Mutational analysis of the tyrosine phosphatome in colorectal cancers

Tyrosine phosphorylation, regulated by protein tyrosine phosphatases (PTPs) and kinases (PTKs), is important in signaling pathways underlying tumorigenesis. A mutational analysis of the tyrosine phosphatase gene superfamily in human cancers identified 83 somatic mutations in six PTPs (PTPRF, PTPRG, PTPRT, PTPN3, PTPN13, PTPN14), affecting 26% of colorectal cancers and a smaller fraction of lung, breast, and gastric cancers. Fifteen mutations were nonsense, frameshift, or splice-site alterations predicted to result in truncated proteins lacking phosphatase activity. Five missense mutations in the most commonly altered PTP (PTPRT) were biochemically examined and found to reduce phosphatase activity. Expression of wild-type but not a mutant PTPRT in human cancer cells inhibited cell growth. These observations suggest that the mutated tyrosine phosphatases are tumor suppressor genes, regulating cellular pathways that may be amenable to therapeutic intervention.     

Entangled images from four-wave mixing

Two beams of light can be quantum mechanically entangled through correlations of their phase and intensity fluctuations. For a pair of spatially extended image-carrying light fields, the concept of entanglement can be applied not only to the entire images but also to their smaller details. We used a spatially multimode amplifier based on four-wave mixing in a hot vapor to produce twin images that exhibit localized entanglement. The images can be bright fields that display position-dependent quantum noise reduction in their intensity difference or vacuum twin beams that are strongly entangled when projected onto a large range of different spatial modes. The high degree of spatial entanglement demonstrates that the system is an ideal source for parallel continuous-variable quantum information protocols.     

Mitotic Golgi partitioning is driven by the membrane-fissioning protein CtBP3/BARS

Organelle inheritance is an essential feature of all eukaryotic cells. As with other organelles, the Golgi complex partitions between daughter cells through the fission of its membranes into numerous tubulovesicular fragments. We found that the protein CtBP3/BARS (BARS) was responsible for driving the fission of Golgi membranes during mitosis in vivo. Moreover, by in vitro analysis, we identified two stages of this Golgi fragmentation process: disassembly of the Golgi stacks into a tubular network, and BARS-dependent fission of these tubules. Finally, this BARS-induced fission of Golgi membranes controlled the G2-to-prophase transition of the cell cycle, and hence cell division.     

A molecular basis for natural selection at the timeless locus in Drosophila melanogaster

Diapause is a protective response to unfavorable environments that results in a suspension of insect development and is most often associated with the onset of winter. The ls-tim mutation in the Drosophila melanogaster clock gene timeless has spread in Europe over the past 10,000 years, possibly because it enhances diapause. We show that the mutant allele attenuates the photosensitivity of the circadian clock and causes decreased dimerization of the mutant TIMELESS protein isoform to CRYPTOCHROME, the circadian photoreceptor. This interaction results in a more stable TIMELESS product. These findings reveal a molecular link between diapause and circadian photoreception.     

Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton

Mice in which all members of the Hox10 or Hox11 paralogous group are disrupted provide evidence that these Hox genes are involved in global patterning of the axial and appendicular skeleton. In the absence of Hox10 function, no lumbar vertebrae are formed. Instead, ribs project from all posterior vertebrae, extending caudally from the last thoracic vertebrae to beyond the sacral region. In the absence of Hox11 function, sacral vertebrae are not formed and instead these vertebrae assume a lumbar identity. The redundancy among these paralogous family members is so great that this global aspect of Hox patterning is not apparent in mice that are mutant for five of the six paralogous alleles.     

Three-dimensional plasmon rulers

Plasmon rulers can be used to determine nanoscale distances within chemical or biological species. They are based on the spectral shift of the scattering spectrum when two plasmonic nanoparticles approach one another. However, the one-dimensionality of current plasmon rulers hampers the comprehensive understanding of many intriguing processes in soft matter, which take place in three dimensions. We demonstrated a three-dimensional plasmon ruler that is based on coupled plasmonic oligomers in combination with high-resolution plasmon spectroscopy. This enables retrieval of the complete spatial configuration of complex macromolecular and biological processes as well as their dynamic evolution.     

Exclusive consolidated memory phases in Drosophila

Two types of consolidated memory have been described in Drosophila, anesthesia-resistant memory (ARM), a shorter-lived form, and stabilized long-term memory (LTM). Until now, it has been thought that ARM and LTM coexist. On the contrary, we show that LTM formation leads to the extinction of ARM. Flies devoid of mushroom body vertical lobes cannot form LTM, but spaced conditioning can still erase their ARM, resulting in a remarkable situation: The more these flies are trained, the less they remember. We propose that ARM acts as a gating mechanism that ensures that LTM is formed only after repetitive and spaced training.     

Erasing the world's slow stain: strategies to beat multidrug-resistant tuberculosis

Multidrug-resistant tuberculosis (MDR) is perceived as a growing hazard to human health worldwide. Judgments about the true scale of the problem, and strategies for containing it, need to come from a balanced appraisal of the epidemiological evidence. We conclude in this review that MDR is, and will probably remain, a locally severe problem; that epidemics can be prevented by fully exploiting the potential of standard short-course chemotherapy (SCC) based on cheap and safe first-line drugs; and that best-practice SCC may even reduce the incidence of MDR where it has already become endemic. On the basis of the available, imperfect data, we recommend a three-part response to the threat of MDR: widespread implementation of SCC as the cornerstone of good tuberculosis control, improved resistance testing and surveillance, and the careful introduction of second-line drugs after a sound evaluation of cost, effectiveness, and feasibility.