Articles in 2007

Previous work has identified several genes where mutations lead to breast cancer, but other genetic and environmental factors must still be accounted for. A large study of genetic association with breast cancer points to four novel genes and many more genetic markers that should be pursued for their link to cancer susceptibility.

A new, transcription-independent function for c-Myc is identified. It is found that c-Myc can bind factors involved in DNA replication, thereby causing DNA damage and affecting cell proliferation. This process may also contribute to oncogenesis.

Attachment of a piece of viral protein to a small RNA achieves transfer of the RNA into neuronal cells in cell culture. This was also able to deliver an antiviral siRNA specifically into the brains of mice infected with encephalitis and achieve 80% protection. This study opens a new potential line of treatment for neuronal disease.

Crystal structures of bacterial RNA polymerase elongation complexes bound to NTP substrate analogues with an antibiotic, revealing the mechanism of substrate loading and antibiotic inhibition.

Crystal structure of bacterial RNA polymerase bound to the DNA template and RNA product, revealing a detailed view of the transcription elongation complex.

Attachment of a piece of viral protein to a small RNA achieves transfer of the RNA into neuronal cells in cell culture. This was also able to deliver an antiviral siRNA specifically into the brains of mice infected with encephalitis and achieve 80% protection. This study opens a new potential line of treatment for neuronal disease.

The next step after sequencing a genome is to figure out how the cell actually uses it as an instruction manual. A large international consortium has examined 1% of the genome for what part is transcribed, where proteins are bound, what the chromatin structure looks like, and how the sequence compares to that of other organisms.

Dopaminergic neurons heavily rely on Ca²⁺ channels to maintain their rhythmic activity, and this reliance increases with age. But adult neurons can be tempted to revert to using the Na⁺/HCN channels, as younger neurons do, by treatment with a commonly used drug.

An exciting genome-wide association study in the British population for seven common diseases. This analysis confirms previously identified loci and provides strong evidence for many novel disease susceptibility loci.

This study provides direct experimental evidence for an important hypothesized mechanism of ageing, showing that the maintenance of adult haematopoietic stem cell function during ageing and haematopoietic stem cell transplantation is critically dependent on DNA repair by the non-homologous end-joining pathway.

It is generally believed that unfertilized oocytes are required for successful somatic cell nuclear transfer, but this paper demonstrates that reprogramming activities persist after fertilization. These findings have important implications for understanding the nature of the nuclear reprogramming activities, the biology of cloned animals and the ongoing efforts to derive patient specific human embryonic stem cell lines.

Four transcription factors Oct4, Sox2, c-Myc and Klf4 are known to convert fibroblasts to pluripotent stem cells, if Fbx15 expression is also selected. But the induced stem cells were shown to be distinct from normal embryonic stem cells. However, if cells expressing Nanog and Oct4 are selected, then the reprogrammed fibroblasts are similar to embryonic stem cells in both biological potency and epigenetic state.

Four transcription factors Oct4, Sox2, c-Myc and Klf4 are known to convert fibroblasts to pluripotent stem cells, if Fbx15 expression is also selected. But the induced stem cells were shown to be distinct from normal embryonic stem cells. However, if cells expressing Nanog and Oct4 are selected, then the reprogrammed fibroblasts are similar to embryonic stem cells in both biological potency and epigenetic state.

It is shown that a small molecule inhibitor can successfully target the adipocyte/macrophage fatty acid-binding protein aP2, and that oral administration of the inhibitor can result in metabolic improvement and decreased atherosclerosis and insulin resistance in mice.

Humans frequently combine probabilities about possible outcomes to reach decisions, but monkeys can also make decisions based on probabilistic information about rewards. Neurons in the parietal cortex reveal the addition and subtraction of probabilistic quantities underlying these decisions.

Increased longevity of diet-restricted Caenorhabditis elegans requires the transcription factor gene skn-1 acting in the ASIs, a pair of neurons in the head. Dietary restriction activates skn-1 in the ASIs, which signals peripheral tissues to increase metabolic activity. These findings demonstrate that increased lifespan in a diet-restricted nematode depends on signalling from central neuronal cells to non-neuronal body tissues, and suggest that the ASIs mediate dietary restriction-induced longevity by an endocrine mechanism.

An in vitro system of lipopolysaccharide tolerance in murine macrophages is used to show that TLR-induced genes fall into two categories on the basis of their functions and regulatory requirements.

Semiconductor nanocrystals seem good candidates for 'soft' optical gain media, but optical gain and lasing is hard to achieve owing to a fundamental optical effect, which involves the problem that at least two excitons need to be present in a nanocrystal to achieve gain, and this limits performance. Here the problem is circumvented by designing nanocrystals with cores and shells made from different semiconductor materials, and in such a way that electrons and holes are separated from each other: this makes possible optical gain based on single excitons, thereby significantly enhancing the promise of semiconductor nanocrystals as practical optical materials for a wide range of lasing applications.

A mouse lymphoma model that shows a similar level of genomic instability generally seen in human cancer has been created. In a comparative genomics approach, recurrent genetic alterations found in this model are used as a filter to identify overlapping alterations in human T-cell acute lymphoblastic lymphomas, including in the FBXW7 and NOTCH genes.