Amyloid Beta Pathology Exacerbates Weight Loss and Brain Cytokine Responses following Low-Dose Lipopolysaccharide in Aged Female Tg2576 Mice

Systemic inflammation has been implicated in the progression of Alzheimer’s disease (AD); however, less is understood about how existing AD pathology contributes to adverse outcomes following acute inflammatory insults. In the present study, our goal was to determine how AD-associated amyloid beta (Aβ) pathology influences the acute neuroinflammatory and behavioral responses to a moderate systemic inflammatory insult. We treated 16–18-month-old female Tg2576 (Tg) mice, which overproduce human Aβ and develop plaques, and age-matched wild-type (WT) littermate mice with an intraperitoneal injection of 0.33 mg/kg lipopolysaccharide (LPS) or saline. Mice were then evaluated over the next 28 h for sickness/depressive-like behaviors (food intake, weight loss, locomotion, and sucrose preference), systemic inflammation (serum amyloid A, SAA), blood-brain barrier (BBB) disruption, astrogliosis (glial fibrillary acidic protein/GFAP), Aβ, and cytokine levels in the brain. We found that LPS caused a larger reduction in body weight in Tg vs. WT mice, but that other behavioral responses to LPS did not differ by genotype. BBB disruption was not apparent in either genotype following LPS. Concentrations of the systemic inflammatory marker, SAA, in the blood and brain were significantly increased with LPS but did not significantly differ by genotype. GFAP was increased in Tg mice vs. WT but was not significantly affected by LPS in either genotype. Finally, LPS-induced increases of eight cytokines (IL-1β, IL-6, IL-12 (p40), IL-10, IL-17A, MIP-1α/CCL3, MIP-1β/CCL4, and RANTES/CCL5) were found to be significantly higher in Tg mice vs. WT. In summary, our data show that Aβ pathology exacerbates the neuroinflammatory response to LPS and identifies cytokines that are selectively regulated by Aβ. The association of worse neuroinflammation with greater weight loss in Tg mice suggests that Aβ pathology could contribute to poor outcomes following a systemic inflammatory insult.     

Proteomic Assessment of Extracellular Vesicles from Canine Tissue Explants as a Pipeline to Identify Molecular Targets in Osteosarcoma: PSMD14/Rpn11 as a Proof of Principle

Osteosarcoma (OS) is a highly malignant bone tumour that has seen little improvement in treatment modalities in the past 30 years. Understanding what molecules contribute to OS biology could aid in the discovery of novel therapies. Extracellular vesicles (EVs) serve as a mode of cell-to-cell communication and have the potential to uncover novel protein signatures. In our research, we developed a novel pipeline to isolate, characterize, and profile EVs from normal bone and osteosarcoma tissue explants from canine OS patients. Proteomic analysis of vesicle preparations revealed a protein signature related to protein metabolism. One molecule of interest, PSMD14/Rpn11, was explored further given its prognostic potential in human and canine OS, and its targetability with the drug capzimin. In vitro experiments demonstrated that capzimin induces apoptosis and reduces clonogenic survival, proliferation, and migration in two metastatic canine OS cell lines. Capzimin also reduces the viability of metastatic human OS cells cultured under 3D conditions that mimic the growth of OS cells at secondary sites. This unique pipeline can improve our understanding of OS biology and identify new prognostic markers and molecular targets for both canine and human OS patients.     

Bubble removal in centrifugal casting: Combined effects of buoyancy and diffusion

This article models bubble removal in centrifugal casting of the thermosetting silicone polydimethylsiloxane (PDMS). Given spin speeds, mold geometry, and resin properties for centrifugal casting, it is possible to predict the amount of spin time required to produce bubble‐free parts. For the particular conditions and materials considered in this work, required spin times range from seconds to minutes. The model itself balances two complementary physical behaviors: bubble dissolution and buoyancy. Diffusion dominates the removal of small bubbles below a critical size, while buoyancy dominates the removal of bubbles above a critical size. To simulate the removal of bubbles from a spinning solution, two first‐order nonlinear differential equations are solved numerically. To verify simulated results, designed sets of experiments related the number of remaining bubbles in cured parts to spin times and speeds. Dow Corning Sylgard 184, Sylgard 186, and 3‐6121 were the silicones tested in this work. POLYM. ENG. SCI., 2012. © 2011 Society of Plastics Engineers     

Further Studies on Sex Pheromones of Female Lygus and Related Bugs: Development of Effective Lures and Investigation of Species-Specificity

Mirid bugs (Heteroptera: Miridae) are important pests of many crops worldwide. In previous work by others and ourselves, several species of Lygus bugs were shown to produce blends of three compounds, hexyl butyrate, (E)-2-hexenyl butyrate, and (E)-4-oxo-2-hexenal. These have been proposed as components of the female-produced sex pheromones, but attraction of males to synthetic lures has been difficult to demonstrate. We studied the volatiles released by females of four species: Lygus rugulipennis, Lygus pratensis, Lygocoris pabulinus, and Liocoris tripustulatus. Analyses of volatiles from individual, undisturbed insects showed that the three compounds were produced in species-specific blends, by females only, or in greater quantities by females than by males. The three compounds were loaded into pipette tips, which released the defined blends over at least 30 days. Traps baited with the blend for L. rugulipennis caught more males than traps baited with virgin females, with all three compounds required for maximum attractiveness. Traps baited with the specific blends for each of the four species caught males of three of the species, indicating considerable cross-attraction. There is evidence that other, non-chemical factors, such as time-of-day of production of pheromone, contribute to species-specificity of attraction. This is the first report of consistent attraction of Lygus bugs to synthetic lures in the field.     

Estimation of ethanol mass delivery to groundwater from silicone polymer mats

Hollow-fiber silicone tubing, coiled and shaped as mats, has been evaluated for its potential to provide predictable delivery of ethanol to aquifers to promote reducing conditions for enhanced bioremediation of a range of contaminants in groundwater. A model was developed to predict the steady-state mass flux of diffusional ethanol delivery to an external aqueous phase from an aqueous ethanol solution present inside the polymer tubing mat, and an effective diffusion coefficient of ethanol through the silicone tubing of 1.22 x 10(-6) cm2 s(-1) was determined experimentally. The model was then validated in column-scale laboratory and field experiments where polymer mats configured as permeable reactive barriers maintained uniform diffusive delivery of ethanol. Steady-state mass flux delivery ratios of ethanol through the polymer tubing wall of 1.45 (+/-0.18) x 10(6) to 1.64 (+/-0.17) x 10(6) s cm(-1) were determined under laboratory conditions, and 2.43 (+/-1.47) x 10(6) s cm(-1) under field conditions, which were found to be statistically similar to model-predicted ethanol mass flux delivery ratios.     

Effects of chondrogenic and osteogenic regulatory factors on composite constructs grown using human mesenchymal stem cells, silk scaffolds and bioreactors.

Human mesenchymal stem cells (hMSCs) isolated from bone marrow aspirates were cultured on silk scaffolds in rotating bioreactors for three weeks with either chondrogenic or osteogenic medium supplements to engineer cartilage- or bone-like tissue constructs. Osteochondral composites formed from these cartilage and bone constructs were cultured for an additional three weeks in culture medium that was supplemented with chondrogenic factors, supplemented with osteogenic factors or unsupplemented. Progression of cartilage and bone formation and the integration between the two regions were assessed by medical imaging (magnetic resonance imaging and micro-computerized tomography imaging), and by biochemical, histological and mechanical assays. During composite culture (three to six weeks), bone-like tissue formation progressed in all three media to a markedly larger extent than cartilage-like tissue formation. The integration of the constructs was most enhanced in composites cultured in chondrogenic medium. The results suggest that tissue composites with well-mineralized regions and substantially less developed cartilage regions can be generated in vitro by culturing hMSCs on silk scaffolds in bioreactors, that hMSCs have markedly higher capacity for producing engineered bone than engineered cartilage, and that chondrogenic factors play major roles at early stages of bone formation by hMSCs and in the integration of the two tissue constructs into a tissue composite.     

Protocol for Candrive II/Ozcandrive,a multicentre prospective older driver cohort study

The Candrive II/Ozcandrive study, a multicentre prospective cohort study examining the predictive validity of tools for assessing fitness to drive, aims to develop an in-office screening tool that will help clinicians identify older drivers who may be unsafe to drive. This paper describes the study protocol. We are following a cohort of drivers aged ≥70 years for up to 4 years. Starting in 2009, 928 participants have been recruited in seven cities in four Canadian provinces, as well as 302 participants in two sites in Melbourne, Australia and Wellington, New Zealand. Participants underwent a comprehensive assessment at baseline and repeat the assessment yearly thereafter, as well as a brief follow-up assessment at 4 and 8 months each year. A recording device is installed in participants’ vehicles to assess driving patterns, and driving records are obtained from licensing authorities to determine the outcomes: at-fault crashes per kilometre driven and violations. To date, the protocol has been generally well adhered to, with 1230 participants, and barriers and challenges are being addressed, as necessary. The Candrive II/Ozcandrive study is unique owing to its size, duration, partnerships with Canadian, Australian and New Zealand stakeholders, and international research collaboration.     

The four-factor model of depressive symptoms in dementia caregivers: A structural equation model of ethnic differences.

Previous studies have suggested that 4 latent constructs (depressed affect, well-being, interpersonal problems, somatic symptoms) underlie the item responses on the Center for Epidemiological Studies Depression (CES-D) Scale. This instrument has been widely used in dementia caregiving research, but the fit of this multifactor model and the explanatory contributions of multifactor models have not been sufficiently examined for caregiving samples. The authors subjected CES-D data (N = 1,183) from the initial Resources for Enhancing Alzheimer's Caregiver Health Study to confirmatory factor analysis methods and found that the 4-factor model provided excellent fit to the observed data. Invariance analyses suggested only minimal item-loading differences across race subgroups and supported the validity of race comparisons on the latent factors. Significant race differences were found on 3 of the 4 latent factors both before and after controlling for demographic covariates. African Americans reported less depressed affect and better well-being than White caregivers, who reported better well-being and fewer interpersonal problems than Hispanic caregivers. These findings clarify and extend previous studies of race differences in depression among diverse samples of dementia caregivers. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Workplace aggression in teenage part-time employees.

Among adult employees, interpersonal injustice and abusive supervision predict aggression toward supervisors at work. The aim of this study was to assess whether similar relationships exist among teenage employees and, further, whether teenagers' reasons for working moderate these relationships. Multiple regression analyses on data from 119 teenage employees showed that financial and personal fulfillment reasons for working moderate the impact of interpersonal injustice and abusive supervision on aggression directed at workplace supervisors. These findings contribute to the understanding of workplace aggression by demonstrating that (a) teenagers engage in this workplace behavior, (b) the predictors are similar to those of adult aggression, and (c) reasons for working play a moderating role among this particular cohort. The possible long-term consequences of teenagers' use of aggression at work are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)