CXCL12 rs1801157 polymorphism and expression in peripheral blood from breast cancer patients

The role of chemokines has been extensively analyzed both in cancer risk and tumor progression. Among different cytokines, CXCR4 and its ligand CXCL12 have been recently subjected to a closer examination. The single-nucleotide polymorphism (SNP) rs1801157 (previously known as CXCL12-A/SDF1-3'A) in the CXCL12 gene and the relative expression of mRNA CXCL12 in peripheral blood were assessed in breast cancer patients, since the chemokine CXCL12 and its receptor CXCR4 regulate leukocyte trafficking and many essential biological processes, including tumor growth, angiogenesis and metastasis of different types of tumors. Genotyping was performed by PCR-RFLP (polymerase chain reaction followed by restriction fragment length polymorphism) using MspI restriction enzyme and the expression analyses by quantitative RT-PCR. No difference in GG genotype and allele A carrier frequencies were observed between breast cancer patients and healthy blood donors and nor when CXCL12 mRNA expression was assessed among patients with different tumor stages. However a significant difference was observed when CXCL12 mRNA relative expression was analyzed in breast cancer patients in accordance to the presence or absence of the CXCL12 rs1801157 allele A. Allele A breast cancer patients presented a mRNA CXCL12 expression about 2.1-fold smaller than GG breast cancer patients. Estrogen positive patients presenting CXCL12 allele A presented a significantly lower expression of CXCL12 in peripheral blood (p=0.039) than GG hormone positive patients. Our findings demonstrated that allele A is associated with low expression of CXCL12 in the peripheral blood from ER-positive breast cancer patients, which suggests implications on breast cancer clinical outcome.     

Fungal lectin of Peltigera canina induces chemotropism of compatible Nostoc cells by constriction-relaxation pulses of cyanobiont cytoskeleton

A glycosylated arginase acting as a fungal lectin from Peltigera canina is able to produce recruitment of cyanobiont Nostoc cells and their adhesion to the hyphal surface. This implies that the cyanobiont would develop organelles to motility toward the chemoattractant. However when visualized by transmission electron microscopy, Nostoc cells recently isolated from P. canina thallus do not reveal any motile, superficial organelles, although their surface was covered by small spindles and serrated layer related to gliding. The use of S-(3,4-dichlorobenzyl)isothiourea, blebbistatin, phalloidin and latrunculin A provide circumstantial evidence that actin microfilaments rather than MreB, the actin-like protein from prokaryota, and probably, an ATPase which develops contractile function similar to that of myosin II, are involved in cell motility. These experimental facts, the absence of superficial elements (fimbriae, pili or flagellum) related to cell movement, and the appearance of sunken cells during of after movement verified by scanning electron microscopy, support the hypothesis that the motility of lichen cyanobionts could be achieved by contraction-relaxation episodes of the cytoskeleton induced by fungal lectin act as a chemoattractant.Key words: F-actin, chemotropism, contractile protein, nostoc, Peltigera canina     

The lectin receptor kinase LecRK-I.9 is a novel Phytophthora resistance component and a potential host target for a RXLR effector

In plants, an active defense against biotrophic pathogens is dependent on a functional continuum between the cell wall (CW) and the plasma membrane (PM). It is thus anticipated that proteins maintaining this continuum also function in defense. The legume-like lectin receptor kinase LecRK-I.9 is a putative mediator of CW-PM adhesions in Arabidopsis and is known to bind in vitro to the Phytophthora infestans RXLR-dEER effector IPI-O via a RGD cell attachment motif present in IPI-O. Here we show that LecRK-I.9 is associated with the plasma membrane, and that two T-DNA insertions lines deficient in LecRK-I.9 (lecrk-I.9) have a 'gain-of-susceptibility' phenotype specifically towards the oomycete Phytophthora brassicae. Accordingly, overexpression of LecRK-I.9 leads to enhanced resistance to P. brassicae. A similar 'gain-of-susceptibility' phenotype was observed in transgenic Arabidopsis lines expressing ipiO (35S-ipiO1). This phenocopy behavior was also observed with respect to other defense-related functions; lecrk-I.9 and 35S-ipiO1 were both disturbed in pathogen- and MAMP-triggered callose deposition. By site-directed mutagenesis, we demonstrated that the RGD cell attachment motif in IPI-O is not only essential for disrupting the CW-PM adhesions, but also for disease suppression. These results suggest that destabilizing the CW-PM continuum is one of the tactics used by Phytophthora to promote infection. As countermeasure the host may want to strengthen CW-PM adhesions and the novel Phytophthora resistance component LecRK-I.9 seems to function in this process.     

Oak trees and soil interactions in Mediterranean forests: a positive feedback model

Questions: What is the spectrum of variability of chemical elements in a Mediterranean forest ecosystem across the different compartments? Do co‐existing tree species with different leaf chemical composition and nutrient cycling distinctly modify soil conditions? Could these species‐specific, tree‐generated soil changes create a potential positive feedback by affecting long‐term species distribution? Location: Mixed oak forests of southern Spain, Los Alcornocales Natural Park. Methods: We sampled and chemically analysed five different ecosystem components: leaves, leaf fall, litter and superficial (0–25 cm) and sub‐superficial (25–50 cm) soil beneath the canopies of evergreen Quercus suber and deciduous Q. canariensis trees. We used multiple co‐inertia analysis (MCoA) to conjointly analyse the patterns of variability and covariation of eight macro‐ and micronutrients determined in each of the sampled ecological materials. We implemented a path analysis to investigate alternative causal models of relationships among the chemical properties of the different ecosystem components. Results: Variability in the concentration of chemical elements was related to the nature of their biogeochemical cycles. However, the rank of element concentration was consistent across ecosystem components. Analysis of co‐inertia (MCoA) revealed that there was a common underlying multivariate pattern of nutrient enrichment in the ecosystem, which supported the hypothesis of a separation in biogeochemical niches between the two co‐existing oak species, with Q. canariensis having richer plant tissues and more fertile soil directly under each tree than Q. suber. The feasibility of a potential tree–soil positive feedback model was the only statistically validated among several alternative (non‐feedback) models tested. Conclusions: In the studied Mediterranean forests, oak species distinctly modify soil fertility conditions through different nutrient return pathways. Further investigation is needed to address whether these tree‐generated soil changes could affect seedling establishment and ultimately influence species distribution.     

The genomic ancestry of individuals from different geographical regions of Brazil is more uniform than expected

Based on pre-DNA racial/color methodology, clinical and pharmacological trials have traditionally considered the different geographical regions of Brazil as being very heterogeneous. We wished to ascertain how such diversity of regional color categories correlated with ancestry. Using a panel of 40 validated ancestry-informative insertion-deletion DNA polymorphisms we estimated individually the European, African and Amerindian ancestry components of 934 self-categorized White, Brown or Black Brazilians from the four most populous regions of the Country. We unraveled great ancestral diversity between and within the different regions. Especially, color categories in the northern part of Brazil diverged significantly in their ancestry proportions from their counterparts in the southern part of the Country, indicating that diverse regional semantics were being used in the self-classification as White, Brown or Black. To circumvent these regional subjective differences in color perception, we estimated the general ancestry proportions of each of the four regions in a form independent of color considerations. For that, we multiplied the proportions of a given ancestry in a given color category by the official census information about the proportion of that color category in the specific region, to arrive at a "total ancestry" estimate. Once such a calculation was performed, there emerged a much higher level of uniformity than previously expected. In all regions studied, the European ancestry was predominant, with proportions ranging from 60.6% in the Northeast to 77.7% in the South. We propose that the immigration of six million Europeans to Brazil in the 19th and 20th centuries--a phenomenon described and intended as the "whitening of Brazil"--is in large part responsible for dissipating previous ancestry dissimilarities that reflected region-specific population histories. These findings, of both clinical and sociological importance for Brazil, should also be relevant to other countries with ancestrally admixed populations.     

A gel-based proteomic method reveals several protein pathway abnormalities in fetal Down syndrome brain

A large series of protein pathway components have been shown to be dysregulated in Down syndrome (DS) brain. No information about pathomechanisms linked to the trisomic state can be obtained from adult DS brain, however, as neurodegeneration occurs from the fourth decade. The aim of the study was to search for protein dysregulation in fetal DS brain before neurodegenerative changes are observed. Proteins were extracted from fetal DS and control frontal cortex, run on 2-DE, followed by quantification of protein spots with subsequent nano-ESI-LC-MS/MS analysis using an ion trap. Aberrant expression of proteins tropomodulin-2, tubulin alpha 1A chain, and alpha-internexin may indicate disturbed synaptic plasticity; fatty acid binding protein 7 suggests impaired maintenance of neuroepithelial cells; and creatine kinase B may reflect defective energy metabolism. RNA binding protein 4B derangement may represent impaired splicing, altered retrotransposon gag domain-containing protein 1 levels may be pointing to altered retrotransposition, and level changes of the potassium-chloride transporter solute carrier family 12 member 7 may lead to impaired ion fluxes with electrophysiological consequences. Taken together, aberrant protein levels from several pathways in fetal DS are challenging as well as fertilizing the area of research and providing the basis for additional neurochemical and functional studies.     

Multilocus analyses of seven candidate genes suggest interacting pathways for obesity-related traits in Brazilian populations

We investigated whether variants in major candidate genes for food intake and body weight regulation contribute to obesity-related traits under a multilocus perspective. We studied 375 Brazilian subjects from partially isolated African-derived populations (quilombos). Seven variants displaying conflicting results in previous reports and supposedly implicated in the susceptibility of obesity-related phenotypes were investigated: β2-adrenergic receptor (ADRB2) (Arg16Gly), insulin induced gene 2 (INSIG2) (rs7566605), leptin (LEP) (A19G), LEP receptor (LEPR) (Gln223Arg), perilipin (PLIN) (6209T > C), peroxisome proliferator-activated receptor-γ (PPARG) (Pro12Ala), and resistin (RETN) (-420 C > G). Regression models as well as generalized multifactor dimensionality reduction (GMDR) were employed to test the contribution of individual effects and higher-order interactions to BMI and waist-hip ratio (WHR) variation and risk of overweight/obesity. The best multilocus association signal identified in the quilombos was further examined in an independent sample of 334 Brazilian subjects of European ancestry. In quilombos, only the PPARG polymorphism displayed significant individual effects (WHR variation, P = 0.028). No association was observed either with the risk of overweight/obesity (BMI ≥ 25 kg/m2), risk of obesity alone (BMI ≥ 30 kg/m2) or BMI variation. However, GMDR analyses revealed an interaction between the LEPR and ADRB2 polymorphisms (P = 0.009) as well as a third-order effect involving the latter two variants plus INSIG2 (P = 0.034) with overweight/obesity. Assessment of the LEPR-ADRB2 interaction in the second sample indicated a marginally significant association (P = 0.0724), which was further verified to be limited to men (P = 0.0118). Together, our findings suggest evidence for a two-locus interaction between the LEPR Gln223Arg and ADRB2 Arg16Gly variants in the risk of overweight/obesity, and highlight further the importance of multilocus effects in the genetic component of obesity.     

Of lice and math: using models to understand and control populations of head lice

In this paper we use detailed data about the biology of the head louse (pediculus humanus capitis) to build a model of the evolution of head lice colonies. Using theory and computer simulations, we show that the model can be used to assess the impact of the various strategies usually applied to eradicate head lice, both conscious (treatments) and unconscious (grooming). In the case of treatments, we study the difference in performance that arises when they are applied in systematic and non-systematic ways. Using some reasonable simplifying assumptions (as random mixing of human groups and the same mobility for all life stages of head lice other than eggs) we model the contagion of pediculosis using only one additional parameter. It is shown that this parameter can be tuned to obtain collective infestations whose characteristics are compatible with what is given in the literature on real infestations. We analyze two scenarios: One where group members begin treatment when a similar number of lice are present in each head, and another where there is one individual who starts treatment with a much larger threshold ("superspreader"). For both cases we assess the impact of several collective strategies of treatment.     

Adaptative response to enhanced basal oxidative damage in sod mutants from Saccharomyces cerevisiae

We investigated the adaptative response of S. cerevisiae in sod mutants (sod1Δ, sod2Δ and sod1Δsod2Δ) after H₂O₂ treatment in the stationary phase. sod2Δ and sod1Δsod2Δ demonstrated the highest levels of GSH in the control, suggesting that pathways which include GSH protect these double mutants against oxidative stress. In addition, sod1Δ and sod1Δsod2Δ had higher iron levels than the wild-type, independently of H₂O₂ stress. Fe levels were increased in sod2Δ following H₂O₂ In addition, the sod2Δ mutant was more sensitive to H₂O₂ treatment than the wild-type. These results suggest that sod2Δ sensibility may be associated with •OH production by the Fenton reaction. This increased iron demand in the sod2Δ mutant may be a reflection of the cells’ efforts to reconstitute proteins that are inactivated in conditions of excess superoxide. MDA levels were assayed by HPLC in these mutants. The highest MDA levels could be observed after 10mM H₂O₂ treatment in the sod1Δsod2Δ double mutant. After treatment with a GSH inhibitor, the MDA level was still higher in the same strain. Thus, both direct and indirect GSH pathways are involved in the protection of lipid membranes and proteins in these mutants and may constitute an adaptative response to enhanced basal oxidative damage produced by superoxide.