Etablierung von SNaPshot-Assays zur Charakterisierung Y-chromosomaler Haplogruppen – ein Teilprojekt zur Bestimmung der Ursprungspopulation unbekannter Tatortspuren

Eine der wichtigsten Methoden in der internationalen Verbrechensbekämpfung ist die Erstellung individualspezifischer Desoxyribonukleinsäure-Profile (engl. deoxyribonucleic acid (DNA)), anhand derer Tatortspuren einem Tatverdächtigen zugeordnet werden können. Gibt es keine Hinweise auf mögliche Tatverdächtige, so kann die Ursprungspopulation einer unbekannten DNA-Spur des Tatortes für die polizeilichen Ermittlungsarbeiten von großer Bedeutung sein. Bei männlichen Spuren liefert, neben autosomalen Einzelnukleotid-Polymorphismen (engl. single nucleotide polymorphisms (SNPs)) und Polymorphismen mitochondrialer DNA (mtDNA), die Y-chromosomale Haplogruppe einen wichtigen Hinweis auf die ursprüngliche Herkunft des Spurenlegers. Sie ist über die Allelausprägung bestimmter Einzelnukleotid-Polymorphismen auf dem Y-Chromosom definiert. Das Vorkommen sowie die Verteilung solcher Haplogruppen kann in unterschiedlichen Populationen stark variieren. In dieser Studie wurden drei Minisequencing-Assays mit insgesamt 45 SNPs des Y-Chromosoms zusammengestellt und etabliert. Der Prozess der Etablierung beinhaltete das Erstellen zuverlässiger Multiplex-Polymerasekettenreaktionen-Assays (engl. polymerase chain reaction (PCR)) und SNaPshot-Multiplex-PCR-Assays, die auch geringe DNA-Mengen sowie degradierte DNA zuverlässig analysieren können. Die Kombination der Y-SNPs in den Minisequencing-Assays erlaubt eine eindeutige Zuordnung zu bestimmten, im Vorfeld ausgesuchten Y-Haplogruppen. Anschließend wurden die erstellten Minisequencing-Assays verifiziert, indem die Verteilung der Y-chromosomalen Haplogruppen in insgesamt 385 Personen aus Nordeuropa, vom Balkan, aus der Türkei, dem Nahen Osten, sowie aus Nord- und Westafrika bestimmt wurde. Dabei konnten metapopulationsspezifische Haplogruppen (Hg), wie beispielsweise Hg E1b1a für Westafrika, ermittelt werden. Es zeigte sich allerdings auch, dass andere Haplogruppen in mehreren Metapopulationen in etwa gleichen Anteilen vorkommen, wie zum Beispiel Haplogruppe J1e in Nordafrika, dem Nahen Osten und der Türkei. Anhand einiger Beispiele konnte nachgewiesen werden, dass die Y-chromosomalen Haplogruppen eine wichtige Ergänzung zur Analyse autosomaler SNPs sind

FIP200 Claw Domain Binding to p62 Promotes Autophagosome Formation at Ubiquitin Condensates

The autophagy cargo receptor p62 facilitates the condensation of misfolded, ubiquitin-positive proteins and their degradation by autophagy, but the molecular mechanism of p62 signaling to the core autophagy machinery is unclear. Here, we show that disordered residues 326–380 of p62 directly interact with the C-terminal region (CTR) of FIP200. Crystal structure determination shows that the FIP200 CTR contains a dimeric globular domain that we designated the “Claw” for its shape. The interaction of p62 with FIP200 is mediated by a positively charged pocket in the Claw, enhanced by p62 phosphorylation, mutually exclusive with the binding of p62 to LC3B, and it promotes degradation of ubiquitinated cargo by autophagy. Furthermore, the recruitment of the FIP200 CTR slows the phase separation of ubiquitinated proteins by p62 in a reconstituted system. Our data provide the molecular basis for a crosstalk between cargo condensation and autophagosome formation

Newly Developed CK1-Specific Inhibitors Show Specifically Stronger Effects on CK1 Mutants and Colon Cancer Cell Lines

Protein kinases of the CK1 family can be involved in numerous physiological and pathophysiological processes. Dysregulated expression and/or activity as well as mutation of CK1 isoforms have previously been linked to tumorigenesis. Among all neoplastic diseases, colon and rectal cancer (CRC) represent the fourth leading cause of cancer related deaths. Since mutations in CK1δ previously found in CRC patients exhibited increased oncogenic features, inhibition of CK1δ is supposed to have promising therapeutic potential for tumors, which present overexpression or mutations of this CK1 isoform. Therefore, it is important to develop new small molecule inhibitors exhibiting higher affinity toward CK1δ mutants. In the present study, we first characterized the kinetic properties of CK1δ mutants, which were detected in different tumor entities. Subsequently, we characterized the ability of several newly developed IWP-based inhibitors to inhibit wild type and CK1δ mutants and we furthermore analyzed their effects on growth inhibition of various cultured colon cancer cell lines. Our results indicate, that these compounds represent a promising base for the development of novel CRC therapy concepts

Measuring Life Skills: Standardizing the Assessment of Youth Development Indicators

While the development of life skills (e.g., communication, problem solving, etc.) is a commonly targeted youth program outcome, the lack of standardized conceptualizations and instrumentation make it difficult to compare impacts across programs and develop validated best practices. In order to promote a more unified approach to life skill development, literature reviews were conducted for 10 life skill domains to identify common definitions and, if available, appropriate outcome measures. Data were then collected from an ethnically diverse sample (N = 758) of elementary, middle, and high school aged youth for the 10 identified instruments. Analyses were conducted to ascertain the psychometric qualities of each measure, the interrelationships among measures, and the measures’ relationships with gender, ethnicity, and school level. Results are discussed in terms of their relevance to life skill theory and measurement

Sea Turtles and Survivability in Demersal Trawl Fisheries: Do Comatose Olive Ridley Sea Turtles Survive Post-Release?

Incidental capture of air‑breathing species in fishing gear is a major source of mortality for many threatened populations. Even when individuals are discarded alive, they may not survive due to direct injury, or due to more cryptic internal physiological injury such as decompression sickness. Post‑release mortality, however, can be difficult to determine. In this pilot study, we deployed survivorship pop‑up archival tags (sPAT) (n = 3) for an air‑breathing species, the olive ridley sea turtle (Lepidochelys olivacea), one of the first studies to do so. We found that at least two of the three turtles survived after being captured in demersal fish trawl nets and being resuscitated from a comatose state following standard UN Food and Agriculture Organization guidelines. One turtle died; however, the absence of a change in light level but continued diving activity suggested that the turtle was likely predated. Whether capture contributed to the turtle’s susceptibility to predation post‑release is unknown, and average tow duration during this fishing trip was similar in duration to that of a turtle that survived (1.5 h). The two surviving turtles displayed normal horizontal and vertical movements based on previous tagging studies. This study suggests that resuscitation techniques may be effective; however, additional study is necessary to increase sample sizes, and to determine the severity of decompression sickness across different levels of activity and in other fishing gears. This will result in better population mortality estimates, as well as highlight techniques to increase post‑release survivorship

The relationship between working conditions and self-rated health among medical doctors: evidence from seven waves of the Medicine In Australia Balancing Employment and Life (Mabel) survey

BACKGROUND: Psychosocial job stressors, such as low control and high demands, have been found to influence the health and wellbeing of doctors. However, past research in this area has relied on cross-sectional data, which limits causal inferences about the influence of psychosocial job stressors on health. In this study, we examine this relationship longitudinally while also assessing whether the relationship between psychosocial job stressors and health is modified by gender. METHODS: The data source was seven annual waves of the Medicine in Australia: Balancing Employment and Life (MABEL) survey. The outcome was self-rated health (measured using the SF-12), and key exposures reflected job control, job demands, work-life balance variables, employment arrangements, and aggression experienced at work. We used longitudinal fixed and random effects regression models to assess within and between-person changes in health. RESULTS: Excessive job demands, low job control, feelings of not being rewarded at work, and work-life imbalance were associated with higher within-person odds of poorer self-rated health. Gender differences were apparent. For female doctors, work arrangements and work-life imbalance were associated with poorer self-rated health whilst task-based job stressors were associated with poorer self-rated health in male doctors. CONCLUSIONS: These results suggest the importance of addressing adverse working environments among doctors

The Grizzly, December 4, 2003

Bringing Washington to Ursinus: Congress to Campus a Success • To Give is Better than to Receive: The Season of Generosity • Saying Goodbye to the Grizzly • Opinions: Holidays Hitting you too Soon?; New Year\u27s Resolutions Through the Years; Necessary Evils of Resolutions; Intramural Sports: Not Just Fun • Final Exam Schedule • Berman Exhibit • ProTheatre Play a Success • Four Women Soccer Players Named All Conference • Men\u27s and Women\u27s Basketball off to a Good Start • Ursinus Wrestling Dominates at Home • Stanton Named Player of the Week • Steroids in Pro Sportshttps://digitalcommons.ursinus.edu/grizzlynews/1550/thumbnail.jp

Reproductive isolation between two populations of Aglaoctenus lagotis , a funnel-web wolf spider

Aglaoctenus lagotis (Lycosidae: Sosippinae) is a spider that, in contrast to the predominant wandering habit of the family, constructs funnel webs. The species is widely distributed throughout the Neotropics and is credited with high levels of intraspecific variation. Here, we evaluate whether reproductive isolating barriers operate between some populations of A. lagotis. We used heterotypic encounters between individuals from two distant localities: southern Uruguay (SU) and Central Argentina (CA). Additionally, we used spiders from an ntermediate locality, western Uruguay (WU), where both forms of the species overlap (SU.WU was used to describe individuals from WU reminiscent of those from SU; and CA.WU was used to describe individuals from WU reminiscent of those from CA). No copulations occurred between SU and CA individuals, whereas a single and atypical copulation occurred between SU.WU and CA.WU individuals. Attacks (only by females on males) were rare. In tests of choice based on silk cues, SU males did not prefer homotypic cues but almost did not court CA females, whereas CA males preferred homotypic cues but usually courted heterotypic females. These findings, with a previously reported temporal asynchrony between populations, suggest the occurrence of reproductive isolation between both spider forms and a speciation process favoured by the wide distribution and plasticity of the species.Fil: González Pérez, María de la Macarena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Diversidad y Ecología Animal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Diversidad y Ecología Animal; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Diversidad Animal I; ArgentinaFil: Peretti, Alfredo Vicente. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Diversidad y Ecología Animal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Diversidad y Ecología Animal; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Cátedra de Diversidad Animal I; ArgentinaFil: Costa, Fernando G.. Instituto de Investigaciones Biológicas "Clemente Estable"; Urugua

The Grizzly, October 16, 2003

Feeling Drained for a Good Cause: Omega Chi Blood Drive • CAB Laugh-off Left Students Rolling in the Aisles • UC in the City Program Announces Easier Access to Philly • Political Pagemakers: Democratic Candidates for President • California Recall Circus has its Star • Club Spotlight: Forensics • Opinions: UC in the City: An Attempt to Fight the Boredom; California Recall Election Democracy at its Best; Video Games as Government Training Tools; Flu Season is Near; Legal BAC Should Still be Lower; Myrin Library: Use It • On the Verge Review: Memorable • Believe it or Not: A Tree in the End Zone • Meet Dr. Zwerling • Job Fair Success • 2003 Homecoming Court • Women\u27s Rugby: A Tough and Spirited Group of Ladies • Field Hockey Team Remains Undefeated in Conference • Men\u27s Soccer Continues to Face Tough Losses • Volleyball 2-3 in Conference Play • Sue Hadfield Named Head Swimming Coachhttps://digitalcommons.ursinus.edu/grizzlynews/1545/thumbnail.jp