Salicylate hydroxylation as an early marker of in vivo oxidative stress in diabetic patients.

In vivo metabolism of salicylic acid produces two main hydroxylated derivatives (2,5- and 2,3-dihydroxybenzoic acid). The former can be produced by enzymatic pathways through the cytochrome P-450 system, while the latter is reported to be solely formed by direct hydroxyl radical attack. Therefore, measurement of 2,3-dihydroxybenzoate, following oral administration of salicylate in its acetylated form (aspirin), has been proposed for assessment of oxidative stress. In this article we report plasma levels of 2,3- and 2,5-dihydroxybenzoates following the administration of 1 g aspirin and plasma levels of thiobarbituric acid-reactive material (TBARM) in well-controlled diabetic patients and in healthy subjects. 2,3-Dihydroxybenzoate levels were significantly higher (23%) in diabetic patients than in controls (63.4 +/- 20.1 versus 49.0 +/- 6.8 nM; p < .05). On the other hand, TBARM values were not significantly different between groups. These results suggest that the method is useful to reveal in vivo oxidative stress independently from the peroxidation of lipids, and they support the hypothesis that oxygen radicals are involved in the pathogenesis of chronic complications of diabetes.     

Biotechnical Characteristics of Root Systems of Typical Mediterranean Species

Quantifying patterns of fine root dynamics is crucial to the understanding of ecosystem structure and function, and in predicting how ecosystems respond to disturbance. Part of this understanding involves consideration of the carbon lost through root turnover. In the context of the rainfall pattern in the tropics, it was hypothesised that rainfall would strongly influence fine root biomass and longevity. A field study was conducted to determine root biomass, elemental composition and the influence of rainfall on longevity of fine roots in a tropical lowland evergreen rainforest at Danum Valley, Sabah, Malaysia. A combination of root coring, elemental analysis and rhizotron observation methods were used. Fine (less than 2 mm diameter) root biomass was relatively low (1700 kg ha −1) compared with previously described rainforest data. Standing root biomass was positively correlated with preceding rainfall, and the low fine root biomass in the dry season contained higher concentrations of N and lower concentrations of P and K than at other times. Observations on rhizotrons demonstrated that the decrease in fine root biomass in the dry season was a product of both a decrease in fine root length appearance and an increase in fine root length disappearance. Fitting an overall model to root survival time showed significant effects of rainfall preceding root disappearance, with the hazard of root disappearance decreasing by 8 for each 1 mm increase in the average daily (30 day) rainfall preceding root disappearance. While it is acknowledged that other factors have a part to play, this work demonstrates the importance of rainfall and soil moisture in influencing root biomass and root disappearance in this tropical rainforest.     

Alpha- and beta-keratins of the snake epidermis

Snake scales contain specialized hard keratins (beta-keratins) and alpha- or cyto-keratins in their epidermis. The number, isoelectric point, and the evolution of these proteins in snakes and their similarity with those of other vertebrates are not known. In the present study, alpha- and beta-keratins of snake molts and of the whole epidermis have been studied by using two-dimensional electrophoresis and immunocytochemistry. Specific keratins in snake epidermis have been identified by using antibodies that recognize acidic and basic cytokeratins and avian or lizard scale beta-keratin. Alpha keratins of 40-70 kDa and isoelectric point (pI) at 4.5-7.0 are present in molts. The study suggests that cytokeratins in snakes are acidic or neutral, in contrast to mammals and birds where basic keratins are also present. Beta keratins of 10-15 kDa and a pI of 6.5-8.5 are found in molts. Some beta-keratins appear as basic proteins (pI 8.2) comparable to those present in the epidermis of other reptiles. Some basic "beta-keratins" associate with cytokeratins as matrix proteins and replace cytokeratins forming the corneous material of the mature beta-layer of snake scales, as in other reptiles. The study also suggests that more forms of beta-keratins (more than three different types) are present in the epidermis of snakes.     

A fluctuation-driven mechanism for slow decision processes in reverberant networks

The spike activity of cells in some cortical areas has been found to be correlated with reaction times and behavioral responses during two-choice decision tasks. These experimental findings have motivated the study of biologically plausible winner-take-all network models, in which strong recurrent excitation and feedback inhibition allow the network to form a categorical choice upon stimulation. Choice formation corresponds in these models to the transition from the spontaneous state of the network to a state where neurons selective for one of the choices fire at a high rate and inhibit the activity of the other neurons. This transition has been traditionally induced by an increase in the external input that destabilizes the spontaneous state of the network and forces its relaxation to a decision state. Here we explore a different mechanism by which the system can undergo such transitions while keeping the spontaneous state stable, based on an escape induced by finite-size noise from the spontaneous state. This decision mechanism naturally arises for low stimulus strengths and leads to exponentially distributed decision times when the amount of noise in the system is small. Furthermore, we show using numerical simulations that mean decision times follow in this regime an exponential dependence on the amplitude of noise. The escape mechanism provides thus a dynamical basis for the wide range and variability of decision times observed experimentally.     

Evolutionary dynamics in an SI epidemic model with phenotype-structured susceptible compartment

When modeling infectious diseases, it is common to assume that infection-derived immunity is either (1) non-existent or (2) perfect and lifelong. However there are many diseases in which infection-derived immunity is known to be present but imperfect. There are various ways in which infection-derived immunity can fail, which can ultimately impact the probability that an individual be reinfected by the same pathogen, as well as the long-run population-level prevalence of the pathogen. Here we discuss seven different models of imperfect infection-derived immunity, including waning, leaky and all-or-nothing immunity. For each model we derive the probability that an infected individual becomes reinfected during their lifetime, given that the system is at endemic equilibrium. This can be thought of as the impact that each of these infection-derived immunity failures have on reinfection. This measure is useful because it provides us with a way to compare different modes of failure of infection-derived immunity.

     

Clinical Evaluation of Rega 8: An Updated Genotypic Interpretation System That Significantly Predicts HIV-Therapy Response

Introduction

Clinically evaluating genotypic interpretation systems is essential to provide optimal guidance in designing potent individualized HIV-regimens. This study aimed at investigating the ability of the latest Rega algorithm to predict virological response on a short and longer period.

Materials & Methods

9231 treatment changes episodes were extracted from an integrated patient database. The virological response after 8, 24 and 48 weeks was dichotomized to success and failure. Success was defined as a viral load below 50 copies/ml or alternatively, a 2 log decrease from the baseline viral load at 8 weeks. The predictive ability of Rega version 8 was analysed in comparison with that of previous evaluated version Rega 5 and two other algorithms (ANRS v2011.05 and Stanford HIVdb v6.0.11). A logistic model based on the genotypic susceptibility score was used to predict virological response, and additionally, confounding factors were added to the model. Performance of the models was compared using the area under the ROC curve (AUC) and a Wilcoxon signed-rank test.

Results

Per unit increase of the GSS reported by Rega 8, the odds on having a successful therapy response on week 8 increased significantly by 81% (OR = 1.81, CI = [1.76–1.86]), on week 24 by 73% (OR = 1.73, CI = [1.69–1.78]) and on week 48 by 85% (OR = 1.85, CI = [1.80–1.91]). No significant differences in AUC were found between the performance of Rega 8 and Rega 5, ANRS v2011.05 and Stanford HIVdb v6.0.11, however Rega 8 had the highest sensitivity: 76.9%, 76.5% and 77.2% on 8, 24 and 48 weeks respectively. Inclusion of additional factors increased the performance significantly.

Conclusion

Rega 8 is a significant predictor for virological response with a better sensitivity than previously, and with rules for recently approved drugs. Additional variables should be taken into account to ensure an effective regimen.     

Tree seedling response to LED spectra: implications for forest restoration

We found that different spectra, provided by light-emitting diodes or a fluorescent lamp, caused different photomorphological responses depending on tree seedling type (coniferous or broad-leaved), species, seedling development stage, and seedling fraction (shoot or root). For two conifers (Picea abies and Pinus sylvestris) soon after germination (≤40 days), more seedling growth was related to a lower ratio of red-to-far-red (R:FR) light. As growth continued to 120 days, spectra with a greater complement of blue light yielded more growth. Roots showed more plasticity to light spectra than shoots. In general for the evergreen broad-leaved Quercus ilex, spectra with additional R:FR than for conifers yielded more growth in the first 57 days. Subsequently as seedlings grew, shoot growth appeared to be influenced less by light source than roots, with root length showing the greatest responses. Our results suggest that manipulating light spectra to foster desired seedling traits may be another tool for use in the production of high-quality seedlings as defined through the Target Plant Concept. Such seedlings are needed for restoration of the two billion hectares of degraded forestland, especially on harsh sites such as those found in the Mediterranean region, and to sequester carbon to mitigate climate change.