Common Muscle Metabolic Signatures Highlight Arginine and Lysine Metabolism as Potential Therapeutic Targets to Combat Unhealthy Aging

Biological aging research is expected to reveal modifiable molecular mechanisms that can be harnessed to slow or possibly reverse unhealthy trajectories. However, there is first an urgent need to define consensus molecular markers of healthy and unhealthy aging. Established aging hallmarks are all linked to metabolism, and a ‘rewired’ metabolic circuitry has been shown to accelerate or delay biological aging. To identify metabolic signatures distinguishing healthy from unhealthy aging trajectories, we performed nontargeted metabolomics on skeletal muscles from 2-month-old and 21-month-old mice, and after dietary and lifestyle interventions known to impact biological aging. We hypothesized that common metabolic signatures would highlight specific pathways and processes promoting healthy aging, while revealing the molecular underpinnings of unhealthy aging. Here, we report 50 metabolites that commonly distinguished aging trajectories in all cohorts, including 18 commonly reduced under unhealthy aging and 32 increased. We stratified these metabolites according to known relationships with various aging hallmarks and found the greatest associations with oxidative stress and nutrient sensing. Collectively, our data suggest interventions aimed at maintaining skeletal muscle arginine and lysine may be useful therapeutic strategies to minimize biological aging and maintain skeletal muscle health, function, and regenerative capacity in old age.     

Molecular Genetics of Conjunctival Melanoma and Prognostic Value of TERT Promoter Mutation Analysis

The aim of this study was exploration of the genetic background of conjunctival melanoma (CM) and correlation with recurrent and metastatic disease. Twenty-eight CM from the Rotterdam Ocular Melanoma Study group were collected and DNA was isolated from the formalin-fixed paraffin embedded tissue. Targeted next-generation sequencing was performed using a panel covering GNAQ, GNA11, EIF1AX, BAP1, BRAF, NRAS, c-KIT, PTEN, SF3B1, and TERT genes. Recurrences and metastasis were present in eight (29%) and nine (32%) CM cases, respectively. TERT promoter mutations were most common (54%), but BRAF (46%), NRAS (21%), BAP1 (18%), PTEN (14%), c-KIT (7%), and SF3B1 (4%) mutations were also observed. No mutations in GNAQ, GNA11, and EIF1AX were found. None of the mutations was significantly associated with recurrent disease. Presence of a TERT promoter mutation was associated with metastatic disease (p-value = 0.008). Based on our molecular findings, CM comprises a separate entity within melanoma, although there are overlapping molecular features with uveal melanoma, such as the presence of BAP1 and SF3B1 mutations. This warrants careful interpretation of molecular data, in the light of clinical findings. About three quarter of CM contain drug-targetable mutations, and TERT promoter mutations are correlated to metastatic disease in CM.     

Validity of residential traffic intensity as an estimate of long-term personal exposure to traffic-related air pollution among adults

The validity of traffic intensity near the home as an estimate for the personal long-term exposure to traffic-related air pollution in an adult population was tested. Personal and near-home outdoor exposure to PM2.5, soot, NO, NO2, and NOx was monitored four to five times during 48 h periods in older adults. A group of 23 participants lived in high traffic intensity streets (>10000 vehicles/(24 h)), and 22 lived in low traffic intensity streets. The relation between average personal exposure and traffic intensity at the residential address was explored by taking indoor sources into account. Large differences in the measured outdoor concentrations between locations in high traffic and low traffic intensity streets were found for soot (68%), NO (127%), and NOx (35%). Differences were smaller for PM2.5 (14%) and NO2 (22%). Slightly elevated ratios were found for personal exposure to soot (1.15; 95% confidence interval (CI), 1.01-1.30)when comparing adults living in high traffic intensity streets with adults living in low traffic intensity streets. For NO, increased personal exposure (1.16) was seen for the same comparison, but this difference failed to reach statistical significance (CI, 0.80-1.66). Traffic intensity on the street of residence predicted personal exposure to soot but not to PM2.5 or nitrogen oxides. Traffic intensity may not correlate well to personal exposure and accordingly substantial misclassification of exposure may occur when traffic intensity is used as an exposure indicator in epidemiological studies. Time spent in traffic and spending time outdoors were associated with increased personal exposure of soot and PM2.5, but not NOx.     

Reed canary grass yield and fuel quality in Estonian farmers’ fields

Reed canary grass (Phalaris arundinacea) is one of the possible raw materials for bioenergy production in northern Europe. Its cultivation is favoured because its high productivity and local origin. However, problems with the biomass quality for combustion have been reported. Usually delayed harvest in spring is suggested to improve the quality and decrease the moisture content of biomass. On the other hand, the feasibility of spring harvest depends on local climatic conditions and may cause yield losses. In current paper we studied reed canary grass fields in Estonia locating on different soil types and cultivated with various varieties. The influence of several fertilisation schemes on biomass yield was analysed. Our results indicated that production was higher on mineral soils than on the organic soil of abandoned peat extraction sites. Even different types of fertilisation did not increase the production on organic soils to the level comparable to those on mineral soils. Among studied varieties ‘Venture’ had the highest production. The highest yield per area was obtained late in the autumn (12.7 t d.w. per ha and 7.2 t d.w. per ha on mineral and organic soils, respectively). By spring the amount of biomass had decreased in all studied sites. Due to wet soil some of the fields remained unharvested, the others had high yield losses during practical harvesting. The chemical analyses did not reveal significant differences in the composition of biomass between late autumn and spring. Therefore we conclude that late autumn harvest should be preferred in local climatic conditions.     

Mechanism of Salmonella reduction in fermented pig feed

To protect consumers from Salmonella infection acquired through the consumption of pork meat, it is necessary to eradicate Salmonella from pork. In order to achieve this, the whole pork production chain should be free from Salmonella, including the pigs at the farm. In epidemiological studies it was concluded that the use of fermented feed plays a significant role in the reduction of Salmonella prevalence in pig farms. However, the mechanism of Salmonella reduction in fermented feed is not known. A controlled feed fermentation was performed using a pure culture of Lactobacillus plantarum. pH reduction, organic acid profiles and bacterial counts were determined. In L plantarum‐fermented feed, lactic acid and acetic acid were produced and the pH dropped to a value below 4.0. Antimicrobial products (bacteriocins) could not be detected. The results showed that the produced lactic and acetic acid and the pH in the feed are responsible for Salmonella reduction in fermented feed. L plantarum did not show any other antimicrobial effect on Salmonella. © 2000 Society of Chemical Industry     

Market power mitigation by regulating contract portfolio risk

Abuse of market power by dominant generation firms is a growing concern in worldwide electricity markets. This paper argues that relying only on general competition rules—as is the case in most European countries—is insufficient and that complementary ex-ante regulation is needed. In particular, regulators should incentivize firms to sign contracts with retailers by regulating their risk exposure. In a simulation model we show that this type of regulation can significantly reduce the deadweight loss in the market, without imposing large costs on regulatees.     

Exploiting Varying Resource Requirements in Wavelet-based Applications in Dynamic Execution Environments

In the context of future dynamic applications, systems will exhibit unpredictably varying platform resource requirements. To deal with this, they will not only need to be programmable in terms of instruction set processors, but also at least partial reconfigurability will be required. In this context, it is important for applications to optimally exploit the memory hierarchy under varying memory availability. This article presents a mapping strategy for wavelet-based applications: depending on the encountered conditions, it switches to different memory optimized instantations or localizations, permitting up to 51% energy gains in memory accesses. Systematic and parameterized mapping guidelines indicate which localization should be selected when, for varying algorithmic wavelet parameters. The results have been formalized and generalized to be applicable to more general wavelet-based applications.     

Computational methods for database repair by signed formulae*

We introduce a simple and practical method for repairing inconsistent databases. Given a possibly inconsistent database, the idea is to properly represent the underlying problem, i.e., to describe the possible ways of restoring its consistency. We do so by what we call signed formulae, and show how the ‘signed theory’ that is obtained can be used by a variety of off-the-shelf computational models in order to compute the corresponding solutions, i.e., consistent repairs of the database. *This paper is a revised and extended version of [9].     

Cohort differences in attitudes toward mental health services among older persons.

In order to investigate historical shifts in attitudes toward mental health and mental health services, two independent samples of older adults separated by a 14-year time interval were administered questionnaires. There were 91 in the 1977 sample (mean age 69.91 yrs) and 116 in the 1991 sample (mean age 71.94 yrs). Four newly created, internally consistent scales assessed multiple dimensions of their mental health attitudes (breadth of conceptions, bias, openness to help, range of problems). Analyses suggested that the younger cohorts of older adults held more positive attitudes toward mental health and mental health services than the older cohorts. These cohort differences remained when controlled for age, level of education, self-reported health, and income. These data indicate a positive cohort shift in attitudes toward mental health, a finding with numerous implications for the design and implementation of mental health services for future cohorts of older persons. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nano-optics with single quantum systems

This paper reviews the recent progress in using single quantum systems, here mainly single fluorescent molecules, as local probes for nano-optical field distributions. We start by discussing the role of the absorption cross-section for the spatial resolution attainable in such experiments and its behaviour for different environmental conditions. It is shown that the spatial distribution of field components in a high-numerical aperture laser focus can be mapped with high precision using single fluorescent molecules embedded in a thin polymer film on glass. With this proof-of-principle experiment as a starting point, the possibility of mapping strongly confined and enhanced nano-optical fields close to material structures, e.g. sharp metal tips, is discussed. The mapping of the spatial distribution of the enhanced field at an etched gold tip using a single molecule is presented as an example. Energy transfer effects and quenching are identified as possible artefacts in this context. Finally, it is demonstrated that the local quenching at a sharp metal structure nevertheless can be exploited as a novel contrast mechanism for ultrahigh-resolution optical microscopy with single-molecule sensitivity.