Distribution of racial elements in the population of Illinois

Thesis (M.A.)--University of Illinois, 1912.Typescript.Includes bibliographical references (leaves 75-80).Ope

Diverse New Microvertebrate Assemblage from the Upper Triassic Cumnock Formation, Sanford Subbasin, North Carolina, USA

The Moncure microvertebrate locality in the Cumnock Formation, Sanford sub-basin, North Carolina, dramatically increases the known Late Triassic age vertebrate assemblage from the Deep River Basin. The 50,000 recovered microvertebrate fossils include osteichthyans, amphibians, and numerous lepidosauromorph, archosauriform, and synapsid amniotes. Actinopterygian fossils consist of thousands of scales, teeth, skull, and lower jaw fragments, principally of redfieldiids and semionotids. Non-tetrapod sarcopterygians include the dipnoan Arganodus sp., the first record of lungfish in the Newark Supergroup. Temnospondyls are comparatively rare but the preserved centra, teeth, and skull fragments probably represent small (juvenile) metoposaurids. Two fragmentary teeth are assigned to the unusual reptile Colognathus obscurus (Case). Poorly preserved but intriguing records include acrodont and pleurodont jaw fragments tentatively assigned to lepidosaurs. Among the archosauriform teeth is a taxon distinct from R. callenderi that we assign to Revueltosaurus olseni new combination, a morphotype best assigned to cf. Galtonia, the first Newark Supergroup record of Crosbysaurus sp., and several other archosauriform tooth morphotypes, as well as grooved teeth assigned to the recently named species Uatchitodon schneideri. Synapsids represented by molariform teeth include both "traversodontids" assigned to aff. Boreogomphodon and the "dromatheriid" Microconodon. These records are biogeographically important, with many new records for the Cumnock Formation and/or the Newark Supergroup. In particular, Colognathus, Crosbysaurus, and Uatchitodon are known from basins of Adamanian age in the southwestern U.S.A. These new records include microvertebrate taxa more typical of non-Newark basins (abundant archosauriforms, temnospondyls, lungfish) as well as more typical Newark osteichthyans and synapsid-rich faunal elements

The transcriptional regulation of the angiotensin-AT2-receptor gene and the AT2R-binding protein gene

Das Hormon Angiotensin II (Ang II) ist das Haupteffektorpeptid des Renin-Angiotensin-Systems (RAS). Es ist neben physiologischen Prozessen auch in die Pathogenese kardiovaskulärer Erkrankungen involviert. Ang II vermittelt seine Wirkung hauptsächlich über zwei membranständige Rezeptoren, den Angiotensin-AT1-Rezeptor (AT1R) und den Angiotensin-AT2-Rezeptor (AT2R), wobei die Stimulation beider Rezeptoren gegensätzliche zelluläre Effekte vermittelt. Die Rolle des AT2R innerhalb kardiovaskulärer Erkrankungen wird in der Literatur kontrovers diskutiert. Unsere Arbeitsgruppe identifizierte kürzlich ein neues AT2R-Interaktionsprotein, das AT2R-binding-Protein (ATBP/ATIP), das mit dem C-Terminus des AT2R im Zytoplasma wechselwirkt. In dieser Arbeit wurden neue transkriptionelle Regulationsmechanismen des AT2R- und des ATIP1-/ATBP50-Gens identifiziert und charakterisiert. Mit Hilfe der RLM-5'-RACE konnte für das humane AT2R-Gen ein transkriptioneller Startpunkt identifiziert werden, der sich 29 bp downstream der TATA-box und 1533 bp upstream vom Translationsstartpunkt befindet. Für das TATA-box-lose ATIP1-Gen wurden zwei transkriptionelle Startpunkte ermittelt, die 293 bp und 304 bp upstream vom Translationsstartpunkt lokalisiert sind. Promotoranalysen weisen auf eine zentrale Funktion der Exon-1-/Intron-1-Region des AT2R-Gens bei der Transkription hin. Unter anderem mittels inverser Klonierungsexperimente konnte gezeigt werden, dass Sequenzen innerhalb dieser Region die Rekrutierung des Transkriptionsapparates vermitteln und dabei einen weiteren Transkriptionsstartpunkt generieren. Der intronische AT2R-Polymorphismus -G1332A wird mit protektiven Effekten bei der myokardialen Hypertrophie von Frauen assoziiert. Die Untersuchung dieses Polymorphismus hat gezeigt, dass Promotoren mit dem G-Allel im Vergleich zu Promotoren mit dem A-Allel generell eine stärkere Promotoraktivität aufweisen. Östrogene scheinen das Verhältnis von AT1R/AT2R zu Gunsten des AT2R zu verschieben. Der potenzielle Einfluss des Hormons 17-Östradiol (E2) auf die Transkription des AT2R- und des ATIP1-Gens wurde mit Hilfe von Promotoranalysen untersucht. Die durchgeführten Experimente zeigten, dass E2 keine regulativen Effekte auf die Transkription beider Zielgene ausübt. Das Protein Poly(ADP-Ribose)-Polymerase-1 (PARP-1) ist in die Ang II-vermittelten Effekte und in die Pathogenese kardiovaskulärer Erkrankungen involviert. Promotorreportergenuntersuchungen der beiden Zielgene haben gezeigt, dass die Promotoraktivität des AT2R-Gens durch die Überexpression von PARP-1 reprimiert und die des ATIP1-Gens induziert wird. Die Inhibierung der enzymatischen PARP-Aktivität oder der zelluläre knockout des PARP-1-Gens resultierten in Bezug auf die Promotoraktivierung in einer Aktivierung des AT2R- und einer Hemmung des ATIP1-/ATBP50-Gens. Diese Ergebnisse wurden zusätzlich durch Untersuchungen auf der entsprechenden mRNA- und Chromatinebene bestätigt. Es konnte gezeigt werden, dass PARP-1 die Transkription des ATIP1-/ATBP50-Gens aktiviert und als Repressor der AT2R-Transkription wirkt. Somit konnte innerhalb dieser Arbeit das Protein PARP-1 als neuer transkriptioneller Modulator des AT2R- und ATIP1-/ATBP50-Gens identifiziert werden.The hormone angiotensin II (Ang II) is the main effector peptide of the renin-angiotensin-system (RAS). In addition to its physiological role, Ang II is also involved in the pathogenesis of cardiovascular diseases. Ang II elicits its effects mainly via two receptors that are located in the cell membrane, the angiotensin-AT1-receptor (AT1R) and the angiotensin-AT2-receptor (AT2R). Stimulation of these receptors leads to opposite cellular effects. In literature the role of the AT2R within cardiovascular diseases is controversially discussed. Recently, our group identified a new AT2R-binding-protein (ATBP/ATIP) that interacts in the cytoplasm with the C-terminus of the AT2R. In this dissertation, the transcriptional regulations of the AT2R- and of the ATIP1-/ATBP50-gene were characterised. Using the RLM-5'-RACE, one transcriptional start site was identified for the human AT2R gene that is located 29 bp downstream of a TATA-box element and 1533 bp upstream of the translational start site. For the TATA-boxless ATIP1-gene two transcriptional start sites were detected 293 bp and 304 bp upstream of the translational start point. Promoter analysis indicated that the exon-1-/intron-1-region of the AT2R-gene is both necessary and sufficient for the transcription of this gene. Inverse cloning experiments revealed that sequences within this region are responsible for recruitment of the transcriptional machinery, thereby generating an alternative start point. The intronic AT2R polymorphism -G1332A is associated with protective effects of myocardial hypertrophy in women. Analysis of this polymorphism has shown that promoters containing the G allele exhibit stronger basal promoter activities compared to promoters carrying the A allele. Estrogens seem to modify the proportion of AT1R/AT2R in favour of AT2R. In this study, promoter analyses were performed to investigate the influence of the hormone 17-beta-estradiol (E2) on the transcription of both target genes. These experiments have shown that E2 has no regulative influence on transcription levels of either the AT2R or the ATIP1 gene. The protein Poly(ADP-Ribose)-Polymerase-1 (PARP-1) is involved in Ang II mediated effects as well as in the pathogenesis of cardiovascular diseases. Promoter analyses of the AT2R and ATIP1 gene have revealed that overexpression of PARP-1 results in a decreased promoter activity of the AT2R gene and an increased activity of the ATIP1-gene. Inhibition of enzymatic PARP-activity or the homozygous cellular knockout of PARP-1 activates the AT2R and inhibits the ATIP1/ATBP50 gene. These results were further verified on mRNA and chromatin level. Additional experiments have shown that PARP-1 activates the transcription of the ATIP1/ATBP50 gene and function as a repressor on AT2R transcription. In this study PARP-1 was identified as a novel transcriptional modulator of the AT2R and the ATIP1/ATBP50 genes

Analysis of 5-hydroxytryptamine 2c receptor gene promoter variants as alcohol-dependence risk factors

To examine whether polymorphic variants of the HTR2C gene are associated with diagnosis of alcohol dependence. We compared allele frequencies of five HTR2C promoter polymorphisms in a Nordic population of alcohol dependent individuals (Males: n = 309; Females: n = 127) and ethnically matched controls (Males: n = 83; Females: n = 190) in whom alcohol dependence was established, or any diagnosis of substance disorder was excluded, respectively. Patients were further subtyped into Type I (late onset) and Type II (early onset) alcoholics. None of the individual polymorphisms indicated significant association with alcohol dependence. A common promoter haplotype (GAGG) exhibited different distribution frequencies between males and females (Type I), however on Bonferroni's multiple-testing correction, this observation proved to be insignificant. Although we report a lack of association between alcohol dependence and five common promoter polymorphisms, and the constituted haplotypes, the analysis tends to indicate gender and sub-type differences. We suggest that a follow up study with larger sample numbers should be performed to improve the power to detect the genetic influences of HTR2C in alcohol dependence