Neurogenomics of speech and language disorders: the road ahead

Next-generation sequencing is set to transform the discovery of genes underlying neurodevelopmental disorders, and so offer important insights into the biological bases of spoken language. Success will depend on functional assessments in neuronal cell lines, animal models and humans themselves.     

Regulatory RNAs derived from transfer RNA?

Four recent studies suggest that cleavages of transfer RNAs generate products with microRNA-like features, with some evidence of function. If their regulatory functions were to be confirmed, these newly revealed RNAs would add to the expanding repertoire of small noncoding RNAs and would also provide new perspectives on the coevolution of transfer RNA and messenger RNA.     

Post-translational heterogeneity of the human vitamin D-binding protein (group-specific component)

The vitamin D-binding protein in human serum (the group-specific component) is an alpha 2-globulin which is genetically polymorphic in all populations studied. Previous work (J. Svasti and B. H. Bowman (1978) J. Biol. Chem. 253, 5188-5194, and J. Svasti, A. Kurosky, A. Bennett, and B. H. Bowman (1979) Biochemistry 18, 1611-1617) has shown that the electrophoretic variations of the proteins controlled by two allelic genes, Gc1 and Gc2, are due to at least three amino acid substitutions between Gc1 and Gc2 (Svasti et al. (1979] and to heterogeneity in the Gc1 phenotype arising from carbohydrate dissimilarities. Gc1 migrates electrophoretically as two protein bands, while Gc2 migrates cathodally as a single band. This study demonstrates a post-translational glycosylation difference occurring in a single area of the Gc1 sequence which accounts for the heterogeneity observed previously. The glycosylation site, a threonine residue, appears to be in a sequence which differs between Gc1 and Gc2. The O-glycosidic bond, which is typical of mucins, is rare in plasma proteins. The cyanogen bromide fragment containing the galactosamine-containing carbohydrate in Gc1 was partially sequenced through 20 residues from the amino terminus. No detectable galactosamine could be found in the homologous cyanogen bromide fragment in Gc2. A new purification procedure for the vitamin D-binding protein in human plasma has been developed. Three chromatographic steps provide purified protein.     

Some aquatic oligochaetes of the Nilgiris,South India

Eight species of aquatic oligochaetes, belonging to the families Naididae and Tubificidae, are reported, of which six species are new to the Nigiris. Tubifex tubifex known from Coonoor is reported again from this area.     

A bacterial clone carrying sequences coding for elongation factor EF-1 alpha from Artemia

A bacterial cDNA clone was identified carrying one third of the nucleotides coding for elongation factor EF-1 alpha from the brine shrimp Artemia. The sequence of codons corresponds with the known sequence of amino acids of EF-1 alpha in the region involved.     

The lifetime of molecular (Davydov) solitons

The lifetime of Davydov solitons in a one-dimensional system is studied theoretically. The process of thermalization and the properties of solitons at finite temperature are investigated and the processes of soliton creation and disintegration are discussed.     

A Two-Layered Targeting Mechanism Underlies Nuclear RNA Sorting by the Human Exosome

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Identification of compound heterozygous DNAH11 variants in a Han-Chinese family with primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a group of genetically and clinically heterogeneous disorders with motile cilia dysfunction. It is clinically characterized by oto-sino-pulmonary diseases and subfertility, and half of the patients have situs inversus (Kartagener syndrome). To identify the genetic cause in a Han-Chinese pedigree, whole-exome sequencing was conducted in the 37-year-old proband, and then, Sanger sequencing was performed on available family members. Minigene splicing assay was applied to verify the impact of the splice-site variant. Compound heterozygous variants including a splice-site variant (c.1974-1G>C, rs1359107415) and a missense variant (c.7787G>A, p.(Arg2596Gln), rs780492669), in the dynein axonemal heavy chain 11 gene (DNAH11) were identified and confirmed as the disease-associated variants of this lineage. The minigene expression in vitro revealed that the c.1974-1G>C variant could cause skipping over exon 12, predicted to result in a truncated protein. This discovery may enlarge the DNAH11 variant spectrum of PCD, promote accurate genetic counselling and contribute to PCD diagnosis.     

Selection and Identification of Aptamers Against B Cell Activating Factor

Systemic lupus erythematosus (SLE) is the most common autoimmune disease in China. B cell activating factor (BAFF) is an important target for the treatment and detection of SLE. It is of great significance to develop novel molecular recognition elements with high affinity for BAFF. In this study, artificial nucleic acid aptamers against BAFF were screened from a 78 nt single-stranded DNA random library by systematic evolution of ligands exponential enrichment (SELEX) in vitro based on several selection and amplification steps. Through ten rounds of selection, the aptamers with high specificity and affinity for BAFF were identified. After high-throughput sequencing, several aptamers were selected and further examined for binding affinity and specificity. The investigation by dot blotting, Eastern blotting analyses and enzyme-linked oligonucleotide assay (ELONA) showed that the aptamers Apt 7 and Apt 12 with dissociation constants of 241.00±19.75 nmol/L and 413.51±46.94 nmol/L were able to recognize BAFF specifically. After molecular docking analysis, Apt 7 was truncated to Apt 7～1, and the dissociation constant was 192.10±28.61 nmol/L. A sandwich ELONA using Apt 7～1 and BAFF antibodies was established to detect BAFF. The detection limit was estimated to be 0.227 nmol/L. This study provides new molecular recognition elements for the detection of BAFF and the study of antagonists.