Sampling Strategy for the Genetic Analysis of Human Remains from Tepe Hissar

Genetic testing has become a critical tool for the examination of ancient human remains. Earlier methods relied exclusively on observations and measurements. DNA analysis can date skeletal remains using radiocarbon dating, identify the sex of the individual, and determine the mtDNA and Y-chromosome haplogroups. Mitochondrial DNA and Y-chromosome haplogroups can be further used to understand kinship, burial practices, and other information about the civilization. For this study, I created a sampling strategy for the genetic analysis of a collection of 397 skeletons excavated during the 1930’s from an Iranian Bronze Age site called Tepe Hissar. DNA analysis can be cost prohibitive and requires samples be extracted and destroyed. A successful sampling strategy mitigates these costs, balancing efficiency and effectiveness to create the smallest sample that remains representative for the entire population. Overall, preservation, location within the site and layers, and their status as an outlier should be considered as major determinants for the representative sample. Preservation is the most important factor followed closely by the status of skeletons as outliers in their respective research studies and the skeletons’ relative geographic location. Although I ranked these factors, all three will be taken into account when determining the final representative sample

Atypical Eating Behaviors Identified in Children with Fetal Alcohol Spectrum Disorders, Aged 3 to 5 Years, Using the Children's Eating Behavior Questionnaire in a Caregiver-Reported Online Survey

Background: Children with fetal alcohol spectrum disorders (FASDs), aged 3 to 5 years, have physical, behavioral, and functional problems. Because of alcohol-related deficits, children with FASDs are at risk for malnutrition; yet, little is known about how FASD affects eating behavior and nutrition. Aim: The purpose of this study was to identify atypical eating behavior in children with FASDs, aged 3 to 5 years, and their associations with socio-demographic characteristics. Method:This descriptive cross-sectional study gathered data from a caregiver-reported online survey targeting the eating behavior of preschool-aged children with FASDs. The survey included the Children's Eating Behavior Questionnaire (CEBQ) and a socio-demographic questionnaire. Participants/Setting:Seventy-four caregivers qualified for the study with nine having two children with FASDs. Responses to survey questions varied since caregivers had permission to omit any question. Results: Significant differences were found between the preschool-aged children with FASDs and Wardle's published normative sample by gender and age. Compared to reported norms, study children scored higher in Desire to Drink, Food Responsiveness, Emotional Overeating, and Food Fussiness, and lower in Enjoyment of Food. Regarding socio-demographic characteristics, there was greater Enjoyment of Food with larger families and Food Avoidance with college-educated caregivers. Conclusion: Children with FASDs, aged 3 to 5 years, have atypical eating behaviors characteristic of maladaptive appetites, overeating under stress, selective eating, slowness in eating, and an excessive need for drinks, in comparison with a published normative sample

Phenotypic and functional characterization of corneal endothelial cells during in vitro expansion.

The advent of cell culture-based methods for the establishment and expansion of human corneal endothelial cells (CEnC) has provided a source of transplantable corneal endothelium, with a significant potential to challenge the one donor-one recipient paradigm. However, concerns over cell identity remain, and a comprehensive characterization of the cultured CEnC across serial passages has not been performed. To this end, we compared two established CEnC culture methods by assessing the transcriptomic changes that occur during in vitro expansion. In confluent monolayers, low mitogenic culture conditions preserved corneal endothelial cell state identity better than culture in high mitogenic conditions. Expansion by continuous passaging induced replicative cell senescence. Transcriptomic analysis of the senescent phenotype identified a cell senescence signature distinct for CEnC. We identified activation of both classic and new cell signaling pathways that may be targeted to prevent senescence, a significant barrier to realizing the potential clinical utility of in vitro expansion

Terrestrial species adapted to sea dispersal: Differences in propagule dispersal of two Caribbean mangroves

A central goal of comparative phylogeography is to understand how species‐specific traits interact with geomorphological history to govern the geographic distribution of genetic variation within species. One key biotic trait with an immense impact on the spatial patterns of intraspecific genetic differentiation is dispersal. Here, we quantify how species‐specific traits directly related to dispersal affect genetic variation in terrestrial organisms with adaptations for dispersal by sea, not land—the mangroves of the Caribbean. We investigate the phylogeography of white mangroves (Laguncularia racemosa, Combretaceae) and red mangroves (Rhizophora mangle, Rhizophoraceae) using chloroplast genomes and nuclear markers (thousands of RAD‐Seq loci) from individuals throughout the Caribbean. Both coastal tree species have viviparous propagules that can float in salt water for months, meaning they are capable of dispersing long distances. Spatially explicit tests of the role of ocean currents on patterning genetic diversity revealed that ocean currents act as a mechanism for facilitating dispersal, but other means of moving genetic material are also important. We measured pollen‐ vs. propagule‐mediated gene flow and discovered that in white mangroves, seeds were more important for promoting genetic connectivity between populations, but in red mangroves, the opposite was true: pollen contributed more. This result challenges our concept of the importance of both proximity to ocean currents for moving mangrove seeds and the extent of long‐distance pollen dispersal. This study also highlights the importance of spatially explicit quantification of both abiotic (ocean currents) and biotic (dispersal) factors contributing to gene flow to understand fully the phylogeographic histories of species.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146564/1/mec14894-sup-0003-FigS3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146564/2/mec14894-sup-0001-FigS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146564/3/mec14894_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146564/4/mec14894.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146564/5/mec14894-sup-0002-FigS2.pd

Determining subpopulation methylation profiles from bisulfite sequencing data of heterogeneous samples using DXM

Epigenetic changes, such as aberrant DNA methylation, contribute to cancer clonal expansion and disease progression. However, identifying subpopulation-level changes in a heterogeneous sample remains challenging. Thus, we have developed a computational approach, DXM, to deconvolve the methylation profiles of major allelic subpopulations from the bisulfite sequencing data of a heterogeneous sample. DXM does not require prior knowledge of the number of subpopulations or types of cells to expect. We benchmark DXM\u27s performance and demonstrate improvement over existing methods. We further experimentally validate DXM predicted allelic subpopulation-methylation profiles in four Diffuse Large B-Cell Lymphomas (DLBCLs). Lastly, as proof-of-concept, we apply DXM to a cohort of 31 DLBCLs and relate allelic subpopulation methylation profiles to relapse. We thus demonstrate that DXM can robustly find allelic subpopulation methylation profiles that may contribute to disease progression using bisulfite sequencing data of any heterogeneous sample

Deep phenotyping of cardiac function in heart transplant patients using cardiovascular systems models

Heart transplant patients are followed with periodic right heart catheterizations (RHCs) to identify post-transplant complications and guide treatment. Post-transplant positive outcomes are associated with a steady reduction of right ventricular and pulmonary arterial pressures, toward normal levels of right-side pressure (about 20mmHg) measured by RHC. This study shows more information about patient progression is obtained by combining standard RHC measures with mechanistic computational cardiovascular systems models. This study shows: to understand how cardiovascular system models can be used to represent a patient's cardiovascular state, and to use these models to track post-transplant recovery and outcome. To obtain reliable parameter estimates comparable within and across datasets, we use sensitivity analysis, parameter subset selection, and optimization to determine patient specific mechanistic parameter that can be reliably extracted from the RHC data. Patient-specific models are identified for ten patients from their first post-transplant RHC and longitudinal analysis is done for five patients. Results of sensitivity analysis and subset selection show we can reliably estimate seven non-measurable quantities including ventricular diastolic relaxation, systemic resistance, pulmonary venous elastance, pulmonary resistance, pulmonary arterial elastance, pulmonary valve resistance and systemic arterial elastance. Changes in parameters and predicted cardiovascular function post-transplant are used to evaluate cardiovascular state during recovery in five patients. Of these five patients, only one patient showed inconsistent trends during recovery in ventricular pressure-volume relationships and power output. At a four-year recovery time point this patient exhibited biventricular failure along with graft dysfunction while the remaining four exhibited no cardiovascular complications.Comment: 53 Pages (including supplement), 9 figures in manuscript, 9 figures in supplemen

Deep phenotyping of cardiac function in heart transplant patients using cardiovascular system models

Heart transplant patients are followed with periodic right heart catheterizations (RHCs) to identify post‐transplant complications and guide treatment. Post‐transplant positive outcomes are associated with a steady reduction of right ventricular and pulmonary arterial pressures, toward normal levels of right‐side pressure (about 20 mmHg) measured by RHC. This study shows that more information about patient progression is obtained by combining standard RHC measures with mechanistic computational cardiovascular system models. The purpose of this study is twofold: to understand how cardiovascular system models can be used to represent a patient’s cardiovascular state, and to use these models to track post‐transplant recovery and outcome. To obtain reliable parameter estimates comparable within and across datasets, we use sensitivity analysis, parameter subset selection, and optimization to determine patient‐specific mechanistic parameters that can be reliably extracted from the RHC data. Patient‐specific models are identified for 10 patients from their first post‐transplant RHC, and longitudinal analysis is carried out for five patients. Results of the sensitivity analysis and subset selection show that we can reliably estimate seven non‐measurable quantities; namely, ventricular diastolic relaxation, systemic resistance, pulmonary venous elastance, pulmonary resistance, pulmonary arterial elastance, pulmonary valve resistance and systemic arterial elastance. Changes in parameters and predicted cardiovascular function post‐transplant are used to evaluate the cardiovascular state during recovery of five patients. Of these five patients, only one showed inconsistent trends during recovery in ventricular pressure–volume relationships and power output. At the four‐year post‐transplant time point this patient exhibited biventricular failure along with graft dysfunction while the remaining four exhibited no cardiovascular complications.Key pointsRight heart catheterization data from clinical records of heart transplant patients are used to identify patient‐specific models of the cardiovascular system.These patient‐specific cardiovascular models represent a snapshot of cardiovascular function at a given post‐transplant recovery time point.This approach is used to describe cardiac function in 10 heart transplant patients, five of which had multiple right heart catheterizations allowing an assessment of cardiac function over time.These patient‐specific models are used to predict cardiovascular function in the form of right and left ventricular pressure‐volume loops and ventricular power, an important metric in the clinical assessment of cardiac function.Outcomes for the longitudinally tracked patients show that our approach was able to identify the one patient from the group of five that exhibited post‐transplant cardiovascular complications.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156242/2/tjp14120.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156242/1/tjp14120_am.pd

Theology, News and Notes - Vol. 05, No. 02

Theology News & Notes was a theological journal published by Fuller Theological Seminary from 1954 through 2014.https://digitalcommons.fuller.edu/tnn/1010/thumbnail.jp

Cornish identities and migration: a multi-scalar approach

The definitive version is available at www.blackwell-synergy.com. 24 month embargo by the publisher. Article will be released July 2009.In this article we argue that theories of transnationalism have value in exploring the historical context of migration and that historical contexts help to shape such theoretical conceptualizations. Historians of migration have now begun to engage more directly with the literature of transnationalism, focusing on the networks that linked settler and home communities. Here we add to this by examining a nineteenth-century migrant community from a British region through the lens of transnationalism, applying the concept to the case of the Cornish, whose economic specialization produced culturally distinct Cornish communities on the mining frontiers of North America, Australia and South Africa. In doing so, we bring together the issues of scale and time. We review the multiple levels of the Cornish transnational space of the late nineteenth century, which exhibited aspects of both core transnationalism and translocalism. This waned, but in the later twentieth century, a renewed interest in a transnational Cornish identity re-emerged, articulating with changing identity claims in Cornwall itself. To capture better the experience of the Cornish over these two very different phases of transnationalism we identify another subset of transnationalism - that of transregionalism.Leverhulme Trus