Complex rearrangements in patients with duplications of MECP2 can occur by fork stalling and template switching

Duplication at the Xq28 band including the MECP2 gene is one of the most common genomic rearrangements identified in neurodevelopmentally delayed males. Such duplications are non-recurrent and can be generated by a non-homologous end joining (NHEJ) mechanism. We investigated the potential mechanisms for MECP2 duplication and examined whether genomic architectural features may play a role in their origin using a custom designed 4-Mb tiling-path oligonucleotide array CGH assay. Each of the 30 patients analyzed showed a unique duplication varying in size from similar to 250 kb to similar to 2.6 Mb. Interestingly, in 77% of these non-recurrent duplications, the distal breakpoints grouped within a 215 kb genomic interval, located 47 kb telomeric to the MECP2 gene. The genomic architecture of this region contains both direct and inverted low-copy repeat (LCR) sequences; this same region undergoes polymorphic structural variation in the general population. Array CGH revealed complex rearrangements in eight patients; in six patients the duplication contained an embedded triplicated segment, and in the other two, stretches of non-duplicated sequences occurred within the duplicated region. Breakpoint junction sequencing was achieved in four duplications and identified an inversion in one patient, demonstrating further complexity. We propose that the presence of LCRs in the vicinity of the MECP2 gene may generate an unstable DNA structure that can induce DNA strand lesions, such as a collapsed fork, and facilitate a Fork Stalling and Template Switching event producing the complex rearrangements involving MECP2.

Induction of Lymphocyte Death by Short- and Long-Duration Triathlon Competitions

LEVADA-PIRES, A. C., M. F. CURY-BOAVENTURA, R. GORJAO, S. M. HIRABARA. E. F. PUGGINA, I. L. PELLEGRINOTTI, L. A. DOMINGUES FILHO, R. CURI, and T. C. PITHON-CURI. Induction of Lymphocyte Death by Short- and Long-Duration Triathlon Competitions. Med. Sci. Sporty Exerc., Vol. 4 1, No. 10, pp. 1896-1901, 2009. Purpose: The effect of triathlon competitions on death of lymphocytes from elite athletes was investigated. Material and Methods: Blood was collected from sedentary volunteers and triathletes at rest and after a short-duration triathlon (SDT) and after a long-duration triathlon (LDT-half Ironman) competitions. Results: The athletes had lowered lymphocyte proliferation capacity compared with sedentary volunteers either at rest or after the competitions. There was no difference in the parameters associated with lymphocyte death when sedentary volunteers were compared with triathletes at rest. Lymphocytes from triathletes after SDT competition showed an increase in DNA fragmentation, phosphatidylserine externalization, and mitochondrial transmembrane depolarization and did not alter membrane integrity when compared with cells from athletes at rest. In contrast, the LDT competition raised the proportion of lymphocytes with loss of membrane integrity when compared with cells from athletes at rest and did not change the apoptotic parameters. The LDT competition induced an increase of reactive oxygen species (ROS) production by lymphocytes compared with triathletes at rest. The SDT competition did not alter ROS production by lymphocytes when compared with cells from triathletes at rest. ROS production by lymphocytes after LDT competition was 60% higher than in SDT. Conclusions: Evidence is presented herein that an LDT competition caused lymphocyte death by necrosis, whereas an SDT induced lymphocyte apoptosis. The mechanism for lymphocyte death induced by the triathlon competitions may involve an increase in ROS production at different extents.

Retinoic Acid and VEGF Delay Smooth Muscle Relative to Endothelial Differentiation to Coordinate Inner and Outer Coronary Vessel Wall Morphogenesis

Rationale: Major coronary vessels derive from the proepicardium, the cellular progenitor of the epicardium, coronary endothelium, and coronary smooth muscle cells (CoSMCs). CoSMCs are delayed in their differentiation relative to coronary endothelial cells (CoEs), such that CoSMCs mature only after CoEs have assembled into tubes. The mechanisms underlying this sequential CoE/CoSMC differentiation are unknown. Retinoic acid (RA) is crucial for vascular development and the main RA-synthesizing enzyme is progressively lost from epicardially derived cells as they differentiate into blood vessel types. In parallel, myocardial vascular endothelial growth factor (VEGF) expression also decreases along coronary vessel muscularization. Objective: We hypothesized that RA and VEGF act coordinately as physiological brakes to CoSMC differentiation. Methods and Results: In vitro assays (proepicardial cultures, cocultures, and RALDH2 [retinaldehyde dehydrogenase-2]/VEGF adenoviral overexpression) and in vivo inhibition of RA synthesis show that RA and VEGF act as repressors of CoSMC differentiation, whereas VEGF biases epicardially derived cell differentiation toward the endothelial phenotype. Conclusion: Experiments support a model in which early high levels of RA and VEGF prevent CoSMC differentiation from epicardially derived cells before RA and VEGF levels decline as an extensive endothelial network is established. We suggest this physiological delay guarantees the formation of a complex, hierarchical, tree of coronary vessels. (Circ Res. 2010;107:204-216.)

Interactions of Diorganolead(IV) with 3-(2-Thienyl)-2-sulfanylpropenoic Acid and/or Thiamine: Chemical and in Vitro and in Vivo Toxicological Results

The reactions of PbR(2)(OAc)(2) (R=Me, Ph) with 3-(2-thienyl)-2-sulfanylpropenoic acid (H(2)tSpa) in methanol or ethanol afforded complexes [PbR(2)(tspa)] that electrospray ionization-mass spectrometry (ESI-MS) and IR data suggest are polymeric. X-ray studies showed that [PbPh(2)(tspa)(dmso)] center dot dmso, crystallized from a solution of [PbPh(2)(tspa)] in dmso, is dimeric, and that [HQ](2)[PbPh(2)(tspa)(2)] (Q=diisopropylamine), obtained after removal of [PbPh(2)(tspa)] from a reaction including Q, contains the monomeric anion [PbPh(2)(tSpa)(2)](2-). In the solid state the lead atoms are O,S-chelated by the tspa ligands in all these products, and in the latter two have distorted octahedral coordination environments. NMR data suggest that tspa(2-) remains coordinated to PbR(2)(2+) in solution in dmso. Neither thiamine nor thiamine diphosphate reacted with PbMe(2)(NO(3))(2) in D(2)O. Prior addition of H(2)tSpa protected LLC center dot PK1 renal proximal tubule cells against PbMe(2)(NO(3))(2); thiamine had no statistically significant effect by itself, but greatly potentiated the action of H(2)tSpa. Administration of either H(2)tspa or thiamine to male albino Sprague-Dawley rats dosed 30 min previously with PbMe(2)(NO(3))(2) was associated with reduced inhibition of delta-ALAD by the organolead compound, and with lower lead levels in kidney and brain, but joint administration of both H(2)tspa and thiamine only lowered lead concentration in the kidney.

Sr and Nd isotope composition of the metamorphic, sedimentary and ultramafic xenoliths of Lanzarote (Canary Islands): Implications for magma sources

The lavas produced by the Timanfaya eruption of 1730-1736 (Lanzarote, Canary Islands) contain a great many sedimentary and metamorphic (metasedimentary), and mafic and ultramafic plutonic xenoliths. Among the metamorphosed carbonate rocks (calc-silicate rocks [CSRs]) are monomineral rocks with forsterite or wollastonite, as well as rocks containing olivine +/- orthopyroxene +/- clinopyroxene +/- plagioclase: their mineralogical compositions are identical to those of the mafic (gabbros) and ultramafic (dunite, wherlite and lherzolite) xenoliths. The (87)Sr/(16)Sr (around 0.703) and (143)Nd/(144)Nd (around 0.512) isotope ratios of the ultramafic and metasedimentary xenoliths are similar, while the (147)Sm/(144)Nd ratios show crustal values (0.13-0.16) in the ultramafic xenoliths and mantle values (0.18-0.25) in some CSRs. The apparent isotopic anomaly of the metamorphic xenoliths can be explained in terms of the heat source (basaltic intrusion) inducing strong isotopic exchange ((87)Sr/(86)Sr and (143)Nd/(144)Nd) between metasedimentary and basaltic rocks. Petrofabric analysis also showed a possible relationship between the ultramafic and metamorphic xenoliths. (C) 2009 Elsevier B.V. All rights reserved.

Electrostatic and Hydrophobic Interactions Involved in CNT Biofunctionalization with Short ss-DNA

This work is aimed at studying the adsorption mechanism of short chain 20-mer pyrimidinic homoss-DNA (oligodeoxyribonucleotide, ODN: polyC(20) and polyT(20)) onto CNT by reflectometry. To analyze the experimental data, the effective-medium theory using the Bruggemann approximation represents a Suitable optical model to account for the surface properties (roughness, thickness, and optical constants) and the size of the adsorbate. Systematic information about the involved interactions is obtained by changing the physicochemical properties of the system. Hydrophobic and electrostatic interactions are evaluated by comparing the adsorption oil hydrophobic CNT and oil hydrophilic silica and by Modulating the ionic Strength With and without Mg(2+). The ODN adsorption process oil CNT is driven by hydrophobic interactions only when the electrostatic repulsion is Suppressed. The adsorption mode results in ODN molecules in a side-on orientation with the bases (nonpolar region) toward the surface. This unfavorable orientation is partially reverse by adding Mg(2+). On the other hand, the adsorption oil silica is dominated by the strong repulsive electrostatic interaction that is screened at high ionic strength or mediated by Mg(2+). The cation-mediated process induces the interaction of the phosphate backbone (polar region) with the surface, leaving the bases free for hybridization. Although the general adsorption behavior of the pyrimidine bases is the same, polyC(20) presents higher affinity for the CNT Surface due to its acid-base properties.

NAVET's Boxes - an Evaluation of the Post-Visit Loan Service at a Science Centre in Borås

Many pedagogues believe science centres to be a good complement to the more formal school teaching. For a visit to a science centre to be as educational as possible, there is a need for pre-visit information of some sort, a guided visit, and post-visit work. Many science centres offer loan services of different kinds. At Navet, a science centre in Borås, teachers can borrow boxes with experiments connected to the different themes they provide. The experiments are supposed to be a continuation of the visit and help settle the knowledge gained during the visit. This thesis is an evaluation of how the boxes function in the schools, and what the teachers think of them. The study was conducted through questionnaires and interviews with both teachers and the staff at Navet. The results of the study are very positive. Many teachers have been involved with Navet from the very beginning and they see a visit to Navet as an integrated part of their teaching. Some boxes work better than others and some might need clearer information, but overall the teachers see the boxes as timesavers, as a way to vary their teaching more easily, and as a help for teachers not specialized in mathematics and science.

Essentialism i religionsundervisningen : Ett religionsdidaktiskt problem

Essentialist concepts of religion are common in the teaching of religion in schools and to a certain extent also in the academic discipline of religious studies. In this article, a number of problems with essentialist perceptions of religion are discussed. In the first part of the article a thesis is maintained, according to which essentialist conceptions of religion or specific religions are too limited to be of value in the teaching of religion. This is done through examples of essentialist expressions about religion. The examples are grouped according to a typology of different kinds of essentialism. Two main categories, each with two sub-categories are identified. Thus, the category of essentialism regarding the substance of religion is divided into transcendental or theological essentialism (which presupposes the existence of a sacred power of some kind, the experience of which is the basis for religion), and core essentialism (where it is presupposed that certain ideas or concepts constitute religion as a general category or specific religions). Likewise, the category of essentialism regarding the function of religion has two sub-categories: positive and negative essentialism. These kinds of essentialism presuppose that religion or specific religions are inherently good or harmful respectively to human beings. Examples from each of these categories are given and discussed. In the second part of the article, Benson Saler’s open concept of religion is presented as an alternative to essentialist or bounded perceptions. It is based on Ludwig Wittgenstein’s idea of family resemblances and on prototype theory. In connection with this, it is argued that a certain kind of conscious ethnocentrism is needed as a point of departure in the study and teaching of religion. The metaphor of education as a journey from the familiar out into the unfamiliar and back again is suggested as a possible pattern for such teaching. Finally,some examples of non-essentialist ways to introduce religions are offered.

Vem är samen? : En läromedelsanalys av hur samisk kultur och identitet presenteras i Undervisningsmaterial i historia och religion

The aim of this essay is to study how the Sami are presented in four textbooks about religion and history that are used in the schools of the majority culture of Sweden today and one book of ideas asto how a textbook could look like from a Sami's perspective. Its aim is not only to study how the Sami are presented but also to discuss how students who read these books could interpret what it means to be a Sami and what their culture is about. It is also meant to discuss how the Sami identitycould be formed. In order to be able to discuss this the essay uses three different kinds of theories about identity and culture. The analysis showed that there is little information about Sami culture, identity, religion and historypresented in the four textbooks used in schools of the majority culture and that these books seem to want students to think that the Sami are troublemakers but are and should be assimilated into the majority culture.

Movies, Mind and Meaning : Studying Audience and Favourite Films

Construction of identity and meaning is becoming increasingly important in both media studies and religion scholarship. (Lövheim, 2004) Meaning construction outside traditional religion has become more interesting for religious studies and what individuals in the audience do with all messages circulated through media in everyday life has attended increasing interest within media studies (Stout and Buddenbaum, 2001). Motion pictures, soap operas and advertising are all examples of media contents which generate ideas among its audience which to a various degree are used as resources within the construction of identity (Jansson, 2001). The investigation of what modern humankind’s world views look like and what components they are composed of, in this context seems to be an important topic of investigation (Holm and Björkqvist, 1996). The ways in which the development of media has effected the daily lives of individuals is interest as is the nature of the self and the ways in which the process of self-formation is affected by the profusion of mediated materials (Thompson, 1995). Film and religion are my interest within this larger frame. The topic is not exactly new but the combination of film and religion has during the last ten years resulted in a rapidly growing number of books by scholars interested in this field (Lyden, 2003). One growing focus is on the role that films can and do play within the emerging and developing valuesystem of people in the West today (Marsh, 2004). The British theologian Clive Marsh’s point of departure is very similar to my own. Viewers bring to a film life-experience, immediate concerns and worldviews and the exploration of this interplay between movies and the interpreting process of meaning making is the very focus in this paper. Theoretically, the semeiological model of Alf Linderman is combined with cultural cognitive approaches used by a number of Scandinavian media scholars developing perspectives in audience theory (Linderman, 1996, Höijer and Werner, 1998). 13 individuals, their favourite movie and what it means to them in their life My aim is to examine how individuals comprehend film and what the meaning process look like. In this paper I present the outcome of 13 interviews with young people about their favourite film. I suggest how it is possible to interpret how they interrelate film comprehension with their personal beliefs and their culturally constructed worldview from a sociocognitive point of view. Examples of films chosen range from Disneys Lion King (1994), sciencefiction and fantasy successes like The Matrix (1999) and Lord of the Rings (2001) or the next best movie ever according to www.IMdb.com The Shawshank Redemption (1994) as well as the Swedish blockbuster Så som i himmelen (2004), aka “As in Heaven”.

Gay and Lesbian Life at Colby 1969-1974

The history of a gay and lesbian student community at Colby seems to point to the difficulty of visibility. For students who were able to find others like themselves, their group of lesbian and gay friends had to remain underground. For students who were grappling with their newly found, socially stigmatized sexuality, the experience was isolating if they did not know where to find others like themselves. This paper seeks to address the social forces that kept sexually variant students from expressing their sexual identities openly on campus. Part of this difficulty is attributable to the compulsory heterosexuality assumed by general American society at the time, manifested in the silence or outright hostility directed against homosexuals. Naturally, Colby students replicated this assumption. Some of the students we interviewed seemed to internalize compulsory heterosexuality, while it was forced upon others. Religion and psychology were two methods of enforcing heterosexuality that were relevant to the people we interviewed. Another significant obstacle to visibility was Colby's location and the nature of Colby's student body. Waterville, unlike more urban cities, did not have a history of gay life, and thus an established gay community or gay identity into which one could be socialized. Colby, as a small, homogeneous and isolated space, posed difficulties in establishing a gay community as the population to draw from was small and regulated.

A Resource Centric Approach For Advancing Collaboration Through Hydrologic Data And Model Sharing

HydroShare is an online, collaborative system being developed for open sharing of hydrologic data and models. The goal of HydroShare is to enable scientists to easily discover and access hydrologic data and models, retrieve them to their desktop or perform analyses in a distributed computing environment that may include grid, cloud or high performance computing model instances as necessary. Scientists may also publish outcomes (data, results or models) into HydroShare, using the system as a collaboration platform for sharing data, models and analyses. HydroShare is expanding the data sharing capability of the CUAHSI Hydrologic Information System by broadening the classes of data accommodated, creating new capability to share models and model components, and taking advantage of emerging social media functionality to enhance information about and collaboration around hydrologic data and models. One of the fundamental concepts in HydroShare is that of a Resource. All content is represented using a Resource Data Model that separates system and science metadata and has elements common to all resources as well as elements specific to the types of resources HydroShare will support. These will include different data types used in the hydrology community and models and workflows that require metadata on execution functionality. The HydroShare web interface and social media functions are being developed using the Drupal content management system. A geospatial visualization and analysis component enables searching, visualizing, and analyzing geographic datasets. The integrated Rule-Oriented Data System (iRODS) is being used to manage federated data content and perform rule-based background actions on data and model resources, including parsing to generate metadata catalog information and the execution of models and workflows. This presentation will introduce the HydroShare functionality developed to date, describe key elements of the Resource Data Model and outline the roadmap for future development.

Clara Nunes como obra de arte: a epistemologia das ciências humanas a partir da cultura musical

The thesis has its largest array in the reorganization of science that is built from the middle of the last century and its horizon reconnection between scientific culture and humanistic culture, and the dialogue between science, art and literature. This epistemological regeneration view of the scientific paradigm incorporates the poetic language and sociological analysis, and brings out a complex, open and transdisciplinary narrative. To undertake this exercise as interlocutors we have thinkers like Nietzsche, Lévi-Strauss, Edgar Morin and Bruno Latour, to name a few, and as a reference for analyzing the entire artistic production of one of the icons of Brazilian music, Clara Nunes. It is problematized up in this work, through the singer s discography, lyrics and fragments of her biography, the construction of a social character that politicized culture, increased the mestizo consciousness of popular imagery, and exceeded the excessively prosaic narratives of the academic and scientific culture. The central argument of the thesis recognizes a Hybrid Subject Clara Nunes, as indeed is what is expected of the politically engaged intellectual in the 21st century