance function.

Expectations and voluntary attrition in nursing students.

This paper presents a series of findings generated during a larger study which aimed to develop a theoretical understanding of the reasons why nursing students voluntarily leave pre-registration nursing programmes. In this study, significant incongruence was found to exist between student expectations of pre-registration nursing programmes and the reality of these programmes following entry. The resulting dissonance was identified as an important factor in student decisions to voluntarily withdraw.

Nature or nurture; BMI and blood pressure at 90. Findings from the Belfast Elderly Longitudinal Free-living Aging STudy (BELFAST).

Hypertension is a key risk factor for stroke, cardiovascular disease and dementia. Although the link between weight, sodium and hypertension is established in younger people, little is known about their inter-relationship in people beyond 80 years of age. Associations between blood pressure, anthropometric indices and sodium were investigated in 495 apparently healthy, community-living participants (age 90, SD 4.

An in vitro study of human lens epithelial cell adhesion to intraocular lenses with and without a fibronectin coating.

Purpose: To demonstrate differences in human lens epithelial cell adhesion to different intraocular lens biomaterials in vitro and to determine whether these differences can be influenced by coating the intraocular lens surface with commercially available fibronectin.

Methods: A prospective laboratory-based study comparing human lens epithelial cell adhesion to silicone (n=18), polymethylmethacrylate (PMMA; n=18), and acrylic (n=18) intraocular lenses in vitro. The three types of intraocular lenses were then coated with fibronectin: silicone (n=6), PMMA (n=6), and acrylic (n=6).

Behaviour of the three-spined stickleback, Gasterosteous aculeatus (Gasterosteidae, Teleostei) in the multispecies freshwater biomonitor: a validation of automated recordings at three levels of ammonia pollution.

The validity of using an automated online biomonitoring system, the multispecies freshwater biomonitor (MFB), in recording the physiological and behavioural activities of the three-spined stickleback Gasterosteous aculeatus, is assessed. The direct impact of the alternating electrical current generated by the impedance converter on fish activity was measured using a repeated measures design, machine on/machine off. Twelve subjects were used in each of three experimental groups: (1).

Mortality in Barrett's oesophagus: results from a population based study.

Background: Patients with Barrett's oesophagus have an increased risk of oesophageal adenocarcinoma but this cancer only accounts for a small proportion of deaths in these patients. Other causes of death are reportedly raised in this group. We examined cause specific mortality among individuals in a population based Barrett's oesophagus register.

Dysfunction of p53 in photocarcinogenesis.

The tumor suppressor protein p53 plays a critical role in the orchestration of the cellular responses to a variety of genotoxic and cytotoxic stresses. Mutations or functional inactivation of p53 seriously compromise these cellular processes and foster tumor development. p53 is the most frequently mutated gene in human cancers and over 90% of human non-melanoma skin cancers (NMSC) harbour p53 mutation.

Secular changes in blood pressure in childhood, adolescence and young adulthood: systematic review of trends from 1948 to 1998.

One plausible reason for the decline in cardiovascular disease (CVD), and in particular stroke, in the last century is population reductions in blood pressure. Blood pressure tracks from childhood into adulthood, and early-life blood pressure is associated with increased cardiovascular risk but few studies have reported on blood pressure trends among young individuals who are free of CVD and not taking antihypertensive medication. Knowledge of such trends may improve understanding of the causes of hypertension and enhance prevention.

In situ high temperature microscopy study of the surface oxidation and phase transformations in titanium alloys.

Two popular commercial titanium alloys, Ti-6Al-4V and Ti-6Al-2Sn-4Zr-2Mo-0.08Si, were used for in situ high temperature microscopy study. The experiments were performed on an optical microscope equipped with high temperature stage using both normal and florescence lights.

BRCA1 regulates the interferon gamma-mediated apoptotic response.

BRCA1 is a tumor suppressor gene implicated in transcriptional regulation. We have generated cell lines with inducible expression of BRCA1 as a tool to identify downstream targets that may be important mediators of BRCA1 function. Oligonucleotide array-based expression profiling identified 11 previously described interferon regulated genes that were up-regulated following inducible expression of BRCA1.

Antisense Bcl-2 oligonucleotide uptake in human transitional cell carcinoma.

Objectives: Antisense oligonucleotides (AO) downregulate Bcl-2 protein expression in various tumours if good target cell uptake is achieved. In this study, uptake of FITC labelled AO (FITC-AO) directed at Bcl-2 was examined in: (1) the RT4 bladder tumour cell line; (2) normal pig urothelium, and (3) human superficial bladder tumours.

Methods: In the RT4 cell line, uptake of FITC-AO, FITC-scrambled and FITC-sense oligonucleotides were quantified by flow cytometry at 4-hour intervals over 24 h.

Isotopic composition of inorganic carbon as an indicator of benzoate degradation by pseudomonas putida: temperature, growth rate and pH effects.

Degradation experiments of benzoate by Pseudomonas putida resulted in enzymatic carbon isotope fractionations. However, isotopic temperature effects between experiments at 20 and 30 degrees C were minor. Averages of the last three values of the CO(2) isotopic composition (delta(13)C(CO2(g))) were more negative than the initial benzoate delta(13)C value (-26.

The effect of alcohol on zinc absorption : Studies using rat small intestinal perfusion.

Two methods of intestinal perfusion are described and used to study the effecs of alcohol on zinc absorption in the rat small intestine. The first method used perfusion of the lumen of the rat small intestinein situ without interruption of the vascular supply. During perfusion with a zinc-containing medium (with and without alcohol), alcohol was found to have no effect on net zinc uptake from the lumen of the intestine.