Chronic Intranasal Treatment with an Anti-Aβ30-42 scFv Antibody Ameliorates Amyloid Pathology in a Transgenic Mouse Model of Alzheimer's Disease

Amyloid-beta peptide (Aβ)-directed active and passive immunization therapeutic strategies reduce brain levels of Aβ, decrease the severity of beta-amyloid plaque pathology and reverse cognitive deficits in mouse models of Alzheimer's disease (AD). As an alternative approach to passive immunization with full IgG molecules, single-chain variable fragment (scFv) antibodies can modulate or neutralize Aβ-related neurotoxicity and inhibit its aggregation in vitro. In this study, we characterized a scFv derived from a full IgG antibody raised against the C-terminus of Aβ, and studied its passage into the brains of APP transgenic mice, as well as its potential to reduce Aβ-related pathology. We found that the scFv entered the brain after intranasal application, and that it bound to beta-amyloid plaques in the cortex and hippocampus of APP transgenic mice. Moreover, the scFv inhibited Aβ fibril formation and Aβ-mediated neurotoxicity in vitro. In a preventative therapeutic approach chronic intranasal treatment with scFv reduced congophilic amyloid angiopathy (CAA) and beta-amyloid plaque numbers in the cortex of APPswe/PS1dE9 mice. This reduction of CAA and plaque pathology was associated with a redistribution of brain Aβ from the insoluble fraction to the soluble peptide pool. Due to their lack of the effector domain of full IgG, scFv may represent an alternative tool for the treatment of Aβ-related pathology without triggering Fc-mediated effector functions. Additionally, our observations support the possibility that Aβ-directed immunotherapy can reduce Aβ deposition in brain vessels in transgenic mice

A Potassium Metal-Organic Framework based on Perylene- 3,4,9,10-tetracarboxylate as Sensing Layer for Humidity Actuators

We have synthesized a novel three-dimensional metal-organic-framework (MOF) based on the perylene-3,4,9,10-tetracarboxylate linker and potassium as metallic centre. We report the formation of this K-based MOF using conventional routes with water as solvent. This material displays intense green photoluminescence at room temperature, and displays an aggregation dependent quenching. Correlation of the optical properties with the crystalline packing was confirmed by DFT calculations. We also demonstrate its potential to build humidity actuators with a reversible and reproducible response, with a change of 5 orders of magnitudes in its impedance at about 40% relative humidity (RH). This 3D-MOF is based on an interesting perylene derivative octadentate ligand, a moiety with interesting fluorescent properties and known component in organic semiconductors. To the best of our knowledge, this is the first time to build such a printed and flexible actuator towards humidity with a reversible response, enabling precise humidity threshold monitoring.This work was supported by the Junta de Andalucía (FQM-1484, and FQM-195). Red Guipuzcoana de Ciencia, Tecnología e Innovación (OF188/2017) and University of the Basque Country (GIU14/01, EHUA16/32). BB acknowledges funding by RyC-2012–10381 contract and computational resources provided by the RES and Alhambra supercomputing facilities. This work was also supported by the German Research Foundation (DFG) and the Technical University of Munich within the Open Access Publishing Funding Programme

Cognitive Neuropsychology of HIV-Associated Neurocognitive Disorders

Advances in the treatment of the human immunodeficiency virus (HIV) have dramatically improved survival rates over the past 10 years, but HIV-associated neurocognitive disorders (HAND) remain highly prevalent and continue to represent a significant public health problem. This review provides an update on the nature, extent, and diagnosis of HAND. Particular emphasis is placed on critically evaluating research within the realm of cognitive neuropsychology that aims to elucidate the component processes of HAND across the domains of executive functions, motor skills, speeded information processing, episodic memory, attention/working memory, language, and visuoperception. In addition to clarifying the cognitive mechanisms of HAND (e.g., impaired cognitive control), the cognitive neuropsychology approach may enhance the ecological validity of neuroAIDS research and inform the development of much needed novel, targeted cognitive and behavioral therapies

Probability Theory in Statistical Physics, Percolation, and Other Random Topics: The Work of C. Newman

In the introduction to this volume, we discuss some of the highlights of the research career of Chuck Newman. This introduction is divided into two main sections, the first covering Chuck's work in statistical mechanics and the second his work in percolation theory, continuum scaling limits, and related topics.Comment: 38 pages (including many references), introduction to Festschrift in honor of C.M. Newma

Late metal–silicate separation on the IAB parent asteroid: constraints from combined W and Pt isotopes and thermal modelling

The short-lived ¹⁸²Hf–¹⁸²W decay system is a powerful chronometer for constraining the timing of metal–silicate separation and core formation in planetesimals and planets. Neutron capture effects on W isotopes, however, significantly hamper the application of this tool. In order to correct for neutron capture effects, Pt isotopes have emerged as a reliable in-situ neutron dosimeter. This study applies this method to IAB iron meteorites, in order to constrain the timing of metal segregation on the IAB parent body.The ε¹⁸²W values obtained for the IAB iron meteorites range from −3.61 ± 0.10 to −2.73 ± 0.09. Correlating εⁱPt with ε¹⁸²W data yields a pre-neutron capture ε¹⁸²W of −2.90 ± 0.06. This corresponds to a metal–silicate separation age of 6.0 ± 0.8 Ma after CAI for the IAB parent body, and is interpreted to represent a body-wide melting event. Later, between 10 and 14 Ma after CAI, an impact led to a catastrophic break-up and subsequent reassembly of the parent body. Thermal models of the interior evolution that are consistent with these estimates suggest that the IAB parent body underwent metal–silicate separation as a result of internal heating by short-lived radionuclides and accreted at around Ma after CAIs with a radius of greater than 60 km