Methyl ({[(4E)-1,3-dimethyl-2,6-di-phenyl-piperidin-4-yl-idene]amino}-oxy)acetate.

In the title compound, C22H26N2O3, the piperidine ring exhibits a chair conformation. The phenyl rings attached to the piperidine at the 2- and 6-positions have axial orientations. These rings make a dihedral angle of 49.75 (11)°. The amino-oxy acetate group attached at the 4-position has an equatorial orientation. In the crystal, inversion dimers linked by pairs of C-H⋯π inter-actions occur.

(E)-3-Methyl-2,6-di-phenyl-piperidin-4-one O-(3-methyl-benzo-yl)oxime.

In the title compound, C26H26N2O2, the piperidine ring exhibits a chair conformation. The phenyl rings are attached to the central heterocycle in an equatorial position. The dihedral angle between the planes of the phenyl rings is 57.58 (8)°. In the crystal, C-H⋯O inter-actions connect the mol-ecules into zigzag chains along [001].

Expression of the X-inactivation-associated gene XIST during spermatogenesis.

Mammalian X-chromosome inactivation is thought to be controlled by the X inactivation centre (XIC, X-controlling element -Xce-in mice). A human gene, XIST and its mouse counterpart, Xist, which map to the XIC/Xce, are expressed exclusively from inactive X chromosomes, suggesting their involvement in the process of X-inactivation. We now report the presence of Xist/XIST transcripts in newborn and adult mouse testes, and in human testicular tissue with normal spermatogenesis, but not in the testes of patients who lack germ cells. Our results indicate that while the X chromosome in males is active in somatic cells, it undergoes inactivation during spermatogenesis.

Cloning and expression of the mouse pseudoautosomal steroid sulphatase gene (Sts).

Steroid sulphatase (STS) is an important enzyme in steroid metabolism. The human STS gene has been cloned and mapped to Xp22.3, proximal to the pseudoautosomal region (PAR). Using quantitative differences in STS activity among various mouse strains, a segregation pattern consistent with autosomal linkage was first reported, but more recent studies have linked Sts to the mouse PAR. Failed attempts to clone the mouse Sts gene using human reagants (STS cDNA and anti-STS antibodies) suggest a substantial divergence between these genes. However, partial amino-terminal sequence from purified rat liver Sts is very similar to its human counterpart, and several domains are conserved among all the sulphatases. We followed a degenerate-primer reverse transcriptase-PCR (RT-PCR) approach to amplify a conserved fragment of the rat Sts cDNA that was then used to clone the mouse Sts cDNA. This 2.3-kb cDNA revealed 75% similarity with rat Sts cDNA, while it was only 63% similar to human STS cDNA. Transfection of STS(-) A9 cells with the mouse Sts cDNA restored STS enzymatic activity. Sts was also mapped physically to the distal end of the mouse sex chromosomes, and our backcross studies placed Sts distal to the 'obligatory' cross-over in male meiosis.

A high resolution deletion map of human chromosome Xp22.

We have developed a 32-interval deletion panel for human chromosome Xp22 spanning about 30 megabases of genomic DNA. DNA samples from 50 patients with chromosomal rearrangements involving Xp22 were tested with 60 markers using a polymerase chain reaction strategy. The ensuing deletion map allowed us to confirm and refine the order of previously isolated and newly developed markers. Our mapping panel will provide the framework for mapping new sequences, for orienting chromosome walks in the region and for projects aimed at isolating genes responsible for diseases mapping to Xp22.

The murine Xe169 gene escapes X-inactivation like its human homologue.

Among a number of genes that escape X-chromosome inactivation in humans, three have been evaluated in mice and unexpectedly all three are subject to X-inactivation. We report here the cloning and expression studies of a novel mouse gene, Xe169, and show that it escapes X-inactivation like its human homologue. Xe169 was assigned to band F2/F3 on the mouse X chromosome by fluorescent in situ hybridization and Southern analysis indicates that the gene is located outside the pseudoautosomal region. Homologous, but divergent, sequences exist on the Y chromosome. In vitro and in vivo studies show that Xe169 is expressed from both the active and the inactive X chromosomes. Xe169 is the first cloned non-pseudoautosomal gene that escapes X-inactivation in mice.

1-Phenyl-2-[4-(trifluoro-meth-yl)phen-yl]-1H-benzimidazole.

In the title mol-ecule, C(20)H(13)F(3)N(2), the benzimidazole unit is close to being planar [maximum deviation = 0.012 (1) Å] and forms dihedral angles of 31.43 (7) and 61.45 (9)° with the 4-(trifluoromethyl)phenyl and 1-phenyl rings, respectively; the dihedral angle between these rings is 60.94 (10)°. In the crystal, C-H⋯F hydrogen bonds link the mol-ecules into chains along the c-axis direction. The CF(3) group is rotationally disordered with an occupancy ratio of 0.557 (8):0.443 (8) for the F atoms.

2-(4-Meth-oxy-phen-yl)-1-phenyl-1H-benzimidazole.

In the title compound, C(20)H(16)N(2)O, the 1H-benzimidazole ring forms dihedral angles of 48.00 (6) and 64.48 (6)°, respectively with the benzene and phenyl rings, which are inclined to one another by 58.51 (7)°. In the crystal, weak C-H⋯π inter-actions are the only inter-molecular inter-actions present.

1-Phenyl-2-p-tolyl-1H-benzimidazole.

In the title compound, C20H16N2, the benzimidazole ring system forms dihedral angles of 28.50 (7) and 72.44 (7)° with the tolyl and phenyl rings, respectively. In the crystal, mol-ecules are linked into chains along the a-axis direction by weak C-H⋯N inter-actions. The crystal structure also features C-H⋯π inter-actions.

1-(3,5-Dimethyl-phen-yl)-2-(4-fluoro-phen-yl)-1H-phenanthro[9,10-d]imidazole.

In the title compound, C29H21FN2, the phenanthro tricyclic ring system is essentially planar with a maximum deviation of 0.030 (2) Šand makes dihedral angles between of 77.96 (6) and 37.18 (7)° with the dimethyl-phenyl and fluoro-phenyl rings, respectively. The crystal packing features weak C-H⋯π inter-actions involving the dimethyl-phenyl and other phenyl rings.

2-(4-Fluoro-phen-yl)-1-(4-meth-oxy-phen-yl)-1H-phenanthro[9,10-d]imidazole.

In the title compound, C28H19FN2O, the phenanthrene fused with an imidazole ring, constituting an essentially planar tetra-cyclic system [maximum deviation = 0.032 (2) Å], makes dihedral angles of 60.83 (4) and 80.55 (4)° with the fluoro-benzene and meth-oxy-benzene rings, respectively. The dihedral angle between the the meth-oxy-benzene and fluoro-benzene rings is 69.45 (6)°. In the crystal, C-H⋯O hydrogen bonds connect the mol-ecules into infinite strands along the b axis. The crystal structure is further consolidated by C-H⋯π inter-actions.

Glycine-d-tartaric acid (1/1).

In the title co-crystal, C(2)H(5)NO(2)·C(4)H(6)O(6), the gylcine mol-ecule is present in the zwitterion form. In the tartaric acid mol-ecule there is a short intra-molecular O-H⋯O contact. In the crystal, the tartaric acid mol-ecules are linked via pairs of O-H⋯O hydrogen bonds, forming inversion dimers. These dimers are linked via a number of O-H⋯O and N-H⋯O hydrogen bonds involving the two components, forming a three-dimensional network.

1-(4-Meth-oxy-phen-yl)-2-[4-(tri-fluoro-meth-yl)phen-yl]-1H-phenanthro[9,10-d]imidazole.

In the title compound, C29H19F3N2O, a phenanthroline-fused imidazole tetra-cyclic system, the fused benzene rings deviate slightly from the central ring and make dihedral angles with this ring of 3.47 (8) and 3.05 (8)°. The tri-fluoro-methyl-phenyl ring is roughly coplanar with the phenanthroline-fused imidazole tetra-cyclic system [dihedral angle = 11.02 (6)°], while the meth-oxy-phenyl ring is almost perpendicular [dihedral angle = 87.65 (6)°]. There are intra-molecular C-H ⋯π inter-actions involving the meth-oxy-phenyl ring and the central phenanthroline ring, as well as an inter-molecular C-H⋯π inter-action involving the phenanthroline ring. In addition, there is an inter-molecular π-π inter-action involving the central phenanthroline ring and the tri-fluoro-methyl-phenyl ring [centroid-centroid distance = 3.685 (2) Å], as well as C-H⋯N inter-actions linking the mol-ecules into dimers.

1-(4-Methyl-phen-yl)-2-[4-(trifluoro-methyl)phen-yl]-1H-phenanthro[9,10-d]imida-zole.

In the title compound, C29H19F3N2, the tetra-cyclic ring system is essentially planar [maximum deviation from the best plane = 0.076 (1) Å] and makes dihedral angles of 78.10 (5) and 33.71 (4)° with the methyl-phenyl and fluoro-phenyl rings, respectively. An intra-molecular C-H⋯π inter-action occurs. In the crystal, pairs of C-H⋯π inter-actions link inversion-related mol-ecules.

Reactivation of an inactive human X chromosome: evidence for X inactivation by DNA methylation.

A mouse-human somatic cell hybrid clone, deficient in hypoxanthine-guanine phosphoribosyltransferase (HPRT) and containing a structurally normal inactive human X chromosome, was isolated. The hybrid cells were treated with 5-azacytidine and tested for the reactivation and expression of human X-linked genes. The frequency of HPRT-positives clones after 5-azacytidine treatment was 1000-fold greater than that observed in untreated hybrid cells. Fourteen independent HPRT-positive clones were isolated and analyzed for the expression of human X markers. Isoelectric focusing showed that the HPRT expressed in these clones is human. One of the 14 clones expressed human glucose-6-phosphate dehydrogenase and another expressed human phosphoglycerate kinase. Since 5-azacytidine treatment results in hypomethylation of DNA, DNA methylation may be a mechanism of human X chromosome inactivation.

Non-inactivation of an x-chromosome locus in man.

Cloned fibroblasts from women heterozygous for X-linked ichthyosis (steroid sulfatase deficiency) were examined to see whether or not this locus is subject to X-inactivation. Of 103 clones examined, all had normal levels of steroid sulfatase activity. Two of the women studied were also heterozygous for glucose-6-phosphate dehydrogenase deficiency. This allowed the demonstration that both X chromosomes were represented as the active X in various clones and that selection did not account for these findings. Thus, the steroid sulfatase locus, like the Xga locus to which it is linked, appears to escape X-inactivation in man.

Hormone-sensitive lipase: sequence, expression, and chromosomal localization to 19 cent-q13.3.

Hormone-sensitive lipase, a key enzyme in fatty acid mobilization, overall energy homeostasis, and possibly steroidogenesis, is acutely controlled through reversible phosphorylation by catecholamines and insulin. The 757-amino acid sequence predicted from a cloned rat adipocyte complementary DNA showed no homology with any other known lipase or protein. The activity-controlling phosphorylation site was localized to Ser563 in a markedly hydrophilic domain, and a lipid-binding consensus site was tentatively identified. One or several messenger RNA species (3.3, 3.5, or 3.9 kilobases) were expressed in adipose and steroidogenic tissues and heart and skeletal muscle. The human hormone-sensitive lipase gene mapped to chromosome 19 cent-q13.3.

A new probe for the diagnosis of myotonic muscular dystrophy.

Myotonic muscular dystrophy (DM) is the most common muscular dystrophy, affecting adults as well as children. It is inherited as an autosomal dominant trait and is characterized by variable expressivity and late age-of-onset. Linkage studies have established the locus on chromosome 19. In order to identify tightly linked probes for diagnosis as well as to define in detail the DM gene region, chromosome 19 libraries were constructed and screened for restriction fragment length polymorphisms tightly linked to DM. A genomic clone, LDR152 (D19S19), was isolated that is tightly linked to DM; recombination fraction = 0.0 (95% confidence limits 0.0-0.03); lod score, 15.4.

Crystal structures of two 4H-chromene derivatives: 2-amino-3-cyano-4-(3,4-di-chloro-phen-yl)-7-hy-droxy-4H-benzo[1,2-b]pyran 1,4-dioxane monosolvate and 2-amino-3-cyano-4-(2,6-di-chloro-phen-yl)-7-hy-droxy-4H-benzo[1,2-b]pyran.

In the title compounds, C16H9Cl2N2O2·C4H8O2 and C16H9Cl2N2O2, the bicyclic 4H-chromene cores are nearly planar with maximum deviations of 0.081 (2) and 0.087 (2) Å. In both structures, the chromene derivative mol-ecules are linked into centrosymmetric dimers by pairs of N-H⋯O hydrogen bonds, forming R2 2 (16) motifs. These dimers are further linked in the 3,4-di-chloro-phenyl derivative by N-H⋯N hydrogen bonds into double layers parallel to (100) and in the 2,6-di-chloro-phenyl derivative by O-H⋯N hydrogen bonds into ribbons along the [10] direction. In the 3,4-di-chloro-phenyl derivative, the 1,4-dioxane solvent mol-ecules are connected to the chromene mol-ecules via O-H⋯O hydrogen bonds.

Cloning and chromosomal localization of a human kidney cDNA involved in cystine, dibasic, and neutral amino acid transport.

We have recently cloned, sequenced, and characterized a rat kidney cDNA (D2) that stimulates cystine as well as dibasic and neutral amino acid transport. In order to evaluate the role of this protein in human inherited diseases such as cystinuria, we have isolated a human D2 clone (D2H) by low stringency screening of a human kidney cDNA library using the radiolabeled D2 insert as a probe. The D2H cDNA is 2284 nucleotides long and encodes a 663 amino acid protein that is 80% identical to the rat D2 amino acid sequence and 86% to that of the rabbit homologue rBAT. Microinjection of in vitro transcribed D2H cRNA into Xenopus oocytes induced uptake of cystine as well as dibasic and neutral amino acids in a pattern similar to that of rat D2 and rabbit rBAT. Both neutral and dibasic amino acids inhibited the D2H-induced uptake of cystine. Northern blot analysis demonstrated that D2H, like D2 and rBAT, is expressed strongly in the kidney and intestine. Southern blot analysis of genomic DNA from a panel of mouse-human somatic cell hybrids showed that the human gene for D2H resides on chromosome 2.