Using C. elegans to decipher the cellular and molecular mechanisms underlying neurodevelopmental disorders

Prova tipográfica (uncorrected proof)Neurodevelopmental disorders such as epilepsy, intellectual disability (ID), and autism spectrum disorders (ASDs) occur in over 2 % of the population, as the result of genetic mutations, environmental factors, or combination of both. In the last years, use of large-scale genomic techniques allowed important advances in the identification of genes/loci associated with these disorders. Nevertheless, following association of novel genes with a given disease, interpretation of findings is often difficult due to lack of information on gene function and effect of a given mutation in the corresponding protein. This brings the need to validate genetic associations from a functional perspective in model systems in a relatively fast but effective manner. In this context, the small nematode, Caenorhabditis elegans, presents a good compromise between the simplicity of cell models and the complexity of rodent nervous systems. In this article, we review the features that make C. elegans a good model for the study of neurodevelopmental diseases. We discuss its nervous system architecture and function as well as the molecular basis of behaviors that seem important in the context of different neurodevelopmental disorders. We review methodologies used to assess memory, learning, and social behavior as well as susceptibility to seizures in this organism. We will also discuss technological progresses applied in C. elegans neurobiology research, such as use of microfluidics and optogenetic tools. Finally, we will present some interesting examples of the functional analysis of genes associated with human neurodevelopmental disorders and how we can move from genes to therapies using this simple model organism.The authors would like to acknowledge Fundação para a Ciência e Tecnologia (FCT) (PTDC/SAU-GMG/112577/2009). AJR and CB are recipients of FCT fellowships: SFRH/BPD/33611/2009 and SFRH/BPD/74452/2010, respectively

Classification of quantum phases for the star-lattice antiferromagnet via a projective symmetry group analysis

We study possible quantum ground states of the Heisenberg antiferromagnet on the star lattice, which may be realized in the recently discovered polymeric iron acetate, Fe-3(mu(3)-O)(mu-OAc)(6)(H2O)(3)[Fe-3(mu(3)-O)(mu-OAc)(7.5)](2)center dot 7H(2)O [Y. Z. Zheng , Angew. Chem. Int. Ed. 46, 6076 (2007)]. Even though the Fe-III moment in this material carries spin-5/2 and the system eventually orders magnetically at low temperatures, the magnetic ordering temperature is much lower than the estimated Curie-Weiss temperature, revealing the frustrated nature of the spin interactions. Anticipating that a lower spin analog of this material may be synthesized in future, we investigate the effect of quantum fluctuations on the star-lattice antiferromagnet using a large-N Sp(N) mean field theory and a projective symmetry group analysis for possible bosonic quantum spin liquid phases. It is found that there exist only two distinct gapped Z(2) spin liquid phases with bosonic spinons for nonvanishing nearest-neighbor valence-bond amplitudes. In particular, the spin liquid phase which has a lower energy in the nearest-neighbor exchange model can be stabilized for relatively higher spin magnitudes. Hence, it is perhaps a better candidate for the realization of quantum spin liquid state. We also determine the magnetic ordering patterns resulting from the condensation of the bosonic spinons in the two different spin liquid phases. We expect these magnetic ordering patterns would directly be relevant for the low temperature ordered phase of the iron acetate. The phase diagram containing all of these phases and various dimerized states are obtained for the nearest-neighbor exchange model and its implications are discussed

Isotopic evidence of particle size-dependent food partitioning in cocultured sea squirt Halocynthia roretzi and Pacific oyster Crassostrea gigas

To examine the trophic relationship between the sea squirt Halocynthia roretzi and the Pacific oyster Crassostrea gigas cocultured in suspension, their delta C-13 and delta N-15 values were monitored monthly on the southern coast of Korea for a period of 2 yr. Suspended particulate organic matter was fractionated as coarse (>20 mu m, CPOM) and fine particles (<20 mu m, FPOM), and the seasonal variations in the delta C-13 and delta N-15 were determined. CPOM delta C-13 was slightly more variable than FPOM delta C-13 over the sampling period, whereas delta N-15 varied less for CPOM than for FPOM. Co- and monocultured sea squirts had a less variable VC, but a more variable delta N-15 than cocultured oysters over the sampling period, The delta C-13 and delta N-15 of cocultured sea squirts were consistently lower than those of cocultured oysters. The more pronounced difference in the delta C-13 between the cocultured suspension feeders was attributed to a striking isotopic change in oysters during their autumn to winter growing period. Differences in the VC were significant between co-, monocultured, and wild sea squirts, but not between co- and monocultured oysters. These suspension feeders can use different POM size fractions within the same habitat. The marked C-13-enrichment in oyster tissues, particularly during their fast growing period, may result from their strong selectivity of diatoms. In contrast, both the C-13- and N-15-depleted values in cocultured sea squirts indicate the importance of pico-/nano-size fractions as their dietary components. Size-related patterns in food resource exploitation between the cocultured suspension feeders may be due to different particle capture mechanisms.X111717sciescopu

A nanohybrid system for taste masking of sildenafil

Ji-Hee Lee1,*, Goeun Choi1,*, Yeon-Ji Oh1, Je Won Park1, Young Bin Choy3, Mung Chul Park1, Yeo Joon Yoon1, Hwa Jeong Lee2, Hee Chul Chang4, Jin-Ho Choy1 1Center for Intelligent Nano-Bio Materials (CINBM), Department of Bioinspired Science and Department of Chemistry and Nano Science, 2Division of Life and Pharmaceutical Sciences and College of Pharmacy, Ewha Womans University, Seoul, Korea; 3Department of Biomedical Engineering, College of Medicine and Institute of Medical and Biological Engineering, Medical Research Center, Seoul National University, Seoul, Korea; 4Global Strategy Center and Pharmaceutical Research Institute, Daewoong Pharmaceutical Co., Ltd., Seoul, Korea*These authors contributed equally to this workAbstract: A nanohybrid was prepared with an inorganic clay material, montmorillonite (MMT), for taste masking of sildenafil (SDN). To further improve the taste-masking efficiency and enhance the drug-release rate, we coated the nanohybrid of SDN&amp;ndash;MMT with a basic polymer, polyvinylacetal diethylaminoacetate (AEA). Powder X-ray diffraction and Fourier transform infrared experiments showed that SDN was successfully intercalated into the interlayer space of MMT. The AEA-coated SDN&amp;ndash;MMT nanohybrid showed drug release was much suppressed at neutral pH (release rate, 4.70 &amp;plusmn; 0.53%), suggesting a potential for drug taste masking at the buccal cavity. We also performed in vitro drug release experiments in a simulated gastric fluid (pH = 1.2) and compared the drug-release profiles of AEA-coated SDN&amp;ndash;MMT and Viagra&amp;reg;, an approved dosage form of SDN. As a result, about 90% of SDN was released from the AEA-coated SDN&amp;ndash;MMT during the first 2 hours while almost 100% of drug was released from Viagra&amp;reg;. However, an in vivo experiment showed that the AEA-coated SDN&amp;ndash;MMT exhibited higher drug exposure than Viagra&amp;reg;. For the AEA-coated SDN&amp;ndash;MMT, the area under the plasma concentration&amp;ndash;time curve from 0 hours to infinity (AUC0-&amp;infin;) and maximum concentration (Cmax) were 78.8 &amp;plusmn; 2.32 &amp;micro;g &amp;bull; hour/mL and 12.4 &amp;plusmn; 0.673 &amp;micro;g/mL, respectively, both of which were larger than those obtained with Viagra&amp;reg; (AUC0-&amp;infin; = 69.2 &amp;plusmn; 3.19 &amp;micro;g &amp;bull; hour/mL; Cmax = 10.5 &amp;plusmn; 0.641 &amp;micro;g/mL). Therefore, we concluded that the MMT-based nanohybrid is a promising delivery system for taste masking of SDN with possibly improved drug exposure.Keywords: montmorillonite, nanohybrids, polyvinylacetal diethylaminoacetate, sildenafil citrate, taste maskin

Transversely isotropic properties of porcine liver tissue: Experiments and constitutive modelling

10.1007/s11517-006-0137-yMedical and Biological Engineering and Computing45199-106MBEC