Interaction between Alzheimer's Aβ(25–35) peptide and phospholipid bilayers: The role of cholesterol

AbstractThere is mounting evidence that the lipid matrix of neuronal cell membranes plays an important role in the accumulation of β-amyloid peptides into senile plaques, one of the hallmarks of Alzheimer's disease (AD). With the aim to clarify the molecular basis of the interaction between amyloid peptides and cellular membranes, we investigated the interaction between a cytotoxic fragment of Aβ(1–42), i.e., Aβ(25–35), and phospholipid bilayer membranes. These systems were studied by Electron Paramagnetic Resonance (EPR) spectroscopy, using phospholipids spin-labeled on the acyl chain. The effect of inclusion of charged phospholipids or/and cholesterol in the bilayer composition was considered in relation to the peptide/membrane interaction. The results show that Aβ(25–35) inserts in bilayers formed by the zwitterionic phospholipid dilauroyl phosphatidylcholine (DLPC), positioning between the outer part of the hydrophobic core and the external hydrophilic layer. This process is not significantly influenced by the inclusion of the anionic phospholipid phosphatidylglycerol (DLPG) in the bilayer, indicating the peptide insertion to be driven by hydrophobic rather than electrostatic interactions. Cholesterol plays a fundamental role in regulating the peptide/membrane association, inducing a membrane transition from a fluid-disordered to a fluid-ordered phase. At low cholesterol content, in the fluid-disordered phase, the insertion of the peptide in the membrane causes a displacement of cholesterol towards the more external part of the membrane. The crowding of cholesterol enhances its rigidifying effect on this region of the bilayer. Finally, the cholesterol-rich fluid-ordered membrane looses the ability to include Aβ(25–35)

Trend of hospital utilization for encephalitis.

SUMMARYEncephalitis generally results in a serious illness requiring hospitalization. The aim of this study was to describe the epidemiology of hospitalization for encephalitis in Italy, taking into account the geographical distribution, aetiology, seasonality and evolution of hospitalization rates over recent years. The mean hospitalization rate was 5·88/100 000. For most of these hospitalizations (n=13 119, 55·6%), no specific cause of encephalitis was reported. The most common aetiological category was 'viral', which accounted for 40·1% (n=4205) of such hospitalizations (rate 1·05/100 000). Within this category, herpes virus was the leading causative agent (n=1579, 0·39/100 000). This report highlights a significant increase of 'viral encephalitis not otherwise specified' (ICD-9 code 049·9)vs. a reduction of all other causes. A seasonal pattern was noted in people aged ⩾65 years in this group. Specific surveillance of encephalitis without known origin should be reinforced in order to identify the potential role of emerging pathogens and to design preventive interventions

Perioperative antibiotic prophylaxis: improved compliance and impact on infection rates.

SUMMARYThe aims of this study were to determine adherence to the perioperative antibiotic prophylaxis (PAP) protocol used at a large Italian teaching hospital during a 6-year period, to assess the variables associated with inappropriate administration, and to measure the impact on surgical site infection (SSI) rates. There were 28 621 patients surveyed of which 74·6% received PAP. An improvement in adherence to the PAP protocol was registered for 58·8% of patients. Significant risk factors were an American Society of Anesthesiologists (ASA) score ⩾2 [odds ratios (OR) from 1·28 (95% confidence interval (CI) 1·19–1·37) to 1·87 (95% CI 1·43–2·44)], prolonged duration of surgery (OR 1·68, 95% CI 1·56–1·82) and urgent surgery (OR 2·16, 95% CI 1·96–2·37). During the study period, a significant reduction in SSIs rates was detected. We concluded that the global reduction of inadequate PAP administration signifies the efficacy of a multidisciplinary quality improvement initiative on antimicrobial utilization, and this is supported by the observed reduction of the SSI rate

Millimeter-wave backscattering measurements with transmitarrays for personal radar applications

The concept of personal radar has recently emerged as an interesting solution for next 5G applications. In fact the high portability of massive antenna arrays at millimeter-waves enables the integration of a radar system in pocket-size devices (i.e. tablets or smartphones) and enhances the possibility to map the surrounding environment by guaranteeing accurate localization together with high-speed communication capabilities. In this paper we investigate for the first time the capability of such personal radar solution using real measured data collected at millimeter-waves as input for the mapping algorithm

Application of transmitarray antennas for indoor mapping at millimeter-waves

Millimeter-waves are expected to play a key role in next 5G scenario due to the availability of a large clean unlicensed bandwidth at 60 GHz and the possibility to realize packed antenna arrays, with a consequent increase of the communication capacity and the introduction of new functionalities, such as high-definition localization and personal radar for automatic environment mapping. In this paper we propose the adoption of millimeter-wave transmitarrays for personal radar applications and we investigate the impact of the radiation pattern characteristics on the map reconstruction accuracy, by analysing how the number of array elements, of quantization bits and the focal distance affect the environment reconstruction performance

A thermodynamic signature of lipid segregation in biomembranes induced by a short peptide derived from glycoprotein gp36 of feline immunodeficiency virus.

The interactions between proteins/peptides and lipid bilayers are fundamental in a variety of key biological processes, and among these, the membrane fusion process operated by viral glycoproteins is one of the most important, being a fundamental step of the infectious event. In the case of the feline immunodeficiency virus (FIV), a small region of the membrane proximal external region (MPER) of the glycoprotein gp36 has been demonstrated to be necessary for the infection to occur, being able to destabilize the membranes to be fused. In this study, we report a physicochemical characterization of the interaction process between an eight-residue peptide, named C8, modeled on that gp36 region and some biological membrane models (liposomes) by using calorimetric and spectroscopic measurements. CD studies have shown that the peptide conformation changes upon binding to the liposomes. Interestingly, the peptide folds from a disordered structure (in the absence of liposomes) to a more ordered structure with a low but significant helix content. Isothermal titration calorimetry (ITC) and differential scanning calorimetry (DSC) results show that C8 binds with high affinity the lipid bilayers and induces a significant perturbation/reorganization of the lipid membrane structure. The type and the extent of such membrane reorganization depend on the membrane composition. These findings provide interesting insights into the role of this short peptide fragment in the mechanism of virus-cell fusion, demonstrating its ability to induce lipid segregation in biomembranes

Brief Training of Psychoneuroendocrinoimmunology-Based Meditation (PNEIMED) Reduces Stress Symptom Ratings and Improves Control on Salivary Cortisol Secretion Under Basal and Stimulated Conditions

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