HomeBank: An Online Repository of Daylong Child-Centered Audio Recordings.

HomeBank is introduced here. It is a public, permanent, extensible, online database of daylong audio recorded in naturalistic environments. HomeBank serves two primary purposes. First, it is a repository for raw audio and associated files: one database requires special permissions, and another redacted database allows unrestricted public access. Associated files include metadata such as participant demographics and clinical diagnostics, automated annotations, and human-generated transcriptions and annotations. Many recordings use the child-perspective LENA recorders (LENA Research Foundation, Boulder, Colorado, United States), but various recordings and metadata can be accommodated. The HomeBank database can have both vetted and unvetted recordings, with different levels of accessibility. Additionally, HomeBank is an open repository for processing and analysis tools for HomeBank or similar data sets. HomeBank is flexible for users and contributors, making primary data available to researchers, especially those in child development, linguistics, and audio engineering. HomeBank facilitates researchers' access to large-scale data and tools, linking the acoustic, auditory, and linguistic characteristics of children's environments with a variety of variables including socioeconomic status, family characteristics, language trajectories, and disorders. Automated processing applied to daylong home audio recordings is now becoming widely used in early intervention initiatives, helping parents to provide richer speech input to at-risk children.

Physical and Genetic Analysis of the CUP1 Tandem Array in the Yeast Saccharomyces cerevisiae

The genomes of many strains of baker’s yeast, Saccharomyces cerevisiae, contain multiple repeats of the copper-binding protein Cup1. Cup1 is a member of the metallothionein family, and is found in a tandem array on chromosome VIII. In this thesis, I describe studies that characterized these tandem arrays and their mechanism of formation across diverse strains of yeast. I show that CUP1 arrays are an illuminating model system for observing recombination in eukaryotes, and describe insights derived from these observations.

In our first study, we analyzed 101 natural isolates of S. cerevisiae in order to examine the diversity of CUP1-containing repeats across different strains. We identified five distinct classes of repeats that contain CUP1. We also showed that some strains have only a single copy of CUP1. By comparing the sequences of all the strains, we were able to elucidate the mechanism of formation of the CUP1 tandem arrays, which involved unequal non-homologous recombination events starting from a strain that had only a single CUP1 gene. Our observation of CUP1 repeat formation allows more general insights about the formation of tandem repeats from single-copy genes in eukaryotes, which is one of the most important mechanisms by which organisms evolve.

In our second study, we delved deeper into our mechanistic investigations by measuring the relative rates of inter-homolog and intra-/inter-sister chromatid recombination in CUP1 tandem arrays. We used a diploid strain that is heterozygous both for insertion of a selectable marker (URA3) inside the tandem array, and also for markers at either end of the array. The intra-/inter-sister chromatid recombination rate turned out to be more than ten-fold greater than the inter-homolog rate. Moreover, we found that loss of the proteins Rad51 and Rad52, which are required for most inter-homolog recombination, did not greatly reduce recombination in the CUP1 tandem repeats. Additionally, we investigated the effects of elevated copper levels on the rate of each type of recombination at the CUP1 locus. Both types of recombination are increased at high concentrations of copper (as is known to be the case for CUP1 transcription). Furthermore, the inter-homolog recombination rate at the CUP1 locus is higher than the average over the genome during mitosis, but is lower than the average during meiosis.

The research described in Chapter 2 is published in 2014.