Formation of eicosanoids, E2/D2 isoprostanes, and docosanoids following decapitation-induced ischemia, measured in high-energy-microwaved rat brain

Inflammatory lipid mediators derived from arachidonic acid (AA) and docosahexaenoic acid (DHA) modify the pathophysiology of brain ischemia. The goal of this work was to investigate the formation of eicosanoids and docosanoids generated from AA and DHA, respectively, during no-flow cerebral ischemia. Rats were subjected to head-focused microwave irradiation 5 min following decapitation (complete ischemia) or prior to decapitation (controls). Brain lipids were extracted and analyzed by reverse-phase liquid chromatography-tandem mass spectrometry. After complete ischemia, brain AA, DHA, and docosapentaenoic acid concentrations increased 18-, 5- and 4-fold compared with controls, respectively. Prostaglandin E(2) (PGE(2)) and PGD(2) could not be detected in control microwaved rat brain, suggesting little endogenous PGE(2)/D(2) production in the brain in the absence of experimental manipulation. Concentrations of thromboxane B(2), E(2)/D(2)-isoprostanes, 5-hydroxyeicosatetraenoic acid (5-HETE), 5-oxo-eicosatetraenoic acid, and 12-HETE were significantly elevated in ischemic brains. In addition, DHA products such as mono-, di- and trihydroxy-DHA were detected in control and ischemic brains. Monohydroxy-DHA, identified as 17-hydroxy-DHA and thought to be the immediate precursor of neuroprotectin D(1), was 6.5-fold higher in ischemic than in control brain. The present study demonstrated increased formation of eicosanoids, E(2)/D(2)-IsoPs, and docosanoids following cerebral ischemia. A balance of these lipid mediators may mediate immediate events of ischemic injury and recovery.     

Microhabitat amelioration and reduced competition among understorey plants as drivers of facilitation across environmental gradients: Towards a unifying framework

Studies of facilitative interactions as drivers of plant richness along environmental gradients often assume the existence of an overarching stress gradient that equally affects the performance of all the species in a given community. However, co-existing species differ in their ecophysiological adaptations, and do not experience the same stress level under particular environmental conditions. Moreover, these studies assume a unimodal relationship between richness and biomass, which is not as general as previously thought. We ignored these assumptions to assess changes in plant–plant interactions and their effect on local species richness across environmental gradients in semi-arid areas of Spain and Australia. We aimed to understand the relative importance of direct (microhabitat amelioration) and indirect (changes in the competitive relationships among the understorey species: niche segregation, competitive exclusion or intransitivity) mechanisms that might underlie the effects of nurse plants on local species richness. By jointly studying these direct and indirect mechanisms using a unifying framework, we found that nurse plants (trees, shrubs and tussock grasses) increased local richness not only by expanding the niche of neighbouring species but also by increasing niche segregation among them, though the latter was not important in all cases. The outcome of the competition-facilitation continuum varied depending on the study area, likely because the different types of stress gradient considered. When driven by both rainfall and temperature, or rainfall alone, the community-wide importance of nurse plants remained constant (Spanish sites), or showed a unimodal relationship along the gradient (Australian sites). This study expands our understanding of the relative roles of plant–plant interactions and environmental conditions as drivers of local species richness in semi-arid environments. The results can also be used to refine predictions about the response of plant communities to environmental change, and to clarify the relative importance of biotic interactions as drivers of such responses.     

Chestnut cultivar diversification process in the Iberian Peninsula, Canary Islands, and Azores

This is a large-scale molecular study based on simple sequence repeat (SSR) loci of the diversification process in chestnut cultivars from Portugal and Spain, from the northern Iberian Peninsula to the Canary Islands and the Azores. A total of 593 grafted chestnut trees (Castanea sativa Mill.) were analysed with 10 SSRs: 292 from Portugal and 301 from Spain. Some of the trees studied were more than 300 years old. Accessions were analysed using a model-based Bayesian procedure to assess the geographical structure and to assign individuals to reconstructed populations based on the SSR genotypes. We found 356 different genotypes with a mean value of clonality of 33% owing to grafting. Mutations accounted for 6%, with hybridization being the main diversification process that can explain the great diversity found. Ten main cultivar groups were detected: four in northern Spain, five in the centre of the Iberian Peninsula, and one in southern Spain related to the centre of the Iberian Peninsula. This work demonstrated that cultivar origin and the diversification process was a combination of clonal propagation of selected seedlings, hybridization, and mutations, which allowed high levels of diversity to be maintained with respect to selected clones for fruit production. Furthermore, seedlings and graft sticks facilitated the transport to new destinations in the colonization process, transporting sometimes more than 3000 km if we consider the Azores and the Canary Islands.     

Molecular modeling of glycosyltransferases involved in the biosynthesis of blood group A,blood group B,Forssman, and iGb3 antigens and their interaction with substrates

A terminal alpha1-3 linked Gal or GalNAc sugar residue is the common structure found in several oligosaccharide antigens, such as blood groups A and B, the xeno-antigen, the Forssman antigen, and the isogloboside 3 (iGb3) glycolipid. The enzymes involved in the addition of this residue display strong amino acid sequence similarities, suggesting a common fold. From a recently solved crystal structure of the bovine alpha3-galactosyltransferase complexed with UDP, homology modeling methods were used to build the four other enzymes of this family in their locked conformation. Nucleotide-sugars, the Mn2+ ion, and oligosaccharide acceptors were docked in the models. Nine different amino acid regions are involved in the substrate binding sites. After geometry optimization of the complexes and analysis of the predicted structures, the basis of the specificities can be rationalized. In the nucleotide-sugar binding site, the specificity between Gal or GalNAc transferase activity is due to the relative size of two clue amino acids. In the acceptor site, the presence of up to three tryptophan residues define the complexity of the oligosaccharide that can be specifically recognized. The modeling study helps in rationalizing the crystallographic data obtained in this family and provides insights on the basis of substrate and donor recognition.     

The causes of epistasis in genetic networks

Epistasis refers to the nonadditive interactions between genes in determining phenotypes. Considerable efforts have shown that, even for a given organism, epistasis may vary both in intensity and sign. Recent comparative studies supported that the overall sign of epistasis switches from positive to negative as the complexity of an organism increases, and it has been hypothesized that this change shall be a consequence of the underlying gene network properties. Why should this be the case? What characteristics of genetic networks determine the sign of epistasis? Here we show, by evolving genetic networks that differ in their complexity and robustness against perturbations but that perform the same tasks, that robustness increased with complexity and that epistasis was positive for small nonrobust networks but negative for large robust ones. Our results indicate that robustness and negative epistasis emerge as a consequence of the existence of redundant elements in regulatory structures of genetic networks and that the correlation between complexity and epistasis is a byproduct of such redundancy, allowing for the decoupling of epistasis from the underlying network complexity.     

Actualización en el manejo de la degeneración macular asociada a la edad

Age-related macular degeneration is the leading cause of legal blindness in people over 50 in developed countries. It is a multifactorial disease resulting from the interaction of genetic and environmental factors, and the age is the only worldwide admitted risk factor. The socioeconomic impact of the disease reaches enormous proportions, if we take into account the high cost of the available antiangiogenic therapy, the strict schedule of medical visits that it requires, and the impairment that it gives rise to. The response to treatment and the visual outcomes improve with early management of the retinal lesions, thus the early diagnosis of the disease in its initial phases, based on self-control with an Amsler grid and with regular ophthalmologic assessments, is essential.     

Prevalence and risk factors of vertebral compression fractures in female SLE patients

Introduction

The present study objective was to evaluate the incidence of methotrexate (MTX)-specific liver lesions from the analysis of a liver biopsy of inflammatory arthritis patients with elevated liver enzymes.

Methods

A case-control study was performed with 1,571 arthritis patients on long-term low-dose MTX therapy. Results of liver biopsy were analyzed in 41 patients with elevated liver enzymes. The expression of autoimmune markers was also assessed. This population was compared with 41 disease control subjects obtained from the same database, also on MTX but without elevated liver enzymes, matched for age, sex and rheumatic disease.

Results

Compared with the disease controls, patients with liver biopsy showed lower disease duration and lower MTX exposure, weekly and cumulative doses, reflecting shorter treatment duration due to liver abnormalities. Liver biopsies showed 17 autoimmune hepatitis-like (AIH-like) lesions, 13 nonalcoholic steatohepatitis-like lesions, seven limited liver lesions, and two primary biliary cirrhoses. However, MTX-specific lesions with dystrophic nuclei in hepatocytes were seen in only two cases. Liver biopsy lesions were associated with autoimmune markers (P = 0.007); notably, AIH-like lesions were associated with rheumatoid arthritis and with the presence of the HLA-DR shared epitope.

Conclusions

MTX-specific liver lesions are rarely observed in arthritis patients under long-term MTX therapy and elevated liver enzymes.     

Variation of heartwood and sapwood in 18-year-old Eucalyptus globulus trees grown with different spacings

Heartwood and sapwood development was studied in 18-year-old Eucalyptus globulus trees from pulpwood plantations with different spacings (3 × 2, 3 × 3, 4 × 3, 4 × 4 and 4 × 5 m), on cross-sectional discs taken at breast height. The trees possessed a large proportion of heartwood, on average 60% of the wood cross-sectional surface. Spacing was a statistically significant source of variation of heartwood area, which ranged between 99 and 206 cm² for the closer (3 × 2) and wider (4 × 5) spacings, respectively. There was a positive and high statistical significant correlation between heartwood diameter and tree diameter (heartwood diameter = −0.272 + 0.616 dbh; r ² = 0.77; P < 0.001), and larger trees contained more heartwood regardless of spacing. Heartwood proportion in cross-section remained practically constant between spacings but increased with tree diameter class: 55.1, 62.2, 65.0 and 69.5% for diameter at breast height classes <15, 15–20, 20–25 and >25 cm, respectively. The sapwood width did not depend on tree diameter growth and remained practically constant at an average of 18 mm (range 15–21 mm), but sapwood area showed a good linear regression with tree diameter. Therefore, tree growth enhancement factors, such as wide spacings, will induce formation of larger heartwoods that can negatively impact raw-material quality for pulping. The increase in heartwood in relation with tree dimensions should therefore be taken into account when designing forest management guidelines.