Segregation of regulatory polymorphisms with effects on the gluteus medius transcriptome in a purebred pig population

Background: The main goal of the present study was to analyse the genetic architecture of mRNA expression in muscle, a tissue with an outmost economic importance for pig breeders. Previous studies have used F2 crosses to detect porcine expression QTL (eQTL), so they contributed with data that mostly represents the between-breed component of eQTL variation. Herewith, we have analysed eQTL segregation in an outbred Duroc population using two groups of animals with divergent fatness profiles. This approach is particularly suitable to analyse the within-breed component of eQTL variation, with a special emphasis on loci involved in lipid metabolism. Methodology/Principal Findings: GeneChip Porcine Genome arrays (Affymetrix) were used to determine the mRNA expression levels of gluteus medius samples from 105 Duroc barrows. A whole-genome eQTL scan was carried out with a panel of 116 microsatellites. Results allowed us to detect 613 genome-wide significant eQTL unevenly distributed across the pig genome. A clear predominance of trans- over cis-eQTL, was observed. Moreover, 11 trans-regulatory hotspots affecting the expression levels of four to 16 genes were identified. A Gene Ontology study showed that regulatory polymorphisms affected the expression of muscle development and lipid metabolism genes. A number of positional concordances between eQTL and lipid trait QTL were also found, whereas limited evidence of a linear relationship between muscle fat deposition and mRNA levels of eQTL regulated genes was obtained. Conclusions/Significance: Our data provide substantial evidence that there is a remarkable amount of within-breed genetic variation affecting muscle mRNA expression. Most of this variation acts in trans and influences biological processes related with muscle development, lipid deposition and energy balance. The identification of the underlying causal mutations and the ascertainment of their effects on phenotypes would allow gaining a fundamental perspective about how complex traits are built at the molecular level.

HIV-1 immune activation induces Siglec-1 expression and enhances viral trans-infection in blood and tissue myeloid cells.

BACKGROUND: Myeloid cells are key players in the recognition and response of the host against invading viruses. Paradoxically, upon HIV-1 infection, myeloid cells might also promote viral pathogenesis through trans-infection, a mechanism that promotes HIV-1 transmission to target cells via viral capture and storage. The receptor Siglec-1 (CD169) potently enhances HIV-1 trans-infection and is regulated by immune activating signals present throughout the course of HIV-1 infection, such as interferon α (IFNα). RESULTS: Here we show that IFNα-activated dendritic cells, monocytes and macrophages have an enhanced ability to capture and trans-infect HIV-1 via Siglec-1 recognition of viral membrane gangliosides. Monocytes from untreated HIV-1-infected individuals trans-infect HIV-1 via Siglec-1, but this capacity diminishes after effective antiretroviral treatment. Furthermore, Siglec-1 is expressed on myeloid cells residing in lymphoid tissues, where it can mediate viral trans-infection. CONCLUSIONS: Siglec-1 on myeloid cells could fuel novel CD4(+) T-cell infections and contribute to HIV-1 dissemination in vivo.

Composição de carotenoides em passifloras do cerrado

O objetivo foi avaliar, por HPLC, a composição qualitativa e quantitativa de carotenoides em maracujás do cerrado. Frutos procedentes de acessos nativos de quatro espécies (Passiflora cincinnata, P. nitida, P. setacea e P. edulis) foram analisados, utilizando, como referência, o maracujá-amarelo comercial (P. edulis). As polpas de maracujá apresentaram neoxantina, violaxantina, cis-violaxantina, anteraxantina, luteína, zeaxantina, β-criptoxantina, poli-cis-caroteno, prolicopeno, cis-ζ-caroteno, trans-ζ-caroteno, trans-β-caroteno, 13-cis-β-caroteno e fitoflueno. Em geral, os teores de carotenoides entre as espécies e entre os acessos da mesma espécie foram significativamente diferentes. A espécie P. edulis apresentou o maior número de carotenoides, com diferença entre os acessos. Em um acesso de P. edulis comercial, foi encontrado o trans-β-caroteno como o carotenoide principal (7,8±0,8 µg g-1) e no outro o trans-ζ-caroteno (11,4±0,4 µg g-1). Dois acessos de P. edulis nativos do Cerrado apresentaram cis-ζ-caroteno como carotenoide majoritário (6,28±0,15 µg g-1 e 12,1±0,7 µg g-1, casca amarela e roxa, respectivamente). O perfil de carotenoides em frutos de espécies de maracujá apresentou diversidade de composição, com potencial de uso para melhoramento genético para agregar maior valor ao produto e estimular o seu consumo.

Concentrations of resveratrol and derivatives in foods and estimation of dietary intake in a Spanish population: European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort

Resveratrol has been shown to have beneficial effects on diseases related to oxidant and/or inflammatory processes and extends the lifespan of simple organisms including rodents. The objective of the present study was to estimate the dietary intake of resveratrol and piceid (R&P) present in foods, and to identify the principal dietary sources of these compounds in the Spanish adult population. For this purpose, a food composition database (FCDB) of R&P in Spanish foods was compiled. The study included 40 685 subjects aged 35-64 years from northern and southern regions of Spain who were included in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort. Usual food intake was assessed by personal interviews using a computerised version of a validated diet history method. An FCDB with 160 items was compiled. The estimated median and mean of R&P intake were 100 and 933 mg/d respectively. Approximately, 32% of the population did not consume RΠ The most abundant of the four stilbenes studied was trans-piceid (53·6 %), followed by trans-resveratrol (20·9 %), cis-piceid (19·3 %) and cis-resveratrol (6·2 %). The most important source of R&P was wines (98·4 %) and grape and grape juices (1·6 %), whereas peanuts, pistachios and berries contributed to less than 0·01 %. For this reason the pattern of intake of R&P was similar to the wine pattern. This is the first time that R&P intake has been estimated in a Mediterranean country.

Effect of feed fat by-products with trans fatty acids and heated oil on cholesterol and oxycholesterols in chicken

Chicken is the most widely consumed meat all over the world due to chickens being easy to rear, their fast growth rate and the meat having good nutritional characteristics. The main objective of this paper was to study the effects of dietary fatty by-products in low, medium and high levels of oxidized lipids and trans fatty acids (TFAs) on the contents of cholesterol and oxycholesterols in meat, liver, and plasma of chickens. A palm fatty acid distillate, before and after hydrogenation, and a sunflower-olive oil blend (70/30, v/v) before and after use in a commercial frying process were used in feeding trials after adding 6% of the fats to the feeds. Highly oxidized lipid and TFA feeds significantly increased the contents of cholesterol and oxycholesterols in all tissues of chicken (0.01 < p <= 0.05). The contents of oxycholesterols in chicken meat, liver and plasma obtained from TFA feeding trials varied between 17 and 48 μg/100 g in meat, 19-42 μg/100 g in liver and 105-126 μg/dL in plasma. In contrast, in the oxidized lipid feeding trials, oxycholesterols varied between 13 and 75 μg/100 g in meat, 30-58 μg/100 g in liver and 66-209 μg/dL in plasma. Meat from chickens fed with feeds containing high levels of TFAs or oxidized lipids may contribute to higher ingestion of cholesterol and oxycholesterols by humans.

Role of CYP2E1-mediated metabolism in the acute and vestibular toxicities of nineteen nitriles in the mouse

Allylnitrile, cis-crotononitrile, and 3,3 -iminodipropionitrile are known to cause vestibular toxicity in rodents, and evidence is available indicating that cis-2-pentenenitrile shares this effect. We evaluated nineteen nitriles for vestibular toxicity in wild type (129S1) and CYP2E1-null mice, including all the above, several neurotoxic nitriles, and structurally similar nitriles. A new acute toxicity test protocol was developed to facilitate evaluation of the vestibular toxicity by a specific behavioral test battery at doses up to sub-lethal levels while using a limited number of animals. A mean number of 8.5±0.3 animals per nitrile, strain and sex was necessary to obtain evidence of vestibular toxicity and optionally an estimation of the lethal dose. For several but not all nitriles, lethal doses significantly increased in CYP2E1-null mice. The protocol revealed the vestibular toxicity of five nitriles, including previously identified ototoxic compounds and one nitrile (trans-crotononitrile) known to have a different profile of neurotoxic effects in the rat. In all five cases, both sexes were affected and no decrease in susceptibility was apparent in CYP2E1-null mice respect to 129S1 mice. Fourteen nitriles caused no vestibular toxicity, including six nitriles tested in CYP2E1-null mice at doses significantly larger than the maximal doses that can be tested in wild type animals. We conclude that only a subset of low molecular weight nitriles is toxic to the vestibular system, that species-dependent differences exist in this vestibular toxicity, and that CYP2E1-mediated metabolism is not involved in this effect of nitriles although it has a role in the acute lethality of some of these compounds

An enantioselective synthetic route to cis-2,4-disubstituted and 2,4-bridged piperidines

A synthetic route to enantiopure cis-2,4-disubstituted and 2,4-bridged piperidines is reported, the key step being a stereoselective conjugate addition of an organocuprate to a phenylglycinol-derived unsaturated lactam bearing a substituent at the 8a-position.

An enantioselective entry to cis-perhydroisoquinolines

An enantioselective route to cis-perhydroisoquinolines, involving a cyclocondensation reaction of (R)-phenylglycinol with a racemic oxoester, a stereoselective conjugate addition to an unsaturated bicyclic lactam, and the closure of the carbocyclic ring by a ring-closing metathesis as the key steps is reported. This route allows the preparation of 3-cyano derivatives as well as cis-octahydroisoquinolines bearing a quaternary center at the C4-position.

Competition in notch signaling with cis enriches cell fate decisions

Notch signaling is involved in cell fate choices during the embryonic development of Metazoa. Commonly, Notch signaling arises from the binding of the Notch receptor to its ligands in adjacent cells driving cell-to-cell communication. Yet, cell-autonomous control of Notch signaling through both ligand-dependent and ligand-independent mechanisms is known to occur as well. Examples include Notch signaling arising in the absence of ligand binding, and cis-inhibition of Notch signaling by titration of the Notch receptor upon binding to its ligands within a single cell. Increasing experimental evidences support that the binding of the Notch receptor with its ligands within a cell (cis-interactions) can also trigger a cell-autonomous Notch signal (cis-signaling), whose potential effects on cell fate decisions and patterning remain poorly understood. To address this question, herein we mathematically and computationally investigate the cell states arising from the combination of cis-signaling with additional Notch signaling sources, which are either cell-autonomous or involve cell-to-cell communication. Our study shows that cis-signaling can switch from driving cis-activation to effectively perform cis-inhibition and identifies under which conditions this switch occurs. This switch relies on the competition between Notch signaling sources, which share the same receptor but differ in their signaling efficiency. We propose that the role of cis-interactions and their signaling on fine-grained patterning and cell fate decisions is dependent on whether they drive cis-inhibition or cis-activation, which could be controlled during development. Specifically, cis-inhibition and not cis-activation facilitates patterning and enriches it by modulating the ratio of cells in the high-ligand expression state, by enabling additional periodic patterns like stripes and by allowing localized patterning highly sensitive to the precursor state and cell-autonomous bistability. Our study exemplifies the complexity of regulations when multiple signalng sources share the same receptor and provides the tools for their characterization.

Trencant espais fixes: programa de prevenció contra l'homo / trans fòbia a l'escola

“Trencant espais fixes: Programa de prevenció contra l’(homo/trans)fòbia a l’escola” és un programa finançat per l’Ajuntament de Barcelona que pren per objectiu prevenir i suprimir l’opressió que reben gais, lesbianes, transsexuals i bisexuals (LGTB) dins del centre educatiu, així com també d’aquells nens i nenes que transgredeixin les normes socials hegemòniques de gènere (establertes dins d’un sistema catalogat com a sexista, patriarcal i heteronormatiu), a través de la formació i apoderament dels docents dels centres educatius públics i concertats dels diferents districtes de Barcelona –fent ús de la prevenció primària, secundària i terciària-. Es pretén fer incís a l’educació de la diversitat afectivo-sexual, a les manifestacions sexistes, al sistema sexe-gènere-desig, als estereotips i prejudicis establerts en la societat i a les diverses dinàmiques de violència, desigualtat i relacions de poder, a fi de sensibilitzar, conscienciar i proporcionar eines als docents per prevenir i poder fer front a les diferents manifestacions discriminatòries a raó d’orientació sexual o identitat de gènere. S’utilitza una metodologia dinàmica i participativa, estructurada en tres sessions de 2,5h en cadascun dels centres educatius inscrits en el programa (a demanda del centre), el qual pren com a principis rectors la perspectiva integral del gènere, la intervenció preventiva, la transversalitat educativa, el procés participatiu i, finalment, l’interseccionalitat de factors identitaris d’una persona. Es pren consideració al Codi Ètic i Deontològic de la professió de Treball Social, ja que el present programa es caracteritza pel seu caràcter sensible i influent en la vida de les persones. Aquets fet suposa certes limitacions pels dinamitzadors dels tallers/sessions, ja sigui per la pròpia sensibilitat o per la manca de participació o de cohesió del grup destinatari.

Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance.

BackgroundBipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain.AimsWe sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL.MethodTo detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals.ResultsIntegrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85×10(-5)). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P = 3.54×10(-8)). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals.ConclusionsOur findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder.

The Vitamin A Derivative All-Trans Retinoic Acid Repairs Amyloid-β-Induced Double-Strand Breaks in Neural Cells and in the Murine Neocortex.

The amyloid-β peptide or Aβ is the key player in the amyloid-cascade hypothesis of Alzheimer's disease. Aβ appears to trigger cell death but also production of double-strand breaks (DSBs) in aging and Alzheimer's disease. All-trans retinoic acid (RA), a derivative of vitamin A, was already known for its neuroprotective effects against the amyloid cascade. It diminishes, for instance, the production of Aβ peptides and their oligomerisation. In the present work we investigated the possible implication of RA receptor (RAR) in repair of Aβ-induced DSBs. We demonstrated that RA, as well as RAR agonist Am80, but not AGN 193109 antagonist, repair Aβ-induced DSBs in SH-SY5Y cells and an astrocytic cell line as well as in the murine cortical tissue of young and aged mice. The nonhomologous end joining pathway and the Ataxia Telangiectasia Mutated kinase were shown to be involved in RA-mediated DSBs repair in the SH-SY5Y cells. Our data suggest that RA, besides increasing cell viability in the cortex of young and even of aged mice, might also result in targeted DNA repair of genes important for cell or synaptic maintenance. This phenomenon would remain functional up to a point when Aβ increase and RA decrease probably lead to a pathological state.

The chemistry of peroxynitrite, a biological toxin

Oxyradicals play a tole in several diseases. While for several decades the hydroxyl radical - produced via the Fenton reaction - has been considered the species that initiates oxyradical damage, new findings suggest that much of this damage can be ascribed to peroxynitrite, O=NOO-, formed from the reaction of the superoxide anion with nitrogen monoxide near activated macrophages. The rate constant for the reaction of this reaction has been investigated by flash photolysis and was found to be significantly higher than previously described in the literature, 1.9 x 10(10) M-1s-1. Studies of the isomerization to nitrate resulted in the discovery of a complex between peroxynitrite and its protonated form with a stability constant of 1 x 10(4) M-1. Some of the harmful reaction of peroxynitrous acid have been ascribed to the hydroxyl radical as a product of homolysis of the O-O bond during the conversion to nitrate. Kinetics of the isomerization reaction as a function of pressure show that the activation volume is only +1.5+1.0 ml mol-1, which is inconsistent with homolysis. Instead, an intermediate, possibly a distorted trans-isomer of O=NOOH could be responsible for the harmful reactions of peroxynitrite.

Trans-equatorial migration and mixing in the wintering areas of a pelagic seabird

Despite increasing interest in long-distance migration, the wintering areas, migration corridors, and population mix in winter quarters of most pelagic marine predators are unknown. Here, we present the first study tracking migration movements of shearwaters through the non-breeding period. We used geolocators (global location sensing [GLS] units based on ambient light levels) to track 22 Cory's shearwaters (Calonectris diomedea) breeding in three different areas. Most birds wintered in one or more of three relatively small areas, all clearly associated with major coastal upwelling systems of the tropical and south Atlantic. Trans-equatorial movements were dominated by prevailing trade winds and westerlies, while calm, oligotrophic areas were avoided. Breeding populations clearly differed in their preference amongst the three major wintering areas, but showed substantial mixing. This illustrates the exceptional value of GLS, not only for determining and describing the influence of oceanographic features on migration patterns, but also for assessing population mix in winter quarters. This knowledge is essential to understanding the impacts of population-level threats, such as longlining, offshore windfarms, and oil spills on multiple breeding sites, and will be critical in devising conservation policies that guarantee the sustainable exploitation of the oceans.