A comparison of the predicted and X-ray structures of angiogenin. Implications for further studies of model building of homologous proteins

The three-dimensional structure of human angiogenin has been determined by X-ray crystallography and is compared here with an earlier model which predicted its structure, based on the homology of angiogenin with bovine pancreatic ribonuclease A. Comparison of the predicted model and crystal structure shows that the active-site histidine residues and the core of the angiogenin molecule, including most of the-strands and-helices, were predicted reasonably well. However, the structure of the surface loop regions and residues near the truncated C-terminus differs significantly. The C-terminal segment includes the active-site residues Asp-116, Gln-117, and Ser-118; Gln-117 in particular has been shown to be important in affecting the ribonucleolytic activity of angiogenin. Also, the orientation of one helix in the model differed from the orientation observed experimentally by about 20°, resulting in a large displacement of this chain segment. The difficulty encountered in predicting the surface loop regions has led to a new algorithm [Palmer and Scheraga (1991),J. Comput. Chem.,12, 505–526; (1992),J. Comput. Chem.,13, 329–350] for predicting the conformations of surface loops.     

An Efficient Optimization Algorithm for Structured Sparse CCA,with Applications to eQTL Mapping

In this paper we develop an efficient optimization algorithm for solving canonical correlation analysis (CCA) with complex structured-sparsity-inducing penalties, including overlapping-group-lasso penalty and network-based fusion penalty. We apply the proposed algorithm to an important genome-wide association study problem, eQTL mapping. We show that, with the efficient optimization algorithm, one can easily incorporate rich structural information among genes into the sparse CCA framework, which improves the interpretability of the results obtained. Our optimization algorithm is based on a general excessive gap optimization framework and can scale up to millions of variables. We demonstrate the effectiveness of our algorithm on both simulated and real eQTL datasets.     

Leapfrog Rotational Algorithms

Abstract

A new implicit rotational integrator for the orientation of rigid molecules is introduced, and compared with an existing explicit integrator. Both algorithms are categorised as leapfrogs since the quantities saved between time steps are on the on-step orientation and the mid-step angular momentum. Orientations may be expressed in terms of principal axis vectors or, as in the implementations used here, quaternions. Thermostatted versions of the algorithms as well as conventional energy-conserving versions are described. The algorithms are extensively tested in simulations of liquid water, the aim being to study the effect of increased time steps on a range of measured properties. The implicit algorithm is superior to the explicit algorithm, and can be used with time steps up to 3 fs with energy-conserving dynamics. When thermostatted, it may be used with time steps up to at least 6 fs.     

Algorithms for task allocation in ants. (A study of temporal polyethism: Theory)

We present an algorithm for allocating individual ants to tasks that relies solely on task change being caused by the unavailability of work. We prove that such an algorithm will allocate the correct number of individuals to each job. Furthermore, we can demonstrate that if such an algorithm is used then an age structure emerges over the ants performing the various tasks. This matches closely with the weak temporal structure over tasks that is observed in Sendova-Franks and Franks (1993. Division of labour in ants nests within highly variable environments. (A study of temporal polyethism: experimental).Bull. math. Biol. 55, 75–96).     

The auto-orientation in high magnetic fields of oxidized cytochrome b562 as source of constraints for solution structure determination

¹⁵N-¹H ¹J couplings were measured at 500 MHz and 800 MHz for ¹⁵N enriched oxidized cytochrome b ₅₆₂ from E. coli. The magnetic field dependence of 70 ¹J values, which could be measured without signal overlap, shows that there is a molecular magnetic anisotropy which provides partial molecular orientation in the magnetic field and, consequently, residual dipolar couplings (rdc). The rdc were used as further constraints to improve the existing structure [Arnesano et al. (1999) Biochemistry, 38, 8657–8670] with a protocol which uses the rhombic anisotropy [Banci et al. (1998) J. Am. Chem. Soc., 120, 12903–12909]. The overall large molecular magnetic anisotropy has been found to be determined by both the low spin iron (III) and the four helix bundle structure magnetic susceptibility anisotropy contributions.     

高亚硝酸盐环境下不同生长速率凡纳滨对虾肠道微生物多样性研究北大核心

【目的】高亚硝酸盐环境中饲养的凡纳滨对虾(Litopenaeus vannamei),在养殖结束时其生长速率和体重往往差异较大。本研究旨在探讨在高亚硝酸盐环境下饲养的对虾生长速率与肠道菌群结构和功能的相关性。【方法】本研究通过收集高亚硝酸盐条件下快速生长对虾(rapidly growing,RG)、正常生长对虾(normally growing,NG)和缓慢生长对虾(slowly growing,SG)的肠道和海水样品,通过16S rRNA基因测序、线性判别分析[line discriminant analysis(LDA)effect size,LEfSe]等进行分析。【结果】发现SG的细菌群落多样性与RG和NG不同。主坐标分析(principal coordinate analysis,PCoA)分析表明,NG的群落组成与RG比SG更相似。通过LEfSe差异分析发现,RG中火色杆菌科(Flammeovirgaceae)、黄杆菌科(Flavobacteraceae)和浮酶菌科(Planctomycetaceae)的丰度较高,而SG中脱硫弧菌科(Desulfovibrionaceae)、希瓦氏菌科(Shewanellaceae)和弧菌科(Vibrionaceae)的丰度显著增加。【结论】本研究发现,在高亚硝酸盐环境下,肠道微生物群落的氮代谢能力是造成对虾不同生长速度的原因。该研究将为虾的工业化养殖提供指导。     

An evolution of pulse speed in arteries

In this work, treating the artery as a thick-walled cylindrical shell made of an incompressible, isotropic and elastic solid, utilizing the large deformation theory and the stress-strain relation proposed by Demiray (1976b,Trans. ASME Ser. E, J. Appl. Mech.,98, 194–197), an explicit expression for the pulse speed is obtained and the effect of lumen pressure and the axial stretch on wave speed is discussed. Numerical results indicate that the wave speed increases with lumen pressure but decreases with the axial stretch. The results of the present model are compared with our previous work (Demiray, 1988,J. Biomech. 21, 55–58) on the same subject.     

Nestbox orientation: a species-specific influence on occupation and breeding success in woodland passerines

Capsule Nestbox orientation has species-specific influences on nestbox occupation and breeding success for woodland passerines.

Aims To determine if nestbox orientation had an influence upon nestbox selection or breeding success for three co-occurring woodland passerines.

Methods We analysed 15 consecutive years of breeding data (1990–2004) from 295 nestboxes in the UK using circular statistical analyses to examine the influence of orientation upon nestbox occupation and breeding success for three species, Blue Tit Cyanistes caeruleus, Great Tit Parus major and Pied Flycatcher Ficedula hypoleuca.

Results The three species used nestboxes of all orientations during the 15-year period. The frequency of nestbox occupation by Great Tits correlated with orientation (the mean number of nests in boxes oriented south-southwest was lower than the mean number of nests in boxes facing other directions). There was no such relationship for Blue Tits or Pied Flycatchers. Nestbox orientation influenced the breeding success of Pied Flycatcher (the mean number of young to fledge from boxes oriented south-southwest was lower than from boxes facing other directions). There was no such relationship for Blue or Great Tits.

Conclusion Nestbox orientation can be an important influence on occupation and breeding success, but this differed between species. Intriguingly, although the directionality reduced nestbox occupation (Great Tit) and breeding success (Pied Flycatcher) was the same (south-southwest), there was a disparity in the influence of orientation for Great Tit (orientation influenced the frequency of occupation but not success) and Pied Flycatcher (orientation did not influence occupation but did affect success). We discuss these disparities, considering the possible influences of mating strategy, breeding phenology, nestbox microclimate and offspring quality.     

Parametric and ensemble sequence alignment algorithms

Recently algorithms for parametric alignment (Watermanet al., 1992,Natl Acad. Sci. USA 89, 6090–6093; Gusfieldet al., 1992,Proceedings of the Third Annual ACM-SIAM Discrete Algorithms) find optimal scores for all penalty parameters, both for global and local sequence alignment. This paper reviews those techniques. Then in the main part of this paper dynamic programming methods are used to compute ensemble alignment, finding all alignment scores for all parameters. Both global and local ensemble alignments are studied, and parametric alignment is used to compute near optimal ensemble alignments.     

茶轮斑病对茶树叶片内生真菌群落结构的影响

[目的] 茶树叶片内生真菌长期与茶树协同进化,互利共生,在生物和非生物胁迫的生态系统中对茶树起着重要的保护作用,其群落结构组成相对稳定,但在外界因素的影响下,也会发生一定的变化。然而,关于生物胁迫对茶树叶片内生真菌群落结构的影响还缺乏系统的研究。因此,对生物胁迫下叶片内生真菌群落结构的多样性研究具有重要意义。[方法] 本研究采用高通量测序技术,测序了茶轮斑病发病茶树叶片和健康茶树叶片的内生真菌ITS rRNA基因的ITS1区序列,对比分析了内生真菌的多样性和群落结构组成。[结果] 结果表明,发病组叶片的内生真菌多样性和物种丰度均低于健康组。在门分类水平上,2组样本的优势菌群均为子囊菌门（Ascomycota）,在属分类水平上,发病组的优势菌群为炭疽菌属（Colletotrichum）和假拟盘多毛孢属（Pseudopestalotiopsis）,而健康组的优势菌为枝孢属（Cladosporium）。此外,2组样本内生真菌在群落结构组成上也有显著差异,发病组中假拟盘多毛孢属（Pseudopestalotiopsis）、炭疽菌属（Colletotrichum）和节菱孢属（Arthrinium）的相对丰度显著高于健康组,健康组中被孢霉属（Mortierella）、曲霉属（Aspergillus）、织球壳菌属（Plectosphaerella）、Lectera、葡孢霉属（Botryotrichum）、青霉菌属（Penicillium）、赤霉属（Gibberella）、毛壳菌属（Chaetomium）、Lulwoana和轮枝孢属（Verticillium）的相对丰度显著高于发病组。[结论] 综上,茶轮斑病的发生改变了茶树叶片内生真菌的群落结构,使少数物种优势生长。通过研究,明确了真菌病害对茶叶内生真菌群落结构的影响,为病菌的致病机理研究奠定基础,为茶树病害防治提供理论依据。     

Development of ETB Selective Agonists: Solution Structure of a Linear Endothelin-1 Analogue,ET-1 [Cys(Acm)1,15, Ala3, Leu7, dAsp8, Aib11]

Abstract

The solution structure of a synthetic ET_B selective agonist, ET-l[Cys(Acm)^1,15, Ala³, Leu⁷, dAsp⁸, Aib¹¹] has been solved by ¹H NMR and molecular modelling studies. Such solution structures of linear modified peptides in aqueous methanol are being used in an ongoing program of research designed to assist in an understanding of the basic structural requirements for the biological activity of vasoconstrictors. The resulting structure of this peptide is characterised by an α-helical conformation between residues Leu⁶-His¹⁶ and by N- and C-termi- ni which assume no defined conformation. A knowledge of the solution structures of this and related peptides, which are ETB selective agonists, are proving to be important in the understanding of how they interact with the ETB receptor.     

A contribution to Rashevsky’s mathematical theory of development

The application of Rashevsky’s transformationT to a primordial graph yields a set of graphs corresponding to different stages in the development of the organism. However, sinceT is multiple-valued the graphs obtained are not ordered. To obtain an ordering, it is first shown that the set of graphs under consideration is equivalent to a well defined setO (for “organism”) ofn-tuples. A metric is then introduced which is based on a biological consideration discussed by Rashevsky (Bull. Math. Biophysics,16, 317–348, 1954). Since a metric implies an ordering of the setO, with a knowledge of the structure of the primordial, one can obtain the developmental sequence. Unfortunately, at present, the structure of the primordial graph is unknown which makes the direct application of the above principle impossible. Consequently, an indirect approach which makes use of more accessible biological phenomena is discussed as well. The hypothesis thatrate of development decreases exponentially and the implications this has with regard to the metric onO are discussed. It is shown that if the hypothesis is accepted the search for the developmental sequence is narrowed.     

Probing membrane protein orientation and structure using fast magic-angle-spinning solid-state NMR

One and two-dimensional solid-state NMR experiments are discussed that permit probing local structure and overall molecular conformation of membrane-embedded polypeptides under Magic Angle Spinning. The functional dependence of a series of anisotropic recoupling schemes is analyzed using theoretical and numerical methods. These studies lead to the construction of a set of polarization dephasing or transfer units that probe local backbone conformation and overall molecular orientation within the same NMR experiment. Experimental results are shown for a randomly oriented peptide and for two model membrane–peptides reconstituted into lipid bilayers and oriented on polymer films according to a method proposed by Bechinger etal. [J. Am. Chem. Soc., 124, (2002), 1146–1147].     

Decisions in Force Field Development: An Alternative to Those Described by Roterman et al.

Abstract

We attempt to give an alternate point of view of the analysis by Roterman et al. (J. Biolmol. Struct. Dyn. 7, 415 (1989)). In particular, we argue for the use of flexible geometry and explicit inclusion of solvent effects in analyzing φ psi; maps of peptides.     

Control and heterologous expression in Escherichia coli of the Klebsiella pneumoniae gene encoding alginate lyase

The gene (aly) encoding the guluronate-specific alginate lyase from Klebsiella pneumoniae has been subcloned into the plasmid vector pHG327, transformed into Escherichia coli, and expressed in this host. Three groups of lyase-positive clones have been identified in which one or more copies of a 1.95-kb Hind III fragment encoding the gene have been inserted. The enzyme is expressed constitutively from its own promoter, but the efficiency depends on the orientation of the insert within the vector. Similarly, enhanced expression by induction of the vector's lac promoter is also orientation-dependent.     

东海北部滨海湿地铁氧化细菌的分布及其对不同氧气穿透深度的响应

【目的】滨海湿地生态系统位于淡水与海水交互地带,含有高浓度Fe²⁺的地下水渗透到沉积物表层形成的湿地径流和周期性潮汐淹水形成的含氧-缺氧界面有利于铁氧化细菌介导的Fe²⁺的生物氧化过程发生。然而,目前缺乏对滨海湿地生态系统中铁氧化细菌类群的全面评估。【方法】以上海崇明西沙湿地公园及浙江舟山市朱家尖岛东沙沙滩两地共5处滨海湿地沉积物为研究对象,分析沉积物的氧气穿透深度等环境参数,并基于16S rRNA基因扩增子测序技术,全面解析不同滨海湿地生态系统中细菌与铁氧化细菌的群落组成与分布特征。【结果】与崇明西沙湿地相比,朱家尖岛东沙沙滩有更深的氧气穿透深度,达到10 mm以上。非度量多尺度分析(non-metric multidimensional scaling, NMDS)统计结果表明,细菌群落结构主要受到区域位置不同导致的环境条件差异的影响,而铁氧化细菌的群落结构则受到采样的区域位置和沉积物氧气穿透深度的共同影响。崇明西沙湿地和朱家尖岛东沙沙滩的优势细菌为蓝细菌门(Cyanobacteria)、γ-变形菌纲(Gammaproteobacteria)、拟杆菌门(Bacteroidetes)、α-变形菌纲(Alphaproteobacteria)和放线菌门(Actinobacteria);优势铁氧化细菌为嘉利翁氏菌属(Gallionella)、红细菌属(Rhodobacter)、Lepthothrix和Sideroxydans。【结论】通过对崇明西沙湿地和朱家尖岛东沙沙滩沉积物中栖息的铁氧化菌的调查发现,铁氧化细菌的群落组成与湿地沉积物类型导致的氧气穿透深度差异具有密切联系。     

Synopsis of the tribe Bocageeae (Annonaceae), with revisions of Cardiopetalum,Froesiodendron, Trigynaea,Bocagea, and Hornschuchia

The tribal name Bocageeae Endlicher is reestablished and the tribe is circumscribed on the basis of solitary internodal ebracteate pedicels that are articulated at the base, and pollen shed in polyads of eight or more grains. Septate anther locules, large pollen size, and seed appendages are prevalent in the tribe. Intectate pollen with free-standing columellae, rare in Annonaceae, occurs not only in the genusTrigynaea but also in some species ofBocagea andHornschuchia. As defined here, the Bocageeae include seven neotropical genera:Cymbopetalum, Porcelia, Bocagea, Cardiopetalum, Froesiodendron, Hornschuchia, andTrigynaea. The latter five genera are revised and the treatments include ten new species:Cardiopetalum plicatum, Froesiodendron urceocalyx, Hornschuchia lianarum, H. santosii, H. leptandra, Trigynaea cinnamomea, T. lanceipetala, T. triplinervis, T. lagaropoda, andT. axilliflora, all from tropical South America. A new combination,Froesiodendron longicuspe, changes the rank of that taxon from subspecies to species.Cardiopetalum surinamense is removed fromFroesiodendron and reassigned toCardiopetalum on the basis of its connate petals, dehiscent monocarps, and seeds with bilobed arils. A cladogram provides an explicit hypothesis of intergeneric relationships in the tribe. The new combinationOnychopetalum periquino, based onTrigynaea periquino, is made.     

An Intriguing Controversy over Protein Structural Class Prediction

A recent report by Bahar et al. [(1997), Proteins 29, 172–185] indicates that the coupling effects among different amino acid components as originally formulated by K. C. Chou [(1995), Proteins 21, 319–344] are important for improving the prediction of protein structural classes. These authors have further proposed a compact lattice model to illuminate the physical insight contained in the component-coupled algorithm. However, a completely opposite result was concluded by Eisenhaber et al. [(1996), Proteins 25, 169–179], using a different dataset constructed according to their definition. To address such an intriguing controversy, tests were conducted by various approaches for the datasets from an objective database, the SCOP database [Murzin et al. (1995), J. Mol. Biol. 247, 536–540]. The results obtained by both self-consistency and jackknife tests indicate that the overall rates of correct prediction by the algorithm incorporating the coupling effect among different amino acid components are significantly higher than those by the algorithms without counting such an effect. This is fully consistent with the physical reality that the folding of a protein is the result of a collective interaction among its constituent amino acid residues, and hence the coupling effects of different amino acid components must be incorporated in order to improve the prediction quality. It was found by a revisiting the calculation procedures by Eisenhaber et al. that there was a conceptual mistake in constructing the structural class datasets and a systematic mistake in applying the component-coupled algorithm. These findings are informative for understanding and utilizing the component-coupled algorithm to study the structural classes of proteins.     

An adjacent arginine, and the phosphorylated tyrosine in the c-Met receptor target sequence, dictates the orientation of c-Cbl binding

Previously, we have demonstrated that the tyrosine phosphorylated hepatocyte growth factor receptor (Met) binds to the c-Cbl phosphotyrosine-recognition, tyrosine kinase binding (TKB) domain in a reverse orientation compared to other c-Cbl binding partners. A Met peptide with the DpYR motif changed to RpYD (MetRD) retains a similar TKB binding affinity as the native Met peptide. However, the TKB: MetRD complex crystal structure reveals a complete reversal of the binding orientation. Collated data indicates that both binding and orientation is dictated by the phosphorylated tyrosine and an adjacent arginine forming intra-peptide hydrogen bonds and aligning unidirectionally with complementary charges in the phosphotyrosine binding pocket of c-Cbl.

Structured summary

c-Cbl and MetRDbind: shown by x-ray crystallography (view interaction)c-Cbl and MetRDbind: shown by mass spectrometry studies of complexes (view interaction)c-Cblbind to Met: shown by surface plasmon resonance (view interactions 1,2)