Antioxidants improve vascular function in children conceived by assisted reproductive technologies: A randomized double-blind placebo-controlled trial.

AIMS Children conceived by assisted reproductive technology (ART) display vascular dysfunction. Its underlying mechanism, potential reversibility and long-term consequences for cardiovascular risk are unknown. In mice, ART induces arterial hypertension and shortens the life span. These problems are related to decreased vascular endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) synthesis. The aim of this study was to determine whether ART-induced vascular dysfunction in humans is related to a similar mechanism and potentially reversible. To this end we tested whether antioxidants improve endothelial function by scavenging free radicals and increasing NO bioavailability. METHODS AND RESULTS In this prospective double-blind placebo controlled study in 21 ART and 21 control children we assessed the effects of a four-week oral supplementation with antioxidant vitamins C (1 g) and E (400 IU) or placebo (allocation ratio 2:1) on flow-mediated vasodilation (FMD) of the brachial artery and pulmonary artery pressure (echocardiography) during high-altitude exposure (3454 m), a manoeuver known to facilitate the detection of pulmonary vascular dysfunction and to decrease NO bioavailability by stimulating oxidative stress. Antioxidant supplementation significantly increased plasma NO measured by ozone-based chemiluminescence (from 21.7 ± 7.9 to 26.9 ± 7.6 µM, p = 0.04) and FMD (from 7.0 ± 2.1 to 8.7 ± 2.0%, p = 0.004) and attenuated altitude-induced pulmonary hypertension (from 33 ± 8 to 28 ± 6 mm Hg, p = 0.028) in ART children, whereas it had no detectable effect in control children. CONCLUSIONS Antioxidant administration to ART children improved NO bioavailability and vascular responsiveness in the systemic and pulmonary circulation. Collectively, these findings indicate that in young individuals ART-induced vascular dysfunction is subject to redox regulation and reversible.

Prevention of vascular dysfunction and arterial hypertension in mice generated by assisted reproductive technologies by addition of melatonin to culture media.

Assisted reproductive technologies (ART) induce vascular dysfunction in humans and mice. In mice, ART-induced vascular dysfunction is related to epigenetic alteration of the endothelial nitric oxide synthase (eNOS) gene, resulting in decreased vascular eNOS expression and nitrite/nitrate synthesis. Melatonin is involved in epigenetic regulation, and its administration to sterile women improves the success rate of ART. We hypothesized that addition of melatonin to culture media may prevent ART-induced epigenetic and cardiovascular alterations in mice. We, therefore, assessed mesenteric-artery responses to acetylcholine and arterial blood pressure, together with DNA methylation of the eNOS gene promoter in vascular tissue and nitric oxide plasma concentration in 12-wk-old ART mice generated with and without addition of melatonin to culture media and in control mice. As expected, acetylcholine-induced mesenteric-artery dilation was impaired (P = 0.008 vs. control) and mean arterial blood pressure increased (109.5 ± 3.8 vs. 104.0 ± 4.7 mmHg, P = 0.002, ART vs. control) in ART compared with control mice. These alterations were associated with altered DNA methylation of the eNOS gene promoter (P < 0.001 vs. control) and decreased plasma nitric oxide concentration (10.1 ± 11.1 vs. 29.5 ± 8.0 μM) (P < 0.001 ART vs. control). Addition of melatonin (10(-6) M) to culture media prevented eNOS dysmethylation (P = 0.005, vs. ART + vehicle), normalized nitric oxide plasma concentration (23.1 ± 14.6 μM, P = 0.002 vs. ART + vehicle) and mesentery-artery responsiveness to acetylcholine (P < 0.008 vs. ART + vehicle), and prevented arterial hypertension (104.6 ± 3.4 mmHg, P < 0.003 vs. ART + vehicle). These findings provide proof of principle that modification of culture media prevents ART-induced vascular dysfunction. We speculate that this approach will also allow preventing ART-induced premature atherosclerosis in humans.

Age in antiretroviral therapy programmes in South Africa: a retrospective, multicentre, observational cohort study.

BACKGROUND As access to antiretroviral therapy (ART) expands, increasing numbers of older patients will start treatment and need specialised long-term care. However, the effect of age in ART programmes in resource-constrained settings is poorly understood. The HIV epidemic is ageing rapidly and South Africa has one of the highest HIV population prevalences worldwide. We explored the effect of age on mortality of patients on ART in South Africa and whether this effect is mediated by baseline immunological status. METHODS In this retrospective cohort analysis, we studied HIV-positive patients aged 16-80 years who started ART for the first time in six large South African cohorts of the International Epidemiologic Databases to Evaluate AIDS-Southern Africa collaboration, in KwaZulu-Natal, Gauteng, and Western Cape (two primary care clinics, three hospitals, and a large rural cohort). The primary outcome was mortality. We ascertained patients' vital status through linkage to the National Population Register. We used inverse probability weighting to correct mortality for loss to follow-up. We estimated mortality using Cox's proportional hazards and competing risks regression. We tested the interaction between baseline CD4 cell count and age. FINDINGS Between Jan 1, 2004, and Dec 31, 2013, 84,078 eligible adults started ART. Of these, we followed up 83,566 patients for 174,640 patient-years. 8% (1817 of 23,258) of patients aged 16-29 years died compared with 19% (93 of 492) of patients aged 65 years or older. The age adjusted mortality hazard ratio was 2·52 (95% CI 2·01-3·17) for people aged 65 years or older compared with those 16-29 years of age. In patients starting ART with a CD4 count of less than 50 cells per μL, the adjusted mortality hazard ratio was 2·52 (2·04-3·11) for people aged 50 years or older compared with those 16-39 years old. Mortality was highest in patients with CD4 counts of less than 50 cells per μL, and 15% (1103 of 7295) of all patients aged 50 years or older starting ART were in this group. The proportion of patients aged 50 years or older enrolling in ART increased with successive years, from 6% (290 of 4999) in 2004 to 10% (961 of 9657) in 2012-13, comprising 9% of total enrolment (7295 of 83 566). At the end of the study, 6304 (14%) of 44,909 patients still alive and in care were aged 50 years or older. INTERPRETATION Health services need reorientation towards HIV diagnosis and starting of ART in older individuals. Policies are needed for long-term care of older people with HIV. FUNDING National Institutes of Health (National Institute of Allergy and Infectious Diseases), US Agency for International Development, and South African Centre for Epidemiological Modelling and Analysis.

Environmental correlates of species rank − abundance distributions in global drylands

Theoretical models predict lognormal species abundance distributions (SADs) in stable and productive environments, with log-series SADs in less stable, dispersal driven communities. We studied patterns of relative species abundances of perennial vascular plants in global dryland communities to: (i) assess the influence of climatic and soil characteristics on the observed SADs, (ii) infer how environmental variability influences relative abundances, and (iii) evaluate how colonisation dynamics and environmental filters shape abundance distributions. We fitted lognormal and log-series SADs to 91 sites containing at least 15 species of perennial vascular plants. The dependence of species relative abundances on soil and climate variables was assessed using general linear models. Irrespective of habitat type and latitude, the majority of the SADs (70.3%) were best described by a lognormal distribution. Lognormal SADs were associated with low annual precipitation, higher aridity, high soil carbon content, and higher variability of climate variables and soil nitrate. Our results do not corroborate models predicting the prevalence of log-series SADs in dryland communities. As lognormal SADs were particularly associated with sites with drier conditions and a higher environmental variability, we reject models linking lognormality to environmental stability and high productivity conditions. Instead our results point to the prevalence of lognormal SADs in heterogeneous environments, allowing for more evenly distributed plant communities, or in stressful ecosystems, which are generally shaped by strong habitat filters and limited colonisation. This suggests that drylands may be resilient to environmental changes because the many species with intermediate relative abundances could take over ecosystem functioning if the environment becomes suboptimal for dominant species.

Characterization of the Putative Xyloglucan Glycosyltransferase GT14 in Arabidopsis thaliana

Plant cell walls largely consist of matrix polysaccharides that are linked to cellulose microfibrils. Xyloglucan, the primary hemicellulose of the cell wall matrix, consists of a repeating glucose tetramer structure with xylose residues attached to the first three units ('XXXG'). In Arabidopsis thaliana, the core XXXG structure is further modified by enzymatic addition of galactose and fucose residues to the xylose side chains to produce XLXG, XXLG, XLLG and XLFG structures. GT14 is a putative glycosyltransferase in the GT47 gene family. Initial predictions of GT14's hydrophobic regions, based on its translated amino acid sequence, are almost identical to its Arabidopsis homolog MUR3, which is a xyloglucan galactosyltransferase targeted to the Golgi membrane. This suggests that, like MUR3, GT14 possesses a transmembrane domain and that it is targeted to the Golgi. The monosaccharide composition of leaves from T-DNA insertion knockouts of GT14 was analyzed by gas-liquid chromatography. The gt14 plants were found to have lower fucose and higher mannose contents than wild type plants. Analysis of cell wall and soluble fractions from gt14 and wild type plants revealed that most of the deficiency in fucose was accounted for in the cell wall, supporting the idea that GT14's target is xyloglucan. Finally, gt14 and wild type plants were transformed with GT14 for complementation and overexpression analysis. The majority of transformed plants did not show significant changes with regard to monosaccharide composition. This may be because the plants were in the T1 generation and, thus, hemizygous. Analysis of homozygous plants in the T2 generation may reveal noticeable changes. Further studies on the xyloglucan composition of gt14 plants are necessary to put the observed reduction in cell wall fucose into a meaningful context.

Simple-Offer vs. Complex-Offer Auctions in Deregulated Electricity Markets

In my recent experimental research of wholesale electricity auctions, I discovered that the complex structure of the offers leaves a lot of room for strategic behavior, which consequently leads to anti- competitive and inefficient outcomes in the market. A specific feature of these complex-offer auctions is that the sellers submit not only the quantities and the minimum prices at which they are willing to sell, but also the start-up fees that are designed to reimburse the fixed start-up costs of the generation plants. In this paper, using the experimental method I compare the performance of two complex-offer auctions (COAs) against the performance of a simple-offer auction (SOA), in which the sellers have to recover all their generation costs --- fixed and variable ---through a uniform market-clearing price. I find that the SOA significantly reduces consumer prices and lowers price volatility. It mitigates anti-competitive effects that are present in the COAs and achieves allocative efficiency more quickly.

A comprehensive review of the environmental impacts and human health risks associated with the occurrence of waste pharmaceuticals in water sources of the United States, and policy implications

The occurrence of waste pharmaceuticals has been identified and well documented in water sources throughout North America and Europe. Many studies have been conducted which identify the occurrence of various pharmaceutical compounds in these waters. This project is an extensive review of the documented evidence of this occurrence published in the scientific literature. This review was performed to determine if this occurrence has a significant impact on the environment and public health. This project and review found that pharmaceuticals such as sex hormone drugs, antibiotic drugs and antineoplastic/cytostatic agents as well as their metabolites have been found to occur in water sources throughout the United States at levels high enough to have noticeable impacts on human health and the environment. It was determined that the primary sources of this occurrence of pharmaceuticals were waste water effluent and solid wastes from sewage treatment plants, pharmaceutical manufacturing plants, healthcare and biomedical research facilities, as well as runoff from veterinary medicine applications (including aquaculture). ^ In addition, current public policies of US governmental agencies such as the Environmental Protection Agency (EPA), Food and Drug Administration (FDA), and Drug Enforcement Agency (DEA) have been evaluated to see if they are doing a sufficient job at controlling this issue. Specific recommendations for developing these EPA, FDA, and DEA policies have been made to mitigate, prevent, or eliminate this issue.^ Other possible interventions such as implementing engineering controls were also evaluated in order to mitigate, prevent and eliminate this issue. These engineering controls include implementing improved current treatment technologies such as the advancement and improvement of waste water treatment processes utilized by conventional sewage treatment and pharmaceutical manufacturing plants. In addition, administrative controls such as the use of “green chemistry” in drug synthesis and design were also explored and evaluated as possible alternatives to mitigate, prevent, or eliminate this issue. Specific recommendations for incorporating these engineering and administrative controls into the applicable EPA, FDA, and DEA policies have also been made.^

Effects of endophyte colonization of Vicia faba (Fabaceae) plants on the life

The effects of fungal endophytes Beauveria bassiana isolates ICIPE 279, G1LU3, S4SU1 and Hypocrea lixii isolate F3ST1 on the life-history of Phaedrotoma scabriventris and Diglyphus isaea, parasitoids of the pea leafminer Liriomyza huidobrensis, were studied in the laboratory. Parasitoids were allowed to parasitize 2nd-3rd L. huidobrensis larvae reared on endophytically-inoculated Vicia faba. In the control, parasitoids were reared on non-inoculated host plants. Parasitism, pupation, adult emergence and survival were recorded. No significant difference was observed between the control and the endophyte-inoculated plants in terms of parasitism rates of P. scabriventris (p = 0.68) and D. isaea (p = 0.45) and adult' survival times (p = 0.06). The survival period of the F1 progeny of P. scabriventris was reduced (p < 0.0001) in B. bassiana S4SU1 to 28 days as compared to more than 40 days for B. bassiana G1LU3, ICIPE 279 and H. lixii F3ST1. However, no significant difference (p = 0.54) was observed in the survival times of the F1 progeny of D. isaea. This study has therefore demonstrated the beneficial effects of both endophytes and parasitoids in L. huidobrensis population suppression.

(Table 1) Chlorophyll concentration and pigment composition of carotenoids in three heathland bryophytes, northern Sweden

Background and Aims: Anthropogenic depletion of stratospheric ozone in Arctic latitudes has resulted in an increase of ultraviolet-B radiation (UV-B) reaching the biosphere. UV-B exposure is known to reduce aboveground biomass and plant height, to increase DNA damage and cause accumulation of UV-absorbing compounds in polar plants. However, many studies on Arctic mosses tended to be inconclusive. The importance of different water availability in influencing UV-B impacts on lower plants in the Arctic has been poorly explored and might partially explain the observed wide variation of responses, given the importance of water in controlling bryophyte physiology. This study aimed to assess the long-term responses of three common sub-Arctic bryophytes to enhanced UV-B radiation (+UV-B) and to elucidate the influence of water supply on those responses. Results: Responses were species specific: H. splendens responded most to +UV-B, with reduction in both annual growth (-22%) and sporophyte production (-44%), together with increased b-carotene, violaxanthin, total chlorophyll and NPQ, and decreased zeaxanthin and de-epoxidation of the xanthophyll cycle pool (DES). Barbilophozia lycopodioides responded less to +UV-B, showing increased b-carotene and sclerophylly and decreased UV-absorbing compounds. Polytrichum commune only showed small morphogenetic changes. No effect of UV-B on bryophyte cover was observed. Water availability had profound effects on bryophyte ecophysiology, and plants showed, in general, lower growth and ETR, together with a higher photoprotection in the drier site. Water availability also influenced bryophyte responses to +UV-B and, in particular, responses were less detectable in the drier site. Conclusions: Impacts of UV-B exposure on Arctic bryophytes were significant, in contrast to modest or absent UV-B effects measured in previous studies. The impacts were more easily detectable in species with high plasticity such as H. splendens and less obvious, or more subtle, under drier conditions. Species biology and water supply greatly influences the impact of UV-B on at least some Arctic bryophytes and could contribute to the wide variation of responses observed previously.

Differential in vitro and in vivo effect of barley cysteine and serine protease inhibitors on phytopathogenic microorganisms

Protease inhibitors from plants have been involved in defence mechanisms against pests and pathogens. Phytocystatins and trypsin/α-amylase inhibitors are two of the best characterized protease inhibitor families in plants. In barley, thirteen cystatins (HvCPI-1 to 13) and the BTI-CMe trypsin inhibitor have been previously studied. Their capacity to inhibit pest digestive proteases, and the negative in vivo effect caused by plants expressing these inhibitors on pests support the defence function of these proteins. Barley cystatins are also able to inhibit in vitro fungal growth. However, the antifungal effect of these inhibitors in vivo had not been previously tested. Moreover, their in vitro and in vivo effect on plant pathogenous bacteria is still unknown. In order to obtain new insights on this feature, in vitro assays were made against different bacterial and fungal pathogens of plants using the trypsin inhibitor BTI-CMe and the thirteen barley cystatins. Most barley cystatins and the BTI-CMe inhibitor were able to inhibit mycelial growth but no bacterial growth. Transgenic Arabidopsis plants independently expressing the BTI-CMe inhibitor and the cystatin HvCPI-6 were tested against the same bacterial and fungal pathogens. Neither the HvCPI-6 expressing transgenic plants nor the BTI-CMe ones were more resistant to plant pathogen fungi and bacteria than control Arabidopsis plants. The differences observed between the in vitro and in planta assays against phytopathogenic fungi are discussed

Helping to Close the Generational Gap in Nuclear: The Seminars and Conferences of Spanish Young Generation in Nuclear (Jóvenes Nucleares)

As in each country of Europe with nuclear power, there is a clear gap between those generation that have built the power plants in the eighties and the new generations with less than ten years of experience in the nuclear field. From its creation, Spanish Young Generation in Nuclear (Jóvenes Nucleares) has as an important scope to help transferring the knowledge between those generations in the way that it can be possible. Some years ago, JJNN have started organizing seminars periodically trying to cover as many areas as possible in the nuclear engineering field, and some of them outside the industry but related with it.

Automatic segmentation of relevant textures in agricultural images

One important issue emerging strongly in agriculture is related with the automatization of tasks, where the optical sensors play an important role. They provide images that must be conveniently processed. The most relevantimage processing procedures require the identification of green plants, in our experiments they come from barley and corn crops including weeds, so that some types of action can be carried out, including site-specific treatments with chemical products or mechanical manipulations. Also the identification of textures belonging to the soil could be useful to know some variables, such as humidity, smoothness or any others. Finally, from the point of view of the autonomous robot navigation, where the robot is equipped with the imaging system, some times it is convenient to know not only the soil information and the plants growing in the soil but also additional information supplied by global references based on specific areas. This implies that the images to be processed contain textures of three main types to be identified: green plants, soil and sky if any. This paper proposes a new automatic approach for segmenting these main textures and also to refine the identification of sub-textures inside the main ones. Concerning the green identification, we propose a new approach that exploits the performance of existing strategies by combining them. The combination takes into account the relevance of the information provided by each strategy based on the intensity variability. This makes an important contribution. The combination of thresholding approaches, for segmenting the soil and the sky, makes the second contribution; finally the adjusting of the supervised fuzzy clustering approach for identifying sub-textures automatically, makes the third finding. The performance of the method allows to verify its viability for automatic tasks in agriculture based on image processing

LHPP, the light-harvesting NADPH:protochlorophyllide (Pchlide) oxido¬reductase:Pchlide complex of etiolated plants, is developmentally expressed across the barley leaf gradient

NADPH:protochlorophyllide oxidoreductase is a key enzyme for the light-induced greening of etiolated angiosperm plants. In barley, two POR proteins exist termed PORA and PORB that have previously been proposed to structurally and functionally cooperate in terms of a higher molecular mass light-harvesting complex named LHPP, in the prolamellar body of etioplasts [Nature 397 (1999) 80]. In this study we examined the expression pattern of LHPP during seedling etiolation and de-etiolation under different experimental conditions. Our results show that LHPP is developmentally expressed across the barley leaf gradient. We further provide evidence that LHPP operates both in plants that etiolate completely before being exposed to white light and in plants that etiolate only partially and begin light-harvesting as soon as traces of light become available in the uppermost parts of the soil. As a result of light absorption, in either case LHPP converts Pchlide a to chlorophyllide (Chlide) a and in turn disintegrates. The released Chlide a, as well as Chlide b produced upon LHPP’s light-dependent dissociation, which leads to the activation of the PORA as a Pchlide b-reducing enzyme, then bind to homologs of water-soluble chlorophyll proteins of Brassicaceae. We propose that these proteins transfer Chlide a and Chlide b to the thylakoids, where their esterification with phytol and assembly into the photosynthetic membrane complexes ultimately takes place. Presumably due to the tight coupling of LHPP synthesis and degradation, as well as WSCP formation and photosynthetic membrane assembly, efficient photo-protection is conferred onto the plant.