1,744 research outputs found

    Disentangling the roles of aneuploidy, chromosomal instability and tumour heterogeneity in developing resistance to cancer therapies.

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    Aneuploidy is defined as the cellular state of having a number of chromosomes that deviates from a multiple of the normal haploid chromosome number of a given organism. Aneuploidy can be present in a static state: Down syndrome individuals stably maintain an extra copy of chromosome 21 in their cells. In cancer cells, however, aneuploidy is usually present in combination with chromosomal instability (CIN) which leads to a continual generation of new chromosomal alterations and the development of intratumour heterogeneity (ITH). The prevalence of cells with specific chromosomal alterations is further shaped by evolutionary selection, for example, during the administration of cancer therapies. Aneuploidy, CIN and ITH have each been individually associated with poor prognosis in cancer, and a wealth of evidence suggests they contribute, either alone or in combination, to cancer therapy resistance by providing a reservoir of potential resistant states, or the ability to rapidly evolve resistance. A full understanding of the contribution and interplay between aneuploidy, CIN and ITH is required to tackle therapy resistance in cancer patients. However, these characteristics often co-occur and are intrinsically linked, presenting a major challenge to defining their individual contributions. Moreover, their accurate measurement in both experimental and clinical settings is a technical hurdle. Here, we attempt to deconstruct the contribution of the individual and combined roles of aneuploidy, CIN and ITH to therapy resistance in cancer, and outline emerging approaches to measure and disentangle their roles as a step towards integrating these principles into cancer therapeutic strategy

    Long-term experiments with an adaptive spherical view representation for navigation in changing environments

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    Real-world environments such as houses and offices change over time, meaning that a mobile robot’s map will become out of date. In this work, we introduce a method to update the reference views in a hybrid metric-topological map so that a mobile robot can continue to localize itself in a changing environment. The updating mechanism, based on the multi-store model of human memory, incorporates a spherical metric representation of the observed visual features for each node in the map, which enables the robot to estimate its heading and navigate using multi-view geometry, as well as representing the local 3D geometry of the environment. A series of experiments demonstrate the persistence performance of the proposed system in real changing environments, including analysis of the long-term stability

    EFEITO DO EXTRATO DE LARANJA AMARGA (CITRUS AURANTIUM) EM ROEDORES OBESOS

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    A obesidade é uma doença presente na sociedade a qual os indivíduos acometidos possuem alterações cardiovasculares e metabólicas que causam efeitos negativos na qualidade de vida e contribuem na evolução de enfermidades. Sendo assim o controle do peso é associado a manutenção da saúde. Neste contexto, há muitas alternativas para alcançar a redução e o controle de peso, uma delas é a utilização de fitoterápicos, como uso da Citrus aurantium sbsp (laranja amarga). A laranja amarga promove aceleração metabólica por meio do seu efeito termo gênico auxiliando na perda e no controle de peso, no entanto, os efeitos adversos desencadeados pelo uso deste fitoterápico não é bem elucidado pela literatura. Afim de compreender os possíveis efeitos adversos causados do uso de laranja amarga no tratamento da obesidade. O presente trabalho foi aprovado pelo comitê de ética animal (CEUA), da Universidade Positivo com o protocolo de aprovação 507-19, e realizado nas dependências da Universidade Positivo, Curitiba, Paraná, no setor Biotério laboratório de criação e experimentação anila. Para isto foram utilizados 50 ratos machos da linhagem Wistar, estes animais foram submetidos a um protocolo dietético de indução de obesidade e diabetes no período de 120 dias, após término deste período, os animais foram agrupados em 5 grupos distintos, cada grupo era composto por 10 unidades experimentais. O grupo controle negativo onde foi administrado apenas água deionizada, controle positivo onde os animais receberam efedrina e os demais grupos receberam 3 diferentes concentrações de Citrus Aurantium sbsp 100, 300 e 1000 mg/kg/dia pelo período de 8 semanas. Ao término do experimento foi observado que não vou houve diferença significativa em relação saciedade e a ação emagrecedora do extrato de laranja amarga nas concentrações testadas, no entanto houve variação no ganho de peso médio dos animais, em comparação com o grupo controle, os demais grupos obtiveram menor ganho peso durante o período de tratamento. Em relação aos efeitos hepáticos houve diferença significativa em todos os grupos testados com intervalo de confiança de 5%, sendo a concentração 1000 mg/kg/dia, a concentração que maior promoveu efeito hepatoprotetor, os níveis de triaglicerídeos e colesterol também foram menores nos grupos testes e controle positivo quando comparados com grupo controle negativo. Em relação aos efeitos comportamentais, animais tratados com extrato de laranja amarga demonstraram comportamentos atípicos relacionados a desconforto e dor abdominal

    Microalgae production in fresh market wastewater and its utilization as a protein substitute in formulated fish feed for oreochromis spp.

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    Rapid growing of human population has led to increasing demand of aquaculture production. Oreochromis niloticus or known as tilapia is one of the most globally cultured freshwater fish due to its great adaptation towards extreme environment. Besides, farming of tilapia not only involves small scales farming for local consumption but also larger scales for international market which contributes to a foreign currency earning. Extensive use of fishmeal as feed for fish and for other animals indirectly caused an increasing depletion of the natural resource and may consequently cause economic and environmental unstable. Microalgae biomass seems to be a promising feedstock in aquaculture industry. It can be used for many purposes such as live food for fish larvae and dried microalgae to substitute protein material in fish feed. The microalgae replacement in fish feed formulation as protein alternative seem potentially beneficial for long term aqua-business sustainability. The present chapter discussed the potential of microalgae as an alternative nutrition in fish feed formulations, specifically Tilapia

    Neurocutaneous Melanosis Presenting as Chronic Partial Epilepsy

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    BACKGROUND: Neurocutaneous melanosis (NCM) is a rare neurocutaneous syndrome characterized by the presence of multiple congenital melanocytic nevi (CMN) and the proliferation of melanocytes in the central nervous system, usually involving the leptomeninges. Chronic partial epilepsy as a sole manifestation is rare in NCM. CASE REPORT: A 32-year-old man suffering from chronic partial epilepsy presented with multiple CMN on his trunk and scalp. Brain MRI demonstrated a focal lesion in the right amygdala that was consistent with interictal epileptiform discharges in the right temporal region on electroencephalography (EEG). An anterior temporal lobectomy was performed, and the pathology investigation revealed numerous melanophages in the amygdala. The patient was seizure-free after surgery. CONCLUSIONS: We report a patient with NCM presenting as chronic partial epilepsy who was successfully treated by anterior temporal lobectomy.ope

    Low Mate Encounter Rate Increases Male Risk Taking in a Sexually Cannibalistic Praying Mantis

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    Male praying mantises are forced into the ultimate trade-off of mating versus complete loss of future reproduction if they fall prey to a female. The balance of this trade-off will depend both on (1) the level of predatory risk imposed by females and (2) the frequency of mating opportunities for males. We report the results of a set of experiments that examine the effects of these two variables on male risk-taking behavior and the frequency of sexual cannibalism in the praying mantis Tenodera sinensis. We experimentally altered the rate at which males encountered females and measured male approach and courtship behavior under conditions of high and low risk of being attacked by females. We show that male risk taking depends on prior access to females. Males with restricted access to females showed greater risk-taking behavior. When males were given daily female encounters, they responded to greater female-imposed risk by slowing their rate of approach and remained a greater distance from a potential mate. In contrast, males without recent access to mates were greater risk-takers; they approached females more rapidly and to closer proximity, regardless of risk. In a second experiment, we altered male encounter rate with females and measured rates of sexual cannibalism when paired with hungry or well-fed females. Greater risk-taking behavior by males with low mate encounter rates resulted in high rates of sexual cannibalism when these males were paired with hungry females

    The MHC Gene Region of Murine Hosts Influences the Differential Tissue Tropism of Infecting Trypanosoma cruzi Strains

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    We have previously demonstrated that both parasite genetic variability and host genetic background were important in determining the differential tissue distribution of the Col1.7G2 and JG T. cruzi monoclonal strains after artificial infections in mice. We observed that the JG strain was most prevalent in hearts of mouse lineages with the MHC haplotype H-2d (BALB/c and DBA2), while Col1.7G2 was predominant in hearts from C57BL/6 mice, which have the H-2b haplotype. To assess whether the MHC gene region indeed influenced tissue tropism of T. cruzi, we used the same two parasite strains to infect C57BL/6 (H-2b) and C57BLKS/J (H-2d) mice; the latter strain results from the introgression of DBA2 MHC region into the C57BL/6 background. We also performed ex vivo infections of cardiac explants from four congenic mice lineages with the H-2b and H-2d haplotypes arranged in two different genetic backgrounds: C57BLKS/J (H-2d) versus C57BL/6 (H-2b) and BALB/c (H-2d) versus BALB/B10-H2b (H-2b). In agreement with our former observations, Col1.7G2 was predominant in hearts from C57BL/6 mice (H-2b), but we observed a clear predominance of the JG strain in hearts from C57BLKS/J animals (H-2d). In the ex vivo experiments Col1.7G2 also prevailed in explants from H-2b animals while no predominance of any of the strains was observed in H-2d mice explants, regardless of the genetic background. These observations clearly demonstrate that the MHC region influences the differential tissue distribution pattern of infecting T. cruzi strains, which by its turn may be in a human infection the determinant for the clinical forms of the Chagas disease

    Acute febrile illness is associated with Rickettsia spp infection in dogs

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    BACKGROUND: Rickettsia conorii is transmitted by Rhipicephalus sanguineus ticks and causes Mediterranean Spotted Fever (MSF) in humans. Although dogs are considered the natural host of the vector, the clinical and epidemiological significance of R. conorii infection in dogs remains unclear. The aim of this prospective study was to investigate whether Rickettsia infection causes febrile illness in dogs living in areas endemic for human MSF. METHODS: Dogs from southern Italy with acute fever (n = 99) were compared with case–control dogs with normal body temperatures (n = 72). Serology and real-time PCR were performed for Rickettsia spp., Ehrlichia canis, Anaplasma phagocytophilum/A. platys and Leishmania infantum. Conventional PCR was performed for Babesia spp. and Hepatozoon spp. Acute and convalescent antibodies to R. conorii, E. canis and A. phagocytophilum were determined. RESULTS: The seroprevalence rates at first visit for R. conorii, E. canis, A. phagocytophilum and L. infantum were 44.8%, 48.5%, 37.8% and 17.6%, respectively. The seroconversion rates for R. conorii, E. canis and A. phagocytophilum were 20.7%, 14.3% and 8.8%, respectively. The molecular positive rates at first visit for Rickettsia spp., E. canis, A. phagocytophilum, A. platys, L. infantum, Babesia spp. and Hepatozoon spp. were 1.8%, 4.1%, 0%, 2.3%, 11.1%, 2.3% and 0.6%, respectively. Positive PCR for E. canis (7%), Rickettsia spp. (3%), Babesia spp. (4.0%) and Hepatozoon spp. (1.0%) were found only in febrile dogs. The DNA sequences obtained from Rickettsia and Babesia PCRs positive samples were 100% identical to the R. conorii and Babesia vogeli sequences in GenBank®, respectively. Febrile illness was statistically associated with acute and convalescent positive R. conorii antibodies, seroconversion to R. conorii, E. canis positive PCR, and positivity to any tick pathogen PCRs. Fourteen febrile dogs (31.8%) were diagnosed with Rickettsia spp. infection based on seroconversion and/or PCR while only six afebrile dogs (12.5%) seroconverted (P = 0.0248). The most common clinical findings of dogs with Rickettsia infection diagnosed by seroconversion and/or PCR were fever, myalgia, lameness, elevation of C-reactive protein, thrombocytopenia and hypoalbuminemia. CONCLUSIONS: This study demonstrates acute febrile illness associated with Rickettsia infection in dogs living in endemic areas of human MSF based on seroconversion alone or in combination with PCR

    Detecting Network Communities: An Application to Phylogenetic Analysis

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    This paper proposes a new method to identify communities in generally weighted complex networks and apply it to phylogenetic analysis. In this case, weights correspond to the similarity indexes among protein sequences, which can be used for network construction so that the network structure can be analyzed to recover phylogenetically useful information from its properties. The analyses discussed here are mainly based on the modular character of protein similarity networks, explored through the Newman-Girvan algorithm, with the help of the neighborhood matrix . The most relevant networks are found when the network topology changes abruptly revealing distinct modules related to the sets of organisms to which the proteins belong. Sound biological information can be retrieved by the computational routines used in the network approach, without using biological assumptions other than those incorporated by BLAST. Usually, all the main bacterial phyla and, in some cases, also some bacterial classes corresponded totally (100%) or to a great extent (>70%) to the modules. We checked for internal consistency in the obtained results, and we scored close to 84% of matches for community pertinence when comparisons between the results were performed. To illustrate how to use the network-based method, we employed data for enzymes involved in the chitin metabolic pathway that are present in more than 100 organisms from an original data set containing 1,695 organisms, downloaded from GenBank on May 19, 2007. A preliminary comparison between the outcomes of the network-based method and the results of methods based on Bayesian, distance, likelihood, and parsimony criteria suggests that the former is as reliable as these commonly used methods. We conclude that the network-based method can be used as a powerful tool for retrieving modularity information from weighted networks, which is useful for phylogenetic analysis
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