Systematic Analysis of Cell Cycle Effects of Common Drugs Leads to the Discovery of a Suppressive Interaction between Gemfibrozil and Fluoxetine

Screening chemical libraries to identify compounds that affect overall cell proliferation is common. However, in most cases, it is not known whether the compounds tested alter the timing of particular cell cycle transitions. Here, we evaluated an FDA-approved drug library to identify pharmaceuticals that alter cell cycle progression in yeast, using DNA content measurements by flow cytometry. This approach revealed strong cell cycle effects of several commonly used pharmaceuticals. We show that the antilipemic gemfibrozil delays initiation of DNA replication, while cells treated with the antidepressant fluoxetine severely delay progression through mitosis. Based on their effects on cell cycle progression, we also examined cell proliferation in the presence of both compounds. We discovered a strong suppressive interaction between gemfibrozil and fluoxetine. Combinations of interest among diverse pharmaceuticals are difficult to identify, due to the daunting number of possible combinations that must be evaluated. The novel interaction between gemfibrozil and fluoxetine suggests that identifying and combining drugs that show cell cycle effects might streamline identification of drug combinations with a pronounced impact on cell proliferation

Genomotyping of Coxiella burnetii Using Microarrays Reveals a Conserved Genomotype for Hard Tick Isolates

C. burnetii is a Gram-negative intracellular Y-proteobacteria that causes the zoonotic disease Q fever. Q fever can manifest as an acute or chronic illness. Different typing methods have been previously developed to classify C. burnetii isolates to explore its pathogenicity. Here, we report a comprehensive genomotyping method based on the presence or absence of genes using microarrays. The genomotyping method was then tested in 52 isolates obtained from different geographic areas, different hosts and patients with different clinical manifestations. The analysis revealed the presence of 10 genomotypes organized into 3 groups, with a topology congruent with that obtained through multi-spacer typing. We also found that only 4 genomotypes were specifically associated with acute Q fever, whereas all of the genomotypes could be associated to chronic human infection. Serendipitously, the genomotyping results revealed that all hard tick isolates, including the Nine Mile strain, belong to the same genomotype

Production of phi mesons at mid-rapidity in sqrt(s_NN) = 200 GeV Au+Au collisions at RHIC

We present the first results of meson production in the K^+K^- decay channel from Au+Au collisions at sqrt(s_NN) = 200 GeV as measured at mid-rapidity by the PHENIX detector at RHIC. Precision resonance centroid and width values are extracted as a function of collision centrality. No significant variation from the PDG accepted values is observed. The transverse mass spectra are fitted with a linear exponential function for which the derived inverse slope parameter is seen to be constant as a function of centrality. These data are also fitted by a hydrodynamic model with the result that the freeze-out temperature and the expansion velocity values are consistent with the values previously derived from fitting single hadron inclusive data. As a function of transverse momentum the collisions scaled peripheral.to.central yield ratio RCP for the is comparable to that of pions rather than that of protons. This result lends support to theoretical models which distinguish between baryons and mesons instead of particle mass for explaining the anomalous proton yield.Comment: 326 authors, 24 pages text, 23 figures, 6 tables, RevTeX 4. To be submitted to Physical Review C as a regular article. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Reading comprehension in autism spectrum disorders: The role of oral language and social functioning

Reading comprehension is an area of difficulty for many individuals with autism spectrum disorders (ASD). According to the Simple View of Reading, word recognition and oral language are both important determinants of reading comprehension ability. We provide a novel test of this model in 100 adolescents with ASD of varying intellectual ability. Further, we explore whether reading comprehension is additionally influenced by individual differences in social behaviour and social cognition in ASD. Adolescents with ASD aged 14-16 years completed assessments indexing word recognition, oral language, reading comprehension, social behaviour and social cognition. Regression analyses show that both word recognition and oral language explain unique variance in reading comprehension. Further, measures of social behaviour and social cognition predict reading comprehension after controlling for the variance explained by word recognition and oral language. This indicates that word recognition, oral language and social impairments may constrain reading comprehension in ASD

Global leaf trait estimates biased due to plasticity in the shade

The study of leaf functional trait relationships, the so-called leaf economics spectrum1,2, is based on the assumption of high-light conditions (as experienced by sunlit leaves). Owing to the exponential decrease of light availability through canopies, however, the vast majority of the world's vegetation exists in at least partial shade. Plant functional traits vary in direct dependence of light availability3, with different traits varying to different degrees, sometimes in conflict with expectations from the economic spectrum3. This means that the derived trait relationships of the global leaf economic spectrum are probably dependent on the extent to which observed data in existing large-scale plant databases represent high-light conditions. Here, using an extensive worldwide database of within-canopy gradients of key physiological, structural and chemical traits3, along with three different global trait databases4,5, we show that: (1) accounting for light-driven trait plasticity can reveal novel trait relationships, particularly for highly plastic traits (for example, the relationship between net assimilation rate per area (Aa) and leaf mass per area (LMA)); and (2) a large proportion of leaf traits in current global plant databases reported as measured in full sun were probably measured in the shade. The results show that even though the majority of leaves exist in the shade, along with a large proportion of observations, our current understanding is too focused on conditions in the sun

Innate Immune Responses of Pulmonary Epithelial Cells to Burkholderia pseudomallei Infection

10.1371/journal.pone.0007308PLoS ONE410