A recent insertion of an alu element on the Y chromosome is a useful marker for human population studies

A member of the Alu family of repeated DNA elements has been identified on the long arm of the human Y chromosome, Yq11. This element, referred to as the Y Alu polymorphic (YAP) element, is present at a specific site on the Y chromosome in some humans and is absent in others. Phylogenetic comparisons with other Alu sequences reveal that the YAP element is a member of the polymorphic subfamily-3 (PSF-3), a previously undefined subfamily of Alu elements. The evolutionary relationships of PSF-3 to other Alu subfamilies support the hypothesis that recently inserted elements result from multiple source genes. The frequency of the YAP element is described in 340 individuals from 14 populations, and the data are combined with those from other populations. There is both significant heterogeneity among populations and a clear pattern in the frequencies of the insertion: sub-Saharan Africans have the highest frequencies, followed by northern Africans, Europeans, Oceanians, and Asians. An interesting exception is the relatively high frequency of the YAP element in Japanese. The greatest genetic distance is observed between the African and non-African populations. The YAP is especially useful for studying human population history from the perspective of male lineages.      

Can Urine Metabolomics Be Helpful in Differentiating Neuropathic and Nociceptive Pain? A Proof-of-Concept Study

The diagnosis of pain nature is a troublesome task and a wrong attribution often leads to an increase of costs and to avoidable pharmaceutical adverse reactions. An objective and specific approach to achieve this diagnosis is highly desirable. The aim of this work was to investigate urine samples collected from patients suffering from pain of different nature by a metabolomics approach based on ¹H NMR spectroscopy and multivariate statistical analysis. We performed a prospective study on 74 subjects: 37 suffering from pain (12 with nociceptive and 25 with neuropathic pain), and 37 controls not suffering from any kind of chronic pain. The application of discriminant analysis on the urine spectral profiles allowed us to classify these two types of pain with high sensibility and specificity. Although the classification relies on the global urine metabolic profile, the individual contribution in discriminating neuropathic pain patients of metabolites such as choline and phosphocholine, taurine and alanine, suggests potential lesions to the nervous system. To the best of our knowledge, this is the first time that a urine metabolomics profile is used to classify these two kinds of pain. This methodology, although based on a limited sample, may constitute the basis for a new helpful tool in the clinical diagnosis.     

A paramutation phenomenon is involved in the genetics of maize low phytic acid1-241 (lpa1-241) trait

So far, in maize, three classes of mutants involved in phytic acid biosynthesis have been isolated: lpa1, lpa2 and lpa3. In 2007, a gene tagging experiment performed by Shi et al. found that mutations in ZmMRP4 (multidrug resistance-associated proteins 4) gene cause lpa1 phenotype. In previous studies, we isolated and described a single recessive lpa mutation (originally named lpa241), which was allelic to the lpa1-1 mutant, and was consequently renamed lpa1-241. It showed a decrease in the expression of the myo-inositol (Ins)-3-phosphate synthase gene (mips1S). In this study, we present genetic and molecular analyses of the lpa1-241 mutation that indicate an epigenetic origin of this trait, that is, a paramutagenic interaction that results in meiotically heritable changes in ZmMRP4 gene expression, causing a strong pleiotropic effect on the whole plant. The use of a 5-Azacytidine treatment provided data suggesting an association between gene methylation and the lpa1-241 phenotype. To our knowledge, this is the first report of a paramutagenic activity not involving flavonoid biosynthesis in maize, but regarding a key enzyme of an important metabolic pathway in plants.     

The effect of genistein supplementation on performance and antioxidant status of Japanese Quail under heat stress

Genistein, a phytoestrogen found in soybeans, is a powerful antioxidant. We evaluated the effects of genistein supplementation on performance, carcass characteristics, levels of malondialdehyde (MDA), homocysteine, vitamins C, E, A in Japanese quail (Coturnix coturnix japonica) exposed to high ambient temperature of 34°C. Two hundred and forty Japanese quails (10 d old) were randomly assigned to eight treatment groups consisting of 10 replicates of three birds. The birds were kept in an environmental controlled room either for 24 h/d at 22°C with (thermoneutral, TN groups) or for 16 h/d at 22°C and for 8 h/d (09.00 am to 05.00 pm) at 34°C (heat stress, HS groups). Birds were fed either a basal (control) diet (TN and HS) or the basal diet supplemented with 200, 400 or 800 mg of genistein per kg of diet. Heat exposure decreased birds' performance when basal diet was fed. Increase in feed intake and body weight, and improvement of feed efficiency and carcass traits were found in genistein-supplemented quails reared under heat stress conditions. Growth rate and feed efficiency improved in quails reared under thermo-neutral conditions as well. Concentration of serum vitamins C, E, and A increased in supplemented birds reared at high temperature, while non-significant changes occurred in TN groups. With genistein supplementation homocysteine levels in serum and MDA levels in serum and liver decreased in all birds of both TN and HS groups. Effects of genistein were relatively greater in heat-stressed quails than in quails kept under thermo-neutral conditions. Results of the present study suggest that supplementation with genistein can be considered to be protective by reducing the negative effects of oxidative stress induced by heat stress in quail.     

An anionic synthetic sugar containing 6-SO(3) -NAcGlc mimics the sulfated cruzipain epitope that plays a central role in immune recognition

Cruzipain (Cz), the major cysteine proteinase of Trypanosoma?cruzi, is a glycoprotein that contains sulfated high-mannose-type oligosaccharides. We have previously determined that these sulfate groups are targets of specific immune responses. In order to evaluate the structural requirements for antibody recognition of Cz, a systematic structure-activity study of the chemical characteristics needed for antibody binding to the Cz sulfated epitope was performed by immunoassays. With this aim, different synthesized molecules were coupled to the proteins BSA and aprotinin and confronted with (a) mouse sera specific for Cz and its carboxy-terminal (C-T) domain, (b) antibodies raised in rabbits immunized with Cz and its C-terminal domain and (c) IgGs purified from human Chagas disease sera. Our results indicate that a glucosamine containing an esterifying sulfate group in position O-6 and an N-acetyl group was the preferred epitope for the immune recognition of sera specific for Cz and its C-T domain. Although to a minor extent, other anionic compounds bearing sulfate groups in different positions and number as well as different anionic charged groups including carboxylated or phosphorylated monosaccharides, disaccharides and oligosaccharides were recognized. In conclusion, we found that synthetic anionic sugar conjugates containing N-acetyl d-glucosamine-6-sulfate sodium salt (GlcNAc6S) competitively inhibit the binding of affinity purified rabbit anti-C-T IgG to the C-T extension of Cz. Extending these findings to the context of natural infection, immune assays performed with Chagas disease serum confirmed that the structure of synthetic GlcNAc6S mimics the N-glycan-linked sulfated epitope displayed in the C-T domain of Cz.     

Shiga Toxin 1 Induces on Lipopolysaccharide-Treated Astrocytes the Release of Tumor Necrosis Factor-alpha that Alter Brain-Like Endothelium Integrity

The hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia and renal dysfunction. The typical form of HUS is generally associated with infections by Gram-negative Shiga toxin (Stx)-producing Escherichia coli (STEC). Endothelial dysfunction induced by Stx is central, but bacterial lipopolysaccharide (LPS) and neutrophils (PMN) contribute to the pathophysiology. Although renal failure is characteristic of this syndrome, neurological complications occur in severe cases and is usually associated with death. Impaired blood-brain barrier (BBB) is associated with damage to cerebral endothelial cells (ECs) that comprise the BBB. Astrocytes (ASTs) are inflammatory cells in the brain and determine the BBB function. ASTs are in close proximity to ECs, hence the study of the effects of Stx1 and LPS on ASTs, and the influence of their response on ECs is essential. We have previously demonstrated that Stx1 and LPS induced activation of rat ASTs and the release of inflammatory factors such as TNF-α, nitric oxide and chemokines. Here, we demonstrate that rat ASTs-derived factors alter permeability of ECs with brain properties (HUVECd); suggesting that functional properties of BBB could also be affected. Additionally, these factors activate HUVECd and render them into a proagregant state promoting PMN and platelets adhesion. Moreover, these effects were dependent on ASTs secreted-TNF-α. Stx1 and LPS-induced ASTs response could influence brain ECs integrity and BBB function once Stx and factors associated to the STEC infection reach the brain parenchyma and therefore contribute to the development of the neuropathology observed in HUS.