Somatic complaints of children in primary care settings often go unexplained despite attempts to determine a cause. Recent research has linked violence exposure to stress symptomatology and associated somatic problems. Unknown, however, is whether specific physical symptom complaints can be attributed, at least in part, to violence exposure. Urban African-American 6- and 7-year-old children (N = 268), residing with their biological mothers, recruited before birth, and without prenatal exposure to hard illicit drugs participated. Children and mothers were evaluated in our hospital-based research laboratory, with teacher data collected by mail. Community violence exposure (Things I Have Seen and Heard), stress symptomatology (Levonn), and somatic complaints (teacher-and self-report items) were assessed. Additional data collected included prenatal alcohol exposure, socioeconomic status, domestic violence, maternal age, stress, somatic complaints and psychopathology, and child depression, abuse, and gender. Community violence witnessing and victimization were associated with stress symptoms (r= .26 and .25, respectively, p < .001); violence victimization was related to decreased appetite (r = .16, p < .01), difficulty sleeping (r = .21, p < .001), and stomachache complaints (r = .13, p < .05); witnessed violence was associated with difficulty sleeping (r = .13, p < .05) and headaches (r = .12, p < .05). All associations remained significant after control for confounding. Community violence exposure accounted for 10% of the variance in child stress symptoms, and children who had experienced community violence victimization had a 28% increased risk of appetite problems, a 94% increased risk of sleeping problems, a 57% increased risk of headaches, and a 174% increased risk of stomachaches. Results provide yet another possibility for clinicians to explore when treating these physical symptoms in children.

lin-28 was first characterized as a developmental timing regulator in Caenorhabditis elegans. Loss of lin-28 function (lin-28(lf)) mutants skip the hypodermal cell fates specific to the 2nd larval stage. Here, we studied two aspects of lin-28 which had not yet been investigated. First, we show that lin-28(lf) mutants exhibit reduced fertility associated with abnormal somatic gonadal morphology. In particular, the abnormal spermatheca-uterine valve morphology of lin-28(lf) hermaphrodites traps embryos in the spermatheca, which disrupts ovulation and causes embryonic lethality. The same genes downstream of lin-28 in the regulation of hypodermal developmental timing also act downstream of lin-28 in somatic gonadal morphogenesis and fertility. Importantly, we find that hypodermal expression, but not somatic gonadal expression, of lin-28 is sufficient for restoring normal somatic gonadal morphology in lin-28(lf) mutants. We propose that the abnormal somatic gonadal morphogenesis of lin-28(lf) hermaphrodites results from temporal discoordination between the accelerated hypodermal development and normally timed somatic gonadal development. Thus, our findings exemplify how a cell-intrinsic developmental timing program can also control proper development of other interacting tissues, cell non-autonomously. We also investigated the expression patterns and functions of two lin-28 isoforms in C. elegans. Our analysis of spatial expression patterns suggests that lin-28a and lin-28b are co-expressed in diverse tissues. Consistently, neither of isoform specific knock-out mutant, lin-28a(lf) or lin-28b(lf), exhibits defects in hypodermal development, somatic gonad, or fertility, indicating functional redundancy of two isoforms. Our study will contribute to further investigation of lin-28 isoforms by providing the mutants of each isoform as well as the primary analysis of their phenotypes.

In a series of body objects, this project aims to discover the specific emotion of hopelessness through the physical sensation of gravity. The project is investigating a femininity concept by exploring the emotions evoked when reading about the myth of Pandora and how she is used in academic reports such as Diseases of Women to argue upon discriminating arguments directed towards a female identity. The outcome of the workshops situate this project in a participatory driven field where somatic experiences make it possible to discuss sensitive topics such as hopelessness and gender equality. The outcome of the project is five sensorial body objects that suggest possibilities in designing wear to trigger emotions. It should be presented as a participatory installation in an exhibition.

Objective 1 was to investigate effects of heat stress and breed on milk and component yield for Holstein and Jersey cows on the same farm. Objective 2 was to determine the effects of breed on udder health as measured by somatic cell count (SCC) during times of heat stress. Data were collected from DHIA records of 142 Jersey cows and 586 Holstein cows from the University herd at Mississippi State University. During heat stress Jersey milk yield and 4% fat corrected milk (FCM) increased (P<0.01). Holstein milk yield and FCM decreased during heat stress (P<0.01). Heat stress affected somatic cell count (SCC) although effects varied by intensity of heat stress. Breed did not have an affect on SCC. Milk fat and protein percentages declined for both breeds in heat stress conditions. Milk fat but not milk protein of Jersey cows increased as stress increased from mild to severe.

Somatic Cell Nuclear Transfer (SCNT), commonly known as cloning, is the transfer of a somatic nucleus into an enucleated oocyte to produce a clone. The chromatin structure of somatic cells permits the expression of certain genes, while silencing the rest of the genome. The cytoplasm of oocytes can reprogram a somatic nucleus by reactivating the genes necessary for embryonic development and silencing the somatic genes. However, the low efficiency of SCNT indicates that successful nuclear reprogramming is a rare event. The objectives of this study were determine the extent of transcriptional reprogramming in bovine blastocysts produced by serial rounds of chromatin transfer (from first and fourth generations), using blastocysts produced by in vitro fertilization (IVF) as controls, to identify cumulative errors in the transcriptome profile. Differentially expressed genes were studied further to determine their function in embryonic development. We identified a set of transcripts consistently misregulated in cloned blastocyst, some of which had a more marked misregulation in the embryos produced by 4 successive rounds of cloning. Among the genes significantly upregulated in both CT groups compared to IVF blastocysts were both de novo DNA methylation enzymes DNMT3A and DNMT3B. Expression patterns, structural and functional analyses were performed for DNA methyltransferases. A high structural and functional conservation was observed for DNA methyltransferases among human, mouse, and bovine species. A set of genes that participate in early embryonic development, chromatin remodeling and DNA methylation were differentially regulated in cloned embryos and had not been fully annotated at the time of the analysis. We annotated those genes and submitted them to the Bovine Genome Sequencing Consortium database. These results have important implications for the selection of models for the study of DNA methylation during early development. The present study provides a valuable data set for identifying possible cumulative errors in somatic cell chromatin transfer that could hinder nuclear reprogramming shedding light on the epigenetic role in reprogramming and cell plasticity.

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Insertion and deletion (indel), a common form of genetic variation, has been shown to cause or contribute to human genetic diseases and cancer. Despite this importance and being the second most abundant variant type in the human genome, indels have not been studied as much as the single nucleotide polymorphism (SNP). With the advance of next-generation sequencing technology, many indel calling tools have been developed. However, performance comparison of commonly used tools has shown that (1) the tools have limited power in identifying indels and there are significant number of indels undetected, and (2) there is significant disagreement among the indel sets produced by the tools. These findings indicate the necessity of improving the existing tools or developing new algorithms to achieve reliable and consistent indel calling results. Two indels are biologically equivalent if the resulting sequences are the same. Storing biologically equivalent indels as distinct entries in databases causes data redundancy and misleads downstream analysis. It is thus desirable to have a unified system for identifying and representing equivalent indels. This dissertation describes UPS-indel, a utility tool that creates a universal positioning system for indels so that equivalent indels can be uniquely determined by their coordinates in the new system. Results show that UPS-indel identifies more redundant indels than existing algorithms. While mapping short reads to the reference genome, a significant number of short reads are unmapped and excluded from downstream analyses, thereby causing information loss in the subsequent variant calling. This dissertation describes Genesis-indel, a computational pipeline that explores the unmapped reads to identify missing novel indels. Results analyzing sequence alignment of 30 breast cancer patients show that Genesis-indel identifies many novel indels that also show significant enrichment in oncogenes and tumor suppressor genes, demonstrating the importance of rescuing indels hidden in the unmapped reads in cancer and disease studies. Somatic mutations play a vital role in transforming healthy cells into cancer cells. Therefore, accurate identification of somatic mutations is essential. Many somatic mutations callers are available with different strengths and weaknesses. An ensemble approach integrating the power of the callers is warranted. This dissertation describes SomaticHunter, an ensemble of two callers, namely Platypus and VarDict. Results on synthetic tumor data show that for both SNPs and indels, SomaticHunter achieves recall comparable to the state-of-the-art somatic mutation callers and the highest precision, resulting in the highest F1 score. / Doctor of Philosophy / Insertion and deletion (indel), a common form of genetic variation in the human genome, is associated with genetic diseases and cancer. However, indels are heavily understudied due to experimental and computational challenges. This dissertation addresses the computational challenges in three aspects. First, the current approach of representing indels is ambiguous and causes significant database redundancy. A universal positioning system, UPS-indel, is proposed to represent equivalent indels unambiguously and the UPS-indel algorithm is theoretically proven to find all equivalent indels and is thus exhaustive. Second, a significant number of indels are hidden in DNA reads not mapped to the reference genome. Genesis-indel, a computational pipeline that explores the unmapped reads to identify novel indels that are initially missed, is developed. Genesis-indel has been shown to uncover indels that can be important genetic markers for breast cancer. Finally, mutations occurring in somatic cells play a vital role in transforming healthy cells into cancer cells. Therefore, accurate identification of somatic mutation is essential for a better understanding of cancer genomes. SomaticHunter, an ensemble of two sensitive variant callers, is developed. Simulated studies using whole genome and whole exome sequences have shown that SomaticHunter achieves recall comparable to state-of-the-art somatic mutation callers while delivering the highest precision and therefore resulting in the highest F1 score among all the callers compared.