A Convenient Synthesis of D-Psicofuranosyl Nucleosides1

Abstract

As part of our studies on the synthesis of conformationally restricted nucleosides of types 1 and 2, where X = CH₂, O or S, we required access to differentially substituted D-psicofuranosyl nucleosides such as 3. As shown in the table, we have developed a convenient approach to such compounds that depends on the direct condensation of the 1,2:3,4-di-O-isopropylidene-β-D-psicofuranose derivative 4 with an appropriate silylated purine or pyrimidine base.² Although the α and β anomers of 3 are formed in a 1:1 ratio, the yields of the β anomers are generally comparable with earlier condensation methods that use psicofuranosyl- halide², 2-benzoates⁴ or 2-nitro derivative⁵. However, the present method has the advantage that the starting sugar 4 is more readily accessible. The precursor 6′-alcohol can be prepared in very large amounts from D-fructose using the method of Prisbe et al.⁴     

Identification of Peanut Green Mosaic Virus Strains in India*

During field surveys, three peanut green mosaic virus isolates differing in symptomatology on groundnut and a few other hosts were collected. Ultrathin sections of infected groundnut leaflets showed cytoplasmic inclusions with pin wheels and scrolls. In enzyme-linked immunosorbent assay they reacted strongly with antisera to peanut green mosaic and soybean mosaic virus antisera, and moderately with adzuki bean mosaic and peanut stripe virus antisera. All isolates also reacted positively with antisera to peanut eye spot, blackeye cowpea mosaic, pea seed-borne mosaic, potato virus Y and tobacco etch viruses, and did not react with antisera to peanut mottle, bean yellow mosaic, bean common mosaic, clover yellow vein and sugarcane mosaic viruses. SDS-PAGE analysis of purified virus preparations of the three isolates showed a single polypeptide with mol. wt. of 34,500 daltons. Based on these results, the three isolates are identified as biologically distinct strains of peanut green mosaic virus.     

Involvement of Vps33a in the Fusion of Uroplakin-Degrading Multivesicular Bodies with Lysosomes

The apical surface of the terminally differentiated mouse bladder urothelium is largely covered by urothelial plaques, consisting of hexagonally packed 16-nm uroplakin particles. These plaques are delivered to the cell surface by fusiform vesicles (FVs) that are the most abundant cytoplasmic organelles. We have analyzed the functional involvement of several proteins in the apical delivery and endocytic degradation of uroplakin proteins. Although FVs have an acidified lumen and Rab27b, which localizes to these organelles, is known to be involved in the targeting of lysosome-related organelles (LROs), FVs are CD63 negative and are therefore not typical LROs. Vps33a is a Sec1-related protein that plays a role in vesicular transport to the lysosomal compartment. A point mutation in mouse Vps33a (Buff mouse) causes albinism and bleeding (Hermansky-Pudlak syndrome) because of abnormalities in the trafficking of melanosomes and platelets. These Buff mice showed a novel phenotype observed in urothelial umbrella cells, where the uroplakin-delivering FVs were almost completely replaced by Rab27b-negative multivesicular bodies (MVBs) involved in uroplakin degradation. MVB accumulation leads to an increase in the amounts of uroplakins, Lysosomal-associated membrane protein (LAMP)-1/2, and the activities of β-hexosaminidase and β-glucocerebrosidase. These results suggest that FVs can be regarded as specialized secretory granules that deliver crystalline arrays of uroplakins to the cell surface, and that the Vps33a mutation interferes with the fusion of MVBs with mature lysosomes thus blocking uroplakin degradation.     

Thiourea-induced thyroid hormone depletion impairs testicular recrudescence in the air-breathing catfish, Clarias gariepinus

We used thiourea-induced thyroid hormone depletion as a strategy to understand the influence of thyroid hormones on testicular recrudescence of the air-breathing catfish, Clarias gariepinus. Treatment with 0.03% thiourea via immersion for 21 days induced hypothyroidism (thyroid hormone depletion) as evidenced by significantly reduced serum T(3) levels. Thiourea-treated males had narrowed seminiferous lobules with fewer spermatozoa in testis, very little or no secretory fluid, reduced protein and sialic acid levels in seminal vesicles when compared to controls. The histological changes were accompanied by reduction in serum and tissue levels of testosterone (T) and 11-ketotestosterone (11-KT), a potent male specific androgen in fish. Qualitative changes in the localization of catfish gonadotropin-releasing hormone (cfGnRH) and luteinizing hormone (LH, heterologous system) revealed a reduction in the distribution of immunoreactive neuronal cells and fibers in thyroid depleted fish. Interestingly, thiourea-withdrawal group showed physiological and histological signs of recovery after 21 days such as reappearance of spermatozoa and partial restoration of 11-KT and T levels. These data demonstrate that thyroid hormones play a significant role in testicular function of catfish. The mechanism of action includes modulating sex steroids either directly or through the hypothalamo (GnRH)-hypophyseal (LH) axis.     

Resistant sources in groundnut germplasm lines against peanut bud necrosis tospovirus disease

Of the 242 groundnut genotypes, tested both in epiphytotic field and laboratory conditions, the genotypes viz., ICGV 90009, ICGV 86699, ICGV 86329, 91177, 91234, ICGV‐94252 and TG 26 were found promising both with low incidence of PBND besides longer incubation periods, DFSA, DLSA and IP 50%. Further, significant positive correlation was found between IP 50% vs DLSA, DFSA and final PBND (%) was negatively correlated with IP 50% and DFSA.     

Human tRNA genes function as chromatin insulators

Insulators help separate active chromatin domains from silenced ones. In yeast, gene promoters act as insulators to block the spread of Sir and HP1 mediated silencing while in metazoans most insulators are multipartite autonomous entities. tDNAs are repetitive sequences dispersed throughout the human genome and we now show that some of these tDNAs can function as insulators in human cells. Using computational methods, we identified putative human tDNA insulators. Using silencer blocking, transgene protection and repressor blocking assays we show that some of these tDNA-containing fragments can function as barrier insulators in human cells. We find that these elements also have the ability to block enhancers from activating RNA pol II transcribed promoters. Characterization of a putative tDNA insulator in human cells reveals that the site possesses chromatin signatures similar to those observed at other better-characterized eukaryotic insulators. Enhanced 4C analysis demonstrates that the tDNA insulator makes long-range chromatin contacts with other tDNAs and ETC sites but not with intervening or flanking RNA pol II transcribed genes.     

A genetic playground for enhancing grain number in cereals

Improving the yield stability of cereal crops with a view to bolstering global food security is an important priority. The components of final grain number per plant at harvest are determined by fertile spikes per plant, number of fertile spikelets per spike and number of grains per spikelet. In this review article, we focus on the genetic factors of floral development and inflorescence architecture known to influence grain number and provide a broad overview of genes and genetic pathways that potentially can be manipulated to increase the yield of cereal crops, in particular wheat (Triticum aestivum) and barley (Hordeum vulgare). In addition, we discuss the outcome of multidisciplinary genomics knowledge to identify potential gene targets to develop conceptual ideotypes to meet the future demand.