Epidermal growth factor-induced ovarian carcinoma cell migration is associated with JAK2/STAT3 signals and changes in the abundance and localization of α6β1 integrin

Peritoneal dissemination of ovarian carcinoma is mediated by epithelial&ndash;mesenchymal interconversions leading to the disruption of cell&ndash;cell contact and modulation of cell&ndash;extracellular matrix (ECM) interactions. The present study was designed to evaluate the effects of epidermal growth factor (EGF) as a modulator of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) signalling and changes in integrin expression during the process similar to EMT. A fibroblastic morphology with reduced intercellular cell contacts and increased cell motility was observed in ovarian cancer cell lines in response to EGF and was concomitant with the up regulation of EMT-associated N-cadherin and vimentin expression. These changes were accompanied by an increase in &alpha;2, &alpha;6 and &beta;1 integrin subunits and activation of JAK2 and STAT3 signalling which was suppressed by a specific JAK2 inhibitor. Consistent with the suppression of STAT3 activity, N-cadherin and vimentin expression were abrogated and was coherent with the loss of cell motility and the expression of &alpha;6 and &beta;1 integrin subunits. Neutralizing antibodies against &alpha;6 and &beta;1 subunits inhibited cancer cell migration. A strong correlation between the expression of N-cadherin, vimentin and JAK2/STAT3 levels were detected in high-grade ovarian tumors and was consistent with the previously reported enhanced expression of &alpha;6 integrin subunit in advanced tumors [Ahmed N, Riley C, Oliva K, Rice G, Quinn M. Ascites induces modulation of &alpha;6&beta;1 integrin and urokinase plasminogen activator receptor expression and associated functions in ovarian carcinoma. British Journal of Cancer 2005;92:1475&ndash;85]. Our data incorporating the clinical samples and the cancer cell lines is the first to demonstrate that JAK2/STAT3 pathway may be one of the downstream events in EMT-like process and &alpha;6&beta;1 integrin-mediated signalling in ovarian carcinomas.<br />

Guest editorial : In Journal of networks, v.6 n.1

In recent years, networking of computing devices has been going through rapid evolution and thus continuing to be an ever expanding area of importance. Different technologies, protocols, services and usage patterns have contributed to the major research interests in this area of computer science. The current special issue is an effort to bring forward some of these interesting developments that are being pursued by researchers at present in different parts of the globe. Our objective is to provide the readership with some insight into the latest innovations in computer networking through this.

Production of inulinase from Kluyveromyces marxianus YS-1 using root extract of Asparagus racemosus

Roots of <i>Asparagus racemosus</i> were used as a source of inulin for the production of inulinase from <i>Kluyveromyces marxianus</i> YS-1. Root extract prepared at 10 kg/cm² for 10 min showed the maximum production of inulinase. Various parameters of fermentation have been examined in order to improve overall enzyme yield. Inulinase yield of 40.5 IU/mL in an optimized medium containing inulin (3.5%), beef extract (0.5%), MnSO₄ (0.5 mM), CoCl₂(0.05 mM), SDS (0.4 mM) and pH 6.5 at 30 &deg;C under agitation (150 rpm) for 60 h has been obtained at shake flask level. After optimization the enzyme production has been increased 6.1 times at flask level. In a bioreactor (working volume 1 L) fermentation medium containing 4% inulin has shown maximum inulinase production (47.3 IU/mL) under optimized parameters of 200 rpm, 0.75 vvm aeration at 30 &deg;C after 60 h.<br />

Training in flexible, intensive insulin management to enable dietary freedom in people with type 1 diabetes : dose adjustment for normal eating (DAFNE) randomised controlled trial

<b>Objectives:</b> To evaluate whether a course teaching flexible intensive insulin treatment combining dietary freedom and insulin adjustment can improve both glycaemic control and quality of life in type 1 diabetes.<br /><br /><b>Design:</b> Randomised design with participants either attending training immediately (immediate DAFNE) or acting as waiting list controls and attending &ldquo;delayed DAFNE&rdquo; training 6 months later.<br />Setting: Secondary care diabetes clinics in three English health districts.<br /><br /><b>Participants: </b>169 adults with type 1 diabetes and moderate or poor glycaemic control.<br /><br /><b>Main outcome measures:</b> Glycated haemoglobin (HbA1c), severe hypoglycaemia, impact of diabetes on quality of life (ADDQoL).<br /><br /><b>Results:</b> At 6 months, HbA1c was significantly better in immediate DAFNE patients (mean 8.4%) than in delayed DAFNE patients (9.4%) (t=6.1, P&lt;0.0001). The impact of diabetes on dietary freedom was significantly improved in immediate DAFNE patients compared with delayed DAFNE patients (t=&minus;5.4, P&lt;0.0001), as was the impact of diabetes on overall quality of life (t=2.9, P&lt;0.01). General wellbeing and treatment satisfaction were also significantly improved, but severe hypoglycaemia, weight, and lipids remained unchanged. Improvements in &ldquo;present quality of life&rdquo; did not reach significance at 6 months but were significant by 1 year.<br /><br /><b>Conclusion:</b> Skills training promoting dietary freedom improved quality of life and glycaemic control in people with type 1 diabetes without worsening severe hypoglycaemia or cardiovascular risk. This approach has the potential to enable more people to adopt intensive insulin treatment and is worthy of further investigation.<br />

Methylmercury-induced inhibition of paraoxonase-1 (PON1)-implications for cardiovascular risk

Methylmercury (MeHg) has been associated with increased risk for cardiovascular disease in some but not all epidemiology studies. These inconsistent results may stem from the fact that exposure typically occurs in the context of fish consumption, which is also associated with cardioprotective factors such as omega-3 fatty acids. Mechanistic information may help to understand whether MeHg represents a risk to cardiovascular health. MeHg is a pro-oxidant that inactivates protein sulfhydryls. These biochemical effects may diminish critical antioxidant defense mechanism(s) involved in protecting against atherosclerosis. One such defense mechanism is paraoxonase-1 (PON1), an enzyme present on high-density lipoproteins and that prevents the oxidation of blood lipids and their deposition in vascular endothelium. PON1 is potentially useful as a clinical biomarker of cardiovascular risk, as well as a critical enzyme in the detoxification of certain organophosphate oxons. MeHg and other metals are known to inhibit PON1 activity in vitro. MeHg is associated with lowered serum PON1 activity in a fish-eating population. The implications of lowering PON1 are evaluated by predicting the shift in PON1 population distribution induced by various doses of MeHg. An MeHg dose of 0.3 &mu;g/kg/d is estimated to decrease the population average PON1 level by 6.1% and to increase population risk of acute cardiovascular events by 9.7%. This evaluation provides a plausible mechanism for MeHg-induced cardiovascular risk and suggests means to quantify the risk. This case study exemplifies the use of upstream disease biomarkers to evaluate the additive effect of chemical toxicity with background disease processes in assessing human risk.

An investigation into the effect of play-based instruction on the development of play skills and oral language: a 6-month longitudinal study

The current study investigated the influence of a play-based curriculum on the development of pretend play skills and oral language in children attending their first year of formal schooling. In this quasi-experimental design, two groups of children were followed longitudinally across the first 6&thinsp;months of their first year at school. The children in the experimental group were attending a school with a play-based curriculum; the children in the control group were attending schools following a traditional curriculum. A total of 54 children (Time 1 M age&thinsp;=&thinsp;5;6, range: 4;10&ndash;6;2&thinsp;years) completed standardised measures of pretend play and narrative language skills upon school entry and again 6&thinsp;months later. The results showed that the children in the play-based group significantly improved on all measures, whereas the children in the traditional group did not. A subset of the sample of children (N&thinsp;=&thinsp;28, Time 1 M age&thinsp;=&thinsp;5;7, range: 5;2 &ndash; 6;1) also completed additional measures of vocabulary and grammar knowledge, and a test of non-verbal IQ. The results suggested that, in addition to improving play skills and narrative language ability, the play-based curriculum also had a positive influence on the acquisition of grammar.