La biologie moléculaire est-elle utile au praticien [Is molecular biology useful to the practitioner?]

The relative importance of molecular biology in clinical practice is often underestimated. However, numerous procedures in clinical diagnosis and new therapeutic drugs have resulted from basic molecular research. Furthermore, understanding of the physiological and physiopathological mechanisms underlying several human diseases has been improved by the results of basic molecular research. For example, cloning of the gene encoding leptin has provided spectacular insights into the understanding of the mechanisms involved in the control of food intake and body weight maintenance in man. In cystic fibrosis, the cloning and identification of several mutations in the gene encoding the chloride channel transmembrane regulator (CFTR) have resolved several important issues in clinical practice: cystic fibrosis constitutes a molecular defect of a single gene. There is a strong correlation between the clinical manifestations or the severity of the disease (phenotype) with the type of mutations present in the CFTR gene (genotype). More recently, identification of mutations in the gene encoding a subunit of the renal sodium channel in the Liddle syndrome has provided important insight into the physiopathological understanding of mechanisms involved in this form of hereditary hypertension. Salt retention and secondary high blood pressure are the result of constitutive activation of the renal sodium channel by mutations in the gene encoding the renal sodium channel. It is speculated that less severe mutations in this channel could result in a less severe form of hypertension which may correspond to patients suffering from high blood pressure with low plasma renin activity. Several tools, most notably PCR, are derived from molecular research and are used in everyday practice, i.e. in prenatal diagnosis and in the diagnosis of several infectious diseases including tuberculosis and hepatitis. Finally, the production of recombinant proteins at lower cost and with fewer side effects is used in everyday clinical practice. Gene therapy remains an extraordinary challenge in correcting severe hereditary or acquired diseases. The use of genetically modified animal cell lines producing growth factors, insulin or erythropoetin, which are subsequently encapsulated and transferred to man, represents an attractive approach for gene therapy.

Molecular mechanisms of follicular associated epithelium differentiation

Les muqueuses respiratoires, genitales et digestives sont continuellement exposées aux antigènes de l?alimentation, à la flore intestinale et aux pathogènes. Cela implique une activité immunologique intense et finement régulée dans ces tissus. On admet que la modulation de ces réponses immunitaires muqueuses s?effectue dans des organes sentinels spécifiques appelés o-MALT (organized mucosal associated lymphoid tissues). Ces processus de modulation et la biologie de ces sites immuno-inducteurs sont peu connus. Ceci est pourtant d?une grande relevance si l?on veut faire un design rationnel de drogues et de vaccins muqueux. Dans l?intestin grèle, ces organes sont composés de follicules multiples et sont appelés plaques de Peyer. Ils sont constitués de follicules enrichis en cellules B comprenant ou non un centre germinatif, de regions interfolliculaires comprenant des cellules T, et d?une région en d ome riche en cellules dendritiques, cellules B naives et cellules T CD4+, surmontée par un epithelium specialisé, le FAE (epithelium associé aux follicules). Le FAE contient des cellules M spécialisées dans le transport de macromolécules et micro-organismes de la lumière intestinale au tissu lymphoide sous-jacent. Ce transport des antigènes est une condition obligatoire pour induire une réponse immunitaire. Les cellules du FAE, outre les cellules M, expriment un programme de différenciation distinct de celui des cellules associées aux villosités. Ceci est characterisé par une baisse des fonctions digestives et de défenses, et l?expression constitutive des chimiokines: CCL20 et CCL25. Le but de l?étude présentée ici est de rechercher les facteurs cellulaires et/ou moléculaire responsables de cette différenciation. Certaines études ont démontré l?importance du contact entre le compartiment mésenchymateux et l?épithelium pour la morphogenèse de ce dernier. En particulier, les molécules de la matrice extracellulaire peuvent activer des gènes clefs qui, à leur tour, vont controler l?adhésion et la differenciation cellulaire. Dans l?intestin, les cellules mésenchymateuses différencient en myofibroblastes qui participent à l?élaboration de la matrice extracellulaire. Dans cette étude, nous avons décrit les différences d?expression de molécules de la matrices sous le FAE et les villosités. Nous avons également montré une absence de myofibroblastes sous le FAE. Suite à plusieurs évidences expérimentales, certains ont proposé une influence des composés présents dans la lumière sur la différenciation et/ou la maturation des plaques de Peyer. La chimiokine CCL20, capable de recruter des cellules initiatrices de la réponse immunitaire, constitue notre seul marqueur positif de FAE. Nous avons pu montrer que la flagelline, un composé du flagelle bactérien, était capable d?induire l?expression de CCL20 in vitro et in vivo. Cet effet n?est pas limité aux cellules du FAE mais est observé sur l?ensemble de l?épithelium intestinal. Molecular mechanisms of FAE differenciation. La signalement induit par la lymphotoxine ß est critique pour l?organogenèse des plaques de Peyer, car des souris déficientes pour cette molécules ou son récepteur n?ont ni plaque de Peyer, ni la plupart des ganglions lymphatiques. Nous avons obtenus plusieurs évidences que la lymphotoxine ß était impliquée dans la régulation du gène CCL20 in vitro et in vivo.<br/><br/>Mucosal surfaces of the respiratory, genital and digestive systems are exposed to food antigens, normal bacterial flora and oral pathogens. This justifies an intense and tuned immunological activity in mucosal tissues. The modulation of immune responses in the mucosa is thought to occur in specific sentinel sites, the organized mucosa associated lymphoid tissues (o-MALT). This immune modulation and the biology of these immune-inductive sites are poorly understood but highly important and relevant in the case of drugs and vaccines design. In the small intestine, these organs (gut associated lymphoid tissue : GALT) consists of single or multiple lymphoid follicles, the so-called Peyer?s patches (PP), with typical B cell-enriched follicles and germinal centers, inter-follicular T cell areas, and a dome region enriched in dendritic cells, naive B cells, and CD4+ T cells under a specialized follicle associated epithelium (FAE). To trigger protective immunity, antigens have to cross the mucosal epithelial barrier. This is achieved by the specialized epithelial M cells of the FAE that are able to take up and transport macromolecules and microorganisms from the environment into the underlying organized lymphoid tissue. The ontogeny of M cells remains controversial: some data are in favor of a distinct cell lineage, while others provide evidence for the conversion of differentiated enterocytes into M cells. In this study we mapped the proliferative, M cells and apoptotic compartments along the FAE. Enterocytes acquire transient M cell features as they leave the crypt and regain enterocyte properties as they move towards the apoptotic compartment at the apex of the FAE, favouring the hypothesis of a plastic phenotype. The follicle-associated epithelium (FAE) is found exclusively over lymphoid follicles in mucosal tissues, including Peyer?s patches. The enterocytes over Peyer?s patches express a distinct phenotype when compared to the villi enterocytes, characterized by the down regulation of digestive and defense functions and the constitutive expression of chemokines, i.e. CCL20 and CCL25. The purpose of this study was to investigate and identify the potential cells and/or molecules instructing FAE differentiation. Contact between the epithelial and the mesenchymal cell compartment is required for gut morphogenesis. Extracellular matrix molecules (ECM) can activate key regulatory genes which in turn control cell adhesion and differentiation. In the gut, mesenchymal cells differentiate into myofibroblats that participate to the elaboration of ECM. We have described a differential expression of extracellular matrix components under the FAE, correlating with the absence of subepithelial myofibroblats. Molecular mechanisms of FAE differenciation. Different studies proposed an influence of the luminal compartment in the differentiation and/or the maturation of PP. CCL20, a chemokine able to recruit cells that initiate adaptive immunity constitutes our first positive FAE molecular marker. We have shown that CCL20 gene expression is inducible in vitro and in vivo in intestinal epithelium by flagellin, a component of bacterial flagella. This effect was not restricted to the FAE. Lymphotoxin ß (LTß) signaling is critical for PPs organogenesis as LT deficient mice as well as LTß-receptor-/- mice lack PPs and most of the lymph nodes (LN). The continuous signaling via LTßR-expressing cells appears necessary for the maintenance throughout the life of PP architecture. We obtained in vitro and in vivo evidence that LTß signalling is involved in CCL20 gene expression.

Avaluació de la flora i vegetació del bosc de ribera dins l'àmbit del projecte "Riberes del Ter"

L’any 2009, els ajuntaments de Manlleu, Les Masies de Voltregà i Torelló, sota la coordinació del Centre d’Estudis dels Rius Mediterranis (CERM, en endavant), varen engegar un projecte anomenat “Riberes del Ter”. Aquest projecte consisteix en la restauració ecològica del bosc de ribera al curs migalt del riu Ter, partint d’acords de custòdia amb els titulars de les finques (públics o privats). L’objectiu dels acords és ordenar els usos que afecten el bosc de ribera per millorar-ne l’estat ecològic i garantir-ne la conservació. Els instruments per aconseguir-ho són les tècniques silvícoles combinades amb la regulació dels usos ramaders, lúdics i de gestió de la biodiversitat (CAMPRODON et al., 2010). Tanmateix, l’avaluació de l’estat de conservació d’espais naturals és part fonamental, tant per la realització d’estudis del medi com també per poder planificar i desenvolupar projectes de restauració. La valoració de la qualitat o naturalitat d’un espai permet realitzar futures comparacions i conèixer d’una forma objectiva l’eficàcia de mesures correctores i treballs de restauració. En aquest sentit, el projecte “Riberes del Ter” es complementa també amb el projecte “RICOVER” (programa Interreg SUDOE 2009-2011) que, de forma prèvia i posterior a les actuacions, permet efectuar un pla de seguiment de variables hidromorfològiques i biològiques (CAMPRODON et al., 2010; ORDEIX et al., 2010). El present treball s’emmarca doncs, dins d’aquest dos projectes, com un primer estudi de vegetació riberenca al llarg del tram de riu afectat pels treballs de restauració, per poder avaluar en la posteritat els resultats de les actuacions de millora de l’entorn del riu.

Contribució al coneixement de la flora catalana occidental, III

En aquest treball s'aporten dades sobre la presència de nous tàxons a la plana occidental catalana, i que impliquen, en la majoria dels casos, ampliar de manera notable l'àrea de distribució de l'espècie. Són de destacar Cheirolophus intybaceus (Lam.) Dostál, Iris spuria L., Lathyrus annuus L., Phagnalon rupestre (L.) DC., Succisa pratensis Moench, Trigonella gladiata Steven ex Bieb. i Orchis laxiflora Lam. subsp. palustris (Jacq.) Bonnier & Layens.

Aportaciones a la Flora del Sudeste Iberico, II.

Aportaciones a la Flora del Sudeste Ibérico, II.

Aportacion al conocimiento de la flora liquenica silicicola de la parte culminal de Sierra Nevada

Aportación al conocimiento de la flora liquénica silicícola de la parte culminal de Sierra Nevada comprendida entre los Peñones de San Francisco (2.500 m) y el Mulhacén (3.482 m). Se da cuenta de 104 especies, en su mayoría nuevas citas para Sierra Nevada, entre las cuales, son táxones nuevos para España los que se citan en el resumen en inglés.

De Flora Dianicae

Breve aportación al catálogo provincial de RIGUAL (Flora y Vegetación de la provincia de Alicante, Inst. Est. Alicantinos, 1972), a la par que se recuerda la estancia de ROUY en este enclave (Excursions botaniques en Espagne. Bull. Soc. Bot. France 31:33-41, 52-56. 1884). En el trabajo de Rouy, que no menciona el señor Rigual, se recogen no pocas novedades, algunas de indudable interés para la flora alicantina. De las mismas, aquí nos limitaremos a transcribir las que hemos podido testificar en el campo. Señalamos con un asterisco (*) las novedades al mencionado catálogo. Coordenadas UTM en cuadrículas de 10 Km de lado. Designación de uso y zona para todas las localidades: 31S. Testimonios: herbario de la Facultad de Farmacia de Barcelona (BCF).

Consideraciones generales sobre la flora del valle de Ribes

Coup d'oeil sur la flore de la vallée de Ribes (Pyrénées catalanes). On fait des commentaires critiques des principales publications apportant des données floristiques sur la contrée: le «Catàlech de la Flora de la Valí de Nuria», d'E. VAYREDA I VILA , la «Flora de la Valí de Nuria i els seus encontorns», de Frère SfeiMNEN, la «Flora de Catalunya», de J. CADEVALL I DARS et la «Végétation alpine des Pyrénées orientales», de J. BRAUNBLANQUET. On donne una liste partielle des espèces l'existence desquelles dans la région malgré y avoir été indiqués par divers auteurs parait inadmissible ou, au moins, fort douteuse. On indique la répartition dans la contrée de quelques plantes appartenant à des éléments phytogéographiques différents et on divise la contrée en des petits territoires, caractérisé chacun d'eux par de divers groupes d'espèces.

Notes sobre la flora de la Terra Baixa Catalana.

Durant les nostres excursions hem aplegat una bona quantitat de dades sobre la flora catalana. D'aquestes dades hem seleccionat les que creiem que son mes intéressants tant per la seva novetat com per la seva raresa. Llevat de molt poques excepcions ara només aportem citacions de plantes de la terra baixa i, en especial, de les serralades costeres catalanes. Ultra la indicació de les dades de localització de cada pianta (comarca, municipi, indret concret i altitud) i d'alguna indicació de l'habitat o l'ecologia, hi afegim la notació del quadrat U.T.M. de 10 km de costat. Remarquem que en alguns casos, quan ens ha estât possible, hi afegim, entre claudàtors, la xifra del quadrat d'U.T.M. d'un quilòmetre de costat. A la llista que segueix, les espècies són disposades per ordre alfabètic.

Biological Flora of the British Isles: Ambrosia artemisiifolia

1. This account presents information on all aspects of the biology of Ambrosia artemisiifolia L. (Common ragweed) that are relevant to understanding its ecology. The main topics are presented within the standard framework of the Biological Flora of the British Isles: distribution, habitat, communities, responses to biotic factors, responses to environment, structure and physiology, phenology, floral and seed characters, herbivores and disease, history, and conservation, impacts and management. 2. Ambrosia artemisiifolia is a monoecious, wind-pollinated, annual herb native to North America whose height varies from 10 cm to 2.5 m according to environmental conditions. It has erect, branched stems and pinnately lobed leaves. Spike-like racemes of male capitula composed of staminate (male) florets terminate the stems, while cyme-like clusters of pistillate (female) florets are arranged in groups the axils of main and lateral stem leaves. 3. Seeds require prolonged chilling to break dormancy. Following seedling emergence in spring, the rate of vegetative growth depends on temperature, but development occurs over a wide thermal range. In temperate European climates, male and female flowers are produced from summer to early autumn (July to October). 4. Ambrosia artemisiifolia is sensitive to freezing. Late spring frosts kill seedlings and the first autumn frosts terminate the growing season. It has a preference for dry soils of intermediate to rich nutrient level. 5. Ambrosia artemisiifolia was introduced into Europe with seed imports from North America in the 19th century. Since World War II, it has become widespread in temperate regions of Europe and is now abundant in open, disturbed habitats as a ruderal and agricultural weed. 6. Recently, the N. American ragweed leaf beetle (Ophraella communa) has been detected in southern Switzerland and northern Italy. This species appears to have the capacity to substantially reduce growth and seed production of A. artemisiifolia. 7. In heavily infested regions of Europe, A. artemisiifolia causes substantial crop-yield losses and its copious, highly allergenic pollen creates considerable public health problems. There is consensus among models that climate change will allow its northward and up-hill spread in Europe.

Mixomicetes nuevos o interesantes para la flora iberica y Balear. III

Señalamos la presencia de Calomyxa metallica, Clastoderma debaryanum y Dianema harveyi en diferentes localidades peninsulares. De dichas especies, no indicadas hasta el momento para la flora española, comentamos la corologia, ecologia y caracteres diferenciales.