Isolation ofiso-butyropyrrothine along with thiolutin and aureothricin from aStreptomyces sp.

Résumé Une nouvelle espèce de Streptomyces (S. pimprina) produit l'iso-butyropyrrothine avec la thiolutine (l'acétopyrrothine), l'aureothricine (la propriopyrrothine) et un antibiotique antifongique du groupe du polyène (heptaène).

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Our thanks are due to Dr.M. J. Thirumalachar for his interest in this work.     

Complete development of human hookworm,Ancylostoma duodenale (Dubini, 1843) in infant rabbits

Summary Establishment of a patent infection ofAncylostoma duodenale in the laboratory host, infant rabbit, is successfully achieved.Acknowledgments. We thank Dr B.B. Gaitondé, Haffkine Institute, for his encouragement and advice in this work.     

On the viability of the No Alternatives Argument

If we cannot directly empirically test the claims of a particular scientific theory directly, then it would be nice to have some other criteria with which to assess its viability. In his 2013 book, String Theory and the Scientific Method, Richard Dawid aims to develop such criteria, with an eye to vindicating research programmess in disciplines where direct empirical data is scant or non-existent. In an accompanying paper, Dawid, Hartmann and Sprenger formalise Dawid's so-called ‘No Alternatives Argument’ (NAA) using a generalised Bayesian framework, as a first step towards formalising Dawid's entire research programme (which itself relies on two further arguments). In this paper, I argue that the formalisation of the NAA cannot play the central role in Dawid's programme as intended. This is based on the observation that not all confirmation is non-negligible confirmation. For Dawid's programme to be useful, it must demonstrate the viability not just of non-empirical theory confirmation, but of non-negligible non-empirical theory confirmation. I argue that Dawid et al.‘s appeal to Bayesian confirmation theory to formalise his NAA cannot guarantee non-negligible confirmation. As a result, I conclude that if Dawid's overall project is to succeed, it must do so without the NAA formalised in this way.     

Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing

Ataxia-telangiectasia (A-T) results from the loss of ataxia-telangiectasia mutated (Atm) function and is characterized by accelerated telomere loss, genomic instability, progressive neurological degeneration, premature ageing and increased neoplasia incidence. Here we evaluate the functional interaction of Atm and telomeres in vivo. We examined the impact of Atm deficiency as a function of progressive telomere attrition at both the cellular and whole-organism level in mice doubly null for Atm and the telomerase RNA component (Terc). These compound mutants showed increased telomere erosion and genomic instability, yet they experienced a substantial elimination of T-cell lymphomas associated with Atm deficiency. A generalized proliferation defect was evident in all cell types and tissues examined, and this defect extended to tissue stem/progenitor cell compartments, thereby providing a basis for progressive multi-organ system compromise, accelerated ageing and premature death. We show that Atm deficiency and telomere dysfunction act together to impair cellular and whole-organism viability, thus supporting the view that aspects of A-T pathophysiology are linked to the functional state of telomeres and its adverse effects on stem/progenitor cell reserves.     

TRAPPI tethers COPII vesicles by binding the coat subunit Sec23

The budding of endoplasmic reticulum (ER)-derived vesicles is dependent on the COPII coat complex. Coat assembly is initiated when Sar1-GTP recruits the cargo adaptor complex, Sec23/Sec24, by binding to its GTPase-activating protein (GAP) Sec23 (ref. 2). This leads to the capture of transmembrane cargo by Sec24 (refs 3, 4) before the coat is polymerized by the Sec13/Sec31 complex. The initial interaction of a vesicle with its target membrane is mediated by tethers. We report here that in yeast and mammalian cells the tethering complex TRAPPI (ref. 7) binds to the coat subunit Sec23. This event requires the Bet3 subunit. In vitro studies demonstrate that the interaction between Sec23 and Bet3 targets TRAPPI to COPII vesicles to mediate vesicle tethering. We propose that the binding of TRAPPI to Sec23 marks a coated vesicle for fusion with another COPII vesicle or the Golgi apparatus. An implication of these findings is that the intracellular destination of a transport vesicle may be determined in part by its coat and its associated cargo.     

New dopamine receptor stimulant drug

Zusammenfassung Es wird der Nachweis erbracht, dass2(p-nitrobenzylthio)-Imidazolin (3H) · HCl (NBTI) Dopamin-Rezeptoren von Mäusen, Ratten und Affen direkt zu stimulieren vermag.

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The authors wish to thank Dr.G. Ullyot, SKF Laboratories, for gifts of NBTI and chlorpromazine; Dr.H. Corrodi, AB Hässle, Göteborg, Sweden, for the methyl ester hydrochlorides ofl-Dopa,-methyl-p-tyrosine andp-chlorophenylalanine; McNeil Laboratories, Inc., Fort Washington, Pennsylvania, for the haloperidol; and Schering Corporation, Bloomfield New Jersey, for perphenazine. Thanks are also due toA. Schindler for his skillful technical assistance.

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Final paper in press, Eur. J. Pharmac. (1972).     

Adenosine 5′-triphosphate sulphurylase fromSpirulina platensis

Summary ATP-sulphurylase from an unicellular blue-green alga,Spirulina platensis was localized in the soluble fractions of cell-free homogenate, and it was stable for over 3 weeks at –6°C.     

Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function

Positional cloning of hereditary deafness genes is a direct approach to identify molecules and mechanisms underlying auditory function. Here we report a locus for dominant deafness, DFNA36, which maps to human chromosome 9q13-21 in a region overlapping the DFNB7/B11 locus for recessive deafness. We identified eight mutations in a new gene, transmembrane cochlear-expressed gene 1 (TMC1), in a DFNA36 family and eleven DFNB7/B11 families. We detected a 1.6-kb genomic deletion encompassing exon 14 of Tmc1 in the recessive deafness (dn) mouse mutant, which lacks auditory responses and has hair-cell degeneration. TMC1 and TMC2 on chromosome 20p13 are members of a gene family predicted to encode transmembrane proteins. Tmc1 mRNA is expressed in hair cells of the postnatal mouse cochlea and vestibular end organs and is required for normal function of cochlear hair cells.