63 research outputs found
The Legislative history of gambling, 1861 - 1915
Nevada’s way of regulating gambling has been of such interest over the past years that it has been given a name, the “Nevada Model”. Interested parties usually are seeking to learn if this model of gambling regulation will work in other political units of this country. The point of this paper is to give some background to the “Nevada Model” by looking at how the acts of the legislature of the state evolved through time. Of equal importance is the understanding of the role the miners played in the formation of Nevada’s culture and lifestyle. The miners brought Nevada its rugged individualism, combined with a sense of risk taking and a desire for wealth. Most of them were single, younger men who had rejected the traditional life-style of farming, family, church and community. The only community they owed allegiance to, or laws that they obeyed, was that of the camp in which they resided, or the rules of the Mining District. It is this mining culture and the resultant lifestyle it perpetuated that did not just permit gambling but, instead, embraced it. A contextual chronological history of each Act of the Legislature from Territorial days through 1915 is contained in the section entitled Context of the Laws. Each of the statutes related to gambling from 1861 to 1915 have been reproduced and can be found in the appendix. This is followed by the Summary, which places each of the three periods of either prohibition or legalization/regulation into perspective of the larger picture of the state’s history. The chapter titled Interpretation is this author’s finding that the geography of the state, coupled with the massive influx of miners following the discovery of rich gold and/or silver lodes, on two separate occasions, is the core reason for the pro-gaming attitudes of the political culture of the state. It was this attitude toward gambling by the political culture that is evidenced by the enactment of gaming statutes by the legislature of the state
An Analysis of the socio-economic impact of casino gaming in Mesquite, Nevada, and its implications for public policy
This study is a preliminary analysis of the socio-economic impact of casino gaming in Mesquite, Nevada. Mesquite is being studied from this perspective in order to provide policymakers with information that will aid in the determination of public policy relevant to and in conjunction with casino gaming activity. A combination of site visits to the area and interviews with casino executive personnel and relevant law enforcement was conducted for the purposes of gathering information for this study. Three police departments (Mesquite, Nevada, Cedar City, Utah and St. George, Utah) were interviewed to determine the crime rate in jurisdiction. Relevant data has been provided by each department, which indicates the rate of Part I and Part II for their respective communities. Additionally, visitor volume and demographics of the gambling population in Mesquite have been provided by the Las Vegas Convention and Visitors Authority (see Exhibits A and B, respectively). Information relevant to the revenue produced in the Mesquite, Nevada area because of the gambling activity has been provided by the Nevada State Gaming Control Board (Exhibit C). A combination of a literature review and demographics provided by the Las Vegas Convention and Visitor’s Authority, was used to provide information relevant to the social issue of compulsive gaming. Issues relevant to the quality-of-life of local resident’s as a result of the implementation of, and increase in, casino gaming in Mesquite, Nevada, have been provided in this study through the use of a comparative model. A study conducted in Cripple Creek, Colorado was used for this purpose due to that community’s introduction of casino gaming into a “small, rural, community,” similar to Mesquite, Nevada. This study is the first of its kind for the area. It is not comprehensive in nature. The study\u27s findings, as discussed in the SUMMARY, and the recommendations, discussed in the CONCLUSION, are based upon this and prior studies on the subject of casino gaming. It is recommended that additional studies on crime and compulsive gaming be conducted to determine what, if any changes, are occurring in these areas as the activity of casino gaming continues or increases in Mesquite, Nevada. Relevant findings (SUMMARY, Chapter 4) confirm the social and economic benefit of the casino gaming activity in Mesquite, Nevada
Conservation of the COP9/signalosome in budding yeast
BACKGROUND: The COP9/signalosome (CSN), a multiprotein complex consisting of eight subunits, is implicated in a wide variety of regulatory processes including cell cycle control, signal transduction, transcriptional activation, and plant photomorphogenesis. Some of these functions have been linked to CSN-associated enzymes, including kinases and an activity that removes the ubiquitin-like protein NEDD8/Rub1p from the cullin subunit of E3 ligases. CSN is highly conserved across species from fission yeast to humans, but sequence comparison has failed to identify the complex in budding yeast, except for a putative CSN5 subunit called Rri1p. RESULTS: We show that disruption of four budding yeast genes, PCI8 and three previously uncharacterized ORFs, which encode proteins interacting with Rrr1p/Csn5p, each results in the accumulation of the cullin Cdc53p exclusively in the Rub1p-modified state. This phenotype, which resembles that of fission yeast csn mutants, is due to a biochemical defect in deneddylation that is complemented by wild-type cell lysate and by purified human CSN in vitro. Although three of the four genes encode proteins with PCI domains conserved in metazoan CSN proteins, their disruption does not confer the DNA damage sensitivity described in some fission yeast csn mutants. CONCLUSIONS: Our studies present unexpected evidence for the conservation of a functional homologue of the metazoan CSN, which mediates control of cullin neddylation in budding yeast
Neurospora COP9 Signalosome Integrity Plays Major Roles for Hyphal Growth, Conidial Development, and Circadian Function
The COP9 signalosome (CSN) is a highly conserved multifunctional complex that has two major biochemical roles: cleaving NEDD8 from cullin proteins and maintaining the stability of CRL components. We used mutation analysis to confirm that the JAMM domain of the CSN-5 subunit is responsible for NEDD8 cleavage from cullin proteins in Neurospora crassa. Point mutations of key residues in the metal-binding motif (EXnHXHX10D) of the CSN-5 JAMM domain disrupted CSN deneddylation activity without interfering with assembly of the CSN complex or interactions between CSN and cullin proteins. Surprisingly, CSN-5 with a mutated JAMM domain partially rescued the phenotypic defects observed in a csn-5 mutant. We found that, even without its deneddylation activity, the CSN can partially maintain the stability of the SCFFWD-1 complex and partially restore the degradation of the circadian clock protein FREQUENCY (FRQ) in vivo. Furthermore, we showed that CSN containing mutant CSN-5 efficiently prevents degradation of the substrate receptors of CRLs. Finally, we found that deletion of the CAND1 ortholog in N. crassa had little effect on the conidiation circadian rhythm. Our results suggest that CSN integrity plays major roles in hyphal growth, conidial development, and circadian function in N. crassa
The Translation Initiation Factor 3f (eIF3f) Exhibits a Deubiquitinase Activity Regulating Notch Activation
The translation initiation factor complex eIF3f has an intrinsic deubiquitinase activity and regulates the Notch signaling pathway
Feinreliefstrukturen des Kolons bei Doppelkontrastaufnahmen : mit bes. BerĂĽcks. d. FrĂĽhformen von Colitis ulcerosa u. Colitis granulomatosa (Morbus Crohn)
Feinreliefstrukturen des Kolons bei Doppelkontrastaufnahmen : mit bes. BerĂĽcks. d. FrĂĽhformen von Colitis ulcerosa u. Colitis granulomatosa (Morbus Crohn)
Die Funktionen des COP9 Signalosoms und des assoziierten USP15 im Ubiquitin-Proteasomsystem
Das COP9 Signalosom (CSN) ist ein hoch konservierter Proteinkomplex, der an der Regulation des Ubiquitin (Ub)-26S Proteasomsystems (UPS) beteiligt ist. Das UPS ist die wichtigste Proteolysemaschinerie in eukaryotischen Zellen, bei der Proteine über eine dreistufige Kaskade der Enzyme E1-E3 mit einer Ub-Kette markiert werden, die als Erkennungssignal für den Abbau durch das 26S Proteasom dient. Das CSN gilt als Paralog zum Lid, einem Subkomplex des 26S Proteasoms, und interagiert mit einer Vielzahl von Proteinen, unter anderem mit E3-Ligasen und Kinasen. In dieser Arbeit konnte die direkte Bindung des CSN an das 26S Proteasom gezeigt werden, was zu einem Einfluss auf die Peptidaseaktivität des 26S Proteasoms in vitro führt. In Flag-Pulldown-Experimenten aus B8 Mausfibroblasten, die stabil mit Flag-CSN2 transfiziert waren, wurde ein vollständiger Flag-CSN-Komplex nachgewiesen, der mit dem 26S Proteasom assoziiert vorliegt. Co-Immunpräzipitationen beider Komplexe in vitro wiesen auf eine konzentrationsabhängige Verdrängung des Lid-Subkomplexes durch das CSN hin. Diese Interaktion führte zur Reduktion der proteolytischen Aktivität des 26S Proteasoms. Darüber hinaus wurde eine assoziierte deubiquitinierende Aktivität am CSN entdeckt und als USP15 identifiziert. Die Charakterisierung von USP15 zeigte, dass es durch die am CSN assoziierte Kinase CK2 phosphoryliert und stabilisiert wird. Erstmalig konnte durch Inhibitorstudien mit ortho-Phenanthrolin eine Metallabhängigkeit der Aktivität von USP15 nachgewiesen werden, die zur Identifizierung eines bisher unbekannten Zn-Fingers führte. Mutationsanalysen des Zn-Fingers zeigen, dass dieser für die Bindung und Spaltung von Ub-Ketten, nicht aber von linearen Ub-Konstrukten, notwendig ist. In Zellexperimenten konnte nachgewiesen werden, dass USP15 die E3 Ligase Rbx1 stabilisiert, was vermutlich auf eine Umkehr der Autoubiquitinierung zurückzuführen ist. Das CSN scheint somit sowohl das 26S Proteasom als auch die E3-Ligasen direkt zu beeinflussen. Die Ergebnisse dieser Arbeit stellen eine Vertiefung der Erkenntnisse über das CSN als Regulator des UPS dar.The COP9 signalosome (CSN) is a conserved protein complex that is involved in the regulation of the ubiquitin (Ub)/26S proteasome system (UPS). The UPS is the most important degradation machinery in eukaryotic cells. By the concerted action of three enzymes, E1-E3, proteins are labelled with a Ub-chain that serves as a recognition signal for the degradation by the 26S proteasome. The CSN is homologous to the lid, a subcomplex of the 26S proteasome, and interacts with numerous proteins, including E3 Ub ligases and kinases. In this study a direct interaction of the CSN with the 26S proteasome could be shown which has consequences for the peptidase activity of the 26S proteasome in vitro. In Flag-pull-down experiments from mouse B8 fibroblasts, that permanently expressed Flag-CSN2, an intact Flag-CSN complex was detected that is associated with the 26S proteasome. Co-immunoprecipitation of both complexes in vitro indicated a concentration-dependent replacement of the lid subcomplex by the CSN. This interaction led to a decrease of the proteolytic activity of the 26S proteasome. Moreover, a deubiquitinating activity associated with the CSN was discovered and identified as USP15. The USP15 was phosphorylated by the CSN-associated kinase CK2 that stabilised the enzyme. For the first time inhibitor studies with ortho-phenanthroline demonstrated a metal-dependency for the activity of USP15 that could be attributed to a formerly unidentified Zn-finger. Mutational analysis of the Zn-finger showed that it is necessary for the binding and cleavage of poly-Ub-chains but not for linear Ub-constructs. Cell culture experiments demonstrated a stabilisation of the E3 ligase Rbx1 by USP15 most likely by reversing its autoubiquitination. Therefore the CSN seems to directly influence the 26S proteasome as well as E3 ligases in their functions. These results expand the present knowledge on the CSN as a regulator of the UPS
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