On the basis of homeo box cross‐homology we have isolated the pair‐rule gene even‐skipped (eve) of Drosophila. The eve transcription unit appears to be less than 1.5 kb in length, and encodes a single mRNA of approximately 1.4 kb. The nucleotide sequence of genomic and cDNA clones indicates that the eve protein is composed of 376 amino acid residues, and that its homeo domain shares only approximately 50% amino acid identity with the homeo domains of previously characterized genes. Using antibodies raised against a beta‐galactosidase fusion protein we show that the eve protein is distributed in a series of seven transverse stripes at the cellular blastoderm stage, and is localized primarily within the nuclear regions of those embryonic cells that express the gene. After gastrulation, seven weakly stained stripes of eve expression appear, resulting in a transient pattern that consists of a total of 14 evenly spaced stripes. Both the original and new stripes gradually disappear during germ band elongation. A second expression pattern emerges during neurogenesis, whereby eve protein is detected in discrete subsets of neurons in each of the ventral ganglia.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery datasets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5×10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signaling and cytokine-cytokine pathways, for which relevant therapies exist.

The pair-rule genes of Drosophila are required for the subdivision of the developing embryo into a repeating series of homologous body segments. One of the pair-rule genes, even-skipped (eve), appears to be particularly important for the overall segmentation pattern since eve- embryos lack all segmental subdivisions in the middle body region. On the basis of homeo box cross-homology we have isolated a gene, S72, which probably corresponds to eve. In embryo tissue sections S72 transcripts show a periodic distribution pattern. The eve- phenotype appears to involve altered patterns of fushi tarazu and engrailed expression. These and other findings suggest that pair-rule gene expression might involve hierarchical cross-regulatory interactions.

The homoeobox gene zerknüllt (zen) plays an important role in the differentiation of dorsal tissues during Drosophila development. zen- embryos show transformations in the dorsal-most regions of the fate map, and lack several tissues that normally derive from these regions, including the amnioserosa and optic lobe. zen displays a simple dorsal on/ventral off pattern as early as cleavage cycle 10-11 (ref. 2). We have prepared a polyclonal antibody against a full-length zen protein, and used this to examine its pattern of expression in mutants that disrupt dorsal-ventral polarity. Most or all of the maternally expressed genes that are involved in this process have been previously identified and fall into two classes, so called 'dorsalizers' and 'ventralizers' (see refs 4-7, reviewed in ref. 8). On the basis of our analysis of zen expression in each of these maternal mutants we propose that one or more of the dorsalizing genes encodes a repressor which inhibits the expression of zen in ventral regions of developing embryos. The ventralizing gene cactus might play an important role in restricting the activity of this repressor to ventral regions, thereby permitting the activation of zen in those dorsal tissues where its function is critically required.