On the codimension of permanental varieties

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The texture-taste connection : Multimodal sensory neurons in fly larvae

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Programmed neurite degeneration in human central nervous system neurons driven by changes in NAD⁺ metabolism

Neurite degeneration (ND) precedes cell death in many neurodegenerative diseases. However, it remains unclear how this compartmentalized cell death process is orchestrated in the central nervous system (CNS). The establishment of a CNS axotomy model (using modified 3D LUHMES cultures) allowed us to study metabolic control of ND in human midbrain-derived neurons without the use of toxicants or other direct disturbance of cellular metabolism. Axotomy lead to a loss of the NAD+ synthesis enzyme NMNAT2 within 2 h and a depletion of NAD+ within 4-6 h. This process appeared specific, as isolated neurites maintained ATP levels and a coupled mitochondrial respiration for at least 6 h. In the peripheral nervous system (PNS) many studies observed that NAD+ metabolism, in particular by the NADase SARM1, plays a major role in the ND occurring after axotomy. Since neither ferroptosis nor necroptosis, nor caspase-dependent apoptosis seemed to be involved in neurite loss, we investigated SARM1 as potential executioner (or controller). Knock-down or expression of a dominant-negative isoform of SARM1 indeed drastically delayed ND. Various modifications of NAD+ metabolism known to modulate SARM1 activity showed the corresponding effects on ND. Moreover, supplementation with NAD+ attenuated ND. As a third approach to investigate the role of altered NAD+ metabolism, we made use of the WLD(s) protein, which has been found in a mutant mouse to inhibit Wallerian degeneration of axons. This protein, which has a stable NMNAT activity, and thus can buffer the loss of NMNAT2, protected the neurites by stabilizing neurite NAD+ levels. Thus CNS-type ND was tightly linked to neurite metabolism in multiple experimental setups. Based on this knowledge, several new strategies for treating neurodegenerative diseases can be envisaged.publishe

Gaze following in pigeons increases with the number of demonstrators

Gaze following, orienting one’s gaze in the same direction as another individual, is a key component of social attention across species, and expected to play an important role in group contexts. To investigate its collective dimension, this study tested whether the number of conspecifics providing a gaze cue influences gaze following in pigeons (Columba livia). Using motion capture to track fine-scale head and body movements, we presented attention-getting stimuli to subsets of pigeons (demonstrators), while others (observers) could not see them. Observer pigeons followed the gaze of demonstrators, specifically toward the target object rather than a perceptually similar distractor, and the frequency increased with the number of demonstrators. We found no evidence for nonlinear effects under our experimental conditions. In group-living species like pigeons, multiple individuals looking in the same direction may serve as a more reliable social signal, highlighting the critical role of collective context in animal social cognition.publishe

Indikation von Uferstrukturbelastungen durch Makrophyten und Makrozoobenthos an Seen in Brandenburg : Teil 2: Einfluss von Trophie (ACP) und Uferstruktur (HyMo) auf biologische Bewertungsmetriks und Zusammensetzung von Makrozoobenthos- (MZB) und Makrophytengemeinschaften (MPH) : Bericht der ARGE „Team Seeufer MMM“ für das Landesamt für Umwelt Brandenburg, Ref. W26, Projekt SuBoLakes (Az. 35825/01), AP 5 der Deutschen Bundesstiftung Umwelt (DBU)

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Facile construction of mechanically robust and highly osteogenic materials for bone regeneration

Hydrogel-based materials exhibit great potential in tissue engineering. However, their mechanical weakness limits applications in hard tissue regeneration, especially under load-bearing conditions. Although various strengthening strategies have been applied, the achieved mechanical response of hydrogels still lags behind the mechanics of natural bone. In this study, we present a novel mineralization approach to fabricate mechanically robust and highly osteogenic mineralized hydrogels. Cross-linking between deprotonated chains of poly(acrylic acid) (PAA) and divalent cations has led to formation of hydrogels with a compressive strength and elastic modulus of 0.3 ± 0.1 kPa and 1.3 ± 0.2 kPa, respectively. Subsequent in situ formation of nano-calcium hydroxide crystals remarkably increased the compressive strength and modulus to 7.9 ± 0.6 MPa and 339.3 ± 31.4 MPa, respectively, surpassing those of trabecular bone. Moreover, the mineralized hydrogels demonstrated remarkable osteogenic potential in vivo, exhibiting immunoregulatory activity, promoting early angiogenesis, and accelerating fracture healing at weeks 4 and 8. The mechanism of osteogenesis was further revealed by transcriptome sequencing, indicating that the mineralized hydrogels regulated the translation of extracellular matrix and biomineralization. Overall, our study presents a pioneering and cost-effective method for fabricating materials with exceptional mechanical strength and strong osteogenic properties, offering a promising avenue for load-bearing bone repair applications of hydrogel-based materials.publishe

Patients with borderline personality disorder show initially reduced psychophysiological relaxation levels but intact relaxation response

Introduction: Borderline Personality Disorder (BPD) is associated with psychological as well as physiological dysregulation in patients, including reduced parasympathetic activity at baseline and difficulties returning to baseline after a stressor. Whether this impacts the relaxation response independent of a stressor has so far not been investigated. Methods: In a within-subject design, we compared two relaxation interventions, a virtual reality nature video, and a paced breathing intervention. We assessed a female-only sample, with 20 BPD patients (meanage = 23.75 ± 4.39) during their inpatient treatment and 22 matched healthy controls (HC; meanage = 22.68 ± 2.68). Psychological relaxation was assessed with the Relaxation State Questionnaire (RSQ) and physiological relaxation with vagally mediated heart rate variability (HRV). Results: We employed multilevel models to test whether BPD significantly influenced the psychophysiological relaxation response. For psychological relaxation, we found an increase in RSQ scores in both groups in response to both interventions. The HC showed overall higher RSQ scores. For physiological relaxation, we found overall higher HRV values in the HC group but no differences in the relaxation response. Conclusion: BPD patients exhibit lower psychophysiological relaxation levels at baseline and throughout the experiment, while there was no significant difference in response to relaxation interventions when compared to HC. Future studies should focus on interventions targeting baseline psychophysiological relaxation in BPD patients.publishe

Testing Strategies for Metabolite-Mediated Neurotoxicity

Compounds, which rely on metabolism to exhibit toxicity, pose a challenge for next-generation risk assessment (NGRA). Since many of the currently available non-animal new approach methods (NAMs) lack metabolic activity, their use may lead to an underestimation of the true hazard to humans (false negative predictions). We explored here strategies to deal with metabolite-mediated toxicity in assays for developmental neurotoxicity. First, we present an overview of substances that may serve as potential positive controls for metabolite-related neurotoxicity. Then, we demonstrate, using the MitoMet (UKN4b) assay, which assesses the adverse effects of chemicals on neurites of human neurons, that some metabolites have a higher toxic potency than their parent compound. Next, we designed a strategy to integrate elements of xenobiotic metabolism into assays used for (developmental) neurotoxicity testing. In the first step of this approach, hepatic post-mitochondrial fractions (S9) were used to generate metabolite mixtures (“metabolisation module”). In the second step, these were applied to a NAM (exemplified by the UKN4b assay) to identify metabolite-mediated toxicity. We demonstrate the applicability and transferability of these approaches to other assays, by an exemplary study on the basis of the cMINC (UKN2) assay, another NAM of the developmental neurotoxicity in vitro battery. Based on the experience gained from these experiments, we discuss key issues to be addressed if this approach is to be used more broadly for NAM in the NGRA context.publishe

Spin polarization of the two-dimensional electron gas at the EuO/SrTiO₃ (001) interface

Spin-polarized two-dimensional electron gases (2DEGs) are of particular interest for functional oxide electronics applications. The redox-created 2DEG residing on the strontium titanate, SrTiO3 (STO), side of a europium monoxide (EuO)/SrTiO3 (001) interface is expected to be significantly spin polarized due to the proximity to the strong (7/..) Heisenberg ferromagnet EuO. We apply magnetic circular dichroism in the angular distribution (MCDAD) of photoemitted electrons to investigate whether and how the induced spin polarization of the 2DEG depends on the dimensionality of the overlaying EuO layer. The experimental data are complemented by density functional theory calculations with a Hubbard term (DFT+). We show that the EuO/STO interfacial 2DEG is spin polarized even for ultrathin EuO overlayers, starting at an EuO threshold thickness of only two monolayers. Additional EuO monolayers even increase the induced magnetic Ti moment and thus the spin polarization of the 2DEG. Our results and the potential to enhance the magnetic order of EuO by other proximity effects indicate that the EuO/STO(001) interface is an ideal template for creating (multi-)functional spin-polarized 2DEGs for application in oxide electronics.publishe

Magnetization-Dependent Critical Current in S-(S/F)-S Junctions : Experimental Realization and Micromagnetic Simulation

The antagonistic properties of superconductors and ferromagnets open up an attractive area of research for energy-efficient computing technologies. The remanent magnetization of ferromagnets, in particular, offers potential for nonvolatile storage solutions. This thesis presents the fabrication and investigation of ferromagnetically constricted superconducting junctions composed of aluminum and cobalt in an S-(S/F)-S geometry. Low-temperature transport measurements reveal that the critical current of these junctions is strongly dependent on the magnetization state of the ferromagnet, enabling the realization of a field-trainable, nonvolatile superconducting switch. The persistence of the controllability in samples with oxidized S/F interface suggests that the control mechanism is predominantly mediated by stray fields. The inverse proximity effect, driven by interfacial diffusion of Cooper pairs, manifests itself in a strong influence on the critical current amplitude of the junction. Micromagnetic simulations conducted in this thesis can replicate the measured phenomenology semi-quantitatively using three-dimensional micromagnetics and a purely stray-field dependent critical current model. The simulations provide microscopic insight into the magnetization dependence of the critical current, successfully replicating critical current jumps in the experiment caused by Barkhausen jumps in the ferromagnet. The results also demonstrate that the grain size of the polycrystalline ferromagnet strongly impacts the observed phenomenology.publishe