Cdc53p acts in concert with Cdc4p and Cdc34p to control the G1 to S phase transition and identifies a conserved family of proteins

Regulation of cell cycle progression occurs in part through the targeted degradation of both activating and inhibitory subunits of the cyclin-dependent kinases. During G1, CDC4, encoding a WD-40 repeat protein, and CDC34, encoding a ubiquitin-conjugating enzyme, are involved in the destruction of these regulators. Here we describe evidence indicating that CDC53 also is involved in this process. Mutations in CDC53 cause a phenotype indistinguishable from those of cdc4 and cdc34 mutations, numerous genetic interactions are seen between these genes, and the encoded proteins are found physically associated in vivo. Cdc53p defines a large family of proteins found in yeasts, nematodes, and humans whose molecular functions are uncharacterized. These results suggest a role for this family of proteins in regulating cell cycle proliferation through protein degradation

Factors Affecting Establishment, Adaptation, and Persistence of Small Populations in Variable Environments

Understanding how genetic and demographic factors affect establishment, adaptation, and persistence of small populations in changing environments is a critical question in fundamental and applied ecological and evolutionary research. My dissertation addresses this question using observational data, experiments, and modeling in three separate studies of plant populations. Chapter 1 investigates divergence of two ecotypes of prairie sunflower in the face of gene flow. This study is relevant for understanding persistence as populations differentially adapt in response to changing and novel habitats. To understand how divergence is maintained, and if each ecotype is expected to persist, I analyze genomic sequence data in combination with demographic data from a reciprocal transplant experiment. I found that i) divergent adaptation is maintained via habitat and life stage specific-selection. And ii) different life history strategies in neighbouring ecotypes appear to have evolved by optimization of different fitness components, which in turn contribute to the persistence of each ecotype in its respective habitat. Chapter 2 investigates the effects of increased genetic variation on population performance across a range of environments. I quantify these effects by using experiments that compare the performance of high versus low genetic diversity lineages of prairie sunflower in plots that vary in biotic and abiotic environmental conditions. My results show that high diversity lineages have either improved average performance, lower sensitivity to environmental variation, or both. Chapter 3 focuses on the development of an analysis method to improve demographic modeling of threatened species when datasets have gaps through time. I validate and apply this method to investigate the dynamics of a rare, endemic plant species; Brandegee's buckwheat. By modeling vital rates, from data with missing years, and their dependence on annual climate, and building an integral projection model, I found that i) this approach can successfully assess current and predict future population viability from data with multi-year gaps. And ii) the focal population of this species is at risk of extirpation, but population dynamics vary considerably across small spatial scales within the population. Together these three projects provide empirical examples of how genetics and environment contribute to population establishment, adaptation, and persistence.</p

Annotations for MIR with Verovio and mei-friend

Digital annotations can be used by MIR systems to record, contextualise, and visualise analytical outputs, or to encode and structure ground truth for processing as an input. We present two related recent developments for the annotation of digital music scores. The first concerns Verovio, a popular music engraving software embedded within many web-based notation tools, previously lacking the capability to flexibly process and display annotations. We describe a new implementation for handling Music Encoding Initiative (MEI) XML elements in Verovio, providing default visualisations alongside identification of annotated elements in SVG graphical output for extensible customisation. Secondly, we introduce mei-friend, an interactive editor for MEI with an embedded Verovio notation viewer, with additional interface support for the creation and editing of annotations

Cue properties change timing strategies in group movement synchronisation

To maintain synchrony in group activities, each individual within the group must continuously correct their movements to remain in time with the temporal cues available. Cues might originate from one or more members of the group. Current research suggests that when synchronising movements, individuals optimise their performance in terms of minimising variability of timing errors (asynchronies) between external cues and their own movements. However, the cost of this is an increase in the timing variability of their own movements. Here we investigate whether an individual’s timing strategy changes according to the task, in a group scenario. To investigate this, we employed a novel paradigm that positioned six individuals to form two chains with common origin and termination on the circumference of a circle. We found that participants with access to timing cues from only one other member used a strategy to minimise their asynchrony variance. In contrast, the participant at the common termination of the two chains, who was required to integrate timing cues from two members, used a strategy that minimised movement variability. We conclude that humans are able to flexibly switch timekeeping strategies to maintain task demands and thus optimise the temporal performance of their movements

The loop-less tmCdc34 E2 mutant defective in polyubiquitination in vitro and in vivo supports yeast growth in a manner dependent on Ubp14 and Cka2

Abstract Background The S73/S97/loop motif is a hallmark of the Cdc34 family of E2 ubiquitin-conjugating enzymes that together with the SCF E3 ubiquitin ligases promote degradation of proteins involved in cell cycle and growth regulation. The inability of the loop-less Δ12Cdc34 mutant to support growth was linked to its inability to catalyze polyubiquitination. However, the loop-less t riple m utant (tm) Cdc34, which not only lacks the loop but also contains the S73K and S97D substitutions typical of the K73/D97/no loop motif present in other E2s, supports growth. Whether tmCdc34 supports growth despite defective polyubiquitination, or the S73K and S97D substitutions, directly or indirectly, correct the defect caused by the loop absence, are unknown. Results tmCdc34 supports yeast viability with normal cell size and cell cycle profile despite producing fewer polyubiquitin conjugates in vivo and in vitro. The in vitro defect in Sic1 substrate polyubiquitination is similar to the defect observed in reactions with Δ12Cdc34 that cannot support growth. The synthesis of free polyubiquitin by tmCdc34 is activated only modestly and in a manner dependent on substrate recruitment to SCFCdc4. Phosphorylation of C-terminal serines in tmCdc34 by Cka2 kinase prevents the synthesis of free polyubiquitin chains, likely by promoting their attachment to substrate. Nevertheless, tm CDC34 yeast are sensitive to loss of the Ubp14 C-terminal ubiquitin hydrolase and DUBs other than Ubp14 inefficiently disassemble polyubiquitin chains produced in tm CDC34 yeast extracts, suggesting that the free chains, either synthesized de novo or recycled from substrates, have an altered structure. Conclusions The catalytic motif replacement compromises polyubiquitination activity of Cdc34 and alters its regulation in vitro and in vivo, but either motif can support Cdc34 function in yeast viability. Robust polyubiquitination mediated by the S73/S97/loop motif is thus not necessary for Cdc34 role in yeast viability, at least under typical laboratory conditions. </jats:sec

Read/Write Digital Libraries for Musicology

The Web and other digital technologies have democratised music creation, reception, and analysis, putting music in the hands, ears, and minds of billions of users. Music digital libraries typically focus on an essential subset of this deluge—commercial and academic publications, and historical materials—but neglect to incorporate contributions by scholars, performers, and enthusiasts, such as annotations or performed interpretations of these artifacts, despite their potential utility for many types of users. In this paper we consider means by which digital libraries for musicology may incorporate such contributions into their collections, adhering to principles of FAIR data management and respecting contributor rights as outlined in the EU’s General Data Protection Regulation. We present an overview of centralised and decentralised approaches to this problem, and propose hybrid solutions in which contributions reside in a) user-controlled personal online datastores, b) decentralised file storage, and c) are published and aggregated into digital library collections. We outline the implementation of these ideas using Solid, a Web decentralisation project building on W3C standard technologies to facilitate publication and control over Linked Data. We demonstrate the feasibility of this approach by implementing prototypes supporting two types of contribution: Web Annotations describing or analysing musical elements in score encodings and music recordings; and, music performances and associated metadata supporting performance analyses across many renditions of a given piece. Finally, we situate these ideas within a wider conception of enriched, decentralised, and interconnected online music repositories

Alleviating the Last Mile of Encoding: The mei-friend Package for the Atom Text Editor

MEC 2021 BEST PAPER AWARD. Though MEI is widely used in music informatics and digital musicology research, the relative lack of authoring software and the specialised nature of its community have limited the availability of high-quality MEI encodings. Translating to MEI from other encoding formats, or generating MEI via optical music recognition processes, is thus a typical component of many MEI-project workflows. However, automated translations rarely achieve results of sufficient quality, a problem well-known in the community and documented in the literature. Final correction and validation by hand is therefore a common requirement. In this paper, we present meifriend, an extension to the Atom text editor, which aims to relieve the degree of manual labour required in this process. The tool facilitates most common MEI editing tasks including the insertion and manipulation of MEI elements, makes the encoded score visible and interactively accessible to the user, and provides quality-of-life conveniences including keyboard shortcuts for editing functions as well as intelligent navigation of the MEI hierarchy. We detail the tool’s implementation, describe its functionalities, and evaluate its responsiveness during the editing process, even when editing very large MEI files