1,721,030 research outputs found
What's New in Laboratory Research?
No full textPsoriasis is a multigenic disease with a number of susceptibility loci on different chromosomes predisposing to the disease, which is in turn triggered by environmental factors. The pathogenesis of psoriasis is characterized by 2 main components, the dysfunctions of the immune system and the alteration of keratinocyte homeostasis. While the Th1 T cell response has long been considered the sole immune agent in the pathomechanisms of psoriasis, recently, the role of IL-23-driven Th17 has been shown to be predominant. Subsequently, only effector memory T cells expressing alpha1beta1 integrin migrate into the epidermis, and psoriasis development is inhibited by blocking this integrin. Psoriatic epidermis contains high amounts of antimicrobial peptides, which have been shown to be a key mediator of plasmocytoid dendritic cell activation in psoriasis. The keratinocyte component has recently regained the central stage, as the abrogation of JunB/activator protein 1 in mouse keratinocytes induces development of psoriasiform lesions in T cell deficient mice. Moreover, inhibition of nerve growth factor and its receptor in keratinocytes strikingly improves psoriatic lesions
Apoptotic pathways in the pathogenesis of pemphigus: targets for new therapies
No full textPemphigus is a group of rare autoimmune blistering diseases of the skin in which autoantibodies to desmosome cadherins, desmogleins, induce loss of cell-cell adhesion (acantholysis). In addition to steric hindrance and activation of intracellular phosphorylation cascade signaling pathways, apoptosis has been suggested to contribute to the mechanism by which pathogenic IgG induces acantholysis. We review the literature examining the role of apoptosis in pemphigus. Current data recognize a central role of apoptosis in the mechanisms of blister induction. In particular, here we stress the key role of FasL in pemphigus, as it is able to first induce apoptosis, then acantholysis. Being pro-apoptotic molecules important in blister formation, they could represent new specific targets for pemphigus treatment
Anoikis is triggered by the association between beta 1B integrin and caspase-8 in human keratinocytes
No full textp75 neurotrophin receptor (NTR) is up-regulated by chemotherapy and induces apoptosis in melanoma cells
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A novel human psoriatic skin equivalent: the importance of transit amplifying keratinocytes
No full textPsoriasis is an immune-mediated disease of the skin characterized
by keratinocyte hyperproliferation, altered differentiation
and resistance to apoptosis. Histologically, psoriasis is represented
by augmented thickness of the epidermal compartment
of the skin, acanthosis and intense immune cell infiltrate. Psoriasis
is thought to be determined by both genetic and environmental
components. Psoriasis has long been considered
only an immunocyte-mediated disease, but recent data demonstrate
the important role of keratinocytes in triggering the
disease. Here we sought to develop an in vitro reconstructed skin model that would display the phenotypic and molecular
characteristics of psoriatic epidermis in a controlled manner
and in the absence of immune cells, providing a tool for the
study of keratinocyte biology and allowing the screening of
antipsoriatic drugs. Human skin equivalents were generated in
the following way: the dermal compartment was a mixture of
rat-tail collagen I and human fibroblasts either from healthy
adult skin or from patients with psoriasis. Given the importance
of transit amplifying (TA) cells in the pathogenesis of
psoriasis, we used either TA cells or stem cells isolated from
healthy human skin for the epidermal compartment. As a control,
we also analysed skin equivalents raised from the total
keratinocyte population. The combination of psoriatic fibroblasts
and normal TA cells produced the best psoriatic
phenotype, with a statistically significant increase of epidermal
thickness, areas of acanthosis and expression of psoriatic markers,
such as S100A7/psoriasin, K16 and phospho-Stat3
(Tyr705). Moreover, given the absence of p75NTR in psoriatic
epidermis and the apoptotic role of p75NTR receptor
mainly expressed by TA keratinocytes, we set up skin reconstructs
with either p75NTR-positive or p75NTR-depleted TA
cells. Skin reconstructs assembled with p75NTR-positive TA
keratinocytes were almost negative for psoriatic markers. By
contrast, skin reconstructs generated from p75NTR-depleted
TA displayed a more psoriasiform phenotype. These results
demonstrate the central role of TA cells in psoriasis together
with the importance of psoriatic fibroblasts in triggering the
psoriatic modifications
A Case Study of Cross-Organizational Co-Design with Public Bodies: Opportunities for a Collaborative Platform
No full textBased on literature on cross-organizational collaboration and on empirical evidence, this paper provides insights on the perceived barriers that large public bodies encounter when launching and managing co-design processes and on how ICT might help to address these issues. We analyzed the case study of a heterogeneous network composed of multiple departments within an Italian central public body and of several related external stakeholders during the ideation stage of a complex strategic planning software. The preliminary findings shed light on the opportunities for digital platforms to enable cross-organizational collaboration and creation practices within Public Administrations. Impact areas are related to building capacity in co-design, to managing the complex dynamics of stakeholder engagement hindered by the pyramidal structure of public bodies, and to clarifying roles and responsibilities, favoring internal communications and handovers
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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