Mechanics and dynamics of X-chromosome pairing at X inactivation

At the onset of X-chromosome inactivation, the vital process whereby female mammalian cells equalize X products with respect to males, the X chromosomes are colocalized along their Xic (X-inactivation center) regions. The mechanism inducing recognition and pairing of the X’s remains, though, elusive. Starting from recent discoveries on the molecular factors and on the DNA sequences (the so-called "pairing sites") involved, we dissect the mechanical basis of Xic colocalization by using a statistical physics model. We show that soluble DNA-specific binding molecules, such as those experimentally identified, can be indeed sufficient to induce the spontaneous colocalization of the homologous chromosomes but only when their concentration, or chemical affinity, rises above a threshold value as a consequence of a thermodynamic phase transition. We derive the likelihood of pairing and its probability distribution. Chromosome dynamics has two stages: an initial independent Brownian diffusion followed, after a characteristic time scale, by recognition and pairing. Finally, we investigate the effects of DNA deletion/insertions in the region of pairing sites and compare model predictions to available experimental data

Risk factors for race-day fatality in flat racing Thoroughbreds in Great Britain (2000 to 2013)

A key focus of the racing industry is to reduce the number of race-day events where horses die suddenly or are euthanased due to catastrophic injury. The objective of this study was therefore to determine risk factors for race-day fatalities in Thoroughbred racehorses, using a cohort of all horses participating in flat racing in Great Britain between 2000 and 2013. Horse-, race- and course-level data were collected and combined with all race-day fatalities, recorded by racecourse veterinarians in a central database. Associations between exposure variables and fatality were assessed using logistic regression analyses for (1) all starts in the dataset and (2) starts made on turf surfaces only. There were 806,764 starts in total, of which 548,571 were on turf surfaces. A total of 610 fatalities were recorded; 377 (61.8%) on turf. In both regression models, increased firmness of the going, increasing racing distance, increasing average horse performance, first year of racing and wearing eye cover for the first time all increased the odds of fatality. Generally, the odds of fatality also increased with increasing horse age whereas increasing number of previous starts reduced fatality odds. In the ‘all starts’ model, horses racing in an auction race were at 1.46 (95% confidence interval (CI) 1.06–2.01) times the odds of fatality compared with horses not racing in this race type. In the turf starts model, horses racing in Group 1 races were at 3.19 (95% CI 1.71–5.93) times the odds of fatality compared with horses not racing in this race type. Identification of novel risk factors including wearing eye cover and race type will help to inform strategies to further reduce the rate of fatality in flat racing horses, enhancing horse and jockey welfare and safety

Effect of Air Injection Depth on Big-bubble Formation in Lamellar Keratoplasty: an Ex Vivo Study

This study evaluated the effect of air injection depth in the big-bubble (BB) technique, which is used for corneal tissue preparation in lamellar keratoplasty. The BB technique was performed on ex vivo human corneoscleral buttons using a depth-sensing needle, based on optical coherence tomography (OCT) imaging technology. The needle tip, equipped with a miniaturized OCT depth-sensing probe, was inserted for air injection at a specified depth. Inside the corneal tissue, our needle obtained OCT line profiles, from which residual thickness below the needle tip was measured. Subjects were classified into Groups I, II, III, and IV based on injection depths of 75-80%, 80-85%, 85-90%, and > 90% of the full corneal thickness, respectively. Both Type I and II BBs were produced when the mean residual thicknesses of air injection were 109.7 +/- 38.0 mu m and 52.4 +/- 19.2 mu m, respectively. Type II BB (4/5) was dominant in group IV. Bubble burst occurred in 1/16 cases of type I BB and 3/16 cases of type II BB, respectively. Injection depth was an important factor in determining the types of BBs produced. Deeper air injection could facilitate formation of Type II BBs, with an increased risk of bubble bursts

Influenza nucleoprotein delivered with aluminium salts protects mice from an influenza virus that expresses an altered nucleoprotein sequence

Influenza virus poses a difficult challenge for protective immunity. This virus is adept at altering its surface proteins, the proteins that are the targets of neutralizing antibody. Consequently, each year a new vaccine must be developed to combat the current recirculating strains. A universal influenza vaccine that primes specific memory cells that recognise conserved parts of the virus could prove to be effective against both annual influenza variants and newly emergent potentially pandemic strains. Such a vaccine will have to contain a safe and effective adjuvant that can be used in individuals of all ages. We examine protection from viral challenge in mice vaccinated with the nucleoprotein from the PR8 strain of influenza A, a protein that is highly conserved across viral subtypes. Vaccination with nucleoprotein delivered with a universally used and safe adjuvant, composed of insoluble aluminium salts, provides protection against viruses that either express the same or an altered version of nucleoprotein. This protection correlated with the presence of nucleoprotein specific CD8 T cells in the lungs of infected animals at early time points after infection. In contrast, immunization with NP delivered with alum and the detoxified LPS adjuvant, monophosphoryl lipid A, provided some protection to the homologous viral strain but no protection against infection by influenza expressing a variant nucleoprotein. Together, these data point towards a vaccine solution for all influenza A subtypes

HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis

Penile verrucous carcinoma is a rare disease and little is known of its aetiology or pathogenesis. In this study we examined cell-cycle proteins expression and correlation with human papillomavirus infection in a series of 15 pure penile verrucous carcinomas from a single centre. Of 148 penile tumours, 15 (10%) were diagnosed as pure verrucous carcinomas. The expression of the cell-cycle-associated proteins p53, p21, RB, p16INK4A and Ki67 were examined by immunohistochemistry. Human papillomavirus infection was determined by polymerase chain reaction to identify a wide range of virus types. The expression of p16INK4A and Ki67 was significantly lower in verrucous carcinoma than in usual type squamous cell carcinoma, whereas the expression of p53, p21 and RB was not significantly different. p53 showed basal expression in contrast to usual type squamous cell carcinoma. Human papillomavirus infection was present in only 3 out of 13 verrucous carcinomas. Unique low-risk, high-risk and mixed viral infections were observed in each of the three cases. In conclusion, lower levels of p16INK4A and Ki67 expressions differentiate penile verrucous carcinoma from usual type squamous cell carcinoma. The low Ki67 index reflects the slow-growing nature of verrucous tumours. The low level of p16INK4A expression and human papillomavirus detection suggests that penile verrucous carcinoma pathogenesis is unrelated to human papillomavirus infection and the oncogenes and tumour suppressor genes classically altered by virus infection.Peer reviewedFinal Accepted Versio

Electrospun poly(vinyl alcohol) nanofibers: effects of degree of hydrolysis and enhanced water stability

ArticlePOLYMER JOURNAL. 42(3):273-276 (2010)journal articl

Formation of Supermassive Black Holes

Evidence shows that massive black holes reside in most local galaxies. Studies have also established a number of relations between the MBH mass and properties of the host galaxy such as bulge mass and velocity dispersion. These results suggest that central MBHs, while much less massive than the host (~ 0.1%), are linked to the evolution of galactic structure. In hierarchical cosmologies, a single big galaxy today can be traced back to the stage when it was split up in hundreds of smaller components. Did MBH seeds form with the same efficiency in small proto-galaxies, or did their formation had to await the buildup of substantial galaxies with deeper potential wells? I briefly review here some of the physical processes that are conducive to the evolution of the massive black hole population. I will discuss black hole formation processes for `seed' black holes that are likely to place at early cosmic epochs, and possible observational tests of these scenarios.Comment: To appear in The Astronomy and Astrophysics Review. The final publication is available at http://www.springerlink.co

Adverse health effects of low levels of perceived control in Swedish and Russian community samples

Background: This cross-sectional study of two middle-aged community samples from Sweden and Russia examined the distribution of perceived control scores in the two populations, investigated differences in individual control items between the populations, and assessed the association between perceived control and self-rated health. Methods: The samples consisted of men and women aged 45–69 years, randomly selected from national and local population registers in southeast Sweden (n = 1007) and in Novosibirsk, Russia (n = 9231). Data were collected by structured questionnaires and clinical measures at a visit to a clinic. The questionnaire covered socioeconomic and lifestyle factors, societal circumstances, and psychosocial measures. Self-rated health was assessed by standard single question with five possible answers, with a cut-off point at the top two alternatives. Results: 32.2 % of Swedish men and women reported good health, compared to 10.3 % of Russian men and women. Levels of perceived control were also significantly lower in Russia than in Sweden and varied by socio-demographic parameters in both populations. Sub-item analysis of the control questionnaire revealed substantial differences between the populations both in the perception of control over life and over health. Logistic regression analysis revealed that the odds ratios (OR) of poor self-rated health were significantly increased in men and women with low perceived control in both countries (OR between 2.61 and 4.26). Conclusion: Although the cross-sectional design does not allow causal inference, these results support the view that perceived control influences health, and that it may mediate the link between socioeconomic hardship and health

Children’s Stories Supporting the Development of Critical Literacy and Intercultural Understanding

This chapter examines the possibilities of applying children’s storybooks in supporting the development of critical literacy as well as intercultural understanding. Valuing and supporting children’s reading is known to provide understanding and empathy towards other human beings. The chapter focuses on theoretical notions related to promoting critical literacies through children’s storybooks, but also includes practical examples of utilizing multicultural children’s stories. The chapter introduces different strategies that parents and teachers can use to support the development of critical literacy, including critical thinking and understanding multiple perspectives. Focus is especially on young children, because they already are capable of moving beyond what is in front of them on the page. Since children’s storybooks offer possibilities for readers to question implicit assumptions about self and others, books can support readers in becoming more culturally aware and sensitive. Consequently, reading storybooks can affect children’s intercultural understanding, and the role of storybooks in children’s moral development – both shaping and changing attitudes – should be seen as transformative.Peer reviewe