Binding of Aβ peptide creates lipid density depression in DMPC bilayer

AbstractUsing isobaric–isothermal replica exchange molecular dynamics and all-atom explicit water model we study the impact of Aβ monomer binding on the equilibrium properties of DMPC bilayer. We found that partial insertion of Aβ peptide into the bilayer reduces the density of lipids in the binding “footprint” and indents the bilayer thus creating a lipid density depression. Our simulations also reveal thinning of the bilayer and a decrease in the area per lipid in the proximity of Aβ. Although structural analysis of lipid hydrophobic core detects disordering in the orientations of lipid tails, it also shows surprisingly minor structural perturbations in the tail conformations. Finally, partial insertion of Aβ monomer does not enhance water permeation through the DMPC bilayer and even causes considerable dehydration of the lipid–water interface. Therefore, we conclude that Aβ monomer bound to the DMPC bilayer fails to perturb the bilayer structure in both leaflets. Limited scope of structural perturbations in the DMPC bilayer caused by Aβ monomer may constitute the molecular basis of its low cytotoxicity

Principal Consumer: President Biden\u27s Approach To Intelligence

United States President Joe Biden has been in government since 1973. Despite the changing nature of international relations since then, his approach to intelligence has remained consistent and stable, including his enthusiasm for national intelligence and uneasiness about militarizing it. This article assesses United States President Joe Biden\u27s approach to intelligence. It evaluates his evolving relationship with the Central Intelligence Agency and the rest of the intelligence community from the early 1970s, when he was elected to Congress, to the early 2020s, when he became the forty-sixth president of the United States. It concludes that, against the ever-changing context of international affairs, from the late Cold War to the global \u27war on terror\u27, Biden\u27s approach to intelligence has remained consistent and stable, showing, on the one hand, enthusiasm for the production of national intelligence, and, on the other, a marked uneasiness about paramilitary covert action and the militarization of intelligence. The discussion that follows speaks to a larger debate, dating to the 1940s and still ongoing, in the executive and legislative branches of government, concerning the purposes and proper use of intelligence. This will interest policy-makers, officials and lawmakers responsible for intelligence and oversight, researchers and practitioners in security and intelligence, and scholars of American foreign relations

Effects of Obesity and Fall Risk on Gait and Posture of Community-Dwelling Older Adults

Epidemiological studies link increased fall risk to obesity in older adults, but the mechanism through which obesity increases falls and fall risks is unknown. This study investigates if obesity (Body Mass Index: BMI\u3e30 kg/m2) influenced gait and standing postural characteristics of community dwelling older adults leading to increased risk of falls. One hundred healthy older adults (age 74.0±7.6 years, range of 56-90 years) living independently in a community participated in this study. Participants’ history of falls over the previous two years was recorded, with emphasis on frequency and characteristics of falls. Participants with at least two falls in the prior year were classified as fallers. Each individual was assessed for postural stability during quiet stance and gait stability during 10 meters walking. Fall risk parameters of postural sway (COP area, velocity, path-length) were measured utilizing a standard forceplate coupled with an accelerometer affixed at the sternum. Additionally, parameters of gait stability (walking velocity, double support time, and double support time variability) were assessed utilizing an accelerometer affixed at the participant’s sternum. Gait and postural stability analyses indicate that obese older adults who fell have significantly altered gait pattern (longer double support time and greater variability) exhibiting a loss of automaticity in walking and, postural instability as compared to their counterparts (i.e., higher sway area and path length, and higher sway velocity) further increasing the risk of a fall given a perturbation. Body weight/BMI is a risk factor for falls in older adults as measured by gait and postural stability parameters

Effects of Rucksack Military Accessory on Gait Dynamic Stability

Various factors are responsible for injuries that occur in the U.S. Army soldiers. In particular, rucksack load carriage equipment influences the stability of the lower extremities and possibly affects gait balance. The objective of this investigation was to assess the gait and local dynamic stability of the lower extremity of five subjects as they performed a simulated rucksack march on a treadmill. The Motek Gait Real-time Interactive Laboratory (GRAIL) was utilized to replicate the environment of the rucksack march. The first walking trial was without a rucksack and the second set was executed with the All-Purpose Lightweight Individual Carrying Equipment (ALICE), an older version of the rucksack, and the third set was executed with the newer rucksack version, Modular Lightweight Load Carrying Equipment (MOLLE). In this experiment, the Inertial Measurement Unit (IMU) system, Dynaport was used to measure the ambulatory data of the subject. This experiment required subjects to walk continuously for 200 seconds with a 20kg rucksack, which simulates the real rucksack march training. To determine the dynamic stability of different load carriage and normal walking condition, Local Dynamic Stability (LDS) was calculated to quantify its stability. The results presented that comparing Maximum Lyapunov Exponent (LyE) of normal walking was significantly lower compared to ALICE (P=0.000007) and MOLLE (P=0.00003), however, between ALICE and MOLLE rucksack walking showed no significant difference (P=0.441). The five subjects showed significantly improved dynamic stability when walking without a rucksack in comparison with wearing the equipment. In conclusion, we discovered wearing a rucksack result in a significant (P \u3c 0.0001) reduction in dynamic stability

Motor Subtypes of Parkinson\u27s Disease can be Identified by Frequency Component of Postural Stability

Parkinson\u27s disease (PD) can be divided into two subtypes based on clinical features€”namely tremor dominant (TD) and postural instability and gait difficulty (PIGD). This categorization is important at the early stage of PD, since identifying the subtypes can help to predict the clinical progression of the disease. Accordingly, correctly diagnosing subtypes is critical in initiating appropriate early interventions and tracking the progression of the disease. However, as the disease progresses, it becomes increasingly difficult to further distinguish those attributes that are relevant to the subtypes. In this study, we investigated whether a method using the standing center of pressure (COP) time series data can separate two subtypes of PD by looking at the frequency component of COP (i.e., COP position and speed). Thirty-six participants diagnosed with PD were evaluated, with their bare feet on the force platform, and were instructed to stand upright with their arms by their sides for 20 s (with their eyes open and closed), which is consistent with the traditional COP measures. Fast Fourier transform (FFT) and wavelet transform (WT) were performed to distinguish between the motor subtypes using the COP measures. The TD group exhibited larger amplitudes at the frequency range of 3-7 Hz when compared to the PIGD group. Both the FFT and WT methods were able to differentiate the subtypes. COP time series information can be used to differentiate between the two motor subtypes of PD, using the frequency component of postural stability

Potential for Using Smartphone Accelerometers in Non-laboratory Environments

In recent years, there has been rising interest in using accelerometers as an alternative instrument to measure the center of pressure. Accelerometers are inexpensive, small, sensitive, and can be readily used in non-laboratory environments. In addition to this, smartphones with built-in accelerometers add to their capability with real-time processing of data from sensors. Clinicians and researchers are currently in disagreement from whether these measurements provide the same physiological information about the participant’s balance. In this study, twelve participants were asked to wear smartphone on their right ASIS using a belt clip and stand still on the forceplate. The data was synchronized using a tap by the right foot and collected over a fifty second period for analysis. Various linear and non-linear measures were extracted from the time series of resultant principal component (PC) scores. The results show high correlation in the COP time series from the two instruments (R=0.86)

Do In-Vehicle Advance Signs Benefit Older and Younger Driver Intersection Performance?

An experimental study was conducted to determine if intersection behavior of those 18 to 24 and 65+ benefited from advanced in-vehicle signs presented in a head-up display (HUD) format. The University of Calgary Driving Simulator (UCDS) was used to determine whether intersection performance improved in the presence of several advanced signs or whether unwanted adaptive behaviors occurred (e.g., increasing speed to run the light instead of stopping). Invehicle signs facilitated an increase in stopping occurrences for both younger and older drivers at intersections with relatively short yellow onsets. In addition, eye movement analysis revealed significant age effects with regard to vertical and horizontal gaze variablity, with younger drivers showing increases in vertical gaze variability compared to the older drivers. Younger drivers also looked more often and had longer percentage of durations fixating on the HUD compared to the older drivers

A deep search for planets in the inner 15 au around Vega

We present the results of a deep high-contrast imaging search for planets around Vega. Vega is an ideal target for high-contrast imaging because it is bright, nearby, and young with a face-on two-belt debris disk which may be shaped by unseen planets. We obtained $J-$ and $H-$band data on Vega with the coronagraphic integral-field spectrograph Project 1640 (P1640) at Palomar Observatory. Two nights of data were obtained in 2016, in poor seeing conditions, and two additional nights in more favorable conditions in 2017. In total, we obtained 5.5 hours of integration time on Vega in moderate to good seeing conditions (<1.5"). We did not detect any low mass companions in this system. Our data present the most sensitive contrast limits around Vega at very small separations (2-15 au) thus far, allowing us to place new constraints on the companions which may be sculpting the Vega system. In addition to new constraints, as the deepest data obtained with P1640, these observations form the final legacy of the now decommissioned instrument.Comment: Accepted for publication in A

Sub-Antarctic and High Antarctic Notothenioid Fishes: Ecology and Adaptational Biology Revealed by the ICEFISH 2004 Cruise of RVIB Nathaniel B. Palmer

The goal of the ICEFISH 2004 cruise, which was conducted on board RVIB Nathaniel B. Palmer and traversed the transitional zones linking the South Atlantic to the Southern Ocean, was to compare the evolution, ecology, adaptational biology, community structure, and population dynamics of Antarctic notothenioid fishes relative to the cool/temperate notothenioids of the sub-Antarctic. To place this work in a comprehensive ecological context, cruise participants surveyed the benthos and geology of the biogeographic provinces and island shelves on either side of the Antarctic Polar Front (or Antarctic Convergence). Genome-enabled comparison of the responses of cold-living and temperate notothenioids to heat stress confirmed the sensitivity of the former to a warming Southern Ocean. Successful implementation of the international and interdisciplinary ICEFISH research cruise provides a model for future exploration of the sub-Antarctic sectors of the Indian and Pacific Oceans