Human epidermal Langerhans cells express the tight junction protein claudin-1 and are present in human genetic claudin-1 deficiency (NISCH syndrome).

Claudin-1 (CLDN1) is a structural tight junction (TJ) protein and is expressed in differentiating keratinocytes and Langerhans cells in the epidermis. Our objective was to identify immunoreactive CLDN1 in human epidermal Langerhans cells and to examine the pattern of epidermal Langerhans cells in genetic human CLDN1 deficiency [neonatal ichthyosis, sclerosing cholangitis (NISCH) syndrome]. Epidermal cells from healthy human skin labelled with CLDN1-specific antibodies were analysed by confocal laser immunofluorescence microscopy and flow cytometry. Skin biopsy sections of two patients with NISCH syndrome were stained with an antibody to CD1a expressed on epidermal Langerhans cells. Epidermal Langerhans cells and a subpopulation of keratinocytes from healthy skin were positive for CLDN1. The gross number and distribution of epidermal Langerhans cells of two patients with molecularly confirmed NISCH syndrome, however, was not grossly altered. Therefore, CLDN1 is unlikely to play a critical role in migration of Langerhans cells (or their precursors) to the epidermis or their positioning within the epidermis. Our findings do not exclude a role of this TJ molecule once Langerhans cells have left the epidermis for draining lymph nodes.

Poesia epica e letteratura femminile nell'Italia del XVII secolo: "L'Enrico, ovvero Bisanzio acquistato" (1635) di Lucrezia Marinelli

Nella mia tesi di dottorato mi concentro sul poema di Lucrezia Marinelli, L'Enrico, ovvero Bisanzio acquistato, pubblicato a Venezia nel 1635, indagando le strategie messe in atto dall'autrice per rivisitare il genere epico in un'ottica di riscatto femminile. Rispetto al canone epico e, in particolare, al modello di riferimento - la Gerusalemme liberata del Tasso - le vicende nodali sono, infatti, riscritte da un punto di vista chiaramente femminile. Pur occupandomi principalmente dell'opera di Marinelli, in alcuni casi nel corso del mio lavoro propongo dei confronti con altri poemi epici e cavallereschi prodotti da donne - in particolare I tredici canti del Floridoro di Moderata Fonte (1581) - volti a mostrare come le scrittrici avessero degli intenti comuni, dialogando in maniera critica con i modelli maschili da cui, tuttavia, traggono ispirazione. Nei primi capitoli del mio lavoro prendo in esame alcuni personaggi tradizionali dell'epica (le guerriere, la maga, ...) presenti ne L'Enrico e ne ripercorro gli episodi topici (le sortite notturne, l'eroe sull'isola, ...) dimostrando come, pur inserendosi coerentemente nel genere epico, siano caratterizzati in modo sostanzialmente diverso rispetto alla precedente tradizione maschile. Il primo capitolo si concentra sulle figure di guerriere, le quali presentano - rispetto ai precedenti modelli - differenze notevoli: non si lasciano coinvolgere in vicende amorose e non finiscono per essere sottomesse o uccise da un uomo, mantenendo così coerentemente intatti i valori di forza e indipendenza. Neppure la maga sull'isola - presa in esame nel capitolo dedicato alle Altre figure di donne idealizzate - è coinvolta in vicende sentimentali o caratterizzata sensualmente. L'autrice la rappresenta, non alla stregua di una tentatrice al servizio delle forze del male, ma come una donna colta, casta e disposta ad aiutare il cavaliere naufragato sulla sua isola. Nello stesso capitolo sono indagate anche altre figure femminili idealizzate, per taluni aspetti meno innovative, ma ugualmente interessanti: la Vergine, la personificazione di Venezia e la Musa. Queste rappresentazioni dal carattere iconico, presentano, infatti, diverse caratteristiche in comune con i personaggi più attivi del poema, le guerriere e la maga. Il capitolo Delle pene e delle tragedie amorose è dedicato all'amore e ai suoi esiti tragici. Le figure di donna coinvolte sono le madri, le mogli e Idillia, in cui è riconoscibile il personaggio topico della "damigella in difficoltà". Queste protagoniste, destinate a soffrire perché abbandonate dall'uomo che amano - il quale sente più forte il richiamo della guerra rispetto a quello dell'amore - servono da exempla, dimostrando che attaccamento affettivo e dipendenza conducono inesorabilmente all'infelicità. Rispetto al canone epico Marinelli riscatta alcune figure femminili, permettendo alle sue guerriere di prendersi la rivincita, vendicando la morte di eroine quali Camilla e Clorinda. Conseguentemente, alcuni guerrieri sono destinati a morire per mano di una donna. Nel quarto capitolo, mi concentro proprio su La sconfitta degli eroi, mettendo in luce come l'autrice proponga una sua personale regola del contrappasso, volta a cambiare (e addirittura invertire) le sorti dei personaggi che animano il suo poema. Questi aspetti risultano essere ancora più significativi se confrontati con l'opera - data alle stampe per la prima volta nel 1600 - intitolata Nobiltà et eccellenza delle donne. In questo trattato Marinelli sosteneva la superiorità del genere femminile su quello maschile. Alcune delle posizioni assunte nello scritto giovanile sono confermate dai personaggi e dalle vicende che animano l'Enrico. Confronti puntuali fra trattato e poema epico sono effettuati nell'ultimo capitolo del mio lavoro, sottolineando come fra le due opere vi siano delle affinità volte a confermare l'eccellenza delle donne.

VOLUMES RELIES du Cabinet des titres : recherches de noblesse, armoriaux, preuves, histoires généalogiques. Terrier de la seigneurie de Louverny, relevant du comté de Rethel, fait pour Gracien de Bournonville. (1539).

Copie collationnée faite en 1573, suivie de quelques autres pièces concernant la même seigneurie.

The human epidermal differentiation complex: cornified envelope precursors, S100 proteins and the 'fused genes' family.

  The skin is essential for survival and protects our body against biological attacks, physical stress, chemical injury, water loss, ultraviolet radiation and immunological impairment. The epidermal barrier constitutes the primordial frontline of this defense established during terminal differentiation. During this complex process proliferating basal keratinocytes become suprabasally mitotically inactive and move through four epidermal layers (basal, spinous, granular and layer, stratum corneum) constantly adapting to the needs of the respective cell layer. As a result, squamous keratinocytes contain polymerized keratin intermediate filament bundles and a water-retaining matrix surrounded by the cross-linked cornified cell envelope (CE) with ceramide lipids attached on the outer surface. These cells are concomitantly insulated by intercellular lipid lamellae and hold together by corneodesmosmes. Many proteins essential for epidermal differentiation are encoded by genes clustered on chromosomal human region 1q21. These genes constitute the 'epidermal differentiation complex' (EDC), which is divided on the basis of common gene and protein structures, in three gene families: (i) CE precursors, (ii) S100A and (iii) S100 fused genes. EDC protein expression is regulated in a gene and tissue-specific manner by a pool of transcription factors. Among them, Klf4, Grhl3 and Arnt are essential, and their deletion in mice is lethal. The importance of the EDC is further reflected by human diseases: FLG mutations are the strongest risk factor for atopic dermatitis (AD) and for AD-associated asthma, and faulty CE formation caused by TG1 deficiency causes life-threatening lamellar ichthyosis. Here, we review the EDC genes and the progress in this field.

Prospective sampling based on model ensembles improves the detection of rare species

Identifying the geographic distribution of populations is a basic, yet crucial step in many fundamental and applied ecological projects, as it provides key information on which many subsequent analyses depend. However, this task is often costly and time consuming, especially where rare species are concerned and where most sampling designs generally prove inefficient. At the same time, rare species are those for which distribution data are most needed for their conservation to be effective. To enhance fieldwork sampling, model-based sampling (MBS) uses predictions from species distribution models: when looking for the species in areas of high habitat suitability, chances should be higher to find them. We thoroughly tested the efficiency of MBS by conducting an important survey in the Swiss Alps, assessing the detection rate of three rare and five common plant species. For each species, habitat suitability maps were produced following an ensemble modeling framework combining two spatial resolutions and two modeling techniques. We tested the efficiency of MBS and the accuracy of our models by sampling 240 sites in the field (30 sitesx8 species). Across all species, the MBS approach proved to be effective. In particular, the MBS design strictly led to the discovery of six sites of presence of one rare plant, increasing chances to find this species from 0 to 50%. For common species, MBS doubled the new population discovery rates as compared to random sampling. Habitat suitability maps coming from the combination of four individual modeling methods predicted well the species' distribution and more accurately than the individual models. As a conclusion, using MBS for fieldwork could efficiently help in increasing our knowledge of rare species distribution. More generally, we recommend using habitat suitability models to support conservation plans.

Adapter and enzymatic functions of proteases in T-cell activation.

Proteases control many vital aspects of humoral and cellular immune responses, including the maturation of cytokines and the killing of target cells. Recently, it has become evident that triggering of the T-cell receptor controls T-cell proliferation through proteases such as mucosa-associated lymphoid tissue 1 (MALT1) and Caspase-8 that act both as adapters and enzymes. Here, we discuss the role of these and other proteases that are relevant to the control of the T-cell response and represent interesting targets of therapeutic immunomodulation.

LIGHT/HVEM/LTβR interaction as a target for the modulation of the allogeneic immune response in transplantation.

The exchange of information during interactions of T cells with dendritic cells, B cells or other T cells regulates the course of T, B and DC-cell activation and their differentiation into effector cells. The tumor necrosis factor superfamily member LIGHT (homologous to lymphotoxin, exhibits inducible expression and competes with HSV glycoprotein D for binding to herpesvirus entry mediator, a receptor expressed on T lymphocytes) is transiently expressed upon T cell activation and modulates CD8 T cell-mediated alloreactive responses upon herpes virus entry mediator (HVEM) and lymphotoxin β receptor (LTβR) engagement. LIGHT-deficient mice, or WT mice treated with LIGHT-targeting decoy receptors HVEM-Ig, LTβR-Ig or sDcR3-Ig, exhibit prolonged graft survival compared to untreated controls, suggesting that LIGHT modulates the course and severity of graft rejection. Therefore, targeting the interaction of LIGHT with HVEM and/or LTβR using recombinant soluble decoy receptors or monoclonal antibodies represent an innovative therapeutic strategy for the prevention and treatment of allograft rejection and for the promotion of donor-specific tolerance.