Functional Analysis of a Novel Potassium Channel (KCNA1) Mutation in Hereditary Mokymia

Myokymia is characterized by spontaneous, involuntary muscle fiber group contraction visible as vermiform movement of the overlying skin. Myokymia with episodic ataxia is a rare, autosomal dominant trait caused by mutations in KCNA1, encoding a voltage-gated potassium channel. In the present study, we report a family with four members affected with myokymia. Additional clinical features included motor delay initially diagnosed as cerebral palsy, worsening with febrile illness, persistent extensor plantar reflex, and absence of epilepsy or episodic ataxia. Mutation analysis revealed a novel c.676C>A substitution in the potassium channel gene KCNA1, resulting in a T226K nonconservative missense mutation in the Kv1.1 subunit in all affected individuals. Electrophysiological studies of the mutant channel expressed in Xenopus oocytes indicated a loss of function. Co-expression of WT and mutant cRNAs significantly reduced whole-oocyte current compared to expression of WT Kv1.1 alone

Power and Equity in the Academy: Change from Within

As an undergraduate music major interested in graduate study in music theory, I asked Joseph Straus, with whom I was taking an independent study in music theory and feminism, if he knew of any  published work  in feminist music theory. The only relevant writing he could think of was Susan McClary’s “Pitches, Expression, Ideology,” from the little-known journal Enclitic (1983). After reading this article (which I still reference when teaching Schubert Lieder), I corresponded with McClary, and we set up a meeting during her visit to New York to speak at the Brecht Forum/ New York Marxist School. We quickly bonded over the fact that we both grew up in the same small town in Illinois—Carbondale—and that in graduate school we both tried desperately to expunge all traces of our distinctive southern Illinois twang. As a first-year music theory graduate student at Harvard eager to bring feminist criticism to my newly chosen subfield, I established a study group for those interested in learning more about what then was a brand-new area of research. The Group for Gender Studies in Music (GGSM) met once a month to discuss the few publications then available in feminist music studies, analyze music by women composers, produce a concert of music by women composers in honor of Women’s History Month, and plan a colloquium series. We found a sympathetic adviser in David Lewin, the senior music theorist on the faculty, and I secured funding from Radcliffe College and several other sources to pay for honoraria and travel for our four invited speakers. Lewin generously wrote a check as seed money to support our group when our request for department funding for our activities was turned down. When I met with the department chair about possible support for GGSM, I was asked to supply a list of names of those who attended our meetings, ostensibly to establish the level of student interest in the group. Our group was more controversial than I had anticipated and I wondered whether there would be negative consequences for anyone involved. (I did not comply with the request for names.) Without support from the department, we could not internally process the donations we received, and had to open an account at a local bank. Meetings of the Group for Gender Studies in Music were very well attended by curious graduate students in music theory, musicology, and ethnomusicology. Word of our colloquium series, advertised in hard-copy posters I prepared with my dot-matrix printer in the days before Facebook, Twitter, and e-mail somehow reached Professor Judith Tick at Northeastern University and Dr. Hugh Morgan Hill, also known as Brother Blue. Dr. Hill was a playwright and storyteller based in Cambridge who had earned a doctorate in storytelling from Union Graduate School (Grimes 2009). He attended McClary’s GGSM colloquium on Laurie Anderson, work she developed into a chapter in Feminine Endings (1991), and he took McClary aside to comment on the significance of her speaking about Anderson within the staid wood-paneled seminar room in Harvard’s historic Paine Hall.[1] While many of my fellow graduate students welcomed the opportunity to engage with this new area of study, most of the faculty did not. Apart from Lewin, no faculty member ever attended a GGSM meeting and few attended our public colloquia, despite the prominence of the speakers we scheduled, including musicologists McClary and Paula Higgins, music theorist Joseph Straus, and composer and theorist Pozzi Escot. Although I had made it clear in my applications to PhD programs that I was determined to bring feminism to music theory, my attempts to initiate thinking at Harvard about gender, feminism, sexuality, race, and music got serious pushback. One graduate student relayed that his adviser mentioned to him that I should not be organizing numerous events he didn’t have time for, because when he didn’t attend, everyone would wonder why he wasn’t there. The department, and the field, were not ready in 1990 for such research directions.[2] During her visit to GGSM, McClary pointedly told me, “it doesn’t have to be this way” (i.e., being miserable in graduate school). While taking a leave of absence from Harvard, I spent a glorious year at the University of Minnesota studying with McClary in the School of Music and with Richard Leppert and Lisette Josephides in the interdisciplinary PhD program in Comparative Studies in Discourse and Society. Working with these cutting-edge scholars and superb teachers proved to be an antidote to my disastrous first year of graduate school. At Minnesota, McClary was a magnet for a cohort of smart, curious, imaginative, and fun graduate students who were all interested in possibilities for new scholarship that brought critical theory, including feminist theory, to the study of all sorts of music, from Beethoven to Madonna, Monteverdi to Prince. McClary’s professional home is often assumed to be musicology, but many of us who have PhDs in music theory consider her to be a theorist. She has always insisted on thinking about how structure and processes are an integral part of the critical questions she raises about representation, narrative, tropes, and musical meaning, viewed through various lenses including gender and sexuality. I took two seminars with her—one on Monteverdi’s madrigals and another on music and postmodernism. The paper I wrote for the latter seminar turned into probably the most widely read piece I’ve published, my article on representations of East Asian women in music by John Mellencamp, David Bowie, and John Zorn (Hisama 1993). After Bowie’s death in 2016, I received calls from journalists who located that article from 1993 and wanted me to comment on Bowie and racism (Tam 2016 and Tandon 2016). Notes For a history of Paine Hall, see Brinkmann and Bannatyne (2010). As of Fall 2018, Harvard has not offered a seminar in gender studies and music. Personal communication with Anne Shreffler, San Antonio, TX, November 2018

Energetics and electronic structures of single walled carbon nanotubes encapsulated in boron nitride nanotubes

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Continuous Fermi level tuning of Nb-doped WSe2 under an external electric field

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Reflections on Nursing Leadership [Complete issue : First Quarter 2000, Vol. 26, 1]

Publishing History: Print issues of Reflections magazine were published from 1975 to 1999 and its successor, Reflections on Nursing Leadership (RNL) began publication in 2000. RNL migrated to an online format, http://www.reflectionsonnursingleadership.org, in 2006 and continues today. RNL is a member benefit of the Honor Society of Nursing, Sigma Theta Tau International (STTI). The historical print issues have been made openly available. Publishing Frequency: Quarterly until its transition to online. It’s now updated virtually every day. Format: Print, 1975 - 2005; Online, 2006 - present Feature Articles in this Issue: Creating a Career Now and Future Primary Care Stragegizing Your Career Eight Skills for a Healthy Career Conquering Stress Re-energizing Hospital Care Nigeria Unnoticed Carrying Your Own Lamp What Matters Most in Nursing\u27s Future? This issue of Reflections in Nursing Scholarship is sixty-three pages in length and contains information of interest to STTI members

Is “incidental finding” the best term?: a study of patients’ preferences

There is debate within the genetics community about the optimal term to describe genetic variants unrelated to the test indication, but potentially important for health. Given the lack of consensus and the importance of adopting terminology that promotes effective clinical communication, we sought the opinion of clinical genetics patients

The GABBR1 locus and the G1465A variant is not associated with temporal lobe epilepsy preceded by febrile seizures

BACKGROUND: Polymorphism G1465A in the GABBR1 gene has been suggested as a risk factor for non-lesional temporal lobe epilepsy (TLE); however, this genetic association study has not been independently replicated. We attempted to replicate this study in our cohort of patients with TLE. Furthermore, we also analyzed the coding sequence of this gene and searched for disease-causing mutations. METHODS: We included 120 unrelated individuals with TLE that was preceded by febrile seizures (FS) who did not have any evidence of structural lesions suggesting secondary epilepsy. 66 individuals had positive family history of TLE epilepsy and 54 were sporadic. Each patient was genotyped for the presence of G1465A polymorphism. All exons of the GABBR1 gene were screened by single strand confirmation polymorphism method. Genotypes were compared with two independent matched control groups. RESULTS: We detected two A alleles of the G1465A polymorphism in one homozygous control subject (0.87% of all alleles) and one A allele in a patient with TLE (0.45%, not significant). Other detected polymorphisms in coding regions had similar frequencies in epilepsy patients and control groups. No disease causing mutations in the GABBR1 gene were detected in patients with sporadic or familial TLE. CONCLUSION: Our results indicate that TLE preceded by FS is not associated with the polymorphisms or mutations in the GABBR1 gene, including the G1465A polymorphism. The proportion of TLE patients with FS in the original study, reporting this positive association, did not differ between allele A negative and positive cases. Thus, our failure to reproduce this result is likely applicable to all non-lesional TLE epilepsies

Rare loss of function variants in candidate genes and risk of colorectal cancer

Although ~ 25% of colorectal cancer or polyp (CRC/P) cases show familial aggregation, current germline genetic testing identifies a causal genotype in the 16 major genes associated with high penetrance CRC/P in only 20% of these cases. As there are likely other genes underlying heritable CRC/P, we evaluated the association of variation at novel loci with CRC/P. We evaluated 158 a priori selected candidate genes by comparing the number of rare potentially disruptive variants (PDVs) found in 84 CRC/P cases without an identified CRC/P risk-associated variant and 2440 controls. We repeated this analysis using an additional 73 CRC/P cases. We also compared the frequency of PDVs in select genes among CRC/P cases with two publicly available data sets. We found a significant enrichment of PDVs in cases vs. controls: 20% of cases vs. 11.5% of controls with ≥ 1 PDV (OR = 1.9, p = 0.01) in the original set of cases. Among the second cohort of CRC/P cases, 18% had a PDV, significantly different from 11.5% (p = 0.02). Logistic regression, adjusting for ancestry and multiple testing, indicated association between CRC/P and PDVs in NTHL1 (p = 0.0001), BRCA2 (p = 0.01) and BRIP1 (p = 0.04). However, there was no significant difference in the frequency of PDVs at each of these genes between all 157 CRC/P cases and two publicly available data sets. These results suggest an increased presence of PDVs in CRC/P cases and support further investigation of the association of NTHL1, BRCA2 and BRIP1 variation with CRC/P