Docteur, j'ai un ganglion [Doctor, I have a lymph node]

To investigate a recently developed lymphadenopathy can be simple or complex. The medical history, presence or not of symptoms, the general physical examination, and the localization and characteristics of the adenopathy, most often lead to a diagnosis and therapy when indicated. Among young adults, the etiology is either infectious or reactive, rarely tumoral, as opposed to elderly persons. The most important step is to look at signs of severity (or non banality) such as an increased size, hard consistency, supra-clavicular location, an immunocompromised host, a history of Tb exposition. If present, these signs will trigger a biopsy with cyto- or histopathological examination mostly to rule out a malignant tumor. This article reviews the practical steps of an investigation of an isolated adenopathy in an adult patient.

NLRC5 exclusively transactivates MHC class I and related genes through a distinctive SXY module.

MHC class II (MHCII) genes are transactivated by the NOD-like receptor (NLR) family member CIITA, which is recruited to SXY enhancers of MHCII promoters via a DNA-binding "enhanceosome" complex. NLRC5, another NLR protein, was recently found to control transcription of MHC class I (MHCI) genes. However, detailed understanding of NLRC5's target gene specificity and mechanism of action remained lacking. We performed ChIP-sequencing experiments to gain comprehensive information on NLRC5-regulated genes. In addition to classical MHCI genes, we exclusively identified novel targets encoding non-classical MHCI molecules having important functions in immunity and tolerance. ChIP-sequencing performed with Rfx5(-/-) cells, which lack the pivotal enhanceosome factor RFX5, demonstrated its strict requirement for NLRC5 recruitment. Accordingly, Rfx5-knockout mice phenocopy Nlrc5 deficiency with respect to defective MHCI expression. Analysis of B cell lines lacking RFX5, RFXAP, or RFXANK further corroborated the importance of the enhanceosome for MHCI expression. Although recruited by common DNA-binding factors, CIITA and NLRC5 exhibit non-redundant functions, shown here using double-deficient Nlrc5(-/-)CIIta(-/-) mice. These paradoxical findings were resolved by using a "de novo" motif-discovery approach showing that the SXY consensus sequence occupied by NLRC5 in vivo diverges significantly from that occupied by CIITA. These sequence differences were sufficient to determine preferential occupation and transactivation by NLRC5 or CIITA, respectively, and the S box was found to be the essential feature conferring NLRC5 specificity. These results broaden our knowledge on the transcriptional activities of NLRC5 and CIITA, revealing their dependence on shared enhanceosome factors but their recruitment to distinct enhancer motifs in vivo. Furthermore, we demonstrated selectivity of NLRC5 for genes encoding MHCI or related proteins, rendering it an attractive target for therapeutic intervention. NLRC5 and CIITA thus emerge as paradigms for a novel class of transcriptional regulators dedicated for transactivating extremely few, phylogenetically related genes.

A nuclear defect in the 4p16 region predisposes to multiple mitochondrial DNA deletions in families with Wolfram syndrome.

Wolfram syndrome is a progressive neurodegenerative disorder transmitted in an autosomal recessive mode. We report two Wolfram syndrome families harboring multiple deletions of mitochondrial DNA. The deletions reached percentages as high as 85-90% in affected tissues such as the central nervous system of one patient, while in other tissues from the same patient and from other members of the family, the percentages of deleted mitochondrial DNA genomes were only 1-10%. Recently, a Wolfram syndrome gene has been linked to markers on 4p16. In both families linkage between the disease locus and 4p16 markers gave a maximum multipoint lod score of 3.79 at theta = 0 (Pi<0.03) with respect to D4S431. In these families, the syndrome was caused by mutations in this nucleus-encoded gene which deleteriously interacts with the mitochondrial genome. This is the first evidence of the implication of both genomes in a recessive disease.

A nuclear defect in the 4p16 region predisposes to multiple mitochondrial DNA deletions in families with Wolfram syndrome.

Wolfram syndrome is a progressive neurodegenerative disorder transmitted in an autosomal recessive mode. We report two Wolfram syndrome families harboring multiple deletions of mitochondrial DNA. The deletions reached percentages as high as 85-90% in affected tissues such as the central nervous system of one patient, while in other tissues from the same patient and from other members of the family, the percentages of deleted mitochondrial DNA genomes were only 1-10%. Recently, a Wolfram syndrome gene has been linked to markers on 4p16. In both families linkage between the disease locus and 4p16 markers gave a maximum multipoint lod score of 3.79 at theta = 0 (Pi<0.03) with respect to D4S431. In these families, the syndrome was caused by mutations in this nucleus-encoded gene which deleteriously interacts with the mitochondrial genome. This is the first evidence of the implication of both genomes in a recessive disease.

Complexitat i fenomen (socio)linguístic

Intermediate phenomena of reality present particular characteristics of systemic self-organization, multilevel interrelations, recursivity, emergence of new «objects» with properties different from those of the elements that form them, and evolutionary dynamics, that probably need the formulation of new theoretical concepts and different paradigm principles. The sciences or perspectives of complexity, or the «complex» thinking, try to respond adequately to this complexity of reality. This approach adopts a multidimensional, integrated and dynamic view of reality: the world is made up of overlapping levels of different elements which produce new properties or new organizations at higher levels. If we conceive what we call languages as simple and decontextualized objects, we can understand some of the more mechanical aspects but we will ignore their conditions of existence, functionality, maintenance, variation, change and extinction.

Gene-disease network analysis reveals functional modules in mendelian, complex and environmental diseases

AbstractBACKGROUND: Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult.PRINCIPAL FINDINGS: We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell.CONCLUSIONS: For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and environmental factors, such as drugs, contribute to diseases.AVAILABILITY: The gene-disease networks used in this study and part of the analysis are available at http://ibi.imim.es/DisGeNET/DisGeNETweb.html#Download

Síria i la responsabilitat de protegir: la crisi d'un principi?

A partir de l’any 2011 i fins l’actualitat, l’onada de protestes i revoltes ciutadanes batejada com “la Primavera Àrab” ha sacsejat el panorama polític de la regió del Mediterrani i de les relacions internacionals. El present treball analitza com el cas de la guerra civil síria (iniciada el març de 2011 i que constitueix un cas enormement complex a causa de la fragmentació de l’oposició, l’elevat nombre d’actors interns i externs que hi intervenen i la seva varietat d’interessos, entre d’altres factors) ha posat en evidència l’efectivitat de la Responsabilitat de Protegir per frenar violacions sistemàtiques dels Drets Humans, tal i com ha evidenciat la incapacitat de la Comunitat Internacional d’actuar de manera cohesionada i efectiva en aquests més de dos anys. A més a més, la impossibilitat de portar a terme una intervenció militar multilateral emparada en el marc de la Responsabilitat de Protegir a causa de factors com el bloqueig del Consell de Seguretat i la incertesa que envolta les possibilitats d’èxit i els mecanismes que s’haurien de seguir durant l’actuació i reconstrucció de l’Estat fa evident la necessitat d’una redefinició del principi perquè aquest doni resposta a aquestes qüestions i pugui constituir un instrument realment efectiu.

Molecular cloning of a novel human I-mfa domain-containing protein that differently regulates human T-cell leukemia virus type I and HIV-1 expression.

Regulation of viral genome expression is the result of complex cooperation between viral proteins and host cell factors. We report here the characterization of a novel cellular factor sharing homology with the specific cysteine-rich C-terminal domain of the basic helix-loop-helix repressor protein I-mfa. The synthesis of this new factor, called HIC for Human I-mfa domain-Containing protein, is controlled at the translational level by two different codons, an ATG and an upstream non-ATG translational initiator, allowing the production of two protein isoforms, p32 and p40, respectively. We show that the HIC protein isoforms present different subcellular localizations, p32 being mainly distributed throughout the cytoplasm, whereas p40 is targeted to the nucleolus. Moreover, in trying to understand the function of HIC, we have found that both isoforms stimulate in T-cells the expression of a luciferase reporter gene driven by the human T-cell leukemia virus type I-long terminal repeat in the presence of the viral transactivator Tax. We demonstrate by mutagenesis that the I-mfa-like domain of HIC is involved in this regulation. Finally, we also show that HIC is able to down-regulate the luciferase expression from the human immunodeficiency virus type 1-long terminal repeat induced by the viral transactivator Tat. From these results, we propose that HIC and I-mfa represent two members of a new family of proteins regulating gene expression and characterized by a particular cysteine-rich C-terminal domain.

Arginase II Promotes Macrophage Inflammatory Responses Through Mitochondrial Reactive Oxygen Species, Contributing to Insulin Resistance and Atherogenesis.

BACKGROUND: Macrophage-mediated chronic inflammation is mechanistically linked to insulin resistance and atherosclerosis. Although arginase I is considered antiinflammatory, the role of arginase II (Arg-II) in macrophage function remains elusive. This study characterizes the role of Arg-II in macrophage inflammatory responses and its impact on obesity-linked type II diabetes mellitus and atherosclerosis. METHODS AND RESULTS: In human monocytes, silencing Arg-II decreases the monocytes' adhesion to endothelial cells and their production of proinflammatory mediators stimulated by oxidized low-density lipoprotein or lipopolysaccharides, as evaluated by real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Macrophages differentiated from bone marrow cells of Arg-II-deficient (Arg-II(-/-)) mice express lower levels of lipopolysaccharide-induced proinflammatory mediators than do macrophages of wild-type mice. Importantly, reintroducing Arg-II cDNA into Arg-II(-/-) macrophages restores the inflammatory responses, with concomitant enhancement of mitochondrial reactive oxygen species. Scavenging of reactive oxygen species by N-acetylcysteine prevents the Arg-II-mediated inflammatory responses. Moreover, high-fat diet-induced infiltration of macrophages in various organs and expression of proinflammatory cytokines in adipose tissue are blunted in Arg-II(-/-) mice. Accordingly, Arg-II(-/-) mice reveal lower fasting blood glucose and improved glucose tolerance and insulin sensitivity. Furthermore, apolipoprotein E (ApoE)-deficient mice with Arg-II deficiency (ApoE(-/-)Arg-II(-/-)) display reduced lesion size with characteristics of stable plaques, such as decreased macrophage inflammation and necrotic core. In vivo adoptive transfer experiments reveal that fewer donor ApoE(-/-)Arg-II(-/-) than ApoE(-/-)Arg-II(+/+) monocytes infiltrate into the plaque of ApoE(-/-)Arg-II(+/+) mice. Conversely, recipient ApoE(-/-)Arg-II(-/-) mice accumulate fewer donor monocytes than do recipient ApoE(-/-)Arg-II(+/+) animals. CONCLUSIONS: Arg-II promotes macrophage proinflammatory responses through mitochondrial reactive oxygen species, contributing to insulin resistance and atherogenesis. Targeting Arg-II represents a potential therapeutic strategy in type II diabetes mellitus and atherosclerosis. (J Am Heart Assoc. 2012;1:e000992 doi: 10.1161/JAHA.112.000992.).

Efectes de les separacions o divorcis en el rendiment acadèmic dels alumnes de 5è i 6è d’una escola local

Aquest Treball Final de Grau aporta els resultats d’un estudi sobre els efectes i condicionats que suposa pel rendiment acadèmic dels alumnes de cicle superior de primària el divorci o la separació dels seus progenitors. Ens trobem davant l’augment del nombre de trencaments familiars, que ha esdevingut un fenomen clarament observable en la societat, es tracta d’un fenomen complex, en el qual entren en joc nombroses variables. I el trencament també suposa conseqüències socials, en primer lloc, pels fills/es. En una primera part ens endinsem en les aportacions i teories que han defensat diversos experts al llarg del temps sobre aquest fet. En una segona part es presenten les conclusions i els acords extrets de diverses entrevistes amb mestres d’una escola local en relació a la possible vinculació entre trencament familiar i rendiment acadèmic. I, per últim, s’acaben comparat les visions dels autors teòrics amb les aportacions i visions dels educadors professionals; per arribar a les principals conclusions que, no es pot generalitzar els efectes negatius de la ruptura, cal veure també les possibilitats positives del moment i, per últim, destacar que la manera amb la qual la família s'afronta a la ruptura té una importància crucial a l'hora de determinar l'impacte d'aquesta la ruptura en els fills.

Anàlisi dels coneixements intuïtius i del canvi conceptual en infants de parvulari, sobre els animals que viuen el seu entorn

En aquest projecte es reflexiona sobre l’ensenyament de les ciències al parvulari i com els infants aprenent conceptes relacionats amb el regne animal. La ciència escolar classifica la gran diversitat d’espècies que formen aquest regne en dos grans blocs, els vertebrats i els invertebrats, però en els patrons que ens ofereixen els animals per descobrir a ull nu aquestes particularitats són molt complexes d’observar. La visió que tenen els infants de parvulari sobre els animals del seu entorn sovint és molt allunyada de la realitat i els alumnes es creen concepcions alternatives per entendre els animals que observen. En l’estudi es realitza un recull de dades, a l’inici i el final d’una unitat didàctica, analitzant les representacions i les diferents formes de classificació dels animals de l’entorn que utilitzen els infants. Les conclusions són una reflexió sobre el perquè d’aquests coneixements alternatius i la manera de com aconseguir un canvi conceptual.

Maria-Mercè Marçal en el mirall : sobre l'imaginari femení i el llenguatge poètic

Per Maria-Mercè Marçal, la poeta no es pot trobar, no es pot veure, en el «mirall del bell», que sempre han fomentat els discursos dominants. El seu és una altra mena de mirall trencat que reflecteix un ésser complex, híbrid i contaminat que lluita «entre un jo que es vol fer i els múltiples personatges que, des del mirall, li retornen una imatge múltiple». En aquest article, per explorar el tema de l’imaginari femení i el llenguatge poètic, hem escollit dialogar amb Maria- Mercè Marçal i examinar tres dels múltiples bocins que conformen la seva imatge en el mirall. Conversem amb dues mares i un pare simbòlics de l’altre cantó del seu espill, tots tres proveïdors de material ideològic i eixos vertebradors dels assaigs marçalians. Es tracta d’intel·lectuals ben diversos: l’escriptora anglesa Virginia Woolf, el filòsof francès Jacques Derrida i la poeta catalana Maria-Antònia Salvà. En definitiva, dividim la investigació en tres apartats, que volen coincidir amb el diàleg que Marçal suposem que hi mantingué. De primer, amb Virginia Woolf, explorem la necessitat de la poeta de descobrir el sentiment de «fúria» que porta a dins per tal d’assumir la irracionalitat del seu llenguatge. Després, ens endinsem en les teories derridianes sobre la dona i l’escriptura, en un intent de demostrar que ambdues són espècies híbrides que viuen en el llindar, en un espai d’entremig. A l’últim, amb Maria-Antònia Salvà, revisem la imatge de la dona-monstre amb la certesa que «el salvatge» i «l’incert » són el motor del llenguatge poètic femení.

L'Experiència autobiogràfica, l'art i el compromís ètic de l'escriptor: tres eixos de la narrativa de Maria Àngels Anglada

L’obra de M. Àngels Anglada constitueix un tramat complex de lectures i influències que s’interpreta a través de nivells de significació i d’interessos que s’entrecreuen. Com a pilar que sosté tot aquest corpus hi ha un gran bagatge clàssic i una vasta formació literària que, juntament amb l’experiència vital i el posicionament ètic de l’autora, proporcionen les claus de lectura dels seus llibres. Partint d’aquesta idea, l’article aprofundeix en els tres aspectes que considerem eixos fonamentals de l’obra de l’escriptora: els elements autobiogràfics, l’art i el compromís social.

El consum multipantalla. Estudi sobre l’ús de mitjans tradicionals i nous per part de nens, joves, adults i gent gran a Catalunya

Des de fa una dècada es parla de la convergència digital, que ha propiciat la conjunció de la informàtica amb els mitjans de comunicació i la interconnexió en xarxa. Actualment circulen amb facilitat suports vells i nous cada vegada més flexibles. La conseqüència per als usuaris és que avui disposen d’una varietat àmplia de continguts connectats permanentment en qualsevol lloc i en qualsevol moment, a través de diverses plataformes i amb una convivència rica i complexa. En aquest context, aquest article mostra les conclusions d’un estudi de camp sobre l’ús, el consum i les preferències de suports i de continguts de la comunicació digital per part de grups d’infants, de joves, d’adults i de gent gran a Catalunya.