Ontogenetic variations in the venom proteome of the Amazonian snake Bothrops atrox

BACKGROUND: Bothrops atrox is responsible for the majority of snakebite accidents in the Brazilian Amazon region. Previous studies have demonstrated that the biological and pharmacological activities of B. atrox venom alter with the age of the animal. Here, we present a comparative proteome analysis of B. atrox venom collected from specimens of three different stages of maturation: juveniles, sub-adults and adults. RESULTS: Optimized conditions for two-dimensional gel electrophoresis (2-DE) of pooled venom samples were achieved using immobilized pH gradient (IPG) gels of non-linear 3–10 pH range during the isoelectric focusing step and 10–20% gradient polyacrylamide gels in the second dimension. Software-assisted analysis of the 2-DE gels images demonstrated differences in the number and intensity of spots in juvenile, sub-adult and adult venoms. Although peptide mass fingerprinting (PMF) failed to identify even a minor fraction of spots, it allowed us to group spots that displayed similar peptide maps. The spots were subjected to a combination of tandem mass spectrometry and Mascot and MS BLAST database searches that identified several classes of proteins, including metalloproteinases, serine proteinases, lectins, phospholipases A(2), L-amino oxidases, nerve growth factors, vascular endothelial growth factors and cysteine-rich secretory proteins. CONCLUSION: The analysis of B. atrox samples from specimens of different ages by 2-DE and mass spectrometry suggested that venom proteome alters upon ontogenetic development. We identified stage specific and differentially expressed polypeptides that may be responsible for the activities of the venom in each developmental stage. The results provide insight into the molecular basis of the relation between symptomatology of snakebite accidents in humans and the venom composition. Our findings underscore the importance of the use of venoms from individual specimen at various stages of maturation for the production of antivenoms

Trypanosoma cruzi alkaline 2-DE: Optimization and application to comparative proteome analysis of flagellate life stages

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

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Editado por: Odílio Benedito Garrido de Assis, Wilson Tadeu Lopes da Silva, Luiz Henrique Capparelli Mattoso

Radiation from a D-dimensional collision of shock waves: first order perturbation theory

We study the spacetime obtained by superimposing two equal Aichelburg-Sexl shock waves in D dimensions traveling, head-on, in opposite directions. Considering the collision in a boosted frame, one shock becomes stronger than the other, and a perturbative framework to compute the metric in the future of the collision is setup. The geometry is given, in first order perturbation theory, as an integral solution, in terms of initial data on the null surface where the strong shock has support. We then extract the radiation emitted in the collision by using a D-dimensional generalisation of the Landau-Lifschitz pseudo-tensor and compute the percentage of the initial centre of mass energy epsilon emitted as gravitational waves. In D=4 we find epsilon=25.0%, in agreement with the result of D'Eath and Payne. As D increases, this percentage increases monotonically, reaching 40.0% in D=10. Our result is always within the bound obtained from apparent horizons by Penrose, in D=4, yielding 29.3%, and Eardley and Giddings, in D> 4, which also increases monotonically with dimension, reaching 41.2% in D=10. We also present the wave forms and provide a physical interpretation for the observed peaks, in terms of the null generators of the shocks.Comment: 27 pages, 11 figures; v2 some corrections, including D dependent factor in epsilon; matches version accepted in JHE

Scaling properties of protein family phylogenies

One of the classical questions in evolutionary biology is how evolutionary processes are coupled at the gene and species level. With this motivation, we compare the topological properties (mainly the depth scaling, as a characterization of balance) of a large set of protein phylogenies with a set of species phylogenies. The comparative analysis shows that both sets of phylogenies share remarkably similar scaling behavior, suggesting the universality of branching rules and of the evolutionary processes that drive biological diversification from gene to species level. In order to explain such generality, we propose a simple model which allows us to estimate the proportion of evolvability/robustness needed to approximate the scaling behavior observed in the phylogenies, highlighting the relevance of the robustness of a biological system (species or protein) in the scaling properties of the phylogenetic trees. Thus, the rules that govern the incapability of a biological system to diversify are equally relevant both at the gene and at the species level.Comment: Replaced with final published versio

Human embryonic stem cells from aneuploid blastocysts identified by pre-implantation genetic screening

Human embryonic stem cells are derived from the inner cell mass of pre-implantation embryos. The cells have unlimited proliferation potential and capacity to differentiate into the cells of the three germ layers. Human embryonic stem cells are used to study human embryogenesis and disease modeling and may in the future serve as cells for cell therapy and drug screening. Human embryonic stem cells are usually isolated from surplus normal frozen embryos and were suggested to be isolated from diseased embryos detected by pre-implantation genetic diagnosis. Here we report the isolation of 12 human embryonic stem cell lines and their thorough characterization. The lines were derived from embryos detected to have aneuploidy by pre-implantation genetic screening. Karyotype analysis of these cell lines showed that they are euploid, having 46 chromosomes. Our interpretation is that the euploid cells originated from mosaic embryos, and in vitro selection favored the euploid cells. The undifferentiated cells exhibited long-term proliferation and expressed markers typical for embryonic stem cells such as OCT4, NANOG, and TRA-1-60. The cells manifested pluripotent differentiation both in vivo and in vitro. To further characterize the different lines, we have analyzed their ethnic origin and the family relatedness among them. The above results led us to conclude that the aneuploid mosaic embryos that are destined to be discarded can serve as source for normal euploid human embryonic stem cell lines. These lines represent various ethnic groups; more lines are needed to represent all populations

ALMA 26 Arcmin2^{2} Survey of GOODS-S at One-millimeter (ASAGAO): Average Morphology of High-zz Dusty Star-Forming Galaxies is an Exponential-Disk (n≃1n \simeq 1)

We present morphological properties of dusty star-forming galaxies at z=1-3 determined with high-resolution (FWHM~0"19) Atacama Large Milllimeter/submilimeter Array (ALMA) 1-mm band maps of our ASAGAO survey covering a 26-arcmin^2 area in GOODS-S. In conjunction with the ALMA archival data, the present sample consists of 42 ALMA sources with a wide rest-frame far-infrared (FIR) luminosity L_FIR range of ~10^11-10^13 Lo. To obtain an average rest-frame FIR profile, we perform individual measurements and careful stacking of the ALMA sources using the uv-visibility method that includes positional-uncertainty and smoothing-effect evaluations through Monte-Carlo simulations. We find that the dusty star-forming galaxies have the average FIR-wavelength Sersic index and effective radius of n_FIR=1.2+/-0.2 and R_e,FIR=1.0-1.3 kpc, respectively, additionally with a point source at the center, indicative of the existence of AGN. The average FIR profile agrees with a morphology of an exponential-disk clearly distinguished from a spheroidal profile (Sersic index of 4). We also examine the rest-frame optical Sersic index n_opt and effective radius R_e,opt with the deep Hubble Space Telescope (HST) images. Interestingly, we obtain n_opt=0.9+/-0.3 (~n_FIR) and R_e,opt=3.2+/-0.6 kpc (>R_e,FIR), suggesting that the FIR-emitting disk is embedded within a larger stellar disk. The rest-frame UV and FIR data of HST and ALMA provide us a radial surface density profile of the total star-formation rate (SFR), where the FIR SFR dominates over the UV SFR at the center. Under the simple assumption of a constant SFR, a compact stellar distribution found in z~1-2 compact quiescent galaxies (cQGs) is well reproduced, while a spheroidal stellar morphology of cQGs (n_opt=4) cannot, suggestive of other important mechanisms such as dynamical dissipation.Comment: 13 pages, 6 figures, ApJ in pres

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis