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Growing evidence supports a link between inflammation and cancer; however, mediators of the transition between inflammation and carcinogenesis remain incompletely understood. Sphingosine-1-phosphate (S1P) lyase (SPL) irreversibly degrades the bioactive sphingolipid S1P and is highly expressed in enterocytes but downregulated in colon cancer. Here, we investigated the role of SPL in colitis-associated cancer (CAC). We generated mice with intestinal epithelium-specific Sgpl1 deletion and chemically induced colitis and tumor formation in these animals. Compared with control animals, mice lacking intestinal SPL exhibited greater disease activity, colon shortening, cytokine levels, S1P accumulation, tumors, STAT3 activation, STAT3-activated microRNAs (miRNAs), and suppression of miR-targeted anti-oncogene products. This phenotype was attenuated by STAT3 inhibition. In fibroblasts, silencing SPL promoted tumorigenic transformation through a pathway involving extracellular transport of S1P through S1P transporter spinster homolog 2 (SPNS2), S1P receptor activation, JAK2/STAT3-dependent miR-181b-1 induction, and silencing of miR-181b-1 target cylindromatosis (CYLD). Colon biopsies from patients with inflammatory bowel disease revealed enhanced S1P and STAT3 signaling. In mice with chemical-induced CAC, oral administration of plant-type sphingolipids called sphingadienes increased colonic SPL levels and reduced S1P levels, STAT3 signaling, cytokine levels, and tumorigenesis, indicating that SPL prevents transformation and carcinogenesis. Together, our results suggest that dietary sphingolipids can augment or prevent colon cancer, depending upon whether they are metabolized to S1P or promote S1P metabolism through the actions of SPL.

Exploration of avian gametologous genes, i.e., homologous genes located on both the Z and W chromosomes, provides a crucial information about the underlying mechanism pertaining to the evolution of these chromosomes. The domestic chicken ( Gallus gallus (Linnaeus 1758); GGA) traditionally serves as the primary reference subject of these comparative cytogenomic studies. Using bioinformatic, molecular (overgo BAC library scanning), and cytogenetic (BAC-based FISH) techniques, we have investigated in detail a pair of UBE2R2 / UBE2R2L gametologs. By screening a gridded genomic jungle fowl BAC library, CHORI-261, with a short labeled UBE2R2L gene fragment called overgo probe, we detected seven specific clones. For three of them, CH261-019I23, CH261-105E16, and CH261-114G22, we identified their precise cytogenetic location on the Gallus gallus W chromosome (GGAW). They also co-localized with the UBAP2L2 gene on the, as was shown previously, along with the CH261-053P09 BAC clone also containing the GGAW-specific UBE2R2L DNA sequence. The fine mapping of the UBE2R2 / UBE2R2L homologs in the chicken genome also shed the light on comparative cytogenetic aspects in birds. Our findings provided further evidence that bird genomes moderately changed only during evolution and are suitable for successful use of interspecies hybridization using both overgo-based BAC library screen and BAC-based FISH.

In 2007, the International Knockout Mouse Consortium (IKMC) made the ambitious promise to generate mutations in virtually every protein-coding gene of the mouse genome in a concerted worldwide action. Now, 5 years later, the IKMC members have developed high-throughput gene trapping and, in particular, gene-targeting pipelines and generated more than 17,400 mutant murine embryonic stem (ES) cell clones and more than 1,700 mutant mouse strains, most of them conditional. A common IKMC web portal (www.knockoutmouse.org) has been established, allowing easy access to this unparalleled biological resource. The IKMC materials considerably enhance functional gene annotation of the mammalian genome and will have a major impact on future biomedical research.

Strategies for assembling large, complex genomes have evolved to include a combination of whole-genome shotgun sequencing and hierarchal map-assisted sequencing 1 , 2 . Whole-genome maps of all types can aid genome assemblies, generally starting with low-resolution cytogenetic maps and ending with the highest resolution of sequence. Fingerprint clone maps are based upon complete restriction enzyme digests of clones representative of the target genome, and ultimately comprise a near-contiguous path of clones across the genome. Such clone-based maps are used to validate sequence assembly order, supply long-range linking information for assembled sequences, anchor sequences to the genetic map and provide templates for closing gaps. Fingerprint maps are also a critical resource for subsequent functional genomic studies, because they provide a redundant and ordered sampling of the genome with clones 3 . In an accompanying paper 4 we describe the draft genome sequence of the chicken, Gallus gallus , the first species sequenced that is both a model organism and a global food source. Here we present a clone-based physical map of the chicken genome at 20-fold coverage, containing 260 contigs of overlapping clones. This map represents approximately 91% of the chicken genome and enables identification of chicken clones aligned to positions in other sequenced genomes.

We have developed a new approach to screen bacterial artificial chromosome (BAC) libraries by recombination selection. To test this method, we constructed an orangutan BAC library using an E. coli strain (DY380) with temperature inducible homologous recombination (HR) capability. We amplified one library segment, induced HR at 42∘C to make it recombination proficient, and prepared electrocompetent cells for transformation with a kanamycin cassette to target sequences in the orangutan genome through terminal recombineering homologies. Kanamycin-resistant colonies were tested for the presence of BACs containing the targeted genes by the use of a PCR-assay to confirm the presence of the kanamycin insertion. The results indicate that this is an effective approach for screening clones. The advantage of recombination screening is that it avoids the high costs associated with the preparation, screening, and archival storage of arrayed BAC libraries. In addition, the screening can be conceivably combined with genetic engineering to create knockout and reporter constructs for functional studies.

A synergistic combination of two next-generation sequencing platforms with a detailed comparative BAC physical contig map provided a cost-effective assembly of the genome sequence of the domestic turkey (Meleagris gallopavo). Heterozygosity of the sequenced source genome allowed discovery of more than 600,000 high quality single nucleotide variants. Despite this heterozygosity, the current genome assembly (~1.1 Gb) includes 917 Mb of sequence assigned to specific turkey chromosomes. Annotation identified nearly 16,000 genes, with 15,093 recognized as protein coding and 611 as non-coding RNA genes. Comparative analysis of the turkey, chicken, and zebra finch genomes, and comparing avian to mammalian species, supports the characteristic stability of avian genomes and identifies genes unique to the avian lineage. Clear differences are seen in number and variety of genes of the avian immune system where expansions and novel genes are less frequent than examples of gene loss. The turkey genome sequence provides resources to further understand the evolution of vertebrate genomes and genetic variation underlying economically important quantitative traits in poultry. This integrated approach may be a model for providing both gene and chromosome level assemblies of other species with agricultural, ecological, and evolutionary interest.

Thin layers of silver nanowires are commonly studied for transparent electronics. However, reports of their terahertz (THz) properties are scarce. Here, we present the electrical and optical properties of thin silver nanowire layers with increasing densities at THz frequencies. We demonstrate that the absorbance, transmittance and reflectance of the metal nanowire layers in the frequency range of 0.2 THz to 1.3 THz is non-monotonic and depends on the nanowire dimensions and filling factor. We also present and validate a theoretical approach describing well the experimental results and allowing the fitting of the THz response of the nanowire layers by a Drude–Smith model of conductivity. Our results pave the way toward the application of silver nanowires as a prospective material for transparent and conductive coatings, and printable antennas operating in the terahertz range—significant for future wireless communication devices.

Materials with tunable dielectric properties are highly relevant for terahertz (THz) applications. Herein, the tuning of the dielectric response of single‐walled carbon nanotube layers by light illumination is studied for applications to THz phase shifters. The dependence of the length of individual nanotubes on the THz photoconductivity of the network is experimentally investigated in the frequency range of 0.2–1 THz by time‐domain spectroscopy (TDS). The effective conductivity of the networks is described by a theoretical model that fits the measured dielectric function. Terahertz phase shifters are realized with the carbon nanotube layers as the optically tunable element deposited on the wall of rectangular dielectric waveguides. The phase of the electromagnetic wave propagating in the waveguide is shown to be tunable by illuminating the nanotubes. A linear phase shift with the frequency is measured between 75 and 500 GHz with a low change in amplitude due to the illumination. The tuning of the dielectric response of single‐walled carbon nanotubes (CNTs) under illumination is studied for applications to THz phase shifters. The dependence of the length of individual nanotubes on the THz photoconductivity of the network is investigated by time‐domain spectroscopy (TDS). Phase shifters are realized with the CNT layers as optically tunable element, integrated with dielectric waveguides.