Cloning, Sequencing, Expression and Characterization of an Alzheimer’s-Specific Monoclonal Antibody

Alzheimer’s disease (AD) is characterized by chronic inflammation and neurodegeneration, which leads to loss of cognitive functions. Dr. Nichols’ research laboratory is studying the neurological effects associated with AD. Amyloid precursor protein (APP) is a membrane spanning protein whose primary function is unknown, but it is associated with many tissue types and found clustered at the synapse of neurons. APP can be cleaved by secretases into 40 or 42 amino acid fragments called amyloid beta protein (Aβ). These cleaved amyloid-β proteins can accumulate (aggregate) and form extracellular plaques in AD brains. Antibodies are normally produced in an adaptive immune response and are a high affinity binding protein that recognizes a specific molecule, whether it be a protein or foreign cellular component. Antibodies are commonly used in the lab to quantify the levels of aggregated proteins, such as Aβ and are often used in immunotherapy clinical trials to target plaques in AD patient’s brains. The aggregates of Aβ assemble into multiple different confirmations, some of which are soluble and others insoluble, but the most toxic and active form is the soluble protofibril form. Antibodies that have been made to be selective for the protofibril form of Aβ are required constantly to study the effect of Aβ. A combination of biological and biochemical techniques has been used to obtain the DNA sequence of a monoclonal antibody (mAbSL). The antibody mAbSL was purified with an affinity column and has been shown to be selective and specific for Aβ protofibrils by a series of immunological techniques, such as enzyme-linked immunosorbent assays (ELISA) and dot blots. With the sequence and means of expression we can create a stock of the antibodies and they will be applied in multiple aspects of this laboratory to help characterize Aβ protofibrils and their effects

Interactions of short-term and chronic treadmill training with aging of the left ventricle of the heart

With aging, there is a decline in cardiac function accompanying increasing risk of arrhythmias. These effects are likely to be mechanistically associated with age-associated changes in calcium regulation within cardiac myocytes. Previous studies suggest that lifelong exercise can potentially reduce age-associated changes in the heart. Although exercise itself is associated with changes in cardiac function, little is known about the interactions of aging and exercise with respect to myocyte calcium regulation. To investigate this, adult (12 months) and old (24 months) C57/Bl6 mice were trained using moderate-intensity treadmill running. In response to 10 weeks’ training, comparable cardiac hypertrophic responses were observed, although aging independently associated with additional cardiac hypertrophy. Old animals also showed increased L- and T-type calcium channels, the sodium–calcium exchange, sarcoendoplasmic reticulum calcium ATPase, and collagen (by 50%, 92%, 66%, 88%, and 113% respectively). Short-term exercise training increased D-type and T-type calcium channels in old animals only, whereas an increase in sodium–calcium exchange was seen only in adult animals. Long-term (12 months) training generally opposed the effects of aging. Significant hypertrophy remained in long-term trained old animals, but levels of sarcoendoplasmic reticulum calcium ATPase, sodium–calcium exchange, and collagen were not significantly different from those found in the adult trained animals

The effect of varying proportion and chop length of lucerne silage in a maize silage-based total mixed ration on diet digestibility and milk yield in dairy cattle

The objective was to assess the effects of inclusion rate and chop length of lucerne silage, when fed in a total mixed ration (TMR), on milk yield, dry matter (DM) intake (DMI) and digestion in dairy cows. Diets were formulated to contain a 50:50 forage:concentrate ratio (DM basis) and to be isonitrogenous (170 g/kg CP). The forage portion of the offered diets was comprised of maize and lucerne silage in proportions (DM basis) of either 25:75 (HL) or 75:25 (LL). Lucerne was harvested and conserved as silage at either a long (L) or short (S) chop length. These variables were combined in a 2x2 factorial arrangement to give four treatments (HLL, HLS, LLL, LLS) which were fed in a Latin square design study to Holstein dairy cows in two separate experiments. Sixteen and 8 multiparous, mid-lactation, cows were used in experiments 1 and 2, respectively. To ensure sufficient silage for both experiments, different cuts of lucerne silage (taken from the same sward) were used for each experiment: first cut for experiment 1 (which was of poorer quality) and second cut for experiment 2. Dry matter intake, milk yield and milk composition where measured in both experiments, and total tract digestibility and nitrogen (N) balance were assessed using four cows in experiment 2. In experiment 1 cows fed LL had increased DMI (+3.2 kg/day), compared with those fed HL. In contrast, there was no difference in DMI due to lucerne silage inclusion rate in experiment 2. A reduction in milk yield was observed with the HL treatment in both experiment 1 and 2 (-3.0 and -2.9 kg/day, respectively). The HL diet had reduced digestibility of DM and organic matter (OM) (-3 and -4%, respectively), and also reduced the efficiency of intake N conversion into milk N (-4%). The S chop length increased total tract digestibility of DM and OM (both +4%), regardless of inclusion rate. Inclusion of lucerne silage at 25% of forage dry matter increased milk yield relative to 75% inclusion, but a S chop length partially mitigated adverse effects of HL on DMI and milk yield in experiment 1 and on DM digestibility in experiment 2

Ozone Response to Aircraft Emissions: Sensitivity Studies with Two-dimensional Models

Our first intercomparison/assessment of the effects of a proposed high-speed civil transport (HSCT) fleet on the stratosphere is presented. These model calculations should be considered more as sensitivity studies, primarily designed to serve the following purposes: (1) to allow for intercomparison of model predictions; (2) to focus on the range of fleet operations and engine specifications giving minimal environmental impact; and (3) to provide the basis for future assessment studies. The basic scenarios were chosen to be as realistic as possible, using the information available on anticipated developments in technology. They are not to be interpreted as a commitment or goal for environmental acceptability

Markers of Field Cancerization: Proposed Clinical Applications in Prostate Biopsies

Field cancerization denotes the occurrence of genetic, epigenetic, and biochemical aberrations in structurally intact cells in histologically normal tissues adjacent to cancerous lesions. This paper tabulates markers of prostate field cancerization known to date and discusses their potential clinical value in the analysis of prostate biopsies, including diagnosis, monitoring progression during active surveillance, and assessing efficacy of presurgical neoadjuvant and focal therapeutic interventions

Store-directed price promotions and communications strategies improve healthier food supply and demand: impact results from a randomized controlled, Baltimore City store-intervention trial

Abstract Objective Small food store interventions show promise to increase healthy food access in under-resourced areas. However, none have tested the impact of price discounts on healthy food supply and demand. We tested the impact of store-directed price discounts and communications strategies, separately and combined, on the stocking, sales and prices of healthier foods and on storeowner psychosocial factors. Design Factorial design randomized controlled trial. Setting Twenty-four corner stores in low-income neighbourhoods of Baltimore City, MD, USA. Subjects Stores were randomized to pricing intervention, communications intervention, combined pricing and communications intervention, or control. Stores that received the pricing intervention were given a 10–30 % price discount by wholesalers on selected healthier food items during the 6-month trial. Communications stores received visual and interactive materials to promote healthy items, including signage, taste tests and refrigerators. Results All interventions showed significantly increased stock of promoted foods v . control. There was a significant treatment effect for daily unit sales of healthy snacks ( β =6·4, 95 % CI 0·9, 11·9) and prices of healthy staple foods ( β =–0·49, 95 % CI –0·90, –0·03) for the combined group v . control, but not for other intervention groups. There were no significant intervention effects on storeowner psychosocial factors. Conclusions All interventions led to increased stock of healthier foods. The combined intervention was effective in increasing sales of healthier snacks, even though discounts on snacks were not passed to the consumer. Experimental research in small stores is needed to understand the mechanisms by which store-directed price promotions can increase healthy food supply and demand

“We can all just get on a bus and go” : Rethinking independent mobility in the context of the universal provision of free bus travel to young Londoners

This paper uses qualitative data from interviews with 118 young Londoners (age 12-18) to examine how the universal provision of free bus travel has affected young people’s independent mobility. Drawing on Sen’s ‘capabilities approach’, we argue that free bus travel enhanced young Londoners’ capability to shape their daily mobility, both directly by increasing financial access and indirectly by facilitating the acquisition of the necessary skills, travelling companions and confidence. These capabilities in turn extended both opportunity freedoms (e.g. facilitating non-“necessary” recreational and social trips) and process freedoms (e.g. feeling more independent by decreasing reliance on parents). Moreover, the universal nature of the entitlement rendered buses a socially inclusive way for groups to travel and spend time together, thereby enhancing group-level capabilities. We believe this attention to individual and group capabilities for self-determination provides the basis for a broader and more child-centred view of ‘independent mobility’ than the typical research focus upon ‘travelling without an adult’ and acquiring parental permissions.Peer reviewe