TY - JOUR A1 - Wilhelmi, Ilka A1 - Neumann, Alexander A1 - Jähnert, Markus A1 - Ouni, Meriem A1 - Schürmann, Annette T1 - Enriched alternative splicing in islets of diabetes-susceptible mice JF - International journal of molecular sciences N2 - Dysfunctional islets of Langerhans are a hallmark of type 2 diabetes (T2D). We hypothesize that differences in islet gene expression alternative splicing which can contribute to altered protein function also participate in islet dysfunction. RNA sequencing (RNAseq) data from islets of obese diabetes-resistant and diabetes-susceptible mice were analyzed for alternative splicing and its putative genetic and epigenetic modulators. We focused on the expression levels of chromatin modifiers and SNPs in regulatory sequences. We identified alternative splicing events in islets of diabetes-susceptible mice amongst others in genes linked to insulin secretion, endocytosis or ubiquitin-mediated proteolysis pathways. The expression pattern of 54 histones and chromatin modifiers, which may modulate splicing, were markedly downregulated in islets of diabetic animals. Furthermore, diabetes-susceptible mice carry SNPs in RNA-binding protein motifs and in splice sites potentially responsible for alternative splicing events. They also exhibit a larger exon skipping rate, e.g., in the diabetes gene Abcc8, which might affect protein function. Expression of the neuronal splicing factor Srrm4 which mediates inclusion of microexons in mRNA transcripts was markedly lower in islets of diabetes-prone compared to diabetes-resistant mice, correlating with a preferential skipping of SRRM4 target exons. The repression of Srrm4 expression is presumably mediated via a higher expression of miR-326-3p and miR-3547-3p in islets of diabetic mice. Thus, our study suggests that an altered splicing pattern in islets of diabetes-susceptible mice may contribute to an elevated T2D risk. KW - alternative splicing KW - epigenetic KW - MicroRNA KW - RNAseq KW - diabetes KW - beta-cell KW - failure Y1 - 2021 U6 - https://doi.org/10.3390/ijms22168597 SN - 1422-0067 VL - 22 IS - 16 PB - Molecular Diversity Preservation International CY - Basel ER - TY - JOUR A1 - Schmicker, Marlen A1 - Frühling, Insa A1 - Menze, Inga A1 - Glanz, Wenzel A1 - Müller, Patrick A1 - Noesselt, Toemme A1 - Müller, Notger Germar T1 - The potential role of gustatory function as an early diagnostic marker for the risk of alzheimer's disease in subjective cognitive decline JF - Journal of Alzheimer's disease reports : JADR N2 - Background: Patients with subjective cognitive decline (SCD) report memory deterioration and are at an increased risk of converting to Alzheimer's disease (AD) although psychophysical testing does not reveal any cognitive deficit. Objective: Here, gustatory function is investigated as a potential predictor for an increased risk of progressive cognitive decline indicating higher AD risk in SCD. Methods: Measures of smell and taste perception as well as neuropsychological data were assessed in patients with subjective cognitive decline (SCD): Subgroups with an increased likelihood of the progression to preclinical AD (SCD+) and those with a lower likelihood (SCD-) were compared to healthy controls (HC), patients with mild cognitive impairment and AD patients. The Sniffin' Sticks test contained 12 items with different qualities and taste was measured with 32 taste stripes (sweet, salty, bitter, sour) of different concentration. Results: Only taste was able to distinguish between HC/SCD- and SCD+ patients. Conclusion: This study provides a first hint of taste as a more sensitive marker than smell for detecting preclinical AD in SCD. Longitudinal observation of cognition and pathology are necessary to further evaluate taste perception as a predictor of pathological objective decline in cognition. KW - Alzheimer's disease KW - dementia KW - diagnostic marker KW - early diagnosis KW - subjective cognitive decline KW - taste Y1 - 2023 U6 - https://doi.org/10.3233/ADR220092 SN - 2542-4823 VL - 7 IS - 1 SP - 249 EP - 262 PB - IOS Press CY - Clifton, VA ER - TY - JOUR A1 - Zhang, Zhihao A1 - Wang, Ting A1 - Kuang, Jin A1 - Herold, Fabian A1 - Ludyga, Sebastian A1 - Li, Jingming A1 - Hall, Daniel L. A1 - Taylor, Alyx A1 - Healy, Sean A1 - Yeung, Albert S. A1 - Kramer, Arthur F. A1 - Zou, Liye T1 - The roles of exercise tolerance and resilience in the effect of physical activity on emotional states among college students JF - International Journal of Clinical and Health Psychology N2 - Background/objective: Negative emotional states, such as depression, anxiety, and stress challenge health care due to their long-term consequences for mental disorders. Accumulating evidence indicates that regular physical activity (PA) can positively influence negative emotional states. Among possible candidates, resilience and exercise tolerance in particular have the potential to partly explain the positive effects of PA on negative emotional states. Thus, the aim of this study was to investigate the association between PA and negative emotional states, and further determine the mediating effects of exercise tolerance and resilience in such a relationship. Method: In total, 1117 Chinese college students (50.4% female, Mage=18.90, SD=1.25) completed a psychosocial battery, including the 21-item Depression Anxiety Stress Scale (DASS-21), the Connor-Davidson Resilience Scale (CD-RISC), the Preference for and Tolerance of the Intensity of Exercise Questionnaire (PRETIE-Q), and the International Physical Activity Questionnaire short form (IPAQ-SF). Regression analysis was used to identify the serial multiple mediation, controlling for gender, age and BMI. Results: PA, exercise intensity-tolerance, and resilience were significantly negatively correlated with negative emotional states (Ps<.05). Further, exercise tolerance and resilience partially mediated the relationship between PA and negative emotional states. Conclusions: Resilience and exercise intensity-tolerance can be achieved through regularly engaging in PA, and these newly observed variables play critical roles in prevention of mental illnesses, especially college students who face various challenges. Recommended amount of PA should be incorporated into curriculum or sport clubs within a campus environment. KW - Exercise tolerance KW - Resilience KW - Physical activity KW - Emotion KW - Depression Y1 - 2022 U6 - https://doi.org/10.1016/j.ijchp.2022.100312 SN - 1697-2600 SN - 1576-7329 VL - 22 IS - 3 PB - Elsevier CY - New York ER - TY - JOUR A1 - Menze, Inga A1 - Müller, Notger Germar A1 - Zähle, Tino A1 - Schmicker, Marlen T1 - Individual response to transcranial direct current stimulation as a function of working memory capacity and electrode montage JF - Frontiers in human neuroscience N2 - Introduction Attempts to improve cognitive abilities via transcranial direct current stimulation (tDCS) have led to ambiguous results, likely due to the method's susceptibility to methodological and inter-individual factors. Conventional tDCS, i.e., using an active electrode over brain areas associated with the targeted cognitive function and a supposedly passive reference, neglects stimulation effects on entire neural networks. Methods We investigated the advantage of frontoparietal network stimulation (right prefrontal anode, left posterior parietal cathode) against conventional and sham tDCS in modulating working memory (WM) capacity dependent transfer effects of a single-session distractor inhibition (DIIN) training. Since previous results did not clarify whether electrode montage drives this individual transfer, we here compared conventional to frontoparietal and sham tDCS and reanalyzed data of 124 young, healthy participants in a more robust way using linear mixed effect modeling. Results The interaction of electrode montage and WM capacity resulted in systematic differences in transfer effects. While higher performance gains were observed with increasing WM capacity in the frontoparietal stimulation group, low WM capacity individuals benefited more in the sham condition. The conventional stimulation group showed subtle performance gains independent of WM capacity. Discussion Our results confirm our previous findings of WM capacity dependent transfer effects on WM by a single-session DIIN training combined with tDCS and additionally highlight the pivotal role of the specific electrode montage. WM capacity dependent differences in frontoparietal network recruitment, especially regarding the parietal involvement, are assumed to underlie this observation. KW - tDCS KW - electrode montage KW - individual differences KW - working memory KW - capacity KW - distractor inhibition KW - frontoparietal network Y1 - 2023 U6 - https://doi.org/10.3389/fnhum.2023.1134632 SN - 1662-5161 VL - 17 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Lehmann, Nico A1 - Kuhn, Yves-Alain A1 - Keller, Martin A1 - Aye, Norman A1 - Herold, Fabian A1 - Draganski, Bogdan A1 - Taube, Wolfgang A1 - Taubert, Marco T1 - Brain activation during active balancing and its behavioral relevance in younger and older adults BT - a functional near-infrared spectroscopy (fNIRS) study JF - Frontiers in Aging Neuroscience N2 - Age-related deterioration of balance control is widely regarded as an important phenomenon influencing quality of life and longevity, such that a more comprehensive understanding of the neural mechanisms underlying this process is warranted. Specifically, previous studies have reported that older adults typically show higher neural activity during balancing as compared to younger counterparts, but the implications of this finding on balance performance remain largely unclear. Using functional near-infrared spectroscopy (fNIRS), differences in the cortical control of balance between healthy younger (n = 27) and older (n = 35) adults were explored. More specifically, the association between cortical functional activity and balance performance across and within age groups was investigated. To this end, we measured hemodynamic responses (i.e., changes in oxygenated and deoxygenated hemoglobin) while participants balanced on an unstable device. As criterion variables for brain-behavior-correlations, we also assessed postural sway while standing on a free-swinging platform and while balancing on wobble boards with different levels of difficulty. We found that older compared to younger participants had higher activity in prefrontal and lower activity in postcentral regions. Subsequent robust regression analyses revealed that lower prefrontal brain activity was related to improved balance performance across age groups, indicating that higher activity of the prefrontal cortex during balancing reflects neural inefficiency. We also present evidence supporting that age serves as a moderator in the relationship between brain activity and balance, i.e., cortical hemodynamics generally appears to be a more important predictor of balance performance in the older than in the younger. Strikingly, we found that age differences in balance performance are mediated by balancing-induced activation of the superior frontal gyrus, thus suggesting that differential activation of this region reflects a mechanism involved in the aging process of the neural control of balance. Our study suggests that differences in functional brain activity between age groups are not a mere by-product of aging, but instead of direct behavioral relevance for balance performance. Potential implications of these findings in terms of early detection of fall-prone individuals and intervention strategies targeting balance and healthy aging are discussed. KW - aging KW - neuroimaging KW - functional near-infrared spectroscopy (fNIRS) KW - balance KW - postural control KW - prefrontal cortex KW - neural inefficiency Y1 - 2022 U6 - https://doi.org/10.3389/fnagi.2022.828474 SN - 1663-4365 VL - 14 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Wang, Chaoxuan A1 - Enssle, Jörg A1 - Pietzner, Anne A1 - Schmöcker, Christoph A1 - Weiland, Linda A1 - Ritter, Oliver A1 - Jaensch, Monique A1 - Elbelt, Ulf A1 - Pagonas, Nikolaos A1 - Weylandt, Karsten-Henrich T1 - Essential polyunsaturated fatty acids in blood from patients with and without catheter-proven coronary artery disease JF - International journal of molecular sciences N2 - Coronary artery disease (CAD) is the leading cause of death worldwide. Statins reduce morbidity and mortality of CAD. Intake of n-3 polyunsaturated fatty acid (n-3 PUFAs), particularly eicosapentaenoic acid (EPA), is associated with reduced morbidity and mortality in patients with CAD. Previous data indicate that a higher conversion of precursor fatty acids (FAs) to arachidonic acid (AA) is associated with increased CAD prevalence. Our study explored the FA composition in blood to assess n-3 PUFA levels from patients with and without CAD. We analyzed blood samples from 273 patients undergoing cardiac catheterization. Patients were stratified according to clinically relevant CAD (n = 192) and those without (n = 81). FA analysis in full blood was performed by gas chromatography. Indicating increased formation of AA from precursors, the ratio of dihomo-gamma-linolenic acid (DGLA) to AA, the delta-5 desaturase index (D5D index) was higher in CAD patients. CAD patients had significantly lower levels of omega-6 polyunsaturated FAs (n-6 PUFA) and n-3 PUFA, particularly EPA, in the blood. Thus, our study supports a role of increased EPA levels for cardioprotection. KW - coronary artery disease KW - triglycerides KW - polyunsaturated fatty acids KW - n-3 PUFA KW - statins KW - arachidonic acid Y1 - 2022 U6 - https://doi.org/10.3390/ijms23020766 SN - 1422-0067 SN - 1661-6596 VL - 23 IS - 2 PB - Molecular Diversity Preservation International CY - Basel ER - TY - JOUR A1 - Klaus, Benita A1 - Müller, Patrick A1 - van Wickeren, Nora A1 - Dordevic, Milos A1 - Schmicker, Marlen A1 - Zdunczyk, Yael A1 - Brigadski, Tanja A1 - Lessmann, Volkmar A1 - Vielhaber, Stefan A1 - Schreiber, Stefanie A1 - Müller, Notger Germar T1 - Structural and functional brain alterations in patients with myasthenia gravis JF - Brain communications N2 - Myasthenia gravis is an autoimmune disease affecting neuromuscular transmission and causing skeletal muscle weakness. Additionally, systemic inflammation, cognitive deficits and autonomic dysfunction have been described. However, little is known about myasthenia gravis-related reorganization of the brain. In this study, we thus investigated the structural and functional brain changes in myasthenia gravis patients. Eleven myasthenia gravis patients (age: 70.64 +/- 9.27; 11 males) were compared to age-, sex- and education-matched healthy controls (age: 70.18 +/- 8.98; 11 males). Most of the patients (n = 10, 0.91%) received cholinesterase inhibitors. Structural brain changes were determined by applying voxel-based morphometry using high-resolution T-1-weighted sequences. Functional brain changes were assessed with a neuropsychological test battery (including attention, memory and executive functions), a spatial orientation task and brain-derived neurotrophic factor blood levels. Myasthenia gravis patients showed significant grey matter volume reductions in the cingulate gyrus, in the inferior parietal lobe and in the fusiform gyrus. Furthermore, myasthenia gravis patients showed significantly lower performance in executive functions, working memory (Spatial Span, P = 0.034, d = 1.466), verbal episodic memory (P = 0.003, d = 1.468) and somatosensory-related spatial orientation (Triangle Completion Test, P = 0.003, d = 1.200). Additionally, serum brain-derived neurotrophic factor levels were significantly higher in myasthenia gravis patients (P = 0.001, d = 2.040). Our results indicate that myasthenia gravis is associated with structural and functional brain alterations. Especially the grey matter volume changes in the cingulate gyrus and the inferior parietal lobe could be associated with cognitive deficits in memory and executive functions. Furthermore, deficits in somatosensory-related spatial orientation could be associated with the lower volumes in the inferior parietal lobe. Future research is needed to replicate these findings independently in a larger sample and to investigate the underlying mechanisms in more detail. Klaus et al. compared myasthenia gravis patients to matched healthy control subjects and identified functional alterations in memory functions as well as structural alterations in the cingulate gyrus, in the inferior parietal lobe and in the fusiform gyrus. KW - myasthenia gravis KW - neuroplasticity KW - VBM KW - neuropsychological testing KW - BDNF Y1 - 2022 U6 - https://doi.org/10.1093/braincomms/fcac018 SN - 2632-1297 VL - 4 IS - 1 PB - Oxford Univ. Press CY - Oxford ER - TY - JOUR A1 - Loss, Julika A1 - Boklage, Evgeniya A1 - Jordan, Susanne A1 - Jenny, Mirjam A. A1 - Weishaar, Heide A1 - El Bcheraoui, Charbel T1 - Risikokommunikation bei der Eindämmung der COVID-19-Pandemie BT - Herausforderungen und Erfolg versprechende Ansätze BT - challenges and promising approaches JF - Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz N2 - Risk communication plays a central role in public health emergencies: it must enable informed decisions, promote protective or life-sustaining behaviour, and maintain trust in public institutions. In addition, uncertainties in knowledge must be named transparently; irrational fears and rumours must be refuted. Success factors for risk communication are the participation of citizens as well as the continuous recording of risk perception and risk competence in population groups. The current COVID-19 (corona virus disease 2019) pandemic poses specific challenges for risk communication. The state of knowledge on many important aspects concerning COVID-19 was and is often uncertain or preliminary, e.g. on transmission, symptoms, long-term effects and immunity. Communication is characterised by scientific language and an array of figures and statistics, which can render the content difficult to understand. Alongside the official announcements and statements by experts, COVID-19 is widely communicated on social media, spreading misinformation and speculation; this "infodemic" can complicate risk communication. Various national and international scientific projects will help tailor risk communication on COVID-19 to target groups and thereby render it more effective. These projects include explorative studies on how people deal with COVID-19-related information; the COVID-19 Snapshot Monitoring (COSMO) project, a regularly conducted online survey on risk perception and protective behaviour; and an interdisciplinary qualitative study that compares the design, implementation and effectiveness of risk communication strategies in four countries. N2 - Risikokommunikation spielt eine zentrale Rolle in Public-Health-Notlagen: Sie muss informierte Entscheidungen ermöglichen, schützendes bzw. lebenserhaltendes Verhalten fördern und das Vertrauen in öffentliche Institutionen bewahren. Zudem müssen Unsicherheiten über wissenschaftliche Erkenntnisse transparent benannt werden, irrationale Ängste und Gerüchte entkräftet werden. Risikokommunikation sollte die Bevölkerung partizipativ einbeziehen. Ihre Risikowahrnehmung und -kompetenz müssen kontinuierlich erfasst werden. In der aktuellen Pandemie der Coronavirus-Krankheit 2019 (COVID-19) ergeben sich spezifische Herausforderungen für die Risikokommunikation. Der Wissensstand zu vielen wichtigen Aspekten, die COVID-19 betreffen, war und ist oftmals unsicher oder vorläufig, z. B. zu Übertragung, Symptomen, Langzeitfolgen und Immunität. Die Kommunikation ist durch wissenschaftliche Sprache sowie eine Vielzahl von Kennzahlen und Statistiken geprägt, was die Verständlichkeit erschweren kann. Neben offiziellen Mitteilungen und Einschätzungen von Expertinnen und Experten wird über COVID-19 in großem Umfang in sozialen Medien kommuniziert, dabei werden auch Fehlinformationen und Spekulationen verbreitet; diese „Infodemie“ erschwert die Risikokommunikation. Nationale wie internationale Forschungsprojekte sollen helfen, die Risikokommunikation zu COVID-19 zielgruppenspezifischer und effektiver zu machen. Dazu gehören u. a. explorative Studien zum Umgang mit COVID-19-bezogenen Informationen, das COVID-19 Snapshot Monitoring (COSMO), ein regelmäßig durchgeführtes Onlinesurvey zu Risikowahrnehmung und Schutzverhalten sowie eine interdisziplinäre qualitative Studie, die die Konzeption, Umsetzung und Wirksamkeit von Risikokommunikationsstrategien vergleichend in 4 Ländern untersucht. T2 - Risk communication in the containment of the COVID-19 pandemic KW - Risk perception KW - Risk competence KW - SARS-CoV‑ 2 KW - Crisis management KW - Media Y1 - 2021 U6 - https://doi.org/10.1007/s00103-021-03283-3 SN - 1436-9990 SN - 1437-1588 VL - 64 IS - 3 SP - 294 EP - 303 PB - Springer CY - Berlin ; Heidelberg ER - TY - JOUR A1 - Hoffmann, Stephanie A1 - Tschorn, Mira A1 - Michalski, Niels A1 - Hoebel, Jens A1 - Förstner, Bernd Rainer A1 - Rapp, Michael A. A1 - Spallek, Jacob T1 - Association of regional socioeconomic deprivation and rurality with global developmental delay in early childhood BT - Data from mandatory school entry examinations in Germany JF - Health & place : an international journal ; a social science & medicine publication ; incorporating Geographia medica N2 - Background: From birth to young adulthood, health and development of young people are strongly linked to their living situation, including their family's socioeconomic position (SEP) and living environment. The impact of regional characteristics on development in early childhood beyond family SEP has been rarely investigated. This study aimed to identify regional predictors of global developmental delay at school entry taking family SEP into consideration. Method: We used representative, population-based data from mandatory school entry examinations of the German federal state of Brandenburg in 2018/2019 with n=22,801 preschool children. By applying binary multilevel models, we hierarchically analyzed the effect of regional deprivation defined by the German Index of Socioeconomic Deprivation (GISD) and rurality operationalized as inverted population density of the children's school district on global developmental delay (GDD) while adjusting for family SEP (low, medium and high) Results: Family SEP was significantly and strongly linked to GDD. Children with the highest family SEP showed a lower odds for GDD compared to a medium SEP (female: OR=4.26, male: OR=3.46) and low SEP (female: OR=16.58, male: OR=12.79). Furthermore, we discovered a smaller, but additional and independent effect of regional socioeconomic deprivation on GDD, with a higher odds for children from a more deprived school district (female: OR=1.35, male: OR=1.20). However, rurality did not show a significant link to GDD in preschool children beyond family SEP and regional deprivation. Conclusion: Family SEP and regional deprivation are risk factors for child development and of particular interest to promote health of children in early childhood and over the life course. KW - Health inequalities KW - Spatial analysis KW - Regional deprivation KW - Rurality KW - Developmental delay KW - Children Y1 - 2022 U6 - https://doi.org/10.1016/j.healthplace.2022.102794 SN - 1353-8292 SN - 1873-2054 VL - 75 PB - Elsevier Science CY - Amsterdam [u.a.] ER - TY - JOUR A1 - Schloßhauer, Jeffrey A1 - Cavak, Niño A1 - Zemella, Anne A1 - Thoring, Lena A1 - Kubick, Stefan T1 - Cell engineering and cultivation of chinese hamster ovary cells for the development of orthogonal eukaryotic cell-free translation systems JF - Frontiers in molecular biosciences N2 - The investigation of protein structures, functions and interactions often requires modifications to adapt protein properties to the specific application. Among many possible methods to equip proteins with new chemical groups, the utilization of orthogonal aminoacyl-tRNA synthetase/tRNA pairs enables the site-specific incorporation of non-canonical amino acids at defined positions in the protein. The open nature of cell-free protein synthesis reactions provides an optimal environment, as the orthogonal components do not need to be transported across the cell membrane and the impact on cell viability is negligible. In the present work, it was shown that the expression of orthogonal aminoacyl-tRNA synthetases in CHO cells prior to cell disruption enhanced the modification of the pharmaceutically relevant adenosine A2a receptor. For this purpose, in complement to transient transfection of CHO cells, an approach based on CRISPR/Cas9 technology was selected to generate a translationally active cell lysate harboring endogenous orthogonal aminoacyl-tRNA synthetase. KW - orthogonal translation KW - cell-free protein synthesis KW - CRISPR KW - amber suppression KW - E. coli tyrosyl-tRNA synthetase KW - M. mazei pyrrolysyl-tRNA synthetase KW - membrane protein KW - C12orf35 Y1 - 2022 U6 - https://doi.org/10.3389/fmolb.2022.832379 SN - 2296-889X VL - 9 PB - Frontiers Media CY - Lausanne ER -