Non-Reproducibility of Oral Rotenone as a Model for Parkinson’s Disease in Mice

Oral rotenone has been proposed as a model for Parkinson’s disease (PD) in mice. To establish the model in our lab and study complex behavior we followed a published treatment regimen. C57BL/6 mice received 30 mg/kg body weight of rotenone once daily via oral administration for 4 and 8 weeks. Motor functions were assessed by RotaRod running. Immunofluorescence studies were used to analyze the morphology of dopaminergic neurons, the expression of alpha-Synuclein (α-Syn), and inflammatory gliosis or infiltration in the substantia nigra. Rotenone-treated mice did not gain body weight during treatment compared with about 4 g in vehicle-treated mice, which was however the only robust manifestation of drug treatment and suggested local gut damage. Rotenone-treated mice had no deficits in motor behavior, no loss or sign of degeneration of dopaminergic neurons, no α-Syn accumulation, and only mild microgliosis, the latter likely an indirect remote effect of rotenone-evoked gut dysbiosis. Searching for explanations for the model failure, we analyzed rotenone plasma concentrations via LC-MS/MS 2 h after administration of the last dose to assess bioavailability. Rotenone was not detectable in plasma at a lower limit of quantification of 2 ng/mL (5 nM), showing that oral rotenone had insufficient bioavailability to achieve sustained systemic drug levels in mice. Hence, oral rotenone caused local gastrointestinal toxicity evident as lack of weight gain but failed to evoke behavioral or biological correlates of PD within 8 weeks.     

Genetic Dissection of Light-Regulated Adventitious Root Induction in Arabidopsis thaliana Hypocotyls

Photomorphogenic responses of etiolated seedlings include the inhibition of hypocotyl elongation and opening of the apical hook. In addition, dark-grown seedlings respond to light by the formation of adventitious roots (AR) on the hypocotyl. How light signaling controls adventitious rooting is less well understood. Hereto, we analyzed adventitious rooting under different light conditions in wild type and photomorphogenesis mutants in Arabidopsis thaliana. Etiolation was not essential for AR formation but raised the competence to form AR under white and blue light. The blue light receptors CRY1 and PHOT1/PHOT2 are key elements contributing to the induction of AR formation in response to light. Furthermore, etiolation-controlled competence for AR formation depended on the COP9 signalosome, E3 ubiquitin ligase CONSTITUTIVELY PHOTOMORPHOGENIC (COP1), the COP1 interacting SUPPRESSOR OF PHYA-105 (SPA) kinase family members (SPA1,2 and 3) and Phytochrome-Interacting Factors (PIF). In contrast, ELONGATED HYPOCOTYL5 (HY5), suppressed AR formation. These findings provide a genetic framework that explains the high and low AR competence of Arabidopsis thaliana hypocotyls that were treated with dark, and light, respectively. We propose that light-induced auxin signal dissipation generates a transient auxin maximum that explains AR induction by a dark to light switch.     

Life stress and treatment course of recurrent depression: II. Postrecovery associations with attrition, symptom course, and recurrence over 3 years.

Life stress was studied in relation to postrecovery attrition, symptom course, and recurrence of depression over 3 yrs. Participants were 67 individuals with recurrent depression who had responded to treatment. Life stress was assessed for the prior 12 wks at acute treatment entry (T1), initial recovery (T2), and after 17 wks of sustained recovery (T3). Severe life events at T1 predicted greater attrition, a more favorable postrecovery symptom course, and a lower likelihood of recurrence over 3 yrs. Life stress at T2 was not predictive of outcomes. Finally, undesirable life events at T3 tended to predict a worse symptom course and a higher likelihood of recurrence, particularly for individuals on medication. The findings are discussed in terms of (a) different processes influenced by life stress over time and (b) limitations of existing longitudinal research for studying the effects of life stress over prolonged intervals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ubiquitin Ligases in Longevity and Aging Skeletal Muscle

The development and prevalence of diseases associated with aging presents a global health burden on society. One hallmark of aging is the loss of proteostasis which is caused in part by alterations to the ubiquitin–proteasome system (UPS) and lysosome–autophagy system leading to impaired function and maintenance of mass in tissues such as skeletal muscle. In the instance of skeletal muscle, the impairment of function occurs early in the aging process and is dependent on proteostatic mechanisms. The UPS plays a pivotal role in degradation of misfolded and aggregated proteins. For the purpose of this review, we will discuss the role of the UPS system in the context of age-related loss of muscle mass and function. We highlight the significant role that E3 ubiquitin ligases play in the turnover of key components (e.g., mitochondria and neuromuscular junction) essential to skeletal muscle function and the influence of aging. In addition, we will briefly discuss the contribution of the UPS system to lifespan. By understanding the UPS system as part of the proteostasis network in age-related diseases and disorders such as sarcopenia, new discoveries can be made and new interventions can be developed which will preserve muscle function and maintain quality of life with advancing age.     

Impact of sensor characteristics on source characterization for dispersion modeling

An accidental or intentional release of hazardous chemical, biological, radiological, or nuclear material into the atmosphere obligates responsible agencies to model its transport and dispersion in order to mitigate the effects. This modeling requires input parameters that may not be known and must therefore be estimated from sensor measurements of the resulting concentration field. The genetic algorithm (GA) method used here has been successful at back-calculating not only these source characteristics but also the meteorological parameters necessary to predict the contaminants subsequent transport and dispersion. This study assesses the impact of sensor thresholds, i.e. the sensor minimum detection limit and saturation level, on the ability of the algorithm to back-calculate modeling variables. The sensitivity of the back-calculation to these sensor constraints is analyzed in the context of an identical twin approach, where the data is simulated using the same Gaussian Puff model that is used in the back-calculation algorithm in order to analyze sensitivity in a controlled environment. The solution is optimized by the GA and further tuned with the Nelder-Mead downhill simplex algorithm. For this back-calculation to be successful, it is important that the sensor capture the maximum concentrations.     

Preparation of glycol derivatives of partially hydrogenated soybean oil fatty acids and their potential as lubricants

Glycol diesters and mixtures of mono- and diesters have been prepared from methyl esters of partially hydrogenated soybean oil fatty acids and diethylene, dipropylene, neopentyl and triethylene glycols. The catalyst used in these reactions was a mixture of calcium acetate/barium acetate (3∶1, w/w). The reactions were carried out under nitrogen with 0.5% catalyst at temperatures in the range of 190–275°C. Borated esters of mixed mono- and diesters were prepared with 0.33 equivalent of boric acid per 1.0 equivalent hydroxyl group on the ester. Refractive indices, viscosities, and flash and fire points were determined for diesters, mixed mono- and diesters, and mixed diesters and borated esters. The viscosities, flash points and fire points indicate that these esters can be used as a component of lubricating oils. Wear-prevention characteristics of mixed diesters and borated esters indicated that they can be used as antifriction additives in lubricating oils. Lecture presented at the joint meeting of the International Society for Fat Research and the American Oil Chemists' Society in Toronto, May 10, 1992.     

Microstructural Design of Silicon Nitride with Improved Fracture Toughness: II, Effects of Yttria and Alumina Additives

Significant improvements in the fracture resistance of self-reinforced silicon nitride ceramics have been obtained by tailoring the chemistry of the intergranular amorphous phase. First, the overall microstructure of the material was controlled by incorporation of a fixed amount of elongated ß-Si₃N₄ seeds into the starting powder to regulate the size and fraction of the large reinforcing grains. With controlled microstructures, the interfacial debond strength between the reinforcement and the intergranular glass was optimized by varying the yttria-to-alumina ratio in the sintering additives. It was found that the steady-state fracture toughness value of these silicon nitrides increased with the Y:Al ratio of the oxide additives. The increased toughness was accompanied by a steeply rising R -curve and extensive interfacial debonding between the elongated ß-Si₃N₄ grains and the intergranular glassy phase. Microstructural analyses indicate that the different fracture behavior is related to the Al (and O) content in the ß´-SiAlON growth layer formed on the elongated ß-Si₃N₄ grains during densification. The results imply that the interfacial bond strength is a function of the extent of Al and Si bonding with N and O in the adjoining phases with an abrupt structural/chemical interface achieved by reducing the Al concentration in both the intergranular phase and the ß´-SiAlON growth layer. Analytical modeling revealed that the residual thermal expansion mismatch stress is not a dominant influence on the interfacial fracture behavior when a distinct ß´-SiAlON growth layer forms. It is concluded that the fracture resistance of self-reinforced silicon nitrides can be improved by optimizing the sintering additives employed.     

Is it safer behind the gates? Crime and gated communities in South Africa

Gated communities have long been seen as a rational response to rising crime levels, yet very little is known about the extent to which residing in a gated community actually reduces an individuals’ risk of criminal victimisation. In this study, we use location quotients to compare the extent of burglary in gated communities with burglary across the entire city of Tshwane, South Africa, as well as compare burglary in gated communities with burglary occurring within a series of buffer intervals immediately surrounding these communities. Finally, we identify what physical characteristics of gated communities differentiate between high and low burglary in these enclaves. Prior to expectations, we found that gated communities (and their immediate surrounding areas) are associated with increased levels of burglary. There are, however, a number of physical characteristics of gated communities which are associated with much lower burglary levels. The implications of our work from a crime prevention and development planning perspective are discussed.     

Expanding the social performance of food production landscapes: measuring health and well-being benefits

Advocates of integrating food production landscapes within urban, suburban, campus and other design arenas cite multiple and integrated benefits, including enhanced food security and quality; land access for small farmers; psychological and social benefits; educational opportunities; and green infrastructure contributions, among others. If performance can be understood as ‘the fulfilment of a claim’ then landscape performance measures for food production would ideally encompass the overall range of cited benefits. Yet in current practice the performance of food production landscapes tends to be measured in limited ways, most often by weight and value of harvest. The aim of this paper is to identify expanded methods and metrics for measuring the performance of food production landscapes, in particular for health and well-being benefits. Through a transdisciplinary literature review, evidence for mental well-being, physical activity and human nutrition benefits of food production landscapes is presented, and performance metrics and evaluation methods are catalogued.