How to obtain an integrated picture of the molecular networks involved in adaptation to microgravity in different biological systems?

Periodically, the European Space Agency (ESA) updates scientific roadmaps in consultation with the scientific community. The ESA SciSpacE Science Community White Paper (SSCWP) 9, "Biology in Space and Analogue Environments", focusses in 5 main topic areas, aiming to address key community-identified knowledge gaps in Space Biology. Here we present one of the identified topic areas, which is also an unanswered question of life science research in Space: "How to Obtain an Integrated Picture of the Molecular Networks Involved in Adaptation to Microgravity in Different Biological Systems?" The manuscript reports the main gaps of knowledge which have been identified by the community in the above topic area as well as the approach the community indicates to address the gaps not yet bridged. Moreover, the relevance that these research activities might have for the space exploration programs and also for application in industrial and technological fields on Earth is briefly discussed.

Laser melting manufacturing of large elements of lunar regolith simulant for paving on the Moon.

The next steps for the expansion of the human presence in the solar system will be taken on the Moon. However, due to the low lunar gravity, the suspended dust generated when lunar rovers move across the lunar soil is a significant risk for lunar missions as it can affect the systems of the exploration vehicles. One solution to mitigate this problem is the construction of roads and landing pads on the Moon. In addition, to increase the sustainability of future lunar missions, in-situ resource utilization (ISRU) techniques must be developed. In this paper, the use of concentrated light for paving on the Moon by melting the lunar regolith is investigated. As a substitute of the concentrated sunlight, a high-power CO2 laser is used in the experiments. With this set-up, a maximum laser spot diameter of 100 mm can be achieved, which translates in high thicknesses of the consolidated layers. Furthermore, the lunar regolith simulant EAC-1A is used as a substitute of the actual lunar soil. At the end of the study, large samples (approximately 250 × 250 mm) with interlocking capabilities were fabricated by melting the lunar simulant with the laser directly on the powder bed. Large areas of lunar soil can be covered with these samples and serve as roads and landing pads, decreasing the propagation of lunar dust. These manufactured samples were analysed regarding their mineralogical composition, internal structure and mechanical properties.

Different gait pattern in adolescence with patellofemoral instability.

BACKGROUND: Patellofemoral instability influences the gait pattern and activity level in adolescents. However, gait biomechanics to cope with recurrent patella instability and its relation to radiological findings has hardly been studied. METHODS: We retrospectively analyzed kinematic and kinetic gait analysis data, magnetic resonance images and X-ray of 32 adolescents with unilateral recurrent patellofemoral instability aged 12 to 18 years. Subjects were assigned to 3 groups based on their sagittal knee moment in the loading response and mid stance phase. Kinematic and kinetic differences among the groups were analyzed using a one-way ANOVA. A multinomial logistic regression model provided a further analysis of the relationship between gait biomechanics and MRI as well as X-ray parameters. FINDINGS: All three groups showed different characteristics of the knee kinematics during loading response and single stance: while the patella-norm-loading group showed a slightly reduced knee flexion (p ã€ˆ0,01), the patella-unloading group kept the knee nearly extended (p < 0,01) and patella-overloading group showed an increased knee flexion (p = 0,01) compared to the other groups. In single stance the patella-overloading group maintained increased knee flexion (p < 0,01) compared to patella-unloading group and patella-norm-loading group. None of the radiological parameters proved to be related to gait patterns. INTERPRETATION: The paper describes different gait coping strategies and their clinical relevance in subjects with patellofemoral instability. However, we did not find any relation of gait biomechanics to skeletal morphology.

Enhancing precision in human neuroscience.

Human neuroscience has always been pushing the boundary of what is measurable. During the last decade, concerns about statistical power and replicability - in science in general, but also specifically in human neuroscience - have fueled an extensive debate. One important insight from this discourse is the need for larger samples, which naturally increases statistical power. An alternative is to increase the precision of measurements, which is the focus of this review. This option is often overlooked, even though statistical power benefits from increasing precision as much as from increasing sample size. Nonetheless, precision has always been at the heart of good scientific practice in human neuroscience, with researchers relying on lab traditions or rules of thumb to ensure sufficient precision for their studies. In this review, we encourage a more systematic approach to precision. We start by introducing measurement precision and its importance for well-powered studies in human neuroscience. Then, determinants for precision in a range of neuroscientific methods (MRI, M/EEG, EDA, Eye-Tracking, and Endocrinology) are elaborated. We end by discussing how a more systematic evaluation of precision and the application of respective insights can lead to an increase in reproducibility in human neuroscience.

EEG Microstates in Social and Affective Neuroscience.

Social interactions require both the rapid processing of multifaceted socio-affective signals (e.g., eye gaze, facial expressions, gestures) and their integration with evaluations, social knowledge, and expectations. Researchers interested in understanding complex social cognition and behavior face a "black box" problem: What are the underlying mental processes rapidly occurring between perception and action and why are there such vast individual differences? In this review, we promote electroencephalography (EEG) microstates as a powerful tool for both examining socio-affective states (e.g., processing whether someone is in need in a given situation) and identifying the sources of heterogeneity in socio-affective traits (e.g., general willingness to help others). EEG microstates are identified by analyzing scalp field maps (i.e., the distribution of the electrical field on the scalp) over time. This data-driven, reference-independent approach allows for identifying, timing, sequencing, and quantifying the activation of large-scale brain networks relevant to our socio-affective mind. In light of these benefits, EEG microstates should become an indispensable part of the methodological toolkit of laboratories working in the field of social and affective neuroscience.

Bulk modulus along jamming transition lines of bidisperse granular packings.

We present three-dimensional discrete element method simulations of bidisperse granular packings to investigate their jamming densities ϕ_{J} and dimensionless bulk moduli K as functions of the size ratio δ and the concentration of small particles X_{S}. We determine the partial and total bulk moduli for packings near their jamming densities, including a second transition that occurs for sufficiently small δ and X_{S} when the system is compressed beyond its first jamming transition. While the first transition is sharp, exclusively with large-large contacts, the second is rather smooth, carried by small-large interactions at densities much higher than the monodisperse random packing baseline, ϕ_{J}^{mono}≈0.64. When only nonrattlers are considered, all the effective transition densities are reduced, and the density of the second transition emerges rather close to the reduced baseline, ϕ[over ̃]_{J}^{mono}≈0.61, due to its smooth nature. At size ratios δ≤0.22 a concentration X_{S}^{*} divides the diagram-either with most small particles nonjammed or jammed jointly with large ones. For X_{S}

Granular piston-probing in microgravity: powder compression, from densification to jamming.

The macroscopic response of granular solids is determined by the microscopic fabric of force chains, which, in turn, is intimately linked to the history of the solid. To query the influence of gravity on powder flow behavior, a granular material is subjected to compression by a piston in a closed container, on-ground and in microgravity (on parabolic flights). Results show that piston-probing densifies the packing, eventually leading to jamming of the material compressed by the piston, regardless of the gravitational environment. The onset of jamming is found to appear at lower packing fraction in microgravity ([Formula: see text]) than on-ground ([Formula: see text]). We interpret these findings as the manifestation of a granular fabric altered by the gravitational force field: in absence of a secondary load (due to gravitational acceleration) to stimulate reorganization in a different direction to the major compression stress, the particles' configuration becomes stable at lower density, as the particles have no external drive to promote reorganization into a denser packing. This is coupled with a change in interparticular force balance which takes place under low gravity, as cohesive interactions become predominant. We propose a combination of microscopic and continuum arguments to rationalize our results.

Active matter in space.

In the last 20 years, active matter has been a highly dynamic field of research, bridging fundamental aspects of non-equilibrium thermodynamics with applications to biology, robotics, and nano-medicine. Active matter systems are composed of units that can harvest and harness energy and information from their environment to generate complex collective behaviours and forms of self-organisation. On Earth, gravity-driven phenomena (such as sedimentation and convection) often dominate or conceal the emergence of these dynamics, especially for soft active matter systems where typical interactions are of the order of the thermal energy. In this review, we explore the ongoing and future efforts to study active matter in space, where low-gravity and microgravity conditions can lift some of these limitations. We envision that these studies will help unify our understanding of active matter systems and, more generally, of far-from-equilibrium physics both on Earth and in space. Furthermore, they will also provide guidance on how to use, process and manufacture active materials for space exploration and colonisation.

Using expectation violation models to improve the outcome of psychological treatments.

Expectations are a central maintaining mechanism in mental disorders and most psychological treatments aim to directly or indirectly modify clinically relevant expectations. Therefore, it is crucial to examine why patients with mental disorders maintain dysfunctional expectations, even in light of disconfirming evidence, and how expectation-violating situations should be created in treatment settings to optimize treatment outcome and reduce the risk of treatment failures. The different psychological subdisciplines offer various approaches for understanding the underlying mechanisms of expectation development, persistence, and change. Here, we convey recommendations on how to improve psychological treatments by considering these different perspectives. Based on our expectation violation model, we argue that the outcome of expectation violation depends on several characteristics: features of the expectation-violating situation; the dynamics between the magnitude of expectation violation and cognitive immunization processes; dealing with uncertainties during and after expectation change; controlled and automatic attention processes; and the costs of expectation changes. Personality factors further add to predict outcomes and may offer a basis for personalized treatment planning. We conclude with a list of recommendations derived from basic psychology that could contribute to improved treatment outcome and to reduced risks of treatment failures.

Alpha-2 Adrenoreceptor Antagonist Yohimbine Potentiates Consolidation of Conditioned Fear.

BACKGROUND: Hyperconsolidation of aversive associations and poor extinction learning have been hypothesized to be crucial in the acquisition of pathological fear. Previous animal and human research points to the potential role of the catecholaminergic system, particularly noradrenaline and dopamine, in acquiring emotional memories. Here, we investigated in a between-participants design with 3 groups whether the noradrenergic alpha-2 adrenoreceptor antagonist yohimbine and the dopaminergic D2-receptor antagonist sulpiride modulate long-term fear conditioning and extinction in humans. METHODS: Fifty-five healthy male students were recruited. The final sample consisted of n = 51 participants who were explicitly aware of the contingencies between conditioned stimuli (CS) and unconditioned stimuli after fear acquisition. The participants were then randomly assigned to 1 of the 3 groups and received either yohimbine (10 mg, n = 17), sulpiride (200 mg, n = 16), or placebo (n = 18) between fear acquisition and extinction. Recall of conditioned (non-extinguished CS+ vs CS-) and extinguished fear (extinguished CS+ vs CS-) was assessed 1 day later, and a 64-channel electroencephalogram was recorded. RESULTS: The yohimbine group showed increased salivary alpha-amylase activity, confirming a successful manipulation of central noradrenergic release. Elevated fear-conditioned bradycardia and larger differential amplitudes of the N170 and late positive potential components in the event-related brain potential indicated that yohimbine treatment (compared with a placebo and sulpiride) enhanced fear recall during day 2. CONCLUSIONS: These results suggest that yohimbine potentiates cardiac and central electrophysiological signatures of fear memory consolidation. They thereby elucidate the key role of noradrenaline in strengthening the consolidation of conditioned fear associations, which may be a key mechanism in the etiology of fear-related disorders.

Osteoarticular Infections in Pediatric Hospitals in Europe: A Prospective Cohort Study From the EUCLIDS Consortium.

Background: Pediatric osteoarticular infections (POAIs) are serious diseases requiring early diagnosis and treatment. Methods: In this prospective multicenter cohort study, children with POAIs were selected from the European Union Childhood Life-threatening Infectious Diseases Study (EUCLIDS) database to analyze their demographic, clinical, and microbiological data. Results: A cohort of 380 patients with POAIs, 203 with osteomyelitis (OM), 158 with septic arthritis (SA), and 19 with both OM and SA, was analyzed. Thirty-five patients were admitted to the Pediatric Intensive Care Unit; out of these, six suffered from shock, one needed an amputation of the right foot and of four left toes, and two had skin transplantation. According to the Pediatric Overall Performance Score, 36 (10.5%) showed a mild overall disability, 3 (0.8%) a moderate, and 1 (0.2%) a severe overall disability at discharge. A causative organism was detected in 65% (247/380) of patients. Staphylococcus aureus (S. aureus) was identified in 57.1% (141/247) of microbiological confirmed cases, including 1 (0.7%) methicillin-resistant S. aureus (MRSA) and 6 (4.2%) Panton-Valentine leukocidin (PVL)-producing S. aureus, followed by Group A Streptococcus (18.2%) and Kingella kingae (8.9%). K. kingae and PVL production in S. aureus were less frequently reported than expected from the literature. Conclusion: POAIs are associated with a substantial morbidity in European children, with S. aureus being the major detected pathogen. In one-third of patients, no causative organism is identified. Our observations show an urgent need for the development of a vaccine against S. aureus and for the development of new microbiologic diagnostic guidelines for POAIs in European pediatric hospitals.

Granular cooling of ellipsoidal particles in microgravity.

A three-dimensional granular gas of ellipsoids is established by exposing the system to the microgravity environment of the International Space Station. We use two methods to measure the dynamics of the constituent particles and report the long-time development of the granular temperature until no further particle movement is detectable. The resulting cooling behavior can be well described by Haff's cooling law with time scale τ. Different analysis methods show evidence of particle clustering towards the end of the experiment. By using the kinetic theory for ellipsoids we compare the translational energy dissipation of individual collision events with the overall cooling time scale τ. The difference from this comparison indicates how energy is distributed in different degrees of freedom including both translation and rotation during the cooling.

A Revised Framework for the Investigation of Expectation Update Versus Maintenance in the Context of Expectation Violations: The ViolEx 2.0 Model.

Expectations are probabilistic beliefs about the future that shape and influence our perception, affect, cognition, and behavior in many contexts. This makes expectations a highly relevant concept across basic and applied psychological disciplines. When expectations are confirmed or violated, individuals can respond by either updating or maintaining their prior expectations in light of the new evidence. Moreover, proactive and reactive behavior can change the probability with which individuals encounter expectation confirmations or violations. The investigation of predictors and mechanisms underlying expectation update and maintenance has been approached from many research perspectives. However, in many instances there has been little exchange between different research fields. To further advance research on expectations and expectation violations, collaborative efforts across different disciplines in psychology, cognitive (neuro)science, and other life sciences are warranted. For fostering and facilitating such efforts, we introduce the ViolEx 2.0 model, a revised framework for interdisciplinary research on cognitive and behavioral mechanisms of expectation update and maintenance in the context of expectation violations. To support different goals and stages in interdisciplinary exchange, the ViolEx 2.0 model features three model levels with varying degrees of specificity in order to address questions about the research synopsis, central concepts, or functional processes and relationships, respectively. The framework can be applied to different research fields and has high potential for guiding collaborative research efforts in expectation research.

Dynamic light scattering from single macroscopic particles.

Here we present a methodology to characterize the light intensity fluctuations that arise from rotations of individual granular particles. We describe a setup for dynamic light scattering measurements on individual macroscopic particles and isolate the contribution from rotations of the individual particles to the obtained correlation functions. The results show that rotation of granular particles results in a significant contribution to scattered light intensity fluctuations, a phenomenon not considered so far in dynamic light scattering measurements on fluidized granular media. The results presented here may thus form the basis for an extended light scattering methodology for granular media, and improve the selection of granular particles according to their dynamic light scattering signal.

Placebo nasal spray protects female participants from experimentally induced sadness and concomitant changes in autonomic arousal.

BACKGROUND: To investigate the powerful placebo effects in antidepressant drug trials and their mechanisms, recent pioneering experimental studies showed that expectation manipulation combined with an active placebo attenuated induced sadness. In the present study, we aimed at extending these findings by assessing the psychophysiological response in addition to mere self-report. METHODS: One hundred and thirteen healthy female students were randomly assigned to a drug expectation group (active placebo, positive treatment expectation), placebo expectation group (active placebo, no treatment expectation), or a no-treatment group (no placebo, no treatment expectation). After placebo intake, sadness was induced by self-deprecating statements using the Velten method combined with sad music, including a rumination phase. Sadness was measured using the Positive and Negative Affect Schedule Expanded Form (PANAS-X). Heart rate and skin conductance were assessed continuously. RESULTS: After mood induction and after rumination, self-reported sadness was significantly lower, and skin conductance level was significantly higher, in the drug expectation group than in the no-treatment group. The mood induction was further accompanied by a heart rate deceleration within all groups. LIMITATIONS: Generalizability is limited by sample selectivity and focusing on sadness as a symptom of depression, exclusively. CONCLUSION: Expectation-induced placebo effects significantly influenced sadness-correlated changes in autonomic arousal, and not only subjectively reported sadness, indicating that placebo effects in the context of affect are not merely due to subjective response bias. The systematic modification of treatment expectation could be utilized in clinical practice to optimize current therapeutic approaches to improve mood regulation.

Does femoral anteversion and internally rotated gait correlate in subjects with patellofemoral instability?

BACKGROUND: Patellar instability is a considerable problem that leads to pain and anxiety during simple functional tasks. Femoral derotational osteotomy has become a common surgical procedure to improve patella mechanics, stability and loading. However, it remains unclear if static (MRI measured) femoral anteversion is sufficient to capture the dynamic femoral rotation during walking and represents a good indication for the surgical procedure. This research investigates the relationship between static femoral anteversion and internally rotated gait in adolescents with patellofemoral instability. METHODS: This retrospective study included 30 adolescents with recurrent patella instability (minimum three patella dislocations) aged 12 to 18 years (28 female/2 male; 22 unilateral/8 bilateral). All participants were assessed with 3D gait analysis and the femoral anteversion was examined using a rotational MRI. Multiple kinematic parameter were correlated with the ipsilateral femoral anteversion and tibia torsion using the Pearson coefficient. FINDINGS: The correlation between parameters of dynamic hip rotation (e.g. maximum and mean internal hip rotation in stance and swing) and MRI measured femoral anteversion (mean 26.5° ± 9°) was weak and did not reach statistical significance. We found 47% (14 out of 30) subjects with increased femoral anteversion but normal hip rotation in stance. INTERPRETATION: There was no relationship between increased femoral anteversion and dynamic hip rotation. Consequently, femoral anteversion should not be used as the only indication for femoral derotational osteotomy. Three-dimensional gait analysis might be necessary to assess the appropriate surgical intervention in adolescents with patello femoral instability.

Force chains in crystalline and frustrated packing visualized by stress-birefringent spheres.

Force networks play an important role in the stability of configurations when granular material is packed into a container. These networks can redirect part of the weight of grains inside a container to the side walls. We employ monodisperse stress-birefringent spheres to visualize the contact forces in a quasi-2D and a nearly-2D configuration of these spheres in a thin cuboid cell. The packing structures are particularly simple: a hexagonal lattice in the ground state when the cell width is equal to the sphere diameter, and a frustrated, slightly distorted lattice in thicker cells. The force redistribution is substantially changed by this geometrical modification. In both cases, we observe an 'inverse' Janssen effect with the pressure decreasing from the top to the bottom of the container when the material is loaded with a weight on top of the vessel.

Prefrontal Theta Oscillations Are Modulated by Estradiol Status During Fear Recall and Extinction Recall.

BACKGROUND: Emerging human studies demonstrate that theta oscillations in the dorsal anterior cingulate cortex are enhanced during fear recall (enhanced fear expression) and reduced during successful extinction recall (reduced fear expression). Although evidence suggests sex differences in fear recall and extinction recall, there are currently no human studies examining the oscillatory foundations of these memory processes separately in men and women. METHODS: Because previous studies suggest that estradiol partially mediates these sex differences, we examined 20 men (low estradiol and low progesterone), 20 women using oral contraceptives (low estradiol and low progesterone), and 20 free-cycling women during midcycle (high estradiol and low progesterone). We used a fear-conditioning procedure, allowing us to separately assess fear recall and extinction recall 24 hours after fear and extinction learning. Skin conductance responses and electroencephalography were recorded during fear recall and extinction recall, and prefrontal oscillations were source localized. RESULTS: We found elevated fear expression during fear recall and impaired extinction recall, as indicated by increased peripheral arousal (skin conductance responses) and fronto-central theta oscillations, source localized in the dorsal anterior cingulate cortex and dorsomedial prefrontal cortex. Importantly, peripheral arousal and dorsal anterior cingulate cortex theta oscillations were stronger in men and women on oral contraceptives than in women from the midcycle group. CONCLUSIONS: Our data show that neural oscillatory and peripheral correlates of heightened fear expression during fear recall and (impaired) extinction recall do not simply differ between sexes but depend on hormonal fluctuations within women.

Learning dynamics of electrophysiological brain signals during human fear conditioning.

Electrophysiological studies in rodents allow recording neural activity during threats with high temporal and spatial precision. Although fMRI has helped translate insights about the anatomy of underlying brain circuits to humans, the temporal dynamics of neural fear processes remain opaque and require EEG. To date, studies on electrophysiological brain signals in humans have helped to elucidate underlying perceptual and attentional processes, but have widely ignored how fear memory traces evolve over time. The low signal-to-noise ratio of EEG demands aggregations across high numbers of trials, which will wash out transient neurobiological processes that are induced by learning and prone to habituation. Here, our goal was to unravel the plasticity and temporal emergence of EEG responses during fear conditioning. To this end, we developed a new sequential-set fear conditioning paradigm that comprises three successive acquisition and extinction phases, each with a novel CS+/CS- set. Each set consists of two different neutral faces on different background colors which serve as CS+ and CS-, respectively. Thereby, this design provides sufficient trials for EEG analyses while tripling the relative amount of trials that tap into more transient neurobiological processes. Consistent with prior studies on ERP components, data-driven topographic EEG analyses revealed that ERP amplitudes were potentiated during time periods from 33-60 ms, 108-200 ms, and 468-820 ms indicating that fear conditioning prioritizes early sensory processing in the brain, but also facilitates neural responding during later attentional and evaluative stages. Importantly, averaging across the three CS+/CS- sets allowed us to probe the temporal evolution of neural processes: Responses during each of the three time windows gradually increased from early to late fear conditioning, while long-latency (460-730 ms) electrocortical responses diminished throughout fear extinction. Our novel paradigm demonstrates how short-, mid-, and long-latency EEG responses change during fear conditioning and extinction, findings that enlighten the learning curve of neurophysiological responses to threat in humans.