The complete genome of an individual by massively parallel DNA sequencing

The association of genetic variation with disease and drug response, and improvements in nucleic acid technologies, have given great optimism for the impact of 'genomic medicine'. However, the formidable size of the diploid human genome, approximately 6 gigabases, has prevented the routine application of sequencing methods to deciphering complete individual human genomes. To realize the full potential of genomics for human health, this limitation must be overcome. Here we report the DNA sequence of a diploid genome of a single individual, James D. Watson, sequenced to 7.4-fold redundancy in two months using massively parallel sequencing in picolitre-size reaction vessels. This sequence was completed in two months at approximately one-hundredth of the cost of traditional capillary electrophoresis methods. Comparison of the sequence to the reference genome led to the identification of 3.3 million single nucleotide polymorphisms, of which 10,654 cause amino-acid substitution within the coding sequence. In addition, we accurately identified small-scale (2-40,000 base pair (bp)) insertion and deletion polymorphism as well as copy number variation resulting in the large-scale gain and loss of chromosomal segments ranging from 26,000 to 1.5 million base pairs. Overall, these results agree well with recent results of sequencing of a single individual by traditional methods. However, in addition to being faster and significantly less expensive, this sequencing technology avoids the arbitrary loss of genomic sequences inherent in random shotgun sequencing by bacterial cloning because it amplifies DNA in a cell-free system. As a result, we further demonstrate the acquisition of novel human sequence, including novel genes not previously identified by traditional genomic sequencing. This is the first genome sequenced by next-generation technologies. Therefore it is a pilot for the future challenges of 'personalized genome sequencing'.     

Leishmania donovani in hamsters: Stimulation of non-specific resistance by some novel glycopeptides and impact on therapeutic efficacy

Summary Several glycopeptides structurally related to muramyl dipeptide (MDP) have been synthesized and evaluated for their ability to stimulate the non-specific resistance of hamsters againstL. donovani infection. These compounds have been named CDRI compounds. The synthetic procedure used for compounds 86/448 and 84/212 is described.MDP and its synthetic congeners were administered as immunostimulants at a prophylactic dose of 3 mg/kg at two weeks interval. The challenge infection (1×10⁷ amastigotes i.c./hamster) was given in between two doses of the compounds. One of the glycopeptides, CDRI comp. 86/448, has been found to be significantly more potent than MDP, effecting 92% inhibition of the challenge dose, whereas MDP produced only 26.5% inhibition. The effect of comp. 86/448 lasted until day 7 of challenge. The efficacy of sodium stibogluconate was appreciably improved in hamsters treated with comp. 86/448.     

Leishmania donovani in hamsters: Stimulation of non-specific resistance by novel lipopeptides and their effect in antileishmanial therapy

Several novel type of lipopeptides were synthesized and evaluated for their ability to stimulate non-specific resistance againstLeishmania donovani infection. Peritoneal macrophages isolated from young male hamsters treated with muramyl dipeptide (MDP) and various synthetic lipopeptides (6 mg/kg i.p.) 7 days earlier, were cultured in vitro and challenged 24 h later withL. donovani promastigotes. One lipopeptide, Central Drug Research Institute (CDRI) compound 86/450, exhibited significantly higher immunostimulatory activity than MDP. Its prophylactic activity was further confirmed in hamsters by giving 2 split doses of 3 mg/kg of the compound spaced at 2 weeks, i.e. on day –7 and +7 of challenge withL. donovani amastigotes. The prophylactic effect lasted for 7 days following the last treatment with compound 86/450. The antileishmanial action of sodium stibogluconate (SAG) was also found to be enhanced by 16% in hamsters primed with compound 86/450.CDRI Communication No. 5034.     

The structure of WI3, the first optically active biflavone of the amentoflavone series

Résumé Araucaria cookii donne les premières bisflavones optiquement actives de la série des amentoflavones. Une analyse complète des spectra de RNM des substances de cette série a été faite. Les déplacements méthoxyliques induits par le solvant s'ajoutent aux résultats de l'analyse de RNM et les confirment.     

Nuclease for DNA apurinic sites in chicken liver

Summary Chicken liver crude extract produced acid-soluble diphenylamine-positive material in the presence of depurinated and alkylated DNA, while the formation of such material from normal and single stranded DNA was comparatively low. The maximum acid-soluble material produced was not increased further by alkali, indicating that the enzymatic action is mostly directed towards apurinic sites.Acknowledgment. The authors are grateful to Council of Scientific and Industrial Research, India, for financial assistance to one of us (R. Y. R.).     

The isolation and characterization of two members of a new series of naturally occurring biflavones

Résumé Quelques bisflavones qui contiennent un lien 6,8 ont été isolées et charactérisées pour la première fois. Les déplacements méthoxyliques permettent de décider si l'on a affaire à des éléments flavanoïdes liées 6, ou 8. Le contrôle enzymique de la production de bisflavones dans le genreAuraucariaceae est démontré.     

Antidesmanol-a new pentacyclic triterpenoid fromAntidesma menasu Miq. ex. Tul.

Summary Antidesmanol (1), a new pentacyclic triterpenoid, has been isolated along with n-tritriacontane, friedelin, canophyllal and canophyllol from the aerial parts ofAntidesma menasu. Based on chemical and spectroscopic evidence, its structure has been established as 3-keto-16-hydroxyfriedelane. n-Tritriacontane and friedelin have shown antiinflammatory and diuretic activities respectively in experimental animals.CDRI Communication No. 2536.