Advanced analog television study final report, 4 nov. - 19 dec. 1963

Information bandwidth reduction for analog television signals - Description of multiple interlace syste

Identification of evolutionary and kinetic drivers of NAD-dependent signaling

Nicotinamide adenine dinucleotide (NAD) provides an important link between metabolism and signal transduction and has emerged as central hub between bioenergetics and all major cellular events. NAD-dependent signaling (e.g., by sirtuins and poly-adenosine diphosphate [ADP] ribose polymerases [PARPs]) consumes considerable amounts of NAD. To maintain physiological functions, NAD consumption and biosynthesis need to be carefully balanced. Using extensive phylogenetic analyses, mathematical modeling of NAD metabolism, and experimental verification, we show that the diversification of NAD-dependent signaling in vertebrates depended on 3 critical evolutionary events: 1) the transition of NAD biosynthesis to exclusive usage of nicotinamide phosphoribosyltransferase (NamPT); 2) the occurrence of nicotinamide N-methyltransferase (NNMT), which diverts nicotinamide (Nam) from recycling into NAD, preventing Nam accumulation and inhibition of NAD-dependent signaling reactions; and 3) structural adaptation of NamPT, providing an unusually high affinity toward Nam, necessary to maintain NAD levels. Our results reveal an unexpected coevolution and kinetic interplay between NNMT and NamPT that enables extensive NAD signaling. This has implications for therapeutic strategies of NAD supplementation and the use of NNMT or NamPT inhibitors in disease treatment

G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling

Ras GTPase-activating protein-binding proteins 1 and 2 (G3BP1 and G3BP2, respectively) are widely recognized as core components of stress granules (SGs). We report that G3BPs reside at the cytoplasmic surface of lysosomes. They act in a non-redundant manner to anchor the tuberous sclerosis complex (TSC) protein complex to lysosomes and suppress activation of the metabolic master regulator mechanistic target of rapamycin complex 1 (mTORC1) by amino acids and insulin. Like the TSC complex, G3BP1 deficiency elicits phenotypes related to mTORC1 hyperactivity. In the context of tumors, low G3BP1 levels enhance mTORC1-driven breast cancer cell motility and correlate with adverse outcomes in patients. Furthermore, G3bp1 inhibition in zebrafish disturbs neuronal development and function, leading to white matter heterotopia and neuronal hyperactivity. Thus, G3BPs are not only core components of SGs but also a key element of lysosomal TSC-mTORC1 signaling

CASE Needs Analysis. Summary. Findings on Competencies for Sustainability-driven Entrepreneurship. Based on interviews with partners from sustainability-driven enterprises and universities

The report represents the main outputs of the needs analysis of work package 1 (WP1) within the CASE project. The specific aim of the report and WP1 is to summarize concrete needs and necessary competencies for sustainability-driven entrepreneurship. For this purpose a qualitative research approach was chosen to bring together perspectives of enterprises and universities concerning a future collaboration as a possible starting-point for a long-lasting multistakeholder network. Furthermore an analysis of best practice examples was necessary in order to create synergies and use existing knowledge and good experiences of teaching towards sustainability-driven entrepreneurship. As the results show, both, companies and universities, are highly aware of the huge challenges for society, economy and natural environment on a global and regional level. That calls for integrated, holistic approaches and for comprehensive socio-economic transformation processes, involving various stakeholders from entrepreneurial, societal and educational contexts. As disciplinary analysis quickly reach their limits, research and practice for sustainability-driven entrepreneurship require comprehensive and integrated approaches. Multistakeholder networks could provide the right learning environments for complex sustainability issues