Relative efficiency of unequal versus equal cluster sizes in cluster randomized trials using generalized estimating equation models

There is growing interest in conducting cluster randomized trials (CRTs). For simplicity in sample size calculation, the cluster sizes are assumed to be identical across all clusters. However, equal cluster sizes are not guaranteed in practice. Therefore, the relative efficiency (RE) of unequal versus equal cluster sizes has been investigated when testing the treatment effect. One of the most important approaches to analyze a set of correlated data is the generalized estimating equation (GEE) proposed by Liang and Zeger, in which the “working correlation structure” is introduced and the association pattern depends on a vector of association parameters denoted by ρ. In this paper, we utilize GEE models to test the treatment effect in a two‐group comparison for continuous, binary, or count data in CRTs. The variances of the estimator of the treatment effect are derived for the different types of outcome. RE is defined as the ratio of variance of the estimator of the treatment effect for equal to unequal cluster sizes. We discuss a commonly used structure in CRTs—exchangeable, and derive the simpler formula of RE with continuous, binary, and count outcomes. Finally, REs are investigated for several scenarios of cluster size distributions through simulation studies. We propose an adjusted sample size due to efficiency loss. Additionally, we also propose an optimal sample size estimation based on the GEE models under a fixed budget for known and unknown association parameter (ρ) in the working correlation structure within the cluster.     

Variation in O-antigens, niche-specific selection and bacterial populations

Bacterial populations usually consist of distinct clones, often apparently adapted to specific niches. A formal model is developed whereby niche-specific selection maintains the polymorphisms involved in clonal adaptation. Infrequent transfer of non-adaptive alleles to a clone is balanced by the selection for the resident adaptive allele. The model can account for the extensive polymorphism in surface antigens observed in bacteria, and also for the existence of sympatric clones of pathogenic species which differ in host range and/or mode of pathogenesis. Niche-specific selection combined with low levels of genetic transfer can also account for the high level of neutral variation in bacteria, and indirectly for their ability to respond rapidly to environmental changes.     

长江安庆新洲水域鱼类群落结构及多样性

沙洲水域环境良好,饵料资源丰富,栖息生境多样,为鱼类的生长繁殖提供了优良的生存环境。为了解长江安庆新洲水域鱼类群落结构特征,于2017年4月、7月、10月和12月对安庆江段新洲水域鱼类群落进行季节性调查。共采集鱼类64种,分属5目11科48属,其中62.5%为鲤科鱼类。以物种数和多样性指数分析群落多样性特征,结果表明新洲水域鱼类种类多样性水平较高。单因素方差分析表明,该群落多样性季节差异显著(P0.05),空间差异不明显。新洲水域鱼类群落优势种为鳊(Parabramis pekinensis Basilewsky, 1855)、鲤(Cyprinus carpio Linnaeus, 1758)、贝氏■(Hemiculter bleekeri Warpachowsky, 1887)、银鮈(Squalidus argentatus Sauvage et Dabry, 1874)和似鳊(Pseudobrama simoni Bleeker, 1864)。4种摄食功能群中,杂食性(42.19%)和肉食性(35.94%)鱼类物种数比例较高;3种生态类群中,淡水定居性鱼类占绝对优势(84.37%);3种栖息水层类型中,底层鱼类物种数比例较高,占37.50%。大型经济鱼类占总渔获物比例低(0.01%),但个体较大,因而相对重要性指数(IRI)高。总体上,新洲鱼类群落多样性和丰富度指数较高,均匀度指数偏低,个体小型化趋势明显。捕捞强度过大、水利工程建设导致的江湖阻隔及外来物种入侵是新洲水域渔业资源衰退的主要因素。由此,建议持续开展长江渔业资源监测,加强长江干流沙洲水域渔业资源保护。     

Evidence for a Functional O-Linked N-Acetylglucosamine (O-GlcNAc) System in the Thermophilic Bacterium Thermobaculum terrenum

Post-translational modification of proteins is a ubiquitous mechanism of signal transduction in all kingdoms of life. One such modification is addition of O-linked N-acetylglucosamine to serine or threonine residues, known as O-GlcNAcylation. This unusual type of glycosylation is thought to be restricted to nucleocytoplasmic proteins of eukaryotes and is mediated by a pair of O-GlcNAc-transferase and O-GlcNAc hydrolase enzymes operating on a large number of substrate proteins. Protein O-GlcNAcylation is responsive to glucose and flux through the hexosamine biosynthetic pathway. Thus, a close relationship is thought to exist between the level of O-GlcNAc proteins within and the general metabolic state of the cell. Although isolated apparent orthologues of these enzymes are present in bacterial genomes, their biological functions remain largely unexplored. It is possible that understanding the function of these proteins will allow development of reductionist models to uncover the principles of O-GlcNAc signaling. Here, we identify orthologues of both O-GlcNAc cycling enzymes in the genome of the thermophilic eubacterium Thermobaculum terrenum. The O-GlcNAcase and O-GlcNAc-transferase are co-expressed and, like their mammalian orthologues, localize to the cytoplasm. The O-GlcNAcase orthologue possesses activity against O-GlcNAc proteins and model substrates. We describe crystal structures of both enzymes, including an O-GlcNAcase·peptide complex, showing conservation of active sites with the human orthologues. Although in vitro activity of the O-GlcNAc-transferase could not be detected, treatment of T. terrenum with an O-GlcNAc-transferase inhibitor led to inhibition of growth. T. terrenum may be the first example of a bacterium possessing a functional O-GlcNAc system.     

Intrinsically Unstructured Sequences in the mRNA 3ʹ UTR Reduce the Ability of Poly(A) Tail to Enhance Translation

The 5? cap and 3? poly(A) tail of mRNA are known to synergistically stimulate translation initiation via the formation of the cap?eIF4E?eIF4G?PABP?poly(A) complex. Most mRNA sequences have an intrinsic propensity to fold into extensive intramolecular secondary structures that result in short end-to-end distances. The inherent compactness of mRNAs might stabilize the cap?eIF4E?eIF4G?PABP?poly(A) complex and enhance cap-poly(A) translational synergy. Here, we test this hypothesis by introducing intrinsically unstructured sequences into the 5? or 3? UTRs of model mRNAs. We found that the introduction of unstructured sequences into the 3? UTR, but not the 5? UTR, decreases mRNA translation in cell-free wheat germ and yeast extracts without affecting mRNA stability. The observed reduction in protein synthesis results from the diminished ability of the poly(A) tail to stimulate translation. These results suggest that base pair formation by the 3? UTR enhances the cap-poly(A) synergy in translation initiation.     

D-loop Dynamics and Near-Atomic-Resolution Cryo-EM Structure of Phalloidin-Bound F-Actin

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Current trends and future directions in flower development research

Flowers, the reproductive structures of the approximately 400 000 extant species of flowering plants, exist in a tremendous range of forms and sizes, mainly due to developmental differences involving the number, arrangement, size and form of the floral organs of which they consist. However, this tremendous diversity is underpinned by a surprisingly robust basic floral structure in which a central group of carpels forms on an axis of determinate growth, almost invariably surrounded by two successive zones containing stamens and perianth organs, respectively. Over the last 25 years, remarkable progress has been achieved in describing the molecular mechanisms that control almost all aspects of flower development, from the phase change that initiates flowering to the final production of fruits and seeds. However, this work has been performed almost exclusively in a small number of eudicot model species, chief among which is Arabidopsis thaliana. Studies of flower development must now be extended to a much wider phylogenetic range of flowering plants and, indeed, to their closest living relatives, the gymnosperms. Studies of further, more wide-ranging models should provide insights that, for various reasons, cannot be obtained by studying the major existing models alone. The use of further models should also help to explain how the first flowering plants evolved from an unknown, although presumably gymnosperm-like ancestor, and rapidly diversified to become the largest major plant group and to dominate the terrestrial flora. The benefits for society of a thorough understanding of flower development are self-evident, as human life depends to a large extent on flowering plants and on the fruits and seeds they produce. In this preface to the Special Issue, we introduce eleven articles on flower development, representing work in both established and further models, including gymnosperms. We also present some of our own views on current trends and future directions of the flower development field.