Exploring the Shivwits production zone

The Shivwits Plateau is situated on the Arizona Strip in the northwest corner of Arizona. It is a relatively unexplored area rich in archaeological resources. This study provides three areas of exploration of the prehistoric Virgin Anasazi Pueblo period. Three research questions are posed. Are there substantial Virgin Puebloan sites on the Shivwits Plateau? Through compiled site data and analysis of settlement models the information supports the conclusion that there was a substantial prehistoric use of the Shivwits Plateau; A specific question about pottery production guides the second part of the research. Was the sherd-tempered Shivwits Plain and Shivwits Corrugated pottery produced on the Shivwits Plateau? Samples collected from five sites on the Plateau are examined. Temporal analysis and characterization cannot support the hypothesis at this time; Integrating the settlement information and the ceramic analysis provides the third area of question. Were the sites on the Shivwits Plateau situated to take advantage of movement of people and goods, particularly the Shivwits Plain and Shivwits Corrugated pottery, between the upland Western Plateaus and the neighboring Lowland Muddy-Virgin Valley? Examining the information from the five sample sites there is not a strong indication these sites were involved in interaction with the lowland. It is important to note that the absence of affirming evidence does not rule out the possibility of pottery production or of sites situated to take advantage of trade or travel. There is simply not enough information available to reach absolute conclusions about the Shivwits Plateau; The primary goal of this research is to provide a base of information about the archaeological potential of the Shivwits Plateau

Genetic and metabolic components in the regulation of serum urate levels in humans

Uric acid is the final breakdown product of purine metabolism in humans and present in the blood as urate. Elevated serum urate levels can cause gout, a painful inflammatory arthritis, and are implicated in a number of common diseases such as cardiovascular disease, metabolic syndrome, and type 2 diabetes. The regulation of serum urate levels is assumed to result from a complex interplay between genetic, environmental, and lifestyle factors. The underlying functional biological processes are still not completely understood. The present thesis aimed to identify genetic and metabolic factors in the regulation of serum urate levels. Therefore, two different hypothesis-free approaches were applied. First, two genome-wide association studies were performed in order to identify genetic loci that are involved in the regulation of serum urate levels within the framework of two huge international consortia. The impact of identified genetic loci was compared between different ancestries. Second, a metabolic network analysis within a population-based study was performed aiming to describe the metabolic vicinity of serum urate. By combining data of approximately 28,000 individuals in a genome-wide association study, nine genetic loci were identified to be involved in the regulation of serum urate levels. The increase of the sample size to a total of approximately 140,000 individuals within a world-wide consortium, combined with a systematic protein-protein interaction network approach, raised the number of detected genetic loci to 28. Although serum urate shows distinct sex differences, an investigation of the X chromosome did not provide additional findings. Whereas the first identified genes were predominantly involved in urate transport, none of the later identified genes are obviously involved in its transport but underline the importance of the metabolic control of its production and excretion. A comparison between results from different ancestries showed that several of the loci found in Europeans do also play a role in non-Europeans. However, results from one ancestry cannot directly be transferred to other ancestries as the genetic architecture at certain loci can vary between ancestries. In the metabolite network analysis, serum urate was not only connected to the well-known purine metabolism, but also to a group of essential amino acids and a group of several steroids. Furthermore, association with uricostatic medication intake was not only connected to purine metabolism but seen for nine metabolites within the network. The findings highlight pathways that are important in the regulation of serum urate and suggest that amino acids as well as steroid hormones play a role in its regulation. The results of both approaches help to better understand the complexity of serum urate regulation in humans, and may help to advance drug development for the treatment and prevention of hyperuricemia and gout.Harnsäure ist im menschlichen Stoffwechsel das Endprodukt aus dem Abbau von Purinen. Ein erhöhter Harnsäurespiegel kann zu Gicht, einer schmerzhaften Gelenksentzündung, führen und spielt bei einer Vielzahl häufiger Erkrankungen, wie zum Beispiel kardiovaskulären Erkrankungen, dem metabolischen Syndrom und Typ 2 Diabetes eine Rolle. Man geht davon aus, dass der Harnsäurespiegel in einem komplexen Zusammenspiel von genetischen Komponenten, Umwelteinflüssen und Lebensstil reguliert wird. Die zugrundeliegenden biologischen Prozesse sind jedoch bisher nicht vollständig bekannt. Ziel der vorliegenden Doktorarbeit war es, sowohl genetische Faktoren als auch Stoffwechselkomponenten zu identifizieren, die Einfluss auf die Regulation des Harnsäurespiegels haben. Dazu wurden zwei hypothesenfreie Ansätze gewählt. Zum einen wurden in großen internationalen Konsortien zwei genomweite Assoziationsstudien durchgeführt, um genetische Einflussfaktoren auf die Regulation des Harnsäurespiegels zu finden. Der Einfluss der identifizierten Regionen wurde daraufhin zwischen verschiedenen Ethnizitäten verglichen. Des Weiteren wurden in einer Netzwerkanalyse in einer populationsbasierten Studie metabolische Einflussfaktoren untersucht. In der ersten genomweiten Assoziationsstudie konnten mit einer Datengrundlage von mehr als 28 000 Individuen neun genetische Regionen mit Einfluss auf die Regulation des Harnsäurespiegels identifiziert werden. Durch eine Erhöhung der Fallzahl auf insgesamt etwa 140 000 innerhalb einer weltweiten Kooperation in Kombination mit einem systematischen Netzwerkansatz basierend auf Protein-Protein-Interaktionen, konnte die Zahl der identifizierten genetischen Regionen auf 28 erhöht werden. Trotz großer Geschlechtsunterschiede im Harnsäurespiegel führte eine Analyse des X-Chromosoms zu keinen zusätzlichen Erkenntnissen. Während die anfangs gefundenen Gene hauptsächlich am Transport der Harnsäure beteiligt sind, kann keines der später gefundenen Gene mit deren Transport in Verbindung gebracht werden; vielmehr deuten diese auf Stoffwechselkomponenten die bei deren Bildung und Ausscheidung eine Rolle zu spielen scheinen. Ein Vergleich der Ergebnisse zwischen Populationen unterschiedlicher Herkunft zeigt, dass Ergebnisse für Europäer häufig auch in anderen Populationen Gültigkeit besitzen, allerdings aufgrund unterschiedlicher genetischer Architektur nicht unbedingt direkt übertragen werden können. In der Metabolitennetzwerkanalyse wurde die Harnsäure nicht nur mit dem Purinstoffwechsel verknüpft, sondern auch mit verschiedenen Aminosäuren und Steroiden. Auch die Wirkung von harnsäuresenkenden Medikamenten war nicht auf die Purine beschränkt, sondern zeigte Auswirkung auf neun Metaboliten im Netzwerk. Die Ergebnisse zeigen Zusammenhänge in der Regulation des Harnsäurespiegels und legen nahe, dass sowohl Aminosäuren als auch Steroide eine Rolle spielen. Die Ergebnisse beider Ansätze helfen, die komplexen Mechanismen in der Regulation der Harnsäure im Menschen besser zu verstehen und werden möglicherweise in der Entwicklung von Medikamenten zur Behandlung und Prävention von Gicht Anwendung finden

Ioncopy: an R Shiny app to call copy number alterations in targeted NGS data

Background: Somatic copy number alterations (CNAs) contribute to the clinically targetable aberrations in the tumor genome. For both routine diagnostics and biomarkers research, CNA analysis in a single assay together with somatic mutations is highly desirable. Results: Ioncopy is a validated method and easy-to-use software for CNA calling from targeted NGS data. Copy number and significance of CNA are estimated for each gene in each sample. Copy number gains and losses are called after multiple testing corrections controlling FWER or FDR. Conclusions: Ioncopy facilitates calling of CNAs in a cohort of tumors tissues with or without using normal (germline) DNA controls

Ultrasound Imaging-Based Methods for Assessing Biological Maturity during Adolescence and Possible Application in Youth Sport: A Scoping Review

Bone maturity is an indicator for estimating the biological maturity of an individual. During adolescence, individuals show heterogeneous growth rates, and thus, differences in biological maturity should be considered in talent identification and development. Radiography of the left hand and wrist is considered the gold standard of biological maturity estimation. The use of ultrasound imaging (US) may be advantageous; however, its validity and reliability are under discussion. The aims of this scoping review are (1) to summarize the different methods for estimating biological maturity by US imaging in adolescents, (2) to obtain an overview of the level of validity and reliability of the methods, and (3) to point out the practicability and usefulness of ultrasound imaging in the field of youth sports. The search included articles published up to November 2022. The inclusion criteria stipulated that participants had to fall within the age range of 8 to 23 years and be free of bone disease and fractures in the region of interest. Nine body regions were investigated, while the hand and wrist were most commonly analyzed. US assessment methods were usually based on the estimation of a bone maturity stage, rather than a decimal bone age. Furthermore, 70% of the assessments were evaluated as applicable, 10% expressed restraint about implementation, and 20% were evaluated as not applicable. When tested, inter- and intra-rater reliability was high to excellent. Despite the absence of ionization, low costs, fast assessment, and accessibility, none of the US assessments could be referred to as a gold standard. If further development succeeds, its application has the potential to incorporate biological age into selection processes. This would allow for more equal opportunities in talent selection and thus make talent development fairer and more efficient

Interleukin-22 predicts severity and death in advanced liver cirrhosis: a prospective cohort study

Background: Interleukin-22 (IL-22), recently identified as a crucial parameter of pathology in experimental liver damage, may determine survival in clinical end-stage liver disease. Systematic analysis of serum IL-22 in relation to morbidity and mortality of patients with advanced liver cirrhosis has not been performed so far. Methods: This is a prospective cohort study including 120 liver cirrhosis patients and 40 healthy donors to analyze systemic levels of IL-22 in relation to survival and hepatic complications. Results: A total of 71% of patients displayed liver cirrhosis-related complications at study inclusion. A total of 23% of the patients died during a mean follow-up of 196 +/- 165 days. Systemic IL-22 was detectable in 74% of patients but only in 10% of healthy donors (P 18 pg/ml, n = 57) showed significantly reduced survival compared to patients with regular ([less than or equal to]18 pg/ml) levels of IL-22 (321 days versus 526 days, P = 0.003). Other factors associated with overall survival were high CRP ([greater than or equal to]2.9 mg/dl, P = 0.005, hazard ratio (HR) 0.314, confidence interval (CI) (0.141 to 0.702)), elevated serum creatinine (P = 0.05, HR 0.453, CI (0.203 to 1.012)), presence of liver-related complications (P = 0.028, HR 0.258 CI (0.077 to 0.862)), model of end stage liver disease (MELD) score [greater than or equal to]20 (P = 0.017, HR 0.364, CI (0.159 to 0.835)) and age (P = 0.011, HR 1.047, CI (1.011 to 1.085)). Adjusted multivariate Cox proportional-hazards analysis identified elevated systemic IL-22 levels as independent predictors of reduced survival (P = 0.007, HR 0.218, CI (0.072 to 0.662)). Conclusions: In patients with liver cirrhosis, elevated systemic IL-22 levels are predictive for reduced survival independently from age, liver-related complications, CRP, creatinine and the MELD score. Thus, processes that lead to a rise in systemic interleukin-22 may be relevant for prognosis of advanced liver cirrhosis

Molecular analysis of the interaction between cardosin A and phospholipase Dα

Cardosin A is an RGD-containing aspartic proteinase from the stigmatic papillae of Cynara cardunculus L. A putative cardosin A-binding protein has previously been isolated from pollen suggesting its potential involvement in pollen2013pistil interaction [Faro C, Ramalho-Santos M, Vieira M, Mendes A, Simões I, Andrade R, Verissimo P, Lin X, Tang J & Pires E (1999) J Biol Chem274, 28724201328729]. Here we report the identification of phospholipase D03B1 as a cardosin A-binding protein. The interaction was confirmed by coimmunoprecipitation studies and pull-down assays. To investigate the structural and molecular determinants involved in the interaction, pull-down assays with cardosin A and various glutathione S-transferase-fused phospholipase D03B1 constructs were performed. Results revealed that the C2 domain of phospholipase D03B1 contains the cardosin A-binding activity. Further assays with mutated recombinant forms of cardosin A showed that the RGD motif as well as the unprecedented KGE motif, which is structurally and charge-wise very similar to RGD, are indispensable for the interaction. Taken together our results indicate that the C2 domain of plant phospholipase D03B1 can act as a cardosin A-binding domain and suggest that plant C2 domains may have an additional role as RGD/KGE-recognition domains