Prepeptide sequence of epidermin, a ribosomally synthesized antibiotic with four sulphide-rings

The genetic basis for the biosynthesis of large polypeptide antibiotics such as nisin has not been explained so far. We show here that the structural gene epiA encoding the antibiotic epidermin from Staphylococcus epidermidis is located on a 54-kilobase plasmid and codes for a 52-amino-acid prepeptide, which is processed to the tetracyclic 21-peptide amide antibiotic. The mature sequence of epidermin corresponds to the C-terminal 22-peptide segment of pre-epidermin and contains the precursor amino acids Ser, Thr and Cys, from which the unusual amino-acid constituents are derived. The more lipophilic epidermin is cleaved at a hydrophilic turn between Arg-1 and Ile+1 from the N-terminal segment-30 to -1, which probably assumes a partially amphiphilic alpha-helix conformation. We propose that the N-terminus (-30 to -1) plays a cooperative role during modification reactions and prevents toxicity of the mature epidermin to the producing strain before the antibiotic is cleaved off and secreted.     

In vivo perfusion of human thyroid tissue with 4-14C-dehydroepiandrosterone and 7α-3H-dehydroepiandrosterone sulfate. Metabolism of steroid conjugates. X

Zusammenfassung Bei der In vivo-Perfusion menschlichen Schilddrüsen-Strumagewebes mit 4-¹⁴C-DHEA und 7-³H-DHEA-Sulfat zeigte es sich, dass unter physiologischen Bedingungen eine beachtliche Hydrolyse von Steroid-Sulfat eintrat. Demgegenüber liess sich keine Steroid-Sulfokinase oder Steroid-Glucuronosyl-Transferase nachweisen. Der Anteil der Metaboliten erreichte in der Fraktion der freien Steroide ungefähr 30% isolierter Verbindungen, in der Fraktion der Steroid-Sulfate jedoch nur etwa 14%. Androstendiol erwies sich als wichtigster Metabolit, gefolgt von Androstendion und Androstentriol.     

A field-portable racetrack and timer for measuring acceleration and speed of small cursorial animals

Summary We describe a relatively inexpensive, field-portable racetrack and timer that can be used to measure acceleration and maximum speed of small cursorial animals. Procedures for interfacing the racetrack to microprocessors are also outlined.This research was supported by NSF DEB 78-12124, the Miller Institute for Basic Research in Science (University of California, Berkeley), and by the Graduate School Research Fund (University of Washington, Seattle). The authors gladly acknowledge the advice of R. Reinstatler, J.R. Simpson, M.O. Smith, and especially A. M. Hawkins.     

Cell cycle determination of phytohemagglutinin-stimulated lymphocytes from the opossum,Didelphis virginiana

Résumé La courbe PLM (pourcentages indiqués de mitoses) pour les lymphocytes d'opossum in vitro a fait preuve d'unT _c (temps générateur) que n'atteignait pas la somme de G₂, S, et M (mitosis). Tandis que les calculations pour les phases de G₂ et S sont représentées avec exactitude sur la courbe, il y a des variations dans le G₁ parmi les population de lymphocytes au fonctionnement divers (au nombre de deux ou peut-être plus parmi cellesci) qui sont responsables de ce désaccord apparent.     

Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans

The functional interaction of BAFF and APRIL with TNF receptor superfamily members BAFFR, TACI and BCMA is crucial for development and maintenance of humoral immunity in mice and humans. Using a candidate gene approach, we identified homozygous and heterozygous mutations in TNFRSF13B, encoding TACI, in 13 individuals with common variable immunodeficiency. Homozygosity with respect to mutations causing the amino acid substitutions S144X and C104R abrogated APRIL binding and resulted in loss of TACI function, as evidenced by impaired proliferative response to IgM-APRIL costimulation and defective class switch recombination induced by IL-10 and APRIL or BAFF. Family members heterozygous with respect to the C104R mutation and individuals with sporadic common variable immunodeficiency who were heterozygous with respect to the amino acid substitutions A181E, S194X and R202H had humoral immunodeficiency. Although signs of autoimmunity and lymphoproliferation are evident, the human phenotype differs from that of the Tnfrsf13b-/- mouse model.     

TACI is mutant in common variable immunodeficiency and IgA deficiency

The tumor necrosis factor receptor family member TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) mediates isotype switching in B cells. We found that 4 of 19 unrelated individuals with common variable immunodeficiency (CVID) and 1 of 16 individuals with IgA deficiency (IgAD) had a missense mutation in one allele of TNFRSF13B (encoding TACI). One of the four individuals with CVID had a single nucleotide insertion in the other TNFRSF13B allele. None of these mutations were present in 50 healthy subjects. TNFRSF13B mutations cosegregated with the phenotype of CVID or IgAD in family members of four index individuals that we studied. B cells from individuals with TACI mutations expressed TACI but did not produce IgG and IgA in response to the TACI ligand APRIL, probably reflecting impaired isotype switching. These results suggest that TACI mutations can result in CVID and IgAD.     

Trans-Planckian philosophy of cosmology

I provide some philosophical groundwork for the recently proposed ‘trans-Planckian censorship’ conjecture in theoretical physics. In particular, I argue that structure formation in early universe cosmology is, at least as we typically understand it, autonomous with regards to quantum gravity, the high energy physics that governs the Planck regime in our universe. Trans-Planckian censorship is then seen as a means of rendering this autonomy an empirical constraint within ongoing quantum gravity research.