Ribozyme-mediated reduction of wild-type and mutant cartilage oligomeric matrix protein (COMP) mRNA and protein.

Dominant-negative mutations in the homopentameric extracellular matrix glycoprotein cartilage oligomeric matrix protein (COMP) result in inappropriate intracellular retention of misfolded COMP in the rough endoplasmic reticulum of chondrocytes, causing chondrocyte cell death, which leads to two skeletal dysplasias: pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (EDM1). COMP null mice show no adverse effects on normal bone development and growth, suggesting a possible therapy involving removal of COMP mRNA. The goal of this study was to assess the ability of a hammerhead ribozyme (Ribo56, designed against the D469del mutation) to reduce COMP mRNA expression. In COS7 cells transfected with plasmids that overexpress wild-type or mutant COMP mRNA and Ribo56, the ribozyme reduced overexpressed normal COMP mRNA by 46% and mutant COMP mRNA by 56% in a dose-dependent manner. Surprisingly, the use of recombinant adenoviruses to deliver wild-type or mutant COMP mRNA and Ribo56 simultaneously into COS7 cells proved problematic for the activity of the ribozyme to reduce COMP expression. However, in normal human costochondral cells (hCCCs) infected only with adenoviruses expressing Ribo56, expression of endogenous wild-type COMP mRNA was reduced in a dose-dependent manner by 50%. In chondrocytes that contain heterozygous COMP mutations (D469del, G427E and D511Y) that cause PSACH, Ribo56 was more effective at reducing COMP mRNA (up to 70%). These results indicate that Ribo56 is effective at reducing mutant and wild-type COMP levels in cells and suggests a possible mode of therapy to reduce the mutant protein load.

Internetbasierte geleitete Selbsthilfe bei verschiedenen Angststörungen: Eine randomisiert kontrollierte Studie zum Vergleich eines individualisierten vs. standardisierten Ansatzes

Hintergrund und Ziel: Internetbasierte psychotherapeutische Interventionen wurden in den letzten Jahren intensiv erforscht. Als besonders vielversprechend haben sich therapeutengeleitete Selbsthilfeprogramme bei verschiedenen Angststörungen erwiesen. Eine neue Entwicklung sind transdiagnostische und individualisierte Ansätze, in welchen auch komorbide Probleme und Störungen, und breitere Patientengruppen angesprochen werden. Beim individualisierten Ansatz werden dem Selbsthilfeprogramm in Abhängigkeit der Probleme der Patienten unterschiedliche Inhalte zugeschaltet. Das Ziel dieser Studie ist die Evaluation einer internetbasierten, individualisierten, geleiteten Selbsthilfeintervention für verschiedene Angststörungen. Methode: In einer kontrolliert-randomisierten Studie wurde der individualisierte Ansatz mit einer standardisierten Intervention, die sich nur auf die primäre Störung der Klienten bezieht, verglichen. 132 StudienteilnehmerInnen, diagnostiziert mit einer Sozialen Angststörung, Panikstörung mit oder ohne Agoraphobie, und/ oder einer Generalisierten Angststörung wurden randomisiert einer der beiden Behandlungsbedingungen oder einer Warteliste zugeteilt. Die Selbsthilfebehandlung dauerte 8 Wochen und wurde von Therapeuten via Email unterstützt. Erhebungszeitpunkte waren Prä, Post und 6 Monate nach Ende der Behandlung. Primäre Ergebnismasse sind störungsübergreifende Masse wie das Beck Angstinventar (BAI) und Daten aus einem diagnostischen Interview. Sekundäre Ergebnismasse sind störungsspezifische Fragebogen. Ergebnisse: Beide Behandlungsgruppen zeigten gegenüber der Warteliste-Kontrollgruppe signifikante Veränderungen auf allen Ergebnismassen. Auf der Basis der Intent-to-treat-Stichprobe betrugen die über die verschiedenen Ergebnismasse gemittelten Effektstärken im Vergleich zur Warteliste-Kontrollgruppe d=.80 für die individualisierte und d=.82 für die standardisierte Behandlungsbedingung. Die Symptomreduktion wurde bis zum 6-Monats-Follow-Up aufrechterhalten. Zwischen den beiden aktiven Behandlungsbedingungen wurden keine Unterschiede gefunden. Diskussion: Die Ergebnisse zeigen, dass sowohl individualisierte wie auch standardisierte internetbasierte Ansätze zur Behandlung verschiedener Angststörungen vielversprechend sind

Contrasting vulnerability and resilience to drought-induced decline of densely planted vs. natural rear-edge Pinus nigra forests

The southernmost European natural and planted pine forests are among the most vulnerable areas to warming-induced drought decline. Both drought stress and management factors (e.g., stand origin or reduced thinning) may induce decline by reducing the water available to trees but their relative importances have not been properly assessed. The role of stand origin - densely planted vs. naturally regenerated stands - as a decline driver can be assessed by comparing the growth and vigor responses to drought of similar natural vs. planted stands. Here, we compare these responses in natural and planted Black pine (Pinus nigra) stands located in southern Spain. We analyze how environmental factors - climatic (temperature and precipitation anomalies) and site conditions - and biotic factors - stand structure (age, tree size, density) and defoliation by the pine processionary moth - drive radial growth and crown condition at stand and tree levels. We also assess the climatic trends in the study area over the last 60 years. We use dendrochronology, linear mixed-effects models of basal area increment and structural equation models to determine how natural and planted stands respond to drought and current competition intensity. We observed that a temperature rise and a decrease in precipitation during the growing period led to increasing drought stress during the late 20th century. Trees from planted stands experienced stronger growth reductions and displayed more severe crown defoliation after severe droughts than those from natural stands. High stand density negatively drove growth and enhanced crown dieback, particularly in planted stands. Also pine processionary moth defoliation was more severe in the growth of natural than in planted stands but affected tree crown condition similarly in both stand types. In response to drought, sharp growth reduction and widespread defoliation of planted Mediterranean pine stands indicate that they are more vulnerable and less resilient to drought stress than natural stands. To mitigate forest decline of planted stands in xeric areas such as the Mediterranean Basin, less dense and more diverse stands should be created through selective thinning or by selecting species or provenances that are more drought tolerant. (C) 2013 Elsevier B.V. All rights reserved.

Minerale der Molybdänitlagerstätte am Alpjuhorn im Baltschiedertal (VS)

Im Zuge einer Masterarbeit an der Universität Bern und am Naturhistorischen Museum der Burger- gemeinde Bern wurde das Molybdänitvorkommen am Alpjuhorn im Baltschiedertal untersucht. Neben Molybdänit wurden auch Scheelit, Ilmenit, Galenit, Ferberit und die Sekundärmineralien Ferrimolybdit und Powellit gefunden. Speziell am Galenit des Alpjuhorns ist, dass er eine oktaedrische Spaltbar- keit aufweist. Das Auftreten von Ferberit ist insofern erwähnenswert, da aus der Schweiz nur wenige Funde von Mineralien der Wolframit-Reihe (Ferberit- Hübnerit) bekannt sind.

An index to identify stroke-related vs incidental patent foramen ovale in cryptogenic stroke

OBJECTIVE We aimed to create an index to stratify cryptogenic stroke (CS) patients with patent foramen ovale (PFO) by their likelihood that the stroke was related to their PFO. METHODS Using data from 12 component studies, we used generalized linear mixed models to predict the presence of PFO among patients with CS, and derive a simple index to stratify patients with CS. We estimated the stratum-specific PFO-attributable fraction and stratum-specific stroke/TIA recurrence rates. RESULTS Variables associated with a PFO in CS patients included younger age, the presence of a cortical stroke on neuroimaging, and the absence of these factors: diabetes, hypertension, smoking, and prior stroke or TIA. The 10-point Risk of Paradoxical Embolism score is calculated from these variables so that the youngest patients with superficial strokes and without vascular risk factors have the highest score. PFO prevalence increased from 23% (95% confidence interval [CI]: 19%-26%) in those with 0 to 3 points to 73% (95% CI: 66%-79%) in those with 9 or 10 points, corresponding to attributable fraction estimates of approximately 0% to 90%. Kaplan-Meier estimated stroke/TIA 2-year recurrence rates decreased from 20% (95% CI: 12%-28%) in the lowest Risk of Paradoxical Embolism score stratum to 2% (95% CI: 0%-4%) in the highest. CONCLUSION Clinical characteristics identify CS patients who vary markedly in PFO prevalence, reflecting clinically important variation in the probability that a discovered PFO is likely to be stroke-related vs incidental. Patients in strata more likely to have stroke-related PFOs have lower recurrence risk.

Recurrent stroke predictors differ in medically treated patients with pathogenic vs other PFOs

OBJECTIVE: To examine predictors of stroke recurrence in patients with a high vs a low likelihood of having an incidental patent foramen ovale (PFO) as defined by the Risk of Paradoxical Embolism (RoPE) score.METHODS: Patients in the RoPE database with cryptogenic stroke (CS) and PFO were classified as having a probable PFO-related stroke (RoPE score of >6, n = 647) and others (RoPE score of dels with component database as a stratification factor. An interaction with RoPE score was checked for the variables that were significant.RESULTS: Follow-up was available for 92%, 79%, and 57% at 1, 2, and 3 years. Overall, a higher recurrence risk was associated with an index TIA. For all other predictors, effects were significantly different in the 2 RoPE score categories. For the low RoPE score group, but not the high RoPE score group, older age and antiplatelet (vs warfarin) treatment predicted recurrence. Conversely, echocardiographic features (septal hypermobility and a small shunt) and a prior (clinical) stroke/TIA were significant predictors in the high but not low RoPE score group.CONCLUSION: Predictors of recurrence differ when PFO relatedness is classified by the RoPE score, suggesting that patients with CS and PFO form a heterogeneous group with different stroke mechanisms. Echocardiographic features were only associated with recurrence in the high RoPE score group.

CAP Reform vs WTO: Crop Diversification or Crop Rotation? : Legal opinion prepared by Dr. Christian Häberli at the request of APRODEV, the Association of World Council of Churches related Development Organisations in Europe

The European Commission’s proposals for the Legislative Framework of the Common Agricultural Policy (CAP) in the period 2014-2020 include, inter alia, the introduction of a “strong greening component”. For the first time, all EU farmers in receipt of support are to “go beyond the requirements of cross compliance and deliver environmental and climate benefits as part of their everyday activities crop diversification as a contribution to all EU farmers in receipt of support go beyond the requirements of cross compliance and deliver environmental and climate benefits as part of their everyday activities.” In a legal opinion prepared at the request of APRODEV, the Association of World Council of Churches related Development Organisations in Europe (www.aprodev.eu), Christian Häberli examines the WTO implications of this proposal, as compared with an alternative proposal to rather link direct payments to crop rotation. The conclusions are twofold: 1. Crop rotation is at least as likely to be found Green Box-compatible as crop diversification. Moreover, it will be more difficult to argue that crop diversification is “not more than minimally production-distorting” because it entails for most farmers less cost and work. 2. Even if (either of the two cropping schemes) were to be found “amber”, the EU would not have to relinquish this conditionality. This is because the direct payments involved would in all likelihood not, together with the other price support instruments, exceed the amount available under the presently scheduled maximum.