@article{VeniaminovaCespuglioCheungetal.2017, author = {Veniaminova, Ekaterina and Cespuglio, Raymond and Cheung, Chi Wai and Umriukhin, Alexei and Markova, Nataliia and Shevtsova, Elena and Lesch, Klaus-Peter and Anthony, Daniel C. and Strekalova, Tatyana}, title = {Autism-like behaviours and memory deficits result from a Western Diet in mice}, series = {Neural Plasticity}, journal = {Neural Plasticity}, doi = {10.1155/2017/9498247}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158211}, pages = {9498247}, year = {2017}, abstract = {Nonalcoholic fatty liver disease, induced by a Western diet (WD), evokes central and peripheral inflammation that is accompanied by altered emotionality. These changes can be associated with abnormalities in social behaviour, hippocampus-dependent cognitive functions, and metabolism. Female C57BL/6J mice were fed with a regular chow or with a WD containing 0.2\% of cholesterol and 21\% of saturated fat for three weeks. WD-treated mice exhibited increased social avoidance, crawl-over and digging behaviours, decreased body-body contacts, and hyperlocomotion. The WD-fed group also displayed deficits in hippocampal-dependent performance such as contextual memory in a fear conditioning and pellet displacement paradigms. A reduction in glucose tolerance and elevated levels of serum cholesterol and leptin were also associated with the WD. The peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1a) mRNA, a marker of mitochondrial activity, was decreased in the prefrontal cortex, hippocampus, hypothalamus, and dorsal raphe, suggesting suppressed brain mitochondrial functions, but not in the liver. This is the first report to show that a WD can profoundly suppress social interactions and induce dominant-like behaviours in na{\"i}ve adult mice. The spectrum of behaviours that were found to be induced are reminiscent of symptoms associated with autism, and, if paralleled in humans, suggest that a WD might exacerbate autism spectrum disorder.}, language = {en} } @article{ShadyElHossaryFouadetal.2017, author = {Shady, Nourhan Hisham and El-Hossary, Ebaa M. and Fouad, Mostafa A. and Gulder, Tobias A. M. and Kamel, Mohamed Salah and Abdelmohsen, Usama Ramadan}, title = {Bioactive natural products of marine sponges from the Genus Hyrtios}, series = {Molecules}, volume = {22}, journal = {Molecules}, number = {5}, doi = {10.3390/molecules22050781}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158227}, pages = {781}, year = {2017}, abstract = {Marine sponges are known as a rich source for novel bioactive compounds with valuable pharmacological potential. One of the most predominant sponge genera is Hyrtios, reported to have various species such as Hyrtios erectus, Hyrtios reticulatus, Hyrtios gumminae, Hyrtios communis, and Hyrtios tubulatus and a number of undescribed species. Members of the genus Hyrtios are a rich source of natural products with diverse and valuable biological activities, represented by different chemical classes including alkaloids, sesterterpenes and sesquiterpenes. This review covers the literature until June 2016, providing a complete survey of all compounds isolated from the genus Hyrtios with their corresponding biological activities whenever applicable.}, language = {en} } @article{ZimmermannSubotaBatrametal.2017, author = {Zimmermann, Henriette and Subota, Ines and Batram, Christopher and Kramer, Susanne and Janzen, Christian J. and Jones, Nicola G. and Engstler, Markus}, title = {A quorum sensing-independent path to stumpy development in Trypanosoma brucei}, series = {PLoS Pathogens}, volume = {13}, journal = {PLoS Pathogens}, number = {4}, doi = {10.1371/journal.ppat.1006324}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158230}, pages = {e1006324}, year = {2017}, abstract = {For persistent infections of the mammalian host, African trypanosomes limit their population size by quorum sensing of the parasite-excreted stumpy induction factor (SIF), which induces development to the tsetse-infective stumpy stage. We found that besides this cell density-dependent mechanism, there exists a second path to the stumpy stage that is linked to antigenic variation, the main instrument of parasite virulence. The expression of a second variant surface glycoprotein (VSG) leads to transcriptional attenuation of the VSG expression site (ES) and immediate development to tsetse fly infective stumpy parasites. This path is independent of SIF and solely controlled by the transcriptional status of the ES. In pleomorphic trypanosomes varying degrees of ES-attenuation result in phenotypic plasticity. While full ES-attenuation causes irreversible stumpy development, milder attenuation may open a time window for rescuing an unsuccessful antigenic switch, a scenario that so far has not been considered as important for parasite survival.}, language = {en} } @article{KoesslerSchwarzWeberetal.2017, author = {Koessler, Juergen and Schwarz, Michaela and Weber, Katja and Etzel, Julia and Koessler, Angela and Boeck, Markus and Kobsar, Anna}, title = {The role of adenosine diphosphate mediated platelet responsiveness for the stability of platelet integrity in citrated whole blood under ex vivo conditions}, series = {PLoS ONE}, volume = {12}, journal = {PLoS ONE}, number = {11}, doi = {10.1371/journal.pone.0188193}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159879}, pages = {e0188193}, year = {2017}, abstract = {Background: Platelets are important for effective hemostasis and considered to be involved in pathophysiological processes, e.g. in cardiovascular diseases. Platelets provided for research or for therapeutic use are frequently separated from citrated whole blood (WB) stored for different periods of time. Although functionally intact platelets are required, the stability of platelet integrity, e.g. adenosine diphosphate (ADP) mediated responsiveness, has never been thoroughly investigated in citrated WB under ex vivo conditions. Objectives: Platelet integrity was evaluated at different time points in citrated WB units, collected from healthy donors and stored for 5 days at ambient temperature. The analysis included the measurement of activation markers, of induced light transmission aggregometry and of purinergic receptor expression or function. Inhibitory pathways were explored by determination of basal vasodilator-stimulated phosphoprotein (VASP)-phosphorylation, intracellular cyclic nucleotide levels and the content of phosphodiesterase 5A. Fresh peripheral blood (PB) samples served as controls. Results: On day 5 of storage, thrombin receptor activating peptide-6 (TRAP-6) stimulated CD62P expression and fibrinogen binding were comparable to PB samples. ADP induced aggregation continuously decreased during storage. Purinergic receptor expression remained unchanged, whereas the P2Y1 activity progressively declined in contrast to preserved P2Y12 and P2X1 function. Inhibitory pathways were unaffected except for a slight elevation of VASP phosphorylation at Ser\(^{239}\) on day 5. Conclusion: After 5 days of storage in citrated WB, platelet responsiveness to TRAP-6 is sufficiently maintained. However, ADP-mediated platelet integrity is more sensitive to deterioration, especially after storage for more than 2 days. Decreasing ADP-induced aggregation is particularly caused by the impairment of the purinergic receptor P2Y1 activity. These characteristics should be considered in the use of platelets from stored citrated WB for experimental or therapeutic issues.}, language = {en} } @article{SchuhmannLanghauserKraftetal.2017, author = {Schuhmann, Michael K. and Langhauser, Friederike and Kraft, Peter and Kleinschnitz, Christoph}, title = {B cells do not have a major pathophysiologic role in acute ischemic stroke in mice}, series = {Journal of Neuroinflammation}, volume = {14}, journal = {Journal of Neuroinflammation}, number = {112}, doi = {10.1186/s12974-017-0890-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158155}, year = {2017}, abstract = {Background Lymphocytes have been shown to play an important role in the pathophysiology of acute ischemic stroke, but the properties of B cells remain controversial. The aim of this study was to unravel the role of B cells during acute cerebral ischemia using pharmacologic B cell depletion, B cell transgenic mice, and adoptive B cell transfer experiments. Methods Transient middle cerebral artery occlusion (60 min) was induced in wild-type mice treated with an anti-CD20 antibody 24 h before stroke onset, JHD\(^{-/-}\) mice and Rag1\(^{-/-}\) mice 24 h after adoptive B cell transfer. Stroke outcome was assessed at days 1 and 3. Infarct volumes were calculated from 2,3,5-triphenyltetrazolium chloride (TTC)-stained brain sections, and neurological scores were evaluated. The local inflammatory response was determined by real-time PCR and immunohistochemistry. Apoptosis was analyzed by TUNEL staining, and astrocyte activation was revealed using immunohistochemistry and Western blot. Results Pharmacologic depletion of B cells did not influence infarct volumes and functional outcome at day 1 after stroke. Additionally, lack of circulating B cells in JHD\(^{-/-}\) mice also failed to influence stroke outcome at days 1 and 3. Furthermore, reconstitution of Rag1\(^{-/-}\) mice with B cells had no influence on infarct volumes. Conclusion Targeting B cells in experimental stroke did not influence lesion volume and functional outcome during the acute phase. Our findings argue against a major pathophysiologic role of B cells during acute ischemic stroke.}, language = {en} } @article{ZappFischerDeuschle2017, author = {Zapp, Angela Alexandra and Fischer, Eva Caroline and Deuschle, Michael}, title = {The effect of agomelatine and melatonin on sleep-related eating: a case report}, series = {Journal of Medical Case Reports}, volume = {11}, journal = {Journal of Medical Case Reports}, number = {275}, doi = {10.1186/s13256-017-1438-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157805}, year = {2017}, abstract = {Background: Sleep-related eating may occur in the context of mental illness, sleep disorders, or psychopharmacological treatment. Frequently, sleep-related eating leads to severe weight gain and, so far, there are no treatment options for the condition. Case presentation: We report the case of a 54-year-old white woman with depression, panic disorder, and sleep apnea under treatment with various antidepressants who developed severe sleep-related eating. Her sleep-related eating completely vanished after addition of agomelatine, it reoccurred after cessation of agomelatine, and vanished again after her re-exposure to another melatonergic drug, extended melatonin. Conclusions: This case suggests that melatonergic drugs lead to relief from sleep-related eating, even when the condition occurs in the context of physical and mental disorders as well as psychopharmacological treatment.}, language = {en} } @article{TiffeWagnerRueckeretal.2017, author = {Tiffe, Theresa and Wagner, Martin and R{\"u}cker, Viktoria and Morbach, Caroline and Gelbrich, G{\"o}tz and St{\"o}rk, Stefan and Heuschmann, Peter U.}, title = {Control of cardiovascular risk factors and its determinants in the general population - findings from the STAAB cohort study}, series = {BMC Cardiovascular Disorders}, volume = {17}, journal = {BMC Cardiovascular Disorders}, number = {276}, doi = {10.1186/s12872-017-0708-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159391}, year = {2017}, abstract = {Background: While data from primary care suggest an insufficient control of vascular risk factors, little is known about vascular risk factor control in the general population. We therefore aimed to investigate the adoption of adequate risk factor control and its determinants in the general population free of cardiovascular disease (CVD). Methods: Data from the Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) Cohort Study, a population-based study of inhabitants aged 30 to 79 years from the general population of W{\"u}rzburg (Germany), were used. Proportions of participants without established CVD meeting targets for risk factor control recommended by 2016 ESC guideline were identified. Determinants of the accumulation of insufficiently controlled vascular risk factors (three or more) were assessed. Results: Between December 2013 and April 2015, 1379 participants without CVD were included; mean age was 53.1 ± 11.9 years and 52.9\% were female; 30.8\% were physically inactive, 55.2\% overweight, 19.3\% current smokers. Hypertension, dyslipidemia, and diabetes mellitus were prevalent in 31.8\%, 57.6\%, and 3.9\%, respectively. Treatment goals were not reached despite medication in 52.7\% of hypertensive, in 37.3\% of hyperlipidemic and in 44.0\% of diabetic subjects. Insufficiently controlled risk was associated with male sex (OR 1.94, 95\%CI 1.44-2.61), higher age (OR for 30-39 years vs. 70-79 years 4.01, 95\%CI 1.94-8.31) and lower level of education (OR for primary vs. tertiary 2.15, 95\%CI 1.48-3.11). Conclusions: In the general population, prevalence of vascular risk factors was high. We found insufficient identification and control of vascular risk factors and a considerable potential to improve adherence to cardiovascular guidelines for primary prevention. Further studies are needed to identify and overcome patient- and physician-related barriers impeding successful control of vascular risk factors in the general population.}, language = {en} } @article{BailNotzRovitusoetal.2017, author = {Bail, Kathrin and Notz, Quirin and Rovituso, Damiano M. and Schampel, Andrea and Wunsch, Marie and Koeniger, Tobias and Schropp, Verena and Bharti, Richa and Scholz, Claus-Juergen and Foerstner, Konrad U. and Kleinschnitz, Christoph and Kuerten, Stefanie}, title = {Differential effects of FTY720 on the B cell compartment in a mouse model of multiple sclerosis.}, series = {Journal of Neuroinflammation}, volume = {14}, journal = {Journal of Neuroinflammation}, number = {148}, doi = {10.1186/s12974-017-0924-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157869}, year = {2017}, abstract = {Background: MP4-induced experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis (MS), which enables targeted research on B cells, currently much discussed protagonists in MS pathogenesis. Here, we used this model to study the impact of the S1P1 receptor modulator FTY720 (fingolimod) on the autoreactive B cell and antibody response both in the periphery and the central nervous system (CNS). Methods: MP4-immunized mice were treated orally with FTY720 for 30 days at the peak of disease or 50 days after EAE onset. The subsequent disease course was monitored and the MP4-specific B cell/antibody response was measured by ELISPOT and ELISA. RNA sequencing was performed to determine any effects on B cell-relevant gene expression. S1P\(_{1}\) receptor expression by peripheral T and B cells, B cell subset distribution in the spleen and B cell infiltration into the CNS were studied by flow cytometry. The formation of B cell aggregates and of tertiary lymphoid organs (TLOs) was evaluated by histology and immunohistochemistry. Potential direct effects of FTY720 on B cell aggregation were studied in vitro. Results: FTY720 significantly attenuated clinical EAE when treatment was initiated at the peak of EAE. While there was a significant reduction in the number of T cells in the blood after FTY720 treatment, B cells were only slightly diminished. Yet, there was evidence for the modulation of B cell receptor-mediated signaling upon FTY720 treatment. In addition, we detected a significant increase in the percentage of B220\(^{+}\) B cells in the spleen both in acute and chronic EAE. Whereas acute treatment completely abrogated B cell aggregate formation in the CNS, the numbers of infiltrating B cells and plasma cells were comparable between vehicle- and FTY720-treated mice. In addition, there was no effect on already developed aggregates in chronic EAE. In vitro B cell aggregation assays suggested the absence of a direct effect of FTY720 on B cell aggregation. However, FTY720 impacted the evolution of B cell aggregates into TLOs. Conclusions: The data suggest differential effects of FTY720 on the B cell compartment in MP4-induced EAE.}, language = {en} } @article{LutzStroblSchuleretal.2017, author = {Lutz, Manfred B. and Strobl, Herbert and Schuler, Gerold and Romani, Nikolaus}, title = {GM-CSF monocyte-derived cells and Langerhans cells as part of the dendritic cell family}, series = {Frontiers in Immunology}, volume = {8}, journal = {Frontiers in Immunology}, number = {1388}, doi = {10.3389/fimmu.2017.01388}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158730}, year = {2017}, abstract = {Dendritic cells (DCs) and macrophages (Mph) share many characteristics as components of the innate immune system. The criteria to classify the multitude of subsets within the mononuclear phagocyte system are currently phenotype, ontogeny, transcription patterns, epigenetic adaptations, and function. More recently, ontogenetic, transcriptional, and proteomic research approaches uncovered major developmental differences between Flt3L-dependent conventional DCs as compared with Mphs and monocyte-derived DCs (MoDCs), the latter mainly generated in vitro from murine bone marrow-derived DCs (BM-DCs) or human CD14\(^{+}\) peripheral blood monocytes. Conversely, in vitro GM-CSF-dependent monocyte-derived Mphs largely resemble MoDCs whereas tissue-resident Mphs show a common embryonic origin from yolk sac and fetal liver with Langerhans cells (LCs). The novel ontogenetic findings opened discussions on the terminology of DCs versus Mphs. Here, we bring forward arguments to facilitate definitions of BM-DCs, MoDCs, and LCs. We propose a group model of terminology for all DC subsets that attempts to encompass both ontogeny and function.}, language = {en} } @article{SteinbornHuestegge2017, author = {Steinborn, Michael B. and Huestegge, Lynn}, title = {Phone conversation while processing information: chronometric analysis of load effects in everyday-media multitasking}, series = {Frontiers in Psychology}, volume = {8}, journal = {Frontiers in Psychology}, number = {896}, doi = {10.3389/fpsyg.2017.00896}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158253}, year = {2017}, abstract = {This is a pilot study that examined the effect of cell-phone conversation on cognition using a continuous multitasking paradigm. Current theorizing argues that phone conversation affects behavior (e.g., driving) by interfering at a level of cognitive processes (not peripheral activity) and by implying an attentional-failure account. Within the framework of an intermittent spare-utilized capacity threading model, we examined the effect of aspects of (secondary-task) phone conversation on (primary-task) continuous arithmetic performance, asking whether phone use makes components of automatic and controlled information-processing (i.e., easy vs. hard mental arithmetic) run more slowly, or alternatively, makes processing run less reliably albeit with the same processing speed. The results can be summarized as follows: While neither expecting a text message nor expecting an impending phone call had any detrimental effects on performance, active phone conversation was clearly detrimental to primary-task performance. Crucially, the decrement imposed by secondary-task (conversation) was not due to a constant slowdown but is better be characterized by an occasional breakdown of information processing, which differentially affected automatic and controlled components of primary-task processing. In conclusion, these findings support the notion that phone conversation makes individuals not constantly slower but more vulnerable to commit attention failure, and in this way, hampers stability of (primary-task) information processing.}, language = {en} }