[Evidence-based health care with pharmaceuticals for rare diseases: the role of digitalisation].

Knowledge generation in the field of drug development for people with rare diseases (RDs) faces particular difficulties. This paper will show what improvements are expected from increasing digitalisation from the perspective of three healthcare institutions: the Federal Institute for Drugs and Medical Devices, the Institute for Quality and Efficiency in Health Care and the Federal Joint Committee.First, the potential of digitalisation to increase the efficiency of clinical development and regulatory decision-making through earlier collaboration of all stakeholders is proposed.

How aligned are the perspectives of EU regulators and HTA bodies? A comparative analysis of regulatory-HTA parallel scientific advice.

Background: In 2010, the European Medicines Agency (EMA) initiated a pilot project on parallel scientific advice with Health Technology Assessment bodies (HTABs) that allows manufacturers to receive simultaneous feedback from both the European Union (EU) regulators and HTABs on their development plans for medicines.

Aims: The present retrospective qualitative analysis aimed to explore how the parallel scientific advice system is working and levels of commonality between the EU regulators and HTABs, and among HTABs, when applicants obtain parallel scientific advice from both a regulatory and an HTA perspective.

Methods: We analysed the minutes of discussion meetings held at the EMA between 2010, when parallel advice was launched, and 1 May 2015, when the cutoff date for data extraction was set.

STK35L1 associates with nuclear actin and regulates cell cycle and migration of endothelial cells.

Background: Migration and proliferation of vascular endothelial cells are essential for repair of injured endothelium and angiogenesis. Cyclins, cyclin-dependent kinases (CDKs), and cyclin-dependent kinase inhibitors play an important role in vascular tissue injury and wound healing. Previous studies suggest a link between the cell cycle and cell migration: cells present in the G(1) phase have the highest potential to migrate.

Identifying and characterizing a novel protein kinase STK35L1 and deciphering its orthologs and close-homologs in vertebrates.

Background: The human kinome containing 478 eukaryotic protein kinases has over 100 uncharacterized kinases with unknown substrates and biological functions. The Ser/Thr kinase 35 (STK35, Clik1) is a member of the NKF 4 (New Kinase Family 4) in the kinome with unknown substrates and biological functions. Various high throughput studies indicate that STK35 could be involved in various human diseases such as colorectal cancer and malaria.

Inhibition of nuclear import of LIMK2 in endothelial cells by protein kinase C-dependent phosphorylation at Ser-283.

LIM kinases (LIMKs) are mainly in the cytoplasm and regulate actin dynamics through cofilin phosphorylation. Recently, it has been reported that nuclear localization of LIMKs can mediate suppression of cyclin D1 expression. Using immunofluorescence monitoring of enhanced green fluorescent protein-tagged LIMK2 in combination with photobleaching techniques and leptomycin B treatment, we demonstrate that LIMK2 shuttles between the cytoplasm and the nucleus in endothelial cells.

Proteomic identification of 3-nitrotyrosine-containing rat cardiac proteins: effects of biological aging.

Proteomic techniques were used to identify cardiac proteins from whole heart homogenate and heart mitochondria of Fisher 344/Brown Norway F1 rats, which suffer protein nitration as a consequence of biological aging. Soluble proteins from young (5 mo old) and old (26 mo old) animals were separated by one- and two-dimensional gel electrophoresis. One- and two-dimensional Western blots with an anti-nitrotyrosine antibody show an age-related increase in the immunoresponse of a few specific proteins, which were identified by nanoelectrospray ionization-tandem mass spectrometry (NSI-MS/MS).