Reversed optimality and predictive ecology: burrowing depth forecasts population change in a bivalve

Optimality reasoning from behavioural ecology can be used as a tool to infer how animals perceive their environment. Using optimality principles in a 'reversed manner' may enable ecologists to predict changes in population size before such changes actually happen. Here we show that a behavioural anti-predation trait (burrowing depth) of the marine bivalve Macoma balthica can be used as an indicator of the change in population size over the year to come. The per capita population growth rate between years t and t+1 correlated strongly with the proportion of individuals living in the dangerous top 4 cm layer of the sediment in year t: the more individuals in the top layer, the steeper the population decline. This is consistent with the prediction based on optimal foraging theory that animals with poor prospects should accept greater risks of predation. This study is among the first to document fitness forecasting in animals.     

Adverse environmental conditions influence age-related innate immune responsiveness

Background-  

The innate immune system plays an important role in the recognition and induction of protective responses against infectious pathogens, whilst there is increasing evidence for a role in mediating chronic inflammatory diseases at older age. Despite indications that environmental conditions can influence the senescence process of the adaptive immune system, it is not known whether the same holds true for the innate immune system. Therefore we studied whether age-related innate immune responses are similar or differ between populations living under very diverse environmental conditions.     

Detection of dementia in primary care: comparison of the original and a modified Mini-Cog Assessment with the Mini-Mental State Examination

Background Dementia is considered widely under-detected in primary care, and general practitioners (GPs) frequently ask for easy to use tools to assist in its early detection.Aim To determine the degree of correlation between the Mini-Cog Assessment (Mini-Cog) as performed by GPs and the Mini-Mental State Examination (MMSE).Design of study This was a prospective study (2005, 2006) comparing two cognitive screening instruments.Setting Ten general practices in Austria, with patients with a hitherto undiagnosed suspicion of dementia seen consecutively.Method Sensitivity, specificity and positive and negative predictive values (PPVs and NPVs) of the Mini-Cog (applying both a colour-coded and the original rating method) were assessed for degree of correlation with the MMSE. In phase one GPs examined patients suspected of having dementia using the Mini-Cog; in phase two a neurologist retested them applying the MMSE, a clock-drawing test (CDT) and a routine clinical examination. A questionnaire on the practicability of the Mini-Cog was answered by GPs.Results Of the 107 patients who participated 86 completed the whole study protocol. The Mini-Cog, as performed by the ten GPs, displayed a sensitivity of 0.85 (95% CI: 0.71, 0.98), a specificity of 0.58 (95% CI: 0.46, 0.71), a PPV of 0.47 (95% CI: 0.33, 0.61) and an NPV of 0.90 (95% CI: 0.80, 0.99) as against the MMSE carried out by neurologists. The GPs judged the Mini-Cog useful and time saving.Conclusion The Mini-Cog has a high sensitivity and acceptable specificity in the general practice setting and has proved to be a practicable tool for the diagnosis of dementia in primary care.     

Selection for Genetic Variation Inducing Pro-Inflammatory Responses under Adverse Environmental Conditions in a Ghanaian Population

Background

Chronic inflammation is involved in the pathogenesis of chronic age-associated, degenerative diseases. Pro-inflammatory host responses that are deleterious later in life may originate from evolutionary selection for genetic variation mediating resistance to infectious diseases under adverse environmental conditions.

Methodology/Principal Findings

In the Upper-East region of Ghana where infection has remained the leading cause of death, we studied the effect on survival of genetic variations at the IL10 gene locus that have been associated with chronic diseases. Here we show that an IL10 haplotype that associated with a pro-inflammatory innate immune response, characterised by low IL-10 (p = 0.028) and high TNF-α levels (p = 1.39×10⁻³), was enriched among Ghanaian elders (p = 2.46×10⁻⁶). Furthermore, in an environment where the source of drinking water (wells/rivers vs. boreholes) influences mortality risks (HR 1.28, 95% CI [1.09–1.50]), we observed that carriers of the pro-inflammatory haplotype have a survival advantage when drinking from wells/rivers but a disadvantage when drinking from boreholes (p_interaction = 0.013). Resequencing the IL10 gene region did not uncover any additional common variants in the pro-inflammatory haplotype to those SNPs that were initially genotyped.

Conclusions/Significance

Altogether, these data lend strong arguments for the selection of pro-inflammatory host responses to overcome fatal infection and promote survival in adverse environments.     

PAHs and their Carcinogenic Potencies in Diesel Fuel and Diesel Generator Exhaust

The PAH profile was characterized in diesel fuel samples collected from different service stations in Agra (India) by using a gas chromatograph equipped with a flame ionization detector (FID). The low molecular weight PAHs were predominant, ranging from 4.4 × 10² to 1.7 × 10³ mg l^{? 1} in fuel. Exhaust emissions from a diesel generator and a four-stroke engine (Skoda) powered by these fuels were monitored by a stack sampler and quantified for PAHs. The high molecular weight PAHs (DbA+IP, BghiP, and BaP, BbF+BkF) were the dominant PAHs in exhaust emissions. Differences in PAH emission factors for the two engines were found and these differences could be related to the combustion conditions affecting the temperature of flue gas. Emission factors and output/input ratio for individual PAHs suggest that the low molecular weight compounds in the fuel contribute to pyrosynthesis of high molecular weight in exhaust. Unburnt fuel partially contributes to low molecular weight PAHs in exhaust. Further, the relative carcinogenic contributions of each compound in the fuel and exhaust were calculated using the TEF approach. DbA + IP and BaP were significant contributors to the carcinogenicity of the PAH mixture in the exhaust.     

Proposed algorithm to investigate latent and occult viruses in vaccine cell substrates by chemical induction

The recent urgency to develop new vaccines for emerging and re-emerging diseases, such as pandemic influenza, has necessitated the use of cell substrates not previously used in the manufacture of licensed vaccines. A major safety concern in the use of novel cell substrates is the presence of potential adventitious agents, such as latent and occult viruses, that may not be detected by currently used conventional assays. In cases where the novel cell substrate is known to be tumorigenic, there are additional safety issues related to tumorigenicity of intact cells and oncogenicity of residual cellular DNA. We have developed a strategy for evaluating vaccine cell substrates for the presence of latent/occult viruses, including endogenous retroviruses, latent RNA viruses and oncogenic DNA viruses, by optimizing conditions for chemical induction of viruses and using a combination of broad and specific assays to enable detection of known and novel viruses.     

Motor unit firing behavior during prolonged 50% MVC dorsiflexion contractions in young and older adults

The purpose of this study was to investigate changes in motor unit firing behavior during prolonged contractions in young and older adults. Motor unit activity was recorded from the tibialis anterior of 16 subjects (8 young and 8 older), while they performed isometric dorsiflexion at 50% MVC until task failure. Mean motor unit firing rate, the standard deviation (SD), and coefficient of variation (CV) of the interspike intervals, and number of doublet discharges were calculated for a total of 52 motor units, tracked for an average of 92.9 ± 68.6 s. There was no age-related difference in the time to task failure. A modest decline in firing rate was observed in 71% of the motor units, with no significant age-related difference. The SD and CV of the interspike interval had a positive slope in 65% and 69% of the motor units, respectively, with no significant age-related differences. The number of doublet discharges remained stable throughout the contraction. Both groups exhibited motor unit dropout (discharge cessation) during the contraction. Thus, a fatiguing task producing modest changes in firing rate in young and older adults is accompanied by an appreciable increase in firing rate variability. The incidence of doublet discharges is not increased during fatiguing contractions.     

Lipid‐Bilayer Permeation of Drug‐Like Compounds

Lipid‐bilayer permeation is determinant for the disposition of xenobiotics in the body. It controls the pharmacokinetic behavior of drugs and is, in many cases, a prerequisite for intracellular targeting. Permeation of in vivo barriers is in general predicted from lipophilicity and related parameters. This article goes beyond the empirical correlations, and elucidates the processes and their interplay determining bilayer permeation. A flip‐flop model for bilayer permeation, which considers the partitioning rate constants beside the translocation rate constants, is compared with the diffusion model based on Fick's first law. According to the flip‐flop model, the ratios of aqueous volumes to barrier area can determine whether partitioning or translocation is rate‐limiting. The flip‐flop model allows permeation of anions and cations, and expands our understanding of pH‐dependent permeation kinetics. Some experimental evidences for ion‐controlled permeation at pH 7 are also included in this work.