Matching Items (4)
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- All Subjects: Paleopathology
- All Subjects: Dynamics
- Creators: Kumar, Sudhir
- Creators: Norris, Annie Laurie
Description
Studies of ancient pathogens are moving beyond simple confirmatory analysis of diseased bone; bioarchaeologists and ancient geneticists are posing nuanced questions and utilizing novel methods capable of confronting the debates surrounding pathogen origins and evolution, and the relationships between humans and disease in the past. This dissertation examines two ancient human diseases through molecular and bioarchaeological lines of evidence, relying on techniques in paleogenetics and phylogenetics to detect, isolate, sequence and analyze ancient and modern pathogen DNA within an evolutionary framework. Specifically this research addresses outstanding issues regarding a) the evolution, origin and phylogenetic placement of the pathogen causing skeletal tuberculosis in New World prior to European contact, and b) the phylogeny and origins of the parasite causing the human leishmaniasis disease complex. An additional chapter presents a review of the major technological and theoretical advances in ancient pathogen genomics to frame the contributions of this work within a rapidly developing field. This overview emphasizes that understanding the evolution of human disease is critical to contextualizing relationships between humans and pathogens, and the epidemiological shifts observed both in the past and in the present era of (re)emerging infectious diseases. These questions continue to be at the forefront of not only pathogen research, but also
bioarchaeological and paleopathological scholarship.
bioarchaeological and paleopathological scholarship.
ContributorsHarkins, Kelly M (Author) / Buikstra, Jane E. (Thesis advisor) / Stone, Anne C (Thesis advisor) / Knudson, Kelly (Committee member) / Kumar, Sudhir (Committee member) / Krause, Johannes (Committee member) / Arizona State University (Publisher)
Created2014
Description
Proteins are a fundamental unit in biology. Although proteins have been extensively studied, there is still much to investigate. The mechanism by which proteins fold into their native state, how evolution shapes structural dynamics, and the dynamic mechanisms of many diseases are not well understood. In this thesis, protein folding is explored using a multi-scale modeling method including (i) geometric constraint based simulations that efficiently search for native like topologies and (ii) reservoir replica exchange molecular dynamics, which identify the low free energy structures and refines these structures toward the native conformation. A test set of eight proteins and three ancestral steroid receptor proteins are folded to 2.7Å all-atom RMSD from their experimental crystal structures. Protein evolution and disease associated mutations (DAMs) are most commonly studied by in silico multiple sequence alignment methods. Here, however, the structural dynamics are incorporated to give insight into the evolution of three ancestral proteins and the mechanism of several diseases in human ferritin protein. The differences in conformational dynamics of these evolutionary related, functionally diverged ancestral steroid receptor proteins are investigated by obtaining the most collective motion through essential dynamics. Strikingly, this analysis shows that evolutionary diverged proteins of the same family do not share the same dynamic subspace. Rather, those sharing the same function are simultaneously clustered together and distant from those functionally diverged homologs. This dynamics analysis also identifies 77% of mutations (functional and permissive) necessary to evolve new function. In silico methods for prediction of DAMs rely on differences in evolution rate due to purifying selection and therefore the accuracy of DAM prediction decreases at fast and slow evolvable sites. Here, we investigate structural dynamics through computing the contribution of each residue to the biologically relevant fluctuations and from this define a metric: the dynamic stability index (DSI). Using DSI we study the mechanism for three diseases observed in the human ferritin protein. The T30I and R40G DAMs show a loss of dynamic stability at the C-terminus helix and nearby regulatory loop, agreeing with experimental results implicating the same regulatory loop as a cause in cataracts syndrome.
ContributorsGlembo, Tyler J (Author) / Ozkan, Sefika B (Thesis advisor) / Thorpe, Michael F (Committee member) / Ros, Robert (Committee member) / Kumar, Sudhir (Committee member) / Shumway, John (Committee member) / Arizona State University (Publisher)
Created2011
Description
Objectives: The objective of this research is to develop a better understanding of the ways in which Transition Analysis estimates differ from traditional estimates in terms of age-at-death point estimation and inter-observer error. Materials and methods: In order to achieve the objectives of the research, 71 adult individuals from an archaeological site in northern Sudan were subjected to Transition Analysis age estimation by the author, a beginner-level osteologist. These estimates were compared to previously produced traditional multifactorial age estimates for these individuals, as well as a small sample of Transition Analysis estimates produced by an intermediate-level investigator. Results: Transition Analysis estimates do not have a high correlation with traditional estimates of age at death, especially when those estimates fall within middle or old adult age ranges. The misalignment of beginner- and intermediate-level Transition Analysis age estimations calls into question intra-method as well as inter-method replicability of age estimations. Discussion: Although the poor overall correlation of Transition Analysis estimates and traditional estimates in this study might be blamed on the relatively low experience level of the analyst, the results cast doubt on the replicability of Transition Analysis estimations, echoing the Bethard's (2005) results on a known-age sample. The results also question the validity of refined age estimates produced for individuals previously estimated to be in the 50+ age range by traditional methods and suggest that Transition Analysis tends to produce younger estimates than its traditional counterparts. Key words: age estimation, Transition Analysis, human osteology, observer error
ContributorsPhillips, Megann M. (Author) / Baker, Brenda (Thesis director) / Norris, Annie Laurie (Committee member) / School of International Letters and Cultures (Contributor) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
This dissertation examines the interrelationships between stress, frailty, growth, mortality, and diet at the Qinifab School site, Sudan, using a combination of osteological, paleopathological, and biogeochemical methods. The skeletal sample, from the fourth cataract region of Nubia, is comprised of 100 individuals from a Late Meroitic to Christian period (~250-1400 CE) cemetery. Standard osteological methods were used to estimate age and sex, and measurements were taken to assess body dimensions. Preadults were aged by dental and skeletal development, producing two independent ages to categorize individuals as developmentally “normal” or “delayed.” Data were collected on nonspecific indicators of stress, including linear enamel hypoplasias (LEHs), porotic hyperostosis (PH), and cribra orbitalia (CO). In preadults, these were compared to World Health Organization (WHO) growth standards to identify individuals who experienced stunting or wasting. For all ages, evidence of stress was compared with age at death and growth/body size. Finally, stable carbon and nitrogen isotope analyses were conducted on bone collagen and carbonate samples from a representative sample of 60 individuals, of which 46 collagen samples and all carbonates had acceptable preservation.“Delayed” preadults generally showed reduced body size relative to “normal” individuals, they were more likely to be stunted, and their growth trajectories were less similar to WHO standards. However, childhood stress had little impact on adult body size. CO occurred at higher frequencies in preadults and individuals with mixed/active lesions died at younger ages. PH rarely developed before age 6 but was present in most individuals over that age. Individuals with earlier formed LEHs tended to experience more stress overall and die younger. Active/mixed CO was associated with stunting in preadults and reduced brachial index in adults.
A greater proportion of individuals in the Christian period were affected by CO compared to the Post-Meroitic. A temporal shift also occurred in diet between the Post-Meroitic and Christian periods based upon the δ13CCOLL and δ15NCOLL values. Lower δ15N and the greater difference in δ13CAP-COLL suggest a shift toward intensified agriculture and decreased use of animal products and a potential dietary etiology for the increase in CO.
ContributorsNorris, Annie Laurie (Author) / Baker, Brenda J (Thesis advisor) / Knudson, Kelly (Committee member) / Dupras, Tosha (Committee member) / Arizona State University (Publisher)
Created2021