Maturation of mammalian H/ACA box snoRNAs: PAPD5-dependent adenylation and PARN-dependent trimming

Small nucleolar and small Cajal body RNAs (snoRNAs and scaRNAs) of the H/ACA box and C/D box type are generated by exonucleolytic shortening of longer precursors. Removal of the last few nucleotides at the 3' end is known to be a distinct step. We report that, in human cells, knock-down of the poly(A) specific ribonuclease (PARN), previously implicated only in mRNA metabolism, causes the accumulation of oligoadenylated processing intermediates of H/ACA box but not C/D box RNAs. In agreement with a role of PARN in snoRNA and scaRNA processing, the enzyme is concentrated in nucleoli and Cajal bodies. Oligo(A) tails are attached to a short stub of intron sequence remaining beyond the mature 3' end of the snoRNAs. The noncanonical poly(A) polymerase PAPD5 is responsible for addition of the oligo(A) tails. We suggest that deadenylation is coupled to clean 3' end trimming, which might serve to enhance snoRNA stability

Artificial Extracellular Matrices Containing Bioactive Glass Nanoparticles Promote Osteogenic Differentiation in Human Mesenchymal Stem Cells

The present study analyzes the capacity of collagen (coll)/sulfated glycosaminoglycan (sGAG)-based surface coatings containing bioactive glass nanoparticles (BGN) in promoting the osteogenic differentiation of human mesenchymal stroma cells (hMSC). Physicochemical characteristics of these coatings and their effects on proliferation and osteogenic differentiation of hMSC were investigated. BGN were stably incorporated into the artificial extracellular matrices (aECM). Oscillatory rheology showed predominantly elastic, gel-like properties of the coatings. The complex viscosity increased depending on the GAG component and was further elevated by adding BGN. BGN-containing aECM showed a release of silicon ions as well as an uptake of calcium ions. hMSC were able to proliferate on coll and coll/sGAG coatings, while cellular growth was delayed on aECM containing BGN. However, a stimulating effect of BGN on ALP activity and calcium deposition was shown. Furthermore, a synergistic effect of sGAG and BGN was found for some donors. Our findings demonstrated the promising potential of aECM and BGN combinations in promoting bone regeneration. Still, future work is required to further optimize the BGN/aECM combination for increasing its combined osteogenic effect

Artificial Extracellular Matrices Containing Bioactive Glass Nanoparticles Promote Osteogenic Differentiation in Human Mesenchymal Stem Cells

The present study analyzes the capacity of collagen (coll)/sulfated glycosaminoglycan (sGAG)-based surface coatings containing bioactive glass nanoparticles (BGN) in promoting the osteogenic differentiation of human mesenchymal stroma cells (hMSC). Physicochemical charac teristics of these coatings and their effects on proliferation and osteogenic differentiation of hMSC were investigated. BGN were stably incorporated into the artificial extracellular matrices (aECM). Oscillatory rheology showed predominantly elastic, gel-like properties of the coatings. The complex viscosity increased depending on the GAG component and was further elevated by adding BGN. BGN-containing aECM showed a release of silicon ions as well as an uptake of calcium ions. hMSC were able to proliferate on coll and coll/sGAG coatings, while cellular growth was delayed on aECM containing BGN. However, a stimulating effect of BGN on ALP activity and calcium deposition was shown. Furthermore, a synergistic effect of sGAG and BGN was found for some donors. Our findings demonstrated the promising potential of aECM and BGN combinations in promoting bone regeneration. Still, future work is required to further optimize the BGN/aECM combination for increasing its combined osteogenic effect

Reconciling safe planetary targets and planetary justice: Why should social scientists engage with planetary targets?

As human activity threatens to make the planet unsafe for humanity and other life forms, scholars are identifying planetary targets set at a safe distance from biophysical thresholds beyond which critical Earth systems may collapse. Yet despite the profound implications that both meeting and transgressing such targets may have for human wellbeing, including the potential for negative trade-offs, there is limited social science analysis that systematically considers the justice dimensions of such targets. Here we assess a range of views on planetary justice and present three arguments associated with why social scientists should engage with the scholarship on safe targets. We argue that complementing safe targets with just targets offers a fruitful approach for considering synergies and trade-offs between environmental and social aspirations and can inform inclusive deliberation on these important issues

Earth system justice needed to identify and live within Earth system boundaries

Living within planetary limits requires attention to justice as biophysical boundaries are not inherently just. Through collaboration between natural and social scientists, the Earth Commission defines and operationalizes Earth system justice to ensure that boundaries reduce harm, increase well-being, and reflect substantive and procedural justice. Such stringent boundaries may also affect ‘just access’ to food, water, energy and infrastructure. We show how boundaries may need to be adjusted to reduce harm and increase access, and challenge inequality to ensure a safe and just future for people, other species and the planet. Earth system justice may enable living justly within boundaries

Earth system boundaries and Earth system justice: Sharing the ecospace

This is the author accepted manuscriptThe literature on planetary and Earth system boundaries calls on humans to live within those boundaries. Sharing such limited ecospace raises questions of justice. Global environmental assessments and scholarship are increasingly paying attention to justice issues, yet inadequately define how to share the limited ecospace. Against this background we ask: how can global environmental assessments’ concerns for justice be enhanced through an Earth system justice (ESJ) framework that guides how the global community could share and flourish within the limited ecospace? Based on an analysis of how justice concerns are addressed in the Assessment of Assessments and global environmental change projects, we build an Earth system justice framework that discusses how ecospace can be shared fairly through the setting of Earth system boundaries and the provision of minimum resource needs for all, and how this can be achieved through an equitable redistribution of resources, rights, and responsibilities focused on addressing inequality, overconsumption, and harmful accumulation.Rockefeller Philanthropy AdvisorsEuropean Research Counci

Isolated talonavicular arthrodesis in patients with rheumatoid arthritis of the foot and tibialis posterior tendon dysfunction

<p>Abstract</p> <p>Background</p> <p>The foot is often affected in patients with rheumatoid arthritis. Subtalar joints are involved more frequently than ankle joints. Deformities of subtalar joints often lead to painful flatfoot and valgus deformity of the heel. Major contributors to the early development of foot deformities include talonavicular joint destruction and tibialis posterior tendon dysfunction, mainly due to its rupture.</p> <p>Methods</p> <p>Between 2002 and 2005 we performed isolated talonavicular arthrodesis in 26 patients; twenty women and six men. Tibialis posterior tendon dysfunction was diagnosed preoperatively by physical examination and by MRI. Talonavicular fusion was achieved via screws in eight patients, memory staples in twelve patients and a combination of screws and memory staples in six cases. The average duration of immobilization after the surgery was four weeks, followed by rehabilitation. Full weight bearing was allowed two to three months after surgery.</p> <p>Results</p> <p>The mean age of the group at the time of the surgery was 43.6 years. MRI examination revealed a torn tendon in nine cases with no significant destruction of the talonavicular joint seen on X-rays. Mean of postoperative followup was 4.5 years (3 to 7 years). The mean of AOFAS Hindfoot score improved from 48.2 preoperatively to 88.6 points at the last postoperative followup. Eighteen patients had excellent results (none, mild occasional pain), six patients had moderate pain of the foot and two patients had severe pain in evaluation with the score. Complications included superficial wound infections in two patients and a nonunion developed in one case.</p> <p>Conclusions</p> <p>Early isolated talonavicular arthrodesis provides excellent pain relief and prevents further progression of the foot deformities in patients with rheumatoid arthritis and tibialis posterior tendon dysfunction.</p