神经系统疾病中的兴奋型毒性问题：新的治疗学挑战

该书由意大利学者Carlo Ferrarese和美国学者M．Flint Beal共同主编。两位主编的初衷是基于目前全球对于老年神经退行性疾病治疗现状的尴尬：现行的药物只能缓解症状，而不能针对病因根治。治疗手段的局限是源于我们对这些疾病时神经细胞死亡的原因和机制不很了解。     

A complex systems science perspective on wireless networks

The paper targets a future world where all wireless networks are self-organising entities and in which the predominant mode of spectrum access is dynamic. The paper explores whether the behaviour of a collection of autonomous self-organising wireless systems can be treated as a complex system and whether complex systems science can shed light on the design and deployment of these networks. The authors focus on networks that self-organise from a frequency perspective to understand the behaviour of a collection of wireless self-organising nodes. Each autonomous network is modelled as a cell in a lattice and follows a simple set of self-organisation rules. Two scenarios are considered, one in which each cell is based on cellular automata and which provides an abstracted view of interference and a second in which each cell uses a self-organising technique which more accurately accounts for interference. The authors use excess entropy to measure complexity and in combination with entropy gain an understanding of the structure emerging in the lattice for the self-organising networks. The authors show that the self-organising systems presented here do exhibit complex behaviour. Finally, the authors look at the robustness of these complex systems and show that they are robust against changes in the environment.     

实测模态下三跨整体桥精细化基准有限元模型

以一座新建的整体式桥台桥梁(简称整体桥)为工程背景,建立服务于健康监测的精细化基准动力有限元模型.将设计阶段基于梁格法建立的全桥三维模型与采用梁-壳单元的精细化模型作为初始有限元模型,把环境激励下获取的实测模态信息(自振频率与振型)作为参照,基于参数灵敏度分析修正了上述两种结构模型.结果表明：尽管两种模型修正后都可以获得与实测模态尤其是频率值较好的吻合度,但修正后的梁格模型的模型参数严重偏离其真实的物理意义,难以作为长期监测的基准模型;而修正后的精细化梁-壳单元模型的模型参数物理意义明确,可以作为计入环境因素影响(如温度、湿度等)的结构长期监测的基准模型.该研究还基于动力试验和模型分析结果讨论了整体桥特有的结构-土相互作用的问题.     

Femtosecond X-ray protein nanocrystallography

X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (～200?nm to 2?μm in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.     

Ctenidins: antimicrobial glycine-rich peptides from the hemocytes of the spider Cupiennius salei

Three novel glycine-rich peptides, named ctenidin 1–3, with activity against the Gram-negative bacterium E. coli, were isolated and characterized from hemocytes of the spider Cupiennius salei. Ctenidins have a high glycine content (>70%), similarly to other glycine-rich peptides, the acanthoscurrins, from another spider, Acanthoscurria gomesiana. A combination of mass spectrometry, Edman degradation, and cDNA cloning revealed the presence of three isoforms of ctenidin, at least two of them originating from simple, intronless genes. The full-length sequences of the ctenidins consist of a 19 amino acid residues signal peptide followed by the mature peptides of 109, 119, or 120 amino acid residues. The mature peptides are post-translationally modified by the cleavage of one or two C-terminal cationic amino acid residue(s) and amidation of the newly created mature C-terminus. Tissue expression analysis revealed that ctenidins are constitutively expressed in hemocytes and to a small extent also in the subesophageal nerve mass.     

A rare variant in MYH6 is associated with high risk of sick sinus syndrome

Through complementary application of SNP genotyping, whole-genome sequencing and imputation in 38,384 Icelanders, we have discovered a previously unidentified sick sinus syndrome susceptibility gene, MYH6, encoding the alpha heavy chain subunit of cardiac myosin. A missense variant in this gene, c.2161C>T, results in the conceptual amino acid substitution p.Arg721Trp, has an allelic frequency of 0.38% in Icelanders and associates with sick sinus syndrome with an odds ratio = 12.53 and P = 1.5 × 10?2?. We show that the lifetime risk of being diagnosed with sick sinus syndrome is around 6% for non-carriers of c.2161C>T but is approximately 50% for carriers of the c.2161C>T variant.