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Induced pluripotent stem cell derived cardiomyocytes (iPSC-CM) have the potential to transform regenerative cardiac medicine and the modelling of cardiac disease. This is of particular importance in the context of diabetic cardiomyopathy where diabetic individuals exhibit reduced cardiac diastolic contractile performance in the absence of vascular disease, significantly contributing towards high cardiovascular morbidity. In this study, the capacity of iPSC-CM to act as a novel cellular model of cardiomyocytes was assessed. The diabetic phenotype is characterised by insulin resistance, therefore there was a specific focus upon metabolic parameters. Despite expressing crucial insulin signalling intermediates and relevant trafficking proteins, it was identified that iPSC-CM do not exhibit insulin-stimulated glucose uptake. iPSC-CM are spontaneously contractile however contraction mediated uptake was not found to mask any insulin response. The fundamental limitation identified in these cells was a critical lack of expression of the insulin sensitive glucose transporter GLUT4. Using comparative immunoblot analysis and the GLUT-selective inhibitor BAY-876 to quantify expression of these transporters, we show that iPSC-CM express high levels of GLUT1 and low levels of GLUT4 compared to primary cardiomyocytes and cultured adipocytes. Interventions to overcome this limitation were unsuccessful. We suggest that the utility of iPSC-CMs to study cardiac metabolic disorders may be limited by their apparent foetal-like phenotype. [ABSTRACT FROM AUTHOR]

An alternative method of deriving the values of the observables of atomic systems is presented. Rather than using operators and eigenvalues the local variables method uses the continuity equation together with current densities derived from wave functions that are solutions of the Dirac or Pauli equation. The method is applied to atomic hydrogen using the usual language of quantum mechanics rather than that of geometric algebra with which the method is often associated. The picture of the atom that emerges is one in which the electron density as a whole is rotating about a central axis. The results challenge some assumptions of conventional quantum mechanics. Electron spin is shown to be a property of the dynamical motion of the electron and not an intrinsic property of the electron, the ground state of hydrogen is shown to have an orbital angular momentum of h, and excited states are shown to have angular momenta that are different from the eigenvalues of the usual quantum mechanical operators. The uncertainty relations are found not to be applicable to the orthogonal components of the angular momentum. No double electron spin gyromagnetic ratio is required to account for the observed magnetic moments, and the behavior of the atom in a magnetic field is described entirely in kinetic terms. [ABSTRACT FROM AUTHOR]

Fontane's theory of the novel is more sophisticated and owes less to the ideas of the Programmatic Realists Julian Schmidt and Otto Ludwig than is generally thought. He rejects tendentiousness, undifferentiated speech, and schematic characterization, believing the novel should show a 'representation of interests' embodied in characters who blend individual and generic traits. And while Schmidt and Ludwig advocate transfiguration of subject-matter as a way of avoiding 'ugliness' and yielding morally prescriptive 'middle-class' fiction, for Fontane it is a way of shaping the social and cultural heterogeneity of reality, ugly and beautiful, without subordinating it to a single world-view. [ABSTRACT FROM AUTHOR]

The romance between Botho and Lene in this novel is founded on a ‘lover's discourse’ (Roland Barthes), that is to say an escape from the description of human behaviour in conventional and impoverishing categories. However, the lovers’ view of each other as ‘special’ and ‘indefinable’ is undermined by other characters, who consciously and unconsciously reintegrate them and their experiences into the readily intelligible template of an officer's premarital affair with a lower-class girl. It is this, and not social pressures per se, that destroys their love. Moreover, Botho himself unwittingly introduces this platitude into his relationship with Lene, thereby destroying it from within. Indeed his initial attraction to her, which he claims is founded on her ‘difference’, is in fact based on seeing in her the artlessness of a simple, unspoilt girl – a stereotype not borne out by Lene's conduct and in any case false to the basis of their intimacy in the non-defining lover's discourse. After his break with Lene and return to the world of platitude, Botho comes to share its desire to reintegrate those who see themselves as living outside its confines, as can be seen from his treatment of his friend Rexin. [ABSTRACT FROM AUTHOR]

Examines Theodor Fontane's novel "Unwiederbringlich," with reference to an analysis made by critic Mikhail Bakhtin. Significance of the novel's characters in displaying discourses; Details of the plot.

Critiques Fontane's book 'Der Stechlin'. Central ideas of the novel; Problems in the presentation of teh book's ideas.

Sp3 is a ubiquitously expressed transcription factor closely related to Sp1 (specificity protein 1). We have disrupted the mouse Sp3 gene by homologous recombination. Sp3-deficient embryos are growth retarded and invariably die at birth of respiratory failure. The cause for the observed breathing defect remains obscure since only minor morphological alterations were observed in the lung, and surfactant protein expression is indistinguishable from that in wild-type mice. Histological examinations of individual organs in Sp3-/- mice show a pronounced defect in late tooth formation. In Sp3 null mice, the dentin/enamel layer of the developing teeth is impaired due to the lack of ameloblast­specific gene products. Comparison of the Sp1 and Sp3 knockout phenotype shows that Sp1 and Sp3 have distinct functions in vivo, but also suggests a degree of functional redundancy. [ABSTRACT FROM AUTHOR]

Focuses on the allegory of reading depicted in the book `Cecile,' by Theodor Fontane. Accounts on the treatments of the category of character in narrative fiction; Structuralist and post-structuralist view on textuality of literary character; Details on the participatory activity of readers in the aspect of the narrative text.

The regulated translocation of the glucose transporter, GLUT4, to the surface of adipocytes and muscle is a key action of insulin. This is underpinned by the delivery and fusion of GLUT4-containing vesicles with the plasma membrane. Recent studies have revealed that a further action of insulin is to mediate the dispersal of GLUT4 molecules away from the site of GLUT4 vesicle fusion with the plasma membrane. Although shown in adipocytes, whether insulin-stimulated dispersal occurs in other cells and/or is exhibited by other proteins remains a matter of debate. Here we show that insulin stimulates GLUT4 dispersal in the plasma membrane of adipocytes, induced pluripotent stem cell-derived cardiomyocytes and HeLa cells, suggesting that this phenomenon is specific to GLUT4 expressed in all cell types. By contrast, insulin-stimulated dispersal of TfR was not observed in HeLa cells, suggesting that the mechanism may be unique to GLUT4. Consistent with dispersal being an important physiological mechanism, we observed that insulin-stimulated GLUT4 dispersal is reduced under conditions of insulin resistance. Adipocytes of different sizes have been shown to exhibit distinct metabolic properties: larger adipocytes exhibit reduced insulin-stimulated glucose transport compared to smaller cells. Here we show that both GLUT4 delivery to the plasma membrane and GLUT4 dispersal are reduced in larger adipocytes, supporting the hypothesis that larger adipocytes are refractory to insulin challenge compared to their smaller counterparts, even within a supposedly homogeneous population of cells. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (KOA) is an age-dependent disease dominantly affected by mechanical loading. Balancing the forces acting on the medial knee compartment has been the focus of KOA interventions. This pilot study investigated the effects of functional electrical stimulation (FES) of the biceps femoris and lateral gastrocnemius on reducing peak knee adduction moment (pKAM) in healthy adults and individuals with medial KOA while stepping on an instrumented elliptical system. Sixteen healthy individuals and five individuals with medial KOA stepped on the robotic stepping system, which measured footplate-reaction forces/torques and ankle kinematics and calculated 3-D knee moments in real time using inverse dynamics. Participants performed four different tasks: regular stepping without FES as the baseline condition, stepping with continuous FES of the lateral gastrocnemius (FESLG), biceps femoris (FESBF), and simultaneous FES of both lateral gastrocnemius and biceps femoris (FESLGBF), throughout the elliptical cycle. The 3-D knee moments, tibia kinematics, and footplate-reaction forces were compared between the baseline and the three FES stepping conditions. Healthy participants demonstrated lower pKAM during each of the three FES conditions compared to baseline (FESLG (p = 0.041), FESBF (p = 0.049), FESLGBF (p = 0.048)). Participants with KOA showed a trend of lower pKAM during FES, which was not statistically significant given the small sample available. Incorporating elliptical + FES as a training strategy is feasible and may help to enhance selective force generation of the targeted muscles and reduce the medial knee compartment loading. [ABSTRACT FROM AUTHOR]

Examines the relationship between political party systems and issue dimensions through a comparative analysis in Israel. Significance of the number of parties and their strengths in characterizing party systems; Issue dimensions of partisan conflict; Correlation of political dimensions in society and parties.

Cardiac cellular responses to acute exercise remain undescribed. We present a model for mimicking acute aerobic endurance exercise to freshly isolated cardiomyocytes by evoking exercise‐like contractions over prolonged periods of time with trains of electrical twitch stimulations. We then investigated immediate contractile, Ca2+, and metabolic responses to acute exercise in perfused freshly isolated left ventricular rat cardiomyocytes, after a matrix‐design optimized protocol and induced a mimic for acute aerobic endurance exercise by trains of prolonged field twitch stimulations. Acute exercise decreased cardiomyocyte fractional shortening 50%–80% (p <.01). This was not explained by changes to intracellular Ca2+ handling (p >.05); rather, we observed a weak insignificant Ca2+ transient increase (p =.11), while myofilament Ca2+ sensitivity increased 20%–70% (p <.05). Acidic pH 6.8 decreased fractional shortening 20%–70% (p <.05) because of 20%–30% decreased Ca2+ transients (p <.05), but no difference occurred between control and acute exercise (p >.05). Addition of 1 or 10 mM La− increased fractional shortening in control (1 mM La−: no difference, p >.05; 10 mM La−: 20%–30%, p <.05) and acute exercise (1 mM La−: 40%–90%, p <.01; 10 mM La−: 50%–100%, p <.01) and rendered acute exercise indifferent from control (p >.05). Intrinsic autofluorescence showed a resting NADstate of 0.59 ± 0.04 and FADstate of 0.17 ± 0.03, while acute exercise decreased NADH/FAD ratio 8% (p <.01), indicating intracellular oxidation. In conclusion, we show a novel approach for studying immediate acute cardiomyocyte responses to aerobic endurance exercise. We find that acute exercise in cardiomyocytes decreases contraction, but Ca2+ handling and myofilament Ca2+ sensitivity compensate for this, while acidosis and reduced energy substrate and mitochondrial ATP generation explain this. Significance statement: Endurance exercise is taxing to the heart and it leads to cardiac exhaustion and fatigue with contractile impairment. However, a mechanism for this has not yet been found, at least partly because this has been impossible to study in heart muscle cells (cardiomyocytes, where contraction occurs) since the process of ascertaining cells after physical exercise in and of itself uncouples the exercise effect. We took a different approach and came up with a novel protocol; instead of exercising animals and then preparing cells, we first prepared cells and then supplied exercise to the cell. This showed that the reduced contractile function during and immediately after exercise was caused by acidosis and metabolic impairments, while Ca2+ lessened the dys‐contraction. [ABSTRACT FROM AUTHOR]

The article discusses the potential of transmissible vaccines (TVs) to revolutionize public health, wildlife conservation, and animal welfare by immunizing wildlife populations at scales necessary to interrupt pathogen transmission. Topics include vaccine safety criteria, staged development with established checkpoints, and equitable partnerships with international governance.