CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs

Primary ciliary dyskinesia (PCD) is an inherited disorder characterized by recurrent infections of the upper and lower respiratory tract, reduced fertility in males and situs inversus in about 50% of affected individuals (Kartagener syndrome). It is caused by motility defects in the respiratory cilia that are responsible for airway clearance, the flagella that propel sperm cells and the nodal monocilia that determine left-right asymmetry. Recessive mutations that cause PCD have been identified in genes encoding components of the outer dynein arms, radial spokes and cytoplasmic pre-assembly factors of axonemal dyneins, but these mutations account for only about 50% of cases of PCD. We exploited the unique properties of dog populations to positionally clone a new PCD gene, CCDC39. We found that loss-of-function mutations in the human ortholog underlie a substantial fraction of PCD cases with axonemal disorganization and abnormal ciliary beating. Functional analyses indicated that CCDC39 localizes to ciliary axonemes and is essential for assembly of inner dynein arms and the dynein regulatory complex.     

基于区间二元语义的动态灰色关联群决策方法及应用

With respect to the problem that index value is ofter given in the form of interval linguistic assessment information in the dynamic multiple attribute group decision making, a novel dynamic grey incidence group decision making methodology based on interval two tuple linguistic information is proposed. Firstly, the algorithms and properties of the interval two tuple linguistic information are used to aggregate the information evaluation matrix. Secondly, the positive and negative ideal schemes for each time period are designed in order to deal with the problem that the expert weights and time weights are known, while index weights are unknown, so that the multi objective programming model with the minimum deviation of the grey incidence degree between each scheme and the positive ideal scheme for each stage is built to determine the index weights. Thirdly, the grey incidence each stage degree with interval two tuple linguistic information between each scheme and the positive and negative ideal scheme for each stage is calculated to establish the optimization model of the optimal membership degree for scheme, so that the expressions form of the optimal membership degree for scheme is determined to solve the optimal membership degree for scheme. Finally, an example validates the feasibility and effectiveness of the novel model. The results show that the proposed method can more precisely deal with the language information and avoid information distortion and loss based on the previous method of processing the language.     

Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor

Ebola virus (EBOV) entry requires the surface glycoprotein (GP) to initiate attachment and fusion of viral and host membranes. Here we report the crystal structure of EBOV GP in its trimeric, pre-fusion conformation (GP1+GP2) bound to a neutralizing antibody, KZ52, derived from a human survivor of the 1995 Kikwit outbreak. Three GP1 viral attachment subunits assemble to form a chalice, cradled by the GP2 fusion subunits, while a novel glycan cap and projected mucin-like domain restrict access to the conserved receptor-binding site sequestered in the chalice bowl. The glycocalyx surrounding GP is likely central to immune evasion and may explain why survivors have insignificant neutralizing antibody titres. KZ52 recognizes a protein epitope at the chalice base where it clamps several regions of the pre-fusion GP2 to the amino terminus of GP1. This structure provides a template for unravelling the mechanism of EBOV GP-mediated fusion and for future immunotherapeutic development.     

Observation of the radiative decay mode of the free neutron

The theory of quantum electrodynamics (QED) predicts that beta decay of the neutron into a proton, electron and antineutrino should be accompanied by a continuous spectrum of soft photons. While this inner bremsstrahlung branch has been previously measured in nuclear beta and electron capture decay, it has never been observed in free neutron decay. Recently, the photon energy spectrum and branching ratio for neutron radiative decay have been calculated using two approaches: a standard QED framework and heavy baryon chiral perturbation theory (an effective theory of hadrons based on the symmetries of quantum chromodynamics). The QED calculation treats the nucleons as point-like, whereas the latter approach includes the effect of nucleon structure in a systematic way. Here we observe the radiative decay mode of free neutrons, measuring photons in coincidence with both the emitted electron and proton. We determined a branching ratio of (3.13 +/- 0.34) x 10(-3) (68 per cent level of confidence) in the energy region between 15 and 340 keV, where the uncertainty is dominated by systematic effects. The value is consistent with the predictions of both theoretical approaches; the characteristic energy spectrum of the radiated photons, which differs from the uncorrelated background spectrum, is also consistent with the calculated spectrum. This result may provide opportunities for more detailed investigations of the weak interaction processes involved in neutron beta decay.     

Outgassing from Amazonian rivers and wetlands as a large tropical source of atmospheric CO2

Terrestrial ecosystems in the humid tropics play a potentially important but presently ambiguous role in the global carbon cycle. Whereas global estimates of atmospheric CO2 exchange indicate that the tropics are near equilibrium or are a source with respect to carbon, ground-based estimates indicate that the amount of carbon that is being absorbed by mature rainforests is similar to or greater than that being released by tropical deforestation (about 1.6 Gt C yr-1). Estimates of the magnitude of carbon sequestration are uncertain, however, depending on whether they are derived from measurements of gas fluxes above forests or of biomass accumulation in vegetation and soils. It is also possible that methodological errors may overestimate rates of carbon uptake or that other loss processes have yet to be identified. Here we demonstrate that outgassing (evasion) of CO2 from rivers and wetlands of the central Amazon basin constitutes an important carbon loss process, equal to 1.2 +/- 0.3 Mg C ha-1 yr-1. This carbon probably originates from organic matter transported from upland and flooded forests, which is then respired and outgassed downstream. Extrapolated across the entire basin, this flux-at 0.5 Gt C yr-1-is an order of magnitude greater than fluvial export of organic carbon to the ocean. From these findings, we suggest that the overall carbon budget of rainforests, summed across terrestrial and aquatic environments, appears closer to being in balance than would be inferred from studies of uplands alone.     

High-throughput oncogene mutation profiling in human cancer

Systematic efforts are underway to decipher the genetic changes associated with tumor initiation and progression. However, widespread clinical application of this information is hampered by an inability to identify critical genetic events across the spectrum of human tumors with adequate sensitivity and scalability. Here, we have adapted high-throughput genotyping to query 238 known oncogene mutations across 1,000 human tumor samples. This approach established robust mutation distributions spanning 17 cancer types. Of 17 oncogenes analyzed, we found 14 to be mutated at least once, and 298 (30%) samples carried at least one mutation. Moreover, we identified previously unrecognized oncogene mutations in several tumor types and observed an unexpectedly high number of co-occurring mutations. These results offer a new dimension in tumor genetics, where mutations involving multiple cancer genes may be interrogated simultaneously and in 'real time' to guide cancer classification and rational therapeutic intervention.     

Genome assembly comparison identifies structural variants in the human genome

Numerous types of DNA variation exist, ranging from SNPs to larger structural alterations such as copy number variants (CNVs) and inversions. Alignment of DNA sequence from different sources has been used to identify SNPs and intermediate-sized variants (ISVs). However, only a small proportion of total heterogeneity is characterized, and little is known of the characteristics of most smaller-sized (<50 kb) variants. Here we show that genome assembly comparison is a robust approach for identification of all classes of genetic variation. Through comparison of two human assemblies (Celera's R27c compilation and the Build 35 reference sequence), we identified megabases of sequence (in the form of 13,534 putative non-SNP events) that were absent, inverted or polymorphic in one assembly. Database comparison and laboratory experimentation further demonstrated overlap or validation for 240 variable regions and confirmed >1.5 million SNPs. Some differences were simple insertions and deletions, but in regions containing CNVs, segmental duplication and repetitive DNA, they were more complex. Our results uncover substantial undescribed variation in humans, highlighting the need for comprehensive annotation strategies to fully interpret genome scanning and personalized sequencing projects.     

Influences of Reactive Compatibilizer R-Styrene-Maleic Anhydride Copolymer on PA6/PP Blends

The effect of R-styrene-maleic anhydride copolymer (RSMA) compatibilzation on Nylon 6 ( PA6 )/polypropylene ( PP ) blends has been investigated experimentally through Molau test,microscopic morphology,and chemical structure.Results show that the moderate R-SMA addition can promote reaction between anhydride in R-SMA and amino in PA6,and lead to a new PA6-gR-SMA copolymer in the blends.Such PA6-g-R-SMA copolymer in the blends can effectively reduce the interfacial tension and PP particle size,and improve the compatibility of two immiscible phases in the blends.The crystallinity of PA6 in PA6/PP blends has greatly decreased by PP blends.The blends have the best comprehensive mechanical and thermal properties when the mass ratio of PA6/PP/R-SMA is 90∶10∶2 to 90∶10∶4.The impact strength of the PA6/PP blends with the compatibilizer is increased bv more than 150 ％.