Role of inorganic phosphate in total biliary phosphorus determination

Summary Total phosphorus, inorganic phosphate, and phospholipids were measured in bile of rats and guinea pigs during choleresis and cholestasis produced by taurocholate and taurolithocholate, respectively. Under either experimental condition, total biliary phosphorus concentrations increased significantly in both species, due primarily to an increase in inorganic phosphate. These studies indicate that, if total phosphorus is taken as an estimate of biliary phospholipid concentration, correction for inorganic phosphate is essential under conditions associated with changes in bile secretory function.This work was supported by grant HD-17556 from the National Institute of Child Health and Human Development.     

The oxidative metabolism ofα-chlorohydrin and the chemical induction of spermatocoeles

Summary -Chlorohydrin (I) is oxidatively metabolized to -chlorolactic acid (III) and oxalic acid (IV). Deposition of calcium oxalate within the renal tubules is responsible for the toxic effects of-chlorohydrin and a similar action on the epididymis or epididymal blood vessels could initiate the formation of spermatocoeles from this and other male antifertility agents.     

Identification of the familial cylindromatosis tumour-suppressor gene

Familial cylindromatosis is an autosomal dominant genetic predisposition to multiple tumours of the skin appendages. The susceptibility gene (CYLD) has previously been localized to chromosome 16q and has the genetic attributes of a tumour-suppressor gene (recessive oncogene). Here we have identified CYLD by detecting germline mutations in 21 cylindromatosis families and somatic mutations in 1 sporadic and 5 familial cylindromas. All mutations predict truncation or absence of the encoded protein. CYLD encodes three cytoskeletal-associated-protein-glycine-conserved (CAP-GLY) domains, which are found in proteins that coordinate the attachment of organelles to microtubules. CYLD also has sequence homology to the catalytic domain of ubiquitin carboxy-terminal hydrolases (UCH).     

Maternal Rnf12/RLIM is required for imprinted X-chromosome inactivation in mice

Two forms of X-chromosome inactivation (XCI) ensure the selective silencing of female sex chromosomes during mouse embryogenesis. Imprinted XCI begins with the detection of Xist RNA expression on the paternal X?chromosome (Xp) at about the four-cell stage of embryonic development. In the embryonic tissues of the inner cell mass, a random form of XCI occurs in blastocysts that inactivates either Xp or the maternal X?chromosome (Xm). Both forms of XCI require the non-coding Xist RNA that coats the inactive X?chromosome from which it is expressed. Xist has crucial functions in the silencing of X-linked genes, including Rnf12 (refs 3, 4) encoding the ubiquitin ligase RLIM (RING finger LIM-domain-interacting protein). Here we show, by targeting a conditional knockout of Rnf12 to oocytes where RLIM accumulates to high levels, that the maternal transmission of the mutant X?chromosome (Δm) leads to lethality in female embryos as a result of defective imprinted XCI. We provide evidence that in Δm female embryos the initial formation of Xist clouds and Xp silencing are inhibited. In contrast, embryonic stem cells lacking RLIM are able to form Xist clouds and silence at least some X-linked genes during random XCI. These results assign crucial functions to the maternal deposit of Rnf12/RLIM for the initiation of imprinted XCI.     

Isolation of complementary DNA clones encoding the human lymphocyte glycoprotein T1/Leu-1

The T1/Leu-1/CD5 molecule, a human T-cell surface glycoprotein of relative molecular mass (Mr) 67,000, has been implicated in the proliferative response of activated T cells and in T-cell helper function. A similar involvement in T-cell proliferation has been reported for Ly-1, the murine homologue of T1. Here we report the complete amino-acid sequence of the T1 precursor molecule deduced from complementary DNA clones. The protein contains a classical signal peptide; a 347-amino-acid extracellular segment; a transmembrane region; and a 93-amino-acid intracellular segment. The extracellular segment contains many cysteine residues and is composed of two related structural domains separated by a proline/threonine-rich region. The T1 molecule has structural features characteristic of other receptor molecules.     

The structure of beta-lactoglobulin and its similarity to plasma retinol-binding protein

Since its first isolation, bovine beta-lactoglobulin (BLG) has been an enigma: although it is abundant in the whey fraction of milk, its function is still not clear. The results of the many physicochemical studies on the protein need a structural interpretation. We report here the structure of the orthorhombic crystal form of cow BLG at pH 7.6, at a resolution of 2.8 A. It has an unusual protein fold, composed of two slabs of antiparallel beta-sheet, which shows a remarkable similarity to plasma retinol-binding protein. A possible binding site for retinol in BLG has been identified by model-building. This suggests a role for BLG in vitamin A transport and we have discovered specific receptors for the BLG-retinol complex in the intestine of neonate calves.