A Note on Testing Equality of Means when Sample Sizes are Random with Application

The problem of testing the equality of means of two normal populations is considered when independent random samples of random sizes are given with the total number of observations from both populations being a fixed number. An application in forestry is discussed.     

Modeling the formation of root apices

The formation of new root apices from small groups of cells with different cellular patterns has been simulated using an existing model based on growth tensors. To generate an apex, a steady growth field was used. The pattern of cells evolved to approach the steady state. Two extreme types of progressions have been obtained : one leading to an apex with a single or a few apical cells, and the other to an apex with a quiescent centre. The change of structure while applying a steady growth tensor indicates that development may involve a succession of discrete growth tensors.     

Assessing population genetic structure and variability with RAPD data: Application to Vaccinium macrocarpon (American Cranberry)

A method for estimating and comparing population genetic variation using random amplified polymorphic DNA (RAPD) profiling is presented. An analysis of molecular variance (AMOVA) is extended to accomodate phenotypic molecular data in diploid populations in Hardy-Weinberg equilibrium or with an assumed degree of selfing. We present a two step strategy: 1) Estimate RAPD site frequencies without preliminary assumptions on the unknown population structure, then perform significance testing for population substructuring. 2) If population structure is evident from the first step, use this data to calculate better estimates for RAPD site frequencies and sub-population variance components. A nonparametric test for the homogeneity of molecular variance (HOMOVA) is also presented. This test was designed to statistically test for differences in intrapopulational molecular variances (heteroscedasticity among populations). These theoretical developments are applied to a RAPD data set in Vaccinium macrocarpon (American cranberry) using small sample sizes, where a gradient of molecular diversity is found between central and marginal populations. The AMOVA and HOMOVA methods provide flexible population analysis tools when using data from RAPD or other DNA methods that provide many polymorphic markers with or without direct allelic data.     

唐古拉山以北地区生态资产核算

生态系统核算可以为生态文明建设提供定量性的决策依据,包括生态资产核算和生态系统服务核算两个方面,生态资产指生产和提供生态系统产品和服务的生态系统。以唐古拉山以北地区(简称唐北地区)为研究对象对其生态资产进行了核算,建立生态资产实物量及变化核算表、损益表,提出了生态资产综合指数。2015年唐北地区草地生态资产面积为21800.01 km~2,其中良级比重最高达68.46%,湿地生态资产面积为4763.01 km~2,其中优级比例最高为59.72%,野生动植物共有138种,其中重点保护动物10种。2015年唐北地区生态资产综合指数为79.77,比2000年降低了3.60%。2000—2015年,湿地、草地生态资产分别增加了164.23、2.82 km~2。2000—2015年湿地生态资产存量增加202.90 km~2,其中由湿地恢复导致面积增加最大为200.50 km~2,存量减少38.63 km~2,其中湿地退化是导致存量减少的主要原因,面积为36.23 km~2,草地存量增加了39.18 km~2,主要是由于湿地退化导致的草地扩张,存量减少36.26 km~2,主要由湿地恢复和荒漠化引起。研究中不同生态资产质量等级的核算以及生态资产综合指数的提出利于生态资产的全面核算和比较,对于建立离任责任制、生态文明建设意义重大。     

Decision analysis approach to risk/benefit evaluation in the ethical review of controlled human infection studies

Risks and benefit evaluation for controlled human infection studies, where healthy volunteers are deliberately exposed to infectious agents to evaluate vaccine efficacy, should be explicit, systematic, thorough, and non-arbitrary. Decision analysis promotes these qualities using four steps: (1) determining explicit criteria and measures for evaluation, (2) identifying alternatives to the study, (3) defining the models used to estimate the measures for each alternative, and (4) running the models to produce the estimates and compare the alternatives. In this paper, we describe how decision analysis might be applied by funders and regulators, as well as by others contemplating the use of novel controlled human infection studies for vaccine development and evaluation.     

Site-Specific Structural Variations Accompanying Tubular Assembly of the HIV-1 Capsid Protein

The 231-residue capsid (CA) protein of human immunodeficiency virus type 1 (HIV-1) spontaneously self-assembles into tubes with a hexagonal lattice that is believed to mimic the surface lattice of conical capsid cores within intact virions. We report the results of solid-state nuclear magnetic resonance (NMR) measurements on HIV-1 CA tubes that provide new information regarding changes in molecular structure that accompany CA self-assembly, local dynamics within CA tubes, and possible mechanisms for the generation of lattice curvature. This information is contained in site-specific assignments of signals in two- and three-dimensional solid-state NMR spectra, conformation-dependent ¹⁵N and ¹³C NMR chemical shifts, detection of highly dynamic residues under solution NMR conditions, measurements of local variations in transverse spin relaxation rates of amide ¹H nuclei, and quantitative measurements of site-specific ¹⁵N–¹⁵N dipole–dipole couplings. Our data show that most of the CA sequence is conformationally ordered and relatively rigid in tubular assemblies and that structures of the N-terminal domain (NTD) and the C-terminal domain (CTD) observed in solution are largely retained. However, specific segments, including the N-terminal β-hairpin, the cyclophilin A binding loop, the inter-domain linker, segments involved in intermolecular NTD–CTD interactions, and the C-terminal tail, have substantial static or dynamical disorder in tubular assemblies. Other segments, including the 3₁₀-helical segment in CTD, undergo clear conformational changes. Structural variations associated with curvature of the CA lattice appear to be localized in the inter-domain linker and intermolecular NTD–CTD interface, while structural variations within NTD hexamers, around local 3-fold symmetry axes, and in CTD–CTD dimerization interfaces are less significant.     

Novel Interaction of the Z-DNA Binding Domain of Human ADAR1 with the Oncogenic c-Myc Promoter G-Quadruplex

Both G-quadruplex and Z-DNA can be formed in G-rich and repetitive sequences on genome, and their formation and biological functions are controlled by specific proteins. Z-DNA binding proteins, such as human ADAR1, have a highly conserved Z-DNA binding domain having selective affinity to Z-DNA. Here, our study identifies the Z-DNA binding domain of human ADAR1 (hZα_ADAR1) as a novel G-quadruplex binding protein that recognizes c-myc promoter G-quadruplex formed in NHEIII₁ region and represses the gene expression. An electrophoretic migration shift assay shows the binding of hZα_ADAR1 to the intramolecular c-myc promoter G-quadruplex-forming DNA oligomer. To corroborate the binding of hZα_ADAR1 to the G-quadruplex, we conducted CD and NMR chemical shift perturbation analyses. CD results indicate that hZα_ADAR1 stabilizes the parallel-stranded conformation of the c-myc G-quadruplex. The NMR chemical shift perturbation data reveal that the G-quadruplex binding region in hZα_ADAR1 was almost identical with the Z-DNA binding region. Finally, promoter assay and Western blot analysis show that hZα_ADAR1 suppresses the c-myc expression promoted by NHEIII₁ region containing the G-quadruplex-forming sequence. This finding suggests a novel function of Z-DNA binding protein as a regulator of G-quadruplex-mediated gene expression.     

Posttranslational Regulation of Human DNA Polymerase ι

Human DNA polymerases (pols) η and ι are Y-family DNA polymerase paralogs that facilitate translesion synthesis past damaged DNA. Both polη and polι can be monoubiquitinated in vivo. Polη has been shown to be ubiquitinated at one primary site. When this site is unavailable, three nearby lysines may become ubiquitinated. In contrast, mass spectrometry analysis of monoubiquitinated polι revealed that it is ubiquitinated at over 27 unique sites. Many of these sites are localized in different functional domains of the protein, including the catalytic polymerase domain, the proliferating cell nuclear antigen-interacting region, the Rev1-interacting region, and its ubiquitin binding motifs UBM1 and UBM2. Polι monoubiquitination remains unchanged after cells are exposed to DNA-damaging agents such as UV light (generating UV photoproducts), ethyl methanesulfonate (generating alkylation damage), mitomycin C (generating interstrand cross-links), or potassium bromate (generating direct oxidative DNA damage). However, when exposed to naphthoquinones, such as menadione and plumbagin, which cause indirect oxidative damage through mitochondrial dysfunction, polι becomes transiently polyubiquitinated via Lys¹¹- and Lys⁴⁸-linked chains of ubiquitin and subsequently targeted for degradation. Polyubiquitination does not occur as a direct result of the perturbation of the redox cycle as no polyubiquitination was observed after treatment with rotenone or antimycin A, which both inhibit mitochondrial electron transport. Interestingly, polyubiquitination was observed after the inhibition of the lysine acetyltransferase KATB3/p300. We hypothesize that the formation of polyubiquitination chains attached to polι occurs via the interplay between lysine acetylation and ubiquitination of ubiquitin itself at Lys¹¹ and Lys⁴⁸ rather than oxidative damage per se.