TY  - JOUR
A1  - Hoffmann, Linda S.
A1  - Etzrodt, Jennifer
A1  - Willkomm, Lena
A1  - Sanyal, Abhishek
A1  - Scheja, Ludger
A1  - Fischer, Alexander W. C.
A1  - Stasch, Johannes-Peter
A1  - Bloch, Wilhelm
A1  - Friebe, Andreas
A1  - Heeren, Joerg
A1  - Pfeifer, Alexander
T1  - Stimulation of soluble guanylyl cyclase protects against obesity by recruiting brown adipose tissue
JF  - Nature Communications
N2  - Obesity is characterized by a positive energy balance and expansion of white adipose tissue (WAT). In contrast, brown adipose tissue (BAT) combusts energy to produce heat. Here we show that a small molecule stimulator (BAY 41-8543) of soluble guanylyl cyclase (sGC), which produces the second messenger cyclic GMP (cGMP), protects against diet-induced weight gain, induces weight loss in established obesity, and also improves the diabetic phenotype. Mechanistically, the haeme-dependent sGC stimulator BAY 41-8543 enhances lipid uptake into BAT and increases whole-body energy expenditure, whereas ablation of the haeme-containing \(\beta\)\(_{1}\)-subunit of sGC severely impairs BAT function. Notably, the sGC stimulator enhances differentiation of human brown adipocytes as well as induces 'browning' of primary white adipocytes. Taken together, our data suggest that sGC is a potential pharmacological target for the treatment of obesity and its comorbidities.
KW  - decompensated heart failure
KW  - mitochondrial biogenesis
KW  - pulmonary hypertension
KW  - nitric oxide
KW  - erectile dysfunction
KW  - beige adipocytes
KW  - fat development
KW  - cGMP
KW  - riociguat
KW  - white
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143127
VL  - 6
IS  - 7235
ER  - 
TY  - JOUR
A1  - Boes, Alexander
A1  - Spiegel, Holger
A1  - Voepel, Nadja
A1  - Edgue, Gueven
A1  - Beiss, Veronique
A1  - Kapelski, Stephanie
A1  - Fendel, Rolf
A1  - Scheuermayer, Matthias
A1  - Pradel, Gabriele
A1  - Bolscher, Judith M.
A1  - Behet, Marije C.
A1  - Dechering, Koen J.
A1  - Hermsen, Cornelus C.
A1  - Sauerwein, Robert W.
A1  - Schillberg, Stefan
A1  - Reimann, Andreas
A1  - Fischer, Rainer
T1  - Analysis of a multi-component multi-stage malaria vaccine candidate—tackling the cocktail challenge
JF  - PLoS ONE
N2  - Combining key antigens from the different stages of the P. falciparum life cycle in the context of a multi-stage-specific cocktail offers a promising approach towards the development of a malaria vaccine ideally capable of preventing initial infection, the clinical manifestation as well as the transmission of the disease. To investigate the potential of such an approach we combined proteins and domains (11 in total) from the pre-erythrocytic, blood and sexual stages of P. falciparum into a cocktail of four different components recombinantly produced in plants. After immunization of rabbits we determined the domain-specific antibody titers as well as component-specific antibody concentrations and correlated them with stage specific in vitro efficacy. Using purified rabbit immune IgG we observed strong inhibition in functional in vitro assays addressing the pre-erythrocytic (up to 80%), blood (up to 90%) and sexual parasite stages (100%). Based on the component-specific antibody concentrations we calculated the IC50 values for the pre-erythrocytic stage (17–25 μg/ml), the blood stage (40–60 μg/ml) and the sexual stage (1.75 μg/ml). While the results underline the feasibility of a multi-stage vaccine cocktail, the analysis of component-specific efficacy indicates significant differences in IC50 requirements for stage-specific antibody concentrations providing valuable insights into this complex scenario and will thereby improve future approaches towards malaria vaccine cocktail development regarding the selection of suitable antigens and the ratios of components, to fine tune overall and stage-specific efficacy.
KW  - malaria
KW  - vaccines
KW  - antibodies
KW  - P. falciparum
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173092
VL  - 10
IS  - 7
ER  - 
TY  - JOUR
A1  - Farmer, Adam D.
A1  - Strzelczyk, Adam
A1  - Finisguerra, Alessandra
A1  - Gourine, Alexander V.
A1  - Gharabaghi, Alireza
A1  - Hasan, Alkomiet
A1  - Burger, Andreas M.
A1  - Jaramillo, Andrés M.
A1  - Mertens, Ann
A1  - Majid, Arshad
A1  - Verkuil, Bart
A1  - Badran, Bashar W.
A1  - Ventura-Bort, Carlos
A1  - Gaul, Charly
A1  - Beste, Christian
A1  - Warren, Christopher M.
A1  - Quintana, Daniel S.
A1  - Hämmerer, Dorothea
A1  - Freri, Elena
A1  - Frangos, Eleni
A1  - Tobaldini, Eleonora
A1  - Kaniusas, Eugenijus
A1  - Rosenow, Felix
A1  - Capone, Fioravante
A1  - Panetsos, Fivos
A1  - Ackland, Gareth L.
A1  - Kaithwas, Gaurav
A1  - O'Leary, Georgia H.
A1  - Genheimer, Hannah
A1  - Jacobs, Heidi I. L.
A1  - Van Diest, Ilse
A1  - Schoenen, Jean
A1  - Redgrave, Jessica
A1  - Fang, Jiliang
A1  - Deuchars, Jim
A1  - Széles, Jozsef C.
A1  - Thayer, Julian F.
A1  - More, Kaushik
A1  - Vonck, Kristl
A1  - Steenbergen, Laura
A1  - Vianna, Lauro C.
A1  - McTeague, Lisa M.
A1  - Ludwig, Mareike
A1  - Veldhuizen, Maria G.
A1  - De Couck, Marijke
A1  - Casazza, Marina
A1  - Keute, Marius
A1  - Bikson, Marom
A1  - Andreatta, Marta
A1  - D'Agostini, Martina
A1  - Weymar, Mathias
A1  - Betts, Matthew
A1  - Prigge, Matthias
A1  - Kaess, Michael
A1  - Roden, Michael
A1  - Thai, Michelle
A1  - Schuster, Nathaniel M.
A1  - Montano, Nicola
A1  - Hansen, Niels
A1  - Kroemer, Nils B.
A1  - Rong, Peijing
A1  - Fischer, Rico
A1  - Howland, Robert H.
A1  - Sclocco, Roberta
A1  - Sellaro, Roberta
A1  - Garcia, Ronald G.
A1  - Bauer, Sebastian
A1  - Gancheva, Sofiya
A1  - Stavrakis, Stavros
A1  - Kampusch, Stefan
A1  - Deuchars, Susan A.
A1  - Wehner, Sven
A1  - Laborde, Sylvain
A1  - Usichenko, Taras
A1  - Polak, Thomas
A1  - Zaehle, Tino
A1  - Borges, Uirassu
A1  - Teckentrup, Vanessa
A1  - Jandackova, Vera K.
A1  - Napadow, Vitaly
A1  - Koenig, Julian
T1  - International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020)
JF  - Frontiers in Human Neuroscience
N2  - Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice.
KW  - transcutaneous vagus nerve stimulation
KW  - minimum reporting standards
KW  - guidelines & recommendations
KW  - transcutaneous auricular vagus nerve stimulation
KW  - transcutaneous cervical vagus nerve stimulation
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234346
SN  - 1662-5161
VL  - 14
ER  -