Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18.

Salmonella enterica serovar Typhi (S. typhi) is the aetiological agent of typhoid fever, a serious invasive bacterial disease of humans with an annual global burden of approximately 16 million cases, leading to 600,000 fatalities. Many S. enterica serovars actively invade the mucosal surface of the intestine but are normally contained in healthy individuals by the local immune defence mechanisms. However, S. typhi has evolved the ability to spread to the deeper tissues of humans, including liver, spleen and bone marrow. Here we have sequenced the 4,809,037-base pair (bp) genome of a S. typhi (CT18) that is resistant to multiple drugs, revealing the presence of hundreds of insertions and deletions compared with the Escherichia coli genome, ranging in size from single genes to large islands. Notably, the genome sequence identifies over two hundred pseudogenes, several corresponding to genes that are known to contribute to virulence in Salmonella typhimurium. This genetic degradation may contribute to the human-restricted host range for S. typhi. CT18 harbours a 218,150-bp multiple-drug-resistance incH1 plasmid (pHCM1), and a 106,516-bp cryptic plasmid (pHCM2), which shows recent common ancestry with a virulence plasmid of Yersinia pestis.     

Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes

The Wellcome Trust Case Control Consortium (WTCCC) primary genome-wide association (GWA) scan on seven diseases, including the multifactorial autoimmune disease type 1 diabetes (T1D), shows associations at P < 5 x 10(-7) between T1D and six chromosome regions: 12q24, 12q13, 16p13, 18p11, 12p13 and 4q27. Here, we attempted to validate these and six other top findings in 4,000 individuals with T1D, 5,000 controls and 2,997 family trios independent of the WTCCC study. We confirmed unequivocally the associations of 12q24, 12q13, 16p13 and 18p11 (P(follow-up) 相似文献   

Genome sequence of Yersinia pestis, the causative agent of plague

The Gram-negative bacterium Yersinia pestis is the causative agent of the systemic invasive infectious disease classically referred to as plague, and has been responsible for three human pandemics: the Justinian plague (sixth to eighth centuries), the Black Death (fourteenth to nineteenth centuries) and modern plague (nineteenth century to the present day). The recent identification of strains resistant to multiple drugs and the potential use of Y. pestis as an agent of biological warfare mean that plague still poses a threat to human health. Here we report the complete genome sequence of Y. pestis strain CO92, consisting of a 4.65-megabase (Mb) chromosome and three plasmids of 96.2 kilobases (kb), 70.3 kb and 9.6 kb. The genome is unusually rich in insertion sequences and displays anomalies in GC base-composition bias, indicating frequent intragenomic recombination. Many genes seem to have been acquired from other bacteria and viruses (including adhesins, secretion systems and insecticidal toxins). The genome contains around 150 pseudogenes, many of which are remnants of a redundant enteropathogenic lifestyle. The evidence of ongoing genome fluidity, expansion and decay suggests Y. pestis is a pathogen that has undergone large-scale genetic flux and provides a unique insight into the ways in which new and highly virulent pathogens evolve.     

The genome of the simian and human malaria parasite Plasmodium knowlesi

Plasmodium knowlesi is an intracellular malaria parasite whose natural vertebrate host is Macaca fascicularis (the 'kra' monkey); however, it is now increasingly recognized as a significant cause of human malaria, particularly in southeast Asia. Plasmodium knowlesi was the first malaria parasite species in which antigenic variation was demonstrated, and it has a close phylogenetic relationship to Plasmodium vivax, the second most important species of human malaria parasite (reviewed in ref. 4). Despite their relatedness, there are important phenotypic differences between them, such as host blood cell preference, absence of a dormant liver stage or 'hypnozoite' in P. knowlesi, and length of the asexual cycle (reviewed in ref. 4). Here we present an analysis of the P. knowlesi (H strain, Pk1(A+) clone) nuclear genome sequence. This is the first monkey malaria parasite genome to be described, and it provides an opportunity for comparison with the recently completed P. vivax genome and other sequenced Plasmodium genomes. In contrast to other Plasmodium genomes, putative variant antigen families are dispersed throughout the genome and are associated with intrachromosomal telomere repeats. One of these families, the KIRs, contains sequences that collectively match over one-half of the host CD99 extracellular domain, which may represent an unusual form of molecular mimicry.     

Coherent quantum state storage and transfer between two phase qubits via a resonant cavity

As with classical information processing, a quantum information processor requires bits (qubits) that can be independently addressed and read out, long-term memory elements to store arbitrary quantum states, and the ability to transfer quantum information through a coherent communication bus accessible to a large number of qubits. Superconducting qubits made with scalable microfabrication techniques are a promising candidate for the realization of a large-scale quantum information processor. Although these systems have successfully passed tests of coherent coupling for up to four qubits, communication of individual quantum states between superconducting qubits via a quantum bus has not yet been realized. Here, we perform an experiment demonstrating the ability to coherently transfer quantum states between two superconducting Josephson phase qubits through a quantum bus. This quantum bus is a resonant cavity formed by an open-ended superconducting transmission line of length 7 mm. After preparing an initial quantum state with the first qubit, this quantum information is transferred and stored as a nonclassical photon state of the resonant cavity, then retrieved later by the second qubit connected to the opposite end of the cavity. Beyond simple state transfer, these results suggest that a high-quality-factor superconducting cavity could also function as a useful short-term memory element. The basic architecture presented here can be expanded, offering the possibility for the coherent interaction of a large number of superconducting qubits.     

Circuit cavity electromechanics in the strong-coupling regime

Demonstrating and exploiting the quantum nature of macroscopic mechanical objects would help us to investigate directly the limitations of quantum-based measurements and quantum information protocols, as well as to test long-standing questions about macroscopic quantum coherence. Central to this effort is the necessity of long-lived mechanical states. Previous efforts have witnessed quantum behaviour, but for a low-quality-factor mechanical system. The field of cavity optomechanics and electromechanics, in which a high-quality-factor mechanical oscillator is parametrically coupled to an electromagnetic cavity resonance, provides a practical architecture for cooling, manipulation and detection of motion at the quantum level. One requirement is strong coupling, in which the interaction between the two systems is faster than the dissipation of energy from either system. Here, by incorporating a free-standing, flexible aluminium membrane into a lumped-element superconducting resonant cavity, we have increased the single-photon coupling strength between these two systems by more than two orders of magnitude, compared to previously obtained coupling strengths. A parametric drive tone at the difference frequency between the mechanical oscillator and the cavity resonance dramatically increases the overall coupling strength, allowing us to completely enter the quantum-enabled, strong-coupling regime. This is evidenced by a maximum normal-mode splitting of nearly six bare cavity linewidths. Spectroscopic measurements of these 'dressed states' are in excellent quantitative agreement with recent theoretical predictions. The basic circuit architecture presented here provides a feasible path to ground-state cooling and subsequent coherent control and measurement of long-lived quantum states of mechanical motion.