Intracellular soluble α-synuclein oligomers reduce pyramidal cell excitability

The presynaptic protein α-synuclein (αSyn) aggregates during Parkinson's disease (PD) to form large proteinaceous amyloid plaques, the spread of which throughout the brain clinically defines the severity of the disease. During early stages of aggregation, αSyn forms soluble annular oligomers that show greater toxicity than much larger fibrils. These oligomers produce toxicity via a number of possible mechanisms, including the production of pore-forming complexes that permeabilize membranes. In the present study, two well-defined species of soluble αSyn oligomers were produced by different protocols: by polymerization of monomer and by sonication of fibrils. The two oligomeric species produced were morphologically similar, with both having an annular structure and consisting of approximately the same number of monomer subunits, although they differed in their secondary structure. Oligomeric and monomeric αSyn were injected directly into the soma of pyramidal neurons in mouse neocortical brain slices during whole-cell patch clamp recording. Using a combined experimental and modelling approach, neuronal parameters were extracted to measure, for the first time in the neocortex, specific changes in neuronal electrophysiology. Both species of oligomer had similar effects: (i) a significant reduction in input resistance and the membrane time constant and (ii) an increase in the current required to trigger an action potential with a resultant reduction in the firing rate. Differences in oligomer secondary structure appeared to produce only subtle differences in the activity of the oligomers. Monomeric αSyn had no effect on neuronal parameters, even at high concentrations. The oligomer-induced fall in neuronal excitability has the potential to impact both network activity and cognitive processing

Evaluating Active U: an Internet-mediated physical activity program.

Background: Engaging in regular physical activity can be challenging, particularly during the winter months. To promote physical activity at the University of Michigan during the winter months, an eight-week Internet-mediated program (Active U) was developed providing participants with an online physical activity log, goal setting, motivational emails, and optional team participation and competition. Methods: This study is a program evaluation of Active U. Approximately 47,000 faculty, staff, and graduate students were invited to participate in the online Active U intervention in the winter of 2007. Participants were assigned a physical activity goal and were asked to record each physical activity episode into the activity log for eight weeks. Statistics for program reach, effectiveness, adoption, and implementation were calculated using the Re-Aim framework. Multilevel regression analyses were used to assess the decline in rates of data entry and goal attainment during the program, to assess the likelihood of joining a team by demographic characteristics, to test the association between various predictors and the number of weeks an individual met his or her goal, and to analyze server load. Results: Overall, 7,483 individuals registered with the Active U website (≈16% of eligible), and 79% participated in the program by logging valid data at least once. Staff members, older participants, and those with a BMI < 25 were more likely to meet their weekly physical activity goals, and average rate of meeting goals was higher among participants who joined a competitive team compared to those who participated individually (IRR = 1.28, P < .001). Conclusion: Internet-mediated physical activity interventions that focus on physical activity logging and goal setting while incorporating team competition may help a significant percentage of the target population maintain their physical activity during the winter months

Impact Of Redesigning A Large-Lecture Introductory Earth Science Course To Increase Student Achievement And Streamline Faculty Workload

A Geological Perspective is a general education survey course for non-science majors at a large southwestern research extensive university.  The class has traditionally served 600 students per semester in four 150-student lectures taught by faculty, and accompanied by optional weekly study groups run by graduate teaching assistants.  We radically redesigned the course to 1) improve student learning and, simultaneously, 2) reduce faculty effort.   Previously optional study groups were replaced by weekly mandatory break-out sessions, run largely by undergraduate peer mentors.  Twice weekly, lectures are brief with a large portion of class time allocated to active learning in small groups.  Completing quizzes on-line reduced grading and allowed students more flexibility.  Evaluation of the redesign (mixed methods, quasi-experimental, two-group, pre-test-post-test, multiple-measures study design) revealed no significant improvements in learner outcomes insofar as the instruments could measure. However, qualitative results reveal that overall students greatly valued their learning experience under the redesign.  In addition, the redesign reduced the departmental cost of the class offering per student by more than half.

Salmonella typhimurium's transthyretin-like protein is a host-specific factor important in fecal survival in chickens.

The transthyretin-like protein (TLP) from Salmonella enterica subspecies I is a periplasmic protein with high level structural similarity to a protein found in mammals and fish. In humans, the protein homologue, transthyretin, binds and carries retinol and thyroxine, and a series of other, unrelated aromatic compounds. Here we show that the amino acid sequence of the TLP from different species, subspecies and serovars of the Salmonella genus is highly conserved and demonstrate that the TLP gene is constitutively expressed in S. Typhimurium and that copper and other divalent metal ions severely inhibit enzyme activity of the TLP, a cyclic amidohydrolase that hydrolyses 5-hydroxyisourate (5-HIU). In order to determine the in vivo role of the S. Typhimurium TLP, we constructed a strain of mouse-virulent S. Typhimurium SL1344 bearing a mutation in the TLP gene (SL1344 ΔyedX). We assessed the virulence of this strain via oral inoculation of mice and chickens. Whilst SL1344 ΔyedX induced a systemic infection in both organisms, the bacterial load detected in the faeces of infected chickens was significantly reduced when compared to the load of S. Typhimurium SL1344. These data demonstrate that the TLP gene is required for survival of S. Typhimurium in a high uric acid environment such as chicken faeces, and that metabolic traits of Salmonellae in natural and contrived hosts may be fundamentally different. Our data also highlight the importance of using appropriate animal models for the study of bacterial pathogenesis especially where host-specific virulence factors or traits are the subject of the study

Ocean warming affects the distribution and abundance of resident fishes by changing their reproductive scope

With ocean warming predicted globally, one of the mechanisms driving distributional shifts and changes in the abundance of resident fishes is reproductive output. The relationship between sea surface temperature and the reproductive activity of a eurythermic, resident coastal species, blacktail seabream Diplodus sargus capensis, was examined in the ‘‘ocean warming’’ hotspot of the northern Benguela. Reproductive activity was found to be restricted to periods when the water temperature dropped below 20 _C. A metadata analysis conducted on the D. sargus sub-species complex similarly showed that reproductive activity was restricted to temperatures between 15 and 20 _C, regardless of the range in ambient water temperature. Based on these findings and using satellite derived SST information, we examined D. s. capensis’s total and seasonal ‘‘reproductive scope’’ that is defined as either the area suitable for spawning each year or the duration of its potential spawning season at a fixed geographical locality, respectively. Trends were examined over the last three decades. Reproductive scope by area was found to be shrinking at a rate of 7 % per decade in southern Angola and expanding at a rate of 6 % per decade in northern Namibia. Reproductive scope by season decreased by 1.05 months per decade in Namibe, southern Angola and increased by 0.76 months per decade in Hentiesbaai, northern Namibia. Changes in reproductive scope may be a driving mechanism of distributional shifts in resident fishes, although the rate of the shifts is likely to be slow. More importantly, changes in reproductive scope will not be uniform throughout fish distributions and will most likely result in heterogeneous variations in fish abundance

Introduction of a pyramid guiding process for general musculoskeletal physical rehabilitation

Successful instruction of a complicated subject as Physical Rehabilitation demands organization. To understand principles and processes of such a field demands a hierarchy of steps to achieve the intended outcome. This paper is intended to be an introduction to a proposed pyramid scheme of general physical rehabilitation principles. The purpose of the pyramid scheme is to allow for a greater understanding for the student and patient. As the respected Food Guide Pyramid accomplishes, the student will further appreciate and apply supported physical rehabilitation principles and the patient will understand that there is a progressive method to their functional healing process

Complications, revision fusions, readmissions, and utilization over a 1-year period after bone morphogenetic protein use during primary cervical spine fusions

Nationwide estimates examining Bone Morphogenetic Protein (BMP) use with cervical spine fusions have been limited to perioperative outcomes

Proposal for Austere Light Attack Aircraft – Project Aardvark

The WickedAir senior design team at the University of Alabama in Huntsville is developing the preliminary design of an aircraft for the AIAA Undergraduate Team Aircraft Design Competition. The RFP calls for an affordable light attack aircraft capable of executing missions currently only feasible with attack helicopters. The aircraft must be able to operate from short austere fields and accommodate a crew of two. Additional design goals include enhanced survivability and the ability for deploying a variety of weapons including an integrated gun for ground targets. The aircraft must accomplish an attack mission with a full weapons load and a long-range ferry mission with a 60% weapons load. Through evaluation of existing attack aircraft and helicopters and initial trade studies, the team has produced a conceptual design for the ZA-13 “Aardvark”. The 12,000 lbf Aardvark has twin turboprop engines mounted on a 6.9 aspect ratio swept wing. Two sponsons offer weapons attachment points similar to those of a helicopter. This design offers low speed performance, a high payload capacity, and a short takeoff length. Specific consideration was given to the effects of foreign object debris and particulate matter pollution with regards to the lifespan and vulnerability of the aircraft in various austere environments. This paper summarizes the detailed design, cost analysis, and mission capabilities behind the current aircraft

Neutral Solar Wind Generated by Lunar Exospheric Dust at the Terminator

We calculate the flux of neutral solar wind observed on the lunar surface at the terminator due to solar wind protons penetrating exospheric dust grains with (1) radii greater than 0.1 microns and (2) radii greater than 0.01 microns. For grains with radii larger than 0.1 microns, the ratio of the neutral solar wind flux produced by exospheric dust to the incident ionized solar wind flux is estimated to be about 10^-4-10^-3 for solar wind speeds in excess of 800 km/s, but much lower (less than 10^-5) at average to slow solar wind speeds. However, when the smaller grain sizes are considered, this ratio is estimated to be greater than 10^-5 at all speeds, and at speeds in excess of 700 km/s reaches about 10^-3. These neutral solar wind fluxes are easily measurable with current low energy neutral atom instrumentation. Observations of neutral solar wind from the surface of the Moon would provide independent information on the distribution of very small dust grains in the lunar exosphere that would complement and constrain optical measurements at ultraviolet and visible wavelengths.Comment: in press in J. Geophys. Re

Supporting the Implementation of Connected Care Technologies in the Veterans Health Administration: Cross-Sectional Survey Findings from the Veterans Engagement with Technology Collaborative (VET-C) Cohort

BACKGROUND: Widespread adoption, use, and integration of patient-facing technologies into the workflow of health care systems has been slow, thus limiting the realization of their potential. A growing body of work has focused on how best to promote adoption and use of these technologies and measure their impacts on processes of care and outcomes. This body of work currently suffers from limitations (eg, cross-sectional analyses, limited patient-generated data linked with clinical records) and would benefit from institutional infrastructure to enhance available data and integrate the voice of the patient into implementation and evaluation efforts. OBJECTIVE: The Veterans Health Administration (VHA) has launched an initiative called the Veterans Engagement with Technology Collaborative cohort to directly address these challenges. This paper reports the process by which the cohort was developed and describes the baseline data being collected from cohort members. The overarching goal of the Veterans Engagement with Technology Collaborative cohort is to directly engage veterans in the evaluation of new VHA patient-facing technologies and in so doing, to create new infrastructure to support related quality improvement and evaluation activities. METHODS: Inclusion criteria for veterans to be eligible for membership in the cohort included being an active user of VHA health care services, having a mobile phone, and being an established user of existing VHA patient-facing technologies as represented by use of the secure messaging feature of VHA\u27s patient portal. Between 2017 and 2018, we recruited veterans who met these criteria and administered a survey to them over the telephone. RESULTS: The majority of participants (N=2727) were male (2268/2727, 83.2%), White (2226/2727, 81.6%), living in their own apartment or house (2519/2696, 93.4%), and had completed some college (1176/2701, 43.5%) or an advanced degree (1178/2701, 43.6%). Cohort members were 59.9 years old, on average. The majority self-reported their health status as being good (1055/2725, 38.7%) or very good (524/2725, 19.2%). Most cohort members owned a personal computer (2609/2725, 95.7%), tablet computer (1616/2716, 59.5%), and/or smartphone (2438/2722, 89.6%). CONCLUSIONS: The Veterans Engagement with Technology Collaborative cohort is an example of a VHA learning health care system initiative designed to support the data-driven implementation of patient-facing technologies into practice and measurement of their impacts. With this initiative, VHA is building capacity for future, rapid, rigorous evaluation and quality improvement efforts to enhance understanding of the adoption, use, and impact of patient-facing technologies