To what degree mental imagery (MI) bears on the same neuronal processes as perception has been a central question in the neurophysiological study of imagery. Sensory-recruitment models suggest that imagery of sensory material heavily relies on the involvement of sensory cortices. Empirical evidence mainly stems from the study of visual imagery and suggests that it depends on the mentally imagined material whether hierarchically lower regions are recruited. However, evidence from other modalities is necessary to infer generalized principles. In this fMRI study we used the somatotopic organization of the primary somatosensory cortex (SI) to test in how far MI of tactile sensations activates topographically sensory brain areas. Participants (N = 19) either perceived or imagined vibrotactile stimuli on their left or right thumbs or big toes. The direct comparison to a corresponding perception condition revealed that SI was somatotopically recruited during imagery. While stimulus driven bottom-up processing induced activity throughout all SI subareas, i.e., BA1, BA3a, BA3b, and BA2 defined by probabilistic cytoarchitectonic maps, top-down recruitment during imagery was limited to the hierarchically highest subarea BA2.

R2-like ligand-binding oxidases (R2lox) assemble a heterodinuclear Mn/Fe cofactor which performs reductive dioxygen (O2) activation, catalyzes formation of a tyrosine–valine ether cross-link in the protein scaffold, and binds a fatty acid in a putative substrate channel. We have previously shown that the N-terminal metal binding site 1 is unspecific for manganese or iron in the absence of O2, but prefers manganese in the presence of O2, whereas the C-terminal site 2 is specific for iron. Here, we analyze the effects of amino acid exchanges in the cofactor environment on cofactor assembly and metalation specificity using X-ray crystallography, X-ray absorption spectroscopy, and metal quantification. We find that exchange of either the cross-linking tyrosine or the valine, regardless of whether the mutation still allows cross-link formation or not, results in unspecific manganese or iron binding at site 1 both in the absence or presence of O2, while site 2 still prefers iron as in the wild-type. In contrast, a mutation that blocks binding of the fatty acid does not affect the metal specificity of either site under anoxic or aerobic conditions, and cross-link formation is still observed. All variants assemble a dinuclear trivalent metal cofactor in the aerobic resting state, independently of cross-link formation. These findings imply that the cross-link residues are required to achieve the preference for manganese in site 1 in the presence of O2. The metalation specificity, therefore, appears to be established during the redox reactions leading to cross-link formation.

Dieser Bericht der AG Open-Access-Strategie Berlin ist in Zusammenarbeit mit den Akteuren des Open-Access-Netzwerks, bestehend aus den Wissenschafts-, Forschungs- und Kultureinrichtungen, und der entsprechenden Ressorts entstanden. Er fasst die Aktivitäten und Ergebnisse der Jahre 2015-2018 zusammen und gibt zudem einen kurzen Ausblick. Der Bericht wurde zur Information der Berliner Abgeordneten über die Ergebnisse und Erfolge der Open-Access-Strategie für Berlin in den Jahren 2015-2018 verfasst und gibt zudem einen kurzen Ausblick auf zukünftige Themenschwerpunkte der AG.

The magnetic field dependence of Chemically Induced Dynamic Nuclear Polarization (CIDNP) in solid-state systems is analyzed theoretically with the aim to explain the puzzling sign change of polarization found at low fields [D. Gräsing et al., Sci. Rep. 7, 12111 (2017)]. We exploit the analysis of polarization in terms of level crossings and level anti-crossings trying to identify the positions of features in the CIDNP field dependence with specific crossings between spin energy levels of the radical pair. Theoretical treatment of solid-state CIDNP reveals a strong orientation dependence of polarization due to the spin dynamics conditioned by anisotropic spin interactions. Specifically, different anisotropic CIDNP mechanisms become active at different magnetic fields and different molecular orientations. Consequently, the field dependence and orientation dependence of polarization need to be analyzed together in order to rationalize experimental observations. By considering both magnetic field and orientation dependence of CIDNP, we are able to explain the previously measured CIDNP field dependence in photosynthetic reaction centers and to obtain a good qualitative agreement between the experimental observations and theoretical results.

In blind people, the visual cortex takes on higher cognitive functions, including language. Why this functional reorganisation mechanistically emerges at the neuronal circuit level is still unclear. Here, we use a biologically constrained network model implementing features of anatomical structure, neurophysiological function and connectivity of fronto-temporal-occipital areas to simulate word-meaning acquisition in visually deprived and undeprived brains. We observed that, only under visual deprivation, distributed word-related neural circuits ‘grew into’ the deprived visual areas, which therefore adopted a linguistic-semantic role. Three factors are crucial for explaining this deprivation-related growth: changes in the network’s activity balance brought about by the absence of uncorrelated sensory input, the connectivity structure of the network, and Hebbian correlation learning. In addition, the blind model revealed long-lasting spiking neural activity compared to the sighted model during word recognition, which is a neural correlate of enhanced verbal working memory. The present neurocomputational model offers a neurobiological account for neural changes following sensory deprivation, thus closing the gap between cellular-level mechanisms, system-level linguistic and semantic function.

Changes in cell function occur by specific patterns of intracellular Ca2+, activating Ca2+-sensitive proteins. The anoctamin (TMEM16) protein family has Ca2+-dependent ion channel activity, which provides transmembrane ion transport, and/or Ca2+-dependent phosphatidyl-scramblase activity. Using amino acid sequence analysis combined with measurements of ion channel function, we clarified the so far unknown Ano4 function as Ca2+-dependent, non-selective monovalent cation channel; heterologous Ano4 expression in HEK293 cells elicits Ca2+ activated conductance with weak selectivity of K+ > Na+ > Li+. Endogenously expressed Ca2+-dependent cation channels in the retinal pigment epithelium were identified as Ano4 by KO mouse-derived primary RPE cells and siRNA against Ano4. Exchanging a negatively charged amino acid in the putative pore region (AA702-855) into a positive one (E775K) turns Ano4-elicited currents into Cl- currents evidencing its importance for ion selectivity. The molecular identification of Ano4 as a Ca2+-activated cation channel advances the understanding of its role in Ca2+ signaling.

Noninvasive early detection of liver cirrhosis and fibrosis is essential for management and therapy. The aim was to investigated whether a combination of the functional parameter relative enhancement (RE) on Gadoxetic Acid magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) and the fibrosis parameter T1ρ distinguishes cirrhosis and healthy liver. We analyzed patients with Gd-EOB-DTPA-enhanced MRI and T1ρ mapping. Signal intensity was measured before and after contrast; RE was calculated. T1ρ was measured with circular regions of interest (T1ρ-cROI). A quotient of RE and T1ρ-cROI was calculated: the fibrosis function quotient (FFQ). Cirrhosis was evaluated based on morphology and secondary changes. 213 datasets were included. The difference between cirrhotic and noncirrhotic liver was 51.11 ms vs. 47.56 ms for T1ρ-cROI (p < 0.001), 0.59 vs. 0.70 for RE (p < 0.001), and 89.53 vs. 70.83 for FFQ (p < 0.001). T1ρ-cROI correlated with RE, r = -0.14 (p < 0.05). RE had an AUC of 0.73. The largest AUC had the FFQ with 0.79. The best cutoff value was 48.34 ms for T1ρ-cROI, 0.70 for RE and 78.59 ms for FFQ. In conclusion T1ρ and RE can distinguish between cirrhotic and noncirrhotic liver. The FFQ, which is the combination of the two, improves diagnostic performance.

Polizeivollzugsbeamte (PVB) sind im Arbeitskontext regelmäßig mit Anfeindungen wie Beleidigungen, Beschimpfungen und Bedrohungen durch Bürger konfrontiert. Um den PVB einen hilfreichen Umgang mit diesen belastenden aber schwer zu verändernden Arbeitsbedingungen zu ermöglichen, wurde der Workshop „Mental stark im Umgang mit schwierigen Bürgern“ konzipiert. Der Workshop richtet sich an alle PVB, die in direktem Kontakt mit Bürgern arbeiten. Zum einen werden Informationen und Wissen zu Stressbewältigung und Emotionsarbeit im Workshop vermittelt, zum anderen werden die PVB zu einer prozessorientierten Entwicklung von konkreten mentalen Strategien im Umgang mit individuell problematischen Situationen in Bürgerkontakten angeleitet. Das Manual zu dem Mitarbeiterworkshop wendet sich an alle, die im Aus- und Fortbildungsbereich der Polizei arbeiten, wie Psychologen oder Verhaltenstrainer. Es liefert Hintergrundwissen zu den Themen Stress- und Stressbewältigung sowie zu Emotionsarbeit. Neben Erläuterungen zu emotions- und handlungsbezogenen Bewältigungsstrategien werden die Anforderungen und Möglichkeiten der Kontrolle über den Emotionsausdruck gegenüber Bürgern betrachtet. Darüber hinaus beinhaltet das Manual konkrete Anleitungen zur Gestaltung des Workshops (Präsentationsfolien inklusive Notizen zur Erläuterung). Ziel des Workshops ist es, die PVB durch die praktische Anwendung der vermittelten Inhalte darin zu unterstützen, ihre Stressbelastung zu reduzieren und ihre Emotionsregulation im Umgang mit schwierigen Bürgern zu verbessern. In der bisherigen Workshop-Evaluation zeigten sich die befragen PVB insgesamt sehr zufrieden mit den durchgeführten Workshops und schätzten die Workshop-Inhalte als nützlich für ihre Tätigkeit als PVB ein.

Background: Gait variability is an established marker of gait function that can be assessed using sensor-based approaches. In clinical settings, spatial constraints and patient condition impede the execution of longer distance walks for the recording of gait parameters. Turning paradigms are often used to overcome these constraints and commercial gait analysis systems algorithmically exclude turns for gait parameters calculations. We investigated the effect of turns in sensor-based assessment of gait variability. Methods: Continuous recordings from 31 patients with movement disorders (ataxia, essential tremor and Parkinson's disease) and 162 healthy elderly (HE) performing level walks including 180° turns were obtained using an inertial sensor system. Accuracy of the manufacturer's algorithm of turn-detection was verified by plotting stride time series. Strides before and after turn events were extracted and compared to respective average of all strides. Coefficient of variation (CoV) of stride length and stride time was calculated for entire set of strides, segments between turns and as cumulative values. Their variance and congruency was used to estimate the number of strides required to reliably assess the magnitude of stride variability. Results: Non-detection of turns in 5.8% of HE lead to falsely increased CoV for these individuals. Even after exclusion of these, strides before/after turns tended to be spatially shorter and temporally longer in all groups, contributing to an increase of CoV at group level and widening of confidence margins with increasing numbers of strides. This could be attenuated by a more generous turn excision as an alternative approach. Correlation analyses revealed excellent consistency for CoVs after at most 20 strides in all groups. Respective stride counts were even lower in patients using a more generous turn excision. Conclusion: Including turns to increase continuous walking distance in spatially confined settings does not necessarily improve the validity and reliability of gait variability measures. Specifically with gait pathology, perturbations of stride characteristics before/after algorithmically excised turns were observed that may increase gait variability with this paradigm. We conclude that shorter distance walks of around 15 strides suffice for reliable and valid recordings of gait variability in the groups studied here.

Background: Migration of physicians has become a global phenomenon with significant implications for the healthcare delivery systems worldwide. The motivations and factors driving physician's migration are complex and continuously evolving. Purpose of this study is to explore the driving forces in a group of Egyptian physicians and final-years medical students preparing to migrate to Germany. Methods: A qualitative study was conducted based on social constructivism epistemology. In five focus group discussions, there participated a total 12 residents and 6 final-year medical students from 7 different training and workplace locations in Egypt. The participants provided information about their motivation and planning for migration. We applied a coding framework based on the concept of push/pull factors and barriers/facilitators for migration, and used Atlas.ti software for analysis. Results: The thematic analysis indicated that the migration within the study's participants results from a specific weighting of push and pull factors. Push factors are considered to be more important than pull factors. Factors related to professional development play a leading role. The route of migration towards Germany is mainly determined by the low hurdle registration and licensing requirements in this destination country compared to other countries. In some cases, Germany is regarded as a "transit country", a step on the road to other European countries. The intent, planning and preparation of migration is assisted considerably by the local formation of a community and culture of migration with multiple ways for information exchange, identity building and social support through face-to-face and online channels. Conclusions: This study specifies - in a group of Egyptian physicians and final-year medical students - the perceived push and pull factors which influenced their intent to migrate to Germany. In addition to the general wealth gap, their particular route of migration is mainly determined by the requirements in licensing and registration procedures for foreign physicians in the potential destination country. The planning and preparation of a move is substantially facilitated by their joining a social network and a community of migrating physicians.

Chronic spontaneous urticaria (CSU) is a skin disease related to autoreactive IgE in at least a subgroup of patients. However, the nature of this autoreactive IgE remains poorly characterized. This investigation had three objectives: first, to quantity CSU autoreactive IgE; second, to recognize the patterns of CSU autoreactive IgE compared with healthy control IgE; and third, to investigate the physiochemical nature of CSU autoreactive IgE. Methods: IgE autoreactivity was assessed in sera from 7 CSU and 7 healthy individuals. Autoantigen recognition patterns were assessed using principal component analysis (PCA) and heatmap visualization. Lipophilicity was assessed using NanoOrange reagent. Results: First, although total IgE levels did not differ significantly, the autoreactive proportion of IgE of CSU patients was 62% +/- 37%, 1000-fold higher than that of healthy controls 0.03% +/- 0.008% (P = 0.0006). Second, CSU autoreactive IgE differed from healthy control IgE by recognizing more and different autoantigens (226 vs. 34; P = 0.01). Third, the median (with 10-90% percentiles) serum level of lipophilic IgE was 39% (38-40%) in 232 CSU patients, 1.4-fold higher than the 28% (26-29%) of 173 healthy controls (P < 0.0001). Furthermore, lipophilicity correlated with autoreactivity (r = 0.8; P < 0.0001), connecting these two observed features. Conclusion: We believe that these novel observations about CSU autoreactive IgE, particularly the finding that it is more lipophilic than that of IgE from healthy individuals, will lead to the development of new diagnostic tests and therapies for autoreactive IgE-mediated diseases.

Total knee arthroplasty aims to mimic the natural knee kinematics by optimizing implant geometry, but it is not clear how loading relates to tibio-femoral anterior-posterior translation or internal-external pivoting. We hypothesised that the point of pivot in the transverse plane is governed by the location of the highest axial force. Tibio-femoral loading was measured using an instrumented tibial component in six total knee arthroplasty patients (aged 65-80y, 5-7y post-op) during 5-6 squat repetitions, while knee kinematics were captured using a mobile video-fluoroscope. In the range of congruent tibio-femoral contact the medial femoral condyle remained approximately static while the lateral condyle translated posteriorly by 4.1 mm (median). Beyond the congruent range, the medial and lateral condyle motions both abruptly changed to anterior sliding by 4.6 mm, and 2.6 mm respectively. On average, both the axial loading and pivot position were more medial near extension, and transferred to the lateral side in flexion. However, no consistent relationship between pivoting and load distribution was found across all patients throughout flexion, with R-2 values ranging from 0.00 to 0.65. Tibio-femoral kinematics is not related to the load distribution alone: medial loading of the knee does not necessarily imply a medial pivot location.

Background: Maladaptive remodeling in pressure overload (PO)-induced left ventricular hypertrophy (LVH) may lead to heart failure. Major sex differences have been reported in this process. The steroid hormone 17β-estradiol, along with its receptors ERα and ERβ, is thought to be crucial for sex differences and is expected to be protective, but this may not hold true for males. Increasing evidence demonstrates a major role for microRNAs (miRNAs) in PO-induced LVH. However, little is known about the effects of biological sex and ERβ on cardiac miRNA regulation and downstream mitochondrial targets. We aimed at the analysis of proteins involved in mitochondrial metabolism testing the hypothesis that they are the target of sex-specific miRNA regulation. Methods: We employed the transverse aortic constriction model in mice and assessed the levels of five mitochondrial proteins, i.e., Auh, Crat, Decr1, Hadha, and Ndufs4. Results: We found a significant decrease of the mitochondrial proteins primarily in the male overloaded heart compared with the corresponding control group. Following computational analysis to identify miRNAs putatively targeting these proteins, our in vitro experiments employing miRNA mimics demonstrated the presence of functional target sites for miRNAs in the 3'-untranslated region of the messenger RNAs coding for these proteins. Next, we assessed the levels of the functionally validated miRNAs under PO and found that their expression was induced only in the male overloaded heart. In contrast, there was no significant effect on miRNA expression in male mice with deficient ERβ. Conclusion: We put forward that the male-specific induction of miRNAs and corresponding downregulation of downstream protein targets involved in mitochondrial metabolism may contribute to sex-specific remodeling in PO-induced LVH.

Streptococcus canis is a zoonotic agent that causes serious invasive diseases in domestic animals and humans, but knowledge about its pathogenic potential and underlying virulence mechanisms is limited. Here, we report on the ability of certain S. canis isolates to form large bacterial aggregates when grown in liquid broth. Bacterial aggregation was attributed to the presence and the self-binding activity of SCM, the M protein of S. canis, as evaluated by bacterial sedimentation assays, immunofluorescence- and electron microscopic approaches. Using a variety of truncated recombinant SCM fragments, we demonstrated that homophilic SCM interactions occur via the N-terminal, but not the C-terminal part, of the mature M protein. Interestingly, when incubated in human plasma, SCM forms soluble protein complexes comprising its known ligands, immunoglobulin G (IgG) and plasminogen (Plg). Co-incubation studies with purified host proteins revealed that SCM-mediated complex formation is based on the interaction of SCM with itself and with IgG, but not with Plg or fibrinogen (Fbg), well-established constituents of M protein-mediated protein complexes in human-associated streptococci. Notably, these soluble, SCM-mediated plasma complexes harbored complement factor C1q, which can induce complement breakdown in the periphery and therefore represent another immune evasion mechanism of SCM.

We investigate the quantum Heisenberg model on the pyrochlore lattice for a generic spin S in the presence of nearest-neighbor J1 and second-nearest-neighbor J2 exchange interactions. By employing the pseudofermion functional renormalization group method, we find, for S=1/2 and S=1, an extended quantum-spin-liquid phase centered around J2=0, which is shown to be robust against the introduction of breathing anisotropy. The effects of temperature, quantum fluctuations, breathing anisotropies, and a J2 coupling on the nature of the scattering profile, and the pinch points, in particular, are studied. For the magnetic phases of the J1−J2 model, quantum fluctuations are shown to renormalize phase boundaries compared to the classical model and to modify the ordering wave vectors of spiral magnetic states, while no new magnetic orders are stabilized.

Elongated landscape features like forest edges, rivers, roads or boundaries of fields are particularly salient landmarks for navigating animals. Here, we ask how honeybees learn such structures and how they are used during their homing flights after being released at an unexpected location (catch-and-release paradigm). The experiments were performed in two landscapes that differed with respect to their overall structure: a rather feature-less landscape, and one rich in close and far distant landmarks. We tested three different forms of learning: learning during orientation flights, learning during training to a feeding site, and learning during homing flights after release at an unexpected site within the explored area. We found that bees use elongated ground structures, e.g., a field boundary separating two pastures close to the hive (Experiment 1), an irrigation channel (Experiment 2), a hedgerow along which the bees were trained (Experiment 3), a gravel road close to the hive and the feeder (Experiment 4), a path along an irrigation channel with its vegetation close to the feeder (Experiment 5) and a gravel road along which bees performed their homing flights (Experiment 6). Discrimination and generalization between the learned linear landmarks and similar ones in the test area depend on their object properties (irrigation channel, gravel road, hedgerow) and their compass orientation. We conclude that elongated ground structures are embedded into multiple landscape features indicating that memory of these linear structures is one component of bee navigation. Elongated structures interact and compete with other references. Object identification is an important part of this process. The objects are characterized not only by their appearance but also by their alignment in the compass. Their salience is highest if both components are close to what had been learned. High similarity in appearance can compensate for (partial) compass misalignment, and vice versa.

As Open access (OA) is often perceived as the end goal of scholarly publishing, much research has focused on flipping subscription journals to an OA model. Focusing on what can happen after the presumed finish line, this study identifies journals that have converted from OA to a subscription model, and places these “reverse flips” within the greater context of scholarly publishing. In particular, we examine specific journal descriptors, such as access mode, publisher, subject area, society affiliation, article volume, and citation metrics, to deepen our understanding of reverse flips. Our results show that at least 152 actively publishing journals have reverse-flipped since 2005, suggesting that this phenomenon does not constitute merely a few marginal outliers, but instead a common pattern within scholarly publishing. Notably, we found that 62% of reverse flips (N = 95) had not been born-OA journals, but had been founded as subscription journals, and hence have experienced a three-stage transformation from closed to open to closed. We argue that reverse flips present a unique perspective on OA, and that further research would greatly benefit from enhanced data and tools for identifying such cases.

The following book was assembled from teaching materials developed for academic Syriac lessons. Over the course of 15 lessons, it addresses all areas of Syriac grammar, with an increasing level of difficulty. The lessons are accompanied by corresponding exercises. The texts used in the exercises are drawn from classical Syriac literature, and serve to illustrate the grammatical themes addressed in the lesson. Each lesson also contains a table of vocabulary prior to the exercises. Knowledge of the vocabulary presented in the lesson is assumed. Beginning with Lesson 8, verb forms are presented separately after the vocabulary table. At the back of the book, you will find a glossary and a bibliography.