Looking for transitions

__Abstract__ Drawing on experience with transition monitoring in 9 different programmes and sectors in the period 2005-2010, his research describes a wide array of monitoring instruments as well as general building blocks for transition monitoring. Given the complexity and uncertainties regarding transitions, programmes generally do not start with well-defined objectives and a clear view of the transition they are pursuing. They develop these over time as well as the networks and innovations necessary to achieve them. Sometimes this ´goal searching´ behaviour is wrongly mistaken as a weakness of such programmes, as it makes it difficult to account for their impacts. However, Taanman finds that this behaviour is not only an emperical fact but also a strong legitimization for these programmes as it addresses key governance, market and system flaws. Transition monitoring supports programme development by providing facts, feedback and reflection on developments at project, programme and transition field levels. The research describes what kind of monitoring information is useful at different points in time as well as modes in which programme managers and outside experts can co-produce this information

Mitochondria as target to inhibit proliferation and induce apoptosis of cancer cells: the effects of doxycycline and gemcitabine

Doxycycline has anti-tumour effects in a range of tumour systems. The aims of this study were to define the role mitochondria play in this process and examine the potential of doxycycline in combination with gemcitabine. We studied the adenocarcinoma cell line A549, its mitochondrial DNA-less derivative A549 ρ° and cultured fibroblasts. Treatment with doxycycline for 5 days resulted in a decrease of mitochondrial-encoded proteins, respiration and membrane potential, and an increase of reactive oxygen species in A549 cells and fibroblasts, but fibroblasts were less affected. Doxycycline slowed proliferation of A549 cells by 35%. Cellular ATP levels did not change. Doxycycline alone had no effect on apoptosis; however, in combination with gemcitabine given during the last 2 days of treatment, doxycycline increased caspase 9 and 3/7 activities, resulting in a further decrease of surviving A549 cells by 59% and of fibroblasts by 24% compared to gemcitabine treatment alone. A549 ρ° cells were not affected by doxycycline. Key effects of doxycycline observed in A549 cells, such as the decrease of mitochondrial-encoded proteins and surviving cells were also seen in the cancer cell lines COLO357 and HT29. Our results suggest that doxycycline suppresses cancer cell proliferation and primes cells for apoptosis by gemcitabine

Mitochondrial cristae remodelling is associated with disrupted OPA1 oligomerisation in the Huntington's disease R6/2 fragment model

There is evidence of an imbalance of mitochondrial fission and fusion in patients with Huntington's disease (HD) and HD animal models. Fission and fusion are important for mitochondrial homeostasis including mitochondrial DNA (mtDNA) maintenance and may be relevant for the selective striatal mtDNA depletion that we observed in the R6/2 fragment HD mouse model. We aimed to investigate the fission/fusion balance and the integrity of the mitochondrial membrane system in cortex and striatum of end-stage R6/2 mice and wild-type animals. Mitochondrial morphology was determined using electron microscopy, and transcript and protein levels of factors that play a key role in fission and fusion, including DRP1, mitofusin 1 and 2, mitofilin and OPA1, and cytochrome c and caspase 3 were assessed by RT-qPCR and immunoblotting. OPA1 oligomerisation was evaluated using blue native gels. In striatum and cortex of R6/2 mice, mitochondrial cristae morphology was abnormal. Mitofilin and the overall levels of the fission and fusion factors were unaffected; however, OPA1 oligomerisation was abnormal in striatum and cortex of R6/2 mice. Mitochondrial and cytoplasmic cytochrome c levels were similar in R6/2 and wild-type mice with no significant increase of activated caspase 3. Our results indicate that the integrity of the mitochondrial cristae is compromised in striatum and cortex of the R6/2 mice and that this is most likely caused by impaired OPA1 oligomerisation

Exploring incumbents' agency: institutional work by grid operators in decentralized energy innovations

The agency of incumbents has gained increasing attention in the study of transitions. Recent studies show that besides being inert and resistant to change, incumbents can also support transitions. We focus on the agency of a particular type of incumbent, grid operators. In several countries, these actors play an active role in institutional change in the energy domain. At the same time, they are engaging in activities to maintain the regime. This paper examines the actions of grid operators when performing institutional work, i.e. when creating, maintaining and disrupting institutions. We conducted a qualitative content analysis of Dutch media to analyze the actions of grid operators while engaging with decentralized energy innovations. We conclude that grid operators are both subject and object of institutional work as part of a distributed, collective process of institutional change. Furthermore, our analysis reflects on their paradoxical position as embedded actors engaging in institutional change.The politics and administration of institutional chang

Sirtuin 5 depletion impairs mitochondrial function in human proximal tubular epithelial cells

Ischemia is a major cause of kidney damage. Proximal tubular epithelial cells (PTECs) are highly susceptible to ischemic insults that frequently cause acute kidney injury (AKI), a potentially life-threatening condition with high mortality. Accumulating evidence has identified altered mitochondrial function as a central pathologic feature of AKI. The mitochondrial NAD+-dependent enzyme sirtuin 5 (SIRT5) is a key regulator of mitochondrial form and function, but its role in ischemic renal injury (IRI) is unknown. SIRT5 expression was increased in murine PTECs after IRI in vivo and in human PTECs (hPTECs) exposed to an oxygen/nutrient deprivation (OND) model of IRI in vitro. SIRT5-depletion impaired ATP production, reduced mitochondrial membrane potential, and provoked mitochondrial fragmentation in hPTECs. Moreover, SIRT5 RNAi exacerbated OND-induced mitochondrial bioenergetic dysfunction and swelling, and increased degradation by mitophagy. These findings suggest SIRT5 is required for normal mitochondrial function in hPTECs and indicate a potentially important role for the enzyme in the regulation of mitochondrial biology in ischemia

Van Afval Af

__Abstract__ Er is in de gemeentelijke afvalwereld consensus dat de toekomst ligt in gesloten materiaalkringlopen. Ook het Verpakkingenakkoord spreekt de ambitie uit dat in de komende tien jaar een versnelling nodig is richting grootschalig hergebruik, sluiten van kringlopen en de ontwikkeling van een goed functionerende circulaire grondstoffenmarkt. Vergelijkbare ambities zijn ook door veel gemeenten individueel en de Rijksoverheid in haar ‘afval is grondstof’ beleid uitgesproken. Die gemeentelijke ambitie – en dan specifiek op het gebied van verpakkingen - is de directe aanleiding voor deze transitie-studie. Het beoogt overzicht en suggesties te bieden aan gemeenten (en andere partijen) over hun rol in de circulaire economie vanuit hun positie in de afvalketen. Veel gemeenten hebben de beleidsvoorbereiding en/of uitvoering bij samenwerkingsverbanden of overheidsgedomineerde bedrijven gelegd. In dit document bedoelen we met gemeenten, tenzij anders vermeld, dus ook de lokale overheid inclusief deze partijen. Tijdens de interviews en sessies bleken de meningen soms verdeeld of het Verpakkingenakkoord op alle punten een stap in de goede richting is. In deze studie gaan we uit er vanuit dat het nu gesloten Verpakkingenakkoord een gegeven is, maar we besteden wel aandacht aan hoe gemeenten de invulling en uitvoering van het Verpakkingenakkoord (en de organisatie van afvalbeheer in het algemeen) de komende jaren kunnen vormgeven en strategisch positie kunnen kiezen