Little Pal Of Long Ago

https://digitalcommons.library.umaine.edu/mmb-vp/4939/thumbnail.jp

Complete haplotype phasing of the MHC and KIR loci with targeted HaploSeq

BackgroundThe MHC and KIR loci are clinically relevant regions of the genome. Typing the sequence of these loci has a wide range of applications including organ transplantation, drug discovery, pharmacogenomics and furthering fundamental research in immune genetics. Rapid advances in biochemical and next-generation sequencing (NGS) technologies have enabled several strategies for precise genotyping and phasing of candidate HLA alleles. Nonetheless, as typing of candidate HLA alleles alone reveals limited aspects of the genetics of MHC region, it is insufficient for the comprehensive utility of the aforementioned applications. For this reason, we believe phasing the entire MHC and KIR locus onto a single locus-spanning haplotype can be a critical improvement for better understanding transplantation biology.ResultsGenerating long-range (>1 Mb) phase information is traditionally very challenging. As proximity-ligation based methods of DNA sequencing preserves chromosome-span phase information, we have utilized this principle to demonstrate its utility towards generating full-length phasing of MHC and KIR loci in human samples. We accurately (~99%) reconstruct the complete haplotypes for over 90% of sequence variants (coding and non-coding) within these two loci that collectively span 4-megabases.ConclusionsBy haplotyping a majority of coding and non-coding alleles at the MHC and KIR loci in a single assay, this method has the potential to assist transplantation matching and facilitate investigation of the genetic basis of human immunity and disease

Bayesian Inference of Spatial Organizations of Chromosomes

Knowledge of spatial chromosomal organizations is critical for the study of transcriptional regulation and other nuclear processes in the cell. Recently, chromosome conformation capture (3C) based technologies, such as Hi-C and TCC, have been developed to provide a genome-wide, three-dimensional (3D) view of chromatin organization. Appropriate methods for analyzing these data and fully characterizing the 3D chromosomal structure and its structural variations are still under development. Here we describe a novel Bayesian probabilistic approach, denoted as “Bayesian 3D constructor for Hi-C data” (BACH), to infer the consensus 3D chromosomal structure. In addition, we describe a variant algorithm BACH-MIX to study the structural variations of chromatin in a cell population. Applying BACH and BACH-MIX to a high resolution Hi-C dataset generated from mouse embryonic stem cells, we found that most local genomic regions exhibit homogeneous 3D chromosomal structures. We further constructed a model for the spatial arrangement of chromatin, which reveals structural properties associated with euchromatic and heterochromatic regions in the genome. We observed strong associations between structural properties and several genomic and epigenetic features of the chromosome. Using BACH-MIX, we further found that the structural variations of chromatin are correlated with these genomic and epigenetic features. Our results demonstrate that BACH and BACH-MIX have the potential to provide new insights into the chromosomal architecture of mammalian cells.Statistic

Top Operations and Maintenance (O&M) Efficiency Opportunities at DoD/Army Sites - A Guide for O&M/Energy Managers and Practitioners

This report, sponsored the Army's Energy Engineering Analysis Program, provides the Operations and Maintenance (O&M) Energy manager and practitioner with useful information about the top O&M opportunities consistently found across the DoD/Army sector. The target is to help the DoD/Army sector develop a well-structured and organized O&M program

Electropolishing Valve Metals with a Sulfuric Acid-Methanol Electrolyte at Low Temperature

This study reports the electropolishing Ti and Nb metals using a fluoride-free electrolyte of sulfuric acid and methanol at low temperature (-70°C) without prior treatment. A fluoride-free electrolyte provides a less hazardous and more environmentally friendly option for electropolishing procedure. Experimental studies are presented on electropolishing with sulfuric acid electrolyte, which provides high quality macro- and micro-smoothing of the metal surfaces. Optimal conditions yielded leveling and brightening of the surface of Ti and Nb metals beyond that of the currently utilized electropolishing procedures with fluoride-containing electrolytes. The root mean squared roughness (Rq) from atomic force microscopy (AFM) analysis was 1.64 and 0.49 nm for Ti and Nb, respectively. Lower temperature experiments led to noticeable kinetic effects, indicated by a dramatic drop in current densities and the expansion of the steady-state current density plateau in anodic polarization curves. In addition, the voltage range of the current plateau expanded with increasing acid concentration. Surface characterization of Ti and Nb metals after polishing provided evidence of salt film formation. In addition, these metals were used as substrates in the formation of nanostructured metal oxides. The overall quality of the polishing led to a dramatic improvement in the uniformity of the nanostructures

Differential gene expression in the cortical sulcus compared to the gyral crest within the early stages of chronic traumatic encephalopathy

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative tauopathy found in individuals with a history of repetitive head impacts (RHI). Previous work has demonstrated that neuroinflammation is involved in CTE pathogenesis, however, the specific inflammatory mechanisms are still unclear. Here, using RNA-sequencing and gene set enrichment analysis (GSEA), we investigated the genetic changes found in tissue taken from the region CTE pathology is first found, the cortical sulcus, and compared it to neighboring gryal crest tissue to identify what pathways were directly related to initial hyperphosphorylated tau (p-tau) deposition. 21 cases were chosen for analysis: 6 cases had no exposure to RHI or presence of neurodegenerative disease (Control), 5 cases had exposure to RHI but no presence of neurodegenerative disease (RHI), and 10 cases had exposure to RHI and low stage CTE (CTE). Two sets of genes were identified: genes that changed in both the sulcus and crest and genes that changed specifically in the sulcus relative to the crest. When examining genes that changed in both the sulcus and crest, GSEA demonstrated an increase in immune related processes and a decrease in neuronal processes in RHI and CTE groups. Sulcal specific alterations were observed to be driven by three mechanisms: anatomy, RHI, or p-tau. First, we observed consistent sulcal specific alterations in immune, extracellular matrix, vascular, neuronal, and endocytosis/exocytosis categories across all groups, suggesting the sulcus has a unique molecular signature compared to the neighboring crest independent of pathology. Second, individuals with a history of RHI demonstrated impairment in metabolic and mitochondrial related processes. Finally, in individuals with CTE, we observed impairment of immune and phagocytic related processes. Overall, this work provides the first observation of biological processes specifically altered in the sulcus that could be directly implicated in CTE pathogenesis and provide novel targets for biomarkers and therapies

Weather, disease, and wheat breeding effects on Kansas wheat varietal yields, 1985 to 2011.

Wheat (Triticum aestivum L.) yields in Kansas have increased due to wheat breeding and improved agronomic practices, but are subject to climate and disease challenges. The objective of this research is to quantify the impact of weather, disease, and genetic improvement on wheat yields of varieties grown in 11 locations in Kansas from 1985 to 2011. Wheat variety yield data from Kansas performance tests were matched with comprehensive location-specific disease and weather data, including seasonal precipitation, monthly air temperature, air temperature and solar radiation around anthesis, and vapor pressure deficit (VPD). The results show that wheat breeding programs increased yield by 34 kg ha⁻¹ yr⁻¹. From 1985 through 2011, wheat breeding increased average wheat yields by 917 kg ha⁻¹, or 27% of total yield. Weather was found to have a large impact on wheat yields. Simulations demonstrated that a 1°C increase in projected mean temperature was associated with a decrease in wheat yields of 715 kg ha⁻¹, or 21%. Weather, diseases, and genetics all had significant impacts on wheat yields in 11 locations in Kansas during 1985 to 2011

Women’s views about current and future management of Ductal Carcinoma in Situ (DCIS): a mixed-methods study

Management of low-risk ductal carcinoma in situ (DCIS) is controversial, with clinical trials currently assessing the safety of active monitoring amidst concern about overtreatment. Little is known about general community views regarding DCIS and its management. We aimed to explore women's understanding and views about low-risk DCIS and current and potential future management options. This mixed-method study involved qualitative focus groups and brief quantitative questionnaires. Participants were screening-aged (50-74 years) women, with diverse socioeconomic backgrounds and no personal history of breast cancer/DCIS, recruited from across metropolitan Sydney, Australia. Sessions incorporated an informative presentation interspersed with group discussions which were audio-recorded, transcribed and analysed thematically. Fifty-six women took part in six age-stratified focus groups. Prior awareness of DCIS was limited, however women developed reasonable understanding of DCIS and the relevant issues. Overall, women expressed substantial support for active monitoring being offered as a management approach for low-risk DCIS, and many were interested in participating in a hypothetical clinical trial. Although some women expressed concern that current management may sometimes represent overtreatment, there were mixed views about personally accepting monitoring. Women noted a number of important questions and considerations that would factor into their decision making. Our findings about women's perceptions of active monitoring for DCIS are timely while results of ongoing clinical trials of monitoring are awaited, and may inform clinicians and investigators designing future, similar trials. Exploration of offering well-informed patients the choice of non-surgical management of low-risk DCIS, even outside a clinical trial setting, may be warranted