746 research outputs found
Lucille Clifton, 5th Annual ODU Literary Festival
No full textLucille Clifton, currently poet laureate of Maryland, is the author of four collections of poetry: Good Times, Good News About the Earth, An Ordinary Woman, and Two-Headed Woman, which was awarded the Juniper Prize by the University of Massachusetts Press. In addition, she is the author of 15 children\u27s books and a family memoir titled Generations. The recipient of two NBA awards, she is an active member of P.E.N. International and the Maryland State Committee for Black Art and Culture. Her memorable poetry reading opened the 1980 ODU Literary Festival. Clifton is a board member of the Associated Writing Programs
Lucille Clifton: 11-12-1987
No full textLucille Clifton was one of America's leading poets.She was the author of six collections of poetry as well as more than a dozen books of fiction and poetry for children. She is interviewed by Stan Rubin and Anthony Piccione.Archived web contentSUNY BrockportWriters Forum Video
Lucille Clifton: 11-12-1987
No full textLucille Clifton was one of America\u27s leading poets.She was the author of six collections of poetry as well as more than a dozen books of fiction and poetry for children. She is interviewed by Stan Rubin and Anthony Piccione.https://digitalcommons.brockport.edu/writers_videos/1045/thumbnail.jp
The length of FOXE1 polyalanine tract in congenital hypothyroidism: Evidence for a pathogenic role from familial, molecular and cohort studies
No full textIntroductionFOXE1 is required for thyroid function and its homozygous mutations cause a rare syndromic form of congenital hypothyroidism (CH). FOXE1 has a polymorphic polyalanine tract whose involvement in thyroid pathology is controversial. Starting from genetic studies in a CH family, we explored the functional role and involvement of FOXE1 variations in a large CH population. MethodsWe applied NGS screening to a large CH family and a cohort of 1752 individuals and validated these results by in silico modeling and in vitro experiments. ResultsA new heterozygous FOXE1 variant segregated with 14-Alanine tract homozygosity in 5 CH siblings with athyreosis. The p.L107V variant demonstrated to significantly reduce the FOXE1 transcriptional activity. The 14-Alanine-FOXE1 displayed altered subcellular localization and significantly impaired synergy with other transcription factors, when compared with the more common 16-Alanine-FOXE1. The CH group with thyroid dysgenesis was largely and significantly enriched with the 14-Alanine-FOXE1 homozygosity. DiscussionWe provide new evidence that disentangle the pathophysiological role of FOXE1 polyalanine tract, thereby significantly broadening the perspective on the role of FOXE1 in the complex pathogenesis of CH. FOXE1 should be therefore added to the group of polyalanine disease-associated transcription factors
Abstract 5475: Functional profiling of germline <i>EPAS1</i> variants associated with pheochromocytoma and paraganglioma
No full textAbstract
Background: Endothelial PAS domain-containing protein 1 (EPAS1), encoding hypoxia-inducible transcription factor 2-alpha (HIF2α), is involved in regulation of cellular hypoxia responses and has been shown to play a role in several cancers including renal cell cancer and pheochromocytoma/paraganglioma (PPGL). HIF2 levels are tightly regulated, being low in normoxia but increased in hypoxia. Studying heritable PPGL syndromes has uncovered diverse genetic events that lead to oxygen-independent HIF stabilization. Using massively parallel sequencing, we noted several germline EPAS1 variants that occurred in subjects also carrying pathogenic mutations in either VHL or SDHB. In addition, two distinct EPAS1 variants were identified in separate individuals who did not harbor germline mutation in other known susceptibility genes. We therefore investigated whether these variants affected EPAS1 function.
Method: Six different EPAS1 variants were identified in the germline of patients with PPGL; p.His194Arg, p.Arg247Ser, p.Phe374Tyr, p.Thr766Pro, p.Pro785Thr and p.Ile789Val. GFP-tagged HIF2α expressing constructs - expressing either empty vector, wildtype or mutant HIF2α- were generated (including positive control p.Pro531Thr) and transfected into HEK293 cells. HEK293 cells transfected with wildtype HIF2α were also subjected to hypoxic conditions for use as a positive control. Co-immunoprecipitation followed by Western blotting analyses were performed to determine whether: a) HIF2α mutants are still able to interact with VHL and ARNT; and b) HIF2α mutants are stabilized under normoxia. Candidate target gene expression (CCND1 and SLC2A) was measured by RT-qPCR.
Results: Western blot analyses showed that p.Arg247Ser, p.Phe374Tyr, p.Pro531Thr and p.Pro785Thr amino acid changes in HIF2α were all more stable than wild-type HIF2α under normoxia. Co-IP of HIF2α with VHL showed significantly reduced interaction with p.Arg247Ser and p.Pro531Thr (p&lt;0.05). Co-IP of HIF2α with ARNT failed to show any effect on interaction occurring as a result of the HIF2α variants. Interestingly only p.Pro531Thr was able to induce CCND1 and SLC2A gene expression (p&lt;0.05).
Conclusion: Germline EPAS1 variants p.Arg247Ser and p.Phe374Tyr share some functional features in common with the known oncogenic somatic variant p.Pro531Thr. These variants may therefore be functionally relevant to developing cancers that are dependent upon pseudo-hypoxia. Whether any of these EPAS1 variants will affect response to HIF2α antagonist therapies is yet unknown and may be of importance.
Citation Format: Edward Kim, Diana E. Benn, Roderick J. Clifton-Bligh, Trisha Dwight. Functional profiling of germline EPAS1 variants associated with pheochromocytoma and paraganglioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5475. doi:10.1158/1538-7445.AM2017-5475</jats:p
Exercise for postmenopausal bone health – Can we raise the bar?
No full textPurpose of Review: This review summarises the latest evidence on effects of exercise on falls prevention, bone mineral density (BMD) and fragility fracture risk in postmenopausal women, explores hypotheses underpinning exercise-mediated effects on BMD and sheds light on innovative concepts to better understand and harness the skeletal benefits of exercise. Recent Findings: Multimodal exercise programs incorporating challenging balance exercises can prevent falls. Emerging clinical trial evidence indicates supervised progressive high-intensity resistance and impact training (HiRIT) is efficacious in increasing lumbar spine BMD and is safe and well-tolerated in postmenopausal women with osteoporosis/osteopenia. There remains uncertainty regarding durability of this load-induced osteogenic response and safety in patients with recent fractures. Muscle-derived myokines and small circulating extracellular vesicles have emerged as potential sources of exercise-induced muscle-bone crosstalk but require validation in postmenopausal women. Summary: Exercise has the potential for multi-modal skeletal benefits with i) HiRIT to build bone, and ii) challenging balance exercises to prevent falls, and ultimately fractures. The therapeutic effect of such exercise in combination with osteoporosis pharmacotherapy should be considered in future trials
Detective quest for author, alter ego Clifton and this thesis
No full textMůj případ Clifton je detektivní spis/esej. Nacházení souvislostí mezi autorem a fiktivní postavou detektiva Cliftona. Součástí této práce jsou autorovy úvahy, reflexe i sebereflexe, popisy situací z reálného života a grafy či obrázky. Jde tedy o pátrání na základě těchto stop a jejich souvislostí, které generují radost z nacházení a objevování, otázky i odpovědi, ale i krizi a zklamání. Vedou však k jisté katarzi, která se v tomto případu zdá být hlavním podezřelým nebo dokonce pachatelem.My case Clifton is a detective essay. Finding connections between the author and the fictional character of Detective Clifton. This work includes the author's, reflection and self-reflection, descriptions of real-life situations and graphs or pictures. It is searching based on these clues and their connections, which generate the joy of finding and discovering, questions and answers, but also crisis and disappointment. However, they lead to some catharsis, which in this case seems to be the main suspect or even the perpetrator
Play-Girl
No full textGift of Richard N. Hurley. Norman Bligh is a pseudonym for American author William Arthur Neubauerhttps://digitalcommons.risd.edu/picturecollection_pulpfictioncovers/1145/thumbnail.jp
Mokita style illustration symposium
No full textFor some it’s a creative straitjacket, for others the Holy Grail – whether it be mimicry or origination, style in illustration can mean polar opposites, and is the subject of the third MOKITA conference at Somerset House. Planned in spring 2014, the subject has been explored in the current issue ofVaroommagazine and discussed at September’s Crowd Talks at Hoxton Gallery. This is an opportunity to further debate and define the term. With an invited panel of speakers and guest chair, both sides of the case will made pitching style versus content, imitation versus sincerity, and semiotics versus aesthetics. Confirmed speakers include George Hardie, Lawrence Zeegen, Luise Vormittag, Catrin Morgan, John O’Reilly, and Crowd Talks. Both the divergent and emergent aspects of 21st-century illustration will be examined in this latest instalment, intended to make a fit-for-purpose architecture for the subject. Purposely not aligned to any single education provider,MOKITAwas founded in 2010 to focus debate on the more uncharted and contentious aspects of illustration as a subject and practice. Its founders are Darryl Clifton (Camberwell College of Arts UAL), Geoff Grandfield (Kingston University London), and Roderick Mills (University of Brighton)
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