Untersuchungen zur Strahlensensitivität von NBS Zellen

Das Nijmegen Breakage Syndrom (NBS) gehört zur Gruppe der humanen, vererbbaren Chromosomeninstabilitätssyndromen mit einem pleiotrophen Phänotyp. Betroffene Personen sind homozygot für eine Mutation im NBS1 Gen, die zu einem Ausfall der Bildung eines funktionellen Genproduktes führt. NBS Patienten reagieren u. a. empfindlicher auf ionisierende Bestrahlung, sind immundefizient und entwickeln mit erhöhter Wahrscheinlichkeit maligne Erkrankungen. Durch die vergleichende Analyse von zwei Zellpaaren mit NBS1-/- lymphoblastoiden Zelllinien und ihren entsprechenden NBS1+/- Linien, die aus Zellen von blutsverwandten Personen generiert wurden, wurden mögliche Ursachen für den auf zellulärer Ebene gut charakterisierten Phänotyp der erhöhten Strahlensensitivität der NBS1-/- Linien untersucht. Die Analyse einer möglichen differentiellen Genexpression in diesen Zelllinien mittels DNA Microarraytechnologie ergab nur ein signifikant minderexprimiertes Gen in den NBS1-/- Linien beider Zellpaare: LCK. Dieses Gen ist an der positiven Regulation der strahleninduzierten Apoptose in B- und T-Zellen beteiligt, weshalb die Rolle von NBS1 für die Regulation der strahleninduzierte Apoptose untersucht wurde. Es konnte gezeigt werden, dass NBS1-/- Zellen verglichen mit den entsprechenden NBS1+/- Zellen eine erhöhte Induktion von Apoptose nach gamma-Bestrahlung aufweisen. Die Analyse des Apoptoseweges demonstrierte die negative Regulation des CD95 vermittelten Weges durch NBS1. Die erhöhte strahleninduzierte Apoptose ist eine gute Erklärungsmöglichkeit für die beschriebene erhöhte Strahlensensitivität von NBS Zellen, da die Reparatur von DNA Doppelstrangbrüchen (DSB) von der NBS1 Mutation nicht beeinträchtigt wird und somit keine Erklärung für diesen Phänotyp bietet. Möglicherweise beeinflusst NBS1 aber die Regulation der beiden DSB Reparaturwege homologe Rekombination oder nicht-homologe Endverknüpfung. Um zukünftig das Ausmaß der Verwendung dieser beiden Reparaturwege in NBS1 defizienten Zellen studieren zu können, wurde ein Vektorsystem entwickelt, das die Quantifizierung der Verwendung dieser DSB Reparaturwege durch Analyse von Fluoreszenzmarken nach sequenzspezifischer Induktion von DSB in vivo ermöglicht. Neben der Rolle von LCK in der Regulation der Apoptose ist LCK als T-zellspezifisches Protein insbesondere an der T-Zellaktivierung beteiligt. Deshalb wurde die Rolle von NBS1 für die Regulation der LCK Expression in einer T-Zelllinie untersucht (Jurkat), um so möglicherweise eine weitere Ursache für die Immundefizienz der NBS Patienten beschreiben zu können. Allerdings ist die LCK Expression in diesen Zellen unabhängig von NBS1

Examining Sport Team Identification, Social Connections, and Social Well-being among High School Students

Past research has found that sport team identification is positively correlated with social psychological health (Phua, 2012; Wann & Weaver, 2009) including work testing adolescent fans (Wann, Brasher, Thomas, & Scheuchner, in press).  The current study was designed to extend previous investigations by examining the relationship between team identification and the establishment and maintenance of social connections.  Data from 177 high school students confirmed expectations as identification with a high school football team was positively correlated with both social well-being and social connections.  However, social connections were not found to mediate the relationship between identification and well-being, contrary to the team identification – social psychological health model (Wann, 2006b)

The RING finger ATPase Rad5p of Saccharomyces cerevisiae contributes to DNA double-strand break repair in a ubiquitin-independent manner

Tolerance to replication-blocking DNA lesions is achieved by means of ubiquitylation of PCNA, the processivity clamp for replicative DNA polymerases, by components of the RAD6 pathway. In the yeast Saccharomyces cerevisiae the ubiquitin ligase (E3) responsible for polyubiquitylation of the clamp is the RING finger protein Rad5p. Interestingly, the RING finger, responsible for the protein's E3 activity, is embedded in a conserved DNA-dependent ATPase domain common to helicases and chromatin remodeling factors of the SWI/SNF family. Here, we demonstrate that the Rad5p ATPase domain provides the basis for a function of the protein in DNA double-strand break repair via a RAD52- and Ku-independent pathway mediated by the Mre11/Rad50/Xrs2 protein complex. This activity is distinct and separable from the contribution of the RING domain to ubiquitin conjugation to PCNA. Moreover, we show that the Rad5 protein physically associates with the single-stranded DNA regions at a processed double-strand break in vivo. Our observations suggest that Rad5p is a multifunctional protein that—by means of independent enzymatic activities inherent in its RING and ATPase domains—plays a modulating role in the coordination of repair events and replication fork progression in response to various different types of DNA lesions

Investigating the Impact of Team Identification on the Willingness to Commit Verbal and Physical Aggression by Youth Baseball Spectators

The current investigation was designed to extend previous work on the aggressive actions of youth baseball spectators (Hennessy & Schwartz, 2007) by incorporating team identification into the research. Team identification, the extent to which a fan feels a psychological connection to a team, (Wann, Melnick, Russell, & Pease, 2001) has been found to be an important predictor of a wide variety of aggressive actions among sport consumers (Wann, 2006). Spectators (N = 80) at youth baseball games completed a questionnaire packet assessing demographics, team identification, vengeance, anger, hostility, and the likelihood of acting in a verbally or physically aggressive manner toward a number of potential targets (e.g., officials, opposing players). Consistent with expectations, team identification predicted a willingness to commit verbally aggressive acts. However, identification did not predict physical aggression

Denture-related stomatitis is associated with endothelial dysfunction

Oral inflammation, such as periodontitis, can lead to endothelial dysfunction, accelerated atherosclerosis, and vascular dysfunction. The relationship between vascular dysfunction and other common forms of oral infections such as denture-related stomatitis (DRS) is unknown. Similar risk factors predispose to both conditions including smoking, diabetes, age, and obesity. Accordingly, we aimed to investigate endothelial function and major vascular disease risk factors in 44 consecutive patients with dentures with clinical and microbiological features of DRS (n = 20) and without DRS (n = 24). While there was a tendency for higher occurrence of diabetes and smoking, groups did not differ significantly in respect to major vascular disease risk factors. Groups did not differ in main ambulatory blood pressure, total cholesterol, or even CRP. Importantly, flow mediated dilatation (FMD) was significantly lower in DRS than in non-DRS subjects, while nitroglycerin induced vasorelaxation (NMD) or intima-media thickness (IMT) was similar. Interestingly, while triglyceride levels were normal in both groups, they were higher in DRS subjects, although they did not correlate with either FMD or NMD. Conclusions. Denture related stomatitis is associated with endothelial dysfunction in elderly patients with dentures. This is in part related to the fact that diabetes and smoking increase risk of both DRS and cardiovascular disease

Thinking like a man? The cultures of science

Culture includes science and science includes culture, but conflicts between the two traditions persist, often seen as clashes between interpretation and knowledge. One way of highlighting this false polarity has been to explore the gendered symbolism of science. Feminism has contributed to science studies and the critical interrogation of knowledge, aware that practical knowledge and scientific understanding have never been synonymous. Persisting notions of an underlying unity to scientific endeavour have often impeded rather than fostered the useful application of knowledge. This has been particularly evident in the recent rise of molecular biology, with its delusory dream of the total conquest of disease. It is equally prominent in evolutionary psychology, with its renewed attempts to depict the fundamental basis of sex differences. Wars over science have continued to intensify over the last decade, even as our knowledge of the political, economic and ideological significance of science funding and research has become ever more apparent

The SPectrometer for Ice Nuclei (SPIN): an instrument to investigate ice nucleation

The SPectrometer for Ice Nuclei (SPIN) is a commercially available ice nucleating particle (INP) counter manufactured by Droplet Measurement Technologies in Boulder, CO. The SPIN is a continuous flow diffusion chamber with parallel plate geometry based on the Zurich Ice Nucleation Chamber and the Portable Ice Nucleation Chamber. This study presents a standard description for using the SPIN instrument and also highlights methods to analyze measurements in more advanced ways. It characterizes and describes the behavior of the SPIN chamber, reports data from laboratory measurements, and quantifies uncertainties associated with the measurements. Experiments with ammonium sulfate are used to investigate homogeneous freezing of deliquesced haze droplets and droplet breakthrough. Experiments with kaolinite, NX illite, and silver iodide are used to investigate heterogeneous ice nucleation. SPIN nucleation results are compared to those from the literature. A machine learning approach for analyzing depolarization data from the SPIN optical particle counter is also presented (as an advanced use). Overall, we report that the SPIN is able to reproduce previous INP counter measurements

Níveis De Estresse Oxidativo Ao Diagnóstico E Sua Associação Com O Perfil De Sobrevida Em Pacientes Portadoras De Câncer De Mama Operáveis Em Estadios Iniciais: Um Estudo Piloto

AAltos níveis de estresse oxidativo têm sido associados pior prognóstico do câncer de mama, mas não se sabe sua relação como possível preditor de sobrevida. Neste estudo investigamos a associação entre os níveis circulantes de estresse oxidativo no momento do diagnóstico e o perfil de sobrevida de pacientes portadoras de tumores de mama operáveis. Foi realizado um estudo prospectivo em uma população de 606 pacientes do sexo feminino com tumores de mama em estadios iniciais entre os anos de 2015-2020. Dentre essas pacientes, 18 vieram a óbito no seguimento do estudo, sendo pareadas com 36 pacientes que permaneceram vivas no período do estudo. Amostras de sangue foram coletadas ao diagnóstico, e os níveis de estresse quantificados por meio da dosagem dos metabólitos do óxido nítrico (NO) e perfil de peroxidação lipídicaplasmática. No grupo óbito, observou-se perfil de lipoperoxidação plasmática e níveis de NO elevados ao diagnóstico, quando comparado ao grupo de pacientes vivas. Altos níveis de lipoperoxidação plasmática foram diretamente relacionados com o desenvolvimento de metástases no grupo de pacientes vivas. Os resultados sugerem que o perfil oxidativo sistêmico aumentado ao diagnóstico observado em portadoras de câncer de mama está diretamente relacionado ao desfecho óbito em 5 anos.