The Hidden Role of Non-Canonical Amyloid beta Isoforms in Alzheimer's Disease

Recent advances have placed the pro-inflammatory activity of amyloid β (Aβ) on microglia cells as the focus of research on Alzheimer’s Disease (AD). Researchers are confronted with an astonishing spectrum of over 100 different Aβ variants with variable length and chemical modifications. With the exception of Aβ1-42 and Aβ1-40, the biological significance of most peptides for AD is as yet insufficiently understood. We therefore aim to provide a comprehensive overview of the contributions of these neglected Aβ variants to microglia activation. First, the impact of Aβ receptors, signaling cascades, scavenger mechanisms, and genetic variations on the physiological responses towards various Aβ species is described. Furthermore, we discuss the importance of different types of amyloid precursor protein processing for the generation of these Aβ variants in microglia, astrocytes, oligodendrocytes, and neurons, and highlight how alterations in secondary structures and oligomerization affect Aβ neurotoxicity. In sum, the data indicate that gene polymorphisms in Aβ-driven signaling pathways in combination with the production and activity of different Aβ variants might be crucial factors for the initiation and progression of different forms of AD. A deeper assessment of their interplay with glial cells may pave the way towards novel therapeutic strategies for individualized medicine

Responses to and Repercussions From Income Volatility in Low- and Moderate-Income Households: Results From a National Survey

This is the second in a series of briefs that the Center for Social Development has produced in partnership with the Aspen Institute’s Expanding Prosperity Impact Collaborative (EPIC) and the Intuit Tax and Financial Center. Thefirst brief highlighted new data on the prevalence of income and expense volatility in low- and moderate-income households. This second brief examines income volatility’s effects on Americans’ financial lives, showing that it is associated with dramatic increases in the likelihood of experiencing several hardships. The findings have broad implications for future research and policy

The Experience of Volatility in Low- and Moderate-Income Households: Results From a National Survey

This is the first in a series of briefs that the Center for Social Development has produced in partnership with the Aspen Institute’s Expanding Prosperity Impact Collaborative (EPIC) and the Intuit Tax and Financial Center. It highlights new data on the prevalence of income and expense volatility in low- and moderate-income households

A complex relationship among chemical concentration, detection threshold and suprathreshold intensity of bitter compounds

Detection thresholds and psychophysical curves were established for caffeine, quinine-HCl (QHCl), and propylthiouracil (PROP) in a sample of 33 subjects (28 female mean age 24 &plusmn; 4). The mean detection threshold (&plusmn;standard error) for caffeine, QHCl, and PROP was 1.2 &plusmn; 0.12, 0.0083 &plusmn; 0.001, and 0.088 &plusmn; 0.07 mM, respectively. Pearson product&ndash;moment analysis revealed no significant correlations between detection thresholds of the compounds. Psychophysical curves were constructed for each bitter compound over 6 concentrations. There were significant correlations between incremental points of the individual psychophysical curves for QHCl and PROP. Regarding caffeine, there was a specific concentration (6 mM) below and above which the incremental steps in bitterness were correlated. Between compounds, analysis of psychophysical curves revealed no correlations with PROP, but there were significant correlations between the bitterness of caffeine and QHCl at higher concentrations on the psychophysical curve (P &lt; 0.05). Correlation analysis of detection threshold and suprathreshold intensity within a compound revealed a significant correlation between PROP threshold and suprathreshold intensity (r = 0.46&ndash;0.4, P &lt; 0.05), a significant negative correlation for QHCl (r = &ndash;0.33 to &ndash;0.4, P &lt; 0.05), and no correlation for caffeine. The results suggest a complex relationship between chemical concentration, detection threshold, and suprathreshold intensity.<br /

On the Occurrence of Finite-Time-Singularities in Epidemic Models of Rupture, Earthquakes and Starquakes

We present a new kind of critical stochastic finite-time-singularity, relying on the interplay between long-memory and extreme fluctuations. We illustrate it on the well-established epidemic-type aftershock (ETAS) model for aftershocks, based solely on the most solidly documented stylized facts of seismicity (clustering in space and in time and power law Gutenberg-Richter distribution of earthquake energies). This theory accounts for the main observations (power law acceleration and discrete scale invariant structure) of critical rupture of heterogeneous materials, of the largest sequence of starquakes ever attributed to a neutron star as well as of earthquake sequences.Comment: Revtex document of 4 pages including 1 eps figur

Rupture by damage accumulation in rocks

The deformation of rocks is associated with microcracks nucleation and propagation, i.e. damage. The accumulation of damage and its spatial localization lead to the creation of a macroscale discontinuity, so-called "fault" in geological terms, and to the failure of the material, i.e. a dramatic decrease of the mechanical properties as strength and modulus. The damage process can be studied both statically by direct observation of thin sections and dynamically by recording acoustic waves emitted by crack propagation (acoustic emission). Here we first review such observations concerning geological objects over scales ranging from the laboratory sample scale (dm) to seismically active faults (km), including cliffs and rock masses (Dm, hm). These observations reveal complex patterns in both space (fractal properties of damage structures as roughness and gouge), time (clustering, particular trends when the failure approaches) and energy domains (power-law distributions of energy release bursts). We use a numerical model based on progressive damage within an elastic interaction framework which allows us to simulate these observations. This study shows that the failure in rocks can be the result of damage accumulation

Liposomes: a new non-pharmacological therapy concept for seasonal-allergic-rhinoconjunctivitis

Mucosal barrier disorders play an important role in the pathomechanism of the allergic disease. A new approach for their treatment uses liposomes, which consist of phospholipids that make up 75% of the protective nasal surfactant layer. Our aim was to investigate the efficacy of liposomal-based therapy, as a comprehensive treatment alternative to guideline cromoglycate-based therapy, in the treatment of seasonal allergic rhinoconjunctivitis (SAR). We compared nasal and conjunctival symptom reduction with LipoNasal n nasal spray used as monotherapy (LNM), or LipoNasal n nasal spray and Tears Again eye spray combination therapy (LTC), against standard cromoglycate combination therapy (CGC). This prospective, controlled, open observational study was conducted monocentrically. According to their symptoms and preferences 72 patients with SAR were distributed in three equal groups. The study comprised two visits at an interval of 7 days. The efficacy was examined by daily documenting nasal and conjunctival symptom scores. The Nasal-Spray-Sensory-Scale and the Eye-Drops/Spray-Sensory-Scale were used to investigate the tolerability. Quality of life (QoL) was evaluated, using the RHINASTHMA QoL German adapted version. LNM achieved significant improvement in nasal (p < 0.001) and conjunctival symptoms (p = 0.050). The symptom reduction using CGC was equally significant. LTC led to significant nasal symptom relief (p = 0.045). QoL did not improve significantly in all groups (p > 0.05). The tolerability of all treatments was good and no adverse reactions were observed. In all treatment groups the improvement of the nasal and conjunctival symptom scores exceeds the minimal clinically important difference (MCID). The results demonstrate good tolerability and efficacy of non-pharmaceutical liposomal-based treatment (LipoNasal n and Tears Again), given as monotherapy or combination therapy, for nasal and conjunctival symptoms caused by SAR. This study indicates that liposomal-based treatment for SAR may be a comparable alternative to cromoglycate therapy. Further studies are needed to verify these findings