Predicting cleavability of peptide sequences by HIV protease via correlation-angle approach

In designing HIV protease inhibitors as potential drugs for AIDS therapy, knowledge about what peptide sequences in polyproteins are cleavable by HIV proteases is very useful. In this article, based on the formulation that any octapeptide can be uniquely expressed as a 160-dimensional vector and the principle that the similarity of any two such vectors is associated with their correlation angle, a new method is proposed to predict the cleavability of a peptide sequence by HIV-1 and HIV-2 proteases. The average predicted accuracy the new method for the 105 peptide sequences whose cleavability by HIV-1 protease is known is 96/105=9.14%, which is about 8% higher than that by the existing method for the same set of data. A considerably high rate of correct prediction was also obtained when the new method was used to predict the HIV-2 protease-cleaved sites in some proteins.     

Double-barreled and Concentric Microelectrodes for Measurement of Extracellular Ion Signals in Brain Tissue

Electrical activity in the brain is accompanied by significant ion fluxes across membranes, resulting in complex changes in the extracellular concentration of all major ions. As these ion shifts bear significant functional consequences, their quantitative determination is often required to understand the function and dysfunction of neural networks under physiological and pathophysiological conditions. In the present study, we demonstrate the fabrication and calibration of double-barreled ion-selective microelectrodes, which have proven to be excellent tools for such measurements in brain tissue. Moreover, so-called “concentric” ion-selective microelectrodes are also described, which, based on their different design, offer a far better temporal resolution of fast ion changes. We then show how these electrodes can be employed in acute brain slice preparations of the mouse hippocampus. Using double-barreled, potassium-selective microelectrodes, changes in the extracellular potassium concentration ([K⁺]_o) in response to exogenous application of glutamate receptor agonists or during epileptiform activity are demonstrated. Furthermore, we illustrate the response characteristics of sodium-sensitive, double-barreled and concentric electrodes and compare their detection of changes in the extracellular sodium concentration ([Na⁺]_o) evoked by bath or pressure application of drugs. These measurements show that while response amplitudes are similar, the concentric sodium microelectrodes display a superior signal-to-noise ratio and response time as compared to the double-barreled design. Generally, the demonstrated procedures will be easily transferable to measurement of other ions species, including pH or calcium, and will also be applicable to other preparations.     

Are the numbers adding up? Exploiting discrepancies among complementary population models

Large carnivores are difficult to monitor because they tend to be sparsely distributed, sensitive to human activity, and associated with complex life histories. Consequently, understanding population trend and viability requires conservationists to cope with uncertainty and bias in population data. Joint analysis of combined data sets using multiple models (i.e., integrated population model) can improve inference about mechanisms (e.g., habitat heterogeneity and food distribution) affecting population dynamics. However, unobserved or unobservable processes can also introduce bias and can be difficult to quantify. We developed a Bayesian hierarchical modeling approach for inference on an integrated population model that reconciles annual population counts with recruitment and survival data (i.e., demographic processes). Our modeling framework is flexible and enables a realistic form of population dynamics by fitting separate density-dependent responses for each demographic process. Discrepancies estimated from shared parameters among different model components represent unobserved additions (i.e., recruitment or immigration) or removals (i.e., death or emigration) when annual population counts are reliable. In a case study of gray wolves in Wisconsin (1980–2011), concordant with policy changes, we estimated that a discrepancy of 0% (1980–1995), −2% (1996–2002), and 4% (2003–2011) in the annual mortality rate was needed to explain annual growth rate. Additional mortality in 2003–2011 may reflect density-dependent mechanisms, changes in illegal killing with shifts in wolf management, and nonindependent censoring in survival data. Integrated population models provide insights into unobserved or unobservable processes by quantifying discrepancies among data sets. Our modeling approach is generalizable to many population analysis needs and allows for identifying dynamic differences due to external drivers, such as management or policy changes.     

Cryptic or pseudocryptic: can morphological methods inform copepod taxonomy? An analysis of publications and a case study of the Eurytemora affinis species complex

Interest in cryptic species has increased significantly with current progress in genetic methods. The large number of cryptic species suggests that the resolution of traditional morphological techniques may be insufficient for taxonomical research. However, some species now considered to be cryptic may, in fact, be designated pseudocryptic after close morphological examination. Thus the “cryptic or pseudocryptic” dilemma speaks to the resolution of morphological analysis and its utility for identifying species. We address this dilemma first by systematically reviewing data published from 1980 to 2013 on cryptic species of Copepoda and then by performing an in‐depth morphological study of the former Eurytemora affinis complex of cryptic species. Analyzing the published data showed that, in 5 of 24 revisions eligible for systematic review, cryptic species assignment was based solely on the genetic variation of forms without detailed morphological analysis to confirm the assignment. Therefore, some newly described cryptic species might be designated pseudocryptic under more detailed morphological analysis as happened with Eurytemora affinis complex. Recent genetic analyses of the complex found high levels of heterogeneity without morphological differences; it is argued to be cryptic. However, next detailed morphological analyses allowed to describe a number of valid species. Our study, using deep statistical analyses usually not applied for new species describing, of this species complex confirmed considerable differences between former cryptic species. In particular, fluctuating asymmetry (FA), the random variation of left and right structures, was significantly different between forms and provided independent information about their status. Our work showed that multivariate statistical approaches, such as principal component analysis, can be powerful techniques for the morphological discrimination of cryptic taxons. Despite increasing cryptic species designations, morphological techniques have great potential in determining copepod taxonomy.     

Structure‐based design of combinatorial mutagenesis libraries

The development of protein variants with improved properties (thermostability, binding affinity, catalytic activity, etc.) has greatly benefited from the application of high‐throughput screens evaluating large, diverse combinatorial libraries. At the same time, since only a very limited portion of sequence space can be experimentally constructed and tested, an attractive possibility is to use computational protein design to focus libraries on a productive portion of the space. We present a general‐purpose method, called “Structure‐based Optimization of Combinatorial Mutagenesis ” (SOCoM ), which can optimize arbitrarily large combinatorial mutagenesis libraries directly based on structural energies of their constituents. SOCoM chooses both positions and substitutions, employing a combinatorial optimization framework based on library‐averaged energy potentials in order to avoid explicitly modeling every variant in every possible library. In case study applications to green fluorescent protein, β‐lactamase, and lipase A, SOCoM optimizes relatively small, focused libraries whose variants achieve energies comparable to or better than previous library design efforts, as well as larger libraries (previously not designable by structure‐based methods) whose variants cover greater diversity while still maintaining substantially better energies than would be achieved by representative random library approaches. By allowing the creation of large‐scale combinatorial libraries based on structural calculations, SOCoM promises to increase the scope of applicability of computational protein design and improve the hit rate of discovering beneficial variants. While designs presented here focus on variant stability (predicted by total energy), SOCoM can readily incorporate other structure‐based assessments, such as the energy gap between alternative conformational or bound states.     

多斑岭鳅嗅觉器官表面超微结构及其形态适应

多斑岭鳅(Oreonectes polystigmus)是营洞穴生活的鱼类,嗅觉器官在其生活中发挥了重要作用。本文对保藏于中国科学院动物研究所鱼类标本馆的4尾多斑岭鳅标本进行解剖,利用扫描电镜观察多斑岭鳅嗅囊上皮超微结构,以期了解嗅觉器官适应洞穴黑暗环境而产生的形态适应。多斑岭鳅的嗅囊呈椭圆型,嗅囊长径平均为2.27 mm,嗅囊长径与眼径比平均为1.36,揭示其为"嗅觉"鱼类。其嗅轴为直线型,嗅囊腔内对称紧密排列2排嗅板,嗅板数为22~24个。单个嗅板呈卜状亚型,舌状突起较发达。观察发现,非感觉纤毛连续广布在嗅板各个部位,但在嗅板近嗅轴处较少,此处裸露的表皮多褶皱,其上分布很多细微小孔。感觉纤毛主要分布于非感觉纤毛分布较稀疏的地方。上皮表面微绒毛多,一般在非感觉纤毛下,前后两端嗅板上的微绒毛数量相对较少。多斑岭鳅嗅囊水动力机制应属嗅上皮纤毛运动机制。嗅孔分布不均,中间嗅板上的嗅孔较嗅轴前、后分布的嗅板为多,同一嗅板上近嗅轴处的嗅孔最多。由于纤毛分布不均,嗅上皮可分为裸露区和非裸露区,一般裸露区和非裸露区边界清晰,嗅轴上非感觉纤毛和微绒毛主要分布在非裸露区的凹槽里。嗅轴和嗅板近嗅轴处裸露区面积较大,嗅轴裸露区上皮被一系列的连续的微脊切割成多边形,多边形内具有许多隆起与小孔。嗅轴处正是嗅囊中水流回流的区域,为感受水中气味的重要位置,推测与洞穴生活的习性有密切关系。多斑岭鳅嗅囊形态属于G型,这类鱼类其嗅觉功能在鱼类生命活动中发挥了重要作用。同近缘的地表种相比,多斑岭鳅具有较多的嗅板数目、较多数量感觉纤毛和微绒毛,且其嗅囊长径与眼球径比值大于1,这些都揭示了其为"嗅觉"鱼类,表现出了对洞穴黑暗环境的适应。     

A new extrinsic sample mean in the shape space with applications to the boundaries of anatomical structures

Shape analysis is of great importance in many fields of medical imaging and computational biology. In this paper, we consider the shape space as the set of smooth planar immersed curves in (parameterized curves) and, using the property of being isometric to a classical manifold immersed in a Euclidean space, we introduce a new extrinsic sample mean and a new extrinsic variance for a finite set of shapes, which are not necessarily star shaped. This is a fundamental tool in medical image analysis, for instance, to assess uncertainties that arise in locating anatomical structures such as the prostate and the bladder. We apply it to a dataset consisting of parallel planar axial CT sections of human prostate, in order to study the variability between boundaries that have been manually delineated by several observers.     

贵阳市城市土地扩展空间的生态适宜性与优化

以贵阳市为例,利用ArcGIS 9.3成本分析得出城镇空间扩展的阻力值,建立“建设用地为源+生态刚性约束+生态功能型阻力要素”的最小累积阻力模型(MCR)应用模式,动态模拟贵阳2010年城市空间扩展的生态阻力,并将其进行生态适宜性分区,分析了2014年新增加城市建设用地与生态适宜性的冲突,根据城市扩展土地空间配置与冲突格局,找出城市空间扩展现状不合理之处.结果表明: 2010—2014年间,生态适宜性分区与研究区城市扩展方向基本吻合,但新增城市建设用地生态冲突比较严重.在新增的城市建设用地中,生态冲突区面积占58.2%,其中,生态调控区占35.4%、限制开发区占13.9%、禁止开发区占8.9%.生态用地冲突加剧会引起生态服务功能及生态安全下降,提出以保留生态用地为目的的城市空间拓展优化路径,为贵阳土地空间格局优化、保障生态安全提供指导.     

Physiological and psychological responses of young males during spring-time walks in urban parks

Background

It is widely believed that contact with the natural environment can improve physical and mental health. Urban green spaces may provide city residents with these benefits; however, there is a lack of empirical field research on the health benefits of urban parks.

Methods

This field experiment was performed in May. Seventeen males aged 21.2 ± 1.7 years (mean ± standard deviation) were instructed to walk predetermined 15-minute courses in an urban park and a nearby city area (control). Heart rate and heart rate variability (HRV) were measured to assess physiological responses. The semantic differential (SD) method, Profile of Mood States (POMS), and State-Trait Anxiety Inventory (STAI) were used to measure psychological responses.

Results

Heart rate was significantly lower while walking in the urban park than while walking in the city street. Furthermore, the urban park walk led to higher parasympathetic nervous activity and lower sympathetic nervous activity compared with the walk through the city street. Subjective evaluations were generally in accordance with physiological reactions, and significantly higher scores were observed for the ‘comfortable’, ‘natural’, and ‘relaxed’ parameters following the urban park walk. After the urban park walk, the score for the ‘vigor’ subscale of the POMS was significantly higher, whereas that for negative feelings such as ‘tension-anxiety’ and ‘fatigue’ was significantly lower. The score for the anxiety dimension of the STAI was also significantly lower after the urban park walk.

Conclusions

Physiological and psychological results from this field experiment provide evidence for the physiological and psychological benefits of urban green spaces. A brief spring-time walk in an urban park shifted sympathetic/parasympathetic balance and improved mood state.     

环境因素对香蕉叶斑病菌喙突脐蠕孢生长和产孢的影响

为进一步明确香蕉叶斑病菌喙突脐蠕孢的生物学特性,调查了部分环境因素(碳氮源、植物成分培养基)对供试菌株(CLER09、D087和JL05)的营养生长和产孢的影响。结果显示,分生孢子主要先从基部萌芽,在28℃下约培养10h后出现两端萌芽;供试菌株对测试的20种碳源及26种氮源显示相似的生长反应,均可利用除菊糖外的测试碳源及氮源进行营养生长和产孢;测试的6种植物成分培养基对供试菌株的营养生长效果皆优于PDA培养基;除燕麦培养基外,其余5种培养基对菌株CLER09和D087的产孢作用均优于PDA培养基;测试的6种培养基对菌株JL05的产孢作用均优于PDA培养基。不同植物成分培养基对该菌分生孢子形态影响较大,以米糠、象草培养基对菌株D087和JL05的分生孢子长度和玉米粉培养基对菌株CLER09的分生孢子宽度的增长效果最为明显。