Novel rearrangement of purines

6-Trichloromethyl-9-methylpurine (1) rearranges to 6-dichloromethyl-9-methyl-8-oxopurine (2) in aqueous mild acidic solution. The rearrangement is rationalized in terms of a reaction involving protonation, covalent hydration, prototropic equilibrium and/or a hydride transfer. An alternative mechanism involving a "positive' halogen compound and hypochlorous acid as an intermediary is also proposed. Compound 1 condenses with 4,5-diaminopyrimidine to give the purine-pyrimidine Schiff base pair 4.     

Novel rearrangement of purines

Summary 6-Trichloromethyl-9-methylpurine (1) rearranges to 6-dichloromethyl-9-methyl-8-oxopurine (2) in aqueous mild acidic solution. The rearrangement is rationalized in terms of a reaction involving protonation, covalent hydration, prototropic equilibrium and/or a hydride transfer. An alternative mechanism involving a positive halogen compound and hypochlorous acid as an intermediary is also proposed. Compound1 condenses with 4,5-diaminopyrimidine to give the purine-pyrimidine Schiff base pair4.Acknowledgments. We are deeply indebted to Professor S. Cohen of the Sackler School of Medicine, Tel Aviv University (Ramat Aviv, Isreal) for his advice and encouragement. Support of this research by the Israel Cancer Association, the Ber-Lamsdorf Foundation Switzerland Israel and by the Advancement of Mankind Foundation, is gratefully acknowledged. We thank Proff. D. Arigoni and A. Eschenmoser, ETH Zürich, for their valuable proposals and comments on the mechanism of the rearrangement.     

Observation of strong coupling between one atom and a monolithic microresonator

Over the past decade, strong interactions of light and matter at the single-photon level have enabled a wide set of scientific advances in quantum optics and quantum information science. This work has been performed principally within the setting of cavity quantum electrodynamics with diverse physical systems, including single atoms in Fabry-Perot resonators, quantum dots coupled to micropillars and photonic bandgap cavities and Cooper pairs interacting with superconducting resonators. Experiments with single, localized atoms have been at the forefront of these advances with the use of optical resonators in high-finesse Fabry-Perot configurations. As a result of the extreme technical challenges involved in further improving the multilayer dielectric mirror coatings of these resonators and in scaling to large numbers of devices, there has been increased interest in the development of alternative microcavity systems. Here we show strong coupling between individual caesium atoms and the fields of a high-quality toroidal microresonator. From observations of transit events for single atoms falling through the resonator's evanescent field, we determine the coherent coupling rate for interactions near the surface of the resonator. We develop a theoretical model to quantify our observations, demonstrating that strong coupling is achieved, with the rate of coherent coupling exceeding the dissipative rates of the atom and the cavity. Our work opens the way for investigations of optical processes with single atoms and photons in lithographically fabricated microresonators. Applications include the implementation of quantum networks, scalable quantum logic with photons, and quantum information processing on atom chips.     

The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA.

Mitochondrial DNA (mtDNA)-depletion syndromes (MDS; OMIM 251880) are phenotypically heterogeneous, autosomal-recessive disorders characterized by tissue-specific reduction in mtDNA copy number. Affected individuals with the hepatocerebral form of MDS have early progressive liver failure and neurological abnormalities, hypoglycemia and increased lactate in body fluids. Affected tissues show both decreased activity of the mtDNA-encoded respiratory chain complexes (I, III, IV, V) and mtDNA depletion. We used homozygosity mapping in three kindreds of Druze origin to map the gene causing hepatocerebral MDS to a region of 6.1 cM on chromosome 2p13, between markers D2S291 and D2S2116. This interval encompasses the gene (DGUOK) encoding the mitochondrial deoxyguanosine kinase (dGK). We identified a single-nucleotide deletion (204delA) within the coding region of DGUOK that segregates with the disease in the three kindreds studied. Western-blot analysis did not detect dGK protein in the liver of affected individuals. The main supply of deoxyribonucleotides (dNTPs) for mtDNA synthesis comes from the salvage pathway initiated by dGK and thymidine kinase-2 (TK2). The association of mtDNA depletion with mutated DGUOK suggests that the salvage-pathway enzymes are involved in the maintenance of balanced mitochondrial dNTP pools.     

Recessive LAMC3 mutations cause malformations of occipital cortical development

The biological basis for regional and inter-species differences in cerebral cortical morphology is poorly understood. We focused on consanguineous Turkish families with a single affected member with complex bilateral occipital cortical gyration abnormalities. By using whole-exome sequencing, we initially identified a homozygous 2-bp deletion in LAMC3, the laminin γ3 gene, leading to an immediate premature termination codon. In two other affected individuals with nearly identical phenotypes, we identified a homozygous nonsense mutation and a compound heterozygous mutation. In human but not mouse fetal brain, LAMC3 is enriched in postmitotic cortical plate neurons, localizing primarily to the somatodendritic compartment. LAMC3 expression peaks between late gestation and late infancy, paralleling the expression of molecules that are important in dendritogenesis and synapse formation. The discovery of the molecular basis of this unusual occipital malformation furthers our understanding of the complex biology underlying the formation of cortical gyrations.     

A chromatin remodelling complex that loads cohesin onto human chromosomes

Nucleosomal DNA is arranged in a higher-order structure that presents a barrier to most cellular processes involving protein DNA interactions. The cellular machinery involved in sister chromatid cohesion, the cohesin complex, also requires access to the nucleosomal DNA to perform its function in chromosome segregation. The machineries that provide this accessibility are termed chromatin remodelling factors. Here, we report the isolation of a human ISWI (SNF2h)-containing chromatin remodelling complex that encompasses components of the cohesin and NuRD complexes. We show that the hRAD21 subunit of the cohesin complex directly interacts with the ATPase subunit SNF2h. Mapping of hRAD21, SNF2h and Mi2 binding sites by chromatin immunoprecipitation experiments reveals the specific association of these three proteins with human DNA elements containing Alu sequences. We find a correlation between modification of histone tails and association of the SNF2h/cohesin complex with chromatin. Moreover, we show that the association of the cohesin complex with chromatin can be regulated by the state of DNA methylation. Finally, we present evidence pointing to a role for the ATPase activity of SNF2h in the loading of hRAD21 on chromatin.     

Wave and defect dynamics in nonlinear photonic quasicrystals

Quasicrystals are unique structures with long-range order but no periodicity. Their properties have intrigued scientists ever since their discovery and initial theoretical analysis. The lack of periodicity excludes the possibility of describing quasicrystal structures with well-established analytical tools, including common notions like Brillouin zones and Bloch's theorem. New and unique features such as fractal-like band structures and 'phason' degrees of freedom are introduced. In general, it is very difficult to directly observe the evolution of electronic waves in solid-state atomic quasicrystals, or the dynamics of the structure itself. Here we use optical induction to create two-dimensional photonic quasicrystals, whose macroscopic nature allows us to explore wave transport phenomena. We demonstrate that light launched at different quasicrystal sites travels through the lattice in a way equivalent to quantum tunnelling of electrons in a quasiperiodic potential. At high intensity, lattice solitons are formed. Finally, we directly observe dislocation dynamics when crystal sites are allowed to interact with each other. Our experimental results apply not only to photonics, but also to other quasiperiodic systems such as matter waves in quasiperiodic traps, generic pattern-forming systems as in parametrically excited surface waves, liquid quasicrystals, and the more familiar atomic quasicrystals.