Effect of different live prey, Grapsus grapsus Linnaeus 1758 and Plagusia depressa Fabricius, 1775 zoeas,over histology and biochemical composition of common octopus, octopus vulgaris Cuvier, 1797 paralarvae

[EN] Since paralarval rearing is still the main bottleneck for the development of octopus culture, the aim of the present study was to obtain some information on the feeding strategy and nutritional requirements during paralarval stage. For that purpose just hatched out octopus paralarvae were fed with live preys in three different combinations, trying to match their natural food: Enriched Artemia metanauplii, Grapsus grapsus zoeas supplemented with enriched Artemia, and Plagusia depressa zoeas supplemented with enriched Artemia. Paralarval treatments were carried out during 28 days in triplicates; fibre glass 120 l tanks in flow through system were used. Growth, in terms of dry body weight, mantle length and width, was determined each seven days. A histological study of the paralarval development was carried out. Biochemical composition of preys and paralarvae were determined. Growth was significantly better in paralarvae fed with zoeas and Artemia than in those fed only with Artemia, from day 8 after hatching. Besides a clear effect on the digestive gland histology morphology was observed.

Crecimiento y supervivencia de paralarvas de O. vulgaris cultivadas bajo diferentes intensidades de luz.

[EN] Paralarval rearing constitutes the main bottleneck to the complete development of octopus culture. This paper try to optimise the larval rearing conditions of Octopus Paralarvae, testing the effect of light intensity (1000, 3000 and 6000 lux ) over growth and paralarval survival. Four fibber glass tanks, 100 litter capacity with an initial density of 20 ind./litter were used for each treatment. All light treatments were fed with the same protocol, just hatching Maja Squinado Zoeas and Artemia metanaulios (72 hours)enriched with a commercial emulsion (Red Pepper Paste, Bernaqua, bva; Belgium). Better growth and survival were found with the highest light intensity treatment.

The effects of supplementation of decapod zoea to Artemia basal diet on the digestive gland histology and the fatty acid composition in common octopus (Octopus vulgaris) paralarvae.

[EN]The present study aimed to evaluate the effect of the supplementation of different crab zoeas to enriched Artemia basal diet for O. vulgaris paralarvae during the first month of life. Paralarvae were fed using: enriched Artemia nauplii alone and Artemia co-fed with either first zoea stages of Grapsus adscensionis or Plagusia depressa. The experiment was carried out over a period of 28 days, in 0.12 m3 tanks with a flow-through rearing system. Growth in dry weightas well as mantle length and width were assessed weekly. Additionally, prey and paralarvae fatty acid composition and digestive gland (DG) histology were evaluated.

Clinical activity of pemphigus vulgaris relates to IgE autoantibodies against desmoglein 3

Pemphigus vulgaris (PV) is a severe autoimmune bullous skin disease and is primarily associated with IgG against desmoglein 3 (dsg3), a desmosomal adhesion protein. In light of the recent association of autoreactive T helper (Th) 2 cells with active PV, the present study sought to relate the occurrence of Th2-regulated dsg3-specific autoantibody subtypes, i.e. IgE and IgG4, in 93 well-characterized PV patients. Patients with acute onset PV (n=37) showed the highest concentrations of serum IgE and IgG4 autoantibodies, which were significantly lower in PV patients in remission (n=14). Furthermore, there was a strong correlation between dsg3-reactive IgE and IgG4 in acute onset, but not in chronic active (n=42) or remittent patients. Additionally, intercellular IgE deposits were detected in the epidermis of acute onset PV. Thus, dsg3-specific IgE and IgG4 autoantibodies are related to acute onset disease which provides additional support to the concept that PV is a Th2-driven autoimmune disorder.

Pemphigus vulgaris identifies plakoglobin as key suppressor of c-Myc in the skin

The autoimmune disease pemphigus vulgaris (PV) manifests as loss of keratinocyte cohesion triggered by autoantibody binding to desmoglein (Dsg)3, an intercellular adhesion molecule of mucous membranes, epidermis, and epidermal stem cells. Here we describe a so far unknown signaling cascade activated by PV antibodies. It extends from a transient enhanced turn over of cell surface-exposed, nonkeratin-anchored Dsg3 and associated plakoglobin (PG), through to depletion of nuclear PG, and as one of the consequences, abrogation of PG-mediated c-Myc suppression. In PV patients (6/6), this results in pathogenic c-Myc overexpression in all targeted tissues, including the stem cell compartments. In summary, these results show that PV antibodies act via PG to abolish the c-Myc suppression required for both maintenance of epidermal stem cells in their niche and controlled differentiation along the epidermal lineage. Besides a completely novel insight into PV pathogenesis, these data identify PG as a potent modulator of epithelial homeostasis via its role as a key suppressor of c-Myc.

Plakoglobin-dependent disruption of the desmosomal plaque in pemphigus vulgaris

We recently reported that the pathogenesis of pemphigus vulgaris (PV), an autoimmune blistering skin disorder, is driven by the accumulation of c-Myc secondary to abrogation of plakoglobin (PG)-mediated transcriptional c-Myc suppression. PG knock-out mouse keratinocytes express high levels of c-Myc and resemble PVIgG-treated wild-type keratinocytes in most respects. However, they fail to accumulate nuclear c-Myc and loose intercellular adhesion in response to PVIgG-treatment like wild-type keratinocytes. This suggested that PG is also required for propagation of the PVIgG-induced events between augmented c-Myc expression and acantholysis. Here, we addressed this possibility by comparing PVIgG-induced changes in the desmosomal organization between wild-type and PG knock-out keratinocytes. We found that either bivalent PVIgG or monovalent PV-Fab (known to trigger blister formation in vivo) disrupt the linear organization of all major desmosomal components along cell borders in wild-type keratinocytes, simultaneously with a reduction in intercellular adhesive strength. In contrast, PV-Fab failed to affect PG knock-out keratinocytes while PVIgG cross-linked their desmosomal cadherins without significantly affecting desmoplakin. These results identify PG as a principle effector of the PVIgG-induced signals downstream of c-Myc that disrupt the desmosomal plaque at the plasma membrane.

Upregulation of c-Myc may contribute to the pathogenesis of canine pemphigus vulgaris

The pathomechanism in human pemphigus vulgaris (PV) has recently been described to rely on generalized c-Myc upregulation in skin and oral mucosa followed by hyperproliferation. Here we assessed whether dogs suffering from PV present the same pathological changes as described for human patients with PV. Using immunofluorescence analysis on patients' biopsy samples, we observed marked nuclear c-Myc accumulation in all layers of the epidermis and oral mucosa in all (3/3) dogs analysed. In addition, c-Myc upregulation was accompanied by an increased number of proliferating Ki67-positive cells. These molecular changes were further paralleled by deregulated expression of wound healing and terminal differentiation markers as observed in human PV. Together these findings suggest a common pathomechanism for both species which is of particular relevance in the light of the recently discussed novel therapeutic strategies aiming at targeting PV antibody-induced signalling cascades.

A new light on an old disease: adhesion signaling in pemphigus vulgaris.

Disruption of desmosomal cadherin adhesion leads to the activation of intracellular signaling pathways that are responsible for blister formation in pemphigus vulgaris (PV). Recent studies corroborate the implication of the p38 mitogen-activated protein kinase in PV blistering via its downstream effector mitogen-activated protein kinase activated protein kinase 2. These insights highlight the key role of cadherins in tissue homeostasis and are expected to change pemphigus management.

EGFR inhibitors erlotinib and lapatinib ameliorate epidermal blistering in pemphigus vulgaris in a non-linear, V-shaped relationship.

Novel insights into intra-cellular signalling involved in pemphigus vulgaris (PV), an autoimmune blistering disease of skin and mucous membranes, are now revealing new therapeutic approaches such as the chemical inhibition of PV-associated signals in conjunction with standard immunosuppressive therapy. However, extensive inhibition of signalling molecules that are required for normal tissue function and integrity may hamper this approach. Using a neonatal PV mouse model, we demonstrate that epidermal blistering can be prevented in a dose-dependent manner by clinically approved EGFR inhibitors erlotinib and lapatinib, but only up to approximately 50% of normal EGFR activity. At lower EGFR activity, blisters again aggravated and were highly exacerbated in mice with a conditional deletion of EGFR. Statistical analysis of the relation between EGFR activity and the extent of skin blistering revealed the best fit with a non-linear, V-shaped curve with a median break point at 52% EGFR activity (P = 0.0005). Moreover, lapatinib (a dual EGFR/ErbB2 inhibitor) but not erlotinib significantly reduced blistering in the oral cavity, suggesting that signalling mechanisms differ between PV predilection sites. Our results demonstrate that future clinical trials evaluating EGFR/ErbB2 inhibitors in PV patients must select treatment doses that retain a specific level of signal molecule activity. These findings may also be of relevance for cancer patients treated with EGFR inhibitors, for whom skin lesions due to extensive EGFR inhibition represent a major threat.