Localism in Finland : The changing role and current crisis of the Finnish municipal system

Peer reviewe

Improving signal detection in emission optical projection tomography via single source multi-exposure image fusion

Abstract We demonstrate a technique to improve structural data obtained from Optical Projection Tomography (OPT) using Image Fusion (IF) and contrast normalization. This enables the visualization of molecular expression patterns in biological specimens with highly variable contrast values. In the approach, termed IF-OPT, different exposures are fused by assigning weighted contrasts to each. When applied to projection images from mouse organs and digital phantoms our results demonstrate the capability of IF-OPT to reveal high and low signal intensity details in challenging specimens. We further provide measurements to highlight the benefits of the new algorithm in comparison to other similar methods

HNF1B controls proximal-intermediate nephron segment identity in vertebrates by regulating Notch signalling components and Irx1/2

Abstract The nephron is a highly specialised segmented structure that provides essential filtration and resorption renal functions. It arises by formation of a polarised renal vesicle that differentiates into a comma-shaped body and then a regionalised S-shaped body (SSB), with the main prospective segments mapped to discrete domains. The regulatory circuits involved in initial nephron patterning are poorly understood. We report here that HNF1B, a transcription factor known to be involved in ureteric bud branching and initiation of nephrogenesis, has an additional role in segment fate acquisition. Hnf1b conditional inactivation in murine nephron progenitors results in rudimentary nephrons comprising a glomerulus connected to the collecting system by a short tubule displaying distal fates. Renal vesicles develop and polarise normally but fail to progress to correctly patterned SSBs. Major defects are evident at late SSBs, with altered morphology, reduction of a proximo-medial subdomain and increased apoptosis. This is preceded by strong downregulation of the Notch pathway components Lfng, Dll1 and Jag1 and the Irx1/2 factors, which are potential regulators of proximal and Henle’s loop segment fates. Moreover, HNF1B is recruited to the regulatory sequences of most of these genes. Overexpression of a HNF1B dominant-negative construct in Xenopus embryos causes downregulation specifically of proximal and intermediate pronephric segment markers. These results show that HNF1B is required for the acquisition of a proximo-intermediate segment fate in vertebrates, thus uncovering a previously unappreciated function of a novel SSB subcompartment in global nephron segmentation and further differentiation

A FRET-based high-throughput screening platform for the discovery of chemical probes targeting the scaffolding functions of human tankyrases

Abstract Tankyrases catalyse poly-ADP-ribosylation of their binding partners and the modification serves as a signal for the subsequent proteasomal degradation of these proteins. Tankyrases thereby regulate the turnover of many proteins involved in multiple and diverse cellular processes, such as mitotic spindle formation, telomere homeostasis and Wnt/β-catenin signalling. In recent years, tankyrases have become attractive targets for the development of inhibitors as potential therapeutics against cancer and fibrosis. Further, it has become clear that tankyrases are not only enzymes, but also act as scaffolding proteins forming large cellular signalling complexes. While many potent and selective tankyrase inhibitors of the poly-ADP-ribosylation function exist, the inhibition of tankyrase scaffolding functions remains scarcely explored. In this work we present a robust, simple and cost-effective high-throughput screening platform based on FRET for the discovery of small molecule probes targeting the protein–protein interactions of tankyrases. Validatory screening with the platform led to the identification of two compounds with modest binding affinity to the tankyrase 2 ARC4 domain, demonstrating the applicability of this approach. The platform will facilitate identification of small molecules binding to tankyrase ARC or SAM domains and help to advance a structure-guided development of improved chemical probes targeting tankyrase oligomerization and substrate protein interactions

Optical studies of nanodiamond-tissue interaction:skin penetration and localization

Abstract In this work, several optical-spectroscopic methods have been used to visualize and investigate the penetration of diamond nanoparticles (NPs) of various sizes (3–150 nm), surface structures and fluorescence properties into the animal skin in vitro. Murine skin samples have been treated with nanodiamond (ND) water suspensions and studied using optical coherence tomography (OCT), confocal and two-photon fluorescence microscopy and fluorescence lifetime imaging (FLIM). An analysis of the optical properties of the used nanodiamonds (NDs) enables the selection of optimal optical methods or their combination for the study of nanodiamond–skin interaction. Among studied NDs, particles of 100 nm in nominal size were shown to be appropriate for multimodal imaging using all three methods. All the applied NDs were able to cross the skin barrier and penetrate the different layers of the epidermis to finally arrive in the hair follicle niches. The results suggest that NDs have the potential for multifunctional applications utilizing multimodal imaging

On the trail of local welfare innovations in rural Finland

Final DraftIn Finland, the rural areas have been most affected by the developments threatening the survival of the welfare state as well as by conflicting efforts to save it. However, there are rural communities that have—as a response to the mainstream policy emphasizing economic efficiency and individual responsibility—developed innovative solutions to secure their welfare. Based on a case study focusing on two of such communities, these local welfare innovations are a result from a combination of external causes and local resources including the sense of community and a diverse enough community structure. The authors argue that in the context of welfare policy, the promotion of local welfare innovation calls for a comprehensive approach, which considers the broader viability dimension of the communities and works towards it in tight collaboration with various actors from different policy fields and societal sectors.peerReviewe

MRNIP interacts with sex body chromatin to support meiotic progression, spermatogenesis, and male fertility in mice

Abstract Meiosis has a principal role in sexual reproduction to generate haploid gametes in both sexes. During meiosis, the cell nucleus hosts a dynamic environment where some genes are transcriptionally activated, and some are inactivated at the same time. This becomes possible through subnuclear compartmentalization. The sex body, sequestering X and Y chromosomes during male meiosis and creating an environment for the meiotic sex chromosome inactivation (MSCI) is one of the best known and studied subnuclear compartments. Herein, we show that MRNIP forms droplet-like accumulations that fuse together to create a distinct subnuclear compartment that partially overlaps with the sex body chromatin during diplotene. We demonstrate that Mrnip−/− spermatocytes have impaired DNA double-strand break (DSB) repair, they display reduced sex body formation and defective MSCI. We show that Mrnip−/− undergoes critical meiocyte loss at the diplotene stage. Furthermore, we determine that DNA DSBs (induced by SPO11) and synapsis initiation (facilitated by SYCP1) precede Mrnip expression in testes. Altogether, our findings indicate that in addition to an emerging role in DNA DSB repair, MRNIP has an essential function in spermatogenesis during meiosis I by forming drop-like accumulations interacting with the sex body