Genetic Predisposition To Acquire a Polybasic Cleavage Site for Highly Pathogenic Avian Influenza Virus Hemagglutinin

Highly pathogenic avian influenza viruses with H5 and H7 hemagglutinin (HA) subtypes evolve from low-pathogenic precursors through the acquisition of multiple basic amino acid residues at the HA cleavage site. Although this mechanism has been observed to occur naturally only in these HA subtypes, little is known about the genetic basis for the acquisition of the polybasic HA cleavage site. Here we show that consecutive adenine residues and a stem-loop structure, which are frequently found in the viral RNA region encoding amino acids around the cleavage site of low-pathogenic H5 and H7 viruses isolated from waterfowl reservoirs, are important for nucleotide insertions into this RNA region. A reporter assay to detect nontemplated nucleotide insertions and deep-sequencing analysis of viral RNAs revealed that an increased number of adenine residues and enlarged stem-loop structure in the RNA region accelerated the multiple adenine and/or guanine insertions required to create codons for basic amino acids. Interestingly, nucleotide insertions associated with the HA cleavage site motif were not observed principally in the viral RNA of other subtypes tested (H1, H2, H3, and H4). Our findings suggest that the RNA editing-like activity is the key mechanism for nucleotide insertions, providing a clue as to why the acquisition of the polybasic HA cleavage site is restricted to the particular HA subtypes. IMPORTANCE Influenza A viruses are divided into subtypes based on the antigenicity of the viral surface glycoproteins hemagglutinin (HA) and neuraminidase. Of the 16 HA subtypes (H1 to -16) maintained in waterfowl reservoirs of influenza A viruses, H5 and H7 viruses often become highly pathogenic through the acquisition of multiple basic amino acid residues at the HA cleavage site. Although this mechanism has been known since the 1980s, the genetic basis for nucleotide insertions has remained unclear. This study shows the potential role of the viral RNA secondary structure for nucleotide insertions and demonstrates a key mechanism explaining why the acquisition of the polybasic HA cleavage site is restricted to particular HA subtypes in nature. Our findings will contribute to better understanding of the ecology of influenza A viruses and will also be useful for the development of genetically modified vaccines against H5 and H7 influenza A viruses with increased stability

精神疾患を有する人への「リカバリーゼミ」の実践～参加者の語りからの評価～

精神疾患を有し精神科デイケアや就労支援などの社会資源につながっていない人へのリカバリー支援としてのプログラム「リカバリーゼミ」を実施した。本研究の目的は、本実践が参加者のリカバリー推進に寄与できたのかを考察することである。研究対象者は5 名で、いずれもひきこもり傾向や何らかの依存傾向があった。実施期間は2015 年5 月～ 2016 年6 月で、基本的に月2 回、1 回2 時間のクローズドグループで実施した。結果はRecovery Assessment Scale：RAS の点数が、参加者5 人中4 名終了時に上昇していた。また、生活も参加者の望む方向へ変化していた。このことより「グループ学習や体験を通して参加者が自身の人生を前向きに捉え、自身の責任において自身の希望や目的に向かって、人生の歩みを進める一助となること」という本プログラムの目的を概ね達成し、各人のリカバリー推進に寄与できたと考える

Generation of spectrum-compatible bi-directional ground motion accelerograms for seismic design of bridges

[16th World Conference on Earthquake Engineering (16WCEE)] Santiago (CL), January 09-13, 2017For the purpose of seismic performance verification of bridges in the process of seismic design, it is desirable to use spectrum-compatible bi-directional accelerograms with well-established multi-dimensional characteristics. In this paper, a method to generate spectrum-compatible bi-directional accelerograms is proposed, in which the complementary normal component wave computed by application of the Hilbert transform to standard accelerograms provided by design specifications is combined with the standard accelerograms. Generation of a set of bi-directional accelerograms by the proposed procedure based on standard accelerogram for Japanese highway bridge design code is demonstrated. It is shown that each orthogonal component of the generated bi-directional accelerogram is approximately compatible with the specified design spectrum, while the intensity of biaxial response spectrum is equivalent to that of the conventional unidirectional input, with respect to the unidirectional elastic response spectrum within the specified natural period range with a sufficient accuracy. Particular features of the effect of bi-directional input to structural model are examined with nonlinear dynamic response analysis of a simplified bridge model consisting of a superstructure, a seismic isolator and a seismic damper to show a typical feature of the effect of bi-directional input ground motions. The comparison reveals that the difference of the evaluated structural responses between the bi-directional and unidirectional input cases appears, and that the degree of the effect depends on the type of standard earthquake accelerograms corresponding to interplate-type earthquake and nearsource earthquake ground motions

Postnatal Changes in Humerus Cortical Bone Thickness Reflect the Development of Metabolic Bone Disease in Preterm Infants

Objective. To use cortical bone thickness (CBT) of the humerus to identify risk factors for the development of metabolic bone disease in preterm infants. Methods. Twenty-seven infants born at <32 weeks of gestational age, with a birth weight of <1,500 g, were enrolled. Humeral CBT was measured from chest radiographs at birth and at 27-28, 31-32, and 36–44 weeks of postmenstrual age (PMA). The risk factors for the development of osteomalacia were statistically analyzed. Results. The humeral CBT at 36–44 weeks of PMA was positively correlated with gestational age and birth weight and negatively correlated with the duration of mechanical ventilation. CBT increased with PMA, except in six very early preterm infants in whom it decreased. Based on logistic regression analysis, gestational age and duration of mechanical ventilation were identified as risk factors for cortical bone thinning. Conclusions. Humeral CBT may serve as a radiologic marker of metabolic bone disease at 36–44 weeks of PMA in preterm infants. Cortical bones of extremely preterm infants are fragile, even when age is corrected for term, and require extreme care to lower the risk of fractures

Post-termination complex disassembly by ribosome recycling factor, a functional tRNA mimic

Ribosome recycling factor (RRF) together with elongation factor G (EF-G) disassembles the post- termination ribosomal complex. Inhibitors of translocation, thiostrepton, viomycin and aminoglycosides, inhibited the release of tRNA and mRNA from the post-termination complex. In contrast, fusidic acid and a GTP analog that fix EF-G to the ribosome, allowing one round of tRNA translocation, inhibited mRNA but not tRNA release from the complex. The release of tRNA is a prerequisite for mRNA release but partially takes place with EF-G alone. The data are consistent with the notion that RRF binds to the A-site and is translocated to the P-site, releasing deacylated tRNA from the P- and E-sites. The final step, the release of mRNA, is accompanied by the release of RRF and EF-G from the ribosome. With the model post-termination complex, 70S ribosomes were released from the post-termination complex by the RRF reaction and were then dissociated into subunits by IF3