Molecular basis for dimer formation of TRbeta variant D355R

Protein quality and stability are critical during protein purification for X-ray crystallography. A target protein that is easy to manipulate and crystallize becomes a valuable product useful for high-throughput crystallography for drug design and discovery. In this work, a single surface mutation, D355R, was shown to be crucial for converting the modestly stable monomeric ligand binding domain of the human thyroid hormone receptor (TR LBD) into a stable dimer. The structure of D335R TR LBD mutant was solved using X-ray crystallography and refined to 2.2 A resolution with R(free)/R values of 24.5/21.7. The crystal asymmetric unit reveals the TR dimer with two molecules of the hormone-bound LBD related by twofold symmetry. The ionic interface between the two LBDs comprises residues within loop H10-H11 and loop H6-H7 as well as the C-terminal halves of helices 8 of both protomers. Direct intermolecular contacts formed between the introduced residue Arg 355 of one TR molecule and Glu 324 of the second molecule become a part of the extended dimerization interface of 1330 A(2) characteristic for a strong complex assembly that is additionally strengthened by buffer solutes.     

A retinal circuit model accounting for wide-field amacrine cells

In previous experimental studies on the visual processing in vertebrates, higher-order visual functions such as the object segregation from background were found even in the retinal stage. Previously, the “linear–nonlinear” (LN) cascade models have been applied to the retinal circuit, and succeeded to describe the input-output dynamics for certain parts of the circuit, e.g., the receptive field of the outer retinal neurons. And recently, some abstract models composed of LN cascades as the circuit elements could explain the higher-order retinal functions. However, in such a model, each class of retinal neurons is mostly omitted and thus, how those neurons play roles in the visual computations cannot be explored. Here, we present a spatio-temporal computational model of the vertebrate retina, based on the response function for each class of retinal neurons and on the anatomical inter-cellular connections. This model was capable of not only reproducing the spatio-temporal filtering properties of the outer retinal neurons, but also realizing the object segregation mechanism in the inner retinal circuit involving the “wide-field” amacrine cells. Moreover, the first-order Wiener kernels calculated for the neurons in our model showed a reasonable fit to the kernels previously measured in the real retinal neuron in situ.     

Efficient Methods for Estimating Amino Acid Replacement Rates

Replacement rate matrices describe the process of evolution at one position in a protein and are used in many applications where proteins are studied with an evolutionary perspective. Several general matrices have been suggested and have proved to be good approximations of the real process. However, there are data for which general matrices are inappropriate, for example, special protein families, certain lineages in the tree of life, or particular parts of proteins. Analysis of such data could benefit from adaption of a data-specific rate matrix. This paper suggests two new methods for estimating replacement rate matrices from independent pairwise protein sequence alignments and also carefully studies Müller-Vingron’s resolvent method. Comprehensive tests on synthetic datasets show that both new methods perform better than the resolvent method in a variety of settings. The best method is furthermore demonstrated to be robust on small datasets as well as practical on very large datasets of real data. Neither short nor divergent sequence pairs have to be discarded, making the method economical with data. A generalization to multialignment data is suggested and used in a test on protein-domain family phylogenies, where it is shown that the method offers family-specific rate matrices that often have a significantly better likelihood than a general matrix. [Reviewing Editor: Dr. Nicolas Galtier]     

A new method to model change in cutaneous blood flow due to mechanical skin irritation part II: parameter identification procedure

Mechanical skin irritation, for example a light scratch with a needle, induces histamine and neuropeptide release on the line of stroke and in the surrounding tissue. Both histamine and neuropeptides are vasodilators. They cause vasodilation by changing the contraction state of the vascular smooth muscles and hence vessel compliance. Smooth muscle contraction state is very difficult to measure in vivo. For that reason we propose in this article an identification procedure to establish an irritation law. The law gives change in vessel compliance as a function of space, time and the intensity of the stroke. We have showed that vessel compliance increases immediately after the stroke not only on the line of stroke, but also in the surrounding tissue. Then, after a short delay, vessel compliance starts decreasing in the surrounding tissue, whereas vessel compliance on the line of stroke keeps increasing. Hence, blood is transported from the surrounding tissue to the line of stroke. In this way, higher blood volume on the line of stroke can be obtained than by only changing vessel compliance locally.     

全球陆地保护地60年增长情况分析和趋势预测

保护地建设已成为全球生物多样性保护的第一道防线。掌握其在不同尺度上的发展状况和变化趋势对保护地规划和建设有重要意义。针对已有研究在时间跨度、空间尺度以及结果对比方面的不足, 本文基于世界保护地数据库(World Database of Protected Areas, http://www.protectedplanet.net), 对全球、洲际、地区及国家尺度1950-2013年陆地保护地的增长情况进行描述和短期预测。结果发现: (1)全球保护地增长速率不断加快, 特别是在20世纪90年代以后。(2)洲际和地区保护地发展大致呈现3种增长趋势: 在美洲及大洋洲, 多数地区的保护地增长速率一直在加快; 在亚洲和欧洲, 多数地区的发展高峰出现在20世纪80、90年代; 在非洲, 多数地区的发展高峰为20世纪70年代及21世纪前10年。(3)各国保护地建设存在不平衡性, 仍有近一半国家的陆地保护地比例小于10%, 但这种差距随时间的推移有缩小的趋势。(4)绝大部分保护地增速均匀性低的国家分布在非洲。(5)虽然全球的《爱知生物多样性目标》在2020年预计不能完成, 但包括中国在内的22个国家有望如期达到目标。本文结果为未来保护地规划和建设工作的开展提供了参考依据。     

γ辐照对小麦种子延迟发光的影响

应用延迟发光的理论与方法,研究了γ辐照对扬麦13、扬麦15两个品种小麦种子的影响。结果表明:被测样品延迟发光的弛豫过程可以用非线性动力学方程Y=b1+b2e-b3t/1+b4t来进行描述,该方程对测量结果拟合的相关系数达到了99%以上。当t=0时,Y0=b1+b2,即样品的初始发光强度,在光照条件一定时,辐照剂量越高,样品的初始发光强度就越低。F测验结果表明不同辐照剂量对小麦种子初始发光强度的影响达到了极显著的水平,即受照剂量越高,初始发光强度越低,而两种供试小麦间的初始发光强度并无显著差异。结合处理种子苗期的生物学观察,样品(即种子)的初始发光强度与幼苗株高具有一致的变化趋势,即种子的初始发光强度越高,幼苗株高也高。因此,对辐射种子延迟发光过程的分析,可能是了解γ辐照对作物种子影响的一种快速可靠的检测方法。     

Bayesian semiparametric intensity estimation for inhomogeneous spatial point processes

In this work we propose a fully Bayesian semiparametric method to estimate the intensity of an inhomogeneous spatial point process. The basic idea is to first convert intensity estimation into a Poisson regression setting via binning data points on a regular grid, and then model the log intensity semiparametrically using an adaptive version of Gaussian Markov random fields to smooth the corresponding counts. The inference is carried by an efficient Markov chain Monte Carlo simulation algorithm. Compared to existing methods for intensity estimation, for example, parametric modeling and kernel smoothing, the proposed estimator not only provides inference regarding the dependence of the intensity function on possible covariates, but also uses information from the data to adaptively determine the amount of smoothing at the local level. The effectiveness of using our method is demonstrated through simulation studies and an application to a rainforest dataset.     

A new semiparametric estimation method for accelerated hazard model

The accelerated hazard model has been proposed for more than a decade. However, its application is still very limited, partly due to the complexity of the existing semiparametric estimation method. We propose a new semiparametric estimation method based on a kernel-smoothed approximation to the limit of a profile likelihood function of the model. The method leads to smooth estimating equations and is easy to use. The estimates from the method are proved to be consistent and asymptotically normal. Our numerical study shows that the new method is more efficient than the existing method. The proposed method is employed to reanalyze the data from a brain tumor treatment study.