90 research outputs found
Pop Culture and Protofeminism: The Novels of Jacqueline Susann and the Second Wave of the Women\u27s Movement.
No full textDisagreement over the label feminist continues to elicit debate within the feminist movement and in society. Some contemporary feminists see protofeminism in Jacqueline Susann\u27s novels.
This work investigates the support Susann\u27s novels offered to the second wave of the feminist movement of the 1960s and the 1970s. A close reading of Susann\u27s best-selling novels, Valley of the Dolls (1966), The Love Machine (1969), and Once is Not Enough (1973) was combined with a study of the author\u27s biography, works by second-wave feminists, and reviews and criticism of the novels. Further evidence was gathered through research of the socioeconomic status of women during relevant periods and viewing the novels from the perspective of the feminist movement\u27s second wave.
Placing the novels in their historical and socio-economic context proved that these works did not offer support to the movement. Instead, they advocated women\u27s continued status as oppressed citizens
Mutations in TAF8 cause a neurodegenerative disorder
No full textAbstract TAF8 is part of the transcription factor II D complex, composed of the TATA-binding protein and 13 TATA-binding protein–associated factors (TAFs). Transcription factor II D is the first general transcription factor recruited at promoters to assemble the RNA polymerase II preinitiation complex. So far disorders related to variants in 5 of the 13 subunits of human transcription factor II D have been described. Recently, a child with a homozygous c.781-1G>A mutation in TAF8 has been reported. Here we describe seven further patients with mutations in TAF8 and thereby confirm the TAF8 related disorder. In two sibling patients, we identified two novel compound heterozygous TAF8 splice site mutations, c.45+4A > G and c.489G>A, which cause aberrant splicing as well as reduced expression and mislocalization of TAF8. In five further patients, the previously described c.781-1G > A mutation was present on both alleles. The clinical phenotype associated with the different TAF8 mutations is characterized by severe psychomotor retardation with almost absent development, feeding problems, microcephaly, growth retardation, spasticity and epilepsy. Cerebral imaging showed hypomyelination, a thin corpus callosum and brain atrophy. Moreover, repeated imaging in the sibling pair demonstrated progressive cerebral and cerebellar atrophy. Consistently, reduced N-acetylaspartate, a marker of neuronal viability, was observed on magnetic resonance spectroscopy. Further review of the literature shows that mutations causing a reduced expression of transcription factor II D subunits have an overlapping phenotype of microcephaly, developmental delay and intellectual disability. Although transcription factor II D plays an important role in RNA polymerase II transcription in all cells and tissues, the symptoms associated with such defects are almost exclusively neurological. This might indicate a specific vulnerability of neuronal tissue to widespread deregulation of gene expression as also seen in Rett syndrome or Cornelia de Lange syndrome
Reproducibility for everyone - a quick primer on how to make your research more reproducible
No full textPerforming science is like running a marathon - it takes a long time to finish, needs good preparation and requires excellent performance. In order to make the outcome of one researchers efforts valuable for other researchers a few best practises should be adopted. This poster describes seven easy steps that every researcher can follow in order to make their own research more reproducible. The seven steps cover data management, documentation and sharing of data, protocols and reagents.
Researchers that adopt some or all of the here presented best practises will benefit in the long term from better visibility of their work and save time in future projects or even during publication of their results.
This poster contains content that was created from the Reproducibility for Everyone community whose members can be found at www.repro4everyone.org and Twitter @repro4everyone. For further questions get in touch with the group or the author of this poster, Susann Auer, over Twitter @SusannAuer or at [email protected].
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Identification of Mutation Spectrum and Characterization of relevant Mutations in Multiple Myeloma
No full textDas Multiple Myelom (MM) ist eine maligne B-Zell-Erkrankung, welche von einer großen Heterogenität auf der biologischen und klinischen Ebene sowie in der Therapieantwort geprägt ist. Durch die biologische Interpretation von whole exome sequencing (WES)-Daten der Tumor- und Normalproben von fünf MM-Patienten und sechs MM-Zelllinien (ZL) sowie dem Einbezug von publizierten next generation sequencing (NGS)-Daten von 38 MM-Patienten konnten in dieser Dissertation sowohl somatische tumorrelevante Mutationen identifiziert als auch ein MM-spezifisches Signaltransduktionsnetzwerk definiert werden. Interessanterweise wurde in fast 100 % der MM-Patienten mindestens eine Mutation und in ~50 % der MM-Patienten sogar mehr als eine Mutation innerhalb dieses Netzwerkes beobachtet, was auf eine inter- und intra-individuelle Signalweg-Redundanz hinweist, die für die individuelle Therapieentscheidung möglicherweise von Bedeutung sein könnte. Außerdem konnte bestätigt werden, dass identische, positionsspezifische und genspezifische Mutationen im MM selten wiederholt auftreten. Als häufig mutierte Gene im MM konnten KRAS, NRAS, LRP1B, FAM46C, WHSC1, ALOX12B, DIS3 und PKHD1 identifiziert werden. Interessanterweise wurde die DIS3-Mutation in der MM-ZL OPM2 gemeinsam mit einer copy neutral loss of heterozygosity (CNLOH) im DIS3-Lokus detektiert, und in der MM-ZL AMO1 wurde eine noch nicht näher charakterisierte KRAS-Mutation in Exon 4 in Verbindung mit einem copy number (CN)-Zugewinn und einer erhöhten KRAS-Genexpression gefunden. DIS3 ist ein enzymatisch aktiver Teil des humanen RNA-Exosom-Komplexes und KRAS ein zentrales Protein im RTK-Signalweg, wodurch genetische Aberrationen in diesen Genen möglicherweise in der Entstehung oder Progression des MMs eine zentrale Rolle spielen. Daher wurde die gesamte coding sequence (CDS) der Gene DIS3 und KRAS an Tumorproben eines einheitlich behandelten Patientensets der DSMM-XI-Studie mit einem Amplikon-Tiefen-Sequenzierungsansatz untersucht. Das Patientenset bestand aus 81 MM-Patienten mit verfügbaren zytogenetischen und klinischen Daten. Dies ergab Aufschluss über die Verteilung der Mutationen innerhalb der Gene und dem Vorkommen der Mutationen in Haupt- und Nebenklonen des Tumors. Des Weiteren wurde die Assoziation der Mutationen mit weiteren klassischen zytogenetischen Alterationen (z.B. Deletion von Chr 13q14, t(4;14)-Translokation) untersucht und der Einfluss der Mutationen in Haupt- und Nebenklonen auf den klinischen Verlauf und die Therapieantwort bestimmt. Besonders hervorzuheben war dabei die Entdeckung von sieben neuen Mutationen sowie drei zuvor unbeschriebenen hot spot-Mutationen an den Aminosäure (AS)-Positionen p.D488, p.E665 und p.R780 in DIS3. Es wurde des Weiteren die Assoziation von DIS3-Mutationen mit einer Chr 13q14-Deletion und mit IGH-Translokationen bestätigt. Interessanterweise wurde ein niedrigeres medianes overall survival (OS) für MM-Patienten mit einer DIS3-Mutation sowie auch eine schlechtere Therapieantwort für MM-Patienten mit einer DIS3-Mutation im Nebenklon im Vergleich zum Hauptklon beobachtet. In KRAS konnten die bereits publizierten Mutationen bestätigt und keine Auswirkungen der KRAS-Mutationen in Haupt- oder Nebenklon auf den klinischen Verlauf oder die Therapieantwort erkannt werden. Erste siRNA vermittelte knockdown-Experimente von KRAS und Überexpressionsexperimente von KRAS-Wildtyp (WT) und der KRAS-Mutationen p.G12A, p.A146T und p.A146V mittels lentiviraler Transfektion zeigten eine Abhängigkeit der Phosphorylierung von MEK1/2 und ERK1/2 von dem KRAS-Mutationsstatus.
Zusammenfassend liefert die vorliegende Dissertation einen detaillierten Einblick in die molekularen Strukturen des MMs, vor allem im Hinblick auf die Rolle von DIS3 und KRAS bei der Tumorentwicklung und dem klinischen Verlauf.Multiple Myeloma (MM) is a malignant B-cell neoplasm that is characterized by a great heterogeneity on the biological and clinical level as well as by a heterogeneous response to therapeutic approaches. Biological interpretation of whole exome sequencing (WES) data of tumor and normal samples of five MM patients and six MM cell lines (CL), as well as the inclusion of published next generation sequencing (NGS) data of 38 MM patients, identified somatic tumor relevant mutations as well as a signal transduction network that was commonly affected in MM. Interestingly, almost 100 % of the MM patients harbored one mutation and ~50 % of the MM patients harbored more than one mutation in different genes of this defined network, which predicted an inter- and intra-individual pathway redundancy that might be of particular importance for individual therapeutic approaches. Furthermore, it was confirmed that the recurrent occurrence of point-specific mutations and even gene specific mutations are rare events in MM. KRAS, NRAS, LRP1B, FAM46C, WHSC1, ALOX12B, DIS3 and PKHD1 were among the most recurrently mutated genes in MM. Of note, one of the DIS3 mutations was accompanied by a copy neutral loss of heterozygosity (CNLOH) in the CL OPM2 and a so far undefined exon 4 mutation in KRAS was associated with an increased copy number (CN) and gene expression level of KRAS in the CL AMO1. DIS3 is one of the active parts of the human RNA exosome complex and KRAS is a central protein in the RTK pathway leading to the hypothesis that one or more genetic abberations within these genes may play an important role in the development and progression of MM. To further investigate this hypothesis the whole coding sequence (CDS) of DIS3 and KRAS of tumor samples of a uniquely treated patient set of the DSMM XI was sequenced using an amplicon deep sequencing approach. The study included 81 MM patients for whom cytogenetic and clinical data were available. This approach revealed information about the mutational landscape within DIS3 and KRAS and the occurrence of mutations in major and minor clones. In addition, we were able to investigate the association of the DIS3 and KRAS mutations with additional cytogenetic alterations (such as deletion of chr 13q14, translocation t(4;14)) and we studied the impact of mutations in major and minor clones on the clinical outcome and response to therapy. In particular, we discovered seven unknown mutations and three previously undescribed hot spot mutations at amino acid positions p.D488, p.E665 and p.R780 in DIS3. An association of DIS3 mutations with deletion of chr 13q14 and IGH-translocations, that was described previously, was confirmed. Interestingly, a trend towards a lower median overall survival of MM patients with a DIS3 mutation was observed. Patients with a DIS3 mutation in the minor clone also showed a worse response to therapy as compared to patients with a mutation in the major clone. Published mutations in KRAS were confirmed. Moreover, we revealed no impact of these mutations (in major or minor clones) on the clinical outcome or response to therapy. First siRNA mediated knockdown experiments on KRAS and lentivirus mediated overexpression of KRAS WT and mutated KRAS (p.G12A, p.A146T and p.A146V) showed that the phosphorylation status of MEK1/2 and ERK1/2 is dependent on the mutation status of KRAS.
In summary, this present doctoral thesis allowed more detailed insights into the molecular structure of MM, specifically with regard to the role of DIS3 and KRAS in tumor development and outcome
Development of the Illinois career readiness scale for college students with disabilities
No full textDespite the association between higher earnings and increased opportunities of employment with post-secondary education, the transition to employment is found to be difficult for college graduates with disabilities. The Illinois Career Readiness Scale (ICRS) was developed to address the career awareness and readiness levels of college students with disabilities. A goal of the ICRS is to address the career development needs and assist students with disabilities in the process of making more informed decisions in their career planning. The ICRS was developed based on the Cognitive Information Processing Theory (Peterson et al., 1991) and the Illinois Work and Well-Being Model (Strauser et al., 2015). The internal consistency was investigated, followed by construct validity by examining the relationship of subscales with appropriate correlational instruments. Multiple linear regression analyses were conducted to determine relationships between subscales of the ICRS and other variables. Preliminary results suggest initial support for the utilization of the ICRS as an instrument to measure an individual’s self-reported career readiness levels.Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2023-05-01The student, Susann Sears, accepted the attached license on 2021-04-08 at 11:05.The student, Susann Sears, submitted this Dissertation for approval on 2021-04-08 at 11:22.This Dissertation was approved for publication on 2021-04-09 at 16:11.DSpace SAF Submission Ingestion Package generated from Vireo submission #16256 on 2021-09-16 at 17:02:39Made available in DSpace on 2021-09-17T02:34:21Z (GMT). No. of bitstreams: 2
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Previous issue date: 2021-04-09Embargo set by: Seth Robbins for item 118490
Lift date: 2023-09-17T02:34:57Z
Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemAuthor requested U of Illinois access only (OA after 2yrs) in Vireo ETD systemU of I Onl
Identifizierung des Mutationsspektrums und Charakterisierung relevanter Mutationen im Multiplen Myelom = Identification of Mutation Spectrum and Characterization of relevant Mutations in Multiple Myeloma
No full textA novel remitting leukodystrophy associated with a variant in FBP2
No full textLeukodystrophies are genetic disorders of cerebral white matter that almost exclusively have a progressive disease course. We became aware of three members of a family with a disorder characterized by a sudden loss of all previously acquired abilities around 1 year of age followed by almost complete recovery within 2 years. Cerebral MRI and myelin sensitive imaging showed a pronounced demyelination that progressed for several months despite signs of clinical improvement and was followed by remyelination. Exome sequencing did not-identify any mutations in known leukodystrophy genes but revealed a heterozygous variant in the FBP2 gene, c.343G>A, p. Val115Met, shared by the affected family members. Cerebral MRI of other family members demonstrated similar white matter abnormalities in all carriers of the variant in FBP2. The FBP2 gene codes for muscle fructose 1,6-bisphosphatase, an enzyme involved in gluconeogenesis that is highly expressed in brain tissue. Biochemical analysis showed that the variant has a dominant negative effect on enzymatic activity, substrate affinity, cooperativity and thermal stability. Moreover, it also affects the non-canonical functions of muscle fructose 1,6-bisphosphatase involved in mitochondrial protection and regulation of several nuclear processes. In patients’ fibroblasts, muscle fructose 1,6-bisphosphatase shows no colocalization with mitochondria and nuclei leading to increased reactive oxygen species production and a disturbed mitochondrial network. In conclusion, the results of this study indicate that the variant in FBP2 disturbs cerebral energy metabolism and is associated with a novel remitting leukodystrophy
A Tide of Change: Stories of Marine Conservation Success
No full textSusann Rossbach from Red Sea Global, Lead Author for Saudi Arabia's Frontiers Planet Prize winning paper, presents compelling evidence that marine conservation success is not only possible, it’s already happening. By analyzing 217 verified case studies, her research reveals the social, ecological, and institutional ingredients behind effective ocean stewardship. Rossbach highlights the power of local engagement, multi-stakeholder collaboration, and targeted action against high-impact pressures like overfishing and pollution, reframing marine conservation as a dynamic, hopeful frontier in achieving global sustainability and staying within planetary boundaries.
The thought piece can be found on the Frontiers Planet Prize website and can be accessed via this link.
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