Impact of genetic SLC28 transporter and ITPA variants on ribavirin serum level, hemoglobin drop and therapeutic response in patients with HCV infection.

BACKGROUND & AIMS: In the last decade, pegylated interferon-α (PegIFN-α) plus ribavirin (RBV) was the standard treatment of chronic hepatitis C for genotype 1, and it remains the standard for genotypes 2 and 3. Recent studies reported associations between RBV-induced anemia and genetic polymorphisms of concentrative nucleoside transporters such as CNT3 (encoded by SLC28A3) and inosine triphosphatase (encoded by ITPA). We aimed at studying genetic determinants of RBV kinetics, efficacy and treatment-associated anemia. METHODS: We included 216 patients from two Swiss study cohorts (61% HCV genotype 1, 39% genotypes 2 or 3). Patients were analyzed for SLC28A2 single nucleotide polymorphism (SNP) rs11854484, SLC28A3 rs56350726, and SLC28A3 rs10868138 as well as ITPA SNPs rs1127354 and rs7270101, and followed for treatment-associated hemoglobin changes and sustained virological response (SVR). In 67 patients, RBV serum levels were additionally measured during treatment. RESULTS: Patients with SLC28A2 rs11854484 genotype TT had higher dosage- and body weight-adjusted RBV levels than those with genotypes TC or CC (p=0.02 and p=0.06 at weeks 4 and 8, respectively). ITPA SNP rs1127354 was associated with hemoglobin drop ≥3 g/dl during treatment, in genotype (relative risk (RR)=2.1, 95% CI 1.3-3.5) as well as allelic analyses (RR=2.0, 95%CI 1.2-3.4). SLC28A3 rs56350726 was associated with SVR in genotype (RR=2.2; 95% CI 1.1-4.3) as well as allelic analyses (RR=2.0, 95% CI 1.1-3.4). CONCLUSIONS: The newly identified association between RBV serum levels and SLC28A2 rs11854484 genotype, as well as the replicated association of ITPA and SLC28A3 genetic polymorphisms with RBV-induced anemia and treatment response, may support individualized treatment of chronic hepatitis C and warrant further investigation in larger studies.

Quality of life transformations before and after kidney transplantation: A prospective qualitative study.

The aim of this IRB-approved study was to analyze prospectively quality of life (QOL) and psychological changes in 30 ESRD patients before and after kidney transplantation (KT). Semi-structured interviews were conducted after inclusion on the waiting list (A). Follow-up interviews were performed 6 months later with patients still awaiting KT (B6, n= 15), and with transplant recipients 6, 12 and 24 months after KT (C6, n=15; C12, n=15; C24, n=14). Qualitative thematic analysis was performed. A: All patients reported loss of freedom, 87% tried to maintain normality; 57% modified medical directives. All mentioned emotional fragility, negative thoughts (43%), and suicidal thoughts (20%) related to loss of QOL from dialysis (D), and professional tension (26%). B6: 40% reported no change compared to baseline, while 60% mentioned increase of illness intrusiveness, 46% D side effects, 40% communication problems, and 33% concerns about the waiting list handling. Fear of emotional breakdown (40%), couple problems (47%), and worsened professional difficulties (20%) were reported. C6: All patients reported recovery of QOL and concerns about acute rejection. 73% were anxious about laboratory results. 93% felt dependent on immunosuppressants (IS), 47% reported difficulties coping with their regimen, and 47% were concerned about side effects; 67% had resumed work, but medical constraints led 40% to professional stigmatization. C12: All enjoyed good QOL. Adherence to IS was mandatory (100%). All were aware of the limited long-term graft survival and 47% anxious about a possible return to D. 60% underlined positive life value; 47% resumed a full time job; 40% were on social security. C24: Good QOL was underlined (86%). Patients stated they would prefer re-TX to resuming D (71%). Post-TX health problems were mentioned (64%); increase of creatinine levels induced fear (36%). 79% complained about side effects. 64% reported changes in life values. This study reveals positive QOL and psychological transformations after KT, which are associated with positive changes related to graft survival and freedom from D. Psychological follow-up should be offered to patients who face relapsing ESRD or post-TX co-morbidities.

La bibliothèque de Fulvio Orsini : contributions à l'histoire des collections d'Italie et à l'étude de la Renaissance / Pierre de Nolhac

Collection : Bibliothèque de l'École des Hautes-Études. Sciences philologiques et historiques ; 74

Antagonistic roles of Notch and p63 in controlling mammary epithelial cell fates.

The breast epithelium has two major compartments, luminal and basal cells, that are established and maintained by poorly understood mechanisms. The p53 homolog, p63, is required for the formation of mammary buds, but its function in the breast after birth is unknown. We show that in primary human breast epithelial cells, maintenance of basal cell characteristics depends on continued expression of the p63 isoform, DeltaNp63, which is expressed in the basal compartment. Forced expression of DeltaNp63 in purified luminal cells confers a basal phenotype. Notch signaling downmodulates DeltaNp63 expression and mimics DeltaNp63 depletion, whereas forced expression of DeltaNp63 partially counteracts the effects of Notch. Consistent with Notch activation specifying luminal cell fate in the mammary gland, Notch signaling activity is specifically detected in mice at sites of pubertal ductal morphogenesis where luminal cell fate is determined. Basal cells in which Notch signaling is active show decreased p63 expression. Both constitutive expression of DeltaNp63 and ablation of Notch signaling are incompatible with luminal cell fate. Thus, the balance between basal and luminal cell compartments of the breast is regulated by antagonistic functions of DeltaNp63 and Notch.Cell Death and Differentiation advance online publication, 9 April 2010; doi:10.1038/cdd.2010.37.

Graeciae antiquae tabula geographica, cujus quinque majores partes sunt Macedonia, Thessalia, Epirus, Achaia, et Peloponnesus, eaeque in minores partes seu populos distinctae... / Authore Nicolae Sanson... 1636

Échelle(s) : [1:2 345 000 environ], Mille passus 100, Stadia 800 [= 7,7 cm]

Mixed testicular germ cell tumor presenting as metastatic pure choriocarcinoma involving the maxillary gingiva.

Gingival metastases are infrequent and invariably associated with a widespread disease and a poor prognosis. Because of their unremarkable clinical appearance, they can be difficult to distinguish from more common gingival hyperplastic or reactive lesions, such as pyogenic granuloma, peripheral giant cell granuloma, and peripheral ossifying granuloma. We are reporting here an unusual case of a 36-year-old man with a mixed testicular germ cell tumor presenting as a metastatic pure choriocarcinoma involving the maxillary gingiva, extending from the first left premolar to the left second maxillary molar, mimicking a 'benign looking' gingival mass. Gingival metastases may be the first manifestation of a widespread metastatic disease and therefore particular attention must be paid to gingival lesions associated with atypical clinical symptoms and/or signs.

High elevation Plantago lanceolata plants are less resistant to herbivory than their low elevation conspecifics: is it just temperature?

Traits that mediate species interactions are evolutionarily shaped by biotic and abiotic drivers, yet we know relatively little about the relative importance of these factors. Herbivore pressure, along with resource availability and third-party' mutualists, are hypothesized to play a major role in the evolution of plant defence traits. Here, we used the model system Plantago lanceolata, which grows along steep elevation gradients in the Swiss Alps, to investigate the effect of elevation, herbivore pressure, mycorrhizal inoculation and temperature on plant resistance. Over a 1200 m elevation gradient, the levels of herbivory and iridoid glycosides (IGs) declined with increasing elevation. By planting seedlings at three different elevations, we further showed that both low-elevation growing conditions and mycorrhizal inoculation resulted in increased plant resistance to herbivores. Finally, using a temperature-controlled experiment comparing high- and low-elevation ecotypes, we showed that high-elevation ecotypes are less resistant to herbivory, and that lower temperatures impair IGs deployment after herbivore attack. We thus propose that both lower herbivore pressure, and colder temperatures relax the defense syndrome of high elevation plants.

Graecia Sophiani / Ex conatibus Geographicis Abrahami Ortelii Antverpiensis

Échelle(s) : [1:3 700 000 environ], Mil. Germ. 40 [= 7,7 cm]

Graeciae Antiquae tabulam hanc geographicam / offert, dedicat, consecrat Nic. Sanson Abbavillaeus

Échelle(s) : [1:1 800 000 ca] Scala Centum M. Passuum sine Octingentorum Stud., Mille Pass. ils Millia 100 = [8 cm], Stadia 800 = [8 cm] (d'après échelles graphiques).

Graeciae Antiquae tabulam hanc geographicam / offert, dedicat, consecrat Nic. Sanson Abbavillaeus

Échelle(s) : [1:1 800 000 ca] Scala Centum M. Passuum sine Octingentorum Stud., Mille Pass. ils Millia 100 = [8 cm], Stadia 800 = [8 cm] (d'après échelles graphiques).

Movement, impacts and management of plant distributions in response to climate change: insights from invasions

A major challenge in this era of rapid climate change is to predict changes in species distributions and their impacts on ecosystems, and, if necessary, to recommend management strategies for maintenance of biodiversity or ecosystem services. Biological invasions, studied in most biomes of the world, can provide useful analogs for some of the ecological consequences of species distribution shifts in response to climate change. Invasions illustrate the adaptive and interactive responses that can occur when species are confronted with new environmental conditions. Invasion ecology complements climate change research and provides insights into the following questions: i) how will species distributions respond to climate change? ii) how will species movement affect recipient ecosystems? and iii) should we, and if so how can we, manage species and ecosystems in the face of climate change? Invasion ecology demonstrates that a trait-based approach can help to predict spread speeds and impacts on ecosystems, and has the potential to predict climate change impacts on species ranges and recipient ecosystems. However, there is a need to analyse traits in the context of life-history and demography, the stage in the colonisation process (e.g., spread, establishment or impact), the distribution of suitable habitats in the landscape, and the novel abiotic and biotic conditions under which those traits are expressed. As is the case with climate change, invasion ecology is embedded within complex societal goals. Both disciplines converge on similar questions of "when to intervene?" and "what to do?" which call for a better understanding of the ecological processes and social values associated with changing ecosystems.

The role of the T-cell receptor (TCR) in alpha beta/gamma delta lineage commitment: clues from intracellular TCR staining.

T cells belong to two mutually exclusive lineages expressing either alpha beta or gamma delta T-cell receptors (TCR). Although alpha beta and gamma delta cells are known to share a common precursor the role of TCR rearrangement and specificity in the lineage commitment process is controversial. Instructive lineage commitment models endow the alpha beta or gamma delta TCR with a deterministic role in lineage choice, whereas separate lineage models invoke TCR-independent lineage commitment followed by TCR-dependent selection and maturation of alpha beta and gamma delta cells. Here we review the published data pertaining to the role of the TCR in alpha beta/gamma delta lineage commitment and provide some additional information obtained from recent intracellular TCR staining studies. We conclude that a variant of the separate lineage model is best able to accommodate all of the available experimental results.

Extraits de CHRONIQUES, et en particulier de textes relatifs à la NORMANDIE.

Contient : Extrait des Annales S. Dionysii ad cyclos paschales [cf. E. Berger, dans Bibl. de l'Ecole des chartes, t. XL, p. 270] ; Extrait de la chronologie des rois de France, de Bernard Gui, d'après un ms. de Petau, communiqué par Camuzat ; Fragment sur Philippe le Bel, par un moine de Saint-Denis (Frère Ives) [cf. Molinier, Sources, n° 2847] ; Extrait du Chronicon Colmariense [Mon. Germ., SS., t. XVII, p. 240] ; Lettre de Philippe IV relative à la bataille de Mons-en-Pévèle, septembre 1304 ; Fragment (1285-1343) de la chronique de l'Anonyme de Caen [Molinier, n° 1163] ; Extraits historiques relatifs aux fils de Philippe le Bel ; Chartes de Guillaume le Conquérant et d'Henri Ier pour l'abbaye de Montebourg ; Notice de la fondation de ladite abbaye ; Gesta abbatum Fontanellensium, rédaction abrégée. Incipit : « Wandregisilus qui et Wando... » [cf. Archiv, VIII, 373] ; Gesta abbatum Fontanellensium, précédés de la Commemoratio Ansberti [cf. éd. Loewenfeld, Hanovre, 1888, in-8°, et D'Achery, Spicil., éd. in-fol., t. II, p. 263] ; Chartes de l'abbaye de Saint-Wandrille (1024-1177) et extraits de pièces des XIIIe et XIVe siècles relatives à la même abbaye ; Extraits de la chronique de Robert de Thorigny, d'après un ms. du Mont-Saint-Michel ; Extraits d'Annales de Rouen, d'après un ms. de Bigot [ms. lat. 5530 ; cf. L. Delisle, dans Hist. littér., t. XXXII, p. 196] ; Chronologia urbis Rothomagensis (94-1549), composée par M. de La Mare ; Chron. Nortmannorum [cf. Duchesne, Rer. Franc. scriptores, t. II, p. 524, et L. Delisle, dans Notices et extraits, t. XXXVIII, p. 697] ; Annales de Saint-Wandrille, dites Chronicon Thosanum, [cf. Hist. littér., t. XXXII, p. 204] ; Eloge en vers de Lanfranc [Mabillon, AA. SS. Ben., t. VI, II, p. 659], d'après un ms. de Saint-Florent-lès-Saumur ; Trêve de Dieu pour la Normandie, du temps de Gullaume le Conquérant ; Extrait d'un ms. intitulé « Cursus Normanniae », communiqué par J. Sirmond ; Notice sur les abbés de Fécamp, jusqu'à Henri de Lorraine (1613-1642), d'après un ms. de M. de la Meschinière ; Catalogue des abbés du même monastère jusqu'à François de Joyeuse (1600-1613) ; Extraits d'un cartulaire de Saint-Michel du Tréport ; Extraits d'un calendrier de la même abbaye ; Extraits de la vie de saint Exupère, évêque de Bayeux ; Vers sur l'abbaye de Jumièges, attribués au moine Adrien (cf. Frère, Bibliogr. normand, t. I, p. 154) ; Extraits d'un calendrier des chanoines d'Eu ; Liste des évêques de Lisieux jusqu'à Guillaume Du Vair (1618-1621) ; Evêques de Bayeux jusqu'à Jacques d'Angennes (1606-1647) ; Evêques de Coutances jusqu'à Nicolas de Briroi (1589-1620) ; Evêques d'Evreux jusqu'à François de Péricard (1613-1646) ; Notes sur les chartes de l'abbaye de Savigny ; Chartes du Breuil-Benoît ; Catalogue des abbés de Jumièges ; Fondation de l'abbaye de Blanchelande (1154), et extraits des chartes de ce monastère ; Notes sur le fouage à lever en Normandie et sur les forteresses occupées par le roi, d'après les registres du Trésor des chartes ; Extraits des archives de Notre-Dame d'Ardenne ; Extraits des archives de Saint-Etienne de Caen ; Chartes diverses relatives à la Normandie (1217-1262) ; Annales d'Avranches, 837-1359 [cf. Hist. de Fr., t. XXIII, p. 568] ; Extraits de deux rédactions de la Vita Vanengi [Bibl. hag. lat., 8811 et 8813] ; Traité entre Abu-Issac et Vibaldus, envoyé de l'empereur Frédéric II (1231), traduction latine par M. Obelius Cicero [Mon. Germ., Const., t. II, p. 187] ; Extraits de chroniques arabes relatifs à l'histoire de Sicile, traduits par le même