The effects of quercetin and kaempferol on multidrug resistance and the expression of related genes in human erythroleukemic K562/A cells

Leukemia chemotherapy is believed to be impeded by multidrug resistance (MDR). Some compounds of flavonoid molecules were previously shown to inhibit drug transporter Pgp or induce apoptosis to sensitize MDR tumors. In this study, we attempted to investigate the possibility and mechanism of quercetin and kaempferol, flavonoid molecules, in reversing MDR. K562/A cells were cultured in vitro with the flavonoids as single and in combination respectively. Cell growth inhibition and adriamycin (ADR) sensitivity were detected by 3-[4,5-dimethylthiazol-2-yl]-2,5 -diphenyltetrazolium bromide (MTT) assay. Cell apoptosis was examined by Annexin V/PI staining method. Moreover, the expression of related genes for drug transporters and apoptosis was also tested after incubation with resveratrol for the first time. Results show a dose dependent manner and synergistic effect of the two compounds on K562/A. Furthermore, some of the genes in drug transporter families such as ATP-binding cassette (ABC) and solute carrier (SLC) and apoptosis related genes such as Bcl-2、tumor necrosis factor (TNF) and tumor necrosis factor receptor (TNFR) families were regulated. The experiment indicates that quercetin and kaempferol may be used as reveratrol in leukemia chemotherapy, but their interaction and difference should be noticed.Key words: Flavonoids, leukemia, multidrug resistance, polymerase chain reaction (PCR) array

Preconditioning for the mixed formulation of linear plane elasticity

In this dissertation, we study the mixed finite element method for the linear plane elasticity problem and iterative solvers for the resulting discrete system. We use the Arnold-Winther Element in the mixed finite element discretization. An overlapping Schwarz preconditioner and a multigrid preconditioner for the discrete system are developed and analyzed. We start by introducing the mixed formulation (stress-displacement formulation) for the linear plane elasticity problem and its discretization. A detailed analysis of the Arnold-Winther Element is given. The finite element discretization of the mixed formulation leads to a symmetric indefinite linear system. Next, we study efficient iterative solvers for the symmetric indefinite linear system which arises from the mixed finite element discretization of the linear plane elasticity problem. The preconditioned Minimum Residual Method is considered. It is shown that the problem of constructing a preconditioner for the indefinite linear system can be reduced to the problem of constructing a preconditioner for the H(div) problem in the Arnold-Winther finite element space. Our main work involves developing an overlapping Schwarz preconditioner and a multigrid preconditioner for the H(div) problem. We give condition number estimates for the preconditioned systems together with supporting numerical results

Use of redundant exclusion PCR to identify a novel Bacillus thuringiensis Cry8 toxin gene from pooled genomic DNA

With the aim of optimizing the cloning of novel genes from a genomic pool containing many previously identified, homologous, genes we designed a redundant exclusion PCR technique. In RE-PCR a pair of generic amplification primers are combined with additional primers that are designed to specifically bind to redundant, unwanted genes that are a subset of those copied by the amplification primers. During RE-PCR the specific primer blocks amplification of the full length redundant gene. Using this method we managed to clone a number of cry8 or cry9 toxin genes from a pool of Bacillus thuringiensis genomic DNA while excluding amplicons for cry9Da, cry9Ea and cry9Eb. The method proved very efficient at increasing the number of rare genes in the resulting library. One such rare, and novel, cry8-like gene was expressed and the encoded toxin was shown to be toxic to Anomola corpulenta

The “Soluble” Adenylyl Cyclase in Sperm Mediates Multiple Signaling Events Required for Fertilization

SummaryMammalian fertilization is dependent upon a series of bicarbonate-induced, cAMP-dependent processes sperm undergo as they “capacitate,” i.e., acquire the ability to fertilize eggs. Male mice lacking the bicarbonate- and calcium-responsive soluble adenylyl cyclase (sAC), the predominant source of cAMP in male germ cells, are infertile, as the sperm are immotile. Membrane-permeable cAMP analogs are reported to rescue the motility defect, but we now show that these “rescued” null sperm were not hyperactive, displayed flagellar angulation, and remained unable to fertilize eggs in vitro. These deficits uncover a requirement for sAC during spermatogenesis and/or epididymal maturation and reveal limitations inherent in studying sAC function using knockout mice. To circumvent this restriction, we identified a specific sAC inhibitor that allowed temporal control over sAC activity. This inhibitor revealed that capacitation is defined by separable events: induction of protein tyrosine phosphorylation and motility are sAC dependent while acrosomal exocytosis is not dependent on sAC

Countdown to 2015 country case studies: What have we learned about processes and progress towards MDGs 4 and 5?

BACKGROUND: Countdown to 2015 was a multi-institution consortium tracking progress towards Millennium Development Goals (MDGs) 4 and 5. Case studies to explore factors contributing to progress (or lack of progress) in reproductive, maternal, newborn and child health (RMNCH) were undertaken in: Afghanistan, Bangladesh, China, Ethiopia, Kenya, Malawi, Niger, Pakistan, Peru, and Tanzania. This paper aims to identify cross-cutting themes on how and why these countries achieved or did not achieve MDG progress. METHODS: Applying a standard evaluation framework, analyses of impact, coverage and equity were undertaken, including a mixed methods analysis of how these were influenced by national context and coverage determinants (including health systems, policies and financing). RESULTS: The majority (7/10) of case study countries met MDG-4 with over two-thirds reduction in child mortality, but none met MDG-5a for 75 % reduction in maternal mortality, although six countries achieved >75 % of this target. None achieved MDG-5b regarding reproductive health. Rates of reduction in neonatal mortality were half or less that for post-neonatal child mortality. Coverage increased most for interventions administered at lower levels of the health system (e.g., immunisation, insecticide treated nets), and these experienced substantial political and financial support. These interventions were associated with ~30-40 % of child lives saved in 2012 compared to 2000, in Ethiopia, Malawi, Peru and Tanzania. Intrapartum care for mothers and newborns - which require higher-level health workers, more infrastructure, and increased community engagement - showed variable increases in coverage, and persistent equity gaps. Countries have explored different approaches to address these problems, including shifting interventions to the community setting and tasks to lower-level health workers. CONCLUSIONS: These Countdown case studies underline the importance of consistent national investment and global attention for achieving improvements in RMNCH. Interventions with major global investments achieved higher levels of coverage, reduced equity gaps and improvements in associated health outcomes. Given many competing priorities for the Sustainable Development Goals era, it is essential to maintain attention to the unfinished RMNCH agenda, particularly health systems improvements for maternal and neonatal outcomes where progress has been slower, and to invest in data collection for monitoring progress and for rigorous analyses of how progress is achieved in different contexts

Potential of pre-contrast T1 mapping as a marker of interstitial fibrosis in severe aortic stenosis

International audiencen.

Non-invasive assessment of interstitial myocardial fibrosis in pressure-overload left ventricular hypertrophy

International audiencen.

Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution