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The three mammalian D-type cyclins are thought to promote progression through the [G.sub.1] phase of the cell cycle as regulatory subunits of cyclin-dependent kinase 4 and 6. In addition, they have been proposed to control the activity of various transcription factors without a partner kinase. Here we describe phenotypic consequences of null mutations in Cyclin D, the single D-type cyclin gene in Drosophila. As previously observed with null mutations in the single Drosophila Cdk4 gene, these mutations do not primarily affect progression through the [G.sub.1] phase. Moreover, the apparently indistinguishable phenotypes of double (CycD) and Cdk4) and single mutants (CycD or Cdk4) argue against major independent functions of Cyclin D and Cdk4. The reduced cellular and organismal growth rates observed in both mutants indicate that Cyclin D-Cdk4 acts as a growth driver.

The European Water Framework Directive (WFD) entered into force in December 2000; it marks a decisive turn in European water governance and related policies, management practices and restoration trends. After 20 years of implementation through two management cycles, EU member states have transposed the WFD requirements into national law, performed baseline assessments of water bodies, and implemented first measures such as hydromorphological river restoration which aims to achieve 'good ecological status', or at least the potential level targeted for that particular water body, by 2027. So far, however, WFD implementation has shown limited success; this weak result has given rise to studies, which are mainly discussions about possible technical limitations of WFD implementation and the appropriateness of monitoring procedures. This paper complements these studies by exploring governance-related bottlenecks that have emerged in the last two decades, as perceived by scientists and practitioners. An online survey was conducted which built on a list of 24 barriers to WFD implementation; these barriers had been identified previously by more than 40 researchers during a workshop in January 2019 and through a literature review. In this survey, the list of perceived barriers to WFD implementation was shared to 130 scientists and practitioners, who were asked to prioritise the items on list. Taken together, four main barriers to WFD implementation were identified: 1) problems related to horizontal intersectoral communication, 2) insufficient land reserves, 3) insufficient staff capacities, and 4) inadequate funding. The results of the analysis of WFD implementation indicated a bottleneck at the governance level that was due to insufficient horizontal collaboration and communication. This result is not in line with previous surveys that identified policy integration as the main bottleneck. We conclude from this that the governance dimension of WFD implementation merits more attention in terms of both research and political consultation in order to identify the needs for action that are key to improved WFD implementation. [ABSTRACT FROM AUTHOR]

As the world's largest payments for ecosystem services (PES) program, China's Sloping Land Conversion Program (SLCP) is designed to combat soil erosion and land degradation by converting cropland on steep slopes into forests. Operating through an incentive-based approach, the SLCP involved 32 million rural households as core agents. This paper aims to fill a research gap regarding how socioeconomic and institutional conditions influence rural households to reach the primary environmental goals. Using fuzzy-set qualitative comparative analysis (fsQCA), we conclude that at the household level, the different pathways to environmental success or failure have been shaped by socioeconomic and institutional conditions in a combinatory manner rather than single conditions alone. Specifically, the combination of household involvement and effective monitoring plays a fundamental role in capacity-building between government and households. We found that financial incentives have a trade-off effect, as they could not only create a positive interaction but also trigger failure in situations with different conditions. Finally, the potential and limits of QCA were discussed, and we call for a more serious reflection on the added value of QCA as an alternative or complementary method to conventional approaches in environmental governance research. [ABSTRACT FROM AUTHOR]

The rising incidence of obesity and related disorders such as diabetes and heart disease has focused considerable attention on the discovery of new therapeutics. One promising approach has been to increase the number or activity of brown-like adipocytes in white adipose depots, as this has been shown to prevent diet-induced obesity and reduce the incidence and severity of type 2 diabetes. Thus, the conversion of fat-storing cells into metabolically active thermogenic cells has become an appealing therapeutic strategy to combat obesity. Here, we report a screening platform for the identification of small molecules capable of promoting a white-to-brown metabolic conversion in human adipocytes. We identified two inhibitors of Janus kinase (JAK) activity with no precedent in adipose tissue biology that stably confer brown-like metabolic activity to white adipocytes. Importantly, these metabolically converted adipocytes exhibit elevated UCP1 expression and increased mitochondrial activity. We further found that repression of interferon signalling and activation of hedgehog signalling in JAK-inactivated adipocytes contributes to the metabolic conversion observed in these cells. Our findings highlight a previously unknown role for the JAK-STAT pathway in the control of adipocyte function and establish a platform to identify compounds for the treatment of obesity. [ABSTRACT FROM AUTHOR]