197 results on '"Kunze A"'
Search Results
2. Can welfare states buffer technostress? Income and technostress in the context of various OECD countries.
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Ann S Lauterbach, Tobias Tober, Florian Kunze, and Marius R Busemeyer
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Medicine ,Science - Abstract
Many workers are experiencing the downsides of being exposed to an overload of information and communication technology (ICT), highlighting the need for resources to cope with the resulting technostress. This article offers a novel cross-level perspective on technostress by examining how the context of the welfare state influences the relationship between income and technostress. Showing that individuals with higher income experience less technostress, this study argues that the welfare state represents an additional coping resource, in particular in the form of unemployment benefits. Since unemployment benefits insure income earners in the case of job loss, the negative effect of income on technostress should increase with higher levels of unemployment generosity. In line with these expectations, empirical results based on original survey data collected in collaboration with the OECD show that the impact of income on technostress varies across welfare state contexts. Implications for public health and policymakers are being discussed.
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- 2023
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3. Investigating the relationship between high-dose norepinephrine administration and the incidence of delayed cerebral infarction in patients with aneurysmal subarachnoid hemorrhage: A single-center retrospective evaluation.
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Andrea Cattaneo, Christoph Wipplinger, Caroline Geske, Florian Semmler, Tamara M Wipplinger, Christoph J Griessenauer, Judith Weiland, Alexandra Beez, Ralf-Ingo Ernestus, Thomas Westermaier, Ekkehard Kunze, and Christian Stetter
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Medicine ,Science - Abstract
BackgroundOne of the longest-standing treatments to prevent delayed cerebral infarction (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH) remains raising the blood pressure to a certain level of mean arterial pressure. This may require high doses of norepinephrine, which has been associated with severe end organ damage. With this study, we aimed to investigate the effects of norepinephrine on the incidence of DCI in a clinical setting.MethodsWe conducted a retrospective evaluation of patients with aSAH admitted to our institution between November 2018 and March 2021. Potential risk factors for DCI were analyzed and significant predictors were assessed by means of a logistic regression analysis to account for potential confounders.ResultsIn this study, 104 patients were included. Hereof, 39 (38%) showed radiologic signs of DCI between day three and 14 post-intervention. These patients had more frequent vasospasms (n = 37 vs. 30, p = 0.022), a higher Hunt & Hess score (3 ± 2 vs. 2 ± 1, p = 0.004), a lower initial Glasgow Coma Scale score (9 ± 5 vs. 12 ± 4, p = 0.003) and received a higher median norepinephrine dose (20,356μg vs. 6,508μg, p < 0.001). A logistic regression analysis revealed that only high-dose norepinephrine administration (OR 2.84, CI 1.56-7.8) and vasospasm (OR 3.07, CI 1.2-7.84) appeared to be significant independent risk factors for DCI.ConclusionOur results indicate a significant association between higher dose norepinephrine administration and the occurrence of DCI. Future research including greater sample sizes and a prospective setting will be necessary to further investigate the relationship.
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- 2023
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4. Can welfare states buffer technostress? Income and technostress in the context of various OECD countries
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Lauterbach, Ann S., primary, Tober, Tobias, additional, Kunze, Florian, additional, and Busemeyer, Marius R., additional
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- 2023
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5. Analysis of two choir outbreaks acting in concert to characterize long- range transmission risks through SARS-CoV-2, Berlin, Germany, 2020.
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Felix Reichert, Oliver Stier, Anne Hartmann, Claudia Ruscher, Annika Brinkmann, Marica Grossegesse, Markus Neumann, Dirk Werber, Marius Hausner, Mareike Kunze, Bettina Weiß, Janine Michel, Andreas Nitsche, Matthias An der Heiden, Martin Kriegel, Victor Max Corman, Terry Carleton Jones, Christian Drosten, Tobias Brommann, and Udo Buchholz
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Medicine ,Science - Abstract
BackgroundSuperspreading events are important drivers of the SARS-CoV-2 pandemic and long-range (LR) transmission is believed to play a major role. We investigated two choir outbreaks with different attack rates (AR) to analyze the contribution of LR transmission and highlight important measures for prevention.MethodsWe conducted two retrospective cohort studies and obtained demographic, clinical, laboratory and contact data, performed SARS-CoV-2 serology, whole genome sequencing (WGS), calculated LR transmission probabilities, measured particle emissions of selected choir members, and calculated particle air concentrations and inhalation doses.ResultsWe included 65 (84%) and 42 (100%) members of choirs 1 and 2, respectively, of whom 58 (89%) and 10 (24%) became cases. WGS confirmed strain identity in both choirs. Both primary cases transmitted presymptomatically. Particle emission rate when singing was 7 times higher compared to talking. In choir 1, the median concentration of primary cases' emitted particles in the room was estimated to be 8 times higher, exposure at least 30 minutes longer and room volume smaller than in choir 2, resulting in markedly different estimated probabilities for LR transmission (mode: 90% vs. 16%, 95% CI: 80-95% vs. 6-36%). According to a risk model, the first transmission in choir 1 occurred likely after 8 minutes of singing.ConclusionsThe attack rate of the two choirs differed significantly reflecting the differences in LR transmission risks. The pooled proportion of cases due to LR transmission was substantial (81%; 55/68 cases) and was facilitated by likely highly infectious primary cases, high particle emission rates, and indoor rehearsing for an extended time. Even in large rooms, singing of an infectious person may lead to secondary infections through LR exposure within minutes. In the context of indoor gatherings without mask-wearing and waning or insufficient immunity, these results highlight the ongoing importance of non-pharmaceutical interventions wherever aerosols can accumulate.
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- 2022
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6. Political context and immigrants’ work-related performance errors: Insights from the National Basketball Association
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Korman, Benjamin A., primary and Kunze, Florian, additional
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- 2023
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7. Alcohol consumption and neurocognitive deficits in people with well-treated HIV in Switzerland.
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Katharine E A Darling, Isabella Locatelli, Nadia Benghalem, Isaure Nadin, Alexandra Calmy, Klemens Gutbrod, Christoph Hauser, Peter Brugger, Barbara Hasse, Helen Kovari, Ursi Kunze, Marcel Stoeckle, Christophe Fux, Stefania Rossi, Caroline Di Benedetto, Severin Früh, Patrick Schmid, Philip E Tarr, Jean-Bernard Daeppen, Renaud Du Pasquier, Matthias Cavassini, and NAMACO Study Group, Swiss HIV Cohort Study
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Medicine ,Science - Abstract
BackgroundHazardous alcohol consumption and HIV infection increase the risk of neurocognitive impairment (NCI). We examined the association between alcohol consumption and specific neurocognitive domain function in people with HIV (PWH) taking modern antiretroviral therapy.MethodsThe Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is a prospective, longitudinal, multicentre and multilingual (French, German and Italian) study of patients aged ≥45 years old enrolled in the Swiss HIV Cohort Study (SHCS). Baseline data from 981 study participants were examined. Five neurocognitive domains were evaluated: motor skills, speed of information processing, attention/working memory, executive function and verbal episodic memory. NCI was examined as binary (presence/absence) and continuous (mean z-score) outcomes against Alcohol Use Disorders Identification Test for Consumption (AUDIT-C) scores using logistic and linear regression models, respectively.ResultsMost participants (96.2%) had undetectable viral loads and 64% were aged >50 years old. Hazardous alcohol consumption was observed in 49.4% of participants and binge drinking in 4.2%. While alcohol consumption frequency and quantity were not associated with NCI, the practice of binge drinking was significantly associated with impaired motor skills and overall neurocognitive function in both binary (odds ratio, OR ≥2.0, P ConclusionsIn this cohort of PWH with well-controlled HIV infection, NCI was associated with the practice of binge drinking rather than alcohol consumption frequency or quantity. Longitudinal analysis of alcohol consumption and NCI in this population is currently underway.
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- 2021
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8. Correction: Engineered human meniscus' matrix-forming phenotype is unaffected by low strain dynamic compression under hypoxic conditions.
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Alexander R A Szojka, Colleen N Moore, Yan Liang, Stephen H J Andrews, Melanie Kunze, Aillette Mulet-Sierra, Nadr M Jomha, and Adetola B Adesida
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Medicine ,Science - Abstract
[This corrects the article DOI: 10.1371/journal.pone.0248292.].
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- 2021
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9. Agonistic autoantibodies against ß2-adrenergic receptor influence retinal microcirculation in glaucoma suspects and patients.
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Bettina Hohberger, Sami Hosari, Gerd Wallukat, Rudolf Kunze, Johann Krebs, Meike Müller, Till Hennig, Robert Lämmer, Folkert Horn, Luis E Muñoz, Martin Herrmann, and Christian Mardin
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Medicine ,Science - Abstract
PurposeAgonistic β2-adrenergic receptor autoantibodies (β2-agAAb) have been observed in sera of patients with ocular hypertension and open-angle glaucoma (OAG). They target the β2-receptors on trabecular meshwork, ciliary body and pericytes (Junemann et al. 2018; Hohberger et al. 2019). In addition to their influence on the intraocular pressure, an association to retinal microcirculation is discussed. This study aimed to investigate foveal avascular zone (FAZ) characteristics by en face OCT angiography (OCT-A) in glaucoma suspects and its relationship to β2-agAAb status in patients with OAG.Material and methodsThirty-four patients (28 OAG, 6 glaucoma suspects) underwent standardized, clinical examination including sensory testing as white-on-white perimetry (Octopus G1, mean defect, MD) and structural measures as retinal nerve fibre layer (RNFL) thickness, neuroretinal rim width (BMO-MRW), retinal ganglion cell layer (RGCL) thickness, and inner nuclear layer (INL) thickness with high-resolution OCT. FAZ characteristics were measured by OCT-A scans of superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). FAZ-R was calculated (area FAZ (SVP)/area FAZ (ICP)). Using cardiomyocyte bioassays we analysed serum samples for the presence of β2-agAAb.Results(I) Total mean FAZ area [mm2]: 0.34±0.16 (SVP), 0.24±0.12 (ICP), and 0.49±0.24 (DCP); mean FAZ-R 1.58±0.94. No correlation was seen for FAZ-R with MD, RNFL, BMO-MRW, RGCL thickness and INL thickness (p>0.05). (II) ß2-agAAb have been observed in 91% patients and showed no correlation with MD, RNFL, BMO-MRW, RGCL thickness and INL thickness (p>0.05). (III) FAZ-R correlated significantly with the β2-agAAb-induced increase of the beat rate of cardiomyocyte (p = 0.028).ConclusionFAZ characteristics did not correlate with any glaucoma associated functional and morphometric follow-up parameter in the present cohort. However, level of β2-agAAb showed a significantly correlation with FAZ-ratio. We conclude that β2-agAAb might be a novel biomarker in glaucoma pathogenesis showing association to FAZ-ratio with OCT-A.
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- 2021
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10. Engineered human meniscus' matrix-forming phenotype is unaffected by low strain dynamic compression under hypoxic conditions.
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Alexander R A Szojka, Colleen N Moore, Yan Liang, Stephen H J Andrews, Melanie Kunze, Aillette Mulet-Sierra, Nadr M Jomha, and Adetola B Adesida
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Medicine ,Science - Abstract
Low oxygen and mechanical loading may play roles in regulating the fibrocartilaginous phenotype of the human inner meniscus, but their combination in engineered tissues remains unstudied. Here, we investigated how continuous low oxygen ("hypoxia") combined with dynamic compression would affect the fibrocartilaginous "inner meniscus-like" matrix-forming phenotype of human meniscus fibrochondrocytes (MFCs) in a porous type I collagen scaffold. Freshly-seeded MFC scaffolds were cultured for 4 weeks in either 3 or 20% O2 or pre-cultured for 2 weeks in 3% O2 and then dynamically compressed for 2 weeks (10% strain, 1 Hz, 1 h/day, 5 days/week), all with or without TGF-β3 supplementation. TGF-β3 supplementation was found necessary to induce matrix formation by MFCs in the collagen scaffold regardless of oxygen tension and application of the dynamic compression loading regime. Neither hypoxia under static culture nor hypoxia combined with dynamic compression had significant effects on expression of specific protein and mRNA markers for the fibrocartilaginous matrix-forming phenotype. Mechanical properties significantly increased over the two-week loading period but were not different between static and dynamic-loaded tissues after the loading period. These findings indicate that 3% O2 applied immediately after scaffold seeding and dynamic compression to 10% strain do not affect the fibrocartilaginous matrix-forming phenotype of human MFCs in this type I collagen scaffold. It is possible that a delayed hypoxia treatment and an optimized pre-culture period and loading regime combination would have led to different outcomes.
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- 2021
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11. Microvesicles from Lactobacillus reuteri (DSM-17938) completely reproduce modulation of gut motility by bacteria in mice.
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Christine L West, Andrew M Stanisz, Yu-Kang Mao, Kevin Champagne-Jorgensen, John Bienenstock, and Wolfgang A Kunze
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Medicine ,Science - Abstract
Microvesicles are small lipid, bilayer structures (20-400 nm in diameter) secreted by bacteria, fungi, archaea and parasites involved in inter-bacterial communication and host-pathogen interactions. Lactobacillus reuteri DSM-17938 (DSM) has been shown to have clinical efficacy in the treatment of infantile colic, diarrhea and constipation. We have shown previously that luminal administration to the mouse gut promotes reduction of jejunal motility but increases that in the colon. The production of microvesicles by DSM has been characterized, but the effect of these microvesicles on gastrointestinal motility has yet to be evaluated. To investigate a potential mechanism for the effects of DSM on the intestine, the bacteria and its products have here been tested for changes in velocity, frequency, and amplitude of contractions in intact segments of jejunum and colon excised from mice. The effect of the parent bacteria (DSM) was compared to the conditioned media in which it was grown, and the microvesicles it produced. The media used to culture the bacteria (broth) was tested as a negative control and the conditioned medium was tested after the microvesicles had been removed. DSM, conditioned medium, and the microvesicles all produced comparable effects in both the jejunum and the colon. The treatments individually decreased the velocity and frequency of propagating contractile cluster contractions in the jejunum and increased them in the colon to a similar degree. The broth control had little effect in both tissues. Removal of the microvesicles from the conditioned medium almost completely eradicated their effect on motility in both tissues. These results show that the microvesicles from DSM alone can completely reproduce the effects of the whole bacteria on gut motility. Furthermore, they suggest a new approach to the formulation of orally active bacterial therapeutics and offer a novel way to begin to identify the active bacterial components.
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- 2020
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12. Pre-/analytical factors affecting whole blood and plasma glucose concentrations in loggerhead sea turtles (Caretta caretta).
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Patricia E Kunze, Justin R Perrault, Yu-Mei Chang, Charles A Manire, Samantha Clark, and Nicole I Stacy
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Medicine ,Science - Abstract
Blood glucose is vital for many physiological pathways and can be quantified by clinical chemistry analyzers and in-house point-of-care (POC) devices. Pre-analytical and analytical factors can influence blood glucose measurements. This project aimed to investigate pre-analytical factors on whole blood and plasma glucose measurements in loggerhead sea turtles (Caretta caretta) by evaluating the effects of storage (refrigeration) up to 48h after sampling and of packed cell volume (PCV) on whole blood glucose analysis by POC glucometer (time series n = 13); and by evaluating the effects of storage (room temperature and refrigeration) on plasma glucose concentrations using a dry slide chemistry analyzer (DCA) at various conditions: immediate processing and delayed plasma separation from erythrocytes at 24h and 48h (time series n = 14). The POC glucometer had overall strong agreement with the DCA (CCC = 0.76, r = 0.84, Cb = 0.90), but consistently overestimated glucose concentrations (mean difference: +0.4 mmol/L). The POC glucometer results decreased significantly over time, resulting in a substantial decline within the first 2h (0.41±0.47 mmol/L; 8±9%) that could potentially alter clinical decisions, thereby highlighting the need for immediate analysis using this method. The effects of PCV on glucose could not be assessed, as the statistical significance was associated with one outlier. Storage method significantly affected plasma glucose measurements using DCA, with room temperature samples resulting in rapid decreases of 3.57±0.89 mmol/L (77±9%) over the first 48h, while refrigerated samples provided consistent plasma glucose results over the same time period (decrease of 0.26±0.23 mmol/L; 6±5%). The results from this study provide new insights into optimal blood sample handling and processing for glucose analysis in sea turtles, show the suitability of the POC glucometer as a rapid diagnostic test, and confirm the reliability of plasma glucose measurements using refrigeration. These findings emphasize the need to consider pre-/analytical factors when interpreting blood glucose results from loggerhead sea turtles.
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- 2020
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13. Correction: Mpp10 represents a platform for the interaction of multiple factors within the 90S pre-ribosome.
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Bebiana Sá-Moura, Markus Kornprobst, Satyavati Kharde, Yasar Luqman Ahmed, Gunter Stier, Ruth Kunze, Irmgard Sinning, and Ed Hurt
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Medicine ,Science - Abstract
[This corrects the article DOI: 10.1371/journal.pone.0183272.].
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- 2020
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14. A genome-wide analysis of DNA methylation identifies a novel association signal for Lp(a) concentrations in the LPA promoter.
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Stefan Coassin, Natascha Hermann-Kleiter, Margot Haun, Simone Wahl, Rory Wilson, Bernhard Paulweber, Sonja Kunze, Thomas Meitinger, Konstantin Strauch, Annette Peters, Melanie Waldenberger, Florian Kronenberg, and Claudia Lamina
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Medicine ,Science - Abstract
Lipoprotein(a) [Lp(a)] is a major cardiovascular risk factor, which is largely genetically determined by one major gene locus, the LPA gene. Many aspects of the transcriptional regulation of LPA are poorly understood and the role of epigenetics has not been addressed yet. Therefore, we conducted an epigenome-wide analysis of DNA methylation on Lp(a) levels in two population-based studies (total n = 2208). We identified a CpG site in the LPA promoter which was significantly associated with Lp(a) concentrations. Surprisingly, the identified CpG site was found to overlap the SNP rs76735376. We genotyped this SNP de-novo in three studies (total n = 7512). The minor allele of rs76735376 (1.1% minor allele frequency) was associated with increased Lp(a) values (p = 1.01e-59) and explained 3.5% of the variation of Lp(a). Statistical mediation analysis showed that the effect on Lp(a) is rather originating from the base change itself and is not mediated by DNA methylation levels. This finding is supported by eQTL data from 208 liver tissue samples from the GTEx project, which shows a significant association of the rs76735376 minor allele with increased LPA expression. To evaluate, whether the association signal at rs76735376 may actually be derived from a stronger eQTL signal in LD with this SNP, eQTL association results of all correlated SNPs (r2≥0.1) were integrated with genetic association results. This analysis pinpointed to rs10455872 as the potential trigger of the effect of rs76735376. Furthermore, both SNPs coincide with short apo(a) isoforms. Adjusting for both, rs10455872 and the apo(a) isoforms diminished the effect size of rs76735376 to 5.38 mg/dL (p = 0.0463). This indicates that the effect of rs76735376 can be explained by both an independent effect of the SNP and a strong correlation with rs10455872 and apo(a) isoforms.
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- 2020
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15. Investigating the relationship between high-dose norepinephrine administration and the incidence of delayed cerebral infarction in patients with aneurysmal subarachnoid hemorrhage: A single-center retrospective evaluation
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Cattaneo, Andrea, primary, Wipplinger, Christoph, additional, Geske, Caroline, additional, Semmler, Florian, additional, Wipplinger, Tamara M., additional, Griessenauer, Christoph J., additional, Weiland, Judith, additional, Beez, Alexandra, additional, Ernestus, Ralf-Ingo, additional, Westermaier, Thomas, additional, Kunze, Ekkehard, additional, and Stetter, Christian, additional
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- 2023
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16. Restraint stress induced gut dysmotility is diminished by a milk oligosaccharide (2'-fucosyllactose) in vitro.
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Sohana Farhin, Annette Wong, Thilini Delungahawatta, Jessica Y Amin, John Bienenstock, Rachael Buck, and Wolfgang A Kunze
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Medicine ,Science - Abstract
BackgroundStress causes severe dysmotility in the mammalian gut. Almost all research done to date has concentrated on prevention of stress-induced altered gut motility but not on treatment. We had previously shown that intraluminal 2'FL could acutely moderate propulsive motility in isolated mouse colonic segments. Because 2'FL appeared to modulate enteric nervous system dependent motility, we wondered if the oligosaccharide could reverse the effects of prior restraint stress, ex vivo. We tested whether 2'FL could benefit the dysmotility of isolated jejunal and colonic segments from animals subjected to prior acute restraint stress.MethodsJejunal and colonic segments were obtained from male Swiss Webster mice that were untreated or subjected to 1 hour of acute restraint stress. Segments were perfused with Krebs buffer and propagating contractile clusters (PCC) digitally video recorded. 2'FL or β-lactose were added to the perfusate at a concentration of 1 mg/ml. Spatiotemporal maps were constructed from paired before and after treatment recordings, each consisting of 20 min duration and PCC analyzed for frequency, velocity and amplitude.Key resultsStress decreased propulsive motility in murine small intestine while increasing it in the colon. 2'FL in jejunum of previously stressed mice produced a 50% increase in PCC velocity (p = 0.0001), a 43% increase in frequency (p = 0.0002) and an insignificant decrease in peak amplitude. For stressed colon, 2'FL reduced the frequency by 23% (p = 0.017) and peak amplitude by 26% (p = 0.011), and was without effect on velocity. β-lactose had negligible or small treatment effects.Conclusions & inferencesWe show that the prebiotic 2'FL may have potential as a treatment for acute stress-induced gut dysmotility, ex vivo, and that, as is the case for certain beneficial microbes, the mechanism occurs in the gut, likely via action on the enteric nervous system.
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- 2019
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17. Simultaneous cardiac and respiratory inhibition during seizure precedes death in the DBA/1 audiogenic mouse model of SUDEP.
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William P Schilling, Morgan K McGrath, Tianen Yang, Patricia A Glazebrook, Carl L Faingold, and Diana L Kunze
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Medicine ,Science - Abstract
This study was designed to evaluate cardiac and respiratory dysfunction in a mouse model of sudden unexpected death in epilepsy i.e., SUDEP. We simultaneously monitored respiration via plethysmography and the electrocardiogram via telemetry before, during, and after an audiogenic seizure. DBA/1 mice responded to an acoustic stimulus with one or two cycles of circling and jumping before entering a clonic/tonic seizure. This was followed by death unless the mice were resuscitated by mechanical ventilation using room air. During the initial clonic phase, respiration declined and cardiac rhythm is slowed. By the tonic phase, respiration had ceased, atrial P-waves were absent or dissociated from the QRS complex, and heart rate had decreased from 771±11 to 252±16 bpm. Heart rate further deteriorated terminating in asystole unless the mice were resuscitated at the end of the tonic phase which resulted in abrupt recovery of P-waves and a return to normal sinus rhythm, associated with gasping. Interestingly, P-waves were preserved in the mice treated with methylatropine during the pre-ictal period (to block parasympathetic stimulation) and heart rate remained unchanged through the end of the tonic phase (765±8 vs. 748±21 bpm), but as in control, methylatropine treated mice died from respiratory arrest. These results demonstrate that a clonic/tonic seizure in the DBA/1 mouse results in abrupt and simultaneous respiratory and cardiac depression. Although death clearly results from respiratory arrest, our results suggest that seizure activates two central nervous system pathways in this model-one inhibits respiratory drive, whereas the other inhibits cardiac function via vagal efferents. The abrupt and simultaneous recovery of both respiration and cardiac function with mechanical ventilation within an early post-ictal timeframe shows that the vagal discharge can be rapidly terminated. Understanding the central mechanism associated with the abrupt cardiorespiratory dysfunction and equally abrupt recovery may provide clues for therapeutic targets for SUDEP.
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- 2019
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18. Zebrafish larvae show negative phototaxis to near-infrared light.
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Sarah Hartmann, Roland Vogt, Jan Kunze, Anna Rauschert, Klaus-Dieter Kuhnert, Josef Wanzenböck, Dunja K Lamatsch, and Klaudia Witte
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Medicine ,Science - Abstract
Zebrafish larvae (Danio rerio) are among the most used model species to test biological effects of different substances in biomedical research, neuroscience and ecotoxicology. Most tests are based on changes in swimming activity of zebrafish larvae by using commercially available high-throughput screening systems. These systems record and analyse behaviour patterns using visible (VIS) and near-infrared (NIR) light sources, to simulate day (VIS) and night (NIR) phases, which allow continuous recording of the behaviour using a NIR sensitive camera. So far, however, the sensitivity of zebrafish larvae to NIR has never been tested experimentally, although being a critical piece of information for interpreting their behaviour under experimental conditions. Here, we investigated the swimming activity of 96 hpf (hours post fertilization) and 120 hpf zebrafish larvae under light sources of NIR at 860 nm and at 960 nm wavelength and under VIS light. A thermal source was simultaneously presented opposite to one of the light sources as control. We found that zebrafish larvae of both larval stages showed a clear negative phototactic response towards 860 nm NIR light and to VIS light, but not to 960 nm NIR light. Our results demonstrated that zebrafish larvae are able to perceive NIR at 860 nm, which is almost identical to the most commonly used light source in commercial screening systems (NIR at 850 nm) to create a dark environment. These tests, however, are not performed in the dark from the zebrafish´s point of view. We recommend testing sensitivity of the used test organism before assuming no interaction with the applied light source of commonly used biosensor test systems. Previous studies on biological effects of substances to zebrafish larvae should be interpreted with caution.
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- 2018
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19. Analysis of two choir outbreaks acting in concert to characterize long- range transmission risks through SARS-CoV-2, Berlin, Germany, 2020
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Reichert, Felix, primary, Stier, Oliver, additional, Hartmann, Anne, additional, Ruscher, Claudia, additional, Brinkmann, Annika, additional, Grossegesse, Marica, additional, Neumann, Markus, additional, Werber, Dirk, additional, Hausner, Marius, additional, Kunze, Mareike, additional, Weiß, Bettina, additional, Michel, Janine, additional, Nitsche, Andreas, additional, an der Heiden, Matthias, additional, Kriegel, Martin, additional, Corman, Victor Max, additional, Jones, Terry Carleton, additional, Drosten, Christian, additional, Brommann, Tobias, additional, and Buchholz, Udo, additional
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- 2022
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20. Mpp10 represents a platform for the interaction of multiple factors within the 90S pre-ribosome.
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Bebiana Sá-Moura, Markus Kornprobst, Satyavati Kharde, Yasar Luqman Ahmed, Gunter Stier, Ruth Kunze, Irmgard Sinning, and Ed Hurt
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Medicine ,Science - Abstract
In eukaryotes, ribosome assembly is a highly complex process that involves more than 200 assembly factors that ensure the folding, modification and processing of the different rRNA species as well as the timely association of ribosomal proteins. One of these factors, Mpp10 associates with Imp3 and Imp4 to form a complex that is essential for the normal production of the 18S rRNA. Here we report the crystal structure of a complex between Imp4 and a short helical element of Mpp10 to a resolution of 1.88 Å. Furthermore, we extend the interaction network of Mpp10 and characterize two novel interactions. Mpp10 is able to bind the ribosome biogenesis factor Utp3/Sas10 through two conserved motifs in its N-terminal region. In addition, Mpp10 interacts with the ribosomal protein S5/uS7 using a short stretch within an acidic loop region. Thus, our findings reveal that Mpp10 provides a platform for the simultaneous interaction with multiple proteins in the 90S pre-ribosome.
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- 2017
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21. Superior Cervical Ganglia Neurons Induce Foxp3+ Regulatory T Cells via Calcitonin Gene-Related Peptide.
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Kirsten Szklany, Evelyn Ruiter, Firoz Mian, Wolfgang Kunze, John Bienenstock, Paul Forsythe, and Khalil Karimi
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Medicine ,Science - Abstract
The nervous and immune systems communicate bidirectionally, utilizing diverse molecular signals including cytokines and neurotransmitters to provide an integrated response to changes in the body's internal and external environment. Although, neuro-immune interactions are becoming better understood under inflammatory circumstances and it has been evidenced that interaction between neurons and T cells results in the conversion of encephalitogenic T cells to T regulatory cells, relatively little is known about the communication between neurons and naïve T cells. Here, we demonstrate that following co-culture of naïve CD4+ T cells with superior cervical ganglion neurons, the percentage of Foxp3 expressing CD4+CD25+ cells significantly increased. This was mediated in part by immune-regulatory cytokines TGF-β and IL-10, as well as the neuropeptide calcitonin gene-related peptide while vasoactive intestinal peptide was shown to play no role in generation of T regulatory cells. Additionally, T cells co-cultured with neurons showed a decrease in the levels of pro-inflammatory cytokine IFN-γ released upon in vitro stimulation. These findings suggest that the generation of Tregs may be promoted by naïve CD4+ T cell: neuron interaction through the release of neuropeptide CGRP.
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- 2016
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22. Vegetation characteristics control local sediment and nutrient retention on but not underneath vegetation in floodplain meadows
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Kretz, Lena, primary, Bondar-Kunze, Elisabeth, additional, Hein, Thomas, additional, Richter, Ronny, additional, Schulz-Zunkel, Christiane, additional, Seele-Dilbat, Carolin, additional, van der Plas, Fons, additional, Vieweg, Michael, additional, and Wirth, Christian, additional
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- 2021
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23. Keep calm and carry on: improved frustration tolerance and processing speed by transcranial direct current stimulation (tDCS).
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Christian Plewnia, Philipp A Schroeder, Roland Kunze, Florian Faehling, and Larissa Wolkenstein
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Medicine ,Science - Abstract
Cognitive control (CC) of attention is a major prerequisite for effective information processing. Emotional distractors can bias and impair goal-directed deployment of attentional resources. Frustration-induced negative affect and cognition can act as internal distractors with negative impact on task performance. Consolidation of CC may thus support task-oriented behavior under challenging conditions. Recently, transcranial direct current stimulation (tDCS) has been put forward as an effective tool to modulate CC. Particularly, anodal, activity enhancing tDCS to the left dorsolateral prefrontal cortex (dlPFC) can increase insufficient CC in depression as indicated by a reduction of attentional biases induced by emotionally salient stimuli. With this study, we provide first evidence that, compared to sham stimulation, tDCS to the left dlPFC enhances processing speed measured by an adaptive version of the Paced Auditory Serial Addition Task (PASAT) that is typically thwarted by frustration. Notably, despite an even larger amount of error-related negative feedback, the task-induced upset was suppressed in the group receiving anodal tDCS. Moreover, inhibition of task-related negative affect was correlated with performance gains, suggesting a close link between enhanced processing speed and consolidation of CC by tDCS. Together, these data provide first evidence that activity enhancing anodal tDCS to the left dlPFC can support focused cognitive processing particularly when challenged by frustration-induced negative affect.
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- 2015
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24. Non-Invasive Acoustical sensing of Drug-Induced Effects on the Contractile Machinery of Human Cardiomyocyte Clusters.
- Author
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Angelika Kunze, Daniella Steel, Kerstin Dahlenborg, Peter Sartipy, and Sofia Svedhem
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Medicine ,Science - Abstract
There is an urgent need for improved models for cardiotoxicity testing. Here we propose acoustic sensing applied to beating human cardiomyocyte clusters for non-invasive, surrogate measuring of the QT interval and other characteristics of the contractile machinery. In experiments with the acoustic method quartz crystal microbalance with dissipation monitoring (QCM-D), the shape of the recorded signals was very similar to the extracellular field potential detected in electrochemical experiments, and the expected changes of the QT interval in response to addition of conventional drugs (E-4031 or nifedipine) were observed. Additionally, changes in the dissipation signal upon addition of cytochalasin D were in good agreement with the known, corresponding shortening of the contraction-relaxation time. These findings suggest that QCM-D has great potential as a tool for cardiotoxicological screening, where effects of compounds on the cardiomyocyte contractile machinery can be detected independently of whether the extracellular field potential is altered or not.
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- 2015
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25. Inflammatory conditions induce IRES-dependent translation of cyp24a1.
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Daniela Rübsamen, Michael M Kunze, Victoria Buderus, Thilo F Brauß, Magdalena M Bajer, Bernhard Brüne, and Tobias Schmid
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Medicine ,Science - Abstract
Rapid alterations in protein expression are commonly regulated by adjusting translation. In addition to cap-dependent translation, which is e.g. induced by pro-proliferative signaling via the mammalian target of rapamycin (mTOR)-kinase, alternative modes of translation, such as internal ribosome entry site (IRES)-dependent translation, are often enhanced under stress conditions, even if cap-dependent translation is attenuated. Common stress stimuli comprise nutrient deprivation, hypoxia, but also inflammatory signals supplied by infiltrating immune cells. Yet, the impact of inflammatory microenvironments on translation in tumor cells still remains largely elusive. In the present study, we aimed at identifying translationally deregulated targets in tumor cells under inflammatory conditions. Using polysome profiling and microarray analysis, we identified cyp24a1 (1,25-dihydroxyvitamin D3 24-hydroxylase) to be translationally upregulated in breast tumor cells co-cultured with conditioned medium of activated monocyte-derived macrophages (CM). Using bicistronic reporter assays, we identified and validated an IRES within the 5' untranslated region (5'UTR) of cyp24a1, which enhances translation of cyp24a1 upon CM treatment. Furthermore, IRES-dependent translation of cyp24a1 by CM was sensitive to phosphatidyl-inositol-3-kinase (PI3K) inhibition, while constitutive activation of Akt sufficed to induce its IRES activity. Our data provide evidence that cyp24a1 expression is translationally regulated via an IRES element, which is responsive to an inflammatory environment. Considering the negative feedback impact of cyp24a1 on the vitamin D responses, the identification of a novel, translational mechanism of cyp24a1 regulation might open new possibilities to overcome the current limitations of vitamin D as tumor therapeutic option.
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- 2014
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26. OMR-arena: automated measurement and stimulation system to determine mouse visual thresholds based on optomotor responses.
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Friedrich Kretschmer, Viola Kretschmer, Vincent P Kunze, and Jutta Kretzberg
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Medicine ,Science - Abstract
Measurement of the optomotor response is a common way to determine thresholds of the visual system in animals. Particularly in mice, it is frequently used to characterize the visual performance of different genetically modified strains or to test the effect of various drugs on visual performance. Several methods have been developed to facilitate the presentation of stimuli using computer screens or projectors. Common methods are either based on the measurement of eye movement during optokinetic reflex behavior or rely on the measurement of head and/or body-movements during optomotor responses. Eye-movements can easily and objectively be quantified, but their measurement requires invasive fixation of the animals. Head movements can be observed in freely moving animals, but until now depended on the judgment of a human observer who reported the counted tracking movements of the animal during an experiment. In this study we present a novel measurement and stimulation system based on open source building plans and software. This system presents appropriate 360° stimuli while simultaneously video-tracking the animal's head-movements without fixation. The on-line determined head gaze is used to adjust the stimulus to the head position, as well as to automatically calculate visual acuity. Exemplary, we show that automatically measured visual response curves of mice match the results obtained by a human observer very well. The spatial acuity thresholds yielded by the automatic analysis are also consistent with the human observer approach and with published results. Hence, OMR-arena provides an affordable, convenient and objective way to measure mouse visual performance.
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- 2013
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27. Agonistic autoantibodies against ß2-adrenergic receptor influence retinal microcirculation in glaucoma suspects and patients
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Hohberger, Bettina, primary, Hosari, Sami, additional, Wallukat, Gerd, additional, Kunze, Rudolf, additional, Krebs, Johann, additional, Müller, Meike, additional, Hennig, Till, additional, Lämmer, Robert, additional, Horn, Folkert, additional, Muñoz, Luis E., additional, Herrmann, Martin, additional, and Mardin, Christian, additional
- Published
- 2021
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28. Correction: Engineered human meniscus’ matrix-forming phenotype is unaffected by low strain dynamic compression under hypoxic conditions
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Szojka, Alexander R. A., primary, Moore, Colleen N., additional, Liang, Yan, additional, Andrews, Stephen H. J., additional, Kunze, Melanie, additional, Mulet-Sierra, Aillette, additional, Jomha, Nadr M., additional, and Adesida, Adetola B., additional
- Published
- 2021
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29. Engineered human meniscus’ matrix-forming phenotype is unaffected by low strain dynamic compression under hypoxic conditions
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Szojka, Alexander R. A., primary, Moore, Colleen N., additional, Liang, Yan, additional, Andrews, Stephen H. J., additional, Kunze, Melanie, additional, Mulet-Sierra, Aillette, additional, Jomha, Nadr M., additional, and Adesida, Adetola B., additional
- Published
- 2021
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30. Correction: Mpp10 represents a platform for the interaction of multiple factors within the 90S pre-ribosome
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Gunter Stier, Bebiana Sá-Moura, Ed Hurt, Satyavati Kharde, Yasar Luqman Ahmed, Irmgard Sinning, Ruth Kunze, and Markus Kornprobst
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Multidisciplinary ,Multiple factors ,Computer science ,Science ,MEDLINE ,Medicine ,Computational biology ,Ribosome - Abstract
[This corrects the article DOI: 10.1371/journal.pone.0183272.].
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- 2020
31. Correction: Mpp10 represents a platform for the interaction of multiple factors within the 90S pre-ribosome
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Sá-Moura, Bebiana, primary, Kornprobst, Markus, additional, Kharde, Satyavati, additional, Ahmed, Yasar Luqman, additional, Stier, Gunter, additional, Kunze, Ruth, additional, Sinning, Irmgard, additional, and Hurt, Ed, additional
- Published
- 2020
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32. A genome-wide analysis of DNA methylation identifies a novel association signal for Lp(a) concentrations in the LPA promoter
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Coassin, Stefan, primary, Hermann-Kleiter, Natascha, additional, Haun, Margot, additional, Wahl, Simone, additional, Wilson, Rory, additional, Paulweber, Bernhard, additional, Kunze, Sonja, additional, Meitinger, Thomas, additional, Strauch, Konstantin, additional, Peters, Annette, additional, Waldenberger, Melanie, additional, Kronenberg, Florian, additional, and Lamina, Claudia, additional
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- 2020
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33. Pre-/analytical factors affecting whole blood and plasma glucose concentrations in loggerhead sea turtles (Caretta caretta)
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Kunze, Patricia E., primary, Perrault, Justin R., additional, Chang, Yu-Mei, additional, Manire, Charles A., additional, Clark, Samantha, additional, and Stacy, Nicole I., additional
- Published
- 2020
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34. Microvesicles from Lactobacillus reuteri (DSM-17938) completely reproduce modulation of gut motility by bacteria in mice
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West, Christine L., primary, Stanisz, Andrew M., additional, Mao, Yu-Kang, additional, Champagne-Jorgensen, Kevin, additional, Bienenstock, John, additional, and Kunze, Wolfgang A., additional
- Published
- 2020
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35. Microvesicles from Lactobacillus reuteri (DSM-17938) completely reproduce modulation of gut motility by bacteria in mice
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Yu-Kang Mao, John Bienenstock, Andrew M. Stanisz, Kevin Champagne-Jorgensen, Christine West, and Wolfgang Kunze
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0301 basic medicine ,Limosilactobacillus reuteri ,Colic ,Pathology and Laboratory Medicine ,Jejunum ,Mice ,Cell-Derived Microparticles ,Lactobacillus ,Medicine and Health Sciences ,Gastrointestinal tract ,Multidisciplinary ,biology ,Chemistry ,Gastrointestinal Motility Disorders ,3. Good health ,medicine.anatomical_structure ,Medicine ,Anatomy ,Pathogens ,Research Article ,Diarrhea ,Pathogen Motility ,Colon ,Virulence Factors ,Science ,030106 microbiology ,Motility ,Gastroenterology and Hepatology ,Infantile colic ,Microbiology ,03 medical and health sciences ,medicine ,Animals ,Humans ,Bacteria ,Probiotics ,Gut Bacteria ,Organisms ,Biology and Life Sciences ,biology.organism_classification ,medicine.disease ,Microvesicles ,Lactobacillus reuteri ,Gastrointestinal Tract ,030104 developmental biology ,Gastrointestinal Motility ,Constipation ,Digestive System - Abstract
Microvesicles are small lipid, bilayer structures (20-400 nm in diameter) secreted by bacteria, fungi, archaea and parasites involved in inter-bacterial communication and host-pathogen interactions. Lactobacillus reuteri DSM-17938 (DSM) has been shown to have clinical efficacy in the treatment of infantile colic, diarrhea and constipation. We have shown previously that luminal administration to the mouse gut promotes reduction of jejunal motility but increases that in the colon. The production of microvesicles by DSM has been characterized, but the effect of these microvesicles on gastrointestinal motility has yet to be evaluated. To investigate a potential mechanism for the effects of DSM on the intestine, the bacteria and its products have here been tested for changes in velocity, frequency, and amplitude of contractions in intact segments of jejunum and colon excised from mice. The effect of the parent bacteria (DSM) was compared to the conditioned media in which it was grown, and the microvesicles it produced. The media used to culture the bacteria (broth) was tested as a negative control and the conditioned medium was tested after the microvesicles had been removed. DSM, conditioned medium, and the microvesicles all produced comparable effects in both the jejunum and the colon. The treatments individually decreased the velocity and frequency of propagating contractile cluster contractions in the jejunum and increased them in the colon to a similar degree. The broth control had little effect in both tissues. Removal of the microvesicles from the conditioned medium almost completely eradicated their effect on motility in both tissues. These results show that the microvesicles from DSM alone can completely reproduce the effects of the whole bacteria on gut motility. Furthermore, they suggest a new approach to the formulation of orally active bacterial therapeutics and offer a novel way to begin to identify the active bacterial components.
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- 2019
36. Simultaneous cardiac and respiratory inhibition during seizure precedes death in the DBA/1 audiogenic mouse model of SUDEP
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Diana L. Kunze, Tianen Yang, Carl L. Faingold, William P. Schilling, Morgan K McGrath, and Patricia A. Glazebrook
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0301 basic medicine ,Critical Care and Emergency Medicine ,Physiology ,Respiratory arrest ,Cardiovascular Physiology ,Methylatropine ,Tonic (physiology) ,chemistry.chemical_compound ,Mice ,Electrocardiography ,0302 clinical medicine ,Heart Rate ,Medicine and Health Sciences ,Medicine ,Respiratory system ,Sudden Unexpected Death in Epilepsy ,Lung ,Multidisciplinary ,Chemical Reactions ,Heart ,Animal Models ,Respiratory Function Tests ,Plethysmography ,Chemistry ,Bioassays and Physiological Analysis ,Experimental Organism Systems ,Neurology ,Mice, Inbred DBA ,Heart Function Tests ,Physical Sciences ,Cardiology ,medicine.symptom ,Research Article ,Cardiac function curve ,medicine.medical_specialty ,Resuscitation ,Science ,Mouse Models ,Research and Analysis Methods ,Methylation ,03 medical and health sciences ,Model Organisms ,Seizures ,Internal medicine ,Heart rate ,Bradycardia ,Animals ,Humans ,Asystole ,Epilepsy ,business.industry ,Clonic Seizures ,Electrophysiological Techniques ,Biology and Life Sciences ,Epileptic Seizures ,medicine.disease ,Disease Models, Animal ,030104 developmental biology ,chemistry ,Control of respiration ,Animal Studies ,Cardiac Electrophysiology ,business ,030217 neurology & neurosurgery ,Biomarkers - Abstract
This study was designed to evaluate cardiac and respiratory dysfunction in a mouse model of sudden unexpected death in epilepsy i.e., SUDEP. We simultaneously monitored respiration via plethysmography and the electrocardiogram via telemetry before, during, and after an audiogenic seizure. DBA/1 mice responded to an acoustic stimulus with one or two cycles of circling and jumping before entering a clonic/tonic seizure. This was followed by death unless the mice were resuscitated by mechanical ventilation using room air. During the initial clonic phase, respiration declined and cardiac rhythm is slowed. By the tonic phase, respiration had ceased, atrial P-waves were absent or dissociated from the QRS complex, and heart rate had decreased from 771±11 to 252±16 bpm. Heart rate further deteriorated terminating in asystole unless the mice were resuscitated at the end of the tonic phase which resulted in abrupt recovery of P-waves and a return to normal sinus rhythm, associated with gasping. Interestingly, P-waves were preserved in the mice treated with methylatropine during the pre-ictal period (to block parasympathetic stimulation) and heart rate remained unchanged through the end of the tonic phase (765±8 vs. 748±21 bpm), but as in control, methylatropine treated mice died from respiratory arrest. These results demonstrate that a clonic/tonic seizure in the DBA/1 mouse results in abrupt and simultaneous respiratory and cardiac depression. Although death clearly results from respiratory arrest, our results suggest that seizure activates two central nervous system pathways in this model-one inhibits respiratory drive, whereas the other inhibits cardiac function via vagal efferents. The abrupt and simultaneous recovery of both respiration and cardiac function with mechanical ventilation within an early post-ictal timeframe shows that the vagal discharge can be rapidly terminated. Understanding the central mechanism associated with the abrupt cardiorespiratory dysfunction and equally abrupt recovery may provide clues for therapeutic targets for SUDEP.
- Published
- 2019
37. Restraint stress induced gut dysmotility is diminished by a milk oligosaccharide (2'-fucosyllactose) in vitro
- Author
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Rachael Buck, Jessica Y. Amin, Sohana Farhin, Wolfgang Kunze, Annette Wong, Thilini Delungahawatta, and John Bienenstock
- Subjects
0301 basic medicine ,Nervous system ,Male ,Restraint, Physical ,medicine.medical_specialty ,Science ,Motility ,Jejunum ,03 medical and health sciences ,chemistry.chemical_compound ,Feces ,Mice ,0302 clinical medicine ,2'-Fucosyllactose ,Internal medicine ,medicine ,Animals ,Gastrointestinal tract ,Multidisciplinary ,Chemistry ,Small intestine ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Medicine ,Enteric nervous system ,Gastrointestinal Motility ,Trisaccharides ,030217 neurology & neurosurgery ,Ex vivo ,Stress, Psychological ,Research Article - Abstract
BackgroundStress causes severe dysmotility in the mammalian gut. Almost all research done to date has concentrated on prevention of stress-induced altered gut motility but not on treatment. We had previously shown that intraluminal 2'FL could acutely moderate propulsive motility in isolated mouse colonic segments. Because 2'FL appeared to modulate enteric nervous system dependent motility, we wondered if the oligosaccharide could reverse the effects of prior restraint stress, ex vivo. We tested whether 2'FL could benefit the dysmotility of isolated jejunal and colonic segments from animals subjected to prior acute restraint stress.MethodsJejunal and colonic segments were obtained from male Swiss Webster mice that were untreated or subjected to 1 hour of acute restraint stress. Segments were perfused with Krebs buffer and propagating contractile clusters (PCC) digitally video recorded. 2'FL or β-lactose were added to the perfusate at a concentration of 1 mg/ml. Spatiotemporal maps were constructed from paired before and after treatment recordings, each consisting of 20 min duration and PCC analyzed for frequency, velocity and amplitude.Key resultsStress decreased propulsive motility in murine small intestine while increasing it in the colon. 2'FL in jejunum of previously stressed mice produced a 50% increase in PCC velocity (p = 0.0001), a 43% increase in frequency (p = 0.0002) and an insignificant decrease in peak amplitude. For stressed colon, 2'FL reduced the frequency by 23% (p = 0.017) and peak amplitude by 26% (p = 0.011), and was without effect on velocity. β-lactose had negligible or small treatment effects.Conclusions & inferencesWe show that the prebiotic 2'FL may have potential as a treatment for acute stress-induced gut dysmotility, ex vivo, and that, as is the case for certain beneficial microbes, the mechanism occurs in the gut, likely via action on the enteric nervous system.
- Published
- 2019
38. Agonistic autoantibodies against ß2-adrenergic receptor influence retinal microcirculation in glaucoma suspects and patients
- Author
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Till L. Hennig, Johann Ferdinand Krebs, Robert Lämmer, Meike Müller, Martin Herrmann, Bettina Hohberger, Christian Y. Mardin, Gerd Wallukat, Luis E. Muñoz, Sami Hosari, Folkert K. Horn, and Rudolf Kunze
- Subjects
Male ,Retinal Ganglion Cells ,Intraocular pressure ,Eye Diseases ,genetic structures ,Physiology ,Ocular hypertension ,Glaucoma ,Cardiovascular Physiology ,chemistry.chemical_compound ,Medical Conditions ,Nerve Fibers ,Animal Cells ,Medicine and Health Sciences ,Neurons ,Cardiomyocytes ,Multidisciplinary ,medicine.anatomical_structure ,Blood Circulation ,Inner nuclear layer ,Medicine ,Female ,Cellular Types ,Anatomy ,Glaucoma, Open-Angle ,Research Article ,medicine.medical_specialty ,Ganglion Cells ,Ocular Anatomy ,Science ,Muscle Tissue ,Microcirculation ,Ciliary body ,Ocular System ,Trabecular Meshwork ,Ophthalmology ,medicine ,Humans ,ddc:610 ,Intraocular Pressure ,Aged ,Autoantibodies ,Muscle Cells ,business.industry ,Biology and Life Sciences ,Afferent Neurons ,Retinal ,Cell Biology ,medicine.disease ,eye diseases ,Biological Tissue ,chemistry ,Cardiovascular and Metabolic Diseases ,Cellular Neuroscience ,Eyes ,Receptors, Adrenergic, beta-2 ,sense organs ,Trabecular meshwork ,business ,Head ,Neuroscience - Abstract
Purpose Agonistic β2-adrenergic receptor autoantibodies (β2-agAAb) have been observed in sera of patients with ocular hypertension and open-angle glaucoma (OAG). They target the β2-receptors on trabecular meshwork, ciliary body and pericytes (Junemann et al. 2018; Hohberger et al. 2019). In addition to their influence on the intraocular pressure, an association to retinal microcirculation is discussed. This study aimed to investigate foveal avascular zone (FAZ) characteristics by en face OCT angiography (OCT-A) in glaucoma suspects and its relationship to β2-agAAb status in patients with OAG. Material and methods Thirty-four patients (28 OAG, 6 glaucoma suspects) underwent standardized, clinical examination including sensory testing as white-on-white perimetry (Octopus G1, mean defect, MD) and structural measures as retinal nerve fibre layer (RNFL) thickness, neuroretinal rim width (BMO-MRW), retinal ganglion cell layer (RGCL) thickness, and inner nuclear layer (INL) thickness with high-resolution OCT. FAZ characteristics were measured by OCT-A scans of superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). FAZ-R was calculated (area FAZ (SVP)/area FAZ (ICP)). Using cardiomyocyte bioassays we analysed serum samples for the presence of β2-agAAb. Results (I) Total mean FAZ area [mm2]: 0.34±0.16 (SVP), 0.24±0.12 (ICP), and 0.49±0.24 (DCP); mean FAZ-R 1.58±0.94. No correlation was seen for FAZ-R with MD, RNFL, BMO-MRW, RGCL thickness and INL thickness (p>0.05). (II) ß2-agAAb have been observed in 91% patients and showed no correlation with MD, RNFL, BMO-MRW, RGCL thickness and INL thickness (p>0.05). (III) FAZ-R correlated significantly with the β2-agAAb-induced increase of the beat rate of cardiomyocyte (p = 0.028). Conclusion FAZ characteristics did not correlate with any glaucoma associated functional and morphometric follow-up parameter in the present cohort. However, level of β2-agAAb showed a significantly correlation with FAZ-ratio. We conclude that β2-agAAb might be a novel biomarker in glaucoma pathogenesis showing association to FAZ-ratio with OCT-A.
- Published
- 2021
39. Pre-/analytical factors affecting whole blood and plasma glucose concentrations in loggerhead sea turtles (Caretta caretta)
- Author
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Yu-Mei Chang, Patricia E. Kunze, Justin R. Perrault, Samantha Clark, Nicole I. Stacy, and Charles A. Manire
- Subjects
Blood Glucose ,Time Factors ,Physiology ,Cell volume ,Biochemistry ,01 natural sciences ,0403 veterinary science ,Plasma ,010104 statistics & probability ,Reptile Physiology ,Glucose Metabolism ,Reference Values ,Specimen Storage ,Blood plasma ,Medicine and Health Sciences ,Blood Glucose Measurement ,Whole blood ,Plasma glucose ,Multidisciplinary ,Organic Compounds ,Chemistry ,Pre analytical ,Monosaccharides ,Eukaryota ,04 agricultural and veterinary sciences ,Blood Sugar ,Turtles ,Body Fluids ,Reptile Biology ,Blood ,Vertebrates ,Physical Sciences ,Medicine ,Carbohydrate Metabolism ,Female ,Anatomy ,Research Article ,040301 veterinary sciences ,Science ,Carbohydrates ,Blood sugar ,Carbohydrate metabolism ,Research and Analysis Methods ,Blood Plasma ,Specimen Handling ,Animal science ,Animals ,Animal Physiology ,0101 mathematics ,Organic Chemistry ,Organisms ,Chemical Compounds ,Reproducibility of Results ,Biology and Life Sciences ,Reptiles ,Vertebrate Physiology ,Glucose ,Metabolism ,Testudines ,Storage and Handling ,Amniotes ,Factor Analysis, Statistical ,Zoology ,Blood Chemical Analysis - Abstract
Blood glucose is vital for many physiological pathways and can be quantified by clinical chemistry analyzers and in-house point-of-care (POC) devices. Pre-analytical and analytical factors can influence blood glucose measurements. This project aimed to investigate pre-analytical factors on whole blood and plasma glucose measurements in loggerhead sea turtles (Caretta caretta) by evaluating the effects of storage (refrigeration) up to 48h after sampling and of packed cell volume (PCV) on whole blood glucose analysis by POC glucometer (time series n = 13); and by evaluating the effects of storage (room temperature and refrigeration) on plasma glucose concentrations using a dry slide chemistry analyzer (DCA) at various conditions: immediate processing and delayed plasma separation from erythrocytes at 24h and 48h (time series n = 14). The POC glucometer had overall strong agreement with the DCA (CCC = 0.76, r = 0.84, Cb = 0.90), but consistently overestimated glucose concentrations (mean difference: +0.4 mmol/L). The POC glucometer results decreased significantly over time, resulting in a substantial decline within the first 2h (0.41±0.47 mmol/L; 8±9%) that could potentially alter clinical decisions, thereby highlighting the need for immediate analysis using this method. The effects of PCV on glucose could not be assessed, as the statistical significance was associated with one outlier. Storage method significantly affected plasma glucose measurements using DCA, with room temperature samples resulting in rapid decreases of 3.57±0.89 mmol/L (77±9%) over the first 48h, while refrigerated samples provided consistent plasma glucose results over the same time period (decrease of 0.26±0.23 mmol/L; 6±5%). The results from this study provide new insights into optimal blood sample handling and processing for glucose analysis in sea turtles, show the suitability of the POC glucometer as a rapid diagnostic test, and confirm the reliability of plasma glucose measurements using refrigeration. These findings emphasize the need to consider pre-/analytical factors when interpreting blood glucose results from loggerhead sea turtles.
- Published
- 2020
40. Simultaneous cardiac and respiratory inhibition during seizure precedes death in the DBA/1 audiogenic mouse model of SUDEP
- Author
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Schilling, William P., primary, McGrath, Morgan K., additional, Yang, Tianen, additional, Glazebrook, Patricia A., additional, Faingold, Carl L., additional, and Kunze, Diana L., additional
- Published
- 2019
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41. Restraint stress induced gut dysmotility is diminished by a milk oligosaccharide (2′-fucosyllactose) in vitro
- Author
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Farhin, Sohana, primary, Wong, Annette, additional, Delungahawatta, Thilini, additional, Amin, Jessica Y., additional, Bienenstock, John, additional, Buck, Rachael, additional, and Kunze, Wolfgang A., additional
- Published
- 2019
- Full Text
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42. Alcohol consumption and neurocognitive deficits in people with well-treated HIV in Switzerland.
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Darling, Katharine E. A., Locatelli, Isabella, Benghalem, Nadia, Nadin, Isaure, Calmy, Alexandra, Gutbrod, Klemens, Hauser, Christoph, Brugger, Peter, Hasse, Barbara, Kovari, Helen, Kunze, Ursi, Stoeckle, Marcel, Fux, Christophe, Rossi, Stefania, Di Benedetto, Caroline, Früh, Severin, Schmid, Patrick, Tarr, Philip E., Daeppen, Jean-Bernard, and Du Pasquier, Renaud
- Subjects
ALCOHOL drinking ,ALCOHOLISM ,BINGE drinking ,HIV infections ,ALCOHOL ,HIV - Abstract
Background: Hazardous alcohol consumption and HIV infection increase the risk of neurocognitive impairment (NCI). We examined the association between alcohol consumption and specific neurocognitive domain function in people with HIV (PWH) taking modern antiretroviral therapy. Methods: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is a prospective, longitudinal, multicentre and multilingual (French, German and Italian) study of patients aged ≥45 years old enrolled in the Swiss HIV Cohort Study (SHCS). Baseline data from 981 study participants were examined. Five neurocognitive domains were evaluated: motor skills, speed of information processing, attention/working memory, executive function and verbal episodic memory. NCI was examined as binary (presence/absence) and continuous (mean z-score) outcomes against Alcohol Use Disorders Identification Test for Consumption (AUDIT-C) scores using logistic and linear regression models, respectively. Results: Most participants (96.2%) had undetectable viral loads and 64% were aged >50 years old. Hazardous alcohol consumption was observed in 49.4% of participants and binge drinking in 4.2%. While alcohol consumption frequency and quantity were not associated with NCI, the practice of binge drinking was significantly associated with impaired motor skills and overall neurocognitive function in both binary (odds ratio, OR ≥2.0, P <0.05) and continuous (mean z-score difference -0.2 to -0.4, P ≤0.01) outcomes. A significant U-shaped distribution of AUDIT-C score was also observed for motor skills and overall neurocognitive function. Conclusions: In this cohort of PWH with well-controlled HIV infection, NCI was associated with the practice of binge drinking rather than alcohol consumption frequency or quantity. Longitudinal analysis of alcohol consumption and NCI in this population is currently underway. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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43. Mpp10 represents a platform for the interaction of multiple factors within the 90S pre-ribosome
- Author
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Satyavati Kharde, Irmgard Sinning, Gunter Stier, Markus Kornprobst, Ed Hurt, Ruth Kunze, Bebiana Sá-Moura, and Yasar Luqman Ahmed
- Subjects
0301 basic medicine ,Ribosome biogenesis ,lcsh:Medicine ,Yeast and Fungal Models ,Ribosome ,Biochemistry ,Protein Structure, Secondary ,Ribosome assembly ,0302 clinical medicine ,Protein structure ,Electron Microscopy ,lcsh:Science ,Ribonucleoprotein ,Microscopy ,Multidisciplinary ,Crystallography ,Chemistry ,Physics ,Nuclear Proteins ,Condensed Matter Physics ,Nucleic acids ,Ribonucleoproteins ,Experimental Organism Systems ,Ribosomal RNA ,Physical Sciences ,Chromatography, Gel ,Crystal Structure ,Saccharomyces Cerevisiae ,Protein Binding ,Research Article ,Ribosomal Proteins ,Cell biology ,Multiple Alignment Calculation ,Saccharomyces cerevisiae Proteins ,Cellular structures and organelles ,Computational biology ,Research and Analysis Methods ,Biosynthesis ,03 medical and health sciences ,Saccharomyces ,Model Organisms ,Ribosomal protein ,Interaction network ,Computational Techniques ,RNA, Ribosomal, 18S ,Solid State Physics ,Non-coding RNA ,lcsh:R ,Organisms ,Fungi ,Correction ,Biology and Life Sciences ,Electron Cryo-Microscopy ,Phosphoproteins ,Yeast ,Split-Decomposition Method ,030104 developmental biology ,RNA ,lcsh:Q ,Ribosomes ,030217 neurology & neurosurgery - Abstract
In eukaryotes, ribosome assembly is a highly complex process that involves more than 200 assembly factors that ensure the folding, modification and processing of the different rRNA species as well as the timely association of ribosomal proteins. One of these factors, Mpp10 associates with Imp3 and Imp4 to form a complex that is essential for the normal production of the 18S rRNA. Here we report the crystal structure of a complex between Imp4 and a short helical element of Mpp10 to a resolution of 1.88 Å. Furthermore, we extend the interaction network of Mpp10 and characterize two novel interactions. Mpp10 is able to bind the ribosome biogenesis factor Utp3/Sas10 through two conserved motifs in its N-terminal region. In addition, Mpp10 interacts with the ribosomal protein S5/uS7 using a short stretch within an acidic loop region. Thus, our findings reveal that Mpp10 provides a platform for the simultaneous interaction with multiple proteins in the 90S pre-ribosome.
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- 2017
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44. Adult hippocampal neurogenesis poststroke: More new granule cells but aberrant morphology and impaired spatial memory
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Max Rudolph, Otto W. Witte, Mihai Ceanga, Florus Woitke, Christoph Redecker, Silke Keiner, Fanny Niv, and Albrecht Kunze
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0301 basic medicine ,Male ,lcsh:Medicine ,Morris water navigation task ,Hippocampal formation ,Vascular Medicine ,law.invention ,Mice ,0302 clinical medicine ,Cognition ,Learning and Memory ,law ,Animal Cells ,Hippocampal Neurogenesis ,Medicine and Health Sciences ,lcsh:Science ,Spatial Memory ,Neurons ,Multidisciplinary ,Neuronal Plasticity ,Neurogenesis ,Granule (cell biology) ,Brain ,Stroke ,Neurology ,Cellular Types ,Anatomy ,Research Article ,Confocal ,Cerebrovascular Diseases ,Biology ,03 medical and health sciences ,Developmental Neuroscience ,Confocal microscopy ,Memory ,Neuroplasticity ,Animals ,Humans ,Maze Learning ,Granule Cells ,Dentate gyrus ,lcsh:R ,Hippocampal Formation ,Adult Neurogenesis ,Biology and Life Sciences ,Cell Biology ,Neuronal Dendrites ,Disease Models, Animal ,030104 developmental biology ,nervous system ,Cellular Neuroscience ,Dentate Gyrus ,Cognitive Science ,lcsh:Q ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Stroke significantly stimulates neurogenesis in the adult dentate gyrus, though the functional role of this postlesional response is mostly unclear. Recent findings suggest that newborn neurons generated in the context of stroke may fail to correctly integrate into pre-existing networks. We hypothesized that increased neurogenesis in the dentate gyrus following stroke is associated with aberrant neurogenesis and impairment of hippocampus-dependent memory. To address these questions we used the middle cerebral artery occlusion model (MCAO) in mice. Animals were housed either under standard conditions or with free access to running wheels. Newborn granule cells were labelled with the thymidine analoque EdU and retroviral vectors. To assess memory performance, we employed a modified version of the Morris water maze (MWM) allowing differentiation between hippocampus dependent and independent learning strategies. Newborn neurons were morphologically analyzed using confocal microscopy and Neurolucida system at 7 weeks. We found that neurogenesis was significantly increased following MCAO. Animals with MCAO needed more time to localize the platform and employed less hippocampus-dependent search strategies in MWM versus controls. Confocal studies revealed an aberrant cell morphology with basal dendrites and an ectopic location (e.g. hilus) of new granule cells born in the ischemic brain. Running increased the number of new neurons but also enhanced aberrant neurogenesis. Running, did not improve the general performance in the MWM but slightly promoted the application of precise spatial search strategies. In conclusion, ischemic insults cause hippocampal-dependent memory deficits which are associated with aberrant neurogenesis in the dentate gyrus indicating ischemia-induced maladaptive plasticity in the hippocampus.
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- 2016
45. Zebrafish larvae show negative phototaxis to near-infrared light
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Hartmann, Sarah, primary, Vogt, Roland, additional, Kunze, Jan, additional, Rauschert, Anna, additional, Kuhnert, Klaus-Dieter, additional, Wanzenböck, Josef, additional, Lamatsch, Dunja K., additional, and Witte, Klaudia, additional
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- 2018
- Full Text
- View/download PDF
46. A model of individualized canonical microcircuits supporting cognitive operations
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Kunze, Tim, primary, Peterson, Andre D. H., additional, Haueisen, Jens, additional, and Knösche, Thomas R., additional
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- 2017
- Full Text
- View/download PDF
47. Sensitivity of Diffusion-Weighted STEAM MRI and EPI-DWI to Infratentorial Ischemic Stroke
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Marc Hohenhaus, Wolf U. Schmidt, Kersten Villringer, Claudia Kunze, Peter Brunecker, Jochen B. Fiebach, Jens Frahm, Klaus-Dietmar Merboldt, and Ahmed A. Khalil
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Male ,Image Processing ,Infarction ,lcsh:Medicine ,Signal-To-Noise Ratio ,600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit ,Pathology and Laboratory Medicine ,Vascular Medicine ,030218 nuclear medicine & medical imaging ,Diagnostic Radiology ,0302 clinical medicine ,Ischemia ,Medicine and Health Sciences ,lcsh:Science ,Stroke ,Aged, 80 and over ,Brain Mapping ,Multidisciplinary ,medicine.diagnostic_test ,Echo-Planar Imaging ,Radiology and Imaging ,Middle Aged ,Magnetic Resonance Imaging ,Neurology ,Engineering and Technology ,Female ,Radiology ,Artifacts ,Research Article ,Adult ,medicine.medical_specialty ,Imaging Techniques ,Brain Morphometry ,Cerebrovascular Diseases ,Neuroimaging ,Research and Analysis Methods ,03 medical and health sciences ,Signs and Symptoms ,Diagnostic Medicine ,medicine ,Humans ,cardiovascular diseases ,Ischemic Stroke ,Aged ,business.industry ,Diffusion Weighted Imaging ,lcsh:R ,Biology and Life Sciences ,Reproducibility of Results ,Magnetic resonance imaging ,medicine.disease ,Diffusion Magnetic Resonance Imaging ,Ischemic stroke ,Signal Processing ,Lesions ,lcsh:Q ,Stimulated echo ,business ,030217 neurology & neurosurgery ,Kappa ,Diffusion MRI ,Neuroscience - Abstract
Objectives To assess the sensitivity of stimulated echo acquisition mode diffusion weighted imaging (STEAM-DWI) to ischemic stroke in comparison to echo-planar imaging diffusion weighted imaging (EPI-DWI) in the infratentorial compartment. Methods Fifty-seven patients presenting with clinical features of infratentorial stroke underwent STEAM-DWI, high-resolution EPI-DWI (HR-DWI, 2.5 mm slice thickness) and low-resolution EPI-DWI (LR-DWI, 5 mm slice thickness). Four readers assessed the presence of ischemic lesions and artifacts. Agreement between sequences and interobserver agreement on the presence of ischemia were calculated. The sensitivities of the DWI sequences were calculated in 45 patients with a confirmed diagnosis of infratentorial stroke. Results Median time from symptom onset to imaging was 24 hours. STEAM- DWI agreed with LR-DWI in 89.5% of cases (kappa = 0.72, p
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- 2016
48. Treatment of ruptured intracranial aneurysms yesterday and now
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Anahi Steiner, Ghassan Kerry, Alexander Hammer, Gholamreza Ranaie, Christian M. Hammer, Stefan Kunze, Ingrid Baer, and Hans-Herbert Steiner
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Male ,Microsurgery ,medicine.medical_treatment ,lcsh:Medicine ,Aneurysm, Ruptured ,Vascular Medicine ,Chi Square Tests ,030218 nuclear medicine & medical imaging ,Nervous System Procedures ,0302 clinical medicine ,Mathematical and Statistical Techniques ,Medizinische Fakultät ,Occlusion ,Medicine and Health Sciences ,Prospective Studies ,lcsh:Science ,Prospective cohort study ,Neuroradiology ,Multidisciplinary ,Endovascular Procedures ,Arteries ,Middle Aged ,Stroke ,Carotid Arteries ,Treatment Outcome ,Neurology ,Physical Sciences ,cardiovascular system ,Female ,Neurosurgery ,Anatomy ,Aneurysms ,Statistics (Mathematics) ,Research Article ,medicine.medical_specialty ,Subarachnoid hemorrhage ,Death Rates ,Cerebrovascular Diseases ,Surgical and Invasive Medical Procedures ,Research and Analysis Methods ,03 medical and health sciences ,Aneurysm ,medicine ,Humans ,ddc:610 ,cardiovascular diseases ,Vascular Diseases ,Mortality ,Statistical Methods ,Statistical Hypothesis Testing ,Aged ,Ischemic Stroke ,Demography ,business.industry ,lcsh:R ,Biology and Life Sciences ,Intracranial Aneurysm ,Clipping (medicine) ,Cerebral Arteries ,Subarachnoid Hemorrhage ,medicine.disease ,Surgery ,People and Places ,Cardiovascular Anatomy ,Blood Vessels ,lcsh:Q ,business ,030217 neurology & neurosurgery ,Mathematics - Abstract
Objective This prospective study is designed to detect changes in the treatment of ruptured intracranial aneurysms over a period of 17 years. Methods We compared 361 treated cases of aneurysm occlusion after subarachnoid hemorrhage from 1997 to 2003 with 281 cases from 2006 to 2014. Specialists of neuroradiology and vascular neurosurgery decided over the modality assignment. We established a prospective data acquisition in both groups to detect significant differences within a follow-up time of one year. With this setting we evaluated the treatment methods over time and compared endovascular with microsurgical treatment. Results When compared to the earlier group, microsurgical treatment was less frequently chosen in the more recent collective because of neck-configuration. Endovascular treatment was chosen more frequently over time (31.9% versus 48.8%). Occurrence of initial symptomatic ischemic stroke was significantly lower in the clipping group compared to the endovascular group and remained stable over time. The number of reinterventions due to refilled treated aneurysms significantly decreased in the endovascular group at one-year follow-up, but the significantly better occlusion- and reintervention-rate of the microsurgical group persisted. The rebleeding rate in the endovascular group at one year follow-up decreased from 6.1% to 2.2% and showed no statistically significant difference to the microsurgical group, anymore (endovascular 2.2% versus microsurgical 0.0%, p = 0.11). Conclusion Microsurgical clipping still has some advantages, however endovascular treatment is improving rapidly.
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- 2016
49. Screening of Compounds against Gardnerella vaginalis Biofilms
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Cornelia Gottschick, Szymon P. Szafrański, Brigitte Kunze, Christoph Abels, Clarissa Masur, Irene Wagner-Döbler, Helena Sztajer, and Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
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0301 basic medicine ,Antibiotics ,lcsh:Medicine ,medicine.disease_cause ,Tobramycin ,Medicine and Health Sciences ,Gardnerella vaginalis ,lcsh:Science ,Staining ,Multidisciplinary ,Vaginal flora ,Antimicrobials ,Organic Compounds ,Monosaccharides ,Drugs ,Crystal Violet Staining ,Vaginosis, Bacterial ,Antimicrobial ,Anti-Bacterial Agents ,Chemistry ,Infectious Diseases ,Physical Sciences ,Female ,Biological Cultures ,Bacterial vaginosis ,medicine.drug ,Research Article ,Cell Culturing Techniques ,Biofilm Culture ,medicine.drug_class ,Urology ,030106 microbiology ,Carbohydrates ,Sexually Transmitted Diseases ,Microbial Sensitivity Tests ,Biology ,Research and Analysis Methods ,Microbiology ,Models, Biological ,03 medical and health sciences ,Bacterial Vaginosis ,Microbial Control ,medicine ,Humans ,Pharmacology ,Genitourinary Infections ,lcsh:R ,Organic Chemistry ,Biofilm ,Chemical Compounds ,Biology and Life Sciences ,Bacteriology ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,Metronidazole ,Glucose ,Specimen Preparation and Treatment ,Biofilms ,lcsh:Q ,Bacterial Biofilms - Abstract
Bacterial vaginosis (BV) is a common infection in reproductive age woman and is characterized by dysbiosis of the healthy vaginal flora which is dominated by Lactobacilli, followed by growth of bacteria like Gardnerella vaginalis. The ability of G. vaginalis to form biofilms contributes to the high rates of recurrence that are typical for BV and which unfortunately make repeated antibiotic therapy inevitable. Here we developed a biofilm model for G. vaginalis and screened a large spectrum of compounds for their ability to prevent biofilm formation and to resolve an existing G. vaginalis biofilm. The antibiotics metronidazole and tobramycin were highly effective in preventing biofilm formation, but had no effect on an established biofilm. The application of the amphoteric tenside sodium cocoamphoacetate (SCAA) led to disintegration of existing biofilms, reducing biomass by 51% and viability by 61% and it was able to increase the effect of metronidazole by 40% (biomass) and 61% (viability). Our data show that attacking the biofilm and the bacterial cells by the combination of an amphoteric tenside with the antibiotic metronidazole might be a useful strategy against BV.
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- 2016
50. Association between DNA Methylation in Whole Blood and Measures of Glucose Metabolism: KORA F4 Study
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Christian Herder, Sonja Kunze, Wolfgang Rathmann, Holger Prokisch, Nadezda V. Volkova, Thomas Illig, Melanie Waldenberger, Harald Grallert, Maren Carstensen-Kirberg, Katharina Schramm, Michael Roden, Christian Gieger, Jennifer Kriebel, Sophie Molnos, Simone Wahl, and Annette Peters
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0301 basic medicine ,Blood Glucose ,Male ,Physiology ,medicine.medical_treatment ,lcsh:Medicine ,Type 2 diabetes ,Biochemistry ,Body Mass Index ,Epigenesis, Genetic ,White Blood Cells ,Endocrinology ,Glucose Metabolism ,Cell Signaling ,Animal Cells ,Germany ,Medicine and Health Sciences ,Insulin ,lcsh:Science ,ATP Binding Cassette Transporter, Subfamily G, Member 1 ,Aged, 80 and over ,education.field_of_study ,Glucose tolerance test ,Multidisciplinary ,DNA methylation ,medicine.diagnostic_test ,Methylation ,Middle Aged ,Chromatin ,ddc ,Nucleic acids ,Phenotype ,CpG site ,Carbohydrate Metabolism ,Glucose metabolism ,White blood cells ,Diabetes mellitus ,Glucose signaling ,Gene expression ,Epigenetics ,Female ,Cellular Types ,DNA modification ,Chromatin modification ,Research Article ,Chromosome biology ,Signal Transduction ,Adult ,medicine.medical_specialty ,Cell biology ,Endocrine Disorders ,Immune Cells ,Population ,Immunology ,Biology ,Glucose Signaling ,03 medical and health sciences ,Internal medicine ,medicine ,Genetics ,Diabetes Mellitus ,Humans ,education ,Aged ,Diabetic Endocrinology ,Blood Cells ,Biology and life sciences ,Endocrine Physiology ,lcsh:R ,Insulin Signaling ,DNA ,Glucose Tolerance Test ,medicine.disease ,Hormones ,030104 developmental biology ,Metabolism ,Glucose ,Diabetes Mellitus, Type 2 ,Metabolic Disorders ,lcsh:Q ,ATP-Binding Cassette Transporters ,CpG Islands ,Genome-Wide Association Study - Abstract
Epigenetic regulation has been postulated to affect glucose metabolism, insulin sensitivity and the risk of type 2 diabetes. Therefore, we performed an epigenome-wide association study for measures of glucose metabolism in whole blood samples of the population-based Cooperative Health Research in the Region of Augsburg F4 study using the Illumina Human Methylation 450 BeadChip. We identified a total of 31 CpG sites where methylation level was associated with measures of glucose metabolism after adjustment for age, sex, smoking, and estimated white blood cell proportions and correction for multiple testing using the Benjamini-Hochberg (B-H) method (four for fasting glucose, seven for fasting insulin, 25 for homeostasis model assessment-insulin resistance [HOMA-IR]; B-H-adjusted p-values between 9.2×10-5 and 0.047). In addition, DNA methylation at cg06500161 (annotated to ABCG1) was associated with all the aforementioned phenotypes and 2-hour glucose (B-H-adjusted p-values between 9.2×10-5 and 3.0×10-3). Methylation status of additional three CpG sites showed an association with fasting insulin only after additional adjustment for body mass index (BMI) (B-H-adjusted p-values = 0.047). Overall, effect strengths were reduced by around 30% after additional adjustment for BMI, suggesting that this variable has an influence on the investigated phenotypes. Furthermore, we found significant associations between methylation status of 21 of the aforementioned CpG sites and 2-hour insulin in a subset of samples with seven significant associations persisting after additional adjustment for BMI. In a subset of 533 participants, methylation of the CpG site cg06500161 (ABCG1) was inversely associated with ABCG1 gene expression (B-Hadjusted p-value = 1.5×10-9). Additionally, we observed an enrichment of the top 1,000 CpG sites for diabetes-related canonical pathways using Ingenuity Pathway Analysis. In conclusion, our study indicates that DNA methylation and diabetes-related traits are associated and that these associations are partially BMI-dependent. Furthermore, the interaction of ABCG1 with glucose metabolism is modulated by epigenetic processes.
- Published
- 2016
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