Generation of optical 'Schrödinger cats' from photon number states

Schr?dinger's cat is a Gedankenexperiment in quantum physics, in which an atomic decay triggers the death of the cat. Because quantum physics allow atoms to remain in superpositions of states, the classical cat would then be simultaneously dead and alive. By analogy, a 'cat' state of freely propagating light can be defined as a quantum superposition of well separated quasi-classical states-it is a classical light wave that simultaneously possesses two opposite phases. Such states play an important role in fundamental tests of quantum theory and in many quantum information processing tasks, including quantum computation, quantum teleportation and precision measurements. Recently, optical Schr?dinger 'kittens' were prepared; however, they are too small for most of the aforementioned applications and increasing their size is experimentally challenging. Here we demonstrate, theoretically and experimentally, a protocol that allows the generation of arbitrarily large squeezed Schr?dinger cat states, using homodyne detection and photon number states as resources. We implemented this protocol with light pulses containing two photons, producing a squeezed Schr?dinger cat state with a negative Wigner function. This state clearly exhibits several quantum phase-space interference fringes between the 'dead' and 'alive' components, and is large enough to become useful for quantum information processing and experimental tests of quantum theory.     

Galectin-3 stabilizes heterogeneous nuclear ribonucleoprotein Q to maintain proliferation of human colon cancer cells

Comparative analysis of proteomes using 5-fluorouracil (5-FU)-resistant human colon cancer cell line revealed that decreased galectin-3 expression was significantly associated with retarded proliferation. However, in the presence of 5-FU proliferation rate of cells with suppressed galectin-3 expression did not differ from that of cells with normal galectin-3 expression, even galectin-3 suppression augmented apoptosis. Mechanism by which galectin-3 regulates cancer cell proliferation has been identified in immunoprecipitates of the anti-galectin-3 antibody. Heterogeneous nuclear ribonucleoprotein Q (hnRNP Q) was identified as a protein interacting with galectin-3. Interestingly, while galectin-3 protein was not affected by the hnRNP Q level, its suppression was accompanied by a decrease in hnRNP Q expression. The present study demonstrates that galectin-3 stabilizes hnRNP Q via complex formation, and reduction in the hnRNP Q level leads to slow proliferation and less susceptibility to 5-FU. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. B.C.Yoo; S-H.Hong; These two authors contributed equally to this work. Received 10 September 2008; received after revision 19 October 2008; accepted 07 November 2008     

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.     

The genome sequence of the rice blast fungus Magnaporthe grisea

Magnaporthe grisea is the most destructive pathogen of rice worldwide and the principal model organism for elucidating the molecular basis of fungal disease of plants. Here, we report the draft sequence of the M. grisea genome. Analysis of the gene set provides an insight into the adaptations required by a fungus to cause disease. The genome encodes a large and diverse set of secreted proteins, including those defined by unusual carbohydrate-binding domains. This fungus also possesses an expanded family of G-protein-coupled receptors, several new virulence-associated genes and large suites of enzymes involved in secondary metabolism. Consistent with a role in fungal pathogenesis, the expression of several of these genes is upregulated during the early stages of infection-related development. The M. grisea genome has been subject to invasion and proliferation of active transposable elements, reflecting the clonal nature of this fungus imposed by widespread rice cultivation.     

Editing-defective tRNA synthetase causes protein misfolding and neurodegeneration

Misfolded proteins are associated with several pathological conditions including neurodegeneration. Although some of these abnormally folded proteins result from mutations in genes encoding disease-associated proteins (for example, repeat-expansion diseases), more general mechanisms that lead to misfolded proteins in neurons remain largely unknown. Here we demonstrate that low levels of mischarged transfer RNAs (tRNAs) can lead to an intracellular accumulation of misfolded proteins in neurons. These accumulations are accompanied by upregulation of cytoplasmic protein chaperones and by induction of the unfolded protein response. We report that the mouse sticky mutation, which causes cerebellar Purkinje cell loss and ataxia, is a missense mutation in the editing domain of the alanyl-tRNA synthetase gene that compromises the proofreading activity of this enzyme during aminoacylation of tRNAs. These findings demonstrate that disruption of translational fidelity in terminally differentiated neurons leads to the accumulation of misfolded proteins and cell death, and provide a novel mechanism underlying neurodegeneration.     

Sojucktang induces apoptosis via loss of mitochondrial membrane potential and caspase-3 activation in KLE human endometrial cancer cells

Sojucktang （SJT） has long been used for the treatment of endometrial diseases in Korea. However, the mechanisms responsible for the SJT-induced apoptosis in endometrial cancer cells remain unclear. In the present study, SJT was demonstrated to show cytotoxic effect and induce apoptotic cell death via mitochondrial regulation in KLE endometrial cancer cells. Linderae Radix, Glycyrrhizae Radix, Zedoariae Rhizoma, Trogopterorum Faeces and Agelicae Gigantis Radix were found to be the potent constituent herbs of SJT to significantly decrease the viability of KLE cells by a tetra zolium salt （XTT） assay. Apoptotic bodies were observed in SJT-treated KLE cells by 4′-6-diamidino-2-phenylindole （DAPI） and TdT-mediated-dUTP nick-end labeling （TUNEL） assay. SJT also increased sub-G1 DNA contents of the cell cycle undergoing apoptosis in a dose-dependent manner. Furthermore, it was observed that SJT activated caspase-3 and cleaved poly （ADP-ribose） polymerase （PARP）, and decreased mitochondrial membrane potential in a dose-dependent manner. Taken together, this study shows that SJT exerts anti-tumor activity against KLE endometrial cancer cells via mitochondrial dependent apoptosis induction.     

Folding-driven synthesis of oligomers.

The biological function of biomacromolecules such as DNA and enzymes depends on their ability to perform and control molecular association, catalysis, self-replication or other chemical processes. In the case of proteins in particular, the dependence of these functions on the three-dimensional protein conformation is long known and has inspired the development of synthetic oligomers and polymers with the capacity to fold in a controlled manner, but it remains challenging to design these so-called 'foldamers' so that they are capable of inducing or controlling chemical processes and interactions. Here we show that the stability gained from folding can be used to control the synthesis of oligomers from short chain segments reversibly ligated through an imine metathesis reaction. That is, folding shifts the ligation equilibrium in favour of conformationally ordered sequences, so that oligomers having the most stable solution structures form preferentially. Crystallization has previously been used to shift an equilibrium in order to indirectly influence the synthesis of small molecules, but the present approach to selectively prepare macromolecules with stable conformations directly connects folding and synthesis, emphasizing molecular function rather than structure in polymer synthesis.     

Stepwise replication identifies a low-producing lymphotoxin-alpha allele as a major risk factor for early-onset leprosy

Host genetics has an important role in leprosy, and variants in the shared promoter region of PARK2 and PACRG were the first major susceptibility factors identified by positional cloning. Here we report the linkage disequilibrium mapping of the second linkage peak of our previous genome-wide scan, located close to the HLA complex. In both a Vietnamese familial sample and an Indian case-control sample, the low-producing lymphotoxin-alpha (LTA)+80 A allele was significantly associated with an increase in leprosy risk (P = 0.007 and P = 0.01, respectively). Analysis of an additional case-control sample from Brazil and an additional familial sample from Vietnam showed that the LTA+80 effect was much stronger in young individuals. In the combined sample of 298 Vietnamese familial trios, the odds ratio of leprosy for LTA+80 AA/AC versus CC subjects was 2.11 (P = 0.000024), which increased to 5.63 (P = 0.0000004) in the subsample of 121 trios of affected individuals diagnosed before 16 years of age. In addition to identifying LTA as a major gene associated with early-onset leprosy, our study highlights the critical role of case- and population-specific factors in the dissection of susceptibility variants in complex diseases.