@article{DavisYuKeenanetal.2013, author = {Davis, Lea K. and Yu, Dongmei and Keenan, Clare L. and Gamazon, Eric R. and Konkashbaev, Anuar I. and Derks, Eske M. and Neale, Benjamin M. and Yang, Jian and Lee, S. Hong and Evans, Patrick and Barr, Cathy L. and Bellodi, Laura and Benarroch, Fortu and Berrio, Gabriel Bedoya and Bienvenu, Oscar J. and Bloch, Michael H. and Blom, Rianne M. and Bruun, Ruth D. and Budman, Cathy L. and Camarena, Beatriz and Campbell, Desmond and Cappi, Carolina and Cardona Silgado, Julio C. and Cath, Danielle C. and Cavallini, Maria C. and Chavira, Denise A. and Chouinard, Sylvian and Conti, David V. and Cook, Edwin H. and Coric, Vladimir and Cullen, Bernadette A. and Deforce, Dieter and Delorme, Richard and Dion, Yves and Edlund, Christopher K. and Egberts, Karin and Falkai, Peter and Fernandez, Thomas V. and Gallagher, Patience J. and Garrido, Helena and Geller, Daniel and Girard, Simon L. and Grabe, Hans J. and Grados, Marco A. and Greenberg, Benjamin D. and Gross-Tsur, Varda and Haddad, Stephen and Heiman, Gary A. and Hemmings, Sian M. J. and Hounie, Ana G. and Illmann, Cornelia and Jankovic, Joseph and Jenike, Micheal A. and Kennedy, James L. and King, Robert A. and Kremeyer, Barbara and Kurlan, Roger and Lanzagorta, Nuria and Leboyer, Marion and Leckman, James F. and Lennertz, Leonhard and Liu, Chunyu and Lochner, Christine and Lowe, Thomas L. and Macciardi, Fabio and McCracken, James T. and McGrath, Lauren M. and Restrepo, Sandra C. Mesa and Moessner, Rainald and Morgan, Jubel and Muller, Heike and Murphy, Dennis L. and Naarden, Allan L. and Ochoa, William Cornejo and Ophoff, Roel A. and Osiecki, Lisa and Pakstis, Andrew J. and Pato, Michele T. and Pato, Carlos N. and Piacentini, John and Pittenger, Christopher and Pollak, Yehunda and Rauch, Scott L. and Renner, Tobias J. and Reus, Victor I. and Richter, Margaret A. and Riddle, Mark A. and Robertson, Mary M. and Romero, Roxana and Ros{\`a}rio, Maria C. and Rosenberg, David and Rouleau, Guy A. and Ruhrmann, Stephan and Ruiz-Linares, Andreas and Sampaio, Aline S. and Samuels, Jack and Sandor, Paul and Sheppard, Broke and Singer, Harvey S. and Smit, Jan H. and Stein, Dan J. and Strengman, E. and Tischfield, Jay A. and Valencia Duarte, Ana V. and Vallada, Homero and Van Nieuwerburgh, Flip and Veenstra-VanderWeele, Jeremy and Walitza, Susanne and Wang, Ying and Wendland, Jens R. and Westenberg, Herman G. M. and Shugart, Yin Yao and Miguel, Euripedes C. and McMahon, William and Wagner, Michael and Nicolini, Humberto and Posthuma, Danielle and Hanna, Gregory L. and Heutink, Peter and Denys, Damiaan and Arnold, Paul D. and Oostra, Ben A. and Nestadt, Gerald and Freimer, Nelson B. and Pauls, David L. and Wray, Naomi R. and Stewart, S. Evelyn and Mathews, Carol A. and Knowles, James A. and Cox, Nancy J. and Scharf, Jeremiah M.}, title = {Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture}, series = {PLoS Genetics}, volume = {9}, journal = {PLoS Genetics}, number = {10}, issn = {1553-7390}, doi = {10.1371/journal.pgen.1003864}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-127377}, pages = {e1003864}, year = {2013}, abstract = {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.}, language = {en} } @article{KressHuettenhoferLandryetal.2013, author = {Kress, Michaela and H{\"u}ttenhofer, Alexander and Landry, Marc and Kuner, Rohini and Favereaux, Alexandre and Greenberg, David and Bednarik, Josef and Heppenstall, Paul and Kronenberg, Florian and Malcangio, Marzia and Rittner, Heike and {\"U}{\c{c}}eyler, Nurcan and Trajanoski, Zlatko and Mouritzen, Peter and Birklein, Frank and Sommer, Claudia and Soreq, Hermona}, title = {microRNAs in nociceptive circuits as predictors of future clinical applications}, series = {Frontiers in Molecular Neuroscience}, volume = {6}, journal = {Frontiers in Molecular Neuroscience}, number = {33}, doi = {10.3389/fnmol.2013.00033}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154597}, year = {2013}, abstract = {Neuro-immune alterations in the peripheral and central nervous system play a role in the pathophysiology of chronic pain, and non-coding RNAs - and microRNAs (miRNAs) in particular - regulate both immune and neuronal processes. Specifically, miRNAs control macromolecular complexes in neurons, glia and immune cells and regulate signals used for neuro-immune communication in the pain pathway. Therefore, miRNAs may be hypothesized as critically important master switches modulating chronic pain. In particular, understanding the concerted function of miRNA in the regulation of nociception and endogenous analgesia and defining the importance of miRNAs in the circuitries and cognitive, emotional and behavioral components involved in pain is expected to shed new light on the enigmatic pathophysiology of neuropathic pain, migraine and complex regional pain syndrome. Specific miRNAs may evolve as new druggable molecular targets for pain prevention and relief. Furthermore, predisposing miRNA expression patterns and inter-individual variations and polymorphisms in miRNAs and/or their binding sites may serve as biomarkers for pain and help to predict individual risks for certain types of pain and responsiveness to analgesic drugs. miRNA-based diagnostics are expected to develop into hands-on tools that allow better patient stratification, improved mechanism-based treatment, and targeted prevention strategies for high risk individuals.}, language = {en} } @article{ViljurAbellaAdameketal.2022, author = {Viljur, Mari-Liis and Abella, Scott R. and Ad{\´a}mek, Martin and Alencar, Janderson Batista Rodrigues and Barber, Nicholas A. and Beudert, Burkhard and Burkle, Laura A. and Cagnolo, Luciano and Campos, Brent R. and Chao, Anne and Chergui, Brahim and Choi, Chang-Yong and Cleary, Daniel F. R. and Davis, Thomas Seth and Dechnik-V{\´a}zquez, Yanus A. and Downing, William M. and Fuentes-Ramirez, Andr{\´e}s and Gandhi, Kamal J. K. and Gehring, Catherine and Georgiev, Kostadin B. and Gimbutas, Mark and Gongalsky, Konstantin B. and Gorbunova, Anastasiya Y. and Greenberg, Cathryn H. and Hylander, Kristoffer and Jules, Erik S. and Korobushkin, Daniil I. and K{\"o}ster, Kajar and Kurth, Valerie and Lanham, Joseph Drew and Lazarina, Maria and Leverkus, Alexandro B. and Lindenmayer, David and Marra, Daniel Magnabosco and Mart{\´i}n-Pinto, Pablo and Meave, Jorge A. and Moretti, Marco and Nam, Hyun-Young and Obrist, Martin K. and Petanidou, Theodora and Pons, Pere and Potts, Simon G. and Rapoport, Irina B. and Rhoades, Paul R. and Richter, Clark and Saifutdinov, Ruslan A. and Sanders, Nathan J. and Santos, Xavier and Steel, Zachary and Tavella, Julia and Wendenburg, Clara and Wermelinger, Beat and Zaitsev, Andrey S. and Thorn, Simon}, title = {The effect of natural disturbances on forest biodiversity: an ecological synthesis}, series = {Biological Reviews}, volume = {97}, journal = {Biological Reviews}, number = {5}, doi = {10.1111/brv.12876}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287168}, pages = {1930 -- 1947}, year = {2022}, abstract = {Disturbances alter biodiversity via their specific characteristics, including severity and extent in the landscape, which act at different temporal and spatial scales. Biodiversity response to disturbance also depends on the community characteristics and habitat requirements of species. Untangling the mechanistic interplay of these factors has guided disturbance ecology for decades, generating mixed scientific evidence of biodiversity responses to disturbance. Understanding the impact of natural disturbances on biodiversity is increasingly important due to human-induced changes in natural disturbance regimes. In many areas, major natural forest disturbances, such as wildfires, windstorms, and insect outbreaks, are becoming more frequent, intense, severe, and widespread due to climate change and land-use change. Conversely, the suppression of natural disturbances threatens disturbance-dependent biota. Using a meta-analytic approach, we analysed a global data set (with most sampling concentrated in temperate and boreal secondary forests) of species assemblages of 26 taxonomic groups, including plants, animals, and fungi collected from forests affected by wildfires, windstorms, and insect outbreaks. The overall effect of natural disturbances on α-diversity did not differ significantly from zero, but some taxonomic groups responded positively to disturbance, while others tended to respond negatively. Disturbance was beneficial for taxonomic groups preferring conditions associated with open canopies (e.g. hymenopterans and hoverflies), whereas ground-dwelling groups and/or groups typically associated with shady conditions (e.g. epigeic lichens and mycorrhizal fungi) were more likely to be negatively impacted by disturbance. Across all taxonomic groups, the highest α-diversity in disturbed forest patches occurred under moderate disturbance severity, i.e. with approximately 55\% of trees killed by disturbance. We further extended our meta-analysis by applying a unified diversity concept based on Hill numbers to estimate α-diversity changes in different taxonomic groups across a gradient of disturbance severity measured at the stand scale and incorporating other disturbance features. We found that disturbance severity negatively affected diversity for Hill number q = 0 but not for q = 1 and q = 2, indicating that diversity-disturbance relationships are shaped by species relative abundances. Our synthesis of α-diversity was extended by a synthesis of disturbance-induced change in species assemblages, and revealed that disturbance changes the β-diversity of multiple taxonomic groups, including some groups that were not affected at the α-diversity level (birds and woody plants). Finally, we used mixed rarefaction/extrapolation to estimate biodiversity change as a function of the proportion of forests that were disturbed, i.e. the disturbance extent measured at the landscape scale. The comparison of intact and naturally disturbed forests revealed that both types of forests provide habitat for unique species assemblages, whereas species diversity in the mixture of disturbed and undisturbed forests peaked at intermediate values of disturbance extent in the simulated landscape. Hence, the relationship between α-diversity and disturbance severity in disturbed forest stands was strikingly similar to the relationship between species richness and disturbance extent in a landscape consisting of both disturbed and undisturbed forest habitats. This result suggests that both moderate disturbance severity and moderate disturbance extent support the highest levels of biodiversity in contemporary forest landscapes.}, language = {en} } @article{ErbacherVaknineMoshitzkyetal.2022, author = {Erbacher, Christoph and Vaknine, Shani and Moshitzky, Gilli and Lobentanzer, Sebastian and Eisenberg, Lina and Evdokimov, Dimitar and Sommer, Claudia and Greenberg, David S. and Soreq, Hermona and {\"U}{\c{c}}eyler, Nurcan}, title = {Distinct CholinomiR blood cell signature as a potential modulator of the cholinergic system in women with fibromyalgia syndrome}, series = {Cells}, volume = {11}, journal = {Cells}, number = {8}, issn = {2073-4409}, doi = {10.3390/cells11081276}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270686}, year = {2022}, abstract = {Fibromyalgia syndrome (FMS) is a heterogeneous chronic pain syndrome characterized by musculoskeletal pain and other key co-morbidities including fatigue and a depressed mood. FMS involves altered functioning of the central and peripheral nervous system (CNS, PNS) and immune system, but the specific molecular pathophysiology remains unclear. Anti-cholinergic treatment is effective in FMS patient subgroups, and cholinergic signaling is a strong modulator of CNS and PNS immune processes. Therefore, we used whole blood small RNA-sequencing of female FMS patients and healthy controls to profile microRNA regulators of cholinergic transcripts (CholinomiRs). We compared microRNA profiles with those from Parkinson's disease (PD) patients with pain as disease controls. We validated the sequencing results with quantitative real-time PCR (qRT-PCR) and identified cholinergic targets. Further, we measured serum cholinesterase activity in FMS patients and healthy controls. Small RNA-sequencing revealed FMS-specific changes in 19 CholinomiRs compared to healthy controls and PD patients. qRT-PCR validated miR-182-5p upregulation, distinguishing FMS patients from healthy controls. mRNA targets of CholinomiRs bone morphogenic protein receptor 2 and interleukin 6 signal transducer were downregulated. Serum acetylcholinesterase levels and cholinesterase activity in FMS patients were unchanged. Our findings identified an FMS-specific CholinomiR signature in whole blood, modulating immune-related gene expression.}, language = {en} }