Overexpression of microRNA-206 in the skeletal muscle from myotonic dystrophy type 1 patients

<p>Abstract</p> <p>Background</p> <p>MicroRNAs are highly conserved, noncoding RNAs involved in post-transcriptional gene silencing. They have been shown to participate in a wide range of biological processes, including myogenesis and muscle regeneration. The goal of this study is to test the hypothesis that myo-miRs (myo = muscle + miR = miRNA) expression is altered in muscle from patients affected by myotonic dystrophy type 1 (DM1), the most frequently inherited neuromuscular disease in adults. In order to gain better insights about the role of miRNAs in the DM1 pathogenesis, we have also analyzed the muscular expression of miR-103 and miR-107, which have been identified <it>in silico </it>as attractive candidates for binding to the <it>DMPK </it>mRNA.</p> <p>Methods</p> <p>To this aim, we have profiled the expression of miR-133 (miR-133a, miR-133b), miR-1, miR-181 (miR-181a, miR-181b, miR-181c) and miR-206, that are specifically induced during myogenesis in cardiac and skeletal muscle tissues. miR-103 and miR-107, highly expressed in brain, heart and muscle have also been included in this study. QRT-PCR experiments have been performed on RNA from vastus lateralis biopsies of DM1 patients (n = 7) and control subjects (n = 4). Results of miRNAs expression have been confirmed by Northern blot, whereas <it>in situ </it>hybridization technique have been performed to localize misexpressed miRNAs on muscle sections from DM1 and control individuals.</p> <p>Results</p> <p>Only miR-206 showed an over-expression in 5 of 7 DM1 patients (threshold = 2, fold change between 1.20 and 13.22, average = 5.37) compared to the control group. This result has been further confirmed by Northern blot analysis (3.37-fold overexpression, <it>R</it>²= 0.89). <it>In situ </it>hybridization localized miR-206 to nuclear site both in normal and DM1 tissues. Cellular distribution in DM1 tissues includes also the nuclear regions of centralized nuclei, with a strong signal corresponding to nuclear clumps.</p> <p>Conclusions</p> <p>This work provides, for the first time, evidences about miRNAs misexpression in DM1 muscle tissues, adding a new element in the pathogenesis of this complex genetic disease.</p

Skin involvement in Dupuytren's disease.

Whether the palmar skin has a role in the development, propagation or recurrence of Dupuytren's disease remains unclear. Clinical assessment for skin involvement is difficult and its correlation with histology uncertain. We prospectively biopsied the palmar skin of consecutive patients undergoing single digit fasciectomy (for primary Dupuytren's disease without clinically involved skin) and dermofasciectomy (for clinically involved skin or recurrence) in order to investigate this relationship. We found dermal fibromatosis in 22 of 44 patients (50%) undergoing fasciectomy and 41 of 59 patients (70%) undergoing dermofasciectomy. Dermal fibromatosis appeared to be associated with greater preoperative angular deformity, presence of palmar nodules and occupations involving manual labour. Dermal fibromatosis exists in the absence of clinical features of skin involvement and we hypothesize that the skin may have a greater role in the development and propagation of Dupuytren's disease than previously thought.III

From Street to Home: Using Photovoice to Better Understand Homelessness in Portland

Homelessness remains a pressing concern in Portland. The homeless-to-housed transition requires more than access to shelter: some individuals have trouble adapting to the change in social contact that accompanies solitary living (indoors); others may face difficulty setting boundaries associated with property (e.g., endangering their lease by having too many guests) or other community-living norms. This study used photovoice, a community-based participatory research method, to explore the dynamics experienced by homelessness survivors. A total of 13 participants were recruited through HEARTH, a research collaborative including researchers from OHSU, PSU, and NCNM along with staff, consumers, and volunteers at Central City Concern, a local agency that provides housing and social services. Participants received photovoice training and collectively took over 500 photographs. Eleven participant presented five photographs and discussed their meaning and significance, Group members described reactions and interpretations of the photographs. The group then selected 50 photographs to include in an upcoming exhibit and placed them into categories of “Street”, “Getting There,” and “Home.” Subcategories were then identified. For example, one subcategory was “waystations” such as the public library or McDonalds. Other subcategories described instrumental activities, but also feelings such as hope and resilience derived from nature and urban scenery. Individuals became homeless for different reasons. Photovoice revealed that, once homeless, these individuals used creative survival skills that colored their experience(s) and distinguished them from the stereotypical homeless person. This poster will document findings of this project and provide suggestions for future photovoice projects with members of marginalized communities

Situated ignorance: the distribution and extension of ignorance in cognitive niches

Ignorance is easily representable as a cognitive property of more than just individual subjects: groups, crowds, and even populations can share the same ignorance regarding particular concepts and ideas. Nevertheless, according to some theories that refer to the extension, distribution, and situatedness of human cognition, ignorance is hardly a state that can be extended, distributed, and situated in the same way in which knowledge is in our eco-cognitive environment. In order to understand how these contradictory takes can come across in a coherent description of ignorance, in this paper I aim at analyzing the impact of the agent’s ignorance in her ecological and cognitive environment, as well as the effect that the surrounding context has on the agent’s epistemological successes and downfalls. To this end I will adopt the cognitive and empirically sensitive perspectives of the distributed cognition, the extended mind and cognitive niches construction theories, which will help me address and answer three topical questions: (a) adopting the theories about the extended mind, the distributed cognition, and the cognitive significance of affordances can we describe ignorance as extended and distributed in spaces, artifacts, and other people? (b) extending or distributing ignorance in one’s eco-cognitive environment has the same cognitive and ecological impact of extending or distributing knowledge? (c) can we recognize instantiations of externalized or distributed ignorance? I will argue that by acknowledging the extended, distributed, and situated dimension of ignorance in cognitive niches we could recognize the impact that our ignorance and uncertainty has on how we manipulate and organize our environment and also how our eco-cognitive frameworks affect the perception of our epistemological states