Multiplatform serum metabolic phenotyping combined with pathway mapping to identify biochemical differences in smokers

Aim: Determining perturbed biochemical functions associated with tobacco smoking should be helpful for establishing causal relationships between exposure and adverse events. Results: A multiplatform comparison of serum of smokers (n = 55) and never-smokers (n = 57) using nuclear magnetic resonance spectroscopy, UPLC–MS and statistical modeling revealed clustering of the classes, distinguished by metabolic biomarkers. The identified metabolites were subjected to metabolic pathway enrichment, modeling adverse biological events using available databases. Perturbation of metabolites involved in chronic obstructive pulmonary disease, cardiovascular diseases and cancer were identified and discussed. Conclusion: Combining multiplatform metabolic phenotyping with knowledge-based mapping gives mechanistic insights into disease development, which can be applied to next-generation tobacco and nicotine products for comparative risk assessment

Spatial fields’ dispersion as a farmer strategy to reduce agro-climatic risk at the household level in pearl millet-based systems in the Sahel: A modeling perspective

The rainfall pattern in the Sahel is very erratic with a high spatial variability. We tested the often reported hypothesis that the dispersion of farmers’ fields around the village territory helps mitigate agro-climatic risk by increasing yield stability from year to year. We also wished to evaluate whether this strategy had an effect on the yield disparity among households in a village. Based on a network of approximately 60 rain gauges spread over 500 km2 in the Fakara region (Southwest Niger), daily rainfall was interpolated at 300 m × 300 m resolution over a 12-year period. This data was used to compute, by means of the APSIM crop simulation model, millet biomass and grain yields at the pixel scale. Simulated yields were combined with the land tenure map of the Banizoumbou village in a GIS to assess millet yield at field and household level. Agro-climatic risk analysis was performed using linear regression between a spatial dispersion index of household fields and the inter-annual (instability) and inter-household (disparity) millet yield variability of 107 households in the village territory. We find that the spatial variability of annual rainfall induces an even higher spatial variability of millet production at pixel, field and household levels. The dispersion of farm fields reduces moderately but significantly the disparity of millet yield between households each year and increases the inter-annual yield stability of a given household. The less the household fields are scattered, the more the presence of a fertility gradient around the village enhances the inter-annual stability but also the disparity between households. Our results provide evidence that field dispersion is an effective strategy to mitigate agro-climatic risk, as claimed by farmers in the Sahelian Niger. Although the results should be confirmed by further research on longer term rainfall spatial data, it is clearly advisable that any land reforms in the area take into account the benefits of field dispersion to mitigate climatic risk

Prevalence of primary headaches in Germany: results of the German Headache Consortium Study

We investigated the prevalence of migraine (MIG), tension-type headache (TTH), and chronic headache in a population-based sample in Germany. A total of 18,000 subjects aged between 18 and 65 years were screened from 2003 until 2005 using a validated questionnaire. Overall 9,944 participants (55.2%) responded (mean age 43 ± 13.1 years, 52.7% women). Headache frequency <15 days/month was reported by 5,350 (55.5%) subjects of whom 1,601 (16.6%, [95% confidence interval (95% CI): 15.9–17.4]) reported episodic MIG, 1,202 (12.5%, 95% CI 11.8–13.1) episodic TTH, and 1,150 (11.9%, [11.3–12.6]) episodic MIG + episodic TTH, 1,396 (14.5%, [13.8–15.2]) unclassifiable headache. In women, episodic MIG peaked between 36 and 40 years, episodic MIG + TTH between 18 and 35 years and episodic TTH between 56 and 66 years. In men, episodic MIG was predominant between 36 and 45 years, episodic MIG + TTH between 26 and 35 years and episodic TTH showed comparable frequency between 36 and 66 years. Headache ≥15 days/month was reported by 2.6% (n = 255, [95% CI 2.3–3]). Chronic MIG was reported by 1.1% (n = 108, [0.91–1.33]), chronic TTH (n = 50, [95% CI 0.4–0.7]), chronic MIG + TTH 0.8% (n = 74, 95% CI 0.6–0.9) and unclassifiable headache 0.2% (n = 23, [95% CI 0.1–0.3]). Chronic headache was more frequent in women compared to men with the highest prevalence between 46 and 65 years. It is of note that the number of subjects with chronic headache is small in all age groups. The results of our large, population-based study provide reliable, age- and sex-specific estimates of the prevalence of primary headache disorders in Germany. The prevalence with respect to episodic and chronic primary headache disorders in Germany is comparable to other European countries and the USA

Constant activity of glutamine synthetase after morphine administration versus proteomic results

Glutamine synthetase is a key enzyme which has a regulatory role in the brain glutamate pool. According to previously published proteomic analysis, it was shown that the expression level of this enzyme is affected by morphine administration. In our study, we examined the activity of glutamine synthetase in various structures of rat brain (cortex, striatum, hippocampus and spinal cord) that are biochemically and functionally involved in drug addiction and antinociception caused by morphine. We were not able to observe any significant changes in the enzyme activity between morphine-treated and control samples despite previously reported changes in the expression levels of this enzyme. These findings stressed the fact that changes observed in the expression of particular proteins during proteomic studies may not be correlated with its activity

Moths Behaving like Butterflies. Evolutionary Loss of Long Range Attractant Pheromones in Castniid Moths: A Paysandisia archon Model

Background: In the course of evolution butterflies and moths developed two different reproductive behaviors. Whereas butterflies rely on visual stimuli for mate location, moths use the"female calling plus male seduction" system, in which females release long-range sex pheromones to attract conspecific males. There are few exceptions from this pattern but in all cases known female moths possess sex pheromone glands which apparently have been lost in female butterflies. In the day-flying moth family Castniidae ("butterfly-moths"), which includes some important crop pests, no pheromones have been found so far. Methodology/Principal Findings: Using a multidisciplinary approach we described the steps involved in the courtship of P. archon, showing that visual cues are the only ones used for mate location; showed that the morphology and fine structure of the antennae of this moth are strikingly similar to those of butterflies, with male sensilla apparently not suited to detect female-released long range pheromones; showed that its females lack pheromone-producing glands, and identified three compounds as putative male sex pheromone (MSP) components of P. archon, released from the proximal halves of male forewings and hindwings. Conclusions/Significance: This study provides evidence for the first time in Lepidoptera that females of a moth do not produce any pheromone to attract males, and that mate location is achieved only visually by patrolling males, which may release a pheromone at short distance, putatively a mixture of Z,E-farnesal, E,E-farnesal, and (E,Z)-2,13-octadecadienol. The outlined behavior, long thought to be unique to butterflies, is likely to be widespread in Castniidae implying a novel, unparalleled butterfly-like reproductive behavior in moths. This will also have practical implications in applied entomology since it signifies that the monitoring/control of castniid pests should not be based on the use of female-produced pheromones, as it is usually done in many moths

Effects of simulated altitude (normobaric hypoxia) on cardiorespiratory parameters and circulating endothelial precursors in healthy subjects

<p>Abstract</p> <p>Background</p> <p>Circulating Endothelial Precursors (PB-EPCs) are involved in the maintenance of the endothelial compartment being promptly mobilized after injuries of the vascular endothelium, but the effects of a brief normobaric hypoxia on PB-EPCs in healthy subjects are scarcely studied.</p> <p>Methods</p> <p>Clinical and molecular parameters were investigated in healthy subjects (n = 8) in basal conditions (T0) and after 1 h of normobaric hypoxia (T1), with Inspiratory Fraction of Oxygen set at 11.2% simulating 4850 mt of altitude. Blood samples were obtained at T0 and T1, as well as 7 days after hypoxia (T2).</p> <p>Results</p> <p>In all studied subjects we observed a prompt and significant increase in PB-EPCs, with a return to basal value at T2. The induction of hypoxia was confirmed by Alveolar Oxygen Partial Pressure (PAO₂) and Spot Oxygen Saturation decreases. Heart rate increased, but arterial pressure and respiratory response were unaffected. The change in PB-EPCs percent from T0 to T1 was inversely related to PAO₂at T1. Rapid (T1) increases in serum levels of hepatocyte growth factor and erythropoietin, as well as in cellular PB-EPCs-expression of Hypoxia Inducible Factor-1α were observed.</p> <p>Conclusion</p> <p>In conclusion, the endothelial compartment seems quite responsive to standardized brief hypoxia, possibly important for PB-EPCs activation and recruitment.</p

Monte Carlo simulation of signals in digital diaphanoscopy of the maxillary sinuses

Digital diaphanoscopy method has potential to separate normal and pathological conditions of the maxillary sinuses. The entirety of all the features of the investigated area (the presence or absence of pathology, its etiology and morphological features) affects the resulting images of the maxillary sinuses by the digital diaphanoscopy. In this work, the MonteCarlo numerical simulation method was used to determine the patterns of propagation of light radiation in biological tissue. A biologically heterogeneous environment, represented by structures of the skull and maxillary sinuses, as well as pathological changes in them was modelled in the TracePro software

Ginsenoside-Rg1 mediates a hypoxia-independent upregulation of hypoxia-inducible factor-1α to promote angiogenesis

Hypoxia-inducible factor (HIF-1) is the key transcription regulator for multiple angiogenic factors and is an appealing target. Ginsenoside-Rg1, a nontoxic saponin isolated from the rhizome of Panax ginseng, exhibits potent proangiogenic activity and has the potential to be developed as a new angiotherapeutic agent. However, the mechanisms by which Rg1 promotes angiogenesis are not fully understood. Here, we show that Rg1 is an effective stimulator of HIF-1α under normal cellular oxygen conditions in human umbilical vein endothelial cells. HIF-1α steady-state mRNA was not affected by Rg1. Rather, HIF-1α protein synthesis was stimulated by Rg1. This effect was associated with constitutive activation of phosphatidylinositol 3-kinase (PI3K)/Akt and its effector p70 S6 kinase (p70S6K), but not extracellular-signal regulated kinase 1/2. We further revealed that HIF-1α induction triggered the expression of target genes, including vascular endothelial growth factor (VEGF). The use of small molecule inhibitors LY294002 or rapamycin to inhibit PI3K/Akt and p70S6K activities, respectively, resulted in diminished HIF-1α activation and subsequent VEGF expression. RNA interference-mediated knockdown of HIF-1α suppressed Rg1-induced VEGF synthesis and angiogenic tube formation, confirming that the effect was HIF-1α specific. Similarly, the angiogenic phenotype could be reversed by inhibition of PI3K/Akt and p70S6K. These results define a hypoxia-independent activation of HIF-1α, uncovering a novel mechanism for Rg1 that could play a major role in angiogenesis and vascular remodeling

Biosynthesis of Vitamin C by Yeast Leads to Increased Stress Resistance

during respiration, or indirectly-caused by other stressing factors. Vitamin C or L-ascorbic acid acts as a scavenger of ROS, thereby potentially protecting cells from harmful oxidative products. While most eukaryotes synthesize ascorbic acid, yeast cells produce erythro-ascorbic acid instead. The actual importance of this antioxidant substance for the yeast is still a subject of scientific debate. is increased, but also the tolerance to low pH and weak organic acids at low pH is increased. cells endogenously producing vitamin C as a cellular model to study the genesis/protection of ROS as well as genotoxicity