Interaction network containing conserved and essential protein complexes in Escherichia coli

Proteins often function as components of multi-subunit complexes. Despite its long history as a model organism, no large-scale analysis of protein complexes in Escherichia coli has yet been reported. To this end, we have targeted DNA cassettes into the E. coli chromosome to create carboxy-terminal, affinity-tagged alleles of 1,000 open reading frames (approximately 23% of the genome). A total of 857 proteins, including 198 of the most highly conserved, soluble non-ribosomal proteins essential in at least one bacterial species, were tagged successfully, whereas 648 could be purified to homogeneity and their interacting protein partners identified by mass spectrometry. An interaction network of protein complexes involved in diverse biological processes was uncovered and validated by sequential rounds of tagging and purification. This network includes many new interactions as well as interactions predicted based solely on genomic inference or limited phenotypic data. This study provides insight into the function of previously uncharacterized bacterial proteins and the overall topology of a microbial interaction network, the core components of which are broadly conserved across Prokaryota.     

Pre-social benefits of extended parental care

The evolution of helping, in which some individuals forfeit their own reproduction and help others to reproduce, is a central problem in evolutionary biology. Recently proposed insurance-based mechanisms rely on a pre-existing life history with a long period of offspring dependency relative to the short life expectancies of adult carers: a lone mother's offspring are doomed if she dies young, whereas after a helper dies, other group members can finish rearing the offspring. A critical question, however, is how this life history could evolve in ancestral non-social populations, as offspring survival would then depend on a single, short-lived carer. Here, we resolve this paradox by focusing on the extended parental care inherent in prolonged dependency. We show experimentally that in non-social wasps, extended care can significantly reduce the impact of interspecific parasites. Under extended care, offspring are less vulnerable by the time they are exposed to parasites, and costs of parasitism are reduced because mothers have the option to terminate investment in failing offspring. By experimentally simulating aspects of extended care in a species where it is lacking, we demonstrate that neither benefit requires specialized behaviour. Such benefits could therefore offset the disadvantage of prolonged dependency in non-social species, thereby facilitating the evolution of helping.     

Altered substrate specificity of herpes simplex virus thymidine kinase confers acyclovir-resistance

Acyclovir (9-[2-hydroxyethoxymethyl]guanine or ACV) is a nucleoside analogue with considerable potential for the treatment of herpes simplex virus (HSV) infections in man. Two virus-coded enzymes are important in the mechanism of action of this drug: thymidine kinase (TK) which initiates its activation by converting it to the monophosphate and DNA polymerase whose action is inhibited by ACV triphosphate. Changes in either gene may confer resistance, but all reported mutations in the TK gene have resulted in failure of the resistant virus to induce appreciable levels of the enzyme. Such TK- mutants arise readily in tissue culture systems where the enzyme is non-essential for virus replication, but in animals they show considerably reduced pathogenicity and neurovirulence. We now describe the isolation of a resistant mutant which induces a TK of altered substrate specificity and we show that this virus retains pathogenicity for mice with only a slight attenuation of neurovirulence.     

Genome-wide association study identifies novel breast cancer susceptibility loci

Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r2 > 0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P < 10(-7)). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P < 0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach.     

单频精密单点定位中基于卡尔曼滤波的、自适应导航算法

提出一种应用于单频精密单点定位的动态实时导航算法,该方法利用卡尔曼滤波对载波相位等观测量进行实时处理,无需静态初始化并能达到较高的定位精度。通过改进基于新息自适应的卡尔曼滤波,提高导航算法在动态环境下的稳定性与定位精度。针对单频定位中的电离层修正问题,通过建立映射模型,将电离层影响作为待估计量进行滤波。在可见星数不小于...