The Centrosomal Kinase Plk1 Localizes to the Transition Zone of Primary Cilia and Induces Phosphorylation of Nephrocystin-1

Polo-like kinase (Plk1) plays a central role in regulating the cell cycle. Plk1-mediated phosphorylation is essential for centrosome maturation, and for numerous mitotic events. Although Plk1 localizes to multiple subcellular sites, a major site of action is the centrosomes, which supports mitotic functions in control of bipolar spindle formation. In G0 or G1 untransformed cells, the centriolar core of the centrosome differentiates into the basal body of the primary cilium. Primary cilia are antenna-like sensory organelles dynamically regulated during the cell cycle. Whether Plk1 has a role in ciliary biology has never been studied. Nephrocystin-1 (NPHP1) is a ciliary protein; loss of NPHP1 in humans causes nephronophthisis (NPH), an autosomal-recessive cystic kidney disease. We here demonstrate that Plk1 colocalizes with nephrocystin-1 to the transition zone of primary cilia in epithelial cells. Plk1 co-immunoprecipitates with NPHP1, suggesting it is part of the nephrocystin protein complex. We identified a candidate Plk1 phosphorylation motif (D/E-X-S/T-φ-X-D/E) in nephrocystin-1, and demonstrated in vitro that Plk1 phosphorylates the nephrocystin N-terminus, which includes the specific PLK1 phosphorylation motif. Further, induced disassembly of primary cilia rapidly evoked Plk1 kinase activity, while small molecule inhibition of Plk1 activity or RNAi-mediated downregulation of Plk1 limited the first and second phase of ciliary disassembly. These data identify Plk1 as a novel transition zone signaling protein, suggest a function of Plk1 in cilia dynamics, and link Plk1 to the pathogenesis of NPH and potentially other cystic kidney diseases

Investigation of scaling laws in a turbulent boundary layer flow with adverse pressure gradient using PIV

We present an experimental investigation and data analysis of a turbulent boundary layer flow at a significant adverse pressure gradient at Reynolds number up to Re-theta=10000. We combine large-scale PIV with microscopic PIV for measuring the near wall region including the viscous sublayer. We investigate scaling laws for the mean velocity and for the total shear stress in the inner layer. In the inner part the mean velocity can be fitted by a log-law. In the outer part of the inner layer the log-law ceases to be valid. Instead, a modified log-law gives a good fit, which is given in terms of the pressure gradient parameter and a parameter for the mean inertial effects. Finally we describe and validate a simple quantitative model for the total shear stress distribution which is local in wall-normal direction without streamwise history effects

Modeling Embedded Software: State of the Art and Beyond

State-of-the-art software development increasingly relies on describing the system (or software) graphically, abstracting from an actual implementation platform, and supporting to generate an executable system out of the model. Similarly, in electrical engineering often graphically represented models are used to describe the controlled system including its low-level control behavior. Since developing embedded software requires using abstract, functional models of the software as well as incorporating aspects from the implemented algorithmic behavior, a suitable model-based development process must integrate models from both fields. By comparing the results from modeling an automotive embedded controller software module with eight different state-of-the art CASE tools, we show what kind of abstractions, views, and models have proven useful in that domain. Furthermore, we show what analytical and generative development steps are currently supported by CASE tools. Based on those experiences and results from other research on efficiency and effectiveness of software engineering techniques and CASE support, we derive the properties of a model-based development process and illustrate it by example support functionalities

Risk of Herpes Zoster incidence and recurrence in adult patients with underlying conditions - a retrospective cohort study based on German claims data, 2007-2018

Witte J, Batram M, Schwarz M, et al. Risk of Herpes Zoster incidence and recurrence in adult patients with underlying conditions - a retrospective cohort study based on German claims data, 2007-2018. In: Abstracts zum 127. Kongress der Deutschen Gesellschaft für Innere Medizin e.V. Der Internist. Vol 62. Heidelberg: Springer ; 2021: 193

Burden of Herpes Zoster in Adult Patients with Underlying Conditions: Analysis of German Claims Data, 2007–2018

Batram M, Witte J, Schwarz M, et al. Burden of Herpes Zoster in Adult Patients with Underlying Conditions: Analysis of German Claims Data, 2007–2018. Dermatology and Therapy. 2021;11:1009–1026