Reduced growth and proliferation dynamics of nasal epithelial stem/progenitor cells in nasal polyps in vitro

10.1038/srep04619Scientific Reports4

Rotation of planet-harbouring stars

The rotation rate of a star has important implications for the detectability, characterisation and stability of any planets that may be orbiting it. This chapter gives a brief overview of stellar rotation before describing the methods used to measure the rotation periods of planet host stars, the factors affecting the evolution of a star's rotation rate, stellar age estimates based on rotation, and an overview of the observed trends in the rotation properties of stars with planets.Comment: 16 pages, 4 figures: Invited review to appear in 'Handbook of Exoplanets', Springer Reference Works, edited by Hans J. Deeg and Juan Antonio Belmont

MSH3 polymorphisms and protein levels affect CAG repeat instability in huntington's disease mice

Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)~100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases

Computational modelling of cancerous mutations in the EGFR/ERK signalling pathway

This article has been made available through the Brunel Open Access Publishing Fund - Copyright @ 2009 Orton et al.BACKGROUND: The Epidermal Growth Factor Receptor (EGFR) activated Extracellular-signal Regulated Kinase (ERK) pathway is a critical cell signalling pathway that relays the signal for a cell to proliferate from the plasma membrane to the nucleus. Deregulation of the EGFR/ERK pathway due to alterations affecting the expression or function of a number of pathway components has long been associated with numerous forms of cancer. Under normal conditions, Epidermal Growth Factor (EGF) stimulates a rapid but transient activation of ERK as the signal is rapidly shutdown. Whereas, under cancerous mutation conditions the ERK signal cannot be shutdown and is sustained resulting in the constitutive activation of ERK and continual cell proliferation. In this study, we have used computational modelling techniques to investigate what effects various cancerous alterations have on the signalling flow through the ERK pathway. RESULTS: We have generated a new model of the EGFR activated ERK pathway, which was verified by our own experimental data. We then altered our model to represent various cancerous situations such as Ras, B-Raf and EGFR mutations, as well as EGFR overexpression. Analysis of the models showed that different cancerous situations resulted in different signalling patterns through the ERK pathway, especially when compared to the normal EGF signal pattern. Our model predicts that cancerous EGFR mutation and overexpression signals almost exclusively via the Rap1 pathway, predicting that this pathway is the best target for drugs. Furthermore, our model also highlights the importance of receptor degradation in normal and cancerous EGFR signalling, and suggests that receptor degradation is a key difference between the signalling from the EGF and Nerve Growth Factor (NGF) receptors. CONCLUSION: Our results suggest that different routes to ERK activation are being utilised in different cancerous situations which therefore has interesting implications for drug selection strategies. We also conducted a comparison of the critical differences between signalling from different growth factor receptors (namely EGFR, mutated EGFR, NGF, and Insulin) with our results suggesting the difference between the systems are large scale and can be attributed to the presence/absence of entire pathways rather than subtle difference in individual rate constants between the systems.This work was funded by the Department of Trade and Industry (DTI), under their Bioscience Beacon project programme. AG was funded by an industrial PhD studentship from Scottish Enterprise and Cyclacel

Prenatal hypoxia induces increased cardiac contractility on a background of decreased capillary density.

Background: Chronic hypoxia in utero (CHU) is one of the most common insults to fetal development and may be associated with poor cardiac recovery from ischaemia-reperfusion injury,yet the effects on normal cardiac mechanical performance are poorly understood. Methods: Pregnant female wistar rats were exposed to hypoxia (12% oxygen, balance nitrogen)for days 10–20 of pregnancy. Pups were born into normal room air and weaned normally. At 10 weeks of age, hearts were excised under anaesthesia and underwent retrograde 'Langendorff' perfusion. Mechanical performance was measured at constant filling pressure (100 cm H2O) with intraventricular balloon. Left ventricular free wall was dissected away and capillary density estimated following alkaline phosphatase staining. Expression of SERCA2a and Nitric Oxide Synthases (NOS) proteins were estimated by immunoblotting. Results: CHU significantly increased body mass (P < 0.001) compared with age-matched control rats but was without effect on relative cardiac mass. For incremental increases in left ventricular balloon volume, diastolic pressure was preserved. However, systolic pressure was significantly greater following CHU for balloon volume = 50 μl (P < 0.01) and up to 200 μl (P < 0.05). For higher balloon volumes systolic pressure was not significantly different from control. Developed pressures were correspondingly increased relative to controls for balloon volumes up to 250 μl (P < 0.05).Left ventricular free wall capillary density was significantly decreased in both epicardium (18%; P <0.05) and endocardium (11%; P < 0.05) despite preserved coronary flow. Western blot analysis revealed no change to the expression of SERCA2a or nNOS but immuno-detectable eNOS protein was significantly decreased (P < 0.001) in cardiac tissue following chronic hypoxia in utero. Conclusion: These data offer potential mechanisms for poor recovery following ischaemia, including decreased coronary flow reserve and impaired angiogenesis with subsequent detrimental effects of post-natal cardiac performance

Epstein–Barr virus serology and gastric cancer incidence and survival

Among 185 cases of gastric cancer and 200 controls in Linxian, China, Epstein–Barr virus (EBV) seropositivity was not associated with increased risk of gastric cancer. High EBV nuclear antigen titres were associated with longer survival in cardia cancer cases, possibly due to chance

Bio-anthropological Studies on Human Skeletons from the 6th Century Tomb of Ancient Silla Kingdom in South Korea

In November and December 2013, unidentified human skeletal remains buried in a mokgwakmyo (a traditional wooden coffin) were unearthed while conducting an archaeological investigation near Gyeongju, which was the capital of the Silla Kingdom (57 BCE– 660 CE) of ancient Korea. The human skeletal remains were preserved in relatively intact condition. In an attempt to obtain biological information on the skeleton, physical anthropological, mitochondrial DNA, stable isotope and craniofacial analyses were carried out. The results indicated that the individual was a female from the Silla period, of 155 ± 5 cm height, who died in her late thirties. The maternal lineage belonged to the haplogroup F1b1a, typical for East Asia, and the diet had been more C3- (wheat, rice and potatoes) than C4-based (maize, millet and other tropical grains). Finally, the face of the individual was reconstructed utilizing the skull (restored from osseous fragments) and three-dimensional computerized modelling system. This study, applying multi-dimensional approaches within an overall bio-anthropological analysis, was the first attempt to collect holistic biological information on human skeletal remains dating to the Silla Kingdom period of ancient Korea

FGF2 regulates melanocytes viability through the STAT3-transactivated PAX3 transcription

PAX3 (paired box 3) is known to have an important role in melanocyte development through modulation of microphthalmia-associated transcription factor transcription. Here we found that PAX3 transcriptional activity could be regulated through FGF2 (basic fibroblast growth factor)-STAT3 (signal transducer and activator of transcription 3) signaling in the pigment cells. To study its function in vivo, we have generated a transgenic mouse model expressing PAX3 driven by tyrosinase promoter in a tissue-specific fashion. These animals exhibit hyperpigmentation in the epidermis, evident in the skin color of their ears and tails. We showed that the darker skin color results from both increased melanocyte numbers and melanin synthesis. Together, our study delineated a novel pathway in the melanocyte lineage, linking FGF2-STAT3 signaling to increased PAX3 transcription. Moreover, our results suggest that this pathway might contribute to the regulation of melanocyte numbers and melanin levels, and thereby provide an alternative strategy to induce pigmentation

Tibiofemoral osteoarthritis affects quality of life and function in elderly Koreans, with women more adversely affected than men

<p>Abstract</p> <p>Background</p> <p>The prevalence of knee osteoarthritis(OA) in East Asia is as common for men and even higher for women than that reported in the Caucasian population. Since both population aging and economic growth have taken place at a much faster pace in Asian countries, such as South Korea, one would expect knee OA to become a major public health problem. However, few studies have examined the influence of knee OA on the quality of life (QoL) and physical function in Asia. The aim of this cross-sectional study is to investigate the influence of knee osteoarthritis (OA) on the quality of life (QoL), function and lower extremity physical performance and the gender difference in its influence in elderly community residents in Korea.</p> <p>Methods</p> <p>Participants were from the population-based Hallym Aging Study (HAS). The mean age of the 504 study subjects was 70.2 years and 274 (54%) were women. Demographic information was obtained by questionnaire, and radiographic evaluations consisted of weight-bearing semi-flexed knee radiographs. Self-reported QoL and function were assessed using Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index and Short Form 12-item (SF-12). Performance-based lower extremity function was assessed using the tests consisting of standing balance, usual walk and chair stands. The odds ratios(ORs) for belonging to the worst quartile of WOMAC and physical performance test were calculated by logistic regression analysis in radiographic knee OA compared to non-OA after adjustment of confounders. Scores for SF-12 items were analyzed using general linear models and means adjusted for age, BMI and OA severity were compared.</p> <p>Results</p> <p>Subjects with radiographic knee OA had significantly increased OR for belonging to the worst WOMAC quartile(for pain, 2.13,95% confidence interval[CI], 1.33-3.40, for stiffness, 2.94,95% CI,1.78-4.86, and for function, 2.97, 95% CI,1.83-4.81) and significantly worse SF-12 scores compared to non-OA after adjustment of age, BMI and sex. Women had worse WOMAC and SF-12 scores compared to men, regardless of the presence of radiographic knee OA after adjustment of age, BMI and OA severity. OA subjects had significantly worse performance score for usual walk and chair stands compared to non-OA subjects, but the ORs were no more significant after adjustment of sex.</p> <p>Conclusions</p> <p>Knee OA negatively affects the QoL and physical function in both genders, but women are more adversely affected than men.</p