Role of Intracellular Amyloid β as Pathway Modulator,Biomarker, and Therapy Target

The β- and γ-secretase-driven cleavage of the amyloid precursor protein (APP) gives rise to the amyloid β peptide, which is believed to be the main driver of neurodegeneration in Alzheimer’s disease (AD). As it is prominently detectable in extracellular plaques in post-mortem AD brain samples, research in recent decades focused on the pathological role of extracellular amyloid β aggregation, widely neglecting the potential meaning of very early generation of amyloid β inside the cell. In the last few years, the importance of intracellular amyloid β (iAβ) as a strong player in neurodegeneration has been indicated by a rising number of studies. In this review, iAβ is highlighted as a crucial APP cleavage fragment, able to manipulate intracellular pathways and foster neurodegeneration. We demonstrate its relevance as a pathological marker and shed light on initial studies aiming to modulate iAβ through pharmacological treatment, which has been shown to have beneficial effects on cognitive properties in animal models. Finally, we display the relevance of viral infections on iAβ generation and point out future directions urgently needed to manifest the potential relevance of iAβ in Alzheimer’s disease.     

Recalibrating the auditory system: A speed-accuracy analysis of intensity perception.

Recalibration in loudness perception refers to an adaptation-like change in relative responsiveness to auditory signals of different sound frequencies. Listening to relatively weak tones at one frequency and stronger tones at another makes the latter appear softer. The authors showed recalibration not only in magnitude estimates of loudness but also in simple response times (RTs) and choice RTs. RTs depend on sound intensity and may serve as surrogates for loudness. Most important, the speeded classification paradigm also provided measures of errors. RTs and errors can serve jointly to distinguish changes in sensitivity from changes in response criterion. The changes in choice RT under different recalibrating conditions were not accompanied by changes in error rates predicted by the speed-accuracy trade-off. These results lend support to the hypothesis that loudness recalibration does not result from shifting decisional criteria but instead reflects a change in the underlying representation of auditory intensity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differences between asthma exacerbations and poor asthma control

BACKGROUND: Increased variation in peak expiratory flow (PEF) is characteristic of poorly controlled asthma, and measurement of diurnal variability of PEF has been recommended for assessment of asthma severity, including during exacerbations. We aimed to test whether asthma exacerbations had the same PEF characteristics as poor asthma control. METHODS: Electronic PEF records from 43 patients with initially poorly controlled asthma were examined for all exacerbations that occurred after PEF reached a plateau with inhaled corticosteroid treatment. Diurnal variability of PEF was compared during exacerbations, run-in (poor asthma control), and the period of stable asthma before each exacerbation. FINDINGS: Diurnal variability was 21.3% during poor asthma control and improved to 5.3% (stable asthma) with inhaled corticosteroid treatment. 40 exacerbations occurred in 26 patients over 2-16 months; 38 (95%) of exacerbations were associated with symptoms of clinical respiratory infection. During exacerbations, consecutive PEF values fell linearly over several days then improved linearly. However, diurnal variability during exacerbations (7.7%) was not significantly higher than during stable asthma (5.4%, p=0.1). PEF data were consistent with impaired response to inhaled beta2-agonist during exacerbations but not during poorly controlled asthma. INTERPRETATION: Asthmatics remain vulnerable to exacerbations during clinical respiratory infections, even after asthma is brought under control. Calculation of diurnal variability may fail to detect important changes in lung function. PEF variation is strikingly different during exacerbations compared with poor asthma control, suggesting differences in beta2-adrenoceptor function between these conditions.     

Women's self-disclosure of HIV infection: Rates, reasons, and reactions.

A survey of 65 ethnically diverse women at 2 outpatient HIV clinics revealed relatively low rates of disclosure of HIV-positive serostatus to extended family members, somewhat higher rates for immediate family members, and highest rates for lovers and friends. Spanish-speaking Latinas were less likely to disclose their serostatus or to discuss HIV-related worries with others than English speaking Latinas, African Americans, and Anglo Americans. Reasons for disclosure and nondisclosure varied by target. In general, targets reacted positively to disclosure. Implications for clinicians treating women with HIV infection are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prevalence of high-risk sex among HIV-positive gay and bisexual men: a longitudinal analysis

INTRODUCTION: This longitudinal study examined the prevalence and demographic correlates of unprotected insertive and receptive anal intercourse among HIV-positive gay and bisexual men who were aware of their serostatus. METHODS: Participants (n = 395), sampled randomly at two HIV outpatient clinics in Los Angeles, completed two waves of self-administered questionnaires (separated by approximately 7-9 months) that measured sexual behaviors in the previous 60 days. RESULTS: The cross-sectional prevalence of unprotected insertive anal intercourse was 11.2% at time 1 and 7.1% at time 2. Longitudinal analysis indicated that nearly 15% of the participants had engaged in that high-risk behavior either at time 1 or time 2 and approximately 4% had engaged in the behavior at each time period. Similar rates of unprotected receptive anal intercourse were observed. These high-risk activities were more prevalent with seropositive and unknown serostatus partners than with seronegative partners. The rate of anal intercourse risk behaviors was higher among asymptomatic men and among those who were exclusively gay. CONCLUSION: The findings demonstrate considerable differences in the prevalence of stable and occasional high-risk sexual behaviors among HIV-positive gay and bisexual men. Simple cross-sectional analyses cannot capture the stability or variation in behavior across time and, thus, may generate misleading conclusions about disease transmission, especially if the partner's HIV serostatus is not considered in the analysis. The findings indicate a need for focused safer-sex interventions for seropositive men. The HIV outpatient clinic is an ideal setting for such interventions.     

High Performing Solid-State Organic Electrochemical Transistors Enabled by Glycolated Polythiophene and Ion-Gel Electrolyte with a Wide Operation Temperature Range from −50 to 110 °C

The development of organic electrochemical transistors (OECTs) capable of maintaining their high amplification, fast transient speed, and operational stability in harsh environments will advance the growth of next-generation wearable and biological electronics. In this study, a high-performance solid-state OECT (SSOECT) is successfully demonstrated, showing a recorded high transconductance of 220 ± 59 S cm⁻¹, ultrafast device speed of ≈10 kHz with excellent operational stability over 10 000 switching cycles, and thermally stable under a wide temperature range from −50 to 110 °C. The developed SSOECTs are successfully used to detect low-amplitude physiological signals, showing a high signal-to-noise-ratio of 32.5 ± 2.1 dB. For the first time, the amplifying power of these SSOECTs is also retained and reliably shown to collect high-quality electrophysiological signals even under harsh temperatures (−50 and 110 °C). The demonstration of high-performing SSOECTs and its application in harsh environment are core steps toward their implementation in next-generation wearable electronics and bioelectronics.     

Impact of extraction conditions and seed variety on the characteristics of pennycress (Thlaspi arvense) protein: a structure and function approach

As the consumer demand for plant proteins continues to grow, the food industry is seeking novel and sustainable protein sources to incorporate in various food products. Pennycress (Thlaspi arvense), a sustainable cover crop, produces oilseeds high in protein, warranting investigation. Accordingly, protein extraction from pennycress was evaluated under various extraction conditions, using alkaline extraction and salt solubilization coupled with ultrafiltration. Given the superior color and functionality of the salt extracted pennycress protein isolate (PcPI), its production was scaled-up about two hundred folds in a pilot plant. Furthermore, a new pennycress accession bred to have zero erucic acid (0EA) was evaluated to determine the impact of seed variety on protein characteristics. Structural and functional characterization was performed on PcPI and compared to native (nSPI) and commercial (cSPI) soy protein isolates. Salt extracted PcPI had comparable gel strength to cSPI, three times higher solubility under acidic conditions, and ~1.5 times better emulsification capacity. PcPI extracted from 0EA was mildly different in structure and functionality from that extracted from wildtype pennycress, with the slight variation attributed to genetic variance. Finally, the protein digestibility-corrected amino acid score (PDCAAS) of the salt extracted PcPI, calculated in vivo (0.72) and in vitro (0.87), was superior or comparable to other plant protein sources. This research provided, for the first time, a comprehensive evaluation of different protein extraction protocols to produce a functional PcPI that can compete with soy protein for various food applications, such as acidic beverages, meat and dairy products, and emulsified systems.     

Integrated software,process, algorithm and application visualization

We present a unifying view of visualization in which comprehensive support for software, algorithm, process and application (including scientific) visualizations is treated as an essential component of the computing environment. We describe our recent work toward making this view a reality: a tool for computer-assisted design of visualizations and a technique for monitoring a computational process in a non-invasive fashion.     

Volumetric Electron Transfer from Metabolites to Chemically Doped Polymer Electrodes

The development of sensor electrode materials for the detection of metabolites will enable point-of-care diagnostic devices for the monitoring and treatment of metabolic diseases such as diabetes. Current state-of-the-art glucose sensing electrodes employ the organic salt tetrathiafulvene tetracyanoquinodimethane (TTF TCNQ) to receive electrons directly from enzymatic reactions of glucose. However, TTF TCNQ is insoluble in most solvents, making it challenging to deposit high-quality electrodes. Furthermore, its hydrophobicity hinders its interface with aqueous solutions in physiological environments. To overcome these issues, TCNQ derivatives are introduced into an electron-rich and hydrophilic conjugated polymer. Thus, a polymeric electrode is demonstrated that is easily solution processible and can undergo volumetric direct electron transfer with glucose reactions throughout its bulk. This study further elucidates the electron transfer mechanism during chemical doping and metabolite sensing reactions to inform general design rules for this new class of glucose sensing materials.