2,756 research outputs found

    The role of exon shuffling in shaping protein-protein interaction networks

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    <p>Abstract</p> <p>Background</p> <p>Physical protein-protein interaction (PPI) is a critical phenomenon for the function of most proteins in living organisms and a significant fraction of PPIs are the result of domain-domain interactions. Exon shuffling, intron-mediated recombination of exons from existing genes, is known to have been a major mechanism of domain shuffling in metazoans. Thus, we hypothesized that exon shuffling could have a significant influence in shaping the topology of PPI networks.</p> <p>Results</p> <p>We tested our hypothesis by compiling exon shuffling and PPI data from six eukaryotic species: <it>Homo sapiens</it>, <it>Mus musculus</it>, <it>Drosophila melanogaster</it>, <it>Caenorhabditis elegans</it>, <it>Cryptococcus neoformans</it> and <it>Arabidopsis thaliana</it>. For all four metazoan species, genes enriched in exon shuffling events presented on average higher vertex degree (number of interacting partners) in PPI networks. Furthermore, we verified that a set of protein domains that are simultaneously promiscuous (known to interact to multiple types of other domains), self-interacting (able to interact with another copy of themselves) and abundant in the genomes presents a stronger signal for exon shuffling.</p> <p>Conclusions</p> <p>Exon shuffling appears to have been a recurrent mechanism for the emergence of new PPIs along metazoan evolution. In metazoan genomes, exon shuffling also promoted the expansion of some protein domains. We speculate that their promiscuous and self-interacting properties may have been decisive for that expansion.</p

    Some integrals ocurring in a topology change problem

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    In a paper presented a few years ago, De Lorenci et al. showed, in the context of canonical quantum cosmology, a model which allowed space topology changes (Phys. Rev. D 56, 3329 (1997)). The purpose of this present work is to go a step further in that model, by performing some calculations only estimated there for several compact manifolds of constant negative curvature, such as the Weeks and Thurston spaces and the icosahedral hyperbolic space (Best space).Comment: RevTeX article, 4 pages, 1 figur

    A genetic network that suppresses genome rearrangements in Saccharomyces cerevisiae and contains defects in cancers.

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    Gross chromosomal rearrangements (GCRs) play an important role in human diseases, including cancer. The identity of all Genome Instability Suppressing (GIS) genes is not currently known. Here multiple Saccharomyces cerevisiae GCR assays and query mutations were crossed into arrays of mutants to identify progeny with increased GCR rates. One hundred eighty two GIS genes were identified that suppressed GCR formation. Another 438 cooperatively acting GIS genes were identified that were not GIS genes, but suppressed the increased genome instability caused by individual query mutations. Analysis of TCGA data using the human genes predicted to act in GIS pathways revealed that a minimum of 93% of ovarian and 66% of colorectal cancer cases had defects affecting one or more predicted GIS gene. These defects included loss-of-function mutations, copy-number changes associated with reduced expression, and silencing. In contrast, acute myeloid leukaemia cases did not appear to have defects affecting the predicted GIS genes

    Ecotoxicity of raw and treated effluents generated by a veterinary medicine industry

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    Effluents from veterinary pharmaceutical industries that formulate medicines are mainly generated during the washing of equipment. The aim of this work was to evaluate the acute toxicity to Daphnia similis and chronic toxicity to Ceriodaphnia dubia of raw and treated effluents generated by a veterinary pharmaceutical industry. The industrial effluent treatment system comprises a step of chemical treatment (coagulation-sedimentation forced) followed by aerobic biological treatment (activated sludge process). Five samplings campaigns were performed from October 2011 to July 2012. The raw effluent samples showed high acute and chronic toxicity (acute: fourth sampling with EC50 - 48-h of <0.001% and chronic: third sampling with IC50 - 7-d of <0.0001%). The chemically treated effluent samples were the most toxic with EC50 - 48-h between <0.001 and 0.1% and IC50 - 7-d between 0.00001 and 0.0001%. This increase in toxicity is probably related to the use of aluminum sulfate as flocculating agent. The biological treatment led to a small reduction in toxicity of the effluents. The selected ecotoxicological tests were adequate for detecting the effluent toxicity and useful for evaluating the efficiency of the steps of the effluent treatment. Improvements in the industrial wastewater treatment system should be implemented in order to reduce the observed toxicity of the final effluent.Efluentes de indústrias farmacêuticas veterinárias, que formulam medicamentos, são gerados principalmente durante a lavagem dos equipamentos. O objetivo desse trabalho foi avaliar a toxicidade aguda para Daphnia similis e crônica para Ceriodaphnia dubia, dos efluentes brutos e tratados gerados por uma indústria farmacêutica veterinária. O sistema de tratamento de efluentes usado é composto por uma etapa de tratamento químico (coagulação-sedimentação forçada) seguida do tratamento biológico aeróbio (processo de lodos ativados). Foram realizadas 5 campanhas de amostragens entre outubro de 2011 e julho de 2012. As amostras de efluentes brutos apresentaram elevada toxicidade aguda e crônica (aguda: quarta campanha com CE50 - 48-h de <0,001% e crônica: terceira campanha com CI50 - 7d <0,0001%). As amostras de efluentes tratados quimicamente foram as mais tóxicas com CE50 - 48-h entre <0,001 e 0,1% e CI50 - 7-d entre 0,00001 e 0,0001%, provavelmente relacionada ao uso de sulfato de alumínio como agente floculante. O tratamento biológico levou a uma pequena diminuição da toxicidade dos efluentes. Os testes ecotoxicológicos foram adequados para detectar a toxicidade dos efluentes e úteis para avaliar a eficiência das etapas do tratamento. Melhorias no sistema de tratamento de efluentes da indústria estudada deveriam ser implementadas visando à redução da toxicidade observada nos efluentes finais.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Universidade Federal de Alfenas Instituto de Ciências da NaturezaUniversidade Estadual de Campinas Laboratório de Ecotoxicologia Aquática e Limnologia Prof. Dr. Abílio LopesUniversidade Federal de São Paulo (UNIFESP) Instituto de Ciências Ambientais, Químicas e FarmacêuticasUNIFESP, Instituto de Ciências Ambientais, Químicas e FarmacêuticasSciEL

    About Starobinsky inflation

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    It is believed that soon after the Planck era, space time should have a semi-classical nature. According to this, the escape from General Relativity theory is unavoidable. Two geometric counter-terms are needed to regularize the divergences which come from the expected value. These counter-terms are responsible for a higher derivative metric gravitation. Starobinsky idea was that these higher derivatives could mimic a cosmological constant. In this work it is considered numerical solutions for general Bianchi I anisotropic space-times in this higher derivative theory. The approach is ``experimental'' in the sense that there is no attempt to an analytical investigation of the results. It is shown that for zero cosmological constant Λ=0\Lambda=0, there are sets of initial conditions which form basins of attraction that asymptote Minkowski space. The complement of this set of initial conditions form basins which are attracted to some singular solutions. It is also shown, for a cosmological constant Λ>0\Lambda> 0 that there are basins of attraction to a specific de Sitter solution. This result is consistent with Starobinsky's initial idea. The complement of this set also forms basins that are attracted to some type of singular solution. Because the singularity is characterized by curvature scalars, it must be stressed that the basin structure obtained is a topological invariant, i.e., coordinate independent.Comment: Version accepted for publication in PRD. More references added, a few modifications and minor correction

    P450-mediated electrochemical sensing of drugs in human plasma for personalized therapy

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    Nowadays, the concept of personalized therapy gains momentum. Pharmacogenomics, which represents a first answer to these needs, has the drawback of neglecting some variations of therapy response due to non-genetic factors. The aim of this paper is to investigate the feasibility of a non-genetic approach to personalized therapy, via the point-of-care drug monitoring in biological fluids with electrochemical biosensors. The proposed biosensor is based on the use of P450 enzymes as probe molecules, thanks to their key role in human metabolism. Multiwalled carbon nanotubes are used to enhance biosensor sensitivity. Results show how the proposed system is capable to detect drug amounts within the corresponding pharmacological ranges in human serum

    Evaluation of patients undergoing placement of zygomatic implants using sinus slot technique

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    Background: This study aimed to evaluate patients undergoing placement of zygomatic implants by Stella and Warner’s technique, considering the survival rate of conventional and zygomatic implants, and assess the health of the maxillary sinuses and the level of patient satisfaction. Methods: In this retrospective cohort study, 28 patients had received a combination of conventional and zygomatic implants (group I) and 14 were rehabilitated with only conventional implants (group II). Results: The results showed that Stella and Warner’s technique, thought to minimize the presence of the implant into the maxillary sinus, improving the emergence of the implant, proved to be effective, allowing a high survival rate of conventional and zygomatic implants (100 %). The follow-up period ranged from a minimum of 15 months to a maximum of 53 months after prosthetic rehabilitation (average of 34 months). No pathological changes were found on the periimplant tissues. Radiographs showed satisfactory bone levels in conventional implants of oral rehabilitation with zygomatic implants and a good positioning of the apex of the zygomatic implants in relation to the zygomaticbone. The tomographic findings revealed no characteristics of sinus disease. There were no cases of obstruction of the maxillary sinus ostium. Conclusions: The placement of zygomatic implants by Stella and Warner’s technique proved to be a predictable technique with high implant survival rate in patients with atrophic maxilla and was not associated with sinus disease in the sample analyzed. However, a long-term follow-up is necessary to confirm the initial findings of this study

    Suppression of Dimer Correlations in the Two-Dimensional J1J_1-J2J_2 Heisenberg Model: an Exact Diagonalization Study

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    We present an exact diagonalization study of the ground state of the spin-half J1J2J_1{-}J_2 model. Dimer correlation functions and the susceptibility associated to the breaking of the translational invariance are calculated for the 4×44\times 4 and the 6×66\times 6 clusters. These results -- especially when compared to the one dimensional case, where the occurrence of a dimerized phase for large enough frustration is well established -- suggest either a homogeneous spin liquid or, possibly, a dimerized state with a rather small order parameter
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