Combining niche modelling and landscape genetics to study local adaptation: A novel approach illustrated using alpine plants

Understanding the factors that shape adaptive genetic variation across species niches has become of paramount importance in evolutionary ecology, especially to understand how adaptation to changing climate affects the geographic range of species. The distribution of adaptive alleles in the ecological niche is determined by the emergence of novel mutations, their fitness consequences and gene flow that connects populations across species niches. Striking demographical differences and source sink dynamics of populations between the centre and the margin of the niche can play a major role in the emergence and spread of adaptive alleles. Although some theoretical predictions have long been proposed, the origin and distribution of adaptive alleles within species niches remain untested. In this paper, we propose and discuss a novel empirical approach that combines landscape genetics with species niche modelling, to test whether alleles that confer local adaptation are more likely to occur in either marginal or central populations of species niches. We illustrate this new approach by using a published data set of 21 alpine plant species genotyped with a total of 2483 amplified fragment length polymorphisms (AFLP), distributed over more than 1733 sampling sites across the Alps. Based on the assumption that alleles that were statistically associated with environmental variables were adaptive, we found that adaptive alleles in the margin of a species niche were also present in the niche centre, which suggests that adaptation originates in the niche centre. These findings corroborate models of species range evolution, in which the centre of the niche contributes to the emergence of novel adaptive alleles, which diffuse towards niche margins and facilitate niche and range expansion through subsequent local adaptation. Although these results need to be confirmed via fitness measurements in natural populations and functionally characterised genetic sequences, this study provides a first step towards understanding how adaptive genetic variation emerges and shapes species niches and geographic ranges along environmental gradients.

MYC-IG rearrangements are negative predictors of survival in DLBCL patients treated with immunochemotherapy: a GELA/LYSA study.

Diffuse large B-cell lymphoma (DLBCL) with MYC rearrangement (MYC-R) carries an unfavorable outcome. We explored the prognostic value of the MYC translocation partner gene in a series of MYC-R de novo DLBCL patients enrolled in first-line prospective clinical trials (Groupe d'Etudes des Lymphomes de l'Adulte/Lymphoma Study Association) and treated with rituximab-anthracycline-based chemotherapy. A total of 774 DLBCL cases characterized for cell of origin by the Hans classifier were analyzed using fluorescence in situ hybridization with BCL2, BCL6, MYC, immunoglobulin (IG)K, and IGL break-apart and IGH/MYC, IGK/MYC, and IGL/MYC fusion probes. MYC-R was observed in 51/574 (8.9%) evaluable DLBCL cases. MYC-R cases were predominantly of the germinal center B-cell-like subtype 37/51 (74%) with no distinctive morphologic and phenotypic features. Nineteen cases were MYC single-hit and 32 cases were MYC double-hit (MYC plus BCL2 and/or BCL6) DLBCL. MYC translocation partner was an IG gene in 24 cases (MYC-IG) and a non-IG gene (MYC-non-IG) in 26 of 50 evaluable cases. Noteworthy, MYC-IG patients had shorter overall survival (OS) (P = .0002) compared with MYC-negative patients, whereas no survival difference was observed between MYC-non-IG and MYC-negative patients. In multivariate analyses, MYC-IG predicted poor progression-free survival (P = .0051) and OS (P = .0006) independently from the International Prognostic Index and the Hans classifier. In conclusion, we show in this prospective randomized trial that the adverse prognostic impact of MYC-R is correlated to the MYC-IG translocation partner gene in DLBCL patients treated with immunochemotherapy. These results may have an important impact on the clinical management of DLBCL patients with MYC-R who should be routinely characterized according to MYC partner gene. These trials are individually registered at www.clinicaltrials.gov as #NCT00144807, #NCT01087424, #NCT00169143, #NCT00144755, #NCT00140660, #NCT00140595, and #NCT00135499.

Syndrome de fatigue chronique [Chronic fatigue syndrome].

Le syndrome de fatigue chronique (SFC) est une pathologie invalidante, moins rare qu'on ne le pense (prévalence de l'ordre de 0,3-0,9 %), qui associe un épuisement physique persistant et inexpliqué à des douleurs diffuses, des troubles du sommeil, des troubles neurocognitifs et neurovégétatifs. Sa physiopathologie est controversée, mais les pistes de recherche actuelles convergent vers une atteinte dysimmunitaire, dans laquelle le stress oxydatif et un dysfonctionnement des mitochondries semblent jouer un rôle. Il n'existe pas de médication ayant démontré une efficacité spécifique pour le traitement du SFC. La prise en charge consiste à limiter les investigations superflues et à encourager le patient vers un reconditionnement à l'effort très progressif, dans le cadre d'un counselling empathique visant à prévenir les pensées négatives. Chronic fatigue syndrome (CFS) is a debilitating disorder, characterized by a severe, persistant and unexplained fatigue, which can be associated with diffuse pain, sleep difficulties, neurocognitive and neurovegetative troubles. Its prevalence has been estimated between 0.3 and 0.9%. Though its physiopathology remains controversial, evidence is growing that dysimmunity, oxidative stress and mitochondrial dysfunction are involved in its pathogeny. No medication has demonstrated specifc efficacy in the CFS. The management of CFS involves limiting unnecessary investigations, promoting graded exercice therapy, and providing empathic counselling in order to prevent negative thoughts.

The paracaspase MALT1: biological function and potential for therapeutic inhibition.

The paracaspase MALT1 has a central role in the activation of lymphocytes and other immune cells including myeloid cells, mast cells and NK cells. MALT1 activity is required not only for the immune response, but also for the development of natural Treg cells that keep the immune response in check. Exaggerated MALT1 activity has been associated with the development of lymphoid malignancies, and recently developed MALT1 inhibitors show promising anti-tumor effects in xenograft models of diffuse large B cell lymphoma. In this review, we provide an overview of the present understanding of MALT1's function, and discuss possibilities for its therapeutic targeting based on recently developed inhibitors and animal models.

Montrer « l'exorcisme » de Sarah Palin sur le web : enquête(s) sur la portée politique d'images religieuses

En septembre 2008, une vidéo est diffusée sur internet montrant Sarah Palin, alors candidate à la vice-présidence des États-Unis, en train de recevoir « une protection contre la sorcellerie » lors d'une célébration religieuse. La séquence est aussitôt reprise par les médias du monde entier qui s'interrogent et enquêtent sur les rapports entre ces images et l'engagement politique de la républicaine. Cet article suit la circulation de la vidéo au travers de différentes scènes de visibilité, allant des médias généralistes au site internet de l'Église où elle a été tournée, en passant par un blog qui a attiré l'attention publique sur ces images. L'enquête met au jour comment ce film a été compris dans ces différents contextes, et montre les effets de ce travail d'interprétation en 2011, suite à l'avènement du Tea Party et à l'horizon de la prochaine échéance présidentielle. La vidéo qui, en 2008, apparaissait dans les médias généralistes comme une illustration de la « bigoterie » de Palin a contribué à figurer, en 2011, une menace « théocratique » pour la démocratie américaine.

From breaking the rule to making the rules : the adoption, entrenchment and diffusion of gender quotas in France

Once a country allergic to any type of preferential treatment or quota measure for women, France has become a country that applies gender quotas to regulate women's presence and representation in politics, the business sector, public bodies, public administration, and even some civil society organizations. While research has concentrated on the adoption of electoral gender quotas in many countries and their international diffusion, few studies focus on explaining the successful diffusion of gender quotas from politics to other domains in the same country. This paper proposes to fill this gap by studying the particularly puzzling case of a country that at one point strongly opposed the adoption of gender quotas in politics, but, in less than a decade, transformed into one of the few countries applying gender quotas across several policy domains. This paper argues that the legal entrenchment of the parity principle, the institutionalization of parity in several successive women's policy agencies, and key players in these newly created agencies are mainly responsible for this unexpected development. The diffusion of gender quotas in France thus offers an illuminating example of under which conditions women's policy agencies can act autonomously to diffuse and impose a new tool for gender equality

Validation du GAP Index, un outil prédictif de mortalité dans la fibrose pulmonaire idiopathique

Fibrose pulmonaire idiopathique La fibrose pulmonaire idiopathique (FPI, Idiopathic Pulmonary Fibrosis) est une maladie diffuse du parenchyme pulmonaire de cause inconnue caractérisée par une aggravation de la dyspnée, une réduction du volume pulmonaire et une altération des échanges gazeux. Elle est la plus fréquente de pneumopathies interstitielles idiopathiques (IIPs, Idiopathic Interstitial Pneumonias), avec une incidence annuelle estimée entre 4,6 et 16,3 pour 100'000 personnes et une prévalence de 13 à 20 cas pour 100 000 personnes. Son évolution est progressive, irréversible et de mauvais pronostic avec une survie médiane de 2 à 3.5 ans et une survie à 5 ans de moins de 20%.

Il viaggio di Faust in Italia : percorsi di ricezione di un mito moderno

La tesi descrive il fenomeno di ricezione del mito faustiano all'interno della tradizione letteraria italiana di Otto e Novecento (1808-1945) nel suo sviluppo diacronico, individuando i nodi processuali emergenti ritenuti sistematici accanto alle tipologie predominanti della risposta testuale e alle più proficue rifunzionalizzazioni letterarie. La storia del mito di Faust è stata considerata aristotelicamente nella sua natura complessa ed evolutiva di fabula rinarrata, e di volta in volta risemantizzata in nuovi sistemi di valori, estetici e ideologici. Ma soprattutto in nuovi sistemi testuali. Scopo primario è stato infatti quello di comprendere come il mito di Faust sia entrato dentro alla cultura letteraria italiana e come abbia agito al suo interno, interferendo con essa. Naturalmente lo scambio e gli sviluppi hanno investito in modo reciproco e la tradizione accogliente e il mito stesso, producendo un allargamento esegetico delle sue possibilità semantiche: è infatti emersa una storia testuale che tematizza nel tempo il medesimo mito lungo assi interpretative anche estremamente divergenti. La ricerca ha portato alla scoperta di una ricca testualità rimossa dal canone della storia della letteratura italiana, anche se spesso prevalgono i testi-documento sui testi esteticamente più validi e significativi in sé; si tratta di una testualità talmente quantitativamente ricca da invitare ad un ripensamento qualitativo del fenomeno generale. Il mito di Faust, per due secoli percepito dalla critica dominante come distante ed estraneo alla cultura letteraria italiana, è invece riuscito ad entrare nella tradizione letteraria italiana, anche se attraverso modalità molto controverse: in linea di massima è potuto passare dal canone statico al canone dinamico laddove ha saputo influenzare e stimolare nuove vie significative di sviluppo formale. Il confronto della cultura letteraria italiana con il mito di Faust è stato in effetti caratterizzato subito da un doppio movimento discratico di rifiuto e dialogo. Il principale fattore di rifiuto è stato di carattere culturale: la difficoltà ad accettare un equilibrio fatto non di antitesi risolte in una sintesi ma di polarità aperte, irrisolte, in perpetuo bilanciamento, anche a livello formale reso in una tragedia franta in scene apparentemente autonome, divisa in due parti così diverse e chiusa da un lieto fine, mal si confaceva ai diffusi canoni classicisti di equilibrio formale, nonché alle esigenze romantiche di poesia moralmente chiara nel suo messaggio. Da qui le diffuse accuse di scarsa chiarezza e ambiguità morale, che andavano direttamente ad incontrarsi e sommarsi con i pregiudizi più propriamente teologico- religiosi di estraneità a quel mito nato come saga luterana dichiaratamente anti-papale. La condanna di carattere moralistico-cattolico risulta nei fatti propria più di certa cultura che non del largo pubblico che invece nel corso dell'Ottocento dimostra di gradire le versioni per musica e balletto di argomento faustiano, per quanto semplificata ed edulcorate rispetto alla leggenda originaria così come rispetto alla tragedia goethiana. Rispetto a tutti questi elementi di resistenza e rifiuto l'opera Mefistofele di Boito si presenta come snodo di opposizione consapevole e riferimento duraturo d'interrogazione critica. La principale linea di avvicinamento invece tra la cultura letteraria italiana e il mito di Faust resta quella del parallelo, già ideato dagli stessi intellettuali tedeschi d'inizio Ottocento, con l'opera ritenuta massima nel nuovo canone nazionale italiano da fine Settecento ad oggi: la Divina Commedia. Tanta critica, almeno fino alla metà del XX secolo, si rifà più o meno esplicitamente a questo parallelo pregiudiziale e testualmente piuttosto infondato ma molto produttivo, come si è attestato, a livello creativo. Questa ricostruzione ha voluto nel suo complesso dimostrare sul campo il valore di questo macrotesto faustiano come una delle vie maestre della dialettica tra tradizione e modernità, ancor più significativa nell'ambito di una cultura letteraria come quella italiana che, dopo l'estinguersi della sua centralità in epoca rinascimentale, si è rivelata particolarmente resistente al dialogo con le altre letterature fino al pieno Novecento.