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Abstract. During mitosis in cultured newt pneumocytes, one or more chromosomes may become positioned well removed (>50 #m) from the polar regions during early prometaphase. As a result, these chromosomes are delayed for up to 5 h in forming an attachment to the spindle. The spatial separation of these chromosomes from the polar microtubule-nucleating centers provides a unique opportunity to study the initial stages of kinetochore fiber formation in living cells. Time-lapse Nomarski-differential interference contrast videomicroscopic observations reveal that lateattaching chromosomes always move, upon attachment, into a single polar region (usually the one closest to the chromosome). During this attachment, the kinetochore region of the chromosome undergoes a variable number of transient poleward tugs that are followed, shortly thereafter, by rapid movement of the chromosome towards the pole. Anti-tubulin immunofluorescence and serial section EM reveal that the kinetochores and kinetochore regions of nonattached chromosomes lack associated microtubules. By contrast, these methods reveal that the attachment and subsequent poleward movement of a chromosome correlates with the association of a single long microtubule with one of the kinetochores of the chromosome. This microtubule traverses the entire distance between the spindle pole and the kinetochore and of_ ten extends well past the kinetochore. From these results, we conclude that the initial attachment of a chromosome to the newt pneumocyte spindle results from an interaction between a single polar-nucleated microtubule and one of the kinetochores on the chromosome. Once this association is established, the kinetochore is rapidly transported poleward along the surface of the microtubule by a mechanism that is not dependent on microtubule depolymerization. Our results further demonstrate that the motors for prometaphase chromosome movement must be either on the surface of the kinetochore (i.e., within the corona but not the plate), distributed along the surface of the kinetochore microtubules, or both.NE of the most important aspects of mitosis is the molecular mechanism by which kinetochores attach to and orient toward the poles of the forming spindle. Chromosome micromanipulation experiments and structural studies have clearly demonstrated that this attachment arises from the formation ofa birefringent fiber (i.e., a kinetochore fiber [K-Fiber]), ~ composed primarily of microtubules (MTs), that connects each kinetochore with a spindle pole (for review see 50). The acquisition of MTs by the prometaphase kinetochore is also a prerequisite for directed chromosome movement (39,40). The exact role kinetochore MTs (K-MTs) play in this process is, however, a subject of considerable controversy. It is unclear whether they directly gener-1. Abbreviations used in this paper: DIC, differential interference contrast; IMF, immunofluorescence; K-Fiber, kinetochore fiber; K-MT, kinetochore microtubule; MT, microtubule; NEB, nuclear envelope breakdown; NP, newt pneumocyte; ...

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The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein‐coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Scientists who plan to publish in British Journal of Pharmacology (BJP) must read this article before undertaking a study. This editorial provides guidance for the design of experiments. We have published previously two guidance documents on experimental design and analysis (Curtis et al., 2015; Curtis et al., 2018). This update clarifies and simplifies the requirements on design and analysis for BJP manuscripts. This editorial also details updated requirements following an audit and discussion on best practice by the BJP editorial board. Explanations for the requirements are provided in the previous articles. Here, we address new issues that have arisen in the course of handling manuscripts and emphasise three aspects of design that continue to present the greatest challenge to authors: randomisation, blinded analysis and balance of group sizes.