Photoemission "experiments" on holographic superconductors

We study the effects of a superconducting condensate on holographic Fermi surfaces. With a suitable coupling between the fermion and the condensate, there are stable quasiparticles with a gap. We find some similarities with the phenomenology of the cuprates: in systems whose normal state is a non-Fermi liquid with no stable quasiparticles, a stable quasiparticle peak appears in the condensed phase.Comment: 14 pages, 13 figures; v2: typos corrected and some clarification adde

AAV-mediated delivery of an anti-BACE1 VHH alleviates pathology in an Alzheimer's disease model

Single domain antibodies (VHHs) are potentially disruptive therapeutics, with important biological value for treatment of several diseases, including neurological disorders. However, VHHs have not been widely used in the central nervous system (CNS), largely because of their restricted blood-brain barrier (BBB) penetration. Here, we propose a gene transfer strategy based on BBB-crossing adeno-associated virus (AAV)-based vectors to deliver VHH directly into the CNS. As a proof-of-concept, we explored the potential of AAV-delivered VHH to inhibit BACE1, a well-characterized target in Alzheimer's disease. First, we generated a panel of VHHs targeting BACE1, one of which, VHH-B9, shows high selectivity for BACE1 and efficacy in lowering BACE1 activity in vitro. We further demonstrate that a single systemic dose of AAV-VHH-B9 produces positive long-term (12 months plus) effects on amyloid load, neuroinflammation, synaptic function, and cognitive performance, in the AppNL-G-F Alzheimer's mouse model. These results constitute a novel therapeutic approach for neurodegenerative diseases, which is applicable to a range of CNS disease targets.We want to thank the collaborators of the VIB Nanobody Core and VIB Protein Core for their valuable contribution to the research presented in this paper. We thank Joost Schymkowitz, Frederic Rousseau, and Roosmarijn Vandenbroucke for discussions and advice. We thank Jeason Haughton for expert support with mouse husbandry. MM was supported by a predoctoral fellowship from the Fonds Wetenschappelijk Onderzoek (FWO) (SB/ 1S48018N). MYR received a postdoctoral fellowship from the FWO (133722/ 1204517N) and acknowledges the continuous support of the Fundacion Cardiovascular de Colombia. SID was supported by The Foundation for Alzheimer Research (SAO-FRA) (P#14006). MGH was supported by the Thierry Latran Foundation (SOD-VIP), FWO (Grant 1513616N), and European Research Council (ERC) (Starting Grant 281961—AstroFunc; Proof of Concept Grant 713755—AD-VIP). He is currently the ERANet Chair (NCBio) at i3S Porto funded by the European Commission (H2020-WIDESPREAD-2018- 2020-6; NCBio; 951923). Work in the BDS Lab is supported by the Opening the Future campaign of the KU Leuven, SAO-FRA (P#16017), FWO, KU Leuven, VIB, a Methusalem grant from KU Leuven and the Flemish Government, the Flanders Network for Dementia Research (VIND, Strategic Basic Research Grant 135043) and the Alzheimer’s Association. BDS is supported by the Geneeskundige Stichting Koningin Elisabeth and the Bax-Vanluffelen Chair for Alzheimer’s disease. The synopsis image was produced by David Pennington (@PenningtonArt.co.uk)

Low hippocampal PI(4,5)P 2 contributes to reduced cognition in old mice as a result of loss of MARCKS

Cognitive and motor performances decline during aging. Although it is clear that such signs reflect synaptic compromise, the underlying mechanisms have not been defined. We found that the levels and activity of the synaptic plasticity modulators phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P 2) and phospholipase Cγ (PLCγ) were substantially reduced in hippocampal synaptic membranes from old mice. In addition, these membranes contained reduced levels of the PI(4,5)P 2-clustering molecule myristoylated alanine-rich C kinase substrate (MARCKS). Consistent with a cause-effect relationship, raising MARCKS levels in the brain of old mice led to increased synaptic membrane clustering of PI(4,5)P 2 and to PLCγ activation. MARCKS overexpression in the hippocampus of old mice or intraventricular perfusion of MARCKS peptide resulted in enhanced long-term potentiation and improved memory. These results reveal one of the mechanisms involved in brain dysfunction during aging. © 2013 Nature America, Inc. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Genetically engineered humanized mouse models for preclinical antibody studies.

The use of genetic engineering has vastly improved our capabilities to create animal models relevant in preclinical research. With the recent advances in gene-editing technologies, it is now possible to very rapidly create highly tunable mouse models as needs arise. Here, we provide an overview of genetic engineering methods, as well as the development of humanized neonatal Fc receptor (FcRn) models and their use for monoclonal antibody in vivo studies