88 research outputs found

    Quantitative Dissection of Clone-Specific Growth Rates in Cultured Malaria Parasites

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    Measurement of parasite proliferation in cultured red blood cells underpins many facets of malaria research, from drug sensitivity assays to assessing the impact of experimentally altered genes on parasite growth, virulence, and fitness. Pioneering efforts to grow Plasmodium falciparum in cultured red blood cells revolutionized malaria research and spurred the development of semi-high throughput growth assays using radio-labeled hypoxanthine, an essential nucleic acid precursor, as a reporter of whole-cycle proliferation (Trager and Jensen, 1976; Desjardins et al., 1979). Use of hypoxanthine (Hx) and other surrogate readouts of whole-cycle proliferation remains the dominant choice in malaria research. While amenable to high-throughput inference of bulk proliferation rates, these assays are blind to the underlying developmental and cellular steps of growth in human red blood cells. Modern whole-genome methods promise to reveal much about basic parasite biology, but progress is hindered by limitations of our ability to precisely quantify the specific development and growth events within the erythrocytic cycle. Here we build on standard visual and Hx-incorporation measures of growth by quantifying sub-phenotypes of a rapid proliferator, the multi-drug resistant clone Dd2, from a standard wild type clone, HB3. These data illustrate differences in cycle duration, merozoite production, and invasion rate and efficiency that underpin Dd2’s average 2-fold proliferation advantage over HB3 per erythrocytic cycle. The ability to measure refined growth phenotypes can inform the development of high-throughput methods to isolate molecular and developmental determinants of differential parasite growth rates

    Water Potential of Aqueous Polyethylene Glycol

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    Identifying novel phenotypes of elevated left ventricular end diastolic pressure using hierarchical clustering of features derived from electromechanical waveform data

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    Introduction Elevated left ventricular end diastolic pressure (LVEDP) is a consequence of compromised left ventricular compliance and an important measure of myocardial dysfunction. An algorithm was developed to predict elevated LVEDP utilizing electro-mechanical (EM) waveform features. We examined the hierarchical clustering of selected features developed from these EM waveforms in order to identify important patient subgroups and assess their possible prognostic significance. Materials and methods Patients presenting with cardiovascular symptoms (N = 396) underwent EM data collection and direct LVEDP measurement by left heart catheterization. LVEDP was classified as non-elevated ( ≤ 12 mmHg) or elevated (≥25 mmHg). The 30 most contributive features to the algorithm output were extracted from EM data and input to an unsupervised hierarchical clustering algorithm. The resultant dendrogram was divided into five clusters, and patient metadata overlaid. Results The cluster with highest LVEDP (cluster 1) was most dissimilar from the lowest LVEDP cluster (cluster 5) in both clustering and with respect to clinical characteristics. In contrast to the cluster demonstrating the highest percentage of elevated LVEDP patients, the lowest was predominantly non-elevated LVEDP, younger, lower BMI, and males with a higher rate of significant coronary artery disease (CAD). The next adjacent cluster (cluster 2) to that of the highest LVEDP (cluster 1) had the second lowest LVEDP of all clusters. Cluster 2 differed from Cluster 1 primarily based on features extracted from the electrical data, and those that quantified predictability and variability of the signal. There was a low predictability and high variability in the highest LVEDP cluster 1, and the opposite in adjacent cluster 2. Conclusion This analysis identified subgroups of patients with varying degrees of LVEDP elevation based on waveform features. An approach to stratify movement between clusters and possible progression of myocardial dysfunction may include changes in features that differentiate clusters; specifically, reductions in electrical signal predictability and increases in variability. Identification of phenotypes of myocardial dysfunction evidenced by elevated LVEDP and knowledge of factors promoting transition to clusters with higher levels of left ventricular filling pressures could permit early risk stratification and improve patient selection for novel therapeutic interventions

    Efeito de várias disponibilidades hídricas, atuando como pré-condicionamento fisiológico durante a germinação das sementes de milho, no desenvolvimento das plântulas

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    The present paper considers the possible effects of physiological pre-treatment during the beginning of corn seeds germination in environments variable as to water availability (0 to -12 atm ). Periods of defficiency followed by 5 days without hydric limitations were compared with a control that remained equally, without reservations as to the disposability of water during 5 days. Results indicated that hydric pre-treatment of seeds can, if property adapted in its details, provide some advantages in the development of the seedlings derived from them. Chemical fungicide treatment of the seeds, submmited to the hydric pre-treatment may not be beneficial to the seedlings; as indicated by, in some isolated cases, the production of abnormalities in the embryonic structures.O presente trabalho buscou estimar os eventuais efeitos de pré-condicionamento fisiológico promovidos, durante o início da germinação das sementes de milho, por ambientes variáveis quanto à disponibilidade de água (0 a -12 atm). Para tanto, os períodos de deficiência eram sucedidos por prazos fixos de 5 dias sem limitações hídricas e comparados com uma testemunha que permaneceu, igualmente, sem restrições quanto à disponibilidade de água durante 5 dias. Os resultados encontrados indicaram que a técnica de pré-condicionamento hídrico das sementes pode, se devidamente adaptada em seus detalhes, propiciar algumas vantagens no desenvolvimento das plântulas delas oriundas. Adicionalmente, o tratamento químico fungicida das sementes, submetidas a pré-condicionamento hídrico, pode não trazer os benefícios esperados às plântulas; há casos isolados, ligados a produção de anormalidades nas estruturas embrionárias, em que o seu efeito é prejudicial

    A Practitioner's View

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