PACAP and VIP have prominent effects on cardiac function in several species, but little is known about their influence on the murine heart. Accordingly, we evaluated the expression of PACAP/VIP receptors in mouse heart and the response of isolated atria to peptide agonists. Quantitative PCR demonstrated that PAC1, VPAC1, and VPAC2 receptor mRNAs are present throughout the mouse heart. Expression of all three receptor transcripts was low, PAC1 being the lowest. No regional differences in expression were detected for individual receptor mRNAs after normalization to L32. Pharmacological effects of PACAP-27, VIP, and the selective PAC1 agonist maxadilan were evaluated in isolated, spontaneously beating atria from C57BL/6 mice of either sex. Incremental additions of PACAP-27 at 1 min intervals caused a concentration-dependent tachycardia with a log EC50=-9.08±0.15 M (n=7) and a maximum of 96.3±5.9% above baseline heart rate. VIP and maxadilan also caused tachycardia but their potencies were about two orders of magnitude less. Increasing the dosing interval to 5 min caused a leftward shift of the concentration-response curve to maxadilan but no changes in the curves for PACAP-27 or VIP. Under this condition, neither the potency nor the efficacy of maxadilan differed from those of PACAP-27. Neither PACAP-27 nor maxadilan caused tachyphylaxis, and maximal responses to maxadilan were maintained for at least 2 h. We conclude that all three VIP/PACAP family receptors are expressed by mouse cardiac tissue, but only PAC1 receptors mediate positive chronotropic responses to PACAP-27 and VIP.

The prevalence and long-term trends of isolated systolic hypertension (ISH) among untreated adults have not been reported. Data from 24,653 participants aged ≥18 years were selected from the National Health and Nutrition Examination Survey 1999-2010. The prevalence and 95% confidence intervals (CIs) of untreated ISH were estimated by conducting the independent survey t-test. The prevalence of untreated ISH was 9.4% and decreased from 10.3% in 1999-2004 to 8.5% in 2005-2010 (P =.00248). Old persons, females, and non-Hispanic blacks had higher prevalence of untreated ISH. Compared with 1999-2004, the prevalence of untreated ISH in 2005-2010 decreased among older (33.6%; 95% CI, 30.9%-36.3% vs. 25.1%; 95% CI, 22.7%-27.5%) and female individuals (8.3%; 95% CI, 7.5-9.2% vs. 11.4%; 95% CI, 10.4-12.3%). The stratified prevalence of untreated ISH declined in 2005-2010 (vs. 1999-2004) for older non-Hispanic whites (24.6% vs. 32.8%; P <.0001) and blacks (27.7% vs. 40.8%; P =.0013), non-Hispanic white females (7.5% vs. 10.8%; P <.0001), older individuals with higher education (21.0% vs. 30.6%; P =.0024), and females with lower education (10.1% vs. 13.1%; P =.006). Untreated ISH is more prevalent in older adults and females. Significant decreases in untreated ISH prevalence over time among these groups suggest that public health measures and/or treatment patterns are trending in the right direction.

The hypothesis that irreversible ischemic injury is related to sub-sarcolemmal blebbing and an inherent osmotic fragility of the blebs was tested by subjecting isolated control and ischemically preconditioned (IPC) or calyculin A (CalA)-pretreated (protected) rabbit cardiomyocytes to ischemic pelleting followed by resuspension in 340, 170 or 85 mosmol medium containing trypan blue. At time points from 0-240 min, osmotic fragility was assessed by the percentage of trypan blue permeable cells. Membrane blebs were visualized with India ink preparations. Bleb formation, following acute hypo-osmotic swelling, developed by 75 min and increased with longer periods of ischemia. Osmotic fragility developed only after 75 min. Cells resuspended in 340 mosmol media did not form blebs and largely retained the ability to exclude trypan blue, even after 240 min ischemia. Although the latent tendency for osmotic blebbing preceded the development of osmotic fragility, most osmotically fragile cells became permeable without evident sarcolemmal bleb formation. The onset of osmotic fragility was delayed in protected cells, but protection did not reduce the bleb formation. It is concluded that blebbing and osmotic fragility are independent manifestations of ischemic injury. The principal locus of irreversible ischemic injury and the protection provided by IPC may lie within the sarcolemma rather than at sarcolemmal attachments to underlying adherens junctions.

The bidirectional link between insufficient sleep and the distress related to a parasomnia known as isolated sleep paralysis (ISP) might lead to chronic health effects. The impact of fear-ridden hallucinations related to this REM sleep disorder can be both distressful and embarrassing for individuals often resulting in a reticence to seek help. This quantitative study was guided by a biopsychosocial approach with an integrated theoretical framework. One aim of the study was to determine if fear parameters of ISP (low and high) differ when considering psychosocial factors and sleep quality, based on the Dysfunctional Beliefs and Attitudes About Sleep Scale, the Social Phobia Inventory, the Locus of Control (LOC) subscales, and the Pittsburg Sleep Quality Inventory. Predictive associations between psychosocial factors and subjective sleep quality (SSQ) were also investigated. Retrospective online data from a sample of 159 participants ages 18 and over were analyzed via MANOVA, multiple regression, and independent samples t-tests. Findings from the MANOVA were significant and showed that participants who experience ISP with more fear scored higher on two measures, external other LOC and social phobia. The MANOVA regarding differences in SSQ in relation to psychosocial variables were not significant, and independent sample t-tests did not differentiate fear parameters for DBAS and SSQ (poor sleep was found for both parameters). Providers of therapeutic treatments should take factors of social phobia and external other LOC into account with regards to poor sleep quality for those distressed by ISP. Sleep quality assessments might benefit those who are afraid to disclose about ISP sleep distress, as long term poor sleep can place some at risk for negative health outcomes.

Chemistry is the study of materials and the changes that materials undergo. One can tune the properties of the known materials and design the novel materials with desired properties knowing what is responsible for the chemical reactivity, structure, and stability of those materials. The unified chemical bonding theory could address all these questions, but we do not have one available yet. The most accepted general theory of chemical bonding was proposed by Lewis in 1916, though Lewis’s theory fails to explain the bonding in materials with delocalized electron density such as sub-nano and nanoclusters, as well as aromatic organic and organometallic molecules. The dissertation presents a set of projects that can be considered the steps towards the development of the unified chemical bonding theory by extending the ideas of Lewis. The dissertation also presents the studies of the properties of multiply charged anions, which tend to undergo Coulomb explosion in the isolated state and release the excess energy stored in them. It is shown how the properties of multiply charged anions can be tuned upon changing the chemical identity of the species or interaction with solvent molecules. Our findings led to the discovery of a new long-lived triply charged anionic species, whose metastability was explained by the existence of a repulsive Coulomb barrier. We also proposed two ways to restore high symmetry of compounds by suppression of the pseudo Jahn-Teller effect, which could lead to the design of new materials with the restored symmetry and therefore the novel properties.

The purpose of this study was to test the effectiveness of the readiness assurance process of team-based learning (TBL) in virtually isolated settings. Many Internet sites offer courses for adults to use on their own without access to mentors or other learners. However, educational theory suggests that people learn better with others than by themselves. The focus of this investigation was whether the inclusion of the readiness assurance process would increase participants’ levels of learning based on Bloom’s revised taxonomy within the limits of virtual isolation. In this study an experimental pretest-posttest design was employed. Using a 2- day mini-course about listening in marriage, 117 participants were randomly assigned to three groups. In the TBL group, married couples worked together following the principles of the readiness assurance process. In the independent group, one spouse from a marriage worked alone, also following the principles of the readiness assurance process. In the baseline group, one spouse from a marriage took the pretest and posttest only. The first posttest, called posttest-L, measured lower levels of learning (remembering and understanding). The second posttest, called posttest-D, measured deeper learning (applying and evaluating). Using ANCOVA with the pretests as the covariates, results showed a statistically significant difference in learning gains between the TBL group and the independent group for lower levels of learning (ES = .39). However, statistical significance was not achieved for deeper learning. Moreover, TBL scores and independent scores were no different from the baseline scores for measures of deeper learning. Along with explanations for these results, limitations of the study are described and suggestions for future research are offered.

Sediment on Cay Sal Bank (CSB) is characterized by its coarse-grain size, poor sorting, predominance of skeletal fragments, and relatively depleted d18O isotope values. CSB is an incipiently drowned platform in close proximity to the Great Bahama Bank (GBB), a carbonate platform which is not incipiently drowned and characterized by fine-grained, non-skeletal sediment. The GBB has locally well-developed oolitic grainstone facies and coral reef margins, which are both lacking on CSB. Platform-top water depths on the GBB are typically 10 m or less, but CSB depth ranges between 7 and 30 m. CSB is devoid of mud, whereas mud-supported depositional texture on GBB comprises 28% of the dataset. Dominant non-skeletal grains are grapestones and pelletoids, and the latter display evidence of micritization. Non-skeletal types on GBB are primarily grapestones and ooids. Surficial sediments from both platforms are primarily composed of aragonite, but high-magnesium calcite is slightly more prevalent on CSB. Similar to other incipiently drowned platforms in the Caribbean, CSB has been subject to rapid Holocene flooding. Common features between these three platforms are a thin sedimentary cover, a dominance of Halimeda plates, and micritized cryptocrystalline grains. Increased nutrient levels have been shown to be related to platform drowning as well as the reduction of coral and algal growth on Serranilla Bank, but rapid Holocene flooding has been more likely for CSB, and appears to be in the second of a three-stage drowning process, ultimately culminating in carbonate platform “turn off”, preventing further carbonate and reef development at the level of GBB.

La mitochondrie est restée longtemps cantonnée au rôle de centrale énergétique cellulaire. On sait désormais qu'elle est aussi la principale source d'espèces réactives oxygénées, impliquées dans le stress oxydant et la signalisation inter- cellulaire. Le dérèglement de l'activité mitochondriale est ainsi susceptible d'être la cause de l'apparition et de la progression de maladies associées au vieillissement, comme le cancer et les maladies neurodégénératives. Dans le cadre de la leucémie aiguë myéloïde, des études menées par l'équipe dirigée par Jean-Emmanuel Sarry du Centre de Recherche en Cancérologie de Toulouse, ont montré qu'il est possible de sensibiliser les cellules jusqu'alors résistantes à la chimiothérapie, en ciblant préalablement la fonction mitochondriale. C'est dans ce contexte que s'inscrit le sujet de cette de thèse, portant sur la conception et la réalisation de micro-capteurs électrochimiques dédiées à l'analyse du métabolisme mitochondrial, à l'échelle de la mitochondrie isolée. La fabrication des microsystèmes s'est déroulée dans la salle blanche du Laboratoire d'Analyse et d'Architecture des Systèmes de Toulouse, sous l'encadrement des chercheurs Jérôme Launay et Pierre Temple-Boyer, spécialisés dans la conception de capteurs pour la détection d'espèces en phase liquide. Finalement, un système complet assurant le couplage à la microscopie et à la gestion des fluides a été fabriqué, validé, et breveté. Les résultats obtenus nous permettent d'envisager l'analyse à l'échelle de la mitochondrie unique par une approche parallélisée, ce qui n'a encore jamais été réalisé. / The role of mitochondria have been restricted to oxidative phosphorylation for a long time. Now it is clear that they are also the main sources of reactive oxygen species, implied in oxidative stress and cell-to-cell signaling. Thus, mitochondrial malfunction is potentially the cause of the appearance and the progression of diseases linked to ageing like cancers and neurodegenerative troubles. In the frame of acute myeloid leukemia, studies governed by Jean-Emmanuel Sarry of the Cancer Research Center of Toulouse, showed that it is possible to improve the efficacy of current chemotherapies by targeting mitochondria's function. In this context, the objective of the thesis presented here consist in the design and the manufacturing of electrochemical micro-sensors, dedicated to the analysis of the metabolic activity of isolated mitochondria. The manufacturing occurred in the clean room facilities of the Laboratory for Analysis and Architecture of Systems of Toulouse under the supervision of Jérôme Launay and Pierre Temple-Boyer, researchers specialized in the development of solutions aiming the detection of species diluted in solution. Finally, a complete system ensuring the coupling with microscopy and fluidics have been realized, validated, and patented. The results obtained allow us to consider the analysis at the scale of the single mitochondrion with a parallelized approach, thing that have never been made.

The environmental and psychosocial adversity inherent in remote polar locales has historically been framed in pathological terms. However, a burgeoning body of evidence suggests that stressful conditions across isolated, confined, and extreme (ICE) environments may elicit positive growth outcomes as well. The purpose of this cross-sectional, retrospective study was to assess the incidence and correlates of PostExpedition Growth (PEG) in returned Antarctic expeditioners. The prevalence of five specific personal growth indicators – ‘new opportunities,’ ‘relating to others,’ ‘personal strength,’ ‘spiritual change,’ and ‘appreciation of life’ – along with individual and group variables that have been associated with growth in trauma-exposed populations (i.e., coping, mindfulness, personality traits, personal value priorities, adverse childhood experiences, and expedition/experience specific variables) were examined using a mixed methods approach. Quantitative results indicate a moderate, positive association between proactive coping and appreciation of life, as well as between universalism (i.e., a sense of harmony or oneness with humanity and the natural world), new possibilities, and appreciation of life. Qualitative findings provide a more nuanced understanding of the five dimensions of PEG and underscore the emergence of a sixth dimension, an enhanced relationship with nature. Further research is needed to illuminate knowledge gaps in ICE environment research, and to help identify potential countermeasures for individuals and groups faced with comparable adversity factors in their immediate environments (i.e., within the current context of COVID-19). A deeper understanding of PEG in ICE environments – as well as promotive factors that strengthen positive outcomes – will serve to inform the development of countermeasures to mitigate health and wellbeing risks following exposure to isolation and confinement in extreme environments. / Graduate / 2022-09-29

京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第18444号 / 理博第4004号 / 新制||理||1577(附属図書館) / 31322 / 京都大学大学院理学研究科数学・数理解析専攻 / (主査)教授 加藤 毅, 教授 堤 誉志雄, 教授 小野 薫 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DFAM