Idiopathic inflammatory myopathy (IIM) summarizes rare, systemic autoimmune conditions primarily characterized by inflammatory damage to the skeletal muscle. Although primary damage occurs to the ...muscle, these IIM-related conditions involve other organs, including the skin, lungs, upper gastrointestinal tract, joints, and heart. While many patients have an adequate response to immunosuppressive treatment, some patients develop rapidly progressive and treatment-resistant life-threatening courses. Treatment-resistant IIM is challenging for the treating physician and requires interdisciplinary and individualized treatment approaches. Extracorporeal therapy is one option for rescue therapy, with immunoadsorption (IA) having proven more effective than plasma exchange regarding the removal of circulating antibodies. Despite its efficacy and desirable safety profile, the clinical value of IA use in IIM is understudied with no controlled trials reported. Here, we present a review of the current knowledge regarding the management of treatment-resistant IIM and the cases of three patients with treatment-resistant IIM (two with dermatomyositis and one with immune-mediated necrotizing myopathy) who have successfully been treated with IA. All patients responded well to the therapy and experienced no IA-related complications. Taken together, we found IA to be a safe and effective treatment option in treatment-resistant IIM.
Acetyl-CoA carboxylase catalyses the ATP-dependent carboxylation of acetyl-CoA, a rate-limiting step in fatty acid biosynthesis
. Eukaryotic acetyl-CoA carboxylases are large, homodimeric ...multienzymes. Human acetyl-CoA carboxylase occurs in two isoforms: the metabolic, cytosolic ACC1, and ACC2, which is anchored to the outer mitochondrial membrane and controls fatty acid β-oxidation
. ACC1 is regulated by a complex interplay of phosphorylation, binding of allosteric regulators and protein-protein interactions, which is further linked to filament formation
. These filaments were discovered in vitro and in vivo 50 years ago
, but the structural basis of ACC1 polymerization and regulation remains unknown. Here, we identify distinct activated and inhibited ACC1 filament forms. We obtained cryo-electron microscopy structures of an activated filament that is allosterically induced by citrate (ACC-citrate), and an inactivated filament form that results from binding of the BRCT domains of the breast cancer type 1 susceptibility protein (BRCA1). While non-polymeric ACC1 is highly dynamic, filament formation locks ACC1 into different catalytically competent or incompetent conformational states. This unique mechanism of enzyme regulation via large-scale conformational changes observed in ACC1 has potential uses in engineering of switchable biosynthetic systems. Dissecting the regulation of acetyl-CoA carboxylase opens new paths towards counteracting upregulation of fatty acid biosynthesis in disease.
Peroxisomal matrix proteins contain either a peroxisomal targeting sequence 1 (PTS1) or a PTS2 that are recognized by the import receptors PEX5 and PEX7, respectively. PEX5 transports the PTS1 ...proteins and the PEX7/PTS2 complex to the docking translocation module (DTM) at the peroxisomal membrane. After cargo release PEX5 is monoubiquitinated and extracted from the peroxisomal membrane by the receptor export machinery (REM) comprising PEX26 and the AAA ATPases PEX1 and PEX6. Here, we investigated the protein interactions of monoubiquitinated PEX5 with the docking proteins PEX13, PEX14 and the REM. "Click" chemistry was used to synthesise monoubiquitinated recombinant PEX5. We found that monoubiquitinated PEX5 binds the PEX7/PTS2 complex and restores PTS2 protein import in vivo in ΔPEX5 fibroblasts. In vitro pull-down assays revealed an interaction of recombinant PEX5 and monoubiquitinated PEX5 with PEX13, PEX14 and with the REM components PEX1, PEX6 and PEX26. The interactions with the docking proteins were independent of the PEX5 ubiquitination status whereas the interactions with the REM components were increased when PEX5 is ubiquitinated.
Dynamics of the electron spin in the Photoelectric Effect was studied in time-reversal via the process of Radiative Recombination. For this the photorecombination into an excited state of an ion and ...its subsequent radiative decay was observed. Pairs of correlated photons were detected in conicidence. Such an observation is the first of its kind for the initial ion as heavy as bare uranium.
Herding cats Hagmann, Jürgen; Chuma, Edward; Ramaru, Joe ...
Responding to Environmental Issues Through Adaptive Collaborative Management,
2023
Book Chapter
High-quality facilitation of social learning processes in Adaptive Collaborative Management (ACM) is key to the success of such processes, whether at community, service provider, managerial or policy ...level. Facilitation is a set of tools and techniques in communication. However, high-quality process facilitation for change is much broader than applied communication tools. It borrows elements from personal and organisational development and change management, and is linked to behavioural change psychology as well as community development, action learning/research and systemic intervention. Communities and forest users are complex organisational entities, often extremely heterogenous and conflictual. Change must be seen and addressed in this complex context. Only well-designed facilitation processes, skills and competences can produce successful processes.
The chapter unpacks good process facilitation based on long-term experience over three decades in Eastern and Southern Africa, Asia and the Caribbean. It elaborates how such facilitation competences can be developed within institutions and communities. Facilitation for change is the backbone of operationalising participation, engagement of people and collaboration. A successful intervention requires far more programme investment in developing good facilitation and process management capacity than typically planned.
This chapter discusses both products representing recent incremental innovations with conventional nanomaterials that are already produced on the scale of megatons per year as well as disruptive ...innovations based on novel nanomaterials. It presents the case studies for composite systems, nanoporous systems, and particle‐based systems. The overview of nanoenabled products and product categories is not organized by chemical substance but instead takes the system perspective by considering the following major categories of nanomaterial systems: composites, dispersions and emulsions, fibers and yarns, nanoporous systems, particle‐based systems, and thin films. Nanocomposite systems are enabled by internally nanostructured materials. That internal structure can be generated by embedding intermediates such as nanomaterial powders or suspensions into a continuous matrix. Nanoporous membranes come in many materials, polymers being the most commonly used due to their cost‐effective production. Membrane‐based separation processes, in contrast to distillation processes, can operate at low energy consumption, that is, under isothermal conditions.
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