Elevated expression of the chemokine-scavenging receptor D6 is associated with impaired lesion development in psoriasis

D6 is a scavenging-receptor for inflammatory CC chemokines that are essential for resolution of inflammatory responses in mice. Here, we demonstrate that D6 plays a central role in controlling cutaneous inflammation, and that D6 deficiency is associated with development of a psoriasis-like pathology in response to varied inflammatory stimuli in mice. Examination of D6 expression in human psoriatic skin revealed markedly elevated expression in both the epidermis and lymphatic endothelium in "uninvolved" psoriatic skin (ie, skin that was more than 8 cm distant from psoriatic plaques). Notably, this increased D6 expression is associated with elevated inflammatory chemokine expression, but an absence of plaque development, in uninvolved skin. Along with our previous observations of the ability of epidermally expressed transgenic D6 to impair cutaneous inflammatory responses, our data support a role for elevated D6 levels in suppressing inflammatory chemokine action and lesion development in uninvolved psoriatic skin. D6 expression consistently dropped in perilesional and lesional skin, coincident with development of psoriatic plaques. D6 expression in uninvolved skin also was reduced after trauma, indicative of a role for trauma-mediated reduction in D6 expression in triggering lesion development. Importantly, D6 is also elevated in peripheral blood leukocytes in psoriatic patients, indicating that upregulation may be a general protective response to inflammation. Together our data demonstrate a novel role for D6 as a regulator of the transition from uninvolved to lesional skin in psoriasis

Digital transformations and the archival nature of surrogates

Large-scale digitization is generating extraordinary collections of visual and textual surrogates, potentially endowed with transcendent long-term cultural and research values. Understanding the nature of digital surrogacy is a substantial intellectual opportunity for archival science and the digital humanities, because of the increasing independence of surrogate collections from their archival sources. The paper presents an argument that one of the most significant requirements for the long-term access to collections of digital surrogates is to treat digital surrogates as archival records that embody traces of their fluid lifecycles and therefore are worthy of management and preservation as archives. It advances a theory of the archival nature of surrogacy founded on longstanding notions of archival quality, the traces of their source and the conditions of their creation, and the functional ‘‘work of the archive.’’ The paper presents evidence supporting a ‘‘secondary provenance’’ derived from re-digitization, re-ingestion of multiple versions, and de facto replacement of the original sources. The design of the underlying research that motivates the paper and summary findings are reported separately. The research has been supported generously by the US Institute of Museum and Library Services.Institute for Museum and Library ServicesPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111825/1/J26 Conway Digital Transformations 2014-pers.pdfDescription of J26 Conway Digital Transformations 2014-pers.pdf : Main articl

Interleukin 15 Levels in Serum May Predict a Severe Disease Course in Patients with Early Arthritis

Background: Interleukin-15 (IL-15) is thought to be involved in the physiopathological mechanisms of RA and it can be detected in the serum and the synovial fluid of inflamed joints in patients with RA but not in patients with osteoarthritis or other inflammatory joint diseases. Therefore, the objective of this work is to analyse whether serum IL-15 (sIL-15) levels serve as a biomarker of disease severity in patients with early arthritis (EA). Methodology and Results: Data from 190 patients in an EA register were analysed (77.2% female; median age 53 years; 6-month median disease duration at entry). Clinical and treatment information was recorded systematically, especially the prescription of disease modifying anti-rheumatic drugs. Two multivariate longitudinal analyses were performed with different dependent variables: 1) DAS28 and 2) a variable reflecting intensive treatment. Both included sIL-15 as predictive variable and other variables associated with disease severity, including rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA). Of the 171 patients (638 visits analysed) completing the follow-up, 71% suffered rheumatoid arthritis and 29% were considered as undifferentiated arthritis. Elevated sIL-15 was detected in 29% of this population and this biomarker did not overlap extensively with RF or ACPA. High sIL-15 levels (β Coefficient [95% confidence interval]: 0.12 [0.06-0.18]; p&0.001) or ACPA (0.34 [0.01-0.67]; p = 0.044) were significantly and independently associated with a higher DAS28 during follow-up, after adjusting for confounding variables such as gender, age and treatment. In addition, those patients with elevated sIL-15 had a significantly higher risk of receiving intensive treatment (RR 1.78, 95% confidence interval 1.18-2.7; p = 0.007). Conclusions: Patients with EA displaying high baseline sIL-15 suffered a more severe disease and received more intensive treatment. Thus, sIL-15 may be a biomarker for patients that are candidates for early and more intensive treatmentThe work of Belen Díaz-Sánchez was supported by the RETICS Programme (Programa de Redes Temáticas de Investigación Colaborativa [Colaborative Research Thematic Network Programme]; RD08/0075 - RIER [Red de Inflamación y Enfermedades Reumáticas; Inflammation and Rheumatic Diseases Network]) from the Instituto de Salud Carlos III, Spain (URL: www.isciii.es) within the VI National Plan for I+D+I 2008–2011 (FEDER). The work of Isidoro González-Álvaro was in part supported by a grant for the Intensification of the Research Tasks in the National Health Care System from Instituto de Salud Carlos III, Spain. The consumables for measurements and data analysis were supported by a Fondo de Investigación Sanitaria grant (08/0754) from the Instituto de Salud Carlos II

Communication media and the dead:from the Stone Age to Facebook

This article argues as follows: (i) The presence of the dead within a society depends in part on available communication technologies, specifically speech, stone, sculpture, writing, printing, photography and phonography (including the mass media), and most recently the internet. (ii) Each communication technology affords possibilities for the dead to construct and legitimate particular social groups and institutions – from the oral construction of kinship, to the megalithic legitimation of the territorial rights of chiefdoms, to the written word’s construction of world religions and nations, to the photographic and phonographic construction of celebrity-based neo-tribalism, and to the digital reconstruction of family and friendship. (iii) Historically, concerns about the dead have on a number of occasions aided the development of new communication technologies – the causal connection between the two can go both ways. The argument is based primarily on critical synthesis of existing research literature

Dizionario della memoria e del ricordo

Anche in Italia, la \uabmemoria\ubb \ue8 diventata un tema della discussione pubblica, e l\u2019imperativo \uabRicorda!\ubb, legato alla trasmissione e all\u2019identit\ue0 delle culture, \ue8 assurto a monito per l\u2019umanit\ue0 di fronte agli orrori del XX secolo, alla sua \uabmemoria del male e tentazione del bene\ubb. D\u2019altro canto, l\u2019introduzione di nuove tecniche di immagazinamento dei dati su base informatica ha reso disponibile una pressoch\ue9 illimitata possibilit\ue0 di raccolta di informazioni e archiviazione di memoria della quale Internet rappresenta la virtuale accessibilit\ue0 indefinita, imponendo tuttavia di interrogarsi sulle forme di discernimento e strutturazione del ricordo, sulla contemporanea necessit\ue0 di memoria e oblio di fronte al rischio di paralisi della conoscenza e alla sua inefficacia per l\u2019azione causati dalla saturazione e dall\u2019eccesso dei dati a disposizione. Inoltre, le nuove ricerche sulla fisiologia della memoria legate ai recenti tumultuosi sviluppi degli studi sul cervello e sui neurotrasmettitori, i modelli psicologici che definiscono la regolazione di ricordo e oblio, dalla psicanalisi al cognitivismo e al connessionismo, la pressione sulla ricerca medica indotta dall\u2019inedita diffusione di patologie della memoria come la demenza di Alzheimer e delle loro devastanti conseguenze sulle vite individuali e sull\u2019organizzazione sociale, hanno modificato in profondit\ue0 e complicato la rappresentazione scientifica del fenomeno. E neppure i tradizionali campi di analisi della trasmissione della memoria culturale (a sua volta complicata dalla trasformazione epocale della mondializzazione), delle letterature, dei modelli pedagogici, delle ipotesi filosofiche sono rimasti immuni dalla spinta problematica proveniente da queste tre grandi correnti di sviluppo della ricerca e sono stati costretti a riformulare la propria impostazione, rivedere criteri di rilevanza e strategie conoscitive. Memoria e ricordo hanno quindi assunto un ruolo centrale in numerosi ambiti del sapere, ma nonostante il tema di fondo e l\u2019oggetto di ricerca comune gli approcci e le tematiche delle diverse direzioni di ricerca ancora lontani gli uni dagli altri. Allo scopo di ricondurli a un quadro comune, questo lessico interdisciplinare presenta il vasto campo delle ricerche sulla memoria nella sua molteplicit\ue0 storica e teorica. Con oltre 450 lemmi aggiornati alle pi\uf9 recenti acquisizioni disciplinari (con relative bibliografie di riferimento) e firmati dai maggiori studiosi tedeschi dell\u2019argomento, esso copre sei discipline di riferimento nelle quali sono studiati il ricordo e la memoria: scienze della cultura, scienze della comunicazione e dei media, neurobiologia, pedagogia, filosofia e psicologia. Grazie anche ai numerosi rimandi trasversali e alla convergenza del contributo di discipline diverse nei singoli lemmi, la ricerca dispone per la prima volta in questa opera di consultazione di una piattaforma comune che consente anche al lettore non specialista l\u2019accesso all\u2019informazione, all\u2019orientamento e alla comprensione dei diversi aspetti degli studi sulla memoria e sul ricordo

Parkinson'sche Erkrankung

Werheid K. Parkinson'sche Erkrankung. In: Pethes N, Ruchatz J, Korte M, eds. Gedächtnis und Erinnerung : ein interdisziplinäres Lexikon. Reinbek: Rowohlt ; 2001: 436 ff

Selective blockade of IL-15 by soluble IL-15 receptor alpha-chain enhances cardiac allograft survival

IL-15 is a T cell growth factor that shares many functional similarities with IL-2 and has recently been shown to be present in tissue and organ allografts, leading to speculation that IL-15 may contribute to graft rejection. Here, we report on the in vivo use of an IL-15 antagonist, a soluble fragment of the murine IL-15R a-chain, to investigate the contribution of IL-15 to the rejection of fully vascularized cardiac allografts in a mouse experimental model. Administration of soluble fragment of the murine IL-15R a-chain (sIL-15Ra) to CBA/Ca (H-2k) recipients for 10 days completely prevented rejection of minor histocompatibility complexmismatched B10.BR (H-2k) heart grafts (median survival time (MST) of >100 days vs MST of 10 days for control recipients) and led to a state of donor-specific immunologic tolerance. Treatment of CBA/Ca recipients with sIL-15Ra alone had only a modest effect on the survival of fully MHC-mismatched BALB/c (H-2d) heart grafts. However, administration of sIL-15Ra together with a single dose of a nondepleting anti-CD4 mAb (YTS 177.9) delayed mononuclear cell infiltration of the grafts and markedly prolonged graft survival (MST of 60 days vs MST of 20 days for treatment with anti-CD4 alone). Prolonged graft survival was accompanied in vitro by reduced proliferation and IFN-g production by spleen cells, whereas CTL and alloantibody levels were similar to those in animals given anti-CD4 mAb alone. These findings demonstrate that IL-15 plays an important role in the rejection of a vascularized organ allograft and that antagonists to IL-15 may be of therapeutic value in preventing allograft rejection