The role of cathepsin C in Papillon-Lefèvre syndrome, prepubertal periodontitis, and aggressive periodontitis

We have previously reported that loss-of-function mutations in the cathepsin C gene (CTSC) result in Papillon Lefevre syndrome, an autosomal recessive condition characterized by palmoplantar keratosis and early,onset, severe periodontitis. Others have also reported CTSC mutations in patients with severe prepubertal periodontitis, but without any skin manifestations. The possible role of CTSC variants in more common types of non-mendelian, early-onset, severe periodontitis ("aggressive periodontitis") has not been investigated. In this study, we have investigated the role of CTSC in all three conditions. We demonstrate that PLS is genetically homogeneous and the mutation spectrum that includes three novel mutations (c.386T>A/p. V129E, c.935A>G/p.Q312R, and c.1235A>G/p.Y412C) in 21 PLS families (including eight from our previous study) provides an insight into structure-function relationships of CTSC. Our data also suggest that a complete loss-of-function appears to be necessary for the manifestation of the phenotype, making it unlikely that weak CTSC mutations are a cause of aggressive periodontitis. This was confirmed by analyses of the CTSC activity in 30 subjects with aggressive periodontitis and age-sex matched controls, which demonstrated that there was no significant difference between these two groups (1,728.7 +/- SD 576.8 mu moles/mg/min vs. 1,678.7 +/- SD 527.2 mu moles/mg/min, respectively, p = 0.73). CTSC mutations were detected in only one of two families with prepubertal periodontitis; these did not form a separate functional class with respect to those observed in classical PLS. The affected individuals in the other prepubertal periodontitis family not only lacked CTSC mutations, but in addition did not share the haplotypes at the CTSC locus. These data suggest that prepubertal periodontitis is a genetically heterogeneous disease that, in some families, just represents a partially penetrant PLS. (C) 2004 Wiley-Liss, Inc.

Hope in the Most Unlikely Spaces: Thawra and the Contemporary Arabic Novel

In the early to mid-twentieth century, many novelists in the Arab world championed Arab nationalism in their literary reflections on the social and political struggles of their countries, depicting these struggles primarily in terms of spatial binaries that pitted the Arab world against the West, even as they imported Western literary models of progress and modernity into their own work. The intense experience of national awakening that infused their writing often placed these authors at a literary disadvantage, for in their literature, all too often the depth and diversity of Arabic cultures and the complexity of socio-political struggles across the Arab world were undermined by restrictive spatial discourses that tended to focus only on particular versions of Arab history and on a seemingly unifying national predicament. Between the Arab defeat of 1967 and the present day, however, an increasing number of Arab authors have turned to less restrictive forms of spatial discourse in search of a language that might offer alternative narratives of hope beyond the predictable, and seemingly thwarted, trajectories of nationalism. This study traces the ways in which contemporary Arab authors from Egypt and the Sudan have endeavoured to re-think and re-define the Arab identity in ever-changing spaces where elements of the local and the global, the traditional and the modern, interact both competitively and harmoniously. I examine the spatial language and the tropes used in three Arabic novels, viewing them through the lens of thawra (revolution) in both its socio-political and artistic manifestations. Linking the manifestations of thawra in each text to different scenes of revolution in the Arab world today, in Chapter Two, I consider how, at a stage when the Sudan of the sixties was both still dealing with colonial withdrawal and struggling to establish itself as a nation-state, the geographical and textual landscapes of Tayeb Salih‟s Season of Migration to the North depict the ongoing dilemma of the Sudanese identity. In Chapter Three, I examine Alaa iii al-Aswany‟s The Yacoubian Building in the context of a socially diseased and politically corrupt Egypt of the nineties: social, political, modern, historical, local, and global elements intertwine in a dizzyingly complex spatial network of associations that sheds light on the complicated reasons behind today‟s Egyptian thawra. In Chapter Four, the final chapter, Gamal al-Ghitani‟s approach to his Egypt in Pyramid Texts drifts far away from Salih‟s anguished Sudan and al-Aswany‟s chaotic Cairo to a realm where thawra manifests itself artistically in a sophisticated spatial language that challenges all forms of spatial hegemony and, consequently, old and new forms of social, political, and cultural oppression in the Arab world.

MARKERS OF CARDIOVASCULAR DYSFUNCTION AFTER PREGNANCIES COMPLICATED BY PRE-ECLAMPSIA

Pre-eclampsia (PE) is a hypertensive disorder of pregnancy characterized by maternal systemic endothelial dysfunction. While the clinical manifestations resolve soon after delivery, a large body of epidemiological evidence indicates significant long-term maternal risk for cardiovascular disease (CVD) after PE. The mechanisms by which PE and future CVD are associated are unclear, although shared constitutional risk factors likely contribute to the features of endothelial dysfunction characteristic to both. We postulate that PE offers a window of opportunity for the identification of unique markers of dysfunction in the earliest stages of disease that may be used to validate cardiovascular risk screening in the early postpartum period. The studies presented in this thesis provide evidence of changes in circulating factors in women with a recent history of PE. Using blood samples collected within the first year of pregnancy, unique patterns of microRNA expression, enrichment of coagulation system proteins and endothelial progenitor cell dysfunction were described. Many of the described changes appear to be independent of cardiovascular risk. In addition to alterations in circulating factors however, longitudinal postpartum assessments demonstrated that microvascular and cardiac abnormalities were evident in the early periods postpartum after a pre-eclamptic pregnancy. Collectively, the data presented in this thesis reveal that physiological alterations in women with a recent history of PE are not necessarily dependent on clinical parameters of cardiovascular risk, and that resulting dysfunction may be demonstrated within the first year postpartum. Importantly, the biomarkers presented herein are all demonstrated elsewhere in the literature to benefit from lifestyle modification and risk reduction. In closing, the findings of this thesis support a need for cardiovascular risk screening based on obstetrical history, namely after pregnancies complicated by PE.

Social exclusion and social capital: A comparison and critique

Social exclusion and social capital are widely used concepts with multiple and ambiguous definitions. Their meanings and indicators partially overlap, and thus they are sometimes used interchangeably to refer to the inter-relations of economy and society. Both ideas could benefit from further specification and differentiation. The causes of social exclusion and the consequences of social capital have received the fullest elaboration, to the relative neglect of the outcomes of social exclusion and the genesis of social capital. This article identifies the similarities and differences between social exclusion and social capital. We compare the intellectual histories and theoretical orientations of each term, their empirical manifestations and their place in public policy. The article then moves on to elucidate further each set of ideas. A central argument is that the conflation of these notions partly emerges from a shared theoretical tradition, but also from insufficient theorizing of the processes in which each phenomenon is implicated. A number of suggestions are made for sharpening their explanatory focus, in particular better differentiating between cause and consequence, contextualizing social relations and social networks, and subjecting the policy 'solutions' that follow from each perspective to critical scrutiny. Placing the two in dialogue is beneficial for the further development of each.

The Hindered Self-Help: Housing Policies, Politics And Poverty In Kolkata, India

The housing dimension in Kolkata has been changing in recent years. Since 1991, the city has initiated housing reform that has taken many forms and manifestations characterized by the reduction in social allocation, cutbacks in public funding and promotion of a real estate culture in close partnership between the state and private actors. There has been increasing concern about the housing condition of the poor in the deserted slums and bustee settlements amidst the evident ‘poor blindness’ in housing and investment policies. Against this background the paper discusses self-help housing in Kolkata. It seeks to answer a simple question – why the concept of self-help has not been recognised as a viable policy option for a city with widespread slums and bustee settlements by visiting the complex urban context of Kolkata set within the city's politics, poverty and policies. The paper concludes that there is a need to recognise the existing structural duality in the city and support self-help housing as a parallel housing approach.

'Last Vegas?'

This article, and the research out of which it springs, has a number of points of origin; it may also have more than one point of conclusion even as it argues that the current manifestation of Las Vegas could well be read as its last. This is not to say that Las Vegas will cease to create its new versions of itself; after all, this is one of the main sustaining factors of Las Vegas’ success in the last two decades as a new Strip on Las Vegas Boulevard has arisen from the demolitions and redesigns of the original Las Vegas Strip of the 1950s and 1960s. What is argued for here is a reading of Vegas as a terminal point within American culture and particularly within its visual realms. Las Vegas’ place within the dynamics of American visual and exhibition culture comes as the latest in a sequence which, since the nineteenth century, has included among its manifestations World’s Fairs, side shows, freak shows and travelling carnivals. America’s experiments in the visual domain have been updated in both the twentieth- and twenty-first centuries in a variety of spectacular forms and entertainment zones (Disneyland, EPCOT, the new Las Vegas). Vegas is the ultimate incarnation of a carnivalised display culture, the city’s casino Strip reclothed primarily as a theme park for digital camera-toting tourists than as a resort for dedicated gamblers. The possibility that the current incarnation of Las Vegas of late 2009 and 2010 will be the last Vegas hovers as a spectral remnant of the economic downturn and financial collapse of 2008, marked by the unfinished skeletons of projected new casino hotels on Las Vegas Boulevard and by a sudden reversal of fortune for the nation’s favourite gaming location.

Maternal imagination: Reconceiving first impressions

The concept of maternal imagination, whereby the disordered thoughts and impressions of pregnant women are used to explain the prevalence of monstrous births, was at its height during the early modern period, albeit it with many prior and subsequent manifestations. Against a more familiar, and enduring, medieval and Renaissance context of supernatural agency at work, the device of MI was seen as a 'naturalistic' model more in keeping with the advent of Enlightenment scientism. Nonetheless, the debate around it was ferocious and indicative more of a masculine anxiety about female desire and generative power than of a concern for impartial explanation. In problematizing a simply descriptive approach to archival material, my purpose is to explore what is at stake in the competing discourses that seem alternately, and even simultaneously, to empower and degrade the place of the mother. What is the unspoken of an historical debate that prefigures our contemporary interest in feminine excess?

Identifying early signs of aggression: psychometric properties of the cardiff infant contentiousness scale

Our aim was to develop an age-appropriate measure of early manifestations of aggression. We constructed a questionnaire about normative developmental milestones into which a set of items measuring infants’ use of physical force against people and expressed anger were included. These items comprise the Cardiff Infant Contentiousness Scale (CICS). Evidence for the reliability and validity of the CICS is provided from analyses of a sample of N5310 British infants, assessed at a mean age of 6 months as part of a larger longitudinal study of the development of aggression. The informants’ CICS ratings demonstrated reasonable levels of internal consistency and interrater agreement. Informants’ ratings were validated by observations of infants’ distress in response to restraint in a car seat. Longitudinal analyses revealed that contentiousness was stable over time and that contentiousness at 6 months predicted infants’ later use of force with peers. When used in the company of other methods, the simple four-item CICS scale could serve as a useful screen for early manifestations of aggressiveness in human infants.

Arteriolar involvement in the microvascular lesions of diabetic retinopathy: Implications for pathogenesis

Diabetic retinopathy (DR) is the most widespread complication of diabetes mellitus and a major cause of blindness in the working population of developed countries. The clinicopathology of the diabetic retina has been extensively studied, although the relative contribution of the various biochemical and molecular sequelae of hyperglycemia remains ill defined. Many neural and microvascular abnormalities occur in the retina of short-term diabetic animals but it remains uncertain how closely these acute changes relate to chronic human disease. It is important to determine the relationship between alterations observed within the first weeks or months in short-term aminal models, and human disease, where clinically manifest retinopathy occurs only after durations of diabetes measured in years. This review is focused on the retinal microvasculature, although it should be appreciated that pathological changes in this system often occur in parallel with abnormalities in the neural parenchyma that may be derivative or even causal. Nevertheless, it is useful to reevaluate the microvascular lesions that are manifest in the retina during diabetes in humans and long-term animal models, since in addition to providing useful clues to the pathogenic basis of DR as a disease entity, it is in the deterrence of such changes that the efficacy of any novel treatment regimes will be measured. In particular, an emphasis will be placed on the relatively unappreciated role of arteriolar dysfunction in the clinical manifestations and pathology of this disease.

Massive stars exploding in a He-rich circumstellar medium - III. SN 2006jc: infrared echoes from new and old dust in the progenitor CSM

We present near- (NIR) and mid-infrared (MIR) photometric data of the Type Ibn supernova (SN) 2006jc obtained with the United Kingdom Infrared Telescope (UKIRT), the Gemini North Telescope and the Spitzer Space Telescope between days 86 and 493 post-explosion. We find that the IR behaviour of SN 2006jc can be explained as a combination of IR echoes from two manifestations of circumstellar material. The bulk of the NIR emission arises from an IR echo from newly condensed dust in a cool dense shell (CDs) produced by the interaction of the ejecta Outward shock with a dense shell of circumstellar material ejected by the progenitor in a luminous blue variable (LBV)-like outburst about two years prior to the SN explosion. The CDs dust mass reaches a modest 3.0 x 10(-4) M-circle dot by day 230. While dust condensation within a CDs formed behind the ejecta inward shock has been proposed before for one event (SN 1998S), SN 2006jc is the first one showing evidence for dust condensation in a CDs formed behind the ejecta outward shock in the circumstellar material. At later epochs, a substantial and growing contribution to the IR fluxes arises from an IR echo from pre-existing dust in the progenitor wind. The mass of the pre-existing circumstellar medium (CSM) dust is at least similar to 8 x 10(-3) M-circle dot. This paper therefore adds to the evidence that mass-loss from the progenitors of core-collapse SNe could be a major source of dust in the Universe. However, yet again, we see no direct evidence that the explosion of an SN produces anything other than a very modest amount of dust.

Religion, Human Rights, Equality and the Public Sphere

This article distinguishes three different conceptions of the relationship between religion and the public sphere. The reconciliation of these different aspects of freedom of religion can be seen to give rise to considerable difficulties in practice, and the legal and political systems of several Western European countries are struggling to cope. Four recurring issues that arise in this context are identified and considered: what is a 'religion' and what are 'religious' beliefs and practices for the purposes of the protection of 'freedom of religion', together with the closely related issue of who decides these questions; what justification there is for a provision guaranteeing freedom of religion at all; which manifestations of religious association are so unacceptable as to take the association outside the protection of freedom of religion altogether; and what weight should be given to freedom of religion when this freedom stands opposed to other values. It is argued that the scope and meaning of human rights in this context is anything but settled and that this gives an opportunity to those who support a role for religion in public life to intervene.

Reproductive disruption in Fasciola hepatica associated with incomplete efficacy of a new experimental formulation of triclabendazole

The objective of the present study was to analyse the reproductive viability (using histopathologic studies) of Fasciola hepatica from cattle artificially infected and treated subcutaneously with a new experimental formulation of triclabendazole (8 mg/kg b.w.). The results of the efficacy controlled test, which only takes into account the presence of live adult flukes, indicated that, whilst in the control group (n=7)533 live specimens were recovered, in the test groups (doses of 8 and 12 mg/kg b.w.) only 195 and 47 adults were recovered, respectively. These numbers indicate efficacies of 69% and 95.6%, respectively. It was observed in that dose of 8 mg/kg b.w. some specimens remained viable, but they were infertile, which severely compromises the biological cycle of the trematode. in the testis tubules of flukes treated with the low dose of TCBZ (8 mg/kg), very few cells were present and the vitelline follicles were markedly reduced in size and each follicle contained very few cells. This would have direct implications for the pathogenesis of the parasitosis since the remaining parasites would produce little clinical-productive manifestations, would stimulate the immune response and would find it difficult to establish future re-infestations/re-infections. Consequently, these observations will also prompt a review of certain methodological and interpretative aspects related to efficacy tests, where the only discriminative factor is the reduction of the adult parasite load. On one hand, histopathological studies could be complementary to the efficacy controlled test for TCBZ or other BZD formulations. (C) 2010 Elsevier B.V. All rights reserved.

Anatomy and physiology of the human eye: effects of mucopolysaccharidoses disease on structure and function - a review

P>The current paper provides an overview of current knowledge on the structure and function of the eye. It describes in depth the different parts of the eye that are involved in the ocular manifestations seen in the mucopolysaccharidoses (MPS). The MPS are a group of rare inheritable lysosomal storage disorders characterized by the accumulation of glycosaminoglycans (GAGs) in cells and tissues all over the body, leading to widespread tissue and organ dysfunction. GAGs also tend to accumulate in several tissues of the eye, leading to various ocular manifestations affecting both the anterior (cornea, conjunctiva) and the posterior parts (retina, sclera, optic nerve) of the eye.

Scurvy in the Great Irish Famine: Evidence of Vitamin C Deficiency From a Mid-19th Century Skeletal Population

Scurvy has increasingly been recognized in archaeological populations since the 1980s but this study represents the first examination of the paleopathological findings of scurvy in a known famine population. The Great Famine (1845–1852) was a watershed in Irish history and resulted in the death of one million people and the mass emigration of just as many. It was initiated by a blight which completely wiped out the potato—virtually the only source of food for the poor of Ireland. This led to mass starvation and a widespread occurrence of infectious and metabolic diseases. A recent discovery of 970 human skeletons from mass burials dating to the height of the famine in Kilkenny City (1847–1851) provided an opportunity to study the skeletal manifestations of scurvy—a disease that became widespread at this time due to the sudden lack of Vitamin C which had previously almost exclusively been provided by the potato. A three-scale diagnostic reliance approach has been employed as a statistical aid for diagnosing the disease in the population. A biocultural approach was adopted to enable the findings to be contextualized and the etiology and impact of the disease explored. The results indicate that scurvy indirectly influenced famine-induced mortality. A sex and stature bias is evident among adults in which males and taller individuals displayed statistically significantly higher levels of scorbutic lesions. The findings have also suggested that new bone formation at the foramen rotundum is a diagnostic criterion for the paleopathological identification of scurvy, particularly among juveniles. Am J Phys Anthropol, 2012. © 2012 Wiley Periodicals, Inc.

Fetal brain function in response to maternal alcohol consumption: Early evidence of damage

Background: Studies of the adverse neurobehavioral effects of maternal alcohol consumption on the fetus have been largely confined to the postnatal period, after exposure to alcohol has finished. This study explored the brain function of the fetus, at the time of exposure to alcohol, to examine its effect on information processing and stability of performance. Methods: Five groups of fetuses, defined by maternal alcohol consumption patterns, were examined: control (no alcohol); moderate (5 to 10 units/wk either drunk evenly across the week or as a binge, in 2 to 3 days); heavy (20+ units/wk drunk evenly or as a binge). Fetal habituation performance was examined on 3 occasions, separated by 7 days, beginning at 35 weeks of gestation. The number of trials required to habituate on each test session and the difference in performance across test sessions were recorded. Results: Fetuses exposed to heavy binge drinking required significantly more trials to habituate and exhibited a greater variability in performance across all test sessions than the other groups. Maternal drinking, either heavily but evenly or moderately as a binge, resulted in poorer habituation, and moderate binge drinking resulted in greater variability compared with no, or even, drinking. Conclusions: Decreased information processing, reflected by poorer habituation, and increased variability in performance may reflect the initial manifestations of structural damage caused by alcohol to the brain. These results will lead to a greater understanding of the effects of alcohol on the fetus's brain, enable the antenatal identification of fetal alcohol spectrum disorders, and lead to the early implementation of better management strategies. © 2012 by the Research Society on Alcoholism.


--------------------------------------------------------------------------------

Reaxys Database Information|