Characterization of Chilling Sensitivity of Tropical and Temperate Grasses

C16-C18 fatty acid composition of some lipids in several species of temperate and tropical grasses were measured. The fatty acid composition of phosphatidylglycerol (PG) and sulfoquinovosyl diglyceride (SQDG) indicated significant differences between temperate and tropical grasses. Especially the differences of the fatty acid composition of PG were remarkable. The unsaturated fatty acid content of PG in tropical grasses was lower than the contents in temperate grasses. These differences constantly appeared through the year. These differences were caused by the low content of polyunsaturated fatty acids, or the low contents of C18 fatty acids

Wet and dry deposition of mineral dust particles in Japan: factors related to temporal variation and spatial distribution

Recent ground networks and satellite remote-sensing observations have provided useful data related to spatial and vertical distributions of mineral dust particles in the atmosphere. However, measurements of temporal variations and spatial distributions of mineral dust deposition fluxes are limited in terms of their duration, location, and processes of deposition. To ascertain temporal variations and spatial distributions of mineral dust deposition using wet and dry processes, weekly deposition samples were obtained at Sapporo, Toyama, Nagoya, Tottori, Fukuoka, and Cape Hedo (Okinawa) in Japan during October 2008–December 2010 using automatic wet and dry separating samplers. Mineral dust weights in water-insoluble residue were estimated from Fe contents measured using an X-ray fluorescence analyser. Wet and dry deposition fluxes of mineral dusts were both high in spring and low in summer, showing similar seasonal variations to frequency of aeolian dust events (Kosa) in Japan. For wet deposition, highest and lowest annual dust fluxes were found at Toyama (9.6 g m⁻² yr⁻¹) and at Cape Hedo (1.7 g m⁻² yr⁻¹) as average values in 2009 and 2010. Higher wet deposition fluxes were observed at Toyama and Tottori, where frequent precipitation (> 60% days per month) was observed during dusty seasons. For dry deposition among Toyama, Tottori, Fukuoka, and Cape Hedo, the highest and lowest annual dust fluxes were found respectively at Fukuoka (5.2 g m⁻² yr⁻¹) and at Cape Hedo (2.0 g m⁻² yr⁻¹) as average values in 2009 and 2010. The average ratio of wet and dry deposition fluxes was the highest at Toyama (3.3) and the lowest at Hedo (0.82), showing a larger contribution of the dry process at western sites, probably because of the distance from desert source regions and because of the effectiveness of the wet process in the dusty season. <br><br> Size distributions of refractory dust particles were obtained using four-stage filtration: > 20, > 10, > 5, and > 1 μm diameter. Weight fractions of the sum of > 20 μm and 10–20 μm (giant fraction) were higher than 50% for most of the event samples. Irrespective of the deposition type, the giant dust fractions generally decreased with increasing distance from the source area, suggesting the selective depletion of larger giant particles during atmospheric transport. Based on temporal variations of PM_c (2.5 < <i>D</i> < 10 μm), ground-based lidar, backward air trajectories, and vertical profiles of potential temperatures, transport processes of dust particles are discussed for events with high-deposition and low-deposition flux with high PM_c. Low dry dust depositions with high PM_c concentrations were observed under stronger (5 K km⁻¹) stratification of potential temperature with thinner and lower (< 2 km) dust distributions because the PM_c fraction of dust particles only survived after depletion of giant dust particles by rapid gravitational settling at the time they reach Japan. In contrast, transport through a thicker (> 2 km) dust layer with weak vertical gradient of potential temperature carry more giant dust particles to Japan. Because giant dust particles are an important mass fraction of dust accumulation, especially in the North Pacific, which is known as a high-nutrient, low-chlorophyll (HNLC) region, the transport height and fraction of giant dust particles are important factors for studying dust budgets in the atmosphere and their role in biogeochemical cycles

Gerstmann-Straussler-Scheinker disease in an Alsatian family: clinical and genetic studies

The clinical progression of Gerstmann-Straussler-Scheinker disease in a family of Alsatian origin is reported. The age of onset and the duration of evolution were variable. The clinical picture became more complex over the generations: in the first generations, isolated dementia and in later generations a triad of pyramidal, pseudobulbar syndromes and dementia associated with spinal cord and cerebellar features. Prion gene analysis showed that four surviving patients carry double missense changes at codons 117 and 129, identical to those found in one case at necropsy and 10 other healthy members of the family. The missense changes were not found in 100 controls. No member of the family had modification of condons 102, 178, or 200. The lod score suggests linkage between the missense change at codon 117 and Gerstmann- Straussler-Scheinker disease in this family

Templated Synthesis of Peptide Nucleic Acids via Sequence-Selective Base-Filling Reactions

The templated synthesis of nucleic acids has previously been achieved through the backbone ligation of preformed nucleotide monomers or oligomers. In contrast, here we demonstrate templated nucleic acid synthesis using a base-filling approach in which individual bases are added to abasic sites of a peptide nucleic acid (PNA). Because nucleobase substrates in this approach are not self-reactive, a base-filling approach may reduce the formation of nontemplated reaction products. Using either reductive amination or amine acylation chemistries, we observed efficient and selective addition of each of the four nucleobases to an abasic site in the middle of the PNA strand. We also describe the addition of single nucleobases to the end of a PNA strand through base filling, as well as the tandem addition of two bases to the middle of the PNA strand. These findings represent an experimental foundation for nonenzymatic information transfer through base filling.Chemistry and Chemical Biolog

Tunicate cytostatic factor TC14-3 induces a polycomb group gene and histone modification through Ca2+ binding and protein dimerization

<p>Abstract</p> <p>Background</p> <p>As many invertebrate species have multipotent cells that undergo cell growth and differentiation during regeneration and budding, many unique and interesting homeostatic factors are expected to exist in those animals. However, our understanding of such factors and global mechanisms remains very poor. Single zooids of the tunicate, <it>Polyandrocarpa </it><it>misakiensis</it>, can give off as many as 40 buds during the life span. Bud development proceeds by means of transdifferentiation of very limited number of cells and tissues. TC14-3 is one of several different but closely related polypeptides isolated from <it>P. misakiensis</it>. It acts as a cytostatic factor that regulates proliferation, adhesion, and differentiation of multipotent cells, although the molecular mechanism remains uncertain. The Polycomb group (PcG) genes are involved in epigenetic control of genomic activity in mammals. In invertebrates except <it>Drosophila</it>, PcG and histone methylation have not been studied so extensively, and genome-wide gene regulation is poorly understood.</p> <p>Results</p> <p>When Phe⁶⁵of TC14-3 was mutated to an acidic amino acid, the resultant mutant protein failed to dimerize. The replacement of Thr⁶⁹with Arg⁶⁹made dimers unstable. When Glu¹⁰⁶was changed to Gly¹⁰⁶, the resultant mutant protein completely lost Ca²⁺binding. All these mutant proteins lacked cytostatic activity, indicating the requirement of protein dimerization and calcium for the activity. <it>Polyandrocarpa </it><it>Eed</it>, a component of PcG, is highly expressed during budding, like TC14-3. When wild-type and mutant TC14-3s were applied in vivo and in vitro to <it>Polyandrocarpa </it>cells, only wild-type TC14-3 could induce <it>Eed </it>without affecting histone methyltransferase gene expression. Eed-expressing cells underwent trimethylation of histone H3 lysine27. <it>PmEed </it>knockdown by RNA interference rescued cultured cells from the growth-inhibitory effects of TC14-3.</p> <p>Conclusion</p> <p>These results show that in <it>P. misakiensis</it>, the cytostatic activity of TC14-3 is mediated by <it>PmEed </it>and resultant histone modification, and that the gene expression requires both the protein dimerization and Ca²⁺-binding of TC14-3. This system consisting of a humoral factor, PcG, and histone methylation would contribute to the homeostatic regulation of cell growth and terminal differentiation of invertebrate multipotent cells.</p

Anti-prion drug mPPIg5 inhibits PrP(C) conversion to PrP(Sc).

Prion diseases, also known as transmissible spongiform encephalopathies, are a group of fatal neurodegenerative diseases that include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle and Creutzfeldt-Jakob disease (CJD) in humans. The 'protein only hypothesis' advocates that PrP(Sc), an abnormal isoform of the cellular protein PrP(C), is the main and possibly sole component of prion infectious agents. Currently, no effective therapy exists for these diseases at the symptomatic phase for either humans or animals, though a number of compounds have demonstrated the ability to eliminate PrPSc in cell culture models. Of particular interest are synthetic polymers known as dendrimers which possess the unique ability to eliminate PrP(Sc) in both an intracellular and in vitro setting. The efficacy and mode of action of the novel anti-prion dendrimer mPPIg5 was investigated through the creation of a number of innovative bio-assays based upon the scrapie cell assay. These assays were used to demonstrate that mPPIg5 is a highly effective anti-prion drug which acts, at least in part, through the inhibition of PrP(C) to PrP(Sc) conversion. Understanding how a drug works is a vital component in maximising its performance. By establishing the efficacy and method of action of mPPIg5, this study will help determine which drugs are most likely to enhance this effect and also aid the design of dendrimers with anti-prion capabilities for the future

Pharmacokinetics of Quinacrine Efflux from Mouse Brain via the P-glycoprotein Efflux Transporter

The lipophilic cationic compound quinacrine has been used as an antimalarial drug for over 75 years but its pharmacokinetic profile is limited. Here, we report on the pharmacokinetic properties of quinacrine in mice. Following an oral dose of 40 mg/kg/day for 30 days, quinacrine concentration in the brain of wild-type mice was maintained at a concentration of ∼1 µM. As a substrate of the P-glycoprotein (P-gp) efflux transporter, quinacrine is actively exported from the brain, preventing its accumulation to levels that may show efficacy in some disease models. In the brains of P-gp–deficient Mdr10/0 mice, we found quinacrine reached concentrations of ∼80 µM without any signs of acute toxicity. Additionally, we examined the distribution and metabolism of quinacrine in the wild-type and Mdr10/0 brains. In wild-type mice, the co-administration of cyclosporin A, a known P-gp inhibitor, resulted in a 6-fold increase in the accumulation of quinacrine in the brain. Our findings argue that the inhibition of the P-gp efflux transporter should improve the poor pharmacokinetic properties of quinacrine in the CNS

Continuous Quinacrine Treatment Results in the Formation of Drug-Resistant Prions

Quinacrine is a potent antiprion compound in cell culture models of prion disease but has failed to show efficacy in animal bioassays and human clinical trials. Previous studies demonstrated that quinacrine inefficiently penetrates the blood-brain barrier (BBB), which could contribute to its lack of efficacy in vivo. As quinacrine is known to be a substrate for P-glycoprotein multi-drug resistance (MDR) transporters, we circumvented its poor BBB permeability by utilizing MDR0/0 mice that are deficient in mdr1a and mdr1b genes. Mice treated with 40 mg/kg/day of quinacrine accumulated up to 100 µM of quinacrine in their brains without acute toxicity. PrPSc levels in the brains of prion-inoculated MDR0/0 mice diminished upon the initiation of quinacrine treatment. However, this reduction was transient and PrPSc levels recovered despite the continuous administration of quinacrine. Treatment with quinacrine did not prolong the survival times of prion-inoculated, wild-type or MDR0/0 mice compared to untreated mice. A similar phenomenon was observed in cultured differentiated prion-infected neuroblastoma cells: PrPSc levels initially decreased after quinacrine treatment then rapidly recovered after 3 d of continuous treatment. Biochemical characterization of PrPSc that persisted in the brains of quinacrine-treated mice had a lower conformational stability and different immunoaffinities compared to that found in the brains of untreated controls. These physical properties were not maintained upon passage in MDR0/0 mice. From these data, we propose that quinacrine eliminates a specific subset of PrPSc conformers, resulting in the survival of drug-resistant prion conformations. Transient accumulation of this drug-resistant prion population provides a possible explanation for the lack of in vivo efficacy of quinacrine and other antiprion drugs