Dynamic Physiological Processes Research Articles

High-speed widefield photoacoustic microscopy of small-animal hemodynamics.

Optical-resolution photoacoustic microscopy (OR-PAM) has become a popular tool in small-animal hemodynamic studies. However, previous OR-PAM techniques variously lacked a high imaging speed and/or a large field of view, impeding the study of highly dynamic physiologic and pathophysiologic processes over a large region of interest. Here we report a high-speed OR-PAM system with an ultra-wide field of view, enabled by an innovative water-immersible hexagon-mirror scanner. By driving the hexagon-mirror scanner with a high-precision DC motor, the new OR-PAM has achieved a cross-sectional frame rate of 900 Hz over a 12-mm scanning range, which is 3900 times faster than our previous motor-scanner-based system and 10 times faster than the MEMS-scanner-based system. Using this hexagon-scanner-based OR-PAM system, we have imaged epinephrine-induced vasoconstriction in the whole mouse ear and vascular reperfusion after ischemic stroke in the mouse cortex in vivo, with a high spatial resolution and high volumetric imaging speed. We expect that the hexagon-scanner-based OR-PAM system will become a powerful tool for small animal imaging where the hemodynamic responses over a large field of view are of interest.

Hormonal Effects on Breast Density, Fibroglandular Tissue, and Background Parenchymal Enhancement.

Breast density, fibroglandular tissue, and background parenchymal enhancement (BPE) are recognized independent biomarkers for breast cancer risk. For this reason, reproducibility and consistency in objective assessment of these parameters at mammography (breast density) and at magnetic resonance imaging (fibroglandular tissue and BPE) are clinically relevant. However, breast density, fibroglandular tissue, and BPE are manifestations of dynamic physiologic processes and may change in response to both endogenous and exogenous hormonal stimulation. It is therefore important for the radiologist to recognize settings in which hormonal stimulation may alter the appearance of these biomarkers at imaging and to appreciate how such changes may affect risk assessment, cancer detection, and even prognosis. The purpose of this review article is therefore to review key features and means of evaluating breast density, fibroglandular tissue, and BPE at imaging; to detail how endogenous and exogenous hormonal stimuli may affect breast density, fibroglandular tissue, and BPE, potentially affecting radiologic interpretation; and, finally, to provide an update regarding current hormone treatment guidelines and indications that may result in imaging changes through hormone modulation. ©RSNA, 2018.

Histone deacetylase 6 controls Notch3 trafficking and degradation in T-cell acute lymphoblastic leukemia cells

Several studies have revealed that endosomal sorting controls the steady-state levels of Notch at the cell surface in normal cells and prevents its inappropriate activation in the absence of ligands. However, whether this highly dynamic physiologic process can be exploited to counteract dysregulated Notch signaling in cancer cells remains unknown. T-ALL is a malignancy characterized by aberrant Notch signaling, sustained by activating mutations in Notch1 as well as overexpression of Notch3, a Notch paralog physiologically subjected to lysosome-dependent degradation in human cancer cells. Here we show that treatment with the pan-HDAC inhibitor Trichostatin A (TSA) strongly decreases Notch3 full-length protein levels in T-ALL cell lines and primary human T-ALL cells xenografted in mice without substantially reducing NOTCH3 mRNA levels. Moreover, TSA markedly reduced the levels of Notch target genes, including pTα, CR2, and DTX-1, and induced apoptosis of T-ALL cells. We further observed that Notch3 was post-translationally regulated following TSA treatment, with reduced Notch3 surface levels and increased accumulation of Notch3 protein in the lysosomal compartment. Surface Notch3 levels were rescued by inhibition of dynein with ciliobrevin D. Pharmacologic studies with HDAC1, 6, and 8-specific inhibitors disclosed that these effects were largely due to inhibition of HDAC6 in T-ALL cells. HDAC6 silencing by specific shRNA was followed by reduced Notch3 expression and increased apoptosis of T-ALL cells. Finally, HDAC6 silencing impaired leukemia outgrowth in mice, associated with reduction of Notch3 full-length protein in vivo. These results connect HDAC6 activity to regulation of total and surface Notch3 levels and suggest HDAC6 as a potential novel therapeutic target to lower Notch signaling in T-ALL and other Notch3-addicted tumors.

The Translational Value of Psychophysiology Methods and Mechanisms: Multilevel, Dynamic, Personalized.

It has been nearly 15 years since Kazdin and Nock published methodological and research recommendations for understanding mechanisms of change in child and adolescent therapy. Their arguments and enthusiasm for research on mechanisms of behavior change (MOBCs) resonated across disciplines and disorders, as it shined a light on the crucial importance of understanding how and for whom treatments instigate behavior change and how therapeutic mechanisms might be extended to "situations and settings of everyday life." Initial efforts focused on how psychotherapy works and linear models, yet the use of theory to guide the study of mechanisms, and laboratory experiments to manipulate them, is broadly applicable. This article considers dynamic physiological processes that support behavior change. Specifically, it examines the utility of psychophysiological methods to measure and promote behavior change. Moreover, it embeds the baroreflex mechanism, a well-defined heart-brain feedback loop, within the theories and strategies of MOBC research. Individuals' subjective and expressive experience of change does not always align with their physiological reactivity. Thus, behavior change may be best understood when concurrently assessed across multiple biobehavioral levels. Further, behavior is initiated in the moment, often before conscious deliberation, suggesting that multilevel behavior change research may benefit from real-time methodological designs. Last, substance use trajectories vary widely, suggesting that different MOBCs are more or less active in individuals depending on their personal constituency and the functional need that their substance use serves; thus, methods that are amenable to personalized modeling approaches are important.

Autophagy promotes metastasis and glycolysis by upregulating MCT1 expression and Wnt/\u03b2-catenin signaling pathway activation in hepatocellular carcinoma cells

BackgroundAutophagy is a dynamic physiological process that can generate energy and nutrients for cell survival during stress. Autophagy can regulate the migration and invasive ability in cancer cells. However, the connection between autophagy and metabolism is unclear. Monocarboxylate transporter 1 (MCT1) plays an important role in lactic acid transport and H+ clearance in cancer cells, and Wnt/β-catenin signaling can increase cancer cell glycolysis. We investigated whether autophagy promotes glycolysis in hepatocellular carcinoma (HCC) cells by activating the Wnt/β-catenin signaling pathway, accompanied by MCT1 upregulation.MethodsAutophagic activity was evaluated using western blotting, immunoblotting, and transmission electron microscopy. The underlying mechanisms of autophagy activation on HCC cell glycolysis were studied via western blotting, and Transwell, lactate, and glucose assays. MCT1 expression was detected using quantitative reverse transcription–PCR (real-time PCR), western blotting, and immunostaining of HCC tissues and the paired adjacent tissues.ResultsAutophagy promoted HCC cell glycolysis accompanied by MCT1 upregulation. Wnt/β-catenin signaling pathway activation mediated the effect of autophagy on HCC cell glycolysis. β-Catenin downregulation inhibited the autophagy-induced glycolysis in HCC cells, and reduced MCT1 expression in the HCC cells. MCT1 was highly expressed in HCC tissues, and high MCT1 expression correlated positively with the expression of microtubule-associated protein light chain 3 (LC3).ConclusionActivation of autophagy can promote metastasis and glycolysis in HCC cells, and autophagy induces MCT1 expression by activating Wnt/β-catenin signaling. Our study describes the connection between autophagy and glucose metabolism in HCC cells and may provide a potential therapeutic target for HCC treatment.

Bone morphogenetic protein-2 associated multiple growth factor delivery for bone tissue regeneration

Administration of growth factors (GFs) and cytokines to damaged bone tissue for the purpose of bone tissue regeneration has been investigated. Among GFs and cytokines, bone morphogenetic protein-2 (BMP-2) is one of the most important stimulatory factors for enhancing the osteoblastic differentiation of progenitor cells and promoting bone formation. Co-delivery of other GFs, including vascular endothelial growth factor, fibroblast growth factor, insulin-like growth factor, and stromal cell-derived factor, with BMP-2 is known to facilitate repair and remodeling of damaged bone tissue. These GFs stimulate various cellular activities, including angiogenesis, migration, proliferation, regulation of proteoglycan level, and stem cell recruitment. Although bone repair and regeneration are dynamic and complex physiological processes involving multiple cell types and cytokines in timed healing cascade stages, BMP-2-associated delivery of dual and/or multiple GFs could promote bone tissue regeneration based on the synergistic effects of GFs compared with single GF treatment. Current engineering approaches emphasize the importance of design parameters for GF delivery systems, such as optimization of the release profiles, stabilities, and bioactivities of cargo GFs, and the physico-chemical properties of scaffold/hydrogel materials. Therefore, this review summarizes BMP-2-associated GF combinations, biological functions, and current delivery strategies utilized in bone tissue engineering for the development of feasible clinical applications.

Proteomic analysis of Bombyx mori molting fluid: Insights into the molting process

Molting is an essential biological process occurring multiple times throughout the life cycle of most Ecdysozoa. Molting fluids accumulate and function in the exuvial space during the molting process. In this study, we used liquid chromatography-tandem mass spectrometry to investigate the molting fluids to analyze the molecular mechanisms of molting in the silkworm, Bombyx mori. In total, 375 proteins were identified in molting fluids from the silkworm at 14–16h before pupation and eclosion, including 12 chitin metabolism-related enzymes, 35 serine proteases, 15 peptidases, and 38 protease inhibitors. Gene ontology analysis indicated that “catalytic” constitutes the most enriched function in the molting fluid. Gene expression patterns and bioinformatic analyses suggested that numerous enzymes are involved in the degradation of cuticle proteins and chitin. Protein-protein interaction network and activity analyses showed that protease inhibitors are involved in the regulation of multiple pathways in molting fluid. Additionally, many immune-related proteins may be involved in the immune defense during molting. These results provide a comprehensive proteomic insight into proteolytic enzymes and protease inhibitors in molting fluid, and will likely improve the current understanding of physiological processes in insect molting. Biological significanceInsect molting constitutes a dynamic physiological process. To better understand this process, we used LC-MS/MS to investigate the proteome of silkworm molting fluids and identified key proteins involved in silkworm molting. The biological processes of the old cuticle degradation pathway and immune defense response were analyzed in the proteome of silkworm molting fluid. We report that protease inhibitors serve as key factors in the regulation of the molting process. The proteomic results provide new insight into biological molting processes in insects.

Host-microbe interaction in the gastrointestinal tract.

SummaryThe gastrointestinal tract is a highly complex organ in which multiple dynamic physiological processes are tightly coordinated while interacting with a dense and extremely diverse microbial population. From establishment in early life, through to host‐microbe symbiosis in adulthood, the gut microbiota plays a vital role in our development and health. The effect of the microbiota on gut development and physiology is highlighted by anatomical and functional changes in germ‐free mice, affecting the gut epithelium, immune system and enteric nervous system. Microbial colonisation promotes competent innate and acquired mucosal immune systems, epithelial renewal, barrier integrity, and mucosal vascularisation and innervation. Interacting or shared signalling pathways across different physiological systems of the gut could explain how all these changes are coordinated during postnatal colonisation, or after the introduction of microbiota into germ‐free models. The application of cell‐based in‐vitro experimental systems and mathematical modelling can shed light on the molecular and signalling pathways which regulate the development and maintenance of homeostasis in the gut and beyond.

A new standard model for milk yield in dairy cows based on udder physiology at the milking-session level

Milk production in dairy cow udders is a complex and dynamic physiological process that has resisted explanatory modelling thus far. The current standard model, Wood’s model, is empirical in nature, represents yield in daily terms, and was published in 1967. Here, we have developed a dynamic and integrated explanatory model that describes milk yield at the scale of the milking session. Our approach allowed us to formally represent and mathematically relate biological features of known relevance while accounting for stochasticity and conditional elements in the form of explicit hypotheses, which could then be tested and validated using real-life data. Using an explanatory mathematical and biological model to explore a physiological process and pinpoint potential problems (i.e., “problem finding”), it is possible to filter out unimportant variables that can be ignored, retaining only those essential to generating the most realistic model possible. Such modelling efforts are multidisciplinary by necessity. It is also helpful downstream because model results can be compared with observed data, via parameter estimation using maximum likelihood and statistical testing using model residuals. The process in its entirety yields a coherent, robust, and thus repeatable, model.

A novel biosensor based on boronic acid functionalized metal-organic frameworks for the determination of hydrogen peroxide released from living cells

In this work, we report a durable and sensitive H2O2 biosensor based on boronic acid functionalized metal-organic frameworks (denoted as MIL-100(Cr)-B) as an efficient immobilization matrix of horseradish peroxidase (HRP). MIL-100(Cr)-B features a hierarchical porous structure, extremely high surface area, and sufficient recognition sites, which can significantly increase HRP loading and prevent them from leakage and deactivation. The H2O2 biosensor can be easily achieved without any complex processing. Meanwhile, the immobilized HRP exhibited enhanced stability and remarkable catalytic activity towards H2O2 reduction. Under optimal conditions, the biosensor showed a fast response time (less than 4s) to H2O2 in a wide linear range of 0.5–3000μM with a low detection limit of 0.1μM, as well as good anti-interference ability and long-term storage stability. These excellent performances substantially enable the proposed biosensor to be used for the real-time detection of H2O2 released from living cells with satisfactory results, thus showing the potential application in the study of H2O2-involved dynamic pathological and physiological process.

Cyclin G1 inhibits the proliferation of mouse endometrial stromal cell in decidualization

Uterine stromal cell decidualization is a dynamic physiological process in which cell proliferation, differentiation and apoptosis are orchestrated and occur in a temporal and cell-specific manner. This process is important for successful embryo implantation. Many cell-cycle regulators are involved in decidualization. The protein cyclin G1 is a unique regulator of the cell cycle with dual functions in cell proliferation. It was reported that cyclin G1 is expressed in mouse uterine stromal cells during the period of peri-implantation. To prove the function of cyclin G1 in mouse uterine stromal cells during this period, immunohistochemistry was used to stain mouse uterine tissues on days 4-8 of pregnancy. The results showed obvious spatial and temporal expression of cyclin G1 in uterine stromal cells, and that it is expressed in the cells of the primary decidual zone (PDZ) on day 5 and secondary decidual zone (SDZ) on days 6 and 7, when the stromal cells experienced active proliferation and differentiation was initiated. Applying the decidualization model of cultured primary stromal cells in vitro, we further revealed that the expression of cyclin G1 is associated with decidualization of stromal cells induced by medroxyprogesterone acetate (MPA) and estradiol-17? (E2). RNA interference was used for the knockdown of cyclin G1 in the induced decidual cells. Flow cytometry analysis indicated that the proportion of cells in the S stage was increased, and decreased in the G2/M phase. Our study indicates that cyclin G1, as a negative regulator of the cell cycle, plays an important role in the process of decidualization in mouse uterine stromal cells by inhibiting cell-cycle progression.

Acetate trafficking in the heart: carnitine acyltransferases matter

Dear Editor, The use of hyperpolarized 13C magnetic resonance to study intermediary metabolism is increasing rapidly, since it allows in vivo noninvasive investigation of dynamic metabolic and physiological processes that were previously experimentally inaccessible. A recent study published in the Journal by Koellish and colleagues used the technique to address the fate of hyperpolarized 13C‐labeled acetate in STZ‐induced diabetic rats (Koellisch et al. 2015a). While the use of this advanced technology is welcome, a basic misinterpretation of the cellular metabolic fate of acetate is apparent in the paper (Koellisch et al. 2015a). In particular, the authors have seriously misrepresented the mechanism of transfer of the …

The associations between serum biomarkers and stenosis of the coronary arteries.

Serum biochemical indices reflect dynamic physiological and pathophysiological processes within the body, the associations between these markers and the number of stenotic coronary arteries have been rarely studied. 627 healthy controls and 1,049 coronary heart disease (CHD) patients were sequentially recruited in our hospital. The association patterns between serum biochemical markers and the numbers of stenotic coronary arteries were evaluated in a cross-sectional manner. Upon binary multiple logistic regression analysis, the risk factor patterns differed by gender. Age, high-density lipoprotein cholesterol (HDL) and homocysteine (HCY) were common risk factors for CHD in both males and females. Upon ordinal multiple logistic regression analysis, age, low-density lipoprotein cholesterol (LDL) and lipoprotein (Lp) (a) increased, and HDL decreased, as the number of stenotic coronary arteries increased in male patients. Age and Lp(a) were positively associated with the number of stenotic coronary arteries and total bilirubin (TBil) was negatively associated with the number of stenotic coronary arteries in female patients. Age and Lp(a) were common risk factors positively associated with the number of stenotic coronary arteries in both male and female patients. HDL and LDL were male-specific risk factors and TBil was a female-specific risk factor for an increasing number of stenotic coronary arteries. In conclusion, serum biomarker levels correlated with the number of stenotic coronary arteries and showed gender different patterns.

Dynamic Proteomic Characteristics and Network Integration Revealing Key Proteins for Two Kernel Tissue Developments in Popcorn.

The formation and development of maize kernel is a complex dynamic physiological and biochemical process that involves the temporal and spatial expression of many proteins and the regulation of metabolic pathways. In this study, the protein profiles of the endosperm and pericarp at three important developmental stages were analyzed by isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with LC-MS/MS in popcorn inbred N04. Comparative quantitative proteomic analyses among developmental stages and between tissues were performed, and the protein networks were integrated. A total of 6,876 proteins were identified, of which 1,396 were nonredundant. Specific proteins and different expression patterns were observed across developmental stages and tissues. The functional annotation of the identified proteins revealed the importance of metabolic and cellular processes, and binding and catalytic activities for the development of the tissues. The whole, endosperm-specific and pericarp-specific protein networks integrated 125, 9 and 77 proteins, respectively, which were involved in 54 KEGG pathways and reflected their complex metabolic interactions. Confirmation for the iTRAQ endosperm proteins by two-dimensional gel electrophoresis showed that 44.44% proteins were commonly found. However, the concordance between mRNA level and the protein abundance varied across different proteins, stages, tissues and inbred lines, according to the gene cloning and expression analyses of four relevant proteins with important functions and different expression levels. But the result by western blot showed their same expression tendency for the four proteins as by iTRAQ. These results could provide new insights into the developmental mechanisms of endosperm and pericarp, and grain formation in maize.

Mouse Endometrium Temporal and Spatial Expression mRNA and MicroRNA Associated With Embryo Implantation.

Embryo implantation is a dynamic physiological process involving morphological and molecular changes in the endometrium during the pre-receptivity, receptivity, and implantation phases. A comprehensive analysis of messenger RNA (mRNA) and microRNA (miRNA) profiles during implantation will likely provide new clues to elucidate the underlying mechanisms governing embryo implantation. We characterized the mRNA and miRNA transcriptomes using next generation sequencing (NGS) of the endometrium 1 day postcoitum (dpc) and 4dpc and the implantation site (IMS) and inter-implantation (IIM) site of the endometrium on 5dpc. Real-time quantitative polymerase chain reaction was performed on selected miRNAs and their predicted target mRNAs to validate their negatively correlated expression. Statistical analysis of the data based on Gene Ontology (GO) group annotation and Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that the genes with significant expression at the IIM site were primarily involved in glucose, protein, and lipoprotein metabolism to provide energy for embryo implantation, while the genes identified at the IMS were involved in RNA functions to produce proteins in support of embryo development and trophoblast invasion. Extracellular matrix (ECM)-receptor interactions between cells and the ECM was the most remarkable event during implantation. The miRNA-mRNA interaction network unraveled the regulatory relationship between miRNAs and mRNAs. Hub miRNAs (mmu-miR-96 and mmu-miR-200b) were identified to target B-cell lymphoma 2 (Bcl-2), Kruppel-like factor 13 (Klf13), and Progesterone receptor (PGR), which are associated with the preparation of the receptive condition or the maintenance of early pregnancy.

Quantitative Redox Imaging Software

A wealth of fluorescent reporters and imaging systems are now available to characterize dynamic physiological processes in living cells with high spatiotemporal resolution. The most reliable probes for quantitative measurements show shifts in their excitation or emission spectrum, rather than just a change in intensity, as spectral shifts are independent of optical path length, illumination intensity, probe concentration, and photobleaching, and they can be easily determined by ratiometric measurements at two wavelengths. A number of ratiometric fluorescent reporters, such as reduction-oxidation-sensitive green fluorescent protein (roGFP), have been developed that respond to the glutathione redox potential and allow redox imaging in vivo. roGFP and its derivatives can be expressed in the cytoplasm or targeted to different organelles, giving fine control of measurements from sub-cellular compartments. Furthermore, roGFP can be imaged with probes for other physiological parameters, such as reactive oxygen species or mitochondrial membrane potential, to give multi-channel, multi-dimensional 4D (x,y,z,t) images. Live cell imaging approaches are needed to capture transient or highly spatially localized physiological behavior from intact, living specimens, which are often not accessible by other biochemical or genetic means. The next challenge is to be able to extract useful data rapidly from such large (GByte) images with due care given to the assumptions used during image processing. This article describes a suite of software programs, available for download, that provide intuitive user interfaces to conduct multi-channel ratio imaging, or alternative analysis methods such as pixel-population statistics or image segmentation and object-based ratio analysis. Antioxid. Redox Signal. 24, 752-762.

Vascular Magnetic Resonance Imaging in Brain Tumors During Antiangiogenic Therapy--Are We There Yet?

Abnormal tumor vasculature is a potent mediator of treatment resistance because it results in heterogeneous perfusion, hypoxia, increased interstitial fluid pressure, and incomplete penetration of cytotoxic chemotherapies. Targeting this abnormal tumor vasculature is a promising therapeutic strategy, but results with antiangiogenic drugs in brain cancer have been mixed. Vasculature's response to treatment is a dynamic physiological process that can change rapidly throughout treatment, so it requires noninvasive techniques to serially monitor these changes in order to improve outcome. We review the role of vascular magnetic resonance imaging to measure tumor response to treatment and highlight opportunities and future avenues for expanding these promising techniques.

Proteomic analysis of porcine endometrial tissue during peri-implantation period reveals altered protein abundance

In mammals, successful pregnancy depends upon the readiness of uterus for implantation, followed by correct communication between the endometrium and the developing conceptus. The objective of this study was to elucidate changes in protein abundance associated with progression of estrous cycle and pregnancy from Day 9 to Day 12. We analyzed porcine endometrial tissue lysates by 2D-DIGE. Abundance of several proteins was altered depending upon the pregnancy status of animals. MALDI-TOF/TOF was used to identify a number of these proteins. Endometrial proteins that increased from Day 9 to Day 12 of cycle included annexin A4, beta-actin, apolipoprotein, ceruloplasmin and afamin. Changes in protein abundances associated with conceptus secreted factors, including haptoglobin, prolyl-4-hydroxylase, aldose-reductase and transthyretin, were also observed. Functional analysis revealed that endometrial proteins with altered abundance on Day 12 irrespective of the reproductive status were related to growth and remodeling, acute phase response and free radical scavenging, whereas transport and small molecule biochemistry were the functions activated in the pregnant endometrium as compared to the cyclic endometrium. These data provide information on dynamic physiological processes associated with uterine endometrial function of the cyclic and pregnant endometrium during period of maternal recognition of pregnancy in pigs and may potentially demonstrate a protein profile associated with successful pregnancy. Biological significanceIn pigs, the fertility rates are generally very high but the early embryonic loss that occurs during the second and third weeks of gestation critically affects the potential litter size. Temporal changes that take place in the uterine environment during the period of early pregnancy in pigs and a cross-talk between the uterus and the embryo play an important role in embryonic survival and successful pregnancy. A better understanding of the molecular changes associated with these processes will pave way for understanding of endometrial functions and help towards increasing embryo survival. In this study, we present a 2D-DIGE based analysis of changes in porcine endometrial proteome that are associated with progression of cycle and progression of pregnancy. The network analysis of the results clearly revealed the pathways that are involved in rendering the endometrium receptive to the presence of embryo and also the changes that are result of molecular communication between the endometrium and the conceptuses. This comprehensive identification of proteomic changes in the porcine endometrium could be a foundation for targeted studies of proteins and pathways potentially involved in abnormal endometrial receptivity, placentation and embryo loss.

Coping strategies during and after spaceflight: Data from retired cosmonauts

Coping is a dynamic physiological and psychological process in response to perceived environmental stress that functions to restore physiological homeostasis and reduce negative affect [1]. Thematic content analysis was employed for references to 13 well-established coping strategies in interviews with 20 retired long-duration male cosmonauts. As in previous research with other space samples [2,3] the retired cosmonauts mentioned Problem-Oriented strategies more frequently than Emotion-Oriented ones. In the present sample, Seeking Social Support, Planful Problem Solving and Endurance/Obedience/Effort were the top three most mentioned coping strategies. Cosmonauts who had spent more than a year in space, compared to those who had spent less than a year, mentioned using Planful Problem Solving more as they recalled their career and retirement. Examining changes over time, spaceflight had a positive effect on Accepting Responsibility. Endurance/Obedience/Effort steadily decreased over time, while we found an inverted-U pattern for Distancing and Self-Control. Additional results in relation to other astronaut samples and the relationship between coping and post-flight growth are discussed.

Tracking the sleep onset process: an empirical model of behavioral and physiological dynamics.

The sleep onset process (SOP) is a dynamic process correlated with a multitude of behavioral and physiological markers. A principled analysis of the SOP can serve as a foundation for answering questions of fundamental importance in basic neuroscience and sleep medicine. Unfortunately, current methods for analyzing the SOP fail to account for the overwhelming evidence that the wake/sleep transition is governed by continuous, dynamic physiological processes. Instead, current practices coarsely discretize sleep both in terms of state, where it is viewed as a binary (wake or sleep) process, and in time, where it is viewed as a single time point derived from subjectively scored stages in 30-second epochs, effectively eliminating SOP dynamics from the analysis. These methods also fail to integrate information from both behavioral and physiological data. It is thus imperative to resolve the mismatch between the physiological evidence and analysis methodologies. In this paper, we develop a statistically and physiologically principled dynamic framework and empirical SOP model, combining simultaneously-recorded physiological measurements with behavioral data from a novel breathing task requiring no arousing external sensory stimuli. We fit the model using data from healthy subjects, and estimate the instantaneous probability that a subject is awake during the SOP. The model successfully tracked physiological and behavioral dynamics for individual nights, and significantly outperformed the instantaneous transition models implicit in clinical definitions of sleep onset. Our framework also provides a principled means for cross-subject data alignment as a function of wake probability, allowing us to characterize and compare SOP dynamics across different populations. This analysis enabled us to quantitatively compare the EEG of subjects showing reduced alpha power with the remaining subjects at identical response probabilities. Thus, by incorporating both physiological and behavioral dynamics into our model framework, the dynamics of our analyses can finally match those observed during the SOP.