Mayo Clinic - AuthorCitation

The IRF5–TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share

Kottyan, Leah C. , Zoller, Erin E., Bene, Jessica, Lu, Xiaoming , Kelly, Jennifer A. , Rupert, Andrew, Lessard, Christopher J. , Vaughn, Samuel , Marion, Miranda C. , Namjou, Bahram , Adler, Adam, Rasmussen, Astrid , Glenn, Stuart B., Montgomery, Courtney G. , Hirschfield, Gideon M. , Coltescu, Catalina, Amos, Chris, Ice, John A. , Registry, for UK Primary Sjögren's Syndrome, Rischmueller, Maureen , Brun, Johan G. , Gøransson, Lasse G. , Harboe, Erna, Omdal, Roald, Cunninghame‐Graham, Deborah S., Vyse, Tim J., Miceli‐Richard, Corinne , Lessard, James, Wahren‐Herlenius, Marie , Kvarnström, Marika , Illei, Gabor G. , Witte, Torsten, Jonsson, Roland , Nordmark, Gunnel , Ng, Wan‐Fai , Registry, for UK Primary Sjögren's Syndrome, Anaya, Juan‐Manuel , Rhodus, Nelson L., Segal, Barbara, Guthridge, Joel M. , Scofield, R. Hal , Alarcón‐Riquelme, Marta E. , Bae, Sang‐Cheol , Boackle, Susan A., Criswell, Lindsey A. , Gilkeson, Gary S. , Jacob, Chaim O., Kimberly, Robert P. , Brown, Elizabeth E. , Edberg, Jeffrey C., Alarcón, Graciela S. , Reveille, John D. , Vilá, Luis M. , Petri, Michelle , Niewold, Timothy B. , Stevens, Anne M., Tsao, Betty P. , Gorlova, Olga Y. , Wakeland, Ward, Radstake, Timothy R. D. J., Martín, Jose‐Ezequiel , Martı́n, Javier , Siminovitch, Katherine, Sivils, Kathy L., Gaffney, Patrick M. , Langefeld, Carl D. , Harley, John B., Kaufman, Kenneth M. , Niewold, Timothy, Weirauch, Matthew T. , Xie, Gang , Li, He , Nath, Swapan Kumar , Mariette, Xavier , Bowman, Simon , Registry, for UK Primary Sjögren's Syndrome, Lester, Sue , Brennan, Michael Thomas , Eriksson, Per , Registry, for UK Primary Sjögren's Syndrome, Merrill, Joan T. , James, Judith A. , Kamen, Diane L. , Ramsey‐Goldman, Rosalind , Freedman, Barry I. , Ying, Binwu , Mayes, Maureen D. , Hirschfield, Gideon M , Kottyan, Leah C , Guthridge, Joel M

Human Molecular Genetics | September 10, 2014 | Volume: 24 | Issue: 2 | Pages: 582-596

10.1093/hmg/ddu455 | PMID 25205108

IC‐P‐062: DATSCAN FINDINGS IN PATIENTS WITH REM SLEEP BEHAVIOR DISORDER AND/OR COGNITIVE IMPAIRMENT

Lowe, Val J. , Graff‐Radford, Jonathan, Peller, Patrick J., Silber, Michael H. , Bennett, Jamie, Aakre, Jeremiah A. , Knopman, David S. , Petersen, Ronald C. , Boeve, Bradley F. , Kantarci, Kejal , Graff‐Radford, Jonathan , Jones, David T. , Mielke, Michelle M. , Ferman, Tanis J. , Louis, Erik K. St. , Smith, Glenn E. , Pankratz, V. Shane , Knopman, David S.

Alzheimer's & Dementia | September 6, 2014 | Volume: 10 | Issue: 4S_Part_6 | Pages: No page available

10.1016/j.jalz.2014.05.067

O4‐06‐05: DATSCAN FINDINGS IN PATIENTS WITH REM SLEEP BEHAVIOR DISORDER AND/OR COGNITIVE IMPAIRMENT

Lowe, Val J. , Graff‐Radford, Jonathan, Peller, Patrick J., Silber, Michael H. , Bennett, Jamie, Aakre, Jeremiah A. , Knopman, David S. , Petersen, Ronald C. , Boeve, Bradley F. , Kantarci, Kejal , Graff‐Radford, Jonathan , Jones, David T. , Mielke, Michelle M. , Ferman, Tanis J. , Louis, Erik K. St. , Smith, Glenn E. , Pankratz, V. Shane , Knopman, David S.

Alzheimer's & Dementia | September 6, 2014 | Volume: 10 | Issue: 4S_Part_4 | Pages: No page available

10.1016/j.jalz.2014.04.419

O2‐10‐02: PRACTICE EFFECTS AND LONGITUDINAL COGNITIVE CHANGE AS A FUNCTION OF AMYLOID AND NEURODEGENERATIVE IMAGING BIOMARKERS IN COGNITIVELY NORMAL INDIVIDUALS

Hagen, Clint , Christianson, Teresa J., Lowe, Val J. , Ivnik, Robert J., Roberts, Rosebud O., Petersen, Ronald C. , Machulda, Mary M. , Mielke, Michelle M. , Pankratz, V. Shane , Jack, Clifford R. , Knopman, David S.

Alzheimer's & Dementia | September 6, 2014 | Volume: 10 | Issue: 4S_Part_2 | Pages: No page available

10.1016/j.jalz.2014.04.211

P4‐089: SELF‐ AND INFORMANT‐RATED DAILY FUNCTION IS ASSOCIATED WITH AMYLOID AND NEURODEGENERATIVE IMAGING IN COGNITIVELY NORMAL INDIVIDUALS

Hagen, Clint , Roberts, Rosebud O., Christianson, Teresa J., Lowe, Val J. , Petersen, Ronald C. , Mielke, Michelle M. , Vemuri, Prashanthi , Machulda, Mary M. , Pankratz, V. Shane , Knopman, David S. , Jack, Clifford R.

Alzheimer's & Dementia | September 6, 2014 | Volume: 10 | Issue: 4S_Part_22 | Pages: No page available

10.1016/j.jalz.2014.05.1604

O1‐11‐03: PREDICTORS AND PROTECTIVE FACTORS FOR COGNITIVE IMPAIRMENT IN VERY OLD COGNITIVELY NORMAL PERSONS

Roberts, Rosebud O., Cha, Ruth H., Petersen, Ronald C. , Cha, Ruth H., Geda, Yonas E. , Pankratz, V. Shane , Boeve, Bradley F. , Mielke, Michelle M. , Machulda, Mary M. , Knopman, David S.

Alzheimer's & Dementia | September 6, 2014 | Volume: 10 | Issue: 4S_Part_1 | Pages: No page available

10.1016/j.jalz.2014.04.118

P1‐323: SLEEP‐RELATED FEATURES AND PERFORMANCE ON A COMPUTERIZED COGNITIVE BATTERY: THE MAYO CLINIC STUDY OF AGING

Boeve, Angelica, Roberts, Rosebud O., Ivnik, Robert J., Fields, Julie A. , Petersen, Ronald C. , Mielke, Michelle M. , Geda, Yonas E. , Machulda, Mary M. , Pankratz, V. Shane , Boeve, Bradley F. , Knopman, David S.

Alzheimer's & Dementia | September 6, 2014 | Volume: 10 | Issue: 4S_Part_11 | Pages: No page available

10.1016/j.jalz.2014.05.564

P2‐153: PHYSICAL EXERCISE AND THE OUTCOME OF INCIDENT DEMENTIA: THE MAYO CLINIC STUDY OF AGING

Feder, Nathanael Tigistu, Bartley, Mairead M. , Acosta, Jazmin I., Roberts, Rosebud O., Christianson, Teresa J., Lowe, Val J. , Petersen, Ronald C. , Knopman, David S. , Pankratz, V. Shane , Mielke, Michelle M. , Stokin, Gorazd B. , Geda, Yonas E.

Alzheimer's & Dementia | September 6, 2014 | Volume: 10 | Issue: 4S_Part_13 | Pages: No page available

10.1016/j.jalz.2014.05.829

O3‐10‐03: SEX AND APOE EFFECTS ON MEMORY PERFORMANCE, NEURODEGENERATION, AND B‐AMYLOID ACROSS THE ADULT LIFESPAN

Wiste, Heather J. , Weigand, Stephen D. , Lowe, Val J. , Gunter, Jeffrey L. , Gregg, Brian E., Rocca, Walter A. , Petersen, Ronald C. , Jack, Clifford R. , Knopman, David S. , Vemuri, Prashanthi , Mielke, Michelle M. , Senjem, Matthew L. , Machulda, Mary M. , Pankratz, V. Shane

Alzheimer's & Dementia | September 6, 2014 | Volume: 10 | Issue: 4S_Part_3 | Pages: No page available

10.1016/j.jalz.2014.04.325

Reduced junctional Na+/Ca2+-exchanger activity contributes to sarcoplasmic reticulum Ca2+ leak in junctophilin-2-deficient mice

Landstrom, Andrew P. , Wang, Qiongling, Munro, Michelle L. , Beavers, David L. , Ackerman, Michael J. , Soeller, Christian , Wehrens, Xander H.T. , Wang, Wei , Landstrom, Andrew P , Wehrens, Xander H T

American Journal of Physiology-Heart and Circulatory Physiology | September 6, 2014 | Volume: 307 | Issue: 9 | Pages: H1317-H1326

10.1152/ajpheart.00413.2014 | PMID 25193470

Expression silencing of junctophilin-2 (JPH2) in mouse heart leads to ryanodine receptor type 2 (RyR2)-mediated sarcoplasmic reticulum (SR) Ca2+ leak and rapid development of heart failure. The mechanism and physiological significance of JPH2 in regulating RyR2-mediated SR Ca2+ leak remains elusive. We sought to elucidate the role of JPH2 in regulating RyR2-mediated SR Ca2+ release in the setting of cardiac failure. Cardiac myocytes isolated from tamoxifen-inducible conditional knockdown mice of JPH2 (MCM-shJPH2) were subjected to confocal Ca2+ imaging. MCM-shJPH2 cardiomyocytes exhibited an increased spark frequency width with altered spark morphology, which caused increased SR Ca2+ leakage. Single channel studies identified an increased RyR2 open probability in MCM-shJPH2 mice. The increase in spark frequency and width was observed only in MCM-shJPH2 and not found in mice with increased RyR2 open probability with native JPH2 expression. Na+/Ca2+-exchanger (NCX) activity was reduced by 50% in MCM-shJPH2 with no detectable change in NCX expression. Additionally, 50% inhibition of NCX through Cd2+ administration alone was sufficient to increase spark width in myocytes obtained from wild-type mice. Additionally, superresolution analysis of RyR2 and NCX colocalization showed a reduced overlap between RyR2 and NCX in MCM-shJPH2 mice. In conclusion, decreased JPH2 expression causes increased SR Ca2+ leakage by directly increasing open probability of RyR2 and by indirectly reducing junctional NCX activity through increased dyadic cleft Ca2+. This demonstrates two novel and independent cellular mechanisms by which JPH2 regulates RyR2-mediated SR Ca2+ leak and heart failure development.

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