31 research outputs found
Adsorption of mono- and multivalent cat- and anions on DNA molecules
Adsorption of monovalent and multivalent cat- and anions on a deoxyribose
nucleic acid (DNA) molecule from a salt solution is investigated by computer
simulation. The ions are modelled as charged hard spheres, the DNA molecule as
a point charge pattern following the double-helical phosphate strands. The
geometrical shape of the DNA molecules is modelled on different levels ranging
from a simple cylindrical shape to structured models which include the major
and minor grooves between the phosphate strands. The densities of the ions
adsorbed on the phosphate strands, in the major and in the minor grooves are
calculated. First, we find that the adsorption pattern on the DNA surface
depends strongly on its geometrical shape: counterions adsorb preferentially
along the phosphate strands for a cylindrical model shape, but in the minor
groove for a geometrically structured model. Second, we find that an addition
of monovalent salt ions results in an increase of the charge density in the
minor groove while the total charge density of ions adsorbed in the major
groove stays unchanged. The adsorbed ion densities are highly structured along
the minor groove while they are almost smeared along the major groove.
Furthermore, for a fixed amount of added salt, the major groove cationic charge
is independent on the counterion valency. For increasing salt concentration the
major groove is neutralized while the total charge adsorbed in the minor groove
is constant. DNA overcharging is detected for multivalent salt. Simulations for
a larger ion radii, which mimic the effect of the ion hydration, indicate an
increased adsorbtion of cations in the major groove.Comment: 34 pages with 14 figure
SPL7013 Gel (VivaGelÂź) Retains Potent HIV-1 and HSV-2 Inhibitory Activity following Vaginal Administration in Humans
SPL7013 Gel (VivaGelÂź) is a microbicide in development for prevention of HIV and HSV. This clinical study assessed retention and duration of antiviral activity following vaginal administration of 3% SPL7013 Gel in healthy women. Participants received 5 single doses of product with â„5 days between doses. A cervicovaginal fluid (CVF) sample was collected using a SoftCupâą pre-dose, and immediately, or 1, 3, 12 or 24 h post-dose. HIV-1 and HSV-2 antiviral activities of CVF samples were determined in cell culture assays. Antiviral activity in the presence of seminal plasma was also tested. Mass and concentration of SPL7013 in CVF samples was determined. Safety was assessed by reporting of adverse events. Statistical analysis was performed using the Wilcoxon signed-rank test with Bonferroni adjustment; pâ€0.003 was significant. Eleven participants completed the study. Inhibition of HIV-1 and HSV-2 by pre-dose CVF samples was negligible. CVF samples obtained immediately after dosing almost completely inhibited (median, interquartile range) HIV-1 [96% (95,97)] and HSV-2 [86% (85,94)], and activity was maintained in all women at 3 h (HIV-1 [96% (95,98), pâ=â0.9]; HSV-2 [94% (91,97), pâ=â0.005]). At 24 h, >90% of initial HIV-1 and HSV-2 inhibition was maintained in 6/11 women. SPL7013 was recovered in CVF samples obtained at baseline (46% of 105 mg dose). At 3 and 24 h, 22 mg and 4 mg SPL7013, respectively, were recovered. More than 70% inhibition of HIV-1 and HSV-2 was observed if there was >0.5 mg SPL7013 in CVF samples. High levels of antiviral activity were retained in the presence of seminal plasma. VivaGel was well tolerated with no signs or symptoms of vaginal, vulvar or cervical irritation reported. Potent antiviral activity was observed against HIV-1 and HSV-2 immediately following vaginal administration of VivaGel, with activity maintained for at least 3 h post-dose. The data provide evidence of antiviral activity in a clinical setting, and suggest VivaGel could be administered up to 3 h before coitus
Phylogenetic analysis of feline immunodeficiency virus strains from State of Minas Gerais, Brazil
Speciesâspecific differences in the ability of feline lentiviral Vif to degrade feline APOBEC3 proteins
Towards a global paradigm for research in early childhood education
Early years education is now a global activity, as school systems expand and diverse programmes become established in countries throughout the world. We inherit a rich legacy of theories, methodologies and evidence, from the vision of early childhood pioneers to the latest empirical research. I want to step back from particular initiatives and research evaluations to consider the underlying images of the child that inform early childhood research and practice.
What would be an appropriate child development paradigm for promoting quality early years education in a global context? I question the adequacy of much theory and research to encompass global childhoods, especially the dangers inherent in current knowledge-imbalances. I ask about the way child development is conceptualised within early childhood work, and the potential of a sociocultural perspective. Finally, I ask about the status of young children themselves within early education research and practice; whether they are viewed as subjects in a child development project, as participants in a process or as consumers of a service. For each theme, I will argue that we are witnessing a paradigm shift which takes us beyond idealisations about normal development, children's nature and their needs. An alternative paradigm emphasises the plurality of pathways through childhood, the respects in which early development and education is a sociocultural process, and the status of children as active participants, with their own perspective on issues in their lives
Detecção do provĂrus da ImunodeficiĂȘncia Felina em gatos domĂ©sticos pela tĂ©cnica de Reação em Cadeia da Polimerase Detection of feline immunodeficiency provirus in domestic cats by polymerase chain reaction
A infecção de gatos domĂ©sticos pelo VĂrus da ImunodeficiĂȘncia Felina (FIV) Ă© um dos modelos mais promissores para o estudo da infecção pelo vĂrus da imunodeficiĂȘncia humana (HIV) que causa a SĂndrome de ImunodeficiĂȘncia Adquirida (AIDS). O FIV causa, em gatos, uma enfermidade similar Ă quela observada em pacientes com AIDS, sobretudo no que diz respeito ao aumento da susceptibilidade a infecçÔes oportunistas. No presente estudo, utilizou-se a Reação em Cadeia da Polimerase (PCR), com o objetivo de detectar o provĂrus do FIV em gatos com sinais clĂnicos de imunodeficiĂȘncia. O fragmento de DNA escolhido como alvo para amplificação situa-se no gene gag do lentivĂrus felino, o qual Ă© conservado entre as diferentes amostras do vĂrus. O DNA utilizado foi extraĂdo a partir de amostras de sangue e de tecidos de animais com suspeita clĂnica de imunodeficiĂȘncia. Das 40 amostras analisadas, 15 foram positivas, das quais 4 foram submetidas Ă hibridização, confirmando a especificidade dos fragmentos amplificados. Esses resultados demonstram a presença do FIV na população de gatos domĂ©sticos do Rio Grande do Sul, Brasil.<br>Feline immunodeficiency virus (FIV) infection of domestic cats is one of the most promising animal models for the infection by the human immunodeficiency virus (HIV) which causes acquired immunodeficiency syndrome (AIDS). Infected cats may develop a disease similar to that observed in AIDS patients, with increased susceptibility to opportunistic infections. In this study we used the polymerase chain reaction (PCR) to detect proviral DNA of feline immunodeficiency virus on the blood and tissue samples from cats with a clinical diagnosis of immunodeficiency. The PCR primers were used to amplify the gag gene, which is conserved among different isolates. From 40 samples analyzed, 15 were positive and 4 of them were submitted to hybridization to confirm the specificity of the amplified fragments. These results confirm the presence of FIV in domestic cats in Rio Grande do Sul, Brazil