Plasmodium kinesin-8X associates with mitotic spindles and is essential for oocyst development during parasite proliferation and transmission

Kinesin-8 proteins are microtubule motors that are often involved in regulation of mitotic spindle length and chromosome alignment. They move towards the plus ends of spindle microtubules and regulate the dynamics of these ends due, at least in some species, to their microtubule depolymerization activity. Plasmodium spp. exhibit an atypical endomitotic cell division in which chromosome condensation and spindle dynamics in the different proliferative stages are not well understood. Genome-wide shared orthology analysis of Plasmodium spp. revealed the presence of two kinesin-8 motor proteins, kinesin-8X and kinesin-8B. Here we studied the biochemical properties of kinesin-8X and its role in parasite proliferation. In vitro, kinesin-8X has motility and depolymerization activities like other kinesin-8 motors. To understand the role of Plasmodium kinesin-8X in cell division, we used fluorescence-tagging and live cell imaging to define its location, and gene targeting to analyse its function, during all proliferative stages of the rodent malaria parasite P. berghei life cycle. The results revealed a spatio-temporal involvement of kinesin-8X in spindle dynamics and an association with both mitotic and meiotic spindles and the putative microtubule organising centre (MTOC). Deletion of the kinesin-8X gene revealed a defect in oocyst development, confirmed by ultrastructural studies, suggesting that this protein is required for oocyst development and sporogony. Transcriptome analysis of Δkinesin-8X gametocytes revealed modulated expression of genes involved mainly in microtubule-based processes, chromosome organisation and the regulation of gene expression, supporting a role for kinesin-8X in cell division. Kinesin-8X is thus required for parasite proliferation within the mosquito and for transmission to the vertebrate host

Dynamic protein methylation in chromatin biology

Post-translational modification of chromatin is emerging as an increasingly important regulator of chromosomal processes. In particular, histone lysine and arginine methylation play important roles in regulating transcription, maintaining genomic integrity, and contributing to epigenetic memory. Recently, the use of new approaches to analyse histone methylation, the generation of genetic model systems, and the ability to interrogate genome wide histone modification profiles has aided in defining how histone methylation contributes to these processes. Here we focus on the recent advances in our understanding of the histone methylation system and examine how dynamic histone methylation contributes to normal cellular function in mammals

Kangaroo Mother Care In Public Hospitals In The State Of São Paulo, Brazil: An Analysis Of The Implementation Process [o Método Mãe Canguru Em Hospitais Públicos Do Estado De São Paulo, Brasil: Uma Análise Do Processo De Implantaç ão]

This study analyzed the implementation of the Kangaroo Mother method in 28 different São Paulo State public hospitals. Teaching hospitals, Baby-Friendly Hospitals, hospitals with human milk banks, and those with more than 12 trained health professionals showed higher implementation scores. Because of staff resistance to family participation in neonatal care, the Kangaroo Mother method is basically applied in-hospital. Changes in the initial training, including manager awareness-raising and proper financial resource allocation, are necessary for implementation, follow-up, assessment, and feedback.223597607(2000) Boletim CIS/2000. N. 2. Mortalidade Infantil, , São Paulo: Secretaria de Estado da Saúde de São PauloLubchenko, L.O., Determinação do peso e idade gestacional (1984) Neonatologia, pp. 207-227. , Avery G, organizador. Rio de Janeiro: Médica e CientíficaLubchenko, L.O., Searls, D.T., Neonatal mortality rate: Relationship to birth weight and gestational age (1972) J Pediatr, (84), p. 4(1994) Manual de Assistência Ao Recém-nascido, , Brasília: Secretaria de Assistência à Saúde, Ministério da SaúdeCattaneo, A., Davanzo, R., Uxa, F., Tamburlini, G., Recommendations for the implementation of Kangaroo Mother Care for low birth weight infants (1998) Acta Paediatr, 87, pp. 440-445. , International Network on Kangaroo Mother Care(1994) Alimentação Infantil - Bases Fisiológicas, , São Paulo: Instituto de Saúde/IBFAN BrasilKennell, J.H., Klaus, M.H., Bonding: Recent observations that alter perinatal care (1998) Pediatr Rev, 9, pp. 4-12Lucas, A., Morley, R., Cole, T.J., Lister, G., Leeson-Payne, C., Breast milk and subsequent intelligence quotient in children born preterm (1992) Lancet, 339, pp. 261-264Bradley, R.H., Casey, P.H., Family environment and behavioral development of low-birth weight children (1992) Dev Med Child Neurol, 34, pp. 822-826Strathearn, L., Gray, P.H., O'Callaghan, M.J., Wood, D.O., Childhood neglect and cognitive development in extremely low birth weight infants: A prospective study (2001) Pediatrics, 108, pp. 142-151Symington, A., Pinelli, J., Developmental care for promoting development and preventing morbidity in preterm infants (2004) The Cochrane Library, (1). , Oxford: Update SoftwareFurman, L., Kennell, J., Breast milk and skin-to-skin kangaroo care for premature infants. Avoiding bonding failure (2000) Acta Paediatr, 89, pp. 1280-1283Charpak, N., Figueroa, Z., Hamel, A., (1999) O Método Mãe Canguru: Pais e Familiares Dos Bebês Prematuros Podem Substituir As Incubadoras, , Rio de Janeiro: McGraw-HillAnderson, G.C., Marks, E.A., Wahlberg, V., Kangaroo care for premature infants (1986) Am J Nurs, 86, pp. 807-809Colonna, F., Uxa, F., Da Graca, A.M., De Vonderweld, U., The "kangaroo-mother" method: Evaluation of an alternative model for the care of low birth weight newborns in developing countries (1990) Int J Gynaecol Obstet, 31, pp. 355-359Ludington-Hoe, S.M., Anderson, G.C., Simpson, S., Hollingsead, A., Argote, L.A., Rey, H., Birth-related fatigue in 34-36 week preterm neonates: Rapid recovery with very early kangaroo (skin-to-skin) care (1999) J Obstet Gynecol Neonatal Nurs, 28, pp. 94-103Ludington-Hoe, S.M., Nguyen, N., Swinth, J.Y., Satyshur, R.D., Kangaroo care compared to incubators in maintaining body warmth in preterm infants (2000) Biol Res Nurs, 2, pp. 60-73Carvalho, M.R., Prochnik, M., Método Mãe-Canguru de Atenção Ao Prematuro, , http://federativo.bndes.gov.br/bf_bancos/experiencias/x0001959.pdfPortaria GM N. 693 - Norma de orientação para a implantação do método canguru Diário Oficial da União 2000, , 5 julNormas de atenção humanizada ao recém-nascido de baixo peso (método canguru) no Estado de São Paulo Diário Oficial do Estado 2001, , 6 jun(1993) Manejo e Promoção Do Aleitamento Materno: Curso de 18 Horas para Equipes de Maternidades, , Brasília: Fundo das Nações Unidas para a InfânciaLevin, A., Humane neonatal care initiative (1999) Acta Paediatr, 88, pp. 353-355(2002) Saúde No Estado de São Paulo: Compromisso Com O Cidadão, , São Paulo: Secretaria de Estado da Saúde de São PauloKirsten, G.F., Bergman, N.J., Hann, F.M., Kangaroo mother care in the nursery (2001) Pediatr Clin North Am, 48, pp. 443-452Toma, T.S., Método Mãe Canguru: O papel dos serviços de saúde e das redes familiares no sucesso do programa (2003) Cad Saúde Pública, 19 (2 SUPPL.), pp. S233-42Lima, G., Quintero-Romero, S., Cattaneo, A., Feasibility, acceptability and cost of kangaroo mother care in Recife, Brazil (2000) Ann Trop Paediatr, 20, pp. 22-26Lincetto, O., Nazir, A.I., Cattaneo, A., Kangaroo mother care with limited resources (2000) J Trop Pediatr, 46, pp. 293-295Cecchetto, S., Mãe canguru: Tecnologia perinatal humana. Parte I: Uma abordagem pela bioética (2002) Amamentação: Bases Científicas para a Prática Profissional, pp. 132-136. , Carvalho MR, Tamez RN, organizadores. Rio de Janeiro: Guanabara KooganNogueira-Martins, M.C.F., (2001) Humanização Das Relações Assistenciais: A Formação Do Profissional de Saúde, , São Paulo: Casa do PsicólogoDenis, J.-L., Champagne, F., Análise da implantação (2000) Avaliação Em Saúde: Dos Modelos Conceituais à Prática Na Análise de Implantação de Programas, pp. 49-88. , Hartz ZMA, organizadora. Rio de Janeiro: Editora FiocruzFurlan, C.E.F.B., Scochi, C.G.S., Furtado, M.C.C., Percepção dos pais sobre a vivência no método mãecanguru (2003) Rev Lat Am Enfermagem, 11, pp. 444-45

Identification of novel sarcoma risk genes using a two-stage genome wide DNA sequencing strategy in cancer cluster families and population case and control cohorts

Background Although familial clustering of cancers is relatively common, only a small proportion of familial cancer risk can be explained by known cancer predisposition genes. Methods In this study we employed a two-stage approach to identify candidate sarcoma risk genes. First, we conducted whole exome sequencing in three multigenerational cancer families ascertained through a sarcoma proband (n = 19) in order to prioritize candidate genes for validation in an independent case-control cohort of sarcoma patients using family-based association and segregation analysis. The second stage employed a burden analysis of rare variants within prioritized candidate genes identified from stage one in 560 sarcoma cases and 1144 healthy ageing controls, for which whole genome sequence was available. Results Variants from eight genes were identified in stage one. Following gene-based burden testing and after correction for multiple testing, two of these genes, ABCB5 and C16orf96, were determined to show statistically significant association with cancer. The ABCB5 gene was found to have a higher burden of putative regulatory variants (OR = 4.9, p-value = 0.007, q-value = 0.04) based on allele counts in sarcoma cases compared to controls. C16orf96, was found to have a significantly lower burden (OR = 0.58, p-value = 0.0004, q-value = 0.003) of regulatory variants in controls compared to sarcoma cases. Conclusions Based on these genetic association data we propose that ABCB5 and C16orf96 are novel candidate risk genes for sarcoma. Although neither of these two genes have been previously associated with sarcoma, ABCB5 has been shown to share clinical drug resistance associations with melanoma and leukaemia and C16orf96 shares regulatory elements with genes that are involved with TNF-alpha mediated apoptosis in a p53/TP53-dependent manner. Future genetic studies in other family and population cohorts will be required for further validation of these novel findings

Phytophthora elongata sp. nov., a novel pathogen from the Eucalyptus marginata forest of Western Australia

A novel homothallic species of Phytophthora producing semipapillate sporangia on sympodially branching sporangiophores, thick-walled oospores in smooth-walled oogonia, and paragynous antheridia is described here as Phytophthora elongata sp. nov. DNA sequencing of the internal transcribed spacer (ITS) DNA and cox1 gene confirm P. elongata as a distinct species within ITS clade 2. It has been isolated in the northern jarrah forest of Western Australia(WA) from the roots and collars of dead and dying Eucalyptus marginata and occasionally Corymbia calophylla in rehabilitated bauxite mine pits. It has also been associated with dead and dying plants of several mid- and understorey species in the northern and southern jarrah forest - Banksia grandis, Leucopogon propinquus, Dryandra squarrosa and an Andersonia sp., as well as the monocotyledonous Xanthorrhoea preissii, X. gracilis and Patersonia xanthina. P. elongata has also been isolated from sandy soils and loams in Victoria in eastern Australia. The pathogenicity of P. elongata to E. marginata and Banksia spp. has been shown in this and earlier studies. Due to the uniformity of the ITS DNA and cox1 sequence data in WA, P. elongata may be the result of a recent clonal introduction. More pathogenicity tests on a wider range of native plant species are needed to assess the host range of P. elongata and its invasive potential in WA

Two novel and potentially endemic species of Phytophthora associated with episodic dieback of Kwongan vegetation in the south-west of Western Australia

Two novel homothallic species of Phytophthora causing dieback of Kwongan vegetation in south-west Western Australia are described here as Phytophthora arenaria sp. nov. and Phytophthora constricta sp. nov. DNA sequencing of the ITS rDNA and cox1 gene confirmed that P. arenaria and P. constricta are unique species residing in ITS clades 4 and 9, respectively. Phytophthora arenaria has been isolated from vegetation occurring on the northern sandplains which are warmer and drier than the southern sandplains from which P. constricta has been predominantly isolated, and both species appear morphologically and physiologically well adapted to the ecosystems in which they occur. Both species have been associated mainly with dead and dying Banksia species and the pathogenicity of both P. arenaria and P. constricta to Banksia attenuata was confirmed in this study. The combination of unique DNA sequences, including considerable variation in cox1 sequence data, thick oospore walls and physiological characteristics that appear to be adaptations favouring survival in the harsh Kwongan ecosystem suggest that these species may be endemic to Western Australia

Cytochrome P450 BM3 Mutants as NOVEL Biocatalytic TOOLS for Regioselective Hydroxylation of Steroids

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