Early onset sebaceous carcinoma

<p>Abstract</p> <p>Background</p> <p>Ocular sebaceous carcinoma can masquerade as benign lesions resulting in delay of diagnosis. Early recognition is even more difficult in young patients where the disease rarely occurs. Here, we provide a clinicopathological correlation of ocular sebaceous carcinoma in a young individual lacking history of hereditary cancer or immunosuppression.</p> <p>Findings</p> <p>A detailed histopathological study including <it>p53 </it>DNA sequencing was performed on an aggressive sebaceous carcinoma presenting in a healthy 32 year-old Caucasian woman. She had no history of retinoblastoma, evidence for a hereditary cancer syndrome, or radiation therapy. However, she potentially was at risk for excessive UV light exposure. A detailed review of the literature is also provided.</p> <p>A moderately well differentiated sebaceous carcinoma was established histopathologically arising from the meibomian gland of the upper eyelid. In most areas, the cytoplasm contained small but distinct Oil-red-O positive vacuoles. Direct sequencing of <it>p53 </it>identified a G:C→A:T mutation at a dipyrimidine site. The mutation results in substitution of arginine for the highly conserved glycine at residue 199 located at the p53 dimer-dimer interface. Energy minimization structural modeling predicts that G199R will neutralize negative charges contributed by nearby inter- and intramonomeric glutamate residues.</p> <p>Discussion</p> <p>This study points to the importance of recognizing that sebaceous carcinoma can occur in young patients with no evidence for hereditary cancer risk or radiation therapy. The G199R substitution is anticipated to alter the stability of the p53 tetrameric complex. The role of UV light in the etiology of sebaceous carcinoma deserves further study. Our findings, taken together with those of others, suggest that different environmental factors could lead to the development of sebaceous carcinoma in different patients.</p

Module structure of interphotoreceptor retinoid-binding protein (IRBP) may provide bases for its complex role in the visual cycle – structure/function study of Xenopus IRBP

<p>Abstract</p> <p>Background</p> <p>Interphotoreceptor retinoid-binding protein's (IRBP) remarkable module structure may be critical to its role in mediating the transport of all-<it>trans and 11-cis </it>retinol, and 11-<it>cis </it>retinal between rods, cones, RPE and Müller cells during the visual cycle. We isolated cDNAs for <it>Xenopus </it>IRBP, and expressed and purified its individual modules, module combinations, and the full-length polypeptide. Binding of all-<it>trans </it>retinol, 11-cis retinal and 9-(9-anthroyloxy) stearic acid were characterized by fluorescence spectroscopy monitoring ligand-fluorescence enhancement, quenching of endogenous protein fluorescence, and energy transfer. Finally, the X-ray crystal structure of module-2 was used to predict the location of the ligand-binding sites, and compare their structures among modules using homology modeling.</p> <p>Results</p> <p>The full-length <it>Xenopus </it>IRBP cDNA codes for a polypeptide of 1,197 amino acid residues beginning with a signal peptide followed by four homologous modules each ~300 amino acid residues in length. Modules 1 and 3 are more closely related to each other than either is to modules 2 and 4. Modules 1 and 4 are most similar to the N- and C-terminal modules of the two module IRBP of teleosts. Our data are consistent with the model that vertebrate IRBPs arose through two genetic duplication events, but that the middle two modules were lost during the evolution of the ray finned fish. The sequence of the expressed full-length IRBP was confirmed by liquid chromatography-tandem mass spectrometry. The recombinant full-length <it>Xenopus </it>IRBP bound all-<it>trans </it>retinol and 11-<it>cis </it>retinaldehyde at 3 to 4 sites with <it>K</it>_<it>d</it>'s of 0.2 to 0.3 μM, and was active in protecting all-<it>trans </it>retinol from degradation. Module 2 showed selectivity for all-<it>trans </it>retinol over 11-cis retinaldehyde. The binding data are correlated to the results of docking of all-<it>trans</it>-retinol to the crystal structure of <it>Xenopus </it>module 2 suggesting two ligand-binding sites. However, homology modeling of modules 1, 3 and 4 indicate that both sites may not be available for binding of ligands in all four modules.</p> <p>Conclusion</p> <p>Although its four modules are homologous and each capable of supporting ligand-binding activity, structural differences between their ligand-binding domains, and interactions between the modules themselves will be critical to understanding IRBP's complex role in the visual cycle.</p

Investigating the Protective Role of IRBP against Oxidative Stress in Diabetic Retinopathy

Introduction: Diabetic retinopathy is an ocular condition caused by a multitude of factors as a result of elevated blood glucose. One of the primary mechanisms of damage is a result of oxidative stress. It has been found that levels of IRBP in the vitreous are decreased in the setting of diabetic retinopathy, which could be associated with damage from resulting oxidative stress. Purpose: This article will address the protective role of IRBP in diabetic retinopathy by discussing the overexpression and under expression of IRBP and its resulting effect on the retina. Increased levels of IRBP in rats with diabetic retinopathy has been shown to prevent, and even reverse, vascular permeability as well as increase neuroretinal responses. Conversely, decreased levels of IRBP are found in patients with diabetes at all stages of ocular disease, which suggests IRBP plays a role in the pathogenesis of diabetic eye disease. IRBP is produced by photoreceptors which decreases expression of IRBP in diabetic retinopathy due to damage and dysfunction. IRBP provides protection by removing retinoid byproducts, which cause oxidative damage upon accumulation. Conclusion: Judging from studies we have on human retinal cells and rats, IRBP may play a protective role against oxidative stress in the retina as well as a critical role in preservation of photoreceptors via metabolism and transport of retinoids. It is important to continue research on IRBP to further clarify this protective role in order to contribute to possible prevention and treatment of diabetic eye disease

Histogenesis of retinal dysplasia in trisomy 13

© 2007 Chan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Los tarayales de la depresión del Ebro

Tamarix-communities belonging to the order Tamaricetalia (class Nerio- Tamaricetea) are phytosociologically reviewed in the Ebro basin. Three associations can be differentiated: Tamaricetum gallicae Br.-Bl. &amp; O. Bolós 1957 (Tamaricion africanae Br.-Bl. &amp; O. Bolós 1957), riparian and subhalophilous; Agrostio-Tamaricetum canariensis Cirujano 1981 (Tamaricion boveano-canariensis Izco, F. Fernández-González &amp; A. Molina 1984), mesohalophilous (subass. tamaricetosum canariensis) or hiperhalophilous (subass. inuletosum crithmoidis nova); and Suaedo braun-blanquetii-Tamaricetum boveanae (Izco &amp; al. 1984) ass. nova (Tamaricion boveano-canariensis), hiperhalophilous and restricted to eastern and lower part of the basin.La revisión de las comunidades de Tamarix en la depresión del Ebro permite reconocer tres asociaciones: Tamaricetum gallicae Br.-Bl. &amp; O. Bolós 1957 (Tamaricion africanae Br.-Bl. &amp; O. BoIós 1957), riparia y subhalófila; Agrostio-Tamaricetum canariensis Cirujano 1981 (Tamaricion boveano-canuriensis Izco, F. Fernández-González &amp; A. Molina 1984), mesohalófila (subass. tamaricetosum canariensis) o hiperhalófila (subass. inuletosum crithmoidis nova); y Suaedo braun-blanquetii-Tamaricetum boveanae (Izco &amp; al. 1984) ass. nova (Tamaricion boveano-canariensis), hiperhalófila y restringida a la parte más baja y oriental de la depresión

Platform Workers in Europe Evidence from the COLLEEM Survey

The recent surge of digital labour platforms has led to new forms of work organisation and tasks distribution across the workforce. This has raised several questions about the functioning and the benefits deriving from the reorganisation of work that those platforms entail and the associated risks. The European Commission assessed online platforms in a May 2016 communication, focusing on both their innovation opportunities and regulatory challenges. In June 2016 the Commission also adopted its European Agenda for the Collaborative Economy, which clarified the concept and provided some guidance on the employment status of platform workers and the EU definition of worker. The European Pillar of Social Rights aims to address some of the policy challenges associated to new forms of employment, including platform work. As accompanying initiatives, the Commission presented in December 2017 a proposal for a new Directive on transparent and predictable working conditions, and in March 2018 a proposal for a Council Recommendation on access to social protection for workers and the self-employed. A crucial issue in designing the policy response to the emergence of digital labour platforms is the lack of reliable evidence. In 2017, the JRC conducted the COLLEEM pilot survey , an initial attempt to provide quantitative evidence on platform work, responding to calls by the European Council and the European Parliament. The survey provides a basis for an initial estimation of platform work in 14 Member States . How many platform workers are there in Europe? The COLLEEM survey contains a direct measure of service provision via platforms by the respondents in 14 EU Member States. It asks whether the respondent has ever gained income from different online sources, among which there are two corresponding to labour service platforms: "providing services via online platforms, where you and the client are matched digitally, payment is conducted digitally via the platform and the work is location-independent, web-based" and "providing services via online platforms, where you and the client are matched digitally, and the payment is conducted digitally via the platform, but work is performed on-location". Estimates indicate that on average 10% of the adult population has ever used online platforms for the provision of some type of labour services. However, less than 8% do this kind of work with some frequency, and less than 6% spend a significant amount of time on it (at least 10 hours per week) or earn a significant amount of income (at least 25% of the total). Main platform workers are defined as those who earn 50% or more of their income via platforms and/or work via platforms more than 20 hours a week. They account for about 2% of the adult population on average. There are significant differences across countries: the UK has the highest incidence of platform work. Other countries with high relative values are Germany, the Netherlands, Spain, Portugal and Italy. By contrast, Finland, Sweden, France, Hungary and Slovakia show very low values compared to the rest. Who are the platform workers? The typical European platform worker is a young male, educated to a degree level. The proportion of women decreases as the intensity of platform work increases. There is, however, substantial heterogeneity across countries. The fact that most platform workers are highly educated is not surprising given that to be able to provide services via platform one needs to be a savvy internet user, and internet use tends to be correlated with higher education. Despite conventional wisdom, a typical platform worker is likely to have a family and kids. Furthermore, regardless of age, platform workers tend to have fewer years of labour market experience than the average worker. Employment status of platform workers The employment status of platform workers is a controversial issue and one of the most relevant from a policy perspective. Estimates from the COLLEEM survey reveal that when asked about their current employment situation, 75.7 % of the platform workers claimed to be an employee (68.1%) or self-employed (7.6%). A first possibility is that platform workers also have a regular job as employees or self-employed (in a more traditional sense) and are therefore covered by standard employment legislation. A second possibility is that platform workers are not really sure of their employment status and may see themselves as employees, only because they provide a certain type of service with regularity through the same platform. This is surprising because in most cases the providers of labour services via platforms are formally independent contractors rather than employees, but it also reflects the uncertainty surrounding this issue in policy and even legal debates around Europe. In short, the labour market status of platform workers remains unclear, even to themselves. Interviewed platform workers declared themselves to be self-employed (as main or side job) in 54% of the cases, while a large minority (38 %) claim to be an employee. What types of services are provided and coordinated via labour platforms? Labour services provided by digital labour platforms can be broadly distinguished as services performed digitally (i.e. micro tasks, clerical and data entry, etc.) or services performed on-location (i.e. transport, delivery, housekeeping, etc.). On average half of the overall platform workers perform both digital and on-location services. According to the level of skills required by different services we can distinguish between: i) professional services (high skills); ii) non-professionals services (medium skills) and iii) on-location services (low skills). The majority of platform workers provide more than one type of services, and are active on two or more platforms, often combining high- and low skilled activities, suggesting that some platform workers may be reducing income risk (and possibly increasing variety in work). The most common labour service provided is 'online clerical and data entry'. However, the largest proportion of platform workers provides professional services. Gender also influences the type of services provided: 'software development' and 'transport' are the most male dominated services. By contrast, 'translation' and 'on-location services' are the mostly female dominated ones. The market for digital services is global and this may lead to some specialisation on services provided for some countries. The majority of the services do not show much variety across countries; however some country patterns could be identified. Slovakia and Croatia appear to specialise in services that require a low-medium level of education. Romania is amongst the top countries for the provision of non-professionals services The Netherlands mostly provides services that require high digital skills such as software and interactive. One third of platform workers have a mismatch between the lower-skilled tasks they perform and their high level of education/skills. What are the motivations and conditions of platform work? Flexibility and autonomy are frequently mentioned motivations for platform work, but these results should be interpreted cautiously: the lack of alternatives is also mentioned as an important motive for working on platforms. The conditions of platform work are more polarised than those of regular workers. Working conditions for platform workers appear to be flexible, but also intense. Platform work can be arduous and, for some workers, involving long hours. Key policy implications The implications of digital labour platforms for work and employment are ambivalent. On the one hand, they can lower the entry barriers to the labour market, facilitate work participation through better matching procedures and ease the working conditions of specific groups (i.e. workers with strong family responsibilities, people with disabilities or health conditions, youth, people not in education, employment or training – NEETs -, older workers, long-term unemployed, people with a migrant background). On the other hand, digital labour platforms typically rely on a workforce of independent contractors whose conditions of employment, representation and social protection are at best unclear, at worst clearly unfavourable. The status of platform workers is probably the most complex policy issue at stake. The actual nature of the employment relationship is nebulous in most cases. This is particularly problematic because employment status is key for access to social security, training entitlements and coverage by legislation on working conditions. Therefore the need for a clarification of the employment status of platform workers appears obvious. The findings presented in this report suggest an emerging phenomenon of increasing importance but still modest in size. If platform work remains significant but small in the future, a two-pronged policy response is likely to suffice, focusing on (i) fully grasping its job creation and innovation opportunities and (ii) adjusting existing labour market institutions and welfare systems to the new reality and mitigating its potentially negative consequences for working careers and working conditions. Examples of this are the proposal for a directive on transparent and predictable working conditions, and the proposal for a Council Recommendation on access to social protection for workers and the self-employed in the social fairness package adopted by the Commission on 13 March 2018 as well as the targeted legislative measures adopted by some countries. However, if platform work continues to grow in size and importance to become a more significant reality in our labour markets, or if some of the key features of platform work spread across other forms of employment as already seem to be happening in some cases, policy interventions may need to be of a more ambitious nature. Indeed, a scenario of general "platformisation" of labour markets and working conditions would require a profound rethinking of labour market institutions and welfare systems. Furthermore, a scenario in which there would be a significant increase in the provision of digitally performed platform work - people providing professional and non-professional labour services from their own places of origin - might lead to more opportunities for people to provide professional and non-professional labour services from their own places of origin – on-location services excluded - through a digital single market. A serious challenge in this scenario is the increased exposure of workers to global competition. From the regulatory point of view, the categories catering for the specificities of platform workers might be in need for a review. In a labour market with more unstable working careers, a wider use of schemes based on personal accounts for workers' entitlements might be required. From the social protection point of view, progress towards insurance models not based on employment status could be necessary.JRC.B.4-Human Capital and Employmen

Human embryonic and neuronal stem cell markers in retinoblastoma

Retinoblastoma (RB) is the most common intraocular tumor of early childhood. The early onset of RB, coupled with our previous findings of cancer stem cell characteristics in RB, led us to hypothesize that subpopulations of RB tumors harbor markers and behaviors characteristic of embryonic and neuronal origin. Our RB sources included: human pathological tissues, and the human RB cell lines Y79 and WERI-RB27. Microarray screening, single and dual-label immunocytochemistry and RT-PCR were performed to detect embryonic and neuronal stem cell markers, such as Oct3/4, Nanog, CD133, and Musashi-1. To test for functional evidence of stem cell behavior, we examined RB cells for their ability to form neurospheres and retain BrdU label as indicators of self-renewal and slow cell cycling, respectively. Microarray comparisons of human RB tumors with normal retinal tissue detected upregulation of a number of genes involved in embryonic development that were also present in Y79 cells, including Oct3/4, Nanog, Musashi-1 and Musashi-2, prominin-1 (CD133), Jagged-2, Reelin, Thy-1, nestin, Meis-1,NCAM, Patched, and Notch4. Expression of Musashi-1, Oct3/4 and Nanog was confirmed by immunostaining and RT-PCR analyses of RB tumors and RB cell lines. CD133 expression was confirmed by PCR analysis. Y79 and WERI-RB27 contained populations of Hoechst-dim/ABCG2-positive cells that co-localized with embryonic stem cell markers Oct3/4-ABCG2 and Nanog-ABCG2. Subpopulations of Y79 and WERI-RB27 cells were label-retaining (as seen by BrdU incorporation) and were able to generate neurospheres, both hallmarks of a stem cell phenotype. Small subpopulation(s) of RB cells express human embryonic and neuronal stem cell markers. There are also subpopulations that demonstrate functional behavior (label retention and self-renewal) consistent with cancer stem cells. These findings support the hypothesis that RB is a heterogeneous tumor comprised of subpopulation(s) with stem cell-like properties