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Scattering studies with low-energy kaon-proton femtoscopy in proton–proton collisions at the LHC
(2020)
Acharya, Shreyasi ; Adamová, Dagmar ; Adhya, Souvik Priyam ; Adler, Alexander ; Adolfsson, Jonatan ; Aggarwal, Madan Mohan ; Aglieri Rinella, Gianluca ; Agnello, Michelangelo ; Agrawal, Neelima ; Ahammed, Zubayer ; Ahmad, Shakeel ; Ahn, Sang Un ; Aiola, Salvatore ; Akindinov, Alexander ; Al-Turany, Mohammad ; Alam, Sk Noor ; Albuquerque, D. S. D. ; Aleksandrov, Dmitry ; Alessandro, Bruno ; Alfanda, Haidar Mas’ud ; Alfaro Molina, Jose Ruben ; Ali, Bushra ; Ali, Yasir ; Alici, Andrea ; Alkin, Anton ; Alme, Johan ; Alt, Torsten ; Altenkämper, Lucas ; Altsybeev, Igor ; Anaam, Mustafa Naji ; Andrei, Cristian ; Andreou, Dimitra ; Andrews, Harry Arthur ; Andronic, Anton ; Angeletti, Massimo ; Anguelov, Venelin ; Anson, Christopher Daniel ; Antičić, Tome ; Antinori, Federico ; Antonioli, Pietro ; Anwar, Rafay ; Apadula, Nicole ; Aphecetche, Laurent Bernard ; Appelshäuser, Harald ; Arcelli, Silvia ; Arnaldi, Roberta ; Arratia, Miguel ; Arsene, Ionut Cristian ; Arslandok, Mesut ; Augustinus, Andre ; Averbeck, Ralf Peter ; Aziz, Sizar ; Azmi, Mohd Danish ; Badalà, Angela ; Baek, Yong Wook ; Bagnasco, Stefano ; Bailhache, Raphaëlle ; Bala, Remu ; Baldisseri, Alberto ; Ball, Markus ; Baral, Rama Chandra ; Barbera, Roberto ; Barioglio, Luca ; Barnaföldi, Gergely Gábor ; Barnby, Lee Stuart ; Barret, Valerie ; Bartalini, Paolo ; Barth, Klaus ; Bartsch, Esther ; Baruffaldi, Filippo ; Bastid, Nicole ; Basu, Sumit ; Batigne, Guillaume ; Batyunya, Boris ; Bätzing, Paul Christoph ; Bauri, Dibakar ; Bazo Alba, José Luis ; Bearden, Ian Gardner ; Bedda, Cristina ; Behera, Nirbhay Kumar ; Belikov, Iouri ; Bellini, Francesca ; Bellwied, Rene ; Belyaev, Vladimir ; Bencédi, Gyula ; Beolè, Stefania ; Bercuci, Alexandru ; Berdnikov, Yaroslav ; Berényi, Dániel ; Bertens, Redmer Alexander ; Berzano, Dario ; Betev, Latchezar ; Bhasin, Anju ; Bhat, Inayat Rasool ; Bhatt, Himani ; Bhattacharjee, Buddhadeb ; Bianchi, Antonio ; Bianchi, Livio ; Bianchi, Nicola ; Bielčík, Jaroslav ; Bielčíková, Jana ; Bilandzic, Ante ; Biro, Gabor ; Biswas, Rathijit ; Biswas, Saikat ; Blair, Justin Thomas ; Blau, Dmitry S. ; Blume, Christoph ; Boca, Gianluigi ; Bock, Friederike ; Bogdanov, Alexey A. ; Boldizsár, László ; Bolozdynya, Alexander I. ; Bombara, Marek ; Bonomi, Germano ; Bonora, Matthias ; Borel, Hervé ; Borissov, Alexander ; Borri, Marcello ; Bossi, Hannah ; Botta, Elena ; Bourjau, Christian ; Bratrud, Lars ; Braun-Munzinger, Peter ; Bregant, Marco ; Broker, Theo Alexander ; Broz, Michal ; Brücken, Erik Jens ; Bruna, Elena ; Bruno, Giuseppe Eugenio ; Buckland, Matthew Daniel ; Budnikov, Dmitry ; Büsching, Henner ; Bufalino, Stefania ; Bugnon, Ophélie ; Bühler, Paul ; Bunčić, Predrag ; Busch, Oliver ; Buthelezi, Edith Zinhle ; Butt, Jamila Bashir ; Buxton, Jesse Thomas ; Caffarri, Davide ; Caliva, Alberto ; Calvo Villar, Ernesto ; Soto Camacho, Rabi ; Camerini, Paolo ; Capon, Aaron Allan ; Carnesecchi, Francesca ; Castillo Castellanos, Javier Ernesto ; Castro, Andrew John ; Casula, Ester Anna Rita ; Catalano, Fabio ; Ceballos Sanchez, Cesar ; Chakraborty, Pritam ; Chandra, Sinjini ; Chang, B. ; Chang, W. ; Chapeland, Sylvain ; Chartier, Marielle ; Chattopadhyay, S. ; Chattopadhyay, S. ; Chauvin, Alex Henri Jean ; Cheshkov, Cvetan Valeriev ; Cheynis, Brigitte ; Chibante Barroso, Vasco Miguel ; Chinellato, David Dobrigkeit ; Cho, Soyeon ; Chochula, Peter ; Chowdhury, Tasnuva ; Christakoglou, Panagiotis ; Christensen, Christian Holm ; Christiansen, Peter L. ; Chujo, Tatsuya ; Cicalò, Corrado ; Cifarelli, Luisa ; Cindolo, Federico ; Cleymans, Jean Willy Andre ; Colamaria, Fabio Filippo ; Colella, Domenico ; Collu, Alberto ; Colocci, Manuel ; Concas, Matteo ; Conesa Balbastre, Gustavo ; Conesa del Valle, Zaida ; Contin, Giacomo ; Contreras Nuno, Jesus Guillermo ; Cormier, Thomas Michael ; Corrales Morales, Yasser ; Cortese, Pietro ; Cosentino, Mauro Rogerio ; Costa, Filippo ; Costanza, Susanna ; Crkovská, Jana ; Crochet, Philippe ; Cuautle Flores, Eleazar ; Cunqueiro Mendez, Leticia ; Dąbrowski, Daniel ; Dahms, Torsten ; Dainese, Andrea ; Damas, F. P. A. ; Dani, Sanskruti ; Danisch, Meike Charlotte ; Danu, Andrea ; Das, Debasish ; Das, Indranil ; Das, Supriya ; Dash, Ajay Kumar ; Dash, Sadhana ; Dashi, Anisa ; De, Sudipan ; De Caro, Annalisa ; De Cataldo, Giacinto ; Conti, Camila de ; Cuveland, Jan de ; De Falco, Alessandro ; De Gruttola, Daniele ; De Marco, Nora ; De Pasquale, Salvatore ; Souza, Rafael Derradi de ; Deb, Suman ; Degenhardt, Hermann Franz ; Deisting, Alexander ; Deja, Kamil Rafal ; Deloff, Andrzej ; Delsanto, Silvia ; Dhankher, Preeti ; Di Bari, Domenico ; Di Mauro, Antonio ; Diaz, R. 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F. ; Wenzel, Sandro Christian ; Wessels, Johannes P. ; Westerhoff, Uwe ; Whitehead, Andile Mothegi ; Widmann, Eberhard ; Wiechula, Jens ; Wikne, Jon ; Wilk, Grzegorz Andrzej ; Wilkinson, Jeremy ; Willems, Guido Alexander ; Willsher, Emily Jade ; Windelband, Bernd ; Witt, William Edward ; Wu, Y. ; Xu, Ran ; Yalcin, Serpil ; Yamakawa, Kosei ; Yang, S. ; Yano, Satoshi ; Yin, Zhongbao ; Yokoyama, Hiroki ; Yoo, In-Kwon ; Yoon, Jin-Hee ; Yuan, S. ; Yüncü, Alperen ; Yurchenko, Volodymyr ; Zaccolo, Valentina ; Zaman, Ali ; Zampolli, Chiara ; Correia Zanoli, Henrique Jose ; Zardoshti, Nima ; Zarochentsev, Andrey ; Závada, Petr ; Zaviyalov, Nikolaj ; Zbroszczyk, Hanna Paulina ; Zhalov, Mikhail ; Zhang, X. ; Zhang, Z. ; Zhao, C. ; Zherebchevskii, Vladimir ; Zhigareva, Natalia ; Zhou, D. ; Zhou, Y. ; Zhou, Z. ; Zhu, J. ; Zhu, Y. ; Zichichi, Antonino ; Zimmermann, Markus ; Zinovjev, Gennady M. ; Zurlo, Nicola
The study of the strength and behaviour of the antikaon-nucleon (K¯¯¯¯N) interaction constitutes one of the key focuses of the strangeness sector in low-energy Quantum Chromodynamics (QCD). In this letter a unique high-precision measurement of the strong interaction between kaons and protons, close and above the kinematic threshold, is presented. The femtoscopic measurements of the correlation function at low pair-frame relative momentum of (K+ p ⊕ K− p¯¯¯) and (K− p ⊕ K+ p¯¯¯) pairs measured in pp collisions at s√ = 5, 7 and 13 TeV are reported. A structure observed around a relative momentum of 58 MeV/c in the measured correlation function of (K− p ⊕ K+ p¯¯¯) with a significance of 4.4. σ constitutes the first experimental evidence for the opening of the (K¯¯¯¯0n⊕K0n¯¯¯) isospin breaking channel due to the mass difference between charged and neutral kaons. The measured correlation functions have been compared to Jülich and Kyoto models in addition to the Coulomb potential. The high-precision data at low relative momenta presented in this work prove femtoscopy to be a powerful complementary tool to scattering experiments and provide new constraints above the K¯¯¯¯N threshold for low-energy QCD chiral models.
Syndikus, Ina ; Petri, Marina ; Macchiavelli, Augusto O. ; Paschalis, Stefanos ; Bertulani, Carlos A. ; Aumann, Thomas ; Álvarez-Pol, Héctor ; Atar, Leyla ; Beceiro-Novo, Saul ; Benlliure Anaya, Jose Fernando ; Boillos Betete, Juan Manuel ; Boretzky, Konstanze ; Garcia Borge, Maria José ; Brown, B. Alex ; Caamaño, Manuel ; Caesar, Christoph ; Casarejos Ruiz, Enrique ; Catford, Wilton N. ; Cederkäll, Joakim ; Chakraborty, S. ; Chulkov, Leonid V. ; Cortina Gil, Dolores ; Cravo, Edgar ; Crespo, Raquel ; Datta Pramanik, Ushasi ; Dillmann, Iris ; Díaz Fernández, Paloma ; Elekes, Zoltán ; Enders, Joachim ; Farinon, Fabio ; Fraile Prieto, Luis Mario ; Galaviz Redondo, Daniel ; Geissel, Hans ; Gernhäuser, Roman ; Golubev, Pavel ; Göbel, Kathrin ; Heil, Michael ; Heine, Marcel ; Heinz, Andreas ; Henriques Correia, Ana Maria ; Holl, Matthias ; Johansson, Håkan T. ; Jonson, Björn ; Kalantar-Nayestanaki, Nasser ; Kanungo, Rituparna ; Kelic-Heil, Aleksandra ; Kröll, Thorsten ; Kurz, Nikolaus ; Langer, Christoph ; Le Bleis, Tudi ; Machado, Jorge ; Marganiec-Gałązka, Justyna ; Nácher González, Enrique ; Nilsson, Thomas ; Nociforo, Chiara ; Panin, Valerii ; Perea Martinez, Angel ; Pietri, Stephane ; Plag, Ralf ; Rahaman, Anisur ; Reifarth, René ; Revel, Aldric ; Ribeiro Jimenez, Guillermo ; Rigollet, Catherine ; Rossi, Dominic M. ; Savran, Deniz ; Scheit, Heiko ; Simon, Haik ; Sorlin, Olivier ; Tengblad, Olof ; Togano, Yasuhiro ; Vandebrouck, Marine ; Volkov, Vasily ; Wamers, Felix ; Wheldon, Carl ; Wilson, Gemma Louise ; Winfield, John S. ; Weick, Helmut ; Woods, Philip John ; Yakorev, Dmitry ; Zhukov, Mikhail V. ; Zilges, Andreas ; Zuber, Kai
The evolution of the traditional nuclear magic numbers away from the valley of stability is an active field of research. Experimental efforts focus on providing key spectroscopic information that will shed light into the structure of exotic nuclei and understanding the driving mechanism behind the shell evolution. In this work, we investigate the spin-orbit shell gap towards the neutron dripline. To do so, we employed (p,2p) quasi-free scattering reactions to measure the proton component of the state of 16,18,20C. The experimental findings support the notion of a moderate reduction of the proton spin-orbit splitting, at variance to recent claims for a prevalent magic number towards the neutron dripline.
Leiblein, Maximilian ; Winkenbach, Andreas Thomas ; Koch, Elias Andreas Thomas ; Schaible, Alexander ; Büchner, Hubert ; Marzi, Ingo ; Henrich, Dirk ; Nau, Christoph
Purpose: The Masquelet technique for the treatment of large bone defects is a two-stage procedure based on an induced membrane. Compared to mature periosteum, the induced membrane differs significantly. However, both play a crucial role in bone regeneration. As part of a histological and radiological post-evaluation of an earlier project, we analyzed the influence of the granule size of the bone void filler Herafill® on development of periosteum regrowth in a critical size defect.
Methods: We compared three different sizes of Herafill® granules (Heraeus Medical GmbH, Wehrheim) in vivo in a rat femoral critical size defect (10 mm) treated with the induced membrane technique. After 8 weeks healing time, femurs were harvested and taken for histological and radiological analysis.
Results: A significantly increased regrowth of periosteum into the defect was found when small granules were used. Large granules showed significantly increased occurrence of bone capping. Small granules lead to significant increase in callus formation in the vicinity to the membrane.
Conclusion: The size of Herafill® granules has significant impact on the development of periosteal-like structures around the defect using Masquelet’s induced membrane technique. Small granules show significantly increased regrowth of periosteum and improved bone formation adjacent to the induced membrane.
Göbel, Kathrin ; Heil, Michael ; Bott, Lukas ; Brandenburg, Leonard ; Caesar, Christoph ; Deuter, Isabell ; Grein, Alexander ; Keliç-Heil, Aleksandra ; Körper, Daniel ; Löher, Bastian ; Reifarth, René ; Savran, Deniz ; Schulte, Hendrik ; Simon, Haik ; Törnqvist, Hans Toshihide ; Almusidi, Tahani ; Álvarez-Pol, Héctor ; Atkins, Liam ; Aumann, Thomas ; Bemmerer, Daniel ; Benlliure Anaya, Jose Fernando ; Boretzky, Konstanze ; Brückner, Benjamin ; Cabanelas Eiras, Pablo ; Casarejos Ruiz, Enrique ; Cederkäll, Joakim ; Chulkov, Leonid V. ; Cortina Gil, Dolores ; Danilov, Andrey ; Erbacher, Philipp ; Escribano Rodriguez, Sonia ; Fülöp, Zsolt ; Falduto, Ashton ; Fiebiger, Stefan ; Gašparić, Igor ; Garcia Borge, Maria José ; Gernhäuser, Roman ; Glorius, Jan ; Gonzales Caamaño, David ; Hartig, Anna-Lena ; Heftrich, Tanja ; Heggen, Henning ; Heine, Marcel ; Heinz, Andreas ; Hensel, Thomas ; Holl, Matthias ; Johansson, Håkan T. ; Jonson, Björn ; Kalantar-Nayestanaki, Nasser ; Kamenyero, Armel ; Khasawneh, Kafa al- ; Kiselev, Oleg A. ; Klenze, Philipp ; Kohls, Marvin ; Kröll, Thorsten ; Kresan, Dmytro ; Kurtulgil, Cem Deniz ; Kurz, Nikolaus ; Langer, Christoph ; Lehr, Christopher ; Litvinov, Yuri A. ; Lorenz, Enis ; Murillo Morales, Silvia ; Nácher González, Enrique ; Nilsson, Thomas ; Park, Joochun ; Paschalis, Stefanos ; Perea Martinez, Angel ; Petri, Marina ; Plag, Ralf ; Ponnath, Lukas ; Popočovski, Romana ; Reich, Markus ; Rhee, Han-Bum ; Rodriguez Sanchez, Jose Luis ; Rossi, Dominic M. ; Scheit, Heiko ; Schmidt, Konrad ; Slavkovská, Zuzana ; Starostin, Viktor ; Storck, Sonja ; Sürder, Christian ; Tanaka, Junki ; Tengblad, Olof ; Thomas, Benedikt ; Typel, Stefan ; Varga, László ; Volk, Klaus ; Volknandt, Meiko ; Wagner, Vadim ; Wamers, Felix ; Weigand, Mario ; Zanetti, Lorenzo
We measured the Coulomb dissociation of 16O into 4He and 12C at the R3B setup in a first campaign within FAIR Phase 0 at GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt. The goal was to improve the accuracy of the experimental data for the 12C(α,γ)16O fusion reaction and to reach lower center-ofmass energies than measured so far.
The experiment required beam intensities of 109 16O ions per second at an energy of 500 MeV/nucleon. The rare case of Coulomb breakup into 12C and 4He posed another challenge: The magnetic rigidities of the particles are so close because of the same mass-to-charge-number ratio A/Z = 2 for 16O, 12C and 4He. Hence, radical changes of the R3B setup were necessary. All detectors had slits to allow the passage of the unreacted 16O ions, while 4He and 12C would hit the detectors' active areas depending on the scattering angle and their relative energies. We developed and built detectors based on organic scintillators to track and identify the reaction products with sufficient precision.
Queck, Alexander David Roger ; Fink, Annika F. ; Sirait-Fischer, Evelyn Nicole Joy ; Rüschenbaum, Sabrina ; Thomas, Dominique Jeanette ; Snodgrass, Ryan G. ; Geisslinger, Gerd ; Baba, Hideo Andreas ; Trebicka, Jonel ; Zeuzem, Stefan ; Weigert, Andreas ; Lange, Christian ; Brüne, Bernhard
Alcoholism is one of the leading and increasingly prevalent reasons of liver associated morbidity and mortality worldwide. Alcoholic hepatitis (AH) constitutes a severe disease with currently no satisfying treatment options. Lipoxin A4 (LXA4), a 15-lipoxygenase (ALOX15)-dependent lipid mediator involved in resolution of inflammation, showed promising pre-clinical results in the therapy of several inflammatory diseases. Since inflammation is a main driver of disease progression in alcoholic hepatitis, we investigated the impact of endogenous ALOX15-dependent lipid mediators and exogenously applied LXA4 on AH development. A mouse model for alcoholic steatohepatitis (NIAAA model) was tested in Alox12/15+/+ and Alox12/15−/− mice, with or without supplementation of LXA4. Absence of Alox12/15 aggravated parameters of liver disease, increased hepatic immune cell infiltration in AH, and elevated systemic neutrophils as a marker for systemic inflammation. Interestingly, i.p. injections of LXA4 significantly lowered transaminase levels only in Alox12/15−/− mice and reduced hepatic immune cell infiltration as well as systemic inflammatory cytokine expression in both genotypes, even though steatosis progressed. Thus, while LXA4 injection attenuated selected parameters of disease progression in Alox12/15−/− mice, its beneficial impact on immunity was also apparent in Alox12/15+/+ mice. In conclusion, pro-resolving lipid mediators may be beneficial to reduce inflammation in alcoholic hepatitis.
Lenz, Maximilian ; Eichler, Amelie ; Kruse, Pia ; Strehl, Andreas ; Rodriguez-Rozada, Silvia ; Goren, Itamar ; Yogev, Nir ; Frank, Stefan ; Waisman, Ari ; Deller, Thomas ; Jung, Steffen ; Maggio, Nicola ; Vlachos, Andreas
Systemic inflammation is associated with alterations in complex brain functions such as learning and memory. However, diagnostic approaches to functionally assess and quantify inflammation-associated alterations in synaptic plasticity are not well-established. In previous work, we demonstrated that bacterial lipopolysaccharide (LPS)-induced systemic inflammation alters the ability of hippocampal neurons to express synaptic plasticity, i.e., the long-term potentiation (LTP) of excitatory neurotransmission. Here, we tested whether synaptic plasticity induced by repetitive magnetic stimulation (rMS), a non-invasive brain stimulation technique used in clinical practice, is affected by LPS-induced inflammation. Specifically, we explored brain tissue cultures to learn more about the direct effects of LPS on neural tissue, and we tested for the plasticity-restoring effects of the anti-inflammatory cytokine interleukin 10 (IL10). As shown previously, 10 Hz repetitive magnetic stimulation (rMS) of organotypic entorhino-hippocampal tissue cultures induced a robust increase in excitatory neurotransmission onto CA1 pyramidal neurons. Furthermore, LPS-treated tissue cultures did not express rMS-induced synaptic plasticity. Live-cell microscopy in tissue cultures prepared from a novel transgenic reporter mouse line [C57BL/6-Tg(TNFa-eGFP)] confirms that ex vivo LPS administration triggers microglial tumor necrosis factor alpha (TNFα) expression, which is ameliorated in the presence of IL10. Consistent with this observation, IL10 hampers the LPS-induced increase in TNFα, IL6, IL1β, and IFNγ and restores the ability of neurons to express rMS-induced synaptic plasticity in the presence of LPS. These findings establish organotypic tissue cultures as a suitable model for studying inflammation-induced alterations in synaptic plasticity, thus providing a biological basis for the diagnostic use of transcranial magnetic stimulation in the context of brain inflammation.
Risk stratification for bipolar disorder using polygenic risk scores among young high-risk adults
(2020)
Biere, Silvia ; Kranz, Thorsten Manfred ; Matura, Silke ; Petrova, Kristiyana ; Streit, Fabian ; Geburtig-Chiocchetti, Andreas ; Grimm, Oliver ; Brum, Murielle ; Brunkhorst-Kanaan, Nathalie ; Oertel, Viola ; Malyshau, Aliaksandr ; Pfennig, Andrea ; Bauer, Michael ; Schulze, Thomas Gerd ; Kittel-Schneider, Sarah ; Reif, Andreas
Objective: Identifying high-risk groups with an increased genetic liability for bipolar disorder (BD) will provide insights into the etiology of BD and contribute to early detection of BD. We used the BD polygenic risk score (PRS) derived from BD genome-wide association studies (GWAS) to explore how such genetic risk manifests in young, high-risk adults. We postulated that BD-PRS would be associated with risk factors for BD.
Methods: A final sample of 185 young, high-risk German adults (aged 18–35 years) were grouped into three risk groups and compared to a healthy control group (n = 1,100). The risk groups comprised 117 cases with attention deficit hyperactivity disorder (ADHD), 45 with major depressive disorder (MDD), and 23 help-seeking adults with early recognition symptoms [ER: positive family history for BD, (sub)threshold affective symptomatology and/or mood swings, sleeping disorder]. BD-PRS was computed for each participant. Logistic regression models (controlling for sex, age, and the first five ancestry principal components) were used to assess associations of BD-PRS and the high-risk phenotypes.
Results: We observed an association between BD-PRS and combined risk group status (OR = 1.48, p < 0.001), ADHD diagnosis (OR = 1.32, p = 0.009), MDD diagnosis (OR = 1.96, p < 0.001), and ER group status (OR = 1.7, p = 0.025; not significant after correction for multiple testing) compared to healthy controls.
Conclusions: In the present study, increased genetic risk for BD was a significant predictor for MDD and ADHD status, but not for ER. These findings support an underlying shared risk for both MDD and BD as well as ADHD and BD. Improving our understanding of the underlying genetic architecture of these phenotypes may aid in early identification and risk stratification.
Zhang, Rong ; Gehlen, Jan ; Kawalia, Amit ; Melissari, Maria-Theodora ; Dakal, Tikam Chand ; Menon, Athira M. ; Höfele, Julia ; Riedhammer, Korbinian ; Waffenschmidt, Lea ; Fabian, Julia ; Breuer, Katinka ; Kalanithy, Jeshurun ; Hilger, Alina Christine ; Sharma, Amit ; Hölscher, Alice ; Boemers, Thomas M. ; Pauly, Markus ; Leutner, Andreas ; Fuchs, Jörg ; Seitz, Guido ; Ludwikowski, Barbara ; Gomez, Barbara ; Hubertus, Jochen ; Heydweiller, Andreas ; Kurz, Ralf ; Leonhardt, Johannes ; Kosch, Ferdinand ; Holland-Cunz, Stefan ; Münsterer, Oliver ; Ure, Beno ; Schmiedeke, Eberhard ; Neser, Jörg ; Degenhardt, Petra ; Märzheuser, Stefanie ; Kleine, Katharina ; Schäfer, Mattias ; Spychalski, Nicole ; Deffaa, Oliver J. ; Gosemann, Jan-Hendrik ; Lacher, Martin ; Heilmann-Heimbach, Stefanie ; Zwink, Nadine ; Jenetzky, Ekkehart ; Ludwig, Michael ; Grote, Phillip ; Schumacher, Johannes ; Thiele, Holger ; Reutter, Heiko
Introduction: Esophageal atresia with or without tracheoesophageal fistula (EA/TEF) occurs approximately 1 in 3.500 live births representing the most common malformation of the upper digestive tract. Only half a century ago, EA/TEF was fatal among affected newborns suggesting that the steady birth prevalence might in parts be due to mutational de novo events in genes involved in foregut development.
Methods: To identify mutational de novo events in EA/TEF patients, we surveyed the exome of 30 case-parent trios. Identified and confirmed de novo variants were prioritized using in silico prediction tools. To investigate the embryonic role of genes harboring prioritized de novo variants we performed targeted analysis of mouse transcriptome data of esophageal tissue obtained at the embryonic day (E) E8.5, E12.5, and postnatal.
Results: In total we prioritized 14 novel de novo variants in 14 different genes (APOL2, EEF1D, CHD7, FANCB, GGT6, KIAA0556, NFX1, NPR2, PIGC, SLC5A2, TANC2, TRPS1, UBA3, and ZFHX3) and eight rare de novo variants in eight additional genes (CELSR1, CLP1, GPR133, HPS3, MTA3, PLEC, STAB1, and PPIP5K2). Through personal communication during the project, we identified an additional EA/TEF case-parent trio with a rare de novo variant in ZFHX3. In silico prediction analysis of the identified variants and comparative analysis of mouse transcriptome data of esophageal tissue obtained at E8.5, E12.5, and postnatal prioritized CHD7, TRPS1, and ZFHX3 as EA/TEF candidate genes. Re-sequencing of ZFHX3 in additional 192 EA/TEF patients did not identify further putative EA/TEF-associated variants.
Conclusion: Our study suggests that rare mutational de novo events in genes involved in foregut development contribute to the development of EA/TEF.
Baumeister, Sarah ; Mößnang, Carolin Ulrike ; Bast, Nico ; Hohmann, Sarah ; Tillmann, Julian ; Goyard, David ; Charman, Tony ; Ambrosino, Sara ; Baron-Cohen, Simon ; Beckmann, Christian F. ; Bölte, Sven ; Bourgeron, Thomas ; Rausch, Annika ; Crawley, Daisy ; Dell'Acqua, Flavio ; Dumas, Guillaume ; Durston, Sarah ; Ecker, Christine ; Floris, Dorothea L. ; Frouin, Vincent ; Hayward, Hannah ; Holt, Rosemary ; Johnson, Mark H. ; Jones, Emily J. H. ; Lai, Meng-Chuan ; Lombardo, Michael V. ; Mason, Luke ; Oldehinkel, Marianne ; Persico, Tony ; San José Cáceres, Antonia ; Wolfers, Thomas ; Spooren, Willibrordus Philippus Johannes Maria ; Loth, Eva ; Murphy, Declan G. M. ; Buitelaar, Jan K. ; Tost, Heike ; Meyer-Lindenberg, Andreas ; Banaschewski, Tobias ; Brandeis, Daniel
Background Reward processing has been proposed to underpin atypical social behavior, a core feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social rewards in ASD. Utilizing a large sample, we aimed to assess altered reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.
Methods Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6-30.5 years) and 181 typically developing (TD) participants (7.6-30.8 years).
Results Across social and monetary reward anticipation, whole-brain analyses (p<0.05, family-wise error-corrected) showed hypoactivation of the right ventral striatum (VS) in ASD. Further, region of interest (ROI) analysis across both reward types yielded hypoactivation in ASD in both the left and right VS. Across delivery of social and monetary reward, hyperactivation of the VS in individuals with ASD did not survive correction for multiple comparisons. Reward type by diagnostic group interactions, and a dimensional analysis of autism trait scores were not significant during anticipation or delivery. Levels of attention-deficit/hyperactivity disorder (ADHD) symptoms did not affect reward processing in ASD.
Conclusions Our results do not support current theories linking atypical social interaction in ASD to specific alterations in processing of social rewards. Instead, they point towards a generalized hypoactivity of VS in ASD during anticipation of both social and monetary rewards. We suggest that this indicates attenuated subjective reward value in ASD independent of social content and ADHD symptoms.
Waidmann, Oliver ; Pleli, Thomas ; Weigert, Andreas ; Imelmann, Esther ; Kakoschky, Bianca ; Schmithals, Jens Christian Johannes ; Döring, Claudia ; Frank, Matthias ; Longerich, Thomas ; Köberle, Verena ; Hansmann, Martin-Leo ; Brüne, Bernhard ; Zeuzem, Stefan ; Piiper, Albrecht ; Đikić, Ivan
The nuclear factor kappa beta (NFκB) signaling pathway plays an important role in liver homeostasis and cancer development. Tax1-binding protein 1 (Tax1BP1) is a regulator of the NFκB signaling pathway, but its role in the liver and hepatocellular carcinoma (HCC) is presently unknown. Here we investigated the role of Tax1BP1 in liver cells and murine models of HCC and liver fibrosis. We applied the diethylnitrosamine (DEN) model of experimental hepatocarcinogenesis in Tax1BP1+/+ and Tax1BP1−/− mice. The amount and subsets of non-parenchymal liver cells in in Tax1BP1+/+ and Tax1BP1−/− mice were determined and activation of NFκB and stress induced signaling pathways were assessed. Differential expression of mRNA and miRNA was determined. Tax1BP1−/− mice showed increased numbers of inflammatory cells in the liver. Furthermore, a sustained activation of the NFκB signaling pathway was found in hepatocytes as well as increased transcription of proinflammatory cytokines in isolated Kupffer cells from Tax1BP1−/− mice. Several differentially expressed mRNAs and miRNAs in livers of Tax1BP1−/− mice were found, which are regulators of inflammation or are involved in cancer development or progression. Furthermore, Tax1BP1−/− mice developed more HCCs than their Tax1BP1+/+ littermates. We conclude that Tax1BP1 protects from liver cancer development by limiting proinflammatory signaling.