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.

Picea abies in Europe: distribution, habitat, usage and threats

Among the coniferous species, Norway spruce (Picea abies (L.) Karst.) is one of the most important trees in Europe both for economic and ecological aspects, with a long tradition of cultivation. It can be a big tree, reaching 50-60 m in height with a straight and regular trunk, particularly used for timber constructions, pulpwood for paper and furniture. This widespread species dominates the Boreal forests in Northern Europe and the subalpine areas of the Alps and Carpathian Mountains. Thanks to its high performances in different site conditions, it can also be found outside its natural distribution on lower elevations in more temperate forests. Norway spruce has been massively planted up to its niche limits, where it is particularly susceptible to heat and drought, due to its shallow root system. For this reason it is expected to be severely affected under global warming conditions. Disturbed and weakened plants can be easily attacked by rot fungi such as Heterobasidion annosum and Armillaria, or by the bark beetles Ips typographus, one of the most destructive spruce forest pests.

Cutting Arcs For Torus Links And Trees

Among all torus links, we characterise those arising as links of simple plane curve singularities by the property that their fibre surfaces admit only a finite number of cutting arcs that preserve fibredness. The same property allows a characterisation of Coxeter-Dynkin trees (i.e., An , Dn , E6 , E7 and E8 ) among all positive tree-like Hopf plumbings.

Primary lowland dipterocarp forest at Danum Valley, Sabah, Malaysia. Species composition and patterns in the understorey

The spatial distributions of species of tree ≥10 cm gbh were examined in two 4 ha plots and related to the local variation in topography and soil chemistry. The plots were similar in their species composition, particularly in terms of the densities of small trees, and they showed very similar edaphic characteristics. Size class distributions varied little within and between plots. Ordination of 0.25 ha subplots highlighted parallel gradients in the vegetation of both plots when the densities of trees ≥10 cm gbh were considered. Focusing on understorey trees in the 10-<50 cm gbh class at the 0.04 ha subplot scale showed a similar vegetation gradient in both plots closely associated with change from lower slope to ridge. No relationship with soil chemistry was found. On the ridges a special group of understorey species formed clumps and these species contributed importantly to the ordinations. Borneo has a regional history of occasionally severe droughts. It is suggested here that the observed patterns in the understorey are due to differential responses to low soil water supply, the ridges probably tending to dryness more than the lower slopes. Within the large and diverse family Euphorbiaceae, which dominates the understorey at Danum, there may be ecophysiological groupings of species. The long-term effects of disturbance interacting with local edaphic factors on forest structure and composition are discussed.

Pollen record from Golkow, Poland

Janczyk-Kopikowa (1966): The series of the organic deposits, developed in the vicinity of Golkow near Warsaw as oil shales and peats, was laid down in a grough valley and now rests on the deposits of the Middle Polish Glaciation (Riss). The organic deposits are overlain by the fluviale deposits of the North Polish Glaciation (Würm). The locality Golkow occurs beyond the extent of the continental glacier of this glaciation. Polen analysis completed by microfloristic examinations allows to determine the age of the organic series that is thought to be Eemian. The pollen diagram from Golkow does not call in question the stratigraphical position of the deposits investigated mainly due to its characteristic features such as minimum content of coniferous trees in the climatic optimum - about 5%, high percentage of Corylus - 77.5% and well developed phase of hornbeam. It may be well compared with other Eemian diagrams from the area of Poland and reveals much similar features. The development of vegetation at Golkow has depended upon the prevailing climate. At first, the cool climate brings about the development of plants having small thermal requirements. Here belong thin, park-like forests with pine and birch (Pinus, Betula) accompanied by the heliophilic plants such as Hippohäe and Ephedra. Improvement of climate that becomes warm and humid provides for development of deciduous forests prevailing in the climatic optimum, of the interglacial. Decrease of temperature causes a repeated change in the type of forest. This latter changes into coniferous forest with prevailing spruce (Picea) and fir (Abies) at the beginning, and then with pine (Pinus) and birch (Betula). During the Eemian Interglacial, the development of plants at Golkow terminates with a new and long-lasting predominance of pine-birch forests. However, such a longevity may be apparent only. Apparent character of this phenomenon is proved by a fact that the pollen spectra of the warm climatic periods have found their reflex in the oil shale that increased considerably slower than the layers off feebly decomposed peat evidencing the existence of cool pine-birch forests from the decline of the Interglacial. The water basin, in which the polen grains were laid down from surrounding plants is characterized by a calm sedimentation as proved by the occurrence of the oil shale. An insignificant water flow left behind some thin sand laminae. The not too deep basin becomes shallower owing to the growing water vegetation, and marshy vegetation. The growing of the plants causes a complete shallowing of the basin and formation of peat bog in situ, as proved by the peat beds occurring in the section. ---- Gadomska (1966): In the vicinity of Golków a series of organic deposits occurs amounting to 6.5-9.3 m in thickness, and consisting of oil shales, lacustrine silts and sands, as well as peats and peaty silts. The organic deposits fill up an old, small, but fairly deep lake basin, probably of finger-lake origin. It may be seen to-day as a slight lowering of the relief, filled up with soaked ground, stretching from north to south. On the basis of palaeobotanical examinations the organic deposits considered are of Eemian Interglacial age (Z. Janczyk-Kopikowa, 1063). The lower part of the organic series consists of a compact oil shale horizon, the maximum thickness of which may attain up to 8 m. The oil shales contain particularly in their upper part, numerous intercalations of arenaceous silts, dark grey or black in colour, or of sands mainly of lacustrine provenance. At the top of the oil shales are found peats, up to 2.5 m in thickness, covered by black, humus silts with numerous plant remains. The Eemian Interglacial deposits are covered by a series of fluviatile sands belonging partly to the Baltic Glaciation (bottom part of the series), partly to the Holocene (top part of the series). The thickness of the sands is 0.5-3.7 m. Higher up, there are found the Holocene and present-day deposits developed as clayey alluvion, or arenaceous slide rocks, or arenaceous-silty soil.

Palynology and radiocarbon dating on sediment profile PG1756 from Lake Billyakh, NE Siberia, Russia

In this study a radiocarbon-dated pollen record from Lake Billyakh (65°17'N, 126°47'E; 340 m a.s.l.) in the Verkhoyansk Mountains was used to reconstruct vegetation and climate change since about 15 kyr BP (1 kyr=1000 cal. yr). The pollen record and pollen-based biome reconstruction suggest that open cool steppe and grass and sedge tundra communities with Poaceae, Cyperaceae, Artemisia, Chenopodiaceae, Caryophyllaceae and Selaginella rupestris dominated the area from 15 to 13.5 kyr BP. On the other hand, the constant presence of Larix pollen in quantities comparable to today's values points to the constant presence of boreal deciduous conifer trees in the regional vegetation during the last glaciation. A major spread of shrub tundra communities, including birch (Betula sect. Nanae), alder (Duschekia fruticosa) and willow (Salix) species, is dated to 13.5-12.7 kyr BP, indicating a noticeable increase in precipitation toward the end of the last glaciation, particularly during the Allerød Interstadial. Between 12.7 and 11.4 kyr BP pollen percentages of herbaceous taxa rapidly increased, whereas shrub taxa percentages decreased, suggesting strengthening of the steppe communities associated with the relatively cold and dry Younger Dryas Stadial. However, the pollen data in hand indicate that Younger Dryas climate was less severe than the climate during the earlier interval from 15 to 13.5 kyr BP. The onset of the Holocene is marked in the pollen record by the highest values of shrub and lowest values of herbaceous taxa, suggesting a return of warmer and wetter conditions after 11.4 kyr BP. Percentages of tree taxa increase gradually and reach maximum values after 7 kyr BP, reflecting the spread of boreal cold deciduous and taiga forests in the region. An interval between 7 and 2 kyr BP is noticeable for the highest percentages of Scots spine (Pinus subgen. Diploxylon), spruce (Picea) and fir (Abies) pollen, indicating mid-Holocene spread of boreal forest communities in response to climate amelioration and degradation of the permafrost layer.

DNA alignment and Bayesian trees of partial sequences of COI, COIII and the haemocyanin functional unit f-g of 28 octopod species

Background: Octopods have successfully colonised the world's oceans from the tropics to the poles. Yet, successful persistence in these habitats has required adaptations of their advanced physiological apparatus to compensate impaired oxygen supply. Their oxygen transporter haemocyanin plays a major role in cold tolerance and accordingly has undergone functional modifications to sustain oxygen release at sub-zero temperatures. However, it remains unknown how molecular properties evolved to explain the observed functional adaptations. We thus aimed to assess whether natural selection affected molecular and structural properties of haemocyanin that explains temperature adaptation in octopods. Results: Analysis of 239 partial sequences of the haemocyanin functional units (FU) f and g of 28 octopod species of polar, temperate, subtropical and tropical origin revealed natural selection was acting primarily on charge properties of surface residues. Polar octopods contained haemocyanins with higher net surface charge due to decreased glutamic acid content and higher numbers of basic amino acids. Within the analysed partial sequences, positive selection was present at site 2545, positioned between the active copper binding centre and the FU g surface. At this site, methionine was the dominant amino acid in polar octopods and leucine was dominant in tropical octopods. Sites directly involved in oxygen binding or quaternary interactions were highly conserved within the analysed sequence. Conclusions: This study has provided the first insight into molecular and structural mechanisms that have enabled octopods to sustain oxygen supply from polar to tropical conditions. Our findings imply modulation of oxygen binding via charge-charge interaction at the protein surface, which stabilize quaternary interactions among functional units to reduce detrimental effects of high pH on venous oxygen release. Of the observed partial haemocyanin sequence, residue 2545 formed a close link between the FU g surface and the active centre, suggesting a role as allosteric binding site. The prevalence of methionine at this site in polar octopods, implies regulation of oxygen affinity via increased sensitivity to allosteric metal binding. High sequence conservation of sites directly involved in oxygen binding indicates that functional modifications of octopod haemocyanin rather occur via more subtle mechanisms, as observed in this study.

Dendritic-Like Reliable Computation in Artificial Neurons

Dendritic computation is a term that has been in neuro physiological research for a long time [1]. It is still controversial and far for been clarified within the concepts of both computation and neurophysiology [2], [3]. In any case, it hasnot been integrated neither in a formal computational scheme or structure, nor into formulations of artificial neural nets. Our objective here is to formulate a type of distributed computation that resembles dendritic trees, in such a way that it shows the advantages of neural network distributed computation, mostly the reliability that is shown under the existence of holes (scotomas) in the computing net, without ?blind spots?.

Local variability of serotinous cones in a Canary Island pine (Pinus canariensis) stand

The endemic Canary Island pine (Pinus canariensis) has an effective strategy to counteract fire disturbance in the short term. It has a mixed strategy that combines the presence of serotinous cones and thick barks with the ability to re-sprout from the trunk after a fire, a rare trait in pine species. High frequency of fires in the Canary Islands is related to human action, as natural fires by lightning or vulcan activity have very low frequency; hence, the how and whys of the presence of serotinous cones in the species is still a topic of debate. Previous studies showed that the frequency of serotinous cones varies from stand to stand. Here, we analyzed the presence of serotinous cones at a local scale. We selected a Canary Island pine stand in the transition zone between dry and humid forests in the south of Tenerife. Branches were pruned from 20 trees in order to evaluate the presence of serotinous vs. non-serotinous cones by direct verticile counting on the branches. The opening temperature of serotinous cones was assessed in the laboratory. Percentages of serotinous vs. non-serotinous cones varied from 0 to 93 %, showing high variability between trees. Opening temperatures were very high (above 65 ºC) as compared to other Mediterranean pine species with serotinous cones

Non-destructive measurement techniques for taper equation development: a study case in the Spanish Northern Iberian Range

In recent years, the technology for measuring the diameter and height of standing trees has improved significantly. These enhancements allow estimation of the volume of standing trees using stem taper equations, which traditionally have been constructed with data from felled trees, in an accurate and economically feasible way. A nondestructive method was evaluated with data from 38 pines and was validated with data from another 38 pines, both in the Northern Iberian Range (Spain). The electronic dendrometer Criterion RD1000 (Laser Technology Inc.) and the laser hypsometer TruPulse (Laser Technology Inc.) were used due to their accuracy and interoperability. The methodology was valid (unbiased and precise) measuring from a distance similar to the height of the tree. In this distance, statistical criteria and plots based on the residuals showed no clear advantage in volume estimation with models fitted with data from destructive methods against models fitted with data from the proposed non-destructive technique. This methodology can be considered useful for individual volume estimation and for developing taper equations.

Teaching art and history to photonics students

The case to be reported in this paper is the teaching of topics involving the relation among Photonics, its history, the international situation and the artistic movements in each period. These kind of new studies correspond to a new tendency in teaching interdisciplinary topics to students coming from different areas. Two main courses, one in History and other one in Art, will be taken as examples. Theses two courses have been taught for several years in Madrid, Spain, for Telecomm students and the results have been very satisfactory