Selective cargo and membrane recognition by SNX17 regulates its interaction with Retriever.

The Retriever complex recycles a wide range of transmembrane proteins from endosomes to the plasma membrane. The cargo adapter protein SNX17 has been implicated in recruiting the Retriever complex to endosomal membranes, yet the details of this interaction have remained elusive. Through biophysical and structural model-guided mutagenesis studies with recombinant proteins and liposomes, we have gained a deeper understanding of this process.

TPR is required for cytoplasmic chromatin fragment formation during senescence.

During oncogene-induced senescence there are striking changes in the organisation of heterochromatin in the nucleus. This is accompanied by activation of a pro-inflammatory gene expression programme - the senescence-associated secretory phenotype (SASP) - driven by transcription factors such as NF-κB. The relationship between heterochromatin re-organisation and the SASP has been unclear.

ERK2 stimulates transcription by anchoring CDK9 to the promoter in a kinase activity-independent manner.

The transcription factor MYC regulates cell proliferation, transformation, and survival in response to growth factor signaling that is mediated in part by the kinase activity of ERK2. Because ERK2 can also bind to DNA to modify gene expression, we investigated whether it more directly regulates transcription. We identified ERK2 binding sites in the promoter and detected ERK2 at the promoter in various serum-stimulated cell types.

Discovery of senolytics using machine learning.

Cellular senescence is a stress response involved in ageing and diverse disease processes including cancer, type-2 diabetes, osteoarthritis and viral infection. Despite growing interest in targeted elimination of senescent cells, only few senolytics are known due to the lack of well-characterised molecular targets. Here, we report the discovery of three senolytics using cost-effective machine learning algorithms trained solely on published data.

Structured Reactors Based on 3D Fe/SiC Catalysts: Understanding the Effects of Mixing.

The application of structured reactors provides a number of advantages in chemical processes. In this paper, two different three-dimensional (3D) Fe/SiC catalysts with a square cell geometry have been manufactured by Robocasting: monoliths ( = 14 and = 15 mm) and meshes ( = 24 and = 2 mm) and studied in the catalytic phenol oxidation by hydrogen peroxide (HO) for the sustainable production of dihydroxybenzenes (DHBZ). The fluid dynamics, catalytic performance, reaction rates, external mass transport limitation, and catalyst stability have been compared in three different reactors, monolithic fixed-bed reactor, multimesh fixed-bed reactor, and monolithic stirrer reactor, at selected operating conditions.