Human T-lymphotropic virus type 1 in coastal natives of British Columbia: phylogenetic affinities and possible origins.

Human T-lymphotropic virus type 1 (HTLV-1) infection has been discovered recently in people of Amerindian descent living in coastal areas of British Columbia, Canada. DNA sequencing combined with phylogenetic analysis and restriction fragment length polymorphism (RFLP) typing of HTLV-1 strains recovered from these British Columbia Indians (BCI) was conducted. Sequence-based phylogenetic trees distributed the BCI isolates among the Japanese subcluster (subcluster B) and the geographically widely distributed subcluster (subcluster A) of the large HTLV-1 cosmopolitan cluster. Long terminal repeat (LTR) RFLP typing revealed three distinct, equally frequent LTR cleavage patterns, two of which were of previously recognized Japanese and widely dispersed cosmopolitan types. A third, new cleavage pattern was detected which may have arisen by recombination between two other HTLV-1 genotypes. Our results suggest multiple origins for HTLV-1 in BCI, which are equally consistent with (i) a cluster of recent sporadic infections, (ii) ancient endemic vertical transmission through Amerindian lineages, or (iii) both.     

SSR based genetic diversity of pigmented and aromatic rice (<Emphasis Type="Italic">Oryza sativa</Emphasis> L.) genotypes of the western Himalayan region of India

A set of 24 of SSR markers were used to estimate the genetic diversity in 16 rice genotypes found in Western Himalayas of Kashmir and Himachal Pradesh, India. The level of polymorphism among the genotypes of rice was evaluated from the number of alleles and PIC value for each of the 24 SSR loci. A total of 68 alleles were detected across the 16 genotypes through the use of these 24 SSR markers The number of alleles per locus generated varied from 2 (RM 338, RM 452, RM 171) to 6 (RM 585, RM 249, RM 481, RM 162). The PIC values varied from 0.36 (RM 1) to 0.86 (RM 249) with an average of 0.62 per locus. Based on information generated, the genotypes got separated in six different clusters. Cluster 1 comprised of 4 genotypes viz; Zag 1, Zag 13, Pusa sugandh 3, and Zag 14, separated from each other at a similarity value of 0.40. Cluster second comprised of 3 landraces viz; Zag 2. Zag 4 and Zag10 separated from each other at a similarity value of 0.45. Cluster third comprised of 3 genotypes viz; Grey rice, Mushk budji and Kamad separated from each other at a similarity value of 0.46. Cluster fourth had 2 landraces viz; Kawa kreed and Loual anzul, and was not sub clustered. Fifth cluster had 3 genotypes viz; Zag 12, Purple rice and Jhelum separated from each other at a similarity value of 0.28. Cluster 6 comprised of a single popular variety i.e. Shalimar rice 1 with independent lineage.     

Metabolomics profiling of concussion in adolescent male hockey players: a novel diagnostic method

Introduction

Concussions are a major health concern as they cause significant acute symptoms and in some athletes, long-term neurologic dysfunction. Diagnosis of concussion can be difficult, as are the decisions to stop play.

Objective

To determine if concussions in adolescent male hockey players could be diagnosed using plasma metabolomics profiling.

Methods

Plasma was obtained from 12 concussed and 17 non-concussed athletes, and assayed for 174 metabolites with proton nuclear magnetic resonance and direct injection liquid chromatography tandem mass spectrometry. Data were analysed with multivariate statistical analysis and machine learning.

Results

The estimated time from concussion occurrence to blood draw at the first clinic visit was 2.3 ± 0.7 days. Using principal component analysis, the leading 10 components, each containing 9 metabolites, were shown to account for 82 % of the variance between cohorts, and relied heavily on changes in glycerophospholipids. Cross-validation of the classifier using a leave-one out approach demonstrated a 92 % accuracy rate in diagnosing a concussion (P < 0.0001). The number of metabolites required to achieve the 92 % diagnostic accuracy was minimized from 174 to as few as 17 metabolites. Receiver operating characteristic analyses generated an area under the curve of 0.91, indicating excellent concussion diagnostic potential.

Conclusion

Metabolomics profiling, together with multivariate statistical analysis and machine learning, identified concussed athletes with >90 % certainty. Metabolomics profiling represents a novel diagnostic method for concussion, and may be amenable to point-of-care testing.

     

BRAIN PROTEINS: QUALITATIVE AND QUANTITATIVE CHANGES, SYNTHESIS AND DEGRADATION DURING FETAL DEVELOPMENT OF THE RABBIT

The composition and metabolism of the proteins of the cerebral pallium of the rabbit during the final one-third of the gestational period were measured. During this period, the brain increased in size almost 10-fold and the migration of neuroblasts to form the cerebral cortex became complete. Concurrent with the marked structural changes, the solubility characteristics and electrophoretic distribution of various brain proteins showed little change. However, at the time of birth and in the adult, significant differences in gel electrophoresis patterns were apparent. The rate of synthesis of protein in brain slices from the fetus of 20 days gestation was 3-fold higher per mg of tissue than in the neonate and about 30-fold higher than in the adult. Activities of acidic and neutral proteases per unit weight were virtually the same and nearly constant throughout the late fetal period. However, during this stage, while rapid growth persists, the total protein synthetic activity of the pallium predominated over the total proteolytic activity, whereas sometime after birth the ratios of these activities reversed consequent to a shutdown of the synthetic process.     

Integration of type B retroviral DNA in virus-induced primary murine thymic lymphomas

In previous studies we described the isolation and characterization of a highly leukemogenic virus, DMBA-LV, isolated from a transplanted, chemical carcinogen-induced thymic lymphoma. The virus is composed of a mixture of two unrelated retroviral genomes, one highly related to type B milk-borne mouse mammary tumor virus isolates and the other partially related to type C viral genomes. In the present study, primary thymic lymphomas induced by DMBA-LV in CFW/D, NIH Swiss, C3H/Bi/Ka, and C57BL/Ka mice were assessed for the presence of newly integrated type B retroviral DNA. All 46 primary thymic lymphomas examined contained one to four newly acquired murine mammary tumor virus proviruses. Based on the sizes of provirus-cell DNA junction fragments, the integration of newly acquired murine mammary tumor virus proviruses did not appear to be random.     

Slipped-strand mispairing: a major mechanism for DNA sequence evolution

Simple repetitive DNA sequences are a widespread and abundant feature of genomic DNA. The following several features characterize such sequences: (1) they typically consist of a variety of repeated motifs of 1-10 bases--but may include much larger repeats as well; (2) larger repeat units often include shorter ones within them; (3) long polypyrimidine and poly-CA tracts are often found; and (4) tandem arrangements of closely related motifs are often found. We propose that slipped-strand mispairing events, in concert with unequal crossing- over, can readily account for all of these features. The frequent occurrence of long tandem repeats of particular motifs (polypyrimidine and poly-CA tracts) appears to result from nonrandom patterns of nucleotide substitution. We argue that the intrahelical process of slipped-strand mispairing is much more likely to be the major factor in the initial expansion of short repeated motifs and that, after initial expansion, simple tandem repeats may be predisposed to further expansion by unequal crossing-over or other interhelical events because of their propensity to mispair. Evidence is presented that single-base repeats (the shortest possible motifs) are represented by longer runs in mammalian introns than would be expected on a random basis, supporting the idea that SSM may be a ubiquitous force in the evolution of the eukaryotic genome. Simple repetitive sequences may therefore represent a natural ground state of DNA unselected for coding functions.      

Complete sequences of the rRNA genes of Drosophila melanogaster

In this, the first of three papers, we present the sequence of the ribosomal RNA (rRNA) genes of Drosophila melanogaster. The gene regions of D. melanogaster rDNA encode four individual rRNAs: 18S (1,995 nt), 5.8S (123 nt), 2S (30 nt), and 28S (3,945 nt). The ribosomal DNA (rDNA) repeat of D. melanogaster is AT rich (65.9% overall), with the spacers being particularly AT rich. Analysis of DNA simplicity reveals that, in contrast to the intergenic spacer (IGS) and the external transcribed spacer (ETS), most of the rRNA gene regions have been refractory to the action of slippage-like events, with the exception of the 28S rRNA gene expansion segments. It would seem that the 28S rRNA can accommodate the products of slippage-like events without loss of activity. In the following two papers we analyze the effects of sequence divergence on the evolution of (1) the 28S gene "expansion segments" and (2) the 28S and 18S rRNA secondary structures among eukaryotic species, respectively. Our detailed analyses reveal, in addition to unequal crossing-over, (1) the involvement of slippage and biased mutation in the evolution of the rDNA multigene family and (2) the molecular coevolution of both expansion segments and the nucleotides involved with compensatory changes required to maintain secondary structures of RNA.      

2’-5’寡聚腺苷酸合成酶（OAS）及其临床意义的研究进展

干扰素作用于靶细胞膜表面的受体后,通过信号转导系统诱导一系列抗病毒蛋白产生,干扰病毒复制以达到抗病毒目的。2’-5’寡聚腺苷酸合成酶（2’．5’oligoadenylatesynthetase,OAS）是干扰素作用于细胞后产生的一种重要的抗病毒蛋白,几十年来,国内外学者对OAS家族及其抗病毒机制进行了大量研究并取得了一定的进展,OAS被dsRNA激活后,催化生成2-5A,2-5A激活核酸内切酶RNaseL,降解病毒RNA,阻断病毒蛋白合成,从而发挥抗病毒作用。体内外研究表明,OAS的表达量或活性的变化可用于评价机体对干扰素的反应,反映干扰素抗病毒效果,另外,它还可作为系统性红斑狼疮的病情活动度的一种检测指标。因此,OAS具有重要的临床应用价值。本文就OAS家族及其抗病毒机制,其测定方法与对于病毒性肝炎和系统性红斑狼疮疾病的临床意义展开综述,以期对OAS的研究和应用提供参考。OAS是典型的干扰素诱导产物,可反映机体内干扰素的抗病毒水平,具有广阔的应用前景。     

免疫毒素的抗肿瘤研究

免疫毒素是由具有导向能力的载体（抗体或细胞因子）和具有细胞毒性的分子（毒素）偶联而成的具有特异性细胞杀伤能力的杂合分子,是一种靶向药物。免疫毒素首先利用肿瘤细胞上导向分子的受体与细胞结合,然后进入细胞,再由毒素发挥蛋白质合成抑制作用,最终导致靶细胞死亡。与其他抗肿瘤药物相比,免疫毒素具有毒性强和特异性高的优点,在肿瘤治疗中显示出巨大的应用前景。简要概述了免疫毒素的作用机理、制备及其抗肿瘤研究进展。