PSD-95 protects synapses from β-amyloid

Beta-amyloid (Aβ) depresses excitatory synapses by a poorly understood mechanism requiring NMDA receptor (NMDAR) function. Here, we show that increased PSD-95, a major synaptic scaffolding molecule, blocks the effects of Aβ on synapses. The protective effect persists in tissue lacking the AMPA receptor subunit GluA1, which prevents the confounding synaptic potentiation by increased PSD-95. Aβ modifies the conformation of the NMDAR C-terminal domain (CTD) and its interaction with protein phosphatase 1 (PP1), producing synaptic weakening. Higher endogenous levels or overexpression of PSD-95 block Aβ-induced effects on the NMDAR CTD conformation, its interaction with PP1, and synaptic weakening. Our results indicate that increased PSD-95 protects synapses from Aβ toxicity, suggesting that low levels of synaptic PSD-95 may be a molecular sign indicating synapse vulnerability to Aβ. Importantly, pharmacological inhibition of its depalmitoylation increases PSD-95 at synapses and rescues deficits caused by Aβ, possibly opening a therapeutic avenue against Alzheimer’s disease

Towards closing the gap between hygroscopic growth and activation for secondary organic aerosol: Part 1 – Evidence from measurements

Secondary Organic Aerosols (SOA) studied in previous laboratory experiments generally showed only slight hygroscopic growth, but a much better activity as a CCN (Cloud Condensation Nucleus) than indicated by the hygroscopic growth. This discrepancy was examined at LACIS (Leipzig Aerosol Cloud Interaction Simulator), using a portable generator that produced SOA particles from the ozonolysis of <i>α</i>-pinene, and adding butanol or butanol and water vapor during some of the experiments. The light scattering signal of dry SOA-particles was measured by the LACIS optical particle spectrometer and was used to derive a refractive index for SOA of 1.45. LACIS also measured the hygroscopic growth of SOA particles up to 99.6% relative humidity (RH), and a CCN counter was used to measure the particle activation. SOA-particles were CCN active with critical diameters of e.g. 100 nm and 55 nm at super-saturations of 0.4% and 1.1%, respectively. But only slight hygroscopic growth with hygroscopic growth factors ≤1.05 was observed at RH<98% RH. At RH>98%, the hygroscopic growth increased stronger than would be expected if a constant hygroscopicity parameter for the particle/droplet solution was assumed. An increase of the hygroscopicity parameter by a factor of 4–6 was observed in the RH-range from below 90% to 99.6%, and this increase continued for increasingly diluted particle solutions for activating particles. This explains an observation already made in the past: that the relation between critical super-saturation and dry diameter for activation is steeper than what would be expected for a constant value of the hygroscopicity. Combining measurements of hygroscopic growth and activation, it was found that the surface tension that has to be assumed to interpret the measurements consistently is greater than 55 mN/m, possibly close to that of pure water, depending on the different SOA-types produced, and therefore only in part accounts for the discrepancy between hygroscopic growth and CCN activity observed for SOA particles in the past

Oxygen tension, H2S, and NO bioavailability:is there an interaction?

Molecular oxygen (O2) is an essential component for survival and development. Variation in O2 levels leads to changes in molecular signaling and ultimately affects the physiological functions of many organisms. Nitric oxide (NO) and hydrogen sulfide (H2S) are two gaseous cellular signaling molecules that play key roles in several physiological functions involved in maintaining vascular homeostasis including vasodilation, anti-inflammation, and vascular growth. Apart from the aforementioned functions, NO and H2S are believed to mediate hypoxic responses and serve as O2 chemosensors in biological systems. In this literature review, we briefly discuss NO and H2S and their roles during hypoxia

Reflection 2 shifting research paradigms: urbanism and culture.

The themes of this book are important and timely, and reflect the increasingly cross-discipline manner in which challenges faced in the built environment must be addressed. This has been reflected of course in the calls and projects supported by major research funders, but one can argue that this in turn simply reflects a recognition in society that urban problems are complex, and require a response which draws on a diversity of expertise. The relationships between people and the constructed environment are dealt with using a range of participants and contexts, and the book serves to demonstrate how the academic and professional communities can work together

Malonylation of GAPDH is an inflammatory signal in macrophages.

Macrophages undergo metabolic changes during activation that are coupled to functional responses. The gram negative bacterial product lipopolysaccharide (LPS) is especially potent at driving metabolic reprogramming, enhancing glycolysis and altering the Krebs cycle. Here we describe a role for the citrate-derived metabolite malonyl-CoA in the effect of LPS in macrophages. Malonylation of a wide variety of proteins occurs in response to LPS. We focused on one of these, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In resting macrophages, GAPDH binds to and suppresses translation of several inflammatory mRNAs, including that encoding TNFα. Upon LPS stimulation, GAPDH undergoes malonylation on lysine 213, leading to its dissociation from TNFα mRNA, promoting translation. We therefore identify for the first time malonylation as a signal, regulating GAPDH mRNA binding to promote inflammation

Direct detection and measurement of wall shear stress using a filamentous bio-nanoparticle

The wall shear stress (WSS) that a moving fluid exerts on a surface affects many processes including those relating to vascular function. WSS plays an important role in normal physiology (e.g. angiogenesis) and affects the microvasculature's primary function of molecular transport. Points of fluctuating WSS show abnormalities in a number of diseases; however, there is no established technique for measuring WSS directly in physiological systems. All current methods rely on estimates obtained from measured velocity gradients in bulk flow data. In this work, we report a nanosensor that can directly measure WSS in microfluidic chambers with sub-micron spatial resolution by using a specific type of virus, the bacteriophage M13, which has been fluorescently labeled and anchored to a surface. It is demonstrated that the nanosensor can be calibrated and adapted for biological tissue, revealing WSS in micro-domains of cells that cannot be calculated accurately from bulk flow measurements. This method lends itself to a platform applicable to many applications in biology and microfluidics

Capturing PM2.5 emissions from 3D printing via nanofiber-based air filter

This study investigated the feasibility of using polycaprolactone (PCL) nanofiber-based air filters to capture PM2.5 particles emitted from fused deposition modeling (FDM) 3D printing. Generation and aggregation of emitted particles were investigated under different testing environments. The results show that: (1) the PCL nanofiber membranes are capable of capturing particle emissions from 3D printing, (2) relative humidity plays a signification role in aggregation of the captured particles, (3) generation and aggregation of particles from 3D printing can be divided into four stages: the PM2.5 concentration and particles size increase slowly (first stage), small particles are continuously generated and their concentration increases rapidly (second stage), small particles aggregate into more large particles and the growth of concentration slows down (third stage), the PM2.5 concentration and particle aggregation sizes increase rapidly (fourth stage), and (4) the ultrafine particles denoted as 鈥渂uilding unit鈥 act as the fundamentals of the aggregated particles. This work has tremendous implications in providing measures for controlling the particle emissions from 3D printing, which would facilitate the extensive application of 3D printing. In addition, this study provides a potential application scenario for nanofiber-based air filters other than laboratory theoretical investigation

Track D Social Science, Human Rights and Political Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138414/1/jia218442.pd

Impacts of adaptation and responsibility framings on attitudes towards climate change mitigation

It is likely that climate change communications and media coverage will increasingly stress the importance of adaptation, yet little is known about whether or how this may affect attitudes towards mitigation. Despite concerns that communicating adaptation could undermine public support for mitigation, previous research has found it can have the opposite effect by increasing risk salience. It is also unclear whether people respond differently to information about mitigation and adaptation depending on whether action is framed as an individual or government responsibility. Using an experimental design, this study sought to examine how public attitudes towards mitigation are influenced by varying climate change messages, and how this might interact with prior attitudes to climate change. UK-based participants (N = 800) read one of four texts in a 2 × 2 design comparing adaptation versus mitigation information and personal versus governmental action. No main effect was found for adaptation versus mitigation framing, nor for individual action versus government policy, but we did observe a series of interaction effects with prior attitudes to climate change. Mitigation and adaptation information affected participants’ responses differently depending on their pre-existing levels of concern about climate change, suggesting that mitigation framings may be more engaging for those with high levels of concern, whereas adaptation framings may be more engaging for low-concern individuals. Government mitigation action appears to engender particularly polarised attitudes according to prior concern. Implications for climate change communications are considered