TY  - JOUR
A1  - El-Helou, Sabine M.
A1  - Biegner, Anika-Kerstin
A1  - Bode, Sebastian
A1  - Ehl, Stephan R.
A1  - Heeg, Maximilian
A1  - Maccari, Maria E.
A1  - Ritterbusch, Henrike
A1  - Speckmann, Carsten
A1  - Rusch, Stephan
A1  - Scheible, Raphael
A1  - Warnatz, Klaus
A1  - Atschekzei, Faranaz
A1  - Beider, Renata
A1  - Ernst, Diana
A1  - Gerschmann, Stev
A1  - Jablonka, Alexandra
A1  - Mielke, Gudrun
A1  - Schmidt, Reinhold E.
A1  - Schürmann, Gesine
A1  - Sogkas, Georgios
A1  - Baumann, Ulrich H.
A1  - Klemann, Christian
A1  - Viemann, Dorothee
A1  - Bernuth, Horst von
A1  - Krüger, Renate
A1  - Hanitsch, Leif G.
A1  - Scheibenbogen, Carmen M.
A1  - Wittke, Kirsten
A1  - Albert, Michael H.
A1  - Eichinger, Anna
A1  - Hauck, Fabian
A1  - Klein, Christoph
A1  - Rack-Hoch, Anita
A1  - Sollinger, Franz M.
A1  - Avila, Anne
A1  - Borte, Michael
A1  - Borte, Stephan
A1  - Fasshauer, Maria
A1  - Hauenherm, Anja
A1  - Kellner, Nils
A1  - Müller, Anna H.
A1  - Ülzen, Anett
A1  - Bader, Peter
A1  - Bakhtiar, Shahrzad
A1  - Lee, Jae-Yun
A1  - Heß, Ursula
A1  - Schubert, Ralf
A1  - Wölke, Sandra
A1  - Zielen, Stefan
A1  - Ghosh, Sujal
A1  - Laws, Hans-Juergen
A1  - Neubert, Jennifer
A1  - Oommen, Prasad T.
A1  - Hönig, Manfred
A1  - Schulz, Ansgar
A1  - Steinmann, Sandra
A1  - Klaus, Schwarz
A1  - Dückers, Gregor
A1  - Lamers, Beate
A1  - Langemeyer, Vanessa
A1  - Niehues, Tim
A1  - Shai, Sonu
A1  - Graf, Dagmar
A1  - Müglich, Carmen
A1  - Schmalzing, Marc T.
A1  - Schwaneck, Eva C.
A1  - Tony, Hans-Peter
A1  - Dirks, Johannes
A1  - Haase, Gabriele
A1  - Liese, Johannes G.
A1  - Morbach, Henner
A1  - Foell, Dirk
A1  - Hellige, Antje
A1  - Wittkowski, Helmut
A1  - Masjosthusmann, Katja
A1  - Mohr, Michael
A1  - Geberzahn, Linda
A1  - Hedrich, Christian M.
A1  - Müller, Christiane
A1  - Rösen-Wolff, Angela
A1  - Roesler, Joachim
A1  - Zimmermann, Antje
A1  - Behrends, Uta
A1  - Rieber, Nikolaus
A1  - Schauer, Uwe
A1  - Handgretinger, Rupert
A1  - Holzer, Ursula
A1  - Henes, Jörg
A1  - Kanz, Lothar
A1  - Boesecke, Christoph
A1  - Rockstroh, Jürgen K.
A1  - Schwarze-Zander, Carolynne
A1  - Wasmuth, Jan-Christian
A1  - Dilloo, Dagmar
A1  - Hülsmann, Brigitte
A1  - Schönberger, Stefan
A1  - Schreiber, Stefan
A1  - Zeuner, Rainald
A1  - Ankermann, Tobias
A1  - Bismarck, Philipp von
A1  - Huppertz, Hans-Iko
A1  - Kaiser-Labusch, Petra
A1  - Greil, Johann
A1  - Jakoby, Donate
A1  - Kulozik, Andreas E.
A1  - Metzler, Markus
A1  - Naumann-Bartsch, Nora
A1  - Sobik, Bettina
A1  - Graf, Norbert
A1  - Heine, Sabine
A1  - Kobbe, Robin
A1  - Lehmberg, Kai
A1  - Müller, Ingo
A1  - Herrmann, Friedrich
A1  - Horneff, Gerd
A1  - Klein, Ariane
A1  - Peitz, Joachim
A1  - Schmidt, Nadine
A1  - Bielack, Stefan
A1  - Groß-Wieltsch, Ute
A1  - Classen, Carl F.
A1  - Klasen, Jessica
A1  - Deutz, Peter
A1  - Kamitz, Dirk
A1  - Lassy, Lisa
A1  - Tenbrock, Klaus
A1  - Wagner, Norbert
A1  - Bernbeck, Benedikt
A1  - Brummel, Bastian
A1  - Lara-Villacanas, Eusebia
A1  - Münstermann, Esther
A1  - Schneider, Dominik T.
A1  - Tietsch, Nadine
A1  - Westkemper, Marco
A1  - Weiß, Michael
A1  - Kramm, Christof
A1  - Kühnle, Ingrid
A1  - Kullmann, Silke
A1  - Girschick, Hermann
A1  - Specker, Christof
A1  - Vinnemeier-Laubenthal, Elisabeth
A1  - Haenicke, Henriette
A1  - Schulz, Claudia
A1  - Schweigerer, Lothar
A1  - Müller, Thomas G.
A1  - Stiefel, Martina
A1  - Belohradsky, Bernd H.
A1  - Soetedjo, Veronika
A1  - Kindle, Gerhard
A1  - Grimbacher, Bodo
T1  - The German national registry of primary immunodeficiencies (2012-2017)
JF  - Frontiers in Immunology
N2  - Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. 

Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. 

Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1-25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0-88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE-syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%-subcutaneous; 29%-intravenous; 1%-unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. 

Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.
KW  - registry for primary immunodeficiency
KW  - primary immunodeficiency (PID)
KW  - German PID-NET registry
KW  - PID prevalence
KW  - European Society for Immunodeficiencies (ESID)
KW  - IgG substitution therapy
KW  - CVID
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226629
VL  - 10
ER  - 
TY  - JOUR
A1  - Davis, Lea K.
A1  - Yu, Dongmei
A1  - Keenan, Clare L.
A1  - Gamazon, Eric R.
A1  - Konkashbaev, Anuar I.
A1  - Derks, Eske M.
A1  - Neale, Benjamin M.
A1  - Yang, Jian
A1  - Lee, S. Hong
A1  - Evans, Patrick
A1  - Barr, Cathy L.
A1  - Bellodi, Laura
A1  - Benarroch, Fortu
A1  - Berrio, Gabriel Bedoya
A1  - Bienvenu, Oscar J.
A1  - Bloch, Michael H.
A1  - Blom, Rianne M.
A1  - Bruun, Ruth D.
A1  - Budman, Cathy L.
A1  - Camarena, Beatriz
A1  - Campbell, Desmond
A1  - Cappi, Carolina
A1  - Cardona Silgado, Julio C.
A1  - Cath, Danielle C.
A1  - Cavallini, Maria C.
A1  - Chavira, Denise A.
A1  - Chouinard, Sylvian
A1  - Conti, David V.
A1  - Cook, Edwin H.
A1  - Coric, Vladimir
A1  - Cullen, Bernadette A.
A1  - Deforce, Dieter
A1  - Delorme, Richard
A1  - Dion, Yves
A1  - Edlund, Christopher K.
A1  - Egberts, Karin
A1  - Falkai, Peter
A1  - Fernandez, Thomas V.
A1  - Gallagher, Patience J.
A1  - Garrido, Helena
A1  - Geller, Daniel
A1  - Girard, Simon L.
A1  - Grabe, Hans J.
A1  - Grados, Marco A.
A1  - Greenberg, Benjamin D.
A1  - Gross-Tsur, Varda
A1  - Haddad, Stephen
A1  - Heiman, Gary A.
A1  - Hemmings, Sian M. J.
A1  - Hounie, Ana G.
A1  - Illmann, Cornelia
A1  - Jankovic, Joseph
A1  - Jenike, Micheal A.
A1  - Kennedy, James L.
A1  - King, Robert A.
A1  - Kremeyer, Barbara
A1  - Kurlan, Roger
A1  - Lanzagorta, Nuria
A1  - Leboyer, Marion
A1  - Leckman, James F.
A1  - Lennertz, Leonhard
A1  - Liu, Chunyu
A1  - Lochner, Christine
A1  - Lowe, Thomas L.
A1  - Macciardi, Fabio
A1  - McCracken, James T.
A1  - McGrath, Lauren M.
A1  - Restrepo, Sandra C. Mesa
A1  - Moessner, Rainald
A1  - Morgan, Jubel
A1  - Muller, Heike
A1  - Murphy, Dennis L.
A1  - Naarden, Allan L.
A1  - Ochoa, William Cornejo
A1  - Ophoff, Roel A.
A1  - Osiecki, Lisa
A1  - Pakstis, Andrew J.
A1  - Pato, Michele T.
A1  - Pato, Carlos N.
A1  - Piacentini, John
A1  - Pittenger, Christopher
A1  - Pollak, Yehunda
A1  - Rauch, Scott L.
A1  - Renner, Tobias J.
A1  - Reus, Victor I.
A1  - Richter, Margaret A.
A1  - Riddle, Mark A.
A1  - Robertson, Mary M.
A1  - Romero, Roxana
A1  - Rosàrio, Maria C.
A1  - Rosenberg, David
A1  - Rouleau, Guy A.
A1  - Ruhrmann, Stephan
A1  - Ruiz-Linares, Andreas
A1  - Sampaio, Aline S.
A1  - Samuels, Jack
A1  - Sandor, Paul
A1  - Sheppard, Broke
A1  - Singer, Harvey S.
A1  - Smit, Jan H.
A1  - Stein, Dan J.
A1  - Strengman, E.
A1  - Tischfield, Jay A.
A1  - Valencia Duarte, Ana V.
A1  - Vallada, Homero
A1  - Van Nieuwerburgh, Flip
A1  - Veenstra-VanderWeele, Jeremy
A1  - Walitza, Susanne
A1  - Wang, Ying
A1  - Wendland, Jens R.
A1  - Westenberg, Herman G. M.
A1  - Shugart, Yin Yao
A1  - Miguel, Euripedes C.
A1  - McMahon, William
A1  - Wagner, Michael
A1  - Nicolini, Humberto
A1  - Posthuma, Danielle
A1  - Hanna, Gregory L.
A1  - Heutink, Peter
A1  - Denys, Damiaan
A1  - Arnold, Paul D.
A1  - Oostra, Ben A.
A1  - Nestadt, Gerald
A1  - Freimer, Nelson B.
A1  - Pauls, David L.
A1  - Wray, Naomi R.
A1  - Stewart, S. Evelyn
A1  - Mathews, Carol A.
A1  - Knowles, James A.
A1  - Cox, Nancy J.
A1  - Scharf, Jeremiah M.
T1  - Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture
JF  - PLoS Genetics
N2  - The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
KW  - TIC disorders
KW  - missing heritability
KW  - complex diseases
KW  - neuropsychiatric disorders
KW  - common SNPS
KW  - gilles
KW  - family
KW  - brain
KW  - expression
KW  - autism
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127377
SN  - 1553-7390
VL  - 9
IS  - 10
ER  - 
TY  - JOUR
A1  - Dornelas, Maria
A1  - Antão, Laura H.
A1  - Moyes, Faye
A1  - Bates, Amanda E.
A1  - Magurran, Anne E.
A1  - Adam, Dušan
A1  - Akhmetzhanova, Asem A.
A1  - Appeltans, Ward
A1  - Arcos, José Manuel
A1  - Arnold, Haley
A1  - Ayyappan, Narayanan
A1  - Badihi, Gal
A1  - Baird, Andrew H.
A1  - Barbosa, Miguel
A1  - Barreto, Tiago Egydio
A1  - Bässler, Claus
A1  - Bellgrove, Alecia
A1  - Belmaker, Jonathan
A1  - Benedetti-Cecchi, Lisandro
A1  - Bett, Brian J.
A1  - Bjorkman, Anne D.
A1  - Błażewicz, Magdalena
A1  - Blowes, Shane A.
A1  - Bloch, Christopher P. Bloch
A1  - Bonebrake, Timothy C.
A1  - Boyd, Susan
A1  - Bradford, Matt
A1  - Brooks, Andrew J.
A1  - Brown, James H.
A1  - Bruelheide, Helge
A1  - Budy, Phaedra
A1  - Carvalho, Fernando
A1  - Castañeda-Moya, Edward
A1  - Chen, Chaolun Allen
A1  - Chamblee, John F.
A1  - Chase, Tory J.
A1  - Siegwart Collier, Laura
A1  - Collinge, Sharon K.
A1  - Condit, Richard
A1  - Cooper, Elisabeth J.
A1  - Cornelissen, J. Hans C.
A1  - Cotano, Unai
A1  - Crow, Shannan Kyle
A1  - Damasceno, Gabriella
A1  - Davies, Claire H.
A1  - Davis, Robert A.
A1  - Day, Frank P.
A1  - Degraer, Steven
A1  - Doherty, Tim S.
A1  - Dunn, Timothy E.
A1  - Durigan, Giselda
A1  - Duffy, J. Emmett
A1  - Edelist, Dor
A1  - Edgar, Graham J.
A1  - Elahi, Robin
A1  - Elmendorf, Sarah C.
A1  - Enemar, Anders
A1  - Ernest, S. K. Morgan
A1  - Escribano, Rubén
A1  - Estiarte, Marc
A1  - Evans, Brian S.
A1  - Fan, Tung-Yung
A1  - Turini Farah, Fabiano
A1  - Loureiro Fernandes, Luiz
A1  - Farneda, Fábio Z.
A1  - Fidelis, Alessandra
A1  - Fitt, Robert
A1  - Fosaa, Anna Maria
A1  - Franco, Geraldo Antonio Daher Correa
A1  - Frank, Grace E.
A1  - Fraser, William R.
A1  - García, Hernando
A1  - Cazzolla Gatti, Roberto
A1  - Givan, Or
A1  - Gorgone-Barbosa, Elizabeth
A1  - Gould, William A.
A1  - Gries, Corinna
A1  - Grossman, Gary D.
A1  - Gutierréz, Julio R.
A1  - Hale, Stephen
A1  - Harmon, Mark E.
A1  - Harte, John
A1  - Haskins, Gary
A1  - Henshaw, Donald L.
A1  - Hermanutz, Luise
A1  - Hidalgo, Pamela
A1  - Higuchi, Pedro
A1  - Hoey, Andrew
A1  - Van Hoey, Gert
A1  - Hofgaard, Annika
A1  - Holeck, Kristen
A1  - Hollister, Robert D.
A1  - Holmes, Richard
A1  - Hoogenboom, Mia
A1  - Hsieh, Chih-hao
A1  - Hubbell, Stephen P.
A1  - Huettmann, Falk
A1  - Huffard, Christine L.
A1  - Hurlbert, Allen H.
A1  - Ivanauskas, Natália Macedo
A1  - Janík, David
A1  - Jandt, Ute
A1  - Jażdżewska, Anna
A1  - Johannessen, Tore
A1  - Johnstone, Jill
A1  - Jones, Julia
A1  - Jones, Faith A. M.
A1  - Kang, Jungwon
A1  - Kartawijaya, Tasrif
A1  - Keeley, Erin C.
A1  - Kelt, Douglas A.
A1  - Kinnear, Rebecca
A1  - Klanderud, Kari
A1  - Knutsen, Halvor
A1  - Koenig, Christopher C.
A1  - Kortz, Alessandra R.
A1  - Král, Kamil
A1  - Kuhnz, Linda A.
A1  - Kuo, Chao-Yang
A1  - Kushner, David J.
A1  - Laguionie-Marchais, Claire
A1  - Lancaster, Lesley T.
A1  - Lee, Cheol Min
A1  - Lefcheck, Jonathan S.
A1  - Lévesque, Esther
A1  - Lightfoot, David
A1  - Lloret, Francisco
A1  - Lloyd, John D.
A1  - López-Baucells, Adrià
A1  - Louzao, Maite
A1  - Madin, Joshua S.
A1  - Magnússon, Borgþór
A1  - Malamud, Shahar
A1  - Matthews, Iain
A1  - McFarland, Kent P.
A1  - McGill, Brian
A1  - McKnight, Diane
A1  - McLarney, William O.
A1  - Meador, Jason
A1  - Meserve, Peter L.
A1  - Metcalfe, Daniel J.
A1  - Meyer, Christoph F. J.
A1  - Michelsen, Anders
A1  - Milchakova, Nataliya
A1  - Moens, Tom
A1  - Moland, Even
A1  - Moore, Jon
A1  - Moreira, Carolina Mathias
A1  - Müller, Jörg
A1  - Murphy, Grace
A1  - Myers-Smith, Isla H.
A1  - Myster, Randall W.
A1  - Naumov, Andrew
A1  - Neat, Francis
A1  - Nelson, James A.
A1  - Nelson, Michael Paul
A1  - Newton, Stephen F.
A1  - Norden, Natalia
A1  - Oliver, Jeffrey C.
A1  - Olsen, Esben M.
A1  - Onipchenko, Vladimir G.
A1  - Pabis, Krzysztof
A1  - Pabst, Robert J.
A1  - Paquette, Alain
A1  - Pardede, Sinta
A1  - Paterson, David M.
A1  - Pélissier, Raphaël
A1  - Peñuelas, Josep
A1  - Pérez-Matus, Alejandro
A1  - Pizarro, Oscar
A1  - Pomati, Francesco
A1  - Post, Eric
A1  - Prins, Herbert H. T.
A1  - Priscu, John C.
A1  - Provoost, Pieter
A1  - Prudic, Kathleen L.
A1  - Pulliainen, Erkki
A1  - Ramesh, B. R.
A1  - Ramos, Olivia Mendivil
A1  - Rassweiler, Andrew
A1  - Rebelo, Jose Eduardo
A1  - Reed, Daniel C.
A1  - Reich, Peter B.
A1  - Remillard, Suzanne M.
A1  - Richardson, Anthony J.
A1  - Richardson, J. Paul
A1  - van Rijn, Itai
A1  - Rocha, Ricardo
A1  - Rivera-Monroy, Victor H.
A1  - Rixen, Christian
A1  - Robinson, Kevin P.
A1  - Rodrigues, Ricardo Ribeiro
A1  - de Cerqueira Rossa-Feres, Denise
A1  - Rudstam, Lars
A1  - Ruhl, Henry
A1  - Ruz, Catalina S.
A1  - Sampaio, Erica M.
A1  - Rybicki, Nancy
A1  - Rypel, Andrew
A1  - Sal, Sofia
A1  - Salgado, Beatriz
A1  - Santos, Flavio A. M.
A1  - Savassi-Coutinho, Ana Paula
A1  - Scanga, Sara
A1  - Schmidt, Jochen
A1  - Schooley, Robert
A1  - Setiawan, Fakhrizal
A1  - Shao, Kwang-Tsao
A1  - Shaver, Gaius R.
A1  - Sherman, Sally
A1  - Sherry, Thomas W.
A1  - Siciński, Jacek
A1  - Sievers, Caya
A1  - da Silva, Ana Carolina
A1  - da Silva, Fernando Rodrigues
A1  - Silveira, Fabio L.
A1  - Slingsby, Jasper
A1  - Smart, Tracey
A1  - Snell, Sara J.
A1  - Soudzilovskaia, Nadejda A.
A1  - Souza, Gabriel B. G.
A1  - Souza, Flaviana Maluf
A1  - Souza, Vinícius Castro
A1  - Stallings, Christopher D.
A1  - Stanforth, Rowan
A1  - Stanley, Emily H.
A1  - Sterza, José Mauro
A1  - Stevens, Maarten
A1  - Stuart-Smith, Rick
A1  - Suarez, Yzel Rondon
A1  - Supp, Sarah
A1  - Tamashiro, Jorge Yoshio
A1  - Tarigan, Sukmaraharja
A1  - Thiede, Gary P.
A1  - Thorn, Simon
A1  - Tolvanen, Anne
A1  - Toniato, Maria Teresa Zugliani
A1  - Totland, Ørjan
A1  - Twilley, Robert R.
A1  - Vaitkus, Gediminas
A1  - Valdivia, Nelson
A1  - Vallejo, Martha Isabel
A1  - Valone, Thomas J.
A1  - Van Colen, Carl
A1  - Vanaverbeke, Jan
A1  - Venturoli, Fabio
A1  - Verheye, Hans M.
A1  - Vianna, Marcelo
A1  - Vieira, Rui P.
A1  - Vrška, Tomáš
A1  - Vu, Con Quang
A1  - Vu, Lien Van
A1  - Waide, Robert B.
A1  - Waldock, Conor
A1  - Watts, Dave
A1  - Webb, Sara
A1  - Wesołowski, Tomasz
A1  - White, Ethan P.
A1  - Widdicombe, Claire E.
A1  - Wilgers, Dustin
A1  - Williams, Richard
A1  - Williams, Stefan B.
A1  - Williamson, Mark
A1  - Willig, Michael R.
A1  - Willis, Trevor J.
A1  - Wipf, Sonja
A1  - Woods, Kerry D.
A1  - Woehler, Eric J.
A1  - Zawada, Kyle
A1  - Zettler, Michael L.
T1  - BioTIME: A database of biodiversity time series for the Anthropocene
JF  - Global Ecology and Biogeography
N2  - Motivation
The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene.

Main types of variables included
The database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record.

Spatial location and grain
BioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km2 (158 cm2) to 100 km2 (1,000,000,000,000 cm2).

Time period and grain
BioTIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year.

Major taxa and level of measurement
BioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates.

Software format
.csv and .SQL.
KW  - biodiversity
KW  - global
KW  - spatial
KW  - species richness
KW  - temporal
KW  - turnover
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222846
VL  - 27
ER  - 
TY  - JOUR
A1  - Müller, Stefanie H.
A1  - Girard, Simon L.
A1  - Hopfner, Franziska
A1  - Merner, Nancy D.
A1  - Bourassa, Cynthia V.
A1  - Lorenz, Delia
A1  - Clark, Lorraine N.
A1  - Tittmann, Lukas
A1  - Soto-Ortolaza, Alexandra I.
A1  - Klebe, Stephan
A1  - Hallett, Mark
A1  - Schneider, Susanne A.
A1  - Hodgkinson, Colin A.
A1  - Lieb, Wolfgang
A1  - Wszolek, Zbigniew K.
A1  - Pendziwiat, Manuela
A1  - Lorenzo-Betancor, Oswaldo
A1  - Poewe, Werner
A1  - Ortega-Cubero, Sara
A1  - Seppi, Klaus
A1  - Rajput, Alex
A1  - Hussl, Anna
A1  - Rajput, Ali H.
A1  - Berg, Daniela
A1  - Dion, Patrick A.
A1  - Wurster, Isabel
A1  - Shulman, Joshua M.
A1  - Srulijes, Karin
A1  - Haubenberger, Dietrich
A1  - Pastor, Pau
A1  - Vilariño-Güell, Carles
A1  - Postuma, Ronald B.
A1  - Bernard, Geneviève
A1  - Ladwig, Karl-Heinz
A1  - Dupré, Nicolas
A1  - Jankovic, Joseph
A1  - Strauch, Konstantin
A1  - Panisset, Michel
A1  - Winkelmann, Juliane
A1  - Testa, Claudia M.
A1  - Reischl, Eva
A1  - Zeuner, Kirsten E.
A1  - Ross, Owen A.
A1  - Arzberger, Thomas
A1  - Chouinard, Sylvain
A1  - Deuschl, Günther
A1  - Louis, Elan D.
A1  - Kuhlenbäumer, Gregor
A1  - Rouleau, Guy A.
T1  - Genome-wide association study in essential tremor identifies three new loci
JF  - Brain
N2  - We conducted a genome-wide association study of essential tremor, a common movement disorder characterized mainly by a postural and kinetic tremor of the upper extremities. Twin and family history studies show a high heritability for essential tremor. The molecular genetic determinants of essential tremor are unknown. We included 2807 patients and 6441 controls of European descent in our two-stage genome-wide association study. The 59 most significantly disease-associated markers of the discovery stage were genotyped in the replication stage. After Bonferroni correction two markers, one (rs10937625) located in the serine/threonine kinase STK32B and one (rs17590046) in the transcriptional coactivator PPARGC1A were associated with essential tremor. Three markers (rs12764057, rs10822974, rs7903491) in the cell-adhesion molecule CTNNA3 were significant in the combined analysis of both stages. The expression of STK32B was increased in the cerebellar cortex of patients and expression quantitative trait loci database mining showed association between the protective minor allele of rs10937625 and reduced expression in cerebellar cortex. We found no expression differences related to disease status or marker genotype for the other two genes. Replication of two lead single nucleotide polymorphisms of previous small genome-wide association studies (rs3794087 in SLC1A2, rs9652490 in LINGO1) did not confirm the association with essential tremor.
KW  - quality-control
KW  - disease
KW  - tool
KW  - movement disorders
KW  - genome-wide association study
KW  - tremor
KW  - genetics
KW  - essential tremor
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186541
VL  - 139
ER  - 
TY  - JOUR
A1  - Maierhofer, Anna
A1  - Flunkert, Julia
A1  - Oshima, Junko
A1  - Martin, George M.
A1  - Poot, Martin
A1  - Nanda, Indrajit
A1  - Dittrich, Marcus
A1  - Müller, Tobias
A1  - Haaf, Thomas
T1  - Epigenetic signatures of Werner syndrome occur early in life and are distinct from normal epigenetic aging processes
JF  - Aging Cell
N2  - Werner Syndrome (WS) is an adult‐onset segmental progeroid syndrome. Bisulfite pyrosequencing of repetitive DNA families revealed comparable blood DNA methylation levels between classical (18 WRN‐mutant) or atypical WS (3 LMNA‐mutant and 3 POLD1‐mutant) patients and age‐ and sex‐matched controls. WS was not associated with either age‐related accelerated global losses of ALU, LINE1, and α‐satellite DNA methylations or gains of rDNA methylation. Single CpG methylation was analyzed with Infinium MethylationEPIC arrays. In a correspondence analysis, atypical WS samples clustered together with the controls and were clearly separated from classical WS, consistent with distinct epigenetic pathologies. In classical WS, we identified 659 differentially methylated regions (DMRs) comprising 3,656 CpG sites and 613 RefSeq genes. The top DMR was located in the HOXA4 promoter. Additional DMR genes included LMNA, POLD1, and 132 genes which have been reported to be differentially expressed in WRN‐mutant/depleted cells. DMRs were enriched in genes with molecular functions linked to transcription factor activity and sequence‐specific DNA binding to promoters transcribed by RNA polymerase II. We propose that transcriptional misregulation of downstream genes by the absence of WRN protein contributes to the variable premature aging phenotypes of WS. There were no CpG sites showing significant differences in DNA methylation changes with age between WS patients and controls. Genes with both WS‐ and age‐related methylation changes exhibited a constant offset of methylation between WRN‐mutant patients and controls across the entire analyzed age range. WS‐specific epigenetic signatures occur early in life and do not simply reflect an acceleration of normal epigenetic aging processes.
KW  - (classical and atypical) Werner syndrome
KW  - bisulfite pyrosequencing
KW  - methylation array
KW  - premature aging
KW  - segmental progeria
KW  - transcription deficiency
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202733
VL  - 18
ER  - 
TY  - JOUR
A1  - Krzymanski, Maciej
A1  - Waaga, Ana M.
A1  - Ulrichs, Karin
A1  - Deja, Aadam
A1  - Oko, Andrzej
A1  - Rommel, Thomas
A1  - Müller-Ruchholtz, Wolfgang
T1  - The influence of MHC class II antigen blockade by perfusion with a monoclonal antibody on rat renal graft survival
N2  - To decrease immunogenicity of the rat kidney, grafts were perfused with an anti-MHC class li monoclonal antibody (mAb ). How effectively this procedure blocked dass li-positive cells, which were mainly dendritic in appearance, was checked by immunostaining renal sections after perfusion and comparing them with in vitro stained sections. Optimum conditions were applied for graft pretreatment before transplantation. This procedure prolonged graft survival, though not satisfactorily from the biological point ofview (9.6 ± 0.8 versus 7.7 ± 0.5 days in the control group; P < 0.02). The dendritic cells were not killed but blocked. Several hours after transplantation, the mAb dissociated from these dass li-positive cells. It was also shown that donor cells migrate into the recipient's spieen early after transplantation. The number of these cells was smaller when the transplanted organ was perfused with the mAb. Further studies are suggested to deplete the graft of donor dendritic cells more adequately. They should also combine graft perfusion with antidass II mAb and recipient immunosuppression at reduced doses.
KW  - Chirurgie
KW  - Class II antigen blockade
KW  - rat
KW  - renal transplantation
KW  - Monoclonal antibody
KW  - dass II antigen blockade
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64431
ER  - 
TY  - JOUR
A1  - Albrecht, Marco
A1  - Sharma, Cynthia M.
A1  - Dittrich, Marcus T.
A1  - Müller, Tobias
A1  - Reinhardt, Richard
A1  - Vogel, Jörg
A1  - Rudel, Thomas
T1  - The Transcriptional Landscape of Chlamydia pneumoniae
N2  - Background: Gene function analysis of the obligate intracellular bacterium Chlamydia pneumoniae is hampered by the facts that this organism is inaccessible to genetic manipulations and not cultivable outside the host. The genomes of several strains have been sequenced; however, very little information is available on the gene structure and transcriptome of C. pneumoniae. Results: Using a differential RNA-sequencing approach with specific enrichment of primary transcripts, we defined the transcriptome of purified elementary bodies and reticulate bodies of C. pneumoniae strain CWL-029; 565 transcriptional start sites of annotated genes and novel transcripts were mapped. Analysis of adjacent genes for cotranscription revealed 246 polycistronic transcripts. In total, a distinct transcription start site or an affiliation to an operon could be assigned to 862 out of 1,074 annotated protein coding genes. Semi-quantitative analysis of mapped cDNA reads revealed significant differences for 288 genes in the RNA levels of genes isolated from elementary bodies and reticulate bodies. We have identified and in part confirmed 75 novel putative non-coding RNAs. The detailed map of transcription start sites at single nucleotide resolution allowed for the first time a comprehensive and saturating analysis of promoter consensus sequences in Chlamydia. Conclusions: The precise transcriptional landscape as a complement to the genome sequence will provide new insights into the organization, control and function of genes. Novel non-coding RNAs and identified common promoter motifs will help to understand gene regulation of this important human pathogen.
KW  - Chlamydia pneumoniae
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-69116
ER  - 
TY  - THES
A1  - Müller, Thomas M.
T1  - Computergestütztes Materialdesign: Mikrostruktur und elektrische Eigenschaften von Zirkoniumdioxid–Aluminiumoxid Keramiken
T1  - Computer-Aided Material Design: Microstructure and Electrical Properties of Zirconia-Alumina-Ceramics
N2  - Die Mikrostruktur von Zirkonoxid–Aluminiumoxid Keramiken wurde im Rasterelektronenmikroskop (REM) untersucht und mittels quantitativer Bildanalyse weiter charakterisiert. Die so erhaltenen spezifischen morphologischen Kennwerte wurden mit denen, die an dreidimensionalen Modellstrukturen äquivalent gewonnen wurden, verglichen. Es wurden modifizierte Voronoistrukturen benutzt, um die beteiligten Phasen in repräsentativen Volumenelementen (RVE) auf Voxelbasis zu erzeugen. Poren wurden an den Ecken und Kanten dieser Strukturen nachträglich hinzugefüg.
Nachdem alle relevanten Kennwerte der Modellstrukturen an die realen keramischen Mikrostrukturen angepasst wurden, musste das RVE für die Finite Element Simulationen (FES) geeignet vernetzt werden. Eine einfache Übernahme der Voxelstrukturen in hexaedrische Elemente führt zu sehr langen Rechenzeiten, und die erforderliche Genauigkeit der FES konnte nicht erreicht werden. Deshalb wurde zunächst eine adaptive Oberflächenvernetzung ausgehend von einem generally classed marching tetrahedra Algorithmus erzeugt. Dabei wurde besonderer Wert auf die Beibehaltung der zuvor angepassten Kennwerte gelegt. Um die Rechenzeiten zu verkürzen ohne die Genauigkeit der FES zu beeinträchtigen, wurden die Oberflächenvernetzungen dergestalt vereinfacht, dass eine hohe Auflösung an den Ecken und Kanten der Strukturen erhalten blieb, während sie an flachen Korngrenzen stark verringert wurde. Auf Basis dieser Oberflächenvernetzung wurden Volumenvernetzungen, inklusive der Abbildung der Korngrenzen durch Volumenelemente, erzeugt und für die FES benutzt. Dazu wurde ein FE-Modell zur Simulation der Impedanzspektren aufgestellt und validiert.
Um das makroskopische elektrische Verhalten der polykristallinen Keramiken zu simulieren, mussten zunächst die elektrischen Eigenschaften der beteiligten Einzelphasen gemessen werden. Dazu wurde eine Anlage zur Impedanzspektroskopie bis 1000 °C aufgebaut und verwendet. Durch weitere Auswertung der experimentellen Daten unter besonderer Berücksichtigung der Korngrenzeffekte wurden die individuellen Phaseneigenschaften erhalten.
Die Zusammensetzung der Mischkeramiken reichte von purem Zirkonoxid (3YSZ) bis zu purem Aluminiumoxid. Es wurde eine sehr gute Übereinstimmung zwischen den experimentellen und simulierten Werten bezüglich der betrachteten elektrischen, mechanischen und thermischen Eigenschaften erreicht. Die FES wurden verwendet, um die Einflüsse verschiedener mikrostruktureller Parameter, wie Porosität, Korngröße und Komposition, auf das makroskopische Materialverhalten näher zu untersuchen.
N2  - The microstructures of zirconia–alumina ceramics are investigated by scanning electron microscopy (SEM) and further characterised by quantitative image analysis. This leads to specific morphological parameters which are compared with the same parameters derived from three-dimensional model structures generated in voxel-based representative volume elements (RVE). Modified Voronoi clusters are employed to represent alumina and zirconia phases. Pores are added at the grain corners and edges respectively.
After adjusting all the relevant morphological parameters of the model to the real ceramics’ microstructure, the RVE has to be meshed for finite element simulations (FES). Hexahedral elements which simply use the voxel structure did not lead to sufficient accuracy of the FES. As a first step, an adapted surface tessellation is generated, using a generally classed marching tetrahedra method. Special care is taken to preserve the topology as well as the individual volumes and interfaces of the model. In terms of processing time and accuracy of the FES it is very important to simplify the initially generated surface mesh in a manner that preserves detailed resolution at corners and along edges, while decimating the number of surface elements in flat regions, i.e. at the grain boundaries. From the surface mesh an adequate tetrahedral volume tessellation, including solid elements representing the grain boundaries, is created, which is used for the FES. Therefore, a FE-model for the simulation of impedance spectra has been established and validated.
To simulate the macroscopic electrical behaviour of polycrystalline ceramics, the electrical properties of the individual constituting phases need to be measured. This is done by impedance spectroscopy up to 1000 °C. Further analysis of the experimental data with special respect to the effect of the grain boundaries is carried out to obtain the individual phases’ properties.
The sample composition was varied from pure zirconia to pure alumina. A very good agreement between experimental and simulated data was achieved in terms of electrical, thermal and mechanical properties. The FES were employed to scrutinize the effects of systematically varying microstructural properties, such as porosity, grain size and composition, on the macroscopic material behaviour.
KW  - Keramischer Werkstoff
KW  - Mikrostruktur–Eigenschafts–Korrelationen
KW  - Mikrostrukturmodellierung
KW  - Impedanzspektroskopie
KW  - Finite Element Simulationen
KW  - Microstructure–Property–Relationship
KW  - Microstructure Modelling
KW  - Impedance Spectroscopy
KW  - Finite Element Simulations
KW  - Mikrostruktur
KW  - Computersimulation
KW  - Finite-Elemente-Methode
KW  - Simulation
KW  - Dreidimensionales Modell
KW  - Gefügekunde
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-110942
ER  - 
TY  - JOUR
A1  - Englmeier, Jana
A1  - Mitesser, Oliver
A1  - Benbow, M. Eric
A1  - Hothorn, Torsten
A1  - von Hoermann, Christian
A1  - Benjamin, Caryl
A1  - Fricke, Ute
A1  - Ganuza, Cristina
A1  - Haensel, Maria
A1  - Redlich, Sarah
A1  - Riebl, Rebekka
A1  - Rojas Botero, Sandra
A1  - Rummler, Thomas
A1  - Steffan-Dewenter, Ingolf
A1  - Stengel, Elisa
A1  - Tobisch, Cynthia
A1  - Uhler, Johannes
A1  - Uphus, Lars
A1  - Zhang, Jie
A1  - Müller, Jörg
T1  - Diverse effects of climate, land use, and insects on dung and carrion decomposition
JF  - Ecosystems
N2  - Land-use intensification and climate change threaten ecosystem functions. A fundamental, yet often overlooked, function is decomposition of necromass. The direct and indirect anthropogenic effects on decomposition, however, are poorly understood. We measured decomposition of two contrasting types of necromass, rat carrion and bison dung, on 179 study sites in Central Europe across an elevational climate gradient of 168–1122 m a.s.l. and within both local and regional land uses. Local land-use types included forest, grassland, arable fields, and settlements and were embedded in three regional land-use types (near-natural, agricultural, and urban). The effects of insects on decomposition were quantified by experimental exclusion, while controlling for removal by vertebrates. We used generalized additive mixed models to evaluate dung weight loss and carrion decay rate along elevation and across regional and local land-use types. We observed a unimodal relationship of dung decomposition with elevation, where greatest weight loss occurred between 600 and 700 m, but no effects of local temperature, land use, or insects. In contrast to dung, carrion decomposition was continuously faster with both increasing elevation and local temperature. Carrion reached the final decomposition stage six days earlier when insect access was allowed, and this did not depend on land-use effect. Our experiment identified different major drivers of decomposition on each necromass form. The results show that dung and carrion decomposition are rather robust to local and regional land use, but future climate change and decline of insects could alter decomposition processes and the self-regulation of ecosystems.
KW  - decay
KW  - ecosystem function
KW  - global change
KW  - land-use intensification
KW  - necrobiome
KW  - urbanization
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325064
SN  - 1432-9840
VL  - 26
IS  - 2
ER  - 
TY  - JOUR
A1  - Pinkawa, Michael
A1  - Aebersold, Daniel M.
A1  - Böhmer, Dirk
A1  - Flentje, Michael
A1  - Ghadjar, Pirus
A1  - Schmidt-Hegemann, Nina-Sophie
A1  - Höcht, Stefan
A1  - Hölscher, Tobias
A1  - Müller, Arndt-Christian
A1  - Niehoff, Peter
A1  - Sedlmayer, Felix
A1  - Wolf, Frank
A1  - Zamboglou, Constantinos
A1  - Zips, Daniel
A1  - Wiegel, Thomas
T1  - Radiotherapy in nodal oligorecurrent prostate cancer
JF  - Strahlentherapie und Onkologie
N2  - Objective
The current article encompasses a literature review and recommendations for radiotherapy in nodal oligorecurrent prostate cancer.

Materials and methods
A literature review focused on studies comparing metastasis-directed stereotactic ablative radiotherapy (SABR) vs. external elective nodal radiotherapy (ENRT) and studies analyzing recurrence patterns after local nodal treatment was performed. The DEGRO Prostate Cancer Expert Panel discussed the results and developed treatment recommendations.

Results
Metastasis-directed radiotherapy results in high local control (often > 90% within a follow-up of 1–2 years) and can be used to improve progression-free survival or defer androgen deprivation therapy (ADT) according to prospective randomized phase II data. Distant progression after involved-node SABR only occurs within a few months in the majority of patients. ENRT improves metastases-free survival rates with increased toxicity in comparison to SABR according to retrospective comparative studies. The majority of nodal recurrences after initial local treatment of pelvic nodal metastasis are detected within the true pelvis and common iliac vessels.

Conclusion
ENRT with or without a boost should be preferred to SABR in pelvic nodal recurrences. In oligometastatic prostate cancer with distant (extrapelvic) nodal recurrences, SABR alone can be performed in selected cases. Application of additional systemic treatments should be based on current guidelines, with ADT as first-line treatment for hormone-sensitive prostate cancer. Only in carefully selected patients can radiotherapy be initially used without additional ADT outside of the current standard recommendations. Results of (randomized) prospective studies are needed for definitive recommendations.
KW  - prostate cancer
KW  - oligorecurrence
KW  - metastasis-directed therapy
KW  - radiation therapy
KW  - androgen deprivation therapy
KW  - stereotactic body radiotherapy
KW  - oligmometastases
KW  - lymph node metastases
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307763
SN  - 0179-7158
SN  - 1439-099X
VL  - 197
IS  - 7
ER  - 
TY  - JOUR
A1  - Fazeli, Gholamreza
A1  - Beer, Katharina B.
A1  - Geisenhof, Michaela
A1  - Tröger, Sarah
A1  - König, Julia
A1  - Müller-Reichert, Thomas
A1  - Wehman, Ann M.
T1  - Loss of the Major Phosphatidylserine or Phosphatidylethanolamine Flippases Differentially Affect Phagocytosis
JF  - Frontiers in Cell and Developmental Biology
N2  - The lipids phosphatidylserine (PtdSer) and phosphatidylethanolamine (PtdEth) are normally asymmetrically localized to the cytosolic face of membrane bilayers, but can both be externalized during diverse biological processes, including cell division, cell fusion, and cell death. Externalized lipids in the plasma membrane are recognized by lipid-binding proteins to regulate the clearance of cell corpses and other cell debris. However, it is unclear whether PtdSer and PtdEth contribute in similar or distinct ways to these processes. We discovered that disruption of the lipid flippases that maintain PtdSer or PtdEth asymmetry in the plasma membrane have opposite effects on phagocytosis in Caenorhabditis elegans embryos. Constitutive PtdSer externalization caused by disruption of the major PtdSer flippase TAT-1 led to increased phagocytosis of cell debris, sometimes leading to two cells engulfing the same debris. In contrast, PtdEth externalization caused by depletion of the major PtdEth flippase TAT-5 or its activator PAD-1 disrupted phagocytosis. These data suggest that PtdSer and PtdEth externalization have opposite effects on phagocytosis. Furthermore, externalizing PtdEth is associated with increased extracellular vesicle release, and we present evidence that the extent of extracellular vesicle accumulation correlates with the extent of phagocytic defects. Thus, a general loss of lipid asymmetry can have opposing impacts through different lipid subtypes simultaneously exerting disparate effects.
KW  - phagocytosis
KW  - lipid asymmetry
KW  - flippase
KW  - phosphatidylserine
KW  - phosphatidylethanolamine
KW  - extracellular vesicle
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-208771
SN  - 2296-634X
VL  - 8
ER  - 
TY  - JOUR
A1  - Schulz, Herbert
A1  - Ruppert, Ann-Kathrin
A1  - Herms, Stefan
A1  - Wolf, Christiane
A1  - Mirza-Schreiber, Nazanin
A1  - Stegle, Oliver
A1  - Czamara, Darina
A1  - Forstner, Andreas J.
A1  - Sivalingam, Sugirthan
A1  - Schoch, Susanne
A1  - Moebus, Susanne
A1  - Pütz, Benno
A1  - Hillmer, Axel
A1  - Fricker, Nadine
A1  - Vatter, Hartmut
A1  - Müller-Myhsok, Bertram
A1  - Nöthen, Markus M.
A1  - Becker, Albert J.
A1  - Hoffmann, Per
A1  - Sander, Thomas
A1  - Cichon, Sven
T1  - Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus
JF  - Nature Communications
N2  - Emerging evidence emphasizes the strong impact of regulatory genomic elements in neurodevelopmental processes and the complex pathways of brain disorders. The present genome-wide quantitative trait loci analyses explore the \(cis\)-regulatory effects of single-nucleotide polymorphisms (SNPs) on DNA methylation (meQTL) and gene expression (eQTL) in 110 human hippocampal biopsies. We identify \(cis\)-meQTLs at 14,118 CpG methylation sites and \(cis\)-eQTLs for 302 3′-mRNA transcripts of 288 genes. Hippocampal \(cis\)-meQTL-CpGs are enriched in flanking regions of active promoters, CpG island shores, binding sites of the transcription factor CTCF and brain eQTLs. \(Cis\)-acting SNPs of hippocampal meQTLs and eQTLs significantly overlap schizophrenia-associated SNPs. Correlations of CpG methylation and RNA expression are found for 34 genes. Our comprehensive maps of \(cis\)-acting hippocampal meQTLs and eQTLs provide a link between disease-associated SNPs and the regulatory genome that will improve the functional interpretation of non-coding genetic variants in the molecular genetic dissection of brain disorders.
KW  - psychiatry
KW  - epigenetics in the nervous system
KW  - epigenomics
KW  - gene expression
KW  - neurological disorders
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173168
VL  - 8
ER  - 
TY  - JOUR
A1  - Katzorke, Andrea
A1  - Zeller, Julia B. M.
A1  - Müller, Laura D.
A1  - Lauer, Martin
A1  - Polak, Thomas
A1  - Reif, Andreas
A1  - Deckert, Jürgen
A1  - Herrmann, Martin J.
T1  - Reduced activity in the right inferior frontal gyrus in elderly APOE-E4 carriers during a verbal fluency task
JF  - Frontiers in Human Neuroscience
N2  - Apolipoprotein-E4 (APOE-E4) is a major genetic risk factor for developing Alzheimer’s disease (AD). The verbal fluency task (VFT), especially the subtask category fluency, has shown to provide a good discrimination between cognitively normal controls and subjects with AD. Interestingly, APOE-E4 seems to have no effect on the behavioral performance during a VFT in healthy elderly. Thus, the purpose of the present study was to reveal possible compensation mechanisms by investigating the effect of APOE-E4 on the hemodynamic response in non-demented elderly during a VFT by using functional near-infrared spectroscopy (fNIRS). We compared performance and hemodynamic response of high risk APOE-E4/E4, -E3/E4 carriers with neutral APOE-E3/E3 non-demented subjects (N = 288; 70–77 years). No difference in performance was found. APOE-E4/E4, -E3/E4 carriers had a decreased hemodynamic response in the right inferior frontal junction (IFJ) with a corresponding higher response in the left middle frontal gyrus (MFG) during category fluency. Performance was correlated with the hemodynamic response in the MFG. We assume a compensation of decreased IFJ brain activation by utilizing the MFG during category fluency and thus resulting in no behavioral differences between APOE-groups during the performance of a VFT.
KW  - psychiatry
KW  - near-infrared spectroscopy
KW  - verbal fluency task
KW  - apolipoprotein-E4
KW  - Alzheimer's disease
KW  - elderly
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171892
VL  - 11
ER  - 
TY  - JOUR
A1  - Doll, Julia
A1  - Vona, Barbara
A1  - Schnapp, Linda
A1  - Rüschendorf, Franz
A1  - Khan, Imran
A1  - Khan, Saadullah
A1  - Muhammad, Noor
A1  - Alam Khan, Sher
A1  - Nawaz, Hamed
A1  - Khan, Ajmal
A1  - Ahmad, Naseer
A1  - Kolb, Susanne M.
A1  - Kühlewein, Laura
A1  - Labonne, Jonathan D. J.
A1  - Layman, Lawrence C.
A1  - Hofrichter, Michaela A. H.
A1  - Röder, Tabea
A1  - Dittrich, Marcus
A1  - Müller, Tobias
A1  - Graves, Tyler D.
A1  - Kong, Il-Keun
A1  - Nanda, Indrajit
A1  - Kim, Hyung-Goo
A1  - Haaf, Thomas
T1  - Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families
JF  - Genes
N2  - The current molecular genetic diagnostic rates for hereditary hearing loss (HL) vary considerably according to the population background. Pakistan and other countries with high rates of consanguineous marriages have served as a unique resource for studying rare and novel forms of recessive HL. A combined exome sequencing, bioinformatics analysis, and gene mapping approach for 21 consanguineous Pakistani families revealed 13 pathogenic or likely pathogenic variants in the genes GJB2, MYO7A, FGF3, CDC14A, SLITRK6, CDH23, and MYO15A, with an overall resolve rate of 61.9%. GJB2 and MYO7A were the most frequently involved genes in this cohort. All the identified variants were either homozygous or compound heterozygous, with two of them not previously described in the literature (15.4%). Overall, seven missense variants (53.8%), three nonsense variants (23.1%), two frameshift variants (15.4%), and one splice-site variant (7.7%) were observed. Syndromic HL was identified in five (23.8%) of the 21 families studied. This study reflects the extreme genetic heterogeneity observed in HL and expands the spectrum of variants in deafness-associated genes.
KW  - genetic diagnosis
KW  - consanguinity
KW  - genome-wide linkage analysis
KW  - hearing loss
KW  - Pakistan
KW  - exome sequencing
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219293
SN  - 2073-4425
VL  - 11
IS  - 11
ER  - 
TY  - JOUR
A1  - Müller, Laura S. M.
A1  - Cosentino, Raúl O.
A1  - Förstner, Konrad U.
A1  - Guizetti, Julien
A1  - Wedel, Carolin
A1  - Kaplan, Noam
A1  - Janzen, Christian J.
A1  - Arampatzi, Panagiota
A1  - Vogel, Jörg
A1  - Steinbiss, Sascha
A1  - Otto, Thomas D.
A1  - Saliba, Antoine-Emmanuel
A1  - Sebra, Robert P.
A1  - Siegel, T. Nicolai
T1  - Genome organization and DNA accessibility control antigenic variation in trypanosomes
JF  - Nature
N2  - Many evolutionarily distant pathogenic organisms have evolved similar survival strategies to evade the immune responses of their hosts. These include antigenic variation, through which an infecting organism prevents clearance by periodically altering the identity of proteins that are visible to the immune system of the host1. Antigenic variation requires large reservoirs of immunologically diverse antigen genes, which are often generated through homologous recombination, as well as mechanisms to ensure the expression of one or very few antigens at any given time. Both homologous recombination and gene expression are affected by three-dimensional genome architecture and local DNA accessibility2,3. Factors that link three-dimensional genome architecture, local chromatin conformation and antigenic variation have, to our knowledge, not yet been identified in any organism. One of the major obstacles to studying the role of genome architecture in antigenic variation has been the highly repetitive nature and heterozygosity of antigen-gene arrays, which has precluded complete genome assembly in many pathogens. Here we report the de novo haplotype-specific assembly and scaffolding of the long antigen-gene arrays of the model protozoan parasite Trypanosoma brucei, using long-read sequencing technology and conserved features of chromosome folding4. Genome-wide chromosome conformation capture (Hi-C) reveals a distinct partitioning of the genome, with antigen-encoding subtelomeric regions that are folded into distinct, highly compact compartments. In addition, we performed a range of analyses—Hi-C, fluorescence in situ hybridization, assays for transposase-accessible chromatin using sequencing and single-cell RNA sequencing—that showed that deletion of the histone variants H3.V and H4.V increases antigen-gene clustering, DNA accessibility across sites of antigen expression and switching of the expressed antigen isoform, via homologous recombination. Our analyses identify histone variants as a molecular link between global genome architecture, local chromatin conformation and antigenic variation.
KW  - histone variants
KW  - genome architecture
KW  - single molecule real time (SMRT)
KW  - brucei genome
KW  - distance-dependent decay
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224265
VL  - 563
ER  - 
TY  - JOUR
A1  - Krah, Franz-Sebastian
A1  - Büntgen, Ulf
A1  - Schaefer, Hanno
A1  - Müller, Jörg
A1  - Andrew, Carrie
A1  - Boddy, Lynne
A1  - Diez, Jeffrey
A1  - Egli, Simon
A1  - Freckleton, Robert
A1  - Gange, Alan C.
A1  - Halvorsen, Rune
A1  - Heegaard, Einar
A1  - Heideroth, Antje
A1  - Heibl, Christoph
A1  - Heilmann-Clausen, Jacob
A1  - Høiland, Klaus
A1  - Kar, Ritwika
A1  - Kauserud, Håvard
A1  - Kirk, Paul M.
A1  - Kuyper, Thomas W.
A1  - Krisai-Greilhuber, Irmgard
A1  - Norden, Jenni
A1  - Papastefanou, Phillip
A1  - Senn-Irlet, Beatrice
A1  - Bässler, Claus
T1  - European mushroom assemblages are darker in cold climates
JF  - Nature Communications
N2  - Thermal melanism theory states that dark-colored ectotherm organisms are at an advantage at low temperature due to increased warming. This theory is generally supported for ectotherm animals, however, the function of colors in the fungal kingdom is largely unknown. Here, we test whether the color lightness of mushroom assemblages is related to climate using a dataset of 3.2 million observations of 3,054 species across Europe. Consistent with the thermal melanism theory, mushroom assemblages are significantly darker in areas with cold climates. We further show differences in color phenotype between fungal lifestyles and a lifestyle differentiated response to seasonality. These results indicate a more complex ecological role of mushroom colors and suggest functions beyond thermal adaption. Because fungi play a crucial role in terrestrial carbon and nutrient cycles, understanding the links between the thermal environment, functional coloration and species’ geographical distributions will be critical in predicting ecosystem responses to global warming.
KW  - evolutionary ecology
KW  - fungal ecology
KW  - fungal evolution
KW  - macroecology
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224815
VL  - 10
ER  - 
TY  - JOUR
A1  - Lehmann, Julian
A1  - Jørgensen, Morten E.
A1  - Fratz, Stefanie
A1  - Müller, Heike M.
A1  - Kusch, Jana
A1  - Scherzer, Sönke
A1  - Navarro-Retamal, Carlos
A1  - Mayer, Dominik
A1  - Böhm, Jennifer
A1  - Konrad, Kai R.
A1  - Terpitz, Ulrich
A1  - Dreyer, Ingo
A1  - Mueller, Thomas D.
A1  - Sauer, Markus
A1  - Hedrich, Rainer
A1  - Geiger, Dietmar
A1  - Maierhofer, Tobias
T1  - Acidosis-induced activation of anion channel SLAH3 in the flooding-related stress response of Arabidopsis
JF  - Current Biology
N2  - Plants, as sessile organisms, gained the ability to sense and respond to biotic and abiotic stressors to survive severe changes in their environments. The change in our climate comes with extreme dry periods but also episodes of flooding. The latter stress condition causes anaerobiosis-triggered cytosolic acidosis and impairs plant function. The molecular mechanism that enables plant cells to sense acidity and convey this signal via membrane depolarization was previously unknown. Here, we show that acidosis-induced anion efflux from Arabidopsis (Arabidopsis thaliana) roots is dependent on the S-type anion channel AtSLAH3. Heterologous expression of SLAH3 in Xenopus oocytes revealed that the anion channel is directly activated by a small, physiological drop in cytosolic pH. Acidosis-triggered activation of SLAH3 is mediated by protonation of histidine 330 and 454. Super-resolution microscopy analysis showed that the increase in cellular proton concentration switches SLAH3 from an electrically silent channel dimer into its active monomeric form. Our results show that, upon acidification, protons directly switch SLAH3 to its open configuration, bypassing kinase-dependent activation. Moreover, under flooding conditions, the stress response of Arabidopsis wild-type (WT) plants was significantly higher compared to SLAH3 loss-of-function mutants. Our genetic evidence of SLAH3 pH sensor function may guide the development of crop varieties with improved stress tolerance.
KW  - SLAH3
KW  - S-type anion channel
KW  - hypoxia
KW  - pH
KW  - cytosolic acidification
KW  - flooding
KW  - PALM
KW  - stoichiometry
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-363320
VL  - 31
ER  -