Extensive characterization of sphere models established from colorectal cancer cell lines

Links between cancer and stem cells have been proposed for many years. As the cancer stem cell (CSC) theory became widely studied, new methods were developed to culture and expand cancer cells with conserved determinants of “stemness”. These cells show increased ability to grow in suspension as spheres in serum-free medium supplemented with growth factors and chemicals. The physiological relevance of this phenomenon in established cancer cell lines remains unclear. Cell lines have traditionally been used to explore tumor biology and serve as preclinical models for the screening of potential therapeutic agents. Here, we grew cell-forming spheres (CFS) from 25 established colorectal cancer cell lines. The molecular and cellular characteristics of CFS were compared to the bulk of tumor cells. CFS could be isolated from 72 % of the cell lines. Both CFS and their parental CRC cell lines were highly tumorigenic. Compared to their parental cells, they showed similar expression of putative CSC markers. The ability of CRC cells to grow as CFS was greatly enhanced by prior treatment with 5-fluorouracil. At the molecular level, CFS and parental CRC cells showed identical gene mutations and very similar genomic profiles, although microarray analysis revealed changes in CFS gene expression that were independent of DNA copy-number. We identified a CFS gene expression signature common to CFS from all CRC cell lines, which was predictive of disease relapse in CRC patients. In conclusion, CFS models derived from CRC cell lines possess interesting phenotypic features that may have clinical relevance for drug resistance and disease relapse.     

Variation in FTO contributes to childhood obesity and severe adult obesity

We identified a set of SNPs in the first intron of the FTO (fat mass and obesity associated) gene on chromosome 16q12.2 that is consistently strongly associated with early-onset and severe obesity in both adults and children of European ancestry with an experiment-wise P value of 1.67 x 10(-26) in 2,900 affected individuals and 5,100 controls. The at-risk haplotype yields a proportion of attributable risk of 22% for common obesity. We conclude that FTO contributes to human obesity and hence may be a target for subsequent functional analyses.     

Effect of different deformation and annealing procedures on non-magnetic textured Cu<Subscript>60</Subscript>Ni<Subscript>40</Subscript> alloy substrates

In this work, a series of specimens was prepared by the casting method. Sharp cube-textured substrates were processed by heavy cold rolling and recrystallization annealing (i.e., the rolling-assisted biaxially textured substrates (RABiTS) method). Both the rolling and the recrystallization texture in the alloy tapes were investigated by X-ray diffraction and electron back-scatter diffraction, respectively. The results showed that a strong copper-type deformation texture was obtained in the heavy cold-rolled substrate. In addition, the recrystallization annealing process was found to be very important for the texture transition in the Cu–Ni alloy substrates. The cube texture content in the Cu₆₀Ni₄₀ alloy substrates reached 99.7% (≤10°) after optimization of the cold-rolling procedure and the recrystallizing heat-treatment process, whereas the content of low-angle grain boundaries (from 2° to 10° misorientation) in the substrate reached 95.1%.     

IgM memory B cells: a mouse/human paradox

Humoral memory is maintained by two types of persistent cells, memory B cells and plasma cells, which have different phenotypes and functions. Long-lived plasma cells can survive for a lifespan within a complex niche in the bone marrow and provide continuous protective serum antibody levels. Memory B cells reside in secondary lymphoid organs, where they can be rapidly mobilized upon a new antigenic encounter. Surface IgG has long been taken as a surrogate marker for memory in the mouse. Recently, however, we have brought evidence for a long-lived IgM memory B cell population in the mouse, while we have also argued that, in humans, these same cells are not classical memory B cells but marginal zone (MZ) B cells which, as opposed to their mouse MZ counterpart, recirculate and carry a mutated B cell receptor. In this review, we will discuss these apparently paradoxical results.     

Highly effective SNP-based association mapping and management of recessive defects in livestock

The widespread use of elite sires by means of artificial insemination in livestock breeding leads to the frequent emergence of recessive genetic defects, which cause significant economic and animal welfare concerns. Here we show that the availability of genome-wide, high-density SNP panels, combined with the typical structure of livestock populations, markedly accelerates the positional identification of genes and mutations that cause inherited defects. We report the fine-scale mapping of five recessive disorders in cattle and the molecular basis for three of these: congenital muscular dystony (CMD) types 1 and 2 in Belgian Blue cattle and ichthyosis fetalis in Italian Chianina cattle. Identification of these causative mutations has an immediate translation into breeding practice, allowing marker assisted selection against the defects through avoidance of at-risk matings.     

Nosiheptide,a sulfur-containing peptide antibiotic isolated fromStreptomyces actuosus 40037

Summary Nosiheptide (9671 R.P.) isolated fromStreptomyces actuosus 40037 (NRRL 2954) is a sulfur-containing polypeptidic antibiotic, quite different from all the other members of this family. Very active in vitro against gram-positive bacteria, it is inactive in vivo in experimentally infected mice. Not toxic, even at high dose, it may be used as a feed additive for chickens and pigs and it shows a favourable effect on the growth and conversion index.     

Optical studies of solid hydrogen to 320 GPa and evidence for black hydrogen

The quest for metallic hydrogen at high pressures represents a longstanding problem in condensed matter physics. Recent calculations have predicted that solid hydrogen should become a molecular metal at pressures above 300 GPa, before transforming into an alkali metal; but the strong quantum nature of the problem makes the predictions difficult. Over a decade ago, an optical study of hydrogen was made using a diamond anvil cell to reach 250 GPa. However, despite many subsequent efforts, quantitative studies at higher pressures have proved difficult and their conclusions controversial. Here we report optical measurements of solid hydrogen up to a pressure of 320 GPa at 100 K. The vibron signature of the H2 molecule persists to at least 316 GPa; no structural changes are detected above 160 GPa, and solid hydrogen is observed to turn completely opaque at 320 GPa. We measure the absorption edge of hydrogen above 300 GPa, observing features characteristic of a direct electronic bandgap. This is at odds with the most recent theoretical calculations that predict much larger direct transition energies and the closure of an indirect gap. We predict that metal hydrogen should be observed at about 450 GPa when the direct gap closes.