Biology subjects

Huber, R.

Publications and source records attributed to Huber, R..

47 records · Page 3Linked to original sources

bioRxiv2021

Closed-loop auditory stimulation method to modulate sleep slow waves and motor learning performance in rats

Slow waves and cognitive output have been modulated in humans by phase-targeted auditory stimulation. However, to advance its technical development and further our understanding, implementation of the method in animal models is indispensable. Here, we report the successful employment of slow waves phase-targeted closed-loop auditory stimulation (CLAS) in rats. To validate this new tool both conceptually and functionally, we tested the effects of up- and down-phase CLAS on proportions and spectral characteristics of sleep, and on learning performance in the single pellet-reaching task, respectively. Without affecting 24-h sleep-wake behavior, CLAS specifically altered delta (slow waves) and sigma (sleep spindles) power persistently over chronic periods of stimulation. Down-phase CLAS exerted a detrimental effect on overall engagement and success rate in the behavioral test, and overall CLAS-dependent spectral changes were positively correlated with learning performance. Altogether, our results provide proof-of-principle evidence that phase-targeted CLAS of slow waves in rodents is efficient, safe and stable over chronic experimental periods, enabling the use of this high-specificity tool for basic and preclinical translational sleep research.

neuroscience↗

bioRxiv2020

Which are the central aspects of infant sleep? Thedynamic of sleep composites across infancy

Sleep is ubiquitous during infancy and important for the well-being of both infant and parent. Therefore, there is large interest to characterize infant sleep with reliable tools, for example by means of combining actigraphy with 24-h-diaries. However, it is critical to select the right variables to characterize sleep. With a principal component analysis, we identified 5 underlying sleep composites from 48 commonly used sleep variables: Sleep Night, Sleep Day, Sleep Activity, Sleep Timing and Sleep Variability. These composites accurately reflect the known changes of sleep throughout infancy as Sleep Day (representing naps), Sleep Activity (representing sleep efficiency and consolidation) and Sleep Variability (representing day-to-day stability) decrease across infancy, while Sleep Night (representing nighttime sleep) slightly increases and Sleep Timing becomes earlier with increasing age. Additionally, we uncover interesting dynamics between the sleep composites and demonstrate that infant sleep is not only highly variable between infants but also considerably dynamic within infants across time. Interestingly, Sleep Day is associated with behavioral development and therefore a potential marker for maturation. We recommend the use of sleep composites or of those specific single variables, which are solid representatives of the sleep composites for more reliable research.

neuroscience↗

bioRxiv2020

Rest is Required to Learn an Appetitively-Reinforced Operant Task in Drosophila

Maladaptive operant conditioning contributes to development of neuropsychiatric disorders. Candidate genes have been identified that contribute to this maladaptive plasticity, but the neural basis of operant conditioning in genetic model organisms remains poorly understood. The fruit fly Drosophila melanogaster is a versatile genetic model organism that readily forms operant associations with punishment stimuli. However, operant conditioning with a food reward has not been demonstrated in flies, limiting the types of neural circuits that can be studied. Here we present the first sucrose-reinforced operant conditioning paradigm for flies. In the paradigm, flies walk along a Y-shaped track with reward locations at the terminus of each hallway. When flies turn in the reinforced direction at the center of the track, sucrose is presented at the end of the hallway. Only flies that rest early in training learn the reward contingency normally. Flies rewarded independently of their behavior do not form a learned association but have the same amount of rest as trained flies, showing that rest is not driven by learning. Optogenetically-induced sleep does not promote learning, indicating that sleep itself is not sufficient for learning the operant task. We validated the sensitivity of this assay to detect the effect of genetic manipulations by testing the classic learning mutant dunce. Dunce flies are learning impaired in the Y-Track task, indicating a likely role for cAMP in the operant coincidence detector. This novel training paradigm will provide valuable insight into the molecular mechanisms of disease and the link between sleep and learning.

neuroscience↗

bioRxiv2020

Dipeptidyl peptidase 9 triggers BRCA2 degradation by the N-degron pathway to promote DNA-damage repair

Dipeptidyl peptidase 9 (DPP9) is a serine protease cleaving N-terminal dipeptides preferentially post-proline with (patho)physiological roles in the immune system and cancer. Only few DPP9 substrates are known. Here we identify an association of human DPP9 with the tumour suppressor BRCA2, a key player in repair of DNA double-strand breaks that promotes the formation of RAD51 filaments. This interaction is triggered by DNA-damage and requires access to the DPP9 active-site. We present crystallographic structures documenting the N-terminal Met1-Pro2 of a BRCA21-40 peptide captured in the DPP9 active-site. Mechanistically, DPP9 targets BRCA2 for degradation by the N-degron pathway, and promotes RAD51 foci formation. Both processes are phenocopied by BRCA2 N-terminal truncation mutants, indicating that DPP9 regulates both stability and the cellular stoichiometric interactome of BRCA2. Consistently, DPP9-deprived cells are hypersensitive to DNA-damage. Together, we identify DPP9 as a regulator of BRCA2, providing a possible explanation for DPP9 involvement in cancer development.

biochemistry↗

bioRxiv2020

Cognitive fluctuations surrounding sleep in daily living

It is well recognized that cognitive output fluctuates surrounding sleep. Such fluctuations are rarely investigated in subjects daily living, partially due to the inaccessibility of sleep laboratory technology and cognitive testing. Here we leverage the continuous and long-term smartphone touchscreen interaction logs to study the patterns of cognitive output surrounding sleep and contrasted these to the patterns underlying physical activity captured from wrist-worn actigraphy. According to spectral density analysis, both cognitive and physical activity was dominated by diurnal ([~]24 h) and infra-radian ([~]7 days) rhythms. However, these rhythms differed in a domain-specific manner. The proxy measures of cognitive performance - tapping speed, unlocking speed, and app locating speed - contained lower-powered diurnal rhythm than physical activity. Still, the amount of smartphone usage showed the strongest diurnal rhythm - even when compared to the ambient luminescence levels experienced according to actigraphy. Interestingly, the cognitive rhythms were not in sync with physical activity, as cognitive measures peaked later in the day and on weekdays rather than weekends. The difference between cognitive and physical activity became vivid during bedtime and subjects routinely interacted with their smartphones during the actigraphy labelled sleep period. The cognitive measures in this period were worse in comparison to the hour before or after sleep. Therefore, smartphones can seamlessly capture the dynamic fluctuations in cognitive output including during spontaneous awakenings. We conclude that the rhythms underlying cognitive activity in the real world are distinct from physical activity and this discord may be a hallmark of modern human behaviour.

animal behavior and cognition↗

bioRxiv2019

Changes in cross-frequency coupling following closed-loop auditory stimulation in non-rapid eye movement sleep

The activity of different brain networks in non-rapid eye movement (NREM) sleep is regulated locally in an experience-dependent manner, reflecting the extent of the network load during wakefulness. In particular, improved task performance after sleep correlates with the local post-learning power increase of neocortical slow waves and faster oscillations such as sleep spindles and their temporal coupling. Recently, it was demonstrated that by targeting slow waves in a particular region at a particular phase with closed-loop auditory stimulation it is possible to locally manipulate slow-wave activity and interact with training-induced neuroplastic changes. Based on this finding, we tested whether closed-loop auditory stimulation targeting the up-phase of slow-waves over the right sensorimotor area might affect power in delta, theta and sigma bands and coupling between these oscillations within the circumscribed region. We demonstrate that while closed-loop auditory stimulation globally enhances power in delta, theta and sigma bands, changes in cross-frequency coupling of these oscillations were more spatially restricted. In particular, stimulation induced a significant decrease of delta-theta coupling in frontal channels, within the area of the strongest baseline coupling between these frequency bands. In contrast, a significant increase in delta-sigma coupling was observed over the right parietal area, located directly posterior to the target electrode. These findings suggest that closed-loop auditory stimulation locally modulates coupling between delta phase and sigma power in a targeted region, which could be used to manipulate sleep-dependent memory formation within the brain network of interest.

neuroscience↗

bioRxiv2019

Electrophysiological measures of sleep pressure during wakefulness in the course of isolation at the Concordia Antarctica station and physical activity as a countermeasure

Concordia station in Antarctica is one of the most remote human outpost on Earth. Because of its geographical location, a winterover at Concordia shares a lot of stressors with a space mission. Following a recent study on the markers of sleep pressure during wakefulness on board of the International Space Station, we were investigating if long term isolation in a space analogue station shows similar effects on sleep pressure. Unlike in space, markers of sleep pressure did not increase during isolations constant darkness period in Antarctica. When measures of sleep pressure were high in the evening, psychological strain was increased, emphasising the importance of keeping sleep pressure under physiological levels during the mission. As a first indication for a countermeasure, we showed that one hour of bicycle exercise during lunch time could decrease sleep pressure. All these observations need to be further studied in a more controlled environment.

neuroscience↗

bioRxiv2018

Capturing sleep-wake cycles by using day-to-day smartphone touchscreen interactions

Body movements drop with sleep and this behavioural signature is widely exploited to infer sleep duration. However, a reduction in body movements may also occur in periods of intense cognitive activity and the ubiquitous use of smartphones may capture these wakeful periods otherwise hidden in the standard measures of sleep. Here we continuously captured the gross body movements using standard wrist-worn accelerometers to quantify sleep (actigraphy) and logged the timing of the day-to-day touchscreen events ( tappigraphy). Using these measures, we addressed how the gross body movements overlap with the cognitively engaging digital behaviour (from n = 84 individuals, accumulating 1384 nights). We find that smartphone use was distributed across a broad spectrum of physical activity levels but consistently peaked at rest. We estimated the putative sleep onset and wake-up times from the actigraphy data to find that these times were well correlated to the estimates from tappigraphy (R2 = 0.9 for sleep onset and wake-up time). However, actigraphy overestimated sleep as virtually all of the users used their phones during the putative sleep period. Interestingly, the probability of touches remained greater than zero for ~ 2 h after the putative sleep onset and ~ 2 h before the putative wake-up time. Our findings suggest that touchscreen interactions are widely integrated into modern sleeping habits - surrounding both sleep onset and waking-up periods - yielding a new approach to measuring sleep. Smartphone taps can be leveraged to update the behavioural signatures of sleep with these peculiarities of modern digital behaviour.

animal behavior and cognition↗

bioRxiv2018

Effects and Feasibility of Hyperthermic Baths for Patients with Depressive Disorder: A Randomized Controlled Clinical Pilot Trial

BackgroundEvaluation of efficacy, safety and feasibility of hyperthermic baths (HTB; head-out-of-water-immersion in 40{degrees}C), twice a week, compared to a physical exercise program (PEP; moderate intensity aerobic exercises) in moderate to severe depression.\n\nMethodSingle-site, open-label randomized controlled 8-week parallel-group pilot study at an university outpatient clinic as part of usual depression care. Medically stable outpatients with depressive disorder (ICD-10: F32/F33) as determined by the 17-item Hamilton Depression Rating Scale (HAM-D) score [≥]18 and a score [≥]2 on item 1 (Depressed Mood) were randomly assigned to receive either two sessions of HTB or PEP per week (40-45 min) provided by two trained doctoral students. An independent biometric center used computer-generated tables to allocate treatments. Primary outcome measure was the change in HAM-D total score from baseline (T0) to the 2-week time point (T1). Linear regression analyses, adjusted for baseline values, were performed to estimate intervention effects on an intention-to-treat (ITT) principle.\n\nFindings45 patients (HTB n = 22; PEP n = 23) were randomized and analyzed according to ITT (mean age = 48.4 years, SD = 11.3, mean HAM-D score = 21.7, SD = 3.2). Baseline-adjusted mean difference was 4.3 points in the HAM-D score in favor of HTB (p<0.001). This improvement was achieved after two weeks. Compliance with the intervention and follow-up was far better in the HTB group (2 vs 13 dropouts). There were no treatment-related serious adverse events. Main limitation: the number of dropouts in the PEP group (13 of 23) was far higher than in other trials investigating exercise in depression (18.1 % dropouts).\n\nConclusionsHTB seems to be a fast-acting, safe and easy accessible method leading to clinically relevant improvement in depressive disorder after two weeks; it is also suitable for persons who have problems performing exercise training.\n\nTrial registrationGerman Clinical Trials Register (DRKS) with the registration number DRKS00011013 (registration date 2016-09-19) before onset of the study.

clinical trials↗

bioRxiv2018

Simultaneous CO2 and CO methanation using microbes

In this study, we developed a method for simultaneous bio-methanation of CO2 and CO with H2 in a single bioreactor using a combination of carboxydotrophic bacteria and methanogenic archaea for industrial applications. Methanogenic archaea generally use H2 and CO2 to produce methane, whereas very few methanogenic archaea methanize CO, and these grow slowly and consequently produce low reactant gas turnover rates. Thus, to achieve fast and simultaneous transformation of CO and CO2, we identified a combination of carboxydotrophic and hydrogenogenic bacteria and methanogenic archaea that can produce H2 and CO2 from CO, and then methanize CO2 and H2. The present screening experiments identified carboxydotrophic bacteria and methanogenic archaea that can cohabitate at the same thermophilic temperature and pH ranges and in the same growth medium. In these experiments, combinations of Carboxydocella thermautotrophica (DSM 12326), Carboxydocella sporoproducens (DSM 16521), and three thermophilic rod-shaped methanogenic archaeal cultures from MicroPyros GmbH formed unique microbial co-cultures that transformed CO2, H2, and CO to methane. The successful combination of these microbes could be used to gasify biowastes, such as sewage sludge, as alternative sources of hydrogen for microbial power-to-gas processes. Accordingly, gasification under these conditions produced H2-rich gas containing CO2 and CO, theoretically allowing various types of biowastes to be converted to biomethane, which is CO2-neutral, storable, and widely applicable as an energy source.

microbiology↗

bioRxiv2017

Diurnal changes in glutamate/glutamine levels of healthy young adults assessed by proton magnetic resonance spectroscopy

Molecular and electrophysiological studies suggest that sleep ensures efficient functioning of the brain by maintaining synaptic homeostasis. The glutamate receptor -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA receptor) is involved in synaptic plasticity processes and it was shown that its expression changes across the sleep wake cycle. Moreover, animal studies have shown that glutamate levels are reduced during non-rapid eye movement (NREM) sleep and that the rate of the decrease is positively correlated with sleep EEG slow wave activity (SWA). In this study, we aimed to assess if proton magnetic resonance spectroscopy (1H-MRS) is sensitive to diurnal changes of glutamate + glutamine (GLX) in healthy young adults and if potential overnight changes of GLX are correlated to SWA. 1H-MRS spectra of 16 adult subjects were measured in the parietal lobe in the evening and in the subsequent morning using a 3T MRI scanner. The night between the scans was recorded with high-density EEG. Our results revealed a significant overnight reduction in GLX levels, whereas other metabolites did not show any significant change. Moreover, the decrease in GLX was positively correlated with the decrease of SWA in the course of the night. Our study demonstrates that quantification of diurnal changes in GLX is possible by means of 1H-MRS and indicates a relationship between changes in GLX and SWA, a marker that is closely linked to the restorative function of sleep. This relationship might be of particular interest in clinical populations in which sleep is disturbed.

neuroscience↗