Innate immunity plays a crucial role in the defense against prokaryotic and eukaryotic pathogens. Major components of this defense are antimicrobial peptides (AMPs). Some AMPs are derived from larger proteins with other recognized functions (e.g., lactoferrin, histones). In this study, we demonstrate the expression of peptides homologous to the β-chain of hemoglobin (Hb-β), one of the two major subunits of this respiratory protein. These Hb-β peptides (HbβP-1, -2 and -3), isolated from gill of the economically important channel catfish (Ictalurus punctatus), had antibacterial activity and were upregulated in gill and skin epithelium in response to parasitic (Ichthyophthirius multifiliis, ich) infection. One peptide (HbβP-1), while having relatively weak antibacterial activity, had antiparasitic activity comparable to that of other potently antiparasitic AMPs. Also, this cidal activity was specifically directed against the trophozoite (trophont) stage of ich at a low concentration (6.2 ug/ml, 1.7 mM) but had no apparent effect on the disseminative (theront) stage or the reproductive (tomont) stage at the highest concentration tested (400 mg/ml, 108 mM). In addition, HbβP-1 was not lytic to channel catfish erythrocytes at the highest concentration tested (400 mg/ml, 108 mM). Immunohistochemistry and in situ hybridization of skin and gill from fish experimentally challenged with ich indicated that the HbβP-1 sequence was both synthesized and expressed in epithelial tissues of skin and gill, which are the target tissues for ich. ?Bug blots? of gill extracts from fish recovering from a bacterial infection suggested that upregulation of these Hb-β related peptides might also occur with other infections. These findings, along with the recent discovery by others that Hb-β is expressed in mammalian macrophages and alveolar epithelium, suggest that hemoglobin-derived AMPs might play a significant role in the non-specific immune response of vertebrates.

Management of feral cats is controversial, and alternatives to lethal control methods are gaining popularity. To evaluate the effectiveness of sterilization programs, nine feral cat colonies were divided into groups of three, managed either by spaying females and castrating males, spaying females and vasectomizing males, or leaving all cats intact. Colonies were followed intensively for four years, and intermittently for three additional years. Most cats were trapped in fewer than ten trap nights each. Breeding females produced a mean of 1.4 litters/year and 3 kittens/litter. Kitten mortality was 75% by 6 months of age. Feral and pet domestic cats had similar baseline health status and prevalences of FIV, FeLV, Cryptosporidium, Giardia, and Toxocara cati, but feral cats had higher prevalences of Bartonalla henselae and Toxoplasma gondii. Castrated male and spayed female cats survived longer than intact male and female cats. Survival times of vasectomized males were equivalent to those of intact males. Control colonies decreased in size and remained stable in composition, while intact colonies increased in size and had high turnover. One neutered colony went extinct and several others had fewer than five cats at the end of the project. Home ranges of both intact and neutered cats were small, usually less than 1 ha. Vasectomized males had larger home ranges than either intact or castrated males, probably because they were searching for intact females. Community-level stakeholder meetings were successful in building consensus among groups, and a basic decision tree for feral cat management was developed. Computer simulation modeling using VORTEX software suggested that harvesting breeding colonies every one or two years at 50% to 100% can keep colonies small, but will not lead to long-term reductions in cat numbers. Models of neutered colonies suggested that 75% to 80% sterilization is necessary to cause population decrease and eventual extinction. The mean estimated time to extinction of 12.8 years fits well with ongoing observations of steady decline in sterilized colonies.

<p>Benzene is an industrial solvent and a ubiquitous environmental pollutant that induces hematopoietic damage; although, the mechanism by which this damage occurs is uncertain. The hematologic effects of benzene vary widely among different mouse strains, and intermittent exposure of mice to benzene is more highly toxic and carcinogenic than low, constant exposure. The goal of the research described in this dissertation was to investigate the sensitivity of two genetically engineered mouse models of carcinogenesis, Tg.AC and p53 +/- mice, and parental strains FVB/N and C57BL/6 respectively, to hematologic toxicicity resulting from inhaled benzene. Tg.AC mice contain an activated v-Ha-ras oncogene, and the p53 +/- mouse is haplosufficient for the p53 gene. Hypotheses of this work included that benzene ishematotoxic, and that greater genotoxic damage caused by benzene would be evident in the p53 +/- mouse. Another hypothesis was that benzene would induce Tg.AC transgene expression in the spleen. The research was divided into three specific aims. First, genotoxicity resulting from exposure to benzene was determined by micronucleus formation in blood. These studies showed a time-dependent, but not a concentration-dependent increase in micronuclei following benzene exposure. The p53 +/- mice were not more sensitive to benzene-induced micronuclei than the parental strain (p53 +/+). For the second specific aim, benzene hematotoxicity was assessed and spleen analyses were conducted. Benzene induced a significant cytopenia and reduced spleen weight in all of the strains examined. The C57BL/6 mice were less sensitive to benzene hematotoxicity than the FVB/N strain for all of the hematologic parameters examined. For the third specific aim, expression of theTg.AC transgene mRNA was assessed by reverse transcriptase-polymerase chain reaction of splenic tissue. Evidence of the Tg.AC transgene expression was absent in these tissues. Overall, the findings showed a marked strain-related difference between FVB/N and C57BL/6 mice in the hematotoxicity of benzene. In most parameters investigated, the Tg.AC or p53+/- genetic alterations were not useful adjuncts for investigating the hematotoxic mechanisms of benzene. Investigation of the genetic differences between these two mouse strains may lead to further understanding of the biological determinants of benzene hematotoxicity.<P>

<p>The swine industry is often implicated as one of the most significant contributors to foodborne Salmonella infections in humans. As the trend in swine production in the United States is toward larger and more intensive farms, but fewer farm units, it is likely that antimicrobial usage is also increasing. The purpose of this research was to study antimicrobial resistance and determine phenotypic and genotypic diversity of multi-drug resistant Salmonella in swine production systems. We found resistance to specific classes of antimicrobials including tetracycline, b-lactams and chloramphenicol to be common and stable over the study period. Over the time period of the study, we also noticed a significant shift in the patterns of multi-drug resistance, despite the fact that no change in antimicrobial usage had taken place, suggesting that other, currently unidentified selective pressures could be of significance. Bacteriophage typing also revealed that two phage types of importance to public health, DT104 and DT193, often had two predominant pentaresistance patterns. Susceptibility testing on a number of human S. Typhimurium isolates, however, revealed that multi-drug resistance was infrequent among isolates originating from humans. The findings in studying the genetic diversity of these Multi-drug resistant strains imply that vertical transmission, most likely originating from the sow farm, is an important source at the nursery stage, but that horizontal transmission of clonal groups is significant at the finishing phase. Resistance genes detected on multi-drug resistant Salmonella Typhimurium DT193 revealed that the resistance genes and locations are specifically different from that of DT104.Overall, the study findings show that antimicrobial resistance in the swine production environment is common and may be linked to the level of antimicrobial usage. Despite the common occurrence of public health important strains among isolates from swine, strains from humans were distinct and were less likely to be resistant to multiple antimicrobials. This area needs to be of high priority for further research to assess the risk of human Salmonella infection from swine or pork products. Further research on the genetic diversity of Salmonella also must be considered in order to identify significant factors contributing to the dissemination of multi-drug resistant Salmonella in modern swine production systems.<P>

<p>ANDERSON, STEVEN PAUL. Gene modulation in peroxisome proliferator-induced hepatocarcinogenesis. (Under the direction of Russell C. Cattley and John M. Cullen). Recognition that peroxisome proliferator chemicals are potent hepatic mitogens and carcinogens in rats and mice has generated concern about possible human health risks associated with exposure to several of these chemicals, many of which have medical or commercial utility. Our broad objective was to improve the estimation of human health risk following peroxisome proliferator exposure by defining a subset of the molecular events associated with the rodent tumors. Our working hypothesis was that peroxisome proliferator-induced tumors in rodents result from specific, peroxisome proliferator-activated receptor-a(Ppara)-modulated changes in gene expression. The research was directed toward three specific aims. First, we sought to identify genes associated with hepatocarcinogenesis induced by the peroxisome proliferator, Wy-14, 643, in the rat. The principle conclusion of these studies - that peroxisome proliferators dysregulate expression of hepatic acute-phase protein genes - suggested possible perturbations in cytokine signaling networks that also regulate cell growth. Second, although Ppara is necessary for the rodent hepatocarcinogenesis induced by peroxisome proliferators, we were interested in identifying more proximate mediators of the increased cell proliferation. Thus, we examined cytokine signaling in mice treated with peroxisome proliferators. We found that peroxisome proliferator-induced increases in cell proliferation is not mediated via Tnfasignaling, but instead may be mediated through interleukin-1b or interleukin-6. Third, because Ppara is necessary for the cell proliferation that follows peroxisome proliferator exposure, we hypothesized that the receptor may play a role in hepatocellular proliferation induced by other stimuli. Following partial hepatectomy, liver regeneration in Ppara-null mice is transiently impaired, and may result from altered expression of genes regulating the G1/S cell cycle checkpoint in hepatocytes from these mice. Overall, our studies suggest that hepatic Ppara activation (1) alters inflammatory mediators, (2) modulates several potentially mitogenic cytokines, and (3) is necessary for normal liver regeneration after partial hepatectomy. Our data, compared with data from similar experiments on human hepatocytes, may provide further clues about the differences and similarities between peroxisome proliferator exposure in humans and laboratory animals.<P>

This work is an attempt to define a comprehensive contemporary model of the causes of wars of secession, state and illustrate its gaps, and develop new theories to accentuate and improve that model, and through comparative case studies perform some elementary tests of their validity. My theoretical paradigm is dependent on an assumption that the ultimate causes, as captured under the rubric of institutions and structures, of an event involving rational but free-willed human beings are inadequate to explaining the onset of radical, extraordinary politics in general and wars of secession in particular. On the contrary, proximate causes, in the form of environmental factors that cannot be classified structural or institutional and which are either deeply influenced by elite decisions or deeply influence elite decisions must be brought into the theoretical chain. Specifically I examine the case of Namibia, focusing on the East Caprivi region where in 1999 a substantial portion of the Lozi population attempted to secede, comparing it to the case of Botswana and another minority, the Kalanga people who dominate the North East District. I find that the two states are (1) structurally and institutionally similar, to the point that were these the only causal factors involved one would assume they would suffer similar behavioral outcomes, (2) divergent in terms of minority political identities and degrees of mobilization, and (3) divergent in terms of a series of internal and external environmental decision that cannot be described as structural or institutional.

Pri ha-Pardes (Früchte des Obstgartens) ist eine Reihe der Vereinigung für Jüdische Studien e.V., welche in Verbindung mit dem Institut für Jüdische Studien der Universität Potsdam publiziert wird. Pri ha-Pardes möchte kleineren wissenschaftlichen Studien, Forschungen am Rande der großen Disziplinen und exzellenten Masterarbeiten eine Publikationsplattform bieten. Der Erstgeburtsstreit der Brüder Jakob und Esau wird seit jeher ethnologisch rezipiert und diente von frühester Zeit an, sowohl auf jüdischer als auch auf christlicher Seite, in vielfacher Auslegung als Grundlage religiöser und ‚politischer’ Identitätsbildung. Im Zuge dieser Deutung geriet jedoch die Frage in den Hintergrund, weshalb Gott ausgerechnet den ‚Betrüger’ Jakob zum dritten Stammvater Israels erwählt. Im vorliegenden vierten Band dieser Reihe stellt sich Daniel Vorpahl genau diesem Problem und klärt in einer ausführlichen exegetischen Untersuchung der biblischen Jakob-Esau-Erzählung Hintergründe, Verlauf und Bedeutung des Betrugsfalls sowie dessen Folgen. Anhand zentraler Bestandteile dieser Tradition, wie dem Motiv des Brüderstreits, der Begriffe Erstgeburtsrecht, Segen und Verheißung, wird darüber hinaus die Stellung der Jakob-Esau- Erzählung innerhalb der gesamten Vätergeschichte beleuchtet. Dabei werden nicht nur die begründeten Umstände Jakobs Erwählung erläutert, sondern vor allem auch die sozialethische Relevanz der Jakob-Esau-Tradition veranschaulicht.

Inhalt: I. Erinnern und Erlösung 1. Gedenken oder Erinnern in der talmudischen Antike 2. Die Transzendentierung des Gedenkens in der frühen Kabbala des 13. Jahrhunderts 3. Die Historisierung und Psychologisierung der theosophischen kabbalistischen Auffassungen vom Gedenken in der lurianischen Kabbala des 16. Jahrhunderts 4. Die psychologisch, individualsoteriologische Deutung des Erinnerns im Chasidismus II. Das Fest und die Erlösung 1. Die talmudischen Deutungen der biblischen Feste 2. Die Sicht der Philosophen des Mittelalters und die Reaktion der Kabbala

Aus dem Inhalt: Es ist auch noch heute keine leichte Aufgabe, das wissenschaftliche Werk Gershom Scholems, schon zu Lebzeiten ein Monument, dessen Größe dem Betrachter kaum überschaubar erscheint, zu würdigen, ohne in schiere Bewunderung und Preisreden zu verfallen - die, wer könnte es bestreiten, hier wie selten am Platze sind. Das Gesagte gilt, auch wenn man nur einen Teilbereich von Scholems wissenschaftlicher Arbeit herausgreift, und nicht zuletzt für den des osteuropäischen Hasidismus. Scholems Arbeiten über den Hasidismus kritisch zu würdigen fällt weitaus schwerer als die Martin Bubers, da man Scholen - anders als Buber - nicht der wenn auch genialen und literarisch beeindruckenden Einseitigkeit eines Buber zeihen kann.

Excerpt: The writings from the thirteenth century called by Gershom Scholem the "Writings of the 'lyyun circle" are one of the most intriguing chapters of early kabbalah - this I need not to elaborate on as it is a well known fact to anyone whoever had read these texts or the literature about them. When reading these texts, one gets the impression as if the authors had at hand a box full of terms and phrases into which everybody could just stick his hand and take terms and phrases out of it in order to arrange them according to his own taste, disregarding the meaning they have in the writings of his fellow kabbalists. The result was, that we now have before us a large number of varying mosaic pictures in which we detect again and again the same mosaic pebbles, however composed differently.