Transient Adaptation Research Articles

Transient Adaptation of Toxoplasma gondii to Exposure by Thiosemicarbazone Drugs That Target Ribosomal Proteins Is Associated with the Upregulated Expression of Tachyzoite Transmembrane Proteins and Transporters.

Thiosemicarbazones and their metal complexes have been studied for their biological activities against bacteria, cancer cells and protozoa. Short-term in vitro treatment with one gold (III) complex (C3) and its salicyl-thiosemicarbazone ligand (C4) selectively inhibited proliferation of T. gondii. Transmission Electron Microscopy (TEM) detected transient structural alterations in the parasitophorous vacuole membrane and the tachyzoite cytoplasm, but the mitochondrial membrane potential appeared unaffected by these compounds. Proteins potentially interacting with C3 and C4 were identified using differential affinity chromatography coupled with mass spectrometry (DAC-MS). Moreover, long-term in vitro treatment was performed to investigate parasitostatic or parasiticidal activity of the compounds. DAC-MS identified 50 ribosomal proteins binding both compounds, and continuous drug treatments for up to 6 days caused the loss of efficacy. Parasite tolerance to both compounds was, however, rapidly lost in their absence and regained shortly after re-exposure. Proteome analyses of six T. gondii ME49 clones adapted to C3 and C4 compared to the non-adapted wildtype revealed overexpression of ribosomal proteins, of two transmembrane proteins involved in exocytosis and of an alpha/beta hydrolase fold domain-containing protein. Results suggest that C3 and C4 may interfere with protein biosynthesis and that adaptation may be associated with the upregulated expression of tachyzoite transmembrane proteins and transporters, suggesting that the in vitro drug tolerance in T. gondii might be due to reversible, non-drug specific stress-responses mediated by phenotypic plasticity.

A general model unifying the adaptive, transient and sustained properties of ON and OFF auditory neural responses.

Sounds are temporal stimuli decomposed into numerous elementary components by the auditory nervous system. For instance, a temporal to spectro-temporal transformation modelling the frequency decomposition performed by the cochlea is a widely adopted first processing step in today's computational models of auditory neural responses. Similarly, increments and decrements in sound intensity (i.e., of the raw waveform itself or of its spectral bands) constitute critical features of the neural code, with high behavioural significance. However, despite the growing attention of the scientific community on auditory OFF responses, their relationship with transient ON, sustained responses and adaptation remains unclear. In this context, we propose a new general model, based on a pair of linear filters, named AdapTrans, that captures both sustained and transient ON and OFF responses into a unifying and easy to expand framework. We demonstrate that filtering audio cochleagrams with AdapTrans permits to accurately render known properties of neural responses measured in different mammal species such as the dependence of OFF responses on the stimulus fall time and on the preceding sound duration. Furthermore, by integrating our framework into gold standard and state-of-the-art machine learning models that predict neural responses from audio stimuli, following a supervised training on a large compilation of electrophysiology datasets (ready-to-deploy PyTorch models and pre-processed datasets shared publicly), we show that AdapTrans systematically improves the prediction accuracy of estimated responses within different cortical areas of the rat and ferret auditory brain. Together, these results motivate the use of our framework for computational and systems neuroscientists willing to increase the plausibility and performances of their models of audition.

A novel method for aero-engine map calibration using adaptation factor surface

High-fidelity component-level models (CLMs) are essential for aero-engine performance modeling, monitoring, and diagnosis, relying heavily on precise component maps. Inaccuracies in these maps can cause significant deviations between predicted and actual measurements. This study introduces a novel wide-range performance adaptation method (WPAM) utilizing adaptation factor surfaces, enabling precise adjustment of speed line operating points. The adaptation factors for the component maps are calculated based on both steady-state and transient measurements using the Levenberg-Marquardt method, with transient adaptation calculations converted into a steady-state solution. Adaptation factor surfaces are constructed using the moving least squares method to modify component maps in both spool speed and β-value directions. Validated on two engines with distinct maps, WPAM significantly enhances CLM accuracy under steady-state and transient conditions, considering multidimensional engine and CLM map discrepancies. It is applicable to degraded and variable geometry engines, exhibiting robustness in handling noisy measurement data.

Unraveling resilience amidst degradation: Recurring loss of freshwater marshes in the Paraná River Delta, Argentina

Wetland ecosystems have experienced several ecological and hydrological impacts in recent decades determined by human activities and natural disturbances. The Lower Delta of the Paraná River, one of the most important wetland ecosystems of South America, has seen significant losses in both the structural and functional components of wetland vegetation. These losses promoted not only a widespread conversion of freshwater marshes into grasslands between 1997 and 2013, but also a decline in ecosystem functional diversity between 2001 and 2015. These processes manifested as abrupt shifts in long-term vegetation dynamics, a distorted, transient, spatially heterogeneous relationship with the hydrologic regime, and altered plant communities. However, recent field observations (2015–2023) have partially challenged previous findings and assumptions. Thus, we ask whether previously observed wetland losses are part of a long-term periodic process, rather than a permanent change. To address this question, we studied land use and land cover conversions through an object-based supervised classification of yearly Landsat composites between 1985 and 2023, trained on 935 ground-truth points. To study the spatial and temporal patterns of wetland gain and loss, we implemented an Intensity Analysis (IA), as well as analyses that capture frequency-specific variations and identify significant shifts in linear trends. We produced a total of 39 land cover maps. The IA revealed non-stationarity at all levels of analysis: interval, category, and transition. The study area exhibited resilient patterns through significant and increasingly short-term, periodic dynamics guiding the gain and loss of freshwater marshes. On the opposite, long-term, negative trends depicted an absolute, sustained loss. These contrasting patterns suggest that despite experiencing absolute loss and degradation, wetland ecosystems thrive by exhibiting transient recovery or adaptation mechanisms. Our study unraveled the complexity of wetland ecosystem dynamics, emphasizing how resilience and degradation interplay in the context of land use intensification.

Lineage tracing reveals transient phenotypic adaptation of tubular cells during acute kidney injury

Tubular injury is the hallmark of acute kidney injury (AKI) with a tremendous impact on patients and health-care systems. During injury, any differentiated proximal tubular cell (PT) may transition into a specific injured phenotype, so-called "scattered tubular cell" (STC)-phenotype. To understand the fate of this specific phenotype, we generated transgenic mice allowing inducible, reversible, and irreversible tagging of these cells in a murine AKI model, the unilateral ischemia-reperfusion injury (IRI). For lineage tracing, we analyzed the kidneys using single-cell profiling during disease development at various time points. Labeled cells, which we defined by established endogenous markers, already appeared 8h after injury and showed a distinct expression set of genes. We show that STCs re-differentiate back into fully differentiated PTs upon the resolution of the injury. In summary, we show the dynamics of the phenotypic transition of PTs during injury, revealing a reversible transcriptional program as an adaptive response during disease.

Polyhexamethylene biguanide promotes adaptive cross-resistance to gentamicin in Escherichia coli biofilms.

Antimicrobial resistance is a critical public health issue that requires a thorough understanding of the factors that influence the selection and spread of antibiotic-resistant bacteria. Biocides, which are widely used in cleaning and disinfection procedures in a variety of settings, may contribute to this resistance by inducing similar defense mechanisms in bacteria against both biocides and antibiotics. However, the strategies used by bacteria to adapt and develop cross-resistance remain poorly understood, particularly within biofilms -a widespread bacterial habitat that significantly influences bacterial tolerance and adaptive strategies. Using a combination of adaptive laboratory evolution experiments, genomic and RT-qPCR analyses, and biofilm structural characterization using confocal microscopy, we investigated in this study how Escherichia coli biofilms adapted after 28 days of exposure to three biocidal active substances and the effects on cross-resistance to antibiotics. Interestingly, polyhexamethylene biguanide (PHMB) exposure led to an increase of gentamicin resistance (GenR) phenotypes in biofilms formed by most of the seven E. coli strains tested. Nevertheless, most variants that emerged under biocidal conditions did not retain the GenR phenotype after removal of antimicrobial stress, suggesting a transient adaptation (adaptive resistance). The whole genome sequencing of variants with stable GenR phenotypes revealed recurrent mutations in genes associated with cellular respiration, including cytochrome oxidase (cydA, cyoC) and ATP synthase (atpG). RT-qPCR analysis revealed an induction of gene expression associated with biofilm matrix production (especially curli synthesis), stress responses, active and passive transport and cell respiration during PHMB exposure, providing insight into potential physiological responses associated with adaptive crossresistance. In addition, confocal laser scanning microscopy (CLSM) observations demonstrated a global effect of PHMB on biofilm architectures and compositions formed by most E. coli strains, with the appearance of dense cellular clusters after a 24h-exposure. In conclusion, our results showed that the PHMB exposure stimulated the emergence of an adaptive cross-resistance to gentamicin in biofilms, likely induced through the activation of physiological responses and biofilm structural modulations altering gradients and microenvironmental conditions in the biological edifice.

Epigenetic-Based Regulation of Transcriptome in Escherichia coli Adaptive Antibiotic Resistance.

Adaptive antibiotic resistance is a transient metabolic adaptation of bacteria limiting their sensitivity to low, progressively increased, concentrations of antibiotics. Unlike innate and acquired resistance, adaptive resistance is dependent on the presence of antibiotics, and it disappears when the triggering factor is removed. Low concentrations of antibiotics are largely diffused in natural environments, in the food industry or in certain body compartments of humans when used therapeutically, or in animals when used for growth promotion. However, molecular mechanisms underlying this phenomenon are still poorly characterized. Here, we present experiments suggesting that epigenetic modifications, triggered by low concentrations of ampicillin, gentamicin, and ciprofloxacin, may modulate the sensitivity of bacteria to antibiotics. The epigenetic modifications we observed were paralleled by modifications of the expression pattern of many genes, including some of those that have been found mutated in strains with permanent antibiotic resistance. As the use of low concentrations of antibiotics is spreading in different contexts, our findings may suggest new targets and strategies to avoid adaptive antibiotic resistance. This might be very important as, in the long run, this transient adaptation may increase the chance, allowing the survival and the flourishing of bacteria populations, of the onset of mutations leading to stable resistance. IMPORTANCE In this study, we characterized the modifications of epigenetic marks and of the whole transcriptome in the adaptive response of Escherichia coli cells to low concentrations of ampicillin, gentamicin, and ciprofloxacin. As the transient adaptation does increase the chance of permanent resistance, possibly allowing the survival and flourishing of bacteria populations where casual mutations providing resistance may give an immediate advantage, the importance of this study is not only in the identification of possible molecular mechanisms underlying adaptive resistance to antibiotics, but also in suggesting new strategies to avoid adaptation.

Composite model-reference adaptive control with least-squares estimator

This work presents a new design of a composite model-reference adaptive control (MRAC) with a least-squares parameter estimator. The objective of the design is to preserve the remarkable transient adaptation characteristic obtained by a modified MRAC algorithm recently introduced and, at the same time, enjoy the superior parameter convergence performance of a least-squares estimator. The algorithm employs two different estimators for the same controller parameter, one updated by a gradient law driven by the tracking error and the other updated by a least-squares algorithm driven by a prediction error. In this way, the performance of each one is kept unchanged. The existence of a Lyapunov function assures the global uniform stability of the proposed composite adaptive scheme and simulation results confirm and illustrate its properties.

Adaptation dynamics between copy-number and point mutations.

Together, copy-number and point mutations form the basis for most evolutionary novelty, through the process of gene duplication and divergence. While a plethora of genomic data reveals the long-term fate of diverging coding sequences and their cis-regulatory elements, little is known about the early dynamics around the duplication event itself. In microorganisms, selection for increased gene expression often drives the expansion of gene copy-number mutations, which serves as a crude adaptation, prior to divergence through refining point mutations. Using a simple synthetic genetic reporter system that can distinguish between copy-number and point mutations, we study their early and transient adaptive dynamics in real time in Escherichia coli. We find two qualitatively different routes of adaptation, depending on the level of functional improvement needed. In conditions of high gene expression demand, the two mutation types occur as a combination. However, under low gene expression demand, copy-number and point mutations are mutually exclusive; here, owing to their higher frequency, adaptation is dominated by copy-number mutations, in a process we term amplification hindrance. Ultimately, due to high reversal rates and pleiotropic cost, copy-number mutations may not only serve as a crude and transient adaptation, but also constrain sequence divergence over evolutionary time scales.

Thermal acclimation results in persistent phosphoproteome changes in the freshwater planarian Crenobia alpina (Tricladida: Planariidae)

Understanding the molecular mechanisms underlying thermal tolerance of aquatic invertebrates can inform predictions about the effects of thermal regime changes on these species. While gene expression and protein abundance changes underlie compensatory responses, little is known about the role of post-translational modifications as thermal tolerance mechanisms. To test the hypothesis that protein phosphorylation changes in response to thermal acclimation, we studied the phosphoproteome of the freshwater planarian Crenobia alpina. This species has a supposedly limited thermal tolerance and is found in cold-stable habitats. We systematically investigated phosphopeptide abundances following 168 h acclimation to 11, 14, 17, and 20 °C, using label-free quantitative phosphoproteomics. We provide a comparative analysis of 2115 phosphosites from 1049 phosphoproteins, whereby little to no differences could be observed between 11, 14, and 17 °C. However, more than 130 phosphopeptides were significantly more abundant and 40 were less abundant following acclimation to 20 °C. These phosphoproteins were functionally associated with the regulation of neuronal processes, cilia, DNA damage repair, aquaporins, and mitochondrial fission and fusion. These data support the hypothesis that phosphorylation plays a role in thermal acclimation responses, suggesting that PTMs are of significance in invertebrate thermal acclimation. PTMs may therefore offer an alternative route of transient protein adaptation to temperature increase in invertebrates, and should not be neglected when trying to understand how molecular system dynamics in response to elevated temperatures.

A nexus of lipid and O-Glcnac metabolism in physiology and disease.

Although traditionally considered a glucose metabolism-associated modification, the O-linked β-N-Acetylglucosamine (O-GlcNAc) regulatory system interacts extensively with lipids and is required to maintain lipid homeostasis. The enzymes of O-GlcNAc cycling have molecular properties consistent with those expected of broad-spectrum environmental sensors. By direct protein-protein interactions and catalytic modification, O-GlcNAc cycling enzymes may provide both acute and long-term adaptation to stress and other environmental stimuli such as nutrient availability. Depending on the cell type, hyperlipidemia potentiates or depresses O-GlcNAc levels, sometimes biphasically, through a diversity of unique mechanisms that target UDP-GlcNAc synthesis and the availability, activity and substrate selectivity of the glycosylation enzymes, O-GlcNAc Transferase (OGT) and O-GlcNAcase (OGA). At the same time, OGT activity in multiple tissues has been implicated in the homeostatic regulation of systemic lipid uptake, storage and release. Hyperlipidemic patterns of O-GlcNAcylation in these cells are consistent with both transient physiological adaptation and feedback uninhibited obesogenic and metabolic dysregulation. In this review, we summarize the numerous interconnections between lipid and O-GlcNAc metabolism. These links provide insights into how the O-GlcNAc regulatory system may contribute to lipid-associated diseases including obesity and metabolic syndrome.

A Novel Data-Driven-Based Component Map Generation Method for Transient Aero-Engine Performance Adaptation

Accurate component maps, which can significantly affect the efficiency, reliability and availability of aero-engines, play a critical role in aero-engine performance simulation. Unfortunately, the information of component maps is insufficient, leading to substantial limitations in practical application, wherein compressors are of particular interest. Here, a data-driven-based compressor map generation approach for transient aero-engine performance adaptation is investigated. A multi-layer perceptron neural network is utilized in simulating the compressor map instead of conventional interpolation schemes, and an adaptive variable learning rate backpropagation (ADVLBP) algorithm is employed to accelerate the convergence and improve the stability in the training process. Aside from that, two different adaptation strategies designed for steady state and transient conditions are implemented to adaptively retrain the compressor network according to measurement deviations until the accuracy requirements are satisfied. The proposed method is integrated into a turbofan component-level model, and simulations reveal that the ADVLBP algorithm has the capability of more rapid convergence compared with conventional training algorithms. In addition, the maximum absolute measurement deviation decreased from 6.35% to 0.44% after steady state adaptation, and excellent agreement between the predictions and benchmark data was obtained after transient adaptation. The results demonstrate the effectiveness and superiority of the proposed component map generation method.

Electroencephalographic response to transient adaptation of vestibular perception.

When given a series of sinusoidal oscillations in which the two hemicycles have equal amplitude but asymmetric velocity, healthy subjects lose perception of the slower hemicycle (SHC), reporting a drift towards the faster hemicycle (FHC). This response is not reflected in the vestibular–ocular reflex, suggesting that the adaptation is of higher order. This study aimed to define EEG correlates of this adaptive response. Twenty‐five subjects underwent a series of symmetric or asymmetric oscillations and reported their perceived head orientation at the end using landmarks in the testing room; this was converted into total position error (TPE). Thirty‐two channel EEG was recorded before, during and after adaptation. Spectral power and coherence were calculated for the alpha, beta, delta and theta frequency bands. Linear mixed models were used to determine a region‐by‐condition effect of the adaptation. TPE was significantly greater in the asymmetric condition and reported error was always in the direction of the FHC. Regardless of condition, alpha desynchronised in response to stimulation, then rebounded back toward baseline values. This pattern was accelerated and attenuated in the prefrontal and occipital regions, respectively, in the asymmetric condition. Functional connectivity networks were identified in the beta and delta frequency bands; these networks, primarily comprising frontoparietal connections, were more coherent during asymmetric stimulation. These findings suggest that the temporary vestibulo‐perceptual ‘neglect’ induced by asymmetric vestibular stimulation may be mediated by alpha rhythms and frontoparietal attentional networks. The results presented further our understanding of brain rhythms and cortical networks involved in vestibular perception and adaptation. Key points Whole‐body asymmetric sinusoidal oscillations, which consist of hemicycles with equal amplitude but differing velocities, can induce transient ‘neglect’ of the slower hemicycle in the vestibular perception of healthy subjects.In this study, we aimed to elucidate EEG correlates of this ‘neglect’, thereby identifying a cortical role in vestibular perception and adaptation.We identified a desynchronisation–resynchronisation response in the alpha frequency band (8–14 Hz) that was accelerated in the prefrontal region and attenuated in the occipital region when exposed to asymmetric, as compared to symmetric, rotations.We additionally identified functional connectivity networks in the beta (14–30 Hz) and delta (1–4 Hz) frequency bands consisting primarily of frontoparietal connections.These results suggest a prominent role of alpha rhythms and frontoparietal attentional networks in vestibular perception and adaptation.

Burmese pythons exhibit a transient adaptation to nutrient overload that prevents liver damage.

As an opportunistic predator, the Burmese python (Python molurus bivittatus) consumes large and infrequent meals, fasting for up to a year. Upon consuming a large meal, the Burmese python exhibits extreme metabolic responses. To define the pathways that regulate these postprandial metabolic responses, we performed a comprehensive profile of plasma metabolites throughout the digestive process. Following ingestion of a meal equivalent to 25% of its body mass, plasma lipoproteins and metabolites, such as chylomicra and bile acids, reach levels observed only in mammalian models of extreme dyslipidemia. Here, we provide evidence for an adaptive response to postprandial nutrient overload by the python liver, a critical site of metabolic homeostasis. The python liver undergoes a substantial increase in mass through proliferative processes, exhibits hepatic steatosis, hyperlipidemia-induced insulin resistance indicated by PEPCK activation and pAKT deactivation, and de novo fatty acid synthesis via FASN activation. This postprandial state is completely reversible. We posit that Burmese pythons evade the permanent hepatic damage associated with these metabolic states in mammals using evolved protective measures to inactivate these pathways. These include a transient activation of hepatic nuclear receptors induced by fatty acids and bile acids, including PPAR and FXR, respectively. The stress-induced p38 MAPK pathway is also transiently activated during the early stages of digestion. Taken together, these data identify a reversible metabolic response to hyperlipidemia by the python liver, only achieved in mammals by pharmacologic intervention. The factors involved in these processes may be relevant to or leveraged for remediating human hepatic pathology.

Experimental evolution of local adaptation under unidimensional and multidimensional selection

Local adaptation is a fundamental evolutionary process generating biological diversity and potentially enabling ecological speciation. Divergent selection underlies the evolution of local adaptation in spatially structured populations by driving their adaptation toward local optima. Environments rarely differ along just one environmental axis; therefore, divergent selection may often be multidimensional. How the dimensionality of divergent selection affects local adaptation is unclear: evolutionary theory predicts that increasing dimensionality will increase local adaptation when associated with stronger overall selection but may have less predictable effects if selection strengths are equal. Experiments are required that allow the effect of the dimensionality of selection on local adaptation to be tested independently of the total strength of selection. We experimentally evolved 32 pairs of monogonont rotifer populations under either unidimensional divergent selection (a single pair of stressors) or multidimensional divergent selection (three pairs of stressors), keeping the total strength of selection equal between treatments. At regular intervals, we assayed fitness in home and away environments to assess local adaptation. We observed an initial increase and subsequent decline of local adaptation in populations exposed to multidimensional selection, compared with a slower but eventually stronger increase in local adaptation in populations exposed to unidimensional selection. Our results contrast with existing predictions, such as the "weak multifarious" and "stronger selection" hypotheses. Instead, we hypothesize that adaptation to multidimensional divergent selection may favor generalist genotypes and only produce transient local adaptation.

Transient Response of a Continuous Glucose Monitor

Blood glucose is indirectly measured with a subcutaneous continuous glucose monitor (CGM). Glucose within the interstitial space is converted into hydrogen peroxide via an enzymatic reaction with glucose oxidase. Electrochemical oxidation of the hydrogen peroxide produces a faradaic current proportional to the hydrogen peroxide concentration. In vitro CGM experiments during transient operation demonstrate a range of time constants in the current response. A transient model adaptation of the steady model from Gao et al. was prepared. [1] The transient responses to potential and glucose steps were investigated experimentally and numerically.The transient current response of an electrochemical system with coupled homogeneous and heterogeneous reactions yields time constants dependent on the charging of the electrode, rates of homogeneous reactions, and mass transfer of the participating species. For nonlinear homogeneous reactions involving species of varying diffusion coefficients, analytic expression of these time constants is nontrivial and more readily obtained numerically.A transient model was discretized in space and time with finite differences and the Crank-Nicolson method. Numerical solutions of the model were obtained with Newman’s BAND algorithm. [2] The model demonstrates the charging current, faradaic current, and concentration profile responses within the sensor. When the model is perturbed with a potential step, the initial response is characterized by a charging current; whereas, larger time constants are due to both the mass transfer to the electrode through diffusion and homogeneous reactions.Steady, transient, and impedance responses of the CGM were experimentally obtained. Steady-state current was measured as a function of glucose concentration which provided an estimate for the permeability of glucose in the sensor. Current response to a glucose step was obtained, and the short-time behavior was fit with a single time constant. An equivalent circuit, fabricated based on the impedance spectra, demonstrated a potential step response similar to the sensor. The influence of dissolved oxygen concentration on the transient response was also investigated.The model was fit to the experimental current responses by adjusting diffusion and partition coefficients, rate and equilibrium constants, and electrolyte resistance and capacitance. The numerical model shows the short time constant is due to charging of the sensor, and the larger time constants are due to diffusion and enzymatic reactions. The large time constants of the current response are significantly larger than those predicted by a simple Gerischer model.[3,4] The presence of both diffusing and non-diffusing species involved in the homogeneous reactions may give rise to current instabilities and time constants.References Gao, M., Harding, M., Kong, R., & Orazem, M. (2018). Mathematical Model for the Electrochemical Impedance Response of a Continuous Glucose Monitor. Electrochimica Acta, 275. 119-132.Newman, J., & Thomas-Alyea, E. (2004). Electrochemical Systems (3rd ed.). NJ: John Wiley & Sons, Hoboken.Gerischer, H. (1951). Wechselstrompolarisation Von Elektroden Mit Einem Potentialbestimenden Schritt Beim Gleichgewichtspotential. Zeitschrift fur Physikalische Chemie, 198. 286-313.Orazem, M., & Tribollet, B. (2017). Electrochemical Impedance Spectroscopy. Hoboken, NJ: John Wiley & Sons. AcknowledgementThe support of Medtronic Diabetes (Northridge, CA), Mike Miller, program monitor, is gratefully acknowledged.

Rapid Transient Transcriptional Adaptation to Hypergravity in Jurkat T Cells Revealed by Comparative Analysis of Microarray and RNA-Seq Data.

Cellular responses to micro- and hypergravity are rapid and complex and appear within the first few seconds of exposure. Transcriptomic analyses are a valuable tool to analyze these genome-wide cellular alterations. For a better understanding of the cellular dynamics upon altered gravity exposure, it is important to compare different time points. However, since most of the experiments are designed as endpoint measurements, the combination of cross-experiment meta-studies is inevitable. Microarray and RNA-Seq analyses are two of the main methods to study transcriptomics. In the field of altered gravity research, both methods are frequently used. However, the generation of these data sets is difficult and time-consuming and therefore the number of available data sets in this research field is limited. In this study, we investigated the comparability of microarray and RNA-Seq data and applied the results to a comparison of the transcriptomics dynamics between the hypergravity conditions during two real flight platforms and a centrifuge experiment to identify temporal adaptation processes. We performed a comparative study on an Affymetrix HTA2.0 microarray and a paired-end RNA-Seq data set originating from the same Jurkat T cell RNA samples from a short-term hypergravity experiment. The overall agreeability was high, with better sensitivity of the RNA-Seq analysis. The microarray data set showed weaknesses on the level of single upregulated genes, likely due to its normalization approach. On an aggregated level of biotypes, chromosomal distribution, and gene sets, both technologies performed equally well. The microarray showed better performance on the detection of altered gravity-related splicing events. We found that all initially altered transcripts fully adapted after 15 min to hypergravity and concluded that the altered gene expression response to hypergravity is transient and fully reversible. Based on the combined multiple-platform meta-analysis, we could demonstrate rapid transcriptional adaptation to hypergravity, the differential expression of the ATPase subunits ATP6V1A and ATP6V1D, and the cluster of differentiation (CD) molecules CD1E, CD2AP, CD46, CD47, CD53, CD69, CD96, CD164, and CD226 in hypergravity. We could experimentally demonstrate that it is possible to develop methodological evidence for the meta-analysis of individual data.

The influences of tunnel lighting environment on drivers’ peripheral visual performance during transient adaptation

Highway tunnel lighting environments include sidewall, pavement, ceiling, etc., their surface luminance were affected by the distribution of luminous flux of the lamps. While driving through a highway tunnel, the driver needs to complete a series of visual tasks. The spatial distribution of the luminance and color on the road surface and sidewall, as well as the correlated color temperature, influence the driver’s visual performance. The process of driving through a highway tunnel lighting environment was simulated in a laboratory where the luminance of the non-uniform visual environment was gradually decreased. The effects of the spatial distribution of the lighting environment parameters on a driver’s visual performance was studied by testing each subject’s reaction times and missed target rates. The tests showed that the spatial distribution of the lighting environment parameters significantly influences a driver’s visual performance, and the effects on test subjects’ peripheral visual performance are different in threshold, transition, and interior zones. The optimization of the spatial distribution of the lighting environment parameters can enhance traffic safety and energy saving of highway tunnel lighting.

Intermittent reloading does not prevent reduction in iron availability and hepcidin upregulation caused by hindlimb unloading.

What is the central question of this study? Could skeletal muscle be involved in microgravity-induced iron misdistribution by modulating expression of hepcidin, the master regulator of iron metabolism? What is the main finding and its importance? We demonstrate, in rats, that hepcidin upregulation is not a transient adaptation associated with early exposure to microgravity and that intermittent reloading does not limit microgravity-induced iron misdistribution despite having a beneficial effect on soleus muscle wasting. In humans, exposure to microgravity during spaceflight causes muscle atrophy, changes in iron storage and a reduction in iron availability. We previously observed that during 7 days of simulated microgravity in rats, hepcidin plays a key role in iron misdistribution, and we suggested that a crosstalk between skeletal muscle and liver could regulate hepcidin synthesis in this context. In the present study in rats, we investigated the medium-term effects of simulated microgravity on iron metabolism. We also tested whether intermittent reloading (IR) to target skeletal muscle atrophy limits iron misdistribution efficiently. For this purpose, Wistar rats underwent 14 days of hindlimb unloading (HU) combined or not combined with daily IR. At the end of this period, the serum iron concentration and transferrin saturation were significantly reduced, whereas hepatic hepcidin mRNA was upregulated. However, the main signalling pathways involved in hepcidin synthesis in the liver (BMP-small mothers against decapentaplegic (SMAD), interleukin-6-STAT3 and ERK1/2) were unaffected. Unlike what was observed after 7days of HU, the iron concentration in the spleen, liver and skeletal muscle was comparable between control animals and those that underwent HU or HU plus IR for 14 days. Despite its beneficial effect on soleus muscle atrophy and slow-to-fast myosin heavy chain distribution, IR did not significantly prevent a reduction in iron availability and hepcidin upregulation. Altogether, these results highlight that iron availability is durably reduced during longer exposure to simulated microgravity and that the related hepcidin upregulation is not a transient adaptation to these conditions. The results also suggest that skeletal muscle does not necessarily play a key role in the iron misdistribution that occurs during simulated microgravity.

Continuous neurally adjusted ventilation: a feasibility study in preterm infants

ObjectivesTo assess the feasibility and tolerance of NeuroPAP, a new non-invasive ventilation mode which continuously adjusts (during both inspiration and expiration) the pressure support proportionally to the diaphragm electrical activity...