Health Literacy: Determinant of Health or Status Indicator?

An increasing burden of preventable diseases, persistent health inequalities, and new infectious diseases call for responsible citizens to take care of their health and health decisions. Therefore, health literacy appears to be a promising concept to foster better health behaviours. However, health literacy is a broad concept and interventions targeting health literacy show mixed results. Against this background, this thesis’ aim is twofold. First, it explores health literacy as determinant of health. Secondly, and entwined with the first, it aims to provide a better conceptual understanding of health literacy. For the empirical analyses, data from Swiss male young adults were used. Three studies were carried out, each with different statistical approaches, to obtain a better understanding of the pathways between health literacy, its contextual factors, and favourable health outcomes. The studies’ results do not support the notion that health literacy – as a distinct phenomenon – has a causal importance to health. Rather, the findings suggest that health literacy should be acknowledged as a multifactorial phenomenon with many different dimensions, dependencies, and conversion factors. The latter either amplify or impede health literacy’s positive effects on health. Finally, the results indicate that potential health literacy interventions are likely to only address a selection of these aspects and may have limited or no benefit on health depending on personal and contextual factors. This umbrella text also presents conceptual work that could not be presented in the three journal articles. The health literacy staircase model (HL-SM) introduced here, describes the embeddedness of health literacy in contextual factors and addresses the complex path from knowledge to decision-making and decision-implementation. Further, it discusses several shortcomings of previous health literacy definitions and conceptualizations that are presented in the introduction section. The HL-SM was developed after the second publication and inspired the third study that explores the role of decision-making ability as a mediator from health literacy to health. This thesis calls for more health literacy research focussing on informed health decision-making in everyday contexts. Further, health literacy research is urged to give more emphasis to the concept’s boundaries, dependencies, and conversion factors. Without paying attention to prevailing contextual factors, there is considerable danger towards an individualization of a primarily societal problem

Electronic structure of (LaNiO3_3)2_2/(LaAlO3_3)N_N heterostructures grown along [111]

The electronic structure of a LaNiO$_3$ bilayer grown along the [111] direction and confined between insulating layers of LaAlO$_3$ is theoretically investigated using a combination of first principle calculations and effective multi-orbital lattice models. The LDA band structure is well reproduced by a tight-binding model for the Ni-$e_g$ orbitals defined on the buckled honeycomb lattice. We highlight peculiar properties of this model which include almost flat bands as well as linear and quadratic band crossing points. The effect of local correlations is discussed within the LDA$+U$ scheme and within the Hartree-Fock approximation for interacting multi-orbital lattice models. Over a wide range of interaction parameters we find that a ferromagnetic phase is energetically favored. We discuss the possibility of additional orbital order which could stabilize a spontaneous Chern insulator with chiral edge modes or a staggered orbital phase with a $\sqrt{3}\times\sqrt{3}$ reconstruction of the unit cell. By studying an interacting nickel-oxygen lattice model we find that the stability of these orbitally ordered phases also depends on the value of the charge-transfer energy. Controlling the charge-transfer energy might therefore be an important step towards engineering exotic electronic phases in certain classes of oxide heterostructures.Comment: 11 pages, 11 figure

Quality control for terms and definitions in ontologies and taxonomies

BACKGROUND: Ontologies and taxonomies are among the most important computational resources for molecular biology and bioinformatics. A series of recent papers has shown that the Gene Ontology (GO), the most prominent taxonomic resource in these fields, is marked by flaws of certain characteristic types, which flow from a failure to address basic ontological principles. As yet, no methods have been proposed which would allow ontology curators to pinpoint flawed terms or definitions in ontologies in a systematic way. RESULTS: We present computational methods that automatically identify terms and definitions which are defined in a circular or unintelligible way. We further demonstrate the potential of these methods by applying them to isolate a subset of 6001 problematic GO terms. By automatically aligning GO with other ontologies and taxonomies we were able to propose alternative synonyms and definitions for some of these problematic terms. This allows us to demonstrate that these other resources do not contain definitions superior to those supplied by GO. CONCLUSION: Our methods provide reliable indications of the quality of terms and definitions in ontologies and taxonomies. Further, they are well suited to assist ontology curators in drawing their attention to those terms that are ill-defined. We have further shown the limitations of ontology mapping and alignment in assisting ontology curators in rectifying problems, thus pointing to the need for manual curation

The calcium sensor Copine-6 regulates spine structural plasticity and learning and memory

Hippocampal long-term potentiation (LTP) represents the cellular response of excitatory synapses to specific patterns of high neuronal activity and is required for learning and memory. Here we identify a mechanism that requires the calcium-binding protein Copine-6 to translate the initial calcium signals into changes in spine structure. We show that Copine-6 is recruited from the cytosol of dendrites to postsynaptic spine membranes by calcium transients that precede LTP. Cpne6 knockout mice are deficient in hippocampal LTP, learning and memory. Hippocampal neurons from Cpne6 knockouts lack spine structural plasticity as do wild-type neurons that express a Copine-6 calcium mutant. The function of Copine-6 is based on its binding, activating and recruiting the Rho GTPase Rac1 to cell membranes. Consistent with this function, the LTP deficit of Cpne6 knockout mice is rescued by the actin stabilizer jasplakinolide. These data show that Copine-6 links activity-triggered calcium signals to spine structural plasticity necessary for learning and memory

Flexibility utilisation of municipalities to optimally use the electricity grid

Electrifying the energy system with heat pumps and electric vehicles is a strategy of many countries to reduce CO2 emissions. Large electrification, however, poses several new challenges for the electricity system, particularly in combination with a simultaneous substitution of nuclear power plants by volatile renewables such as photovoltaics. The increasing consumption of electricity and the growing number of installed photovoltaic systems are pushing the existing electrical grid to its limits. Today’s grid must be expanded with smart controllers and their components regulated. For this purpose, an understanding of flexible participants such as boilers, heat pumps and electric vehicles, and new production facilities such as photovoltaic systems must be built up. The aim of this poster is to present municipality flexibility potential and the proposed energy scheduler for flexible loads shifting to the optimal place, considering defined restrictions. The results are used to calculate the new parameters for the locally installed model predictive controllers, which control appliances according to the scheduler setpoints, to optimally utilise flexibilities for peak shaving

The immune receptor Tim-3 acts as a trafficker in a Tim-3/galectin-9 autocrine loop in human myeloid leukemia cells

The immune receptor Tim-3 is often highly expressed in human acute myeloid leukemia (AML) cells where it acts as a growth factor and inflammatory receptor. Recently, it has been demonstrated that Tim-3 forms an autocrine loop with its natural ligand galectin-9 in human AML cells. However, the pathophysiological functions of Tim-3 in human AML cells remain unclear. Here, we report for the first time that Tim-3 is required for galectin-9 secretion in human AML cells. However, this effect is cell-type specific and was found so far to be applicable only to myeloid (and not, for example, lymphoid) leukemia cells. We concluded that AML cells might use Tim-3 as a trafficker for the secretion of galectin-9 which can then be possibly used to impair the anticancer activities of cytotoxic T cells and natural killer (NK) cells

Neuronal LRP4 regulates synapse formation in the developing CNS

The low-density lipoprotein receptor-related protein 4 (LRP4) is essential in muscle fibers for the establishment of the neuromuscular junction. Here, we show that LRP4 is also expressed by embryonic cortical and hippocampal neurons, and that downregulation of LRP4 in these neurons causes a reduction in density of synapses and number of primary dendrites. Accordingly, overexpression of LRP4 in cultured neurons had the opposite effect inducing more but shorter primary dendrites with an increased number of spines. Transsynaptic tracing mediated by rabies virus revealed a reduced number of neurons presynaptic to the cortical neurons in which LRP4 was knocked down. Moreover, neuron-specific knockdown of LRP4 by in utero electroporation of LRP4 miRNA in vivo also resulted in neurons with fewer primary dendrites and a lower density of spines in the developing cortex and hippocampus. Collectively, our results demonstrate an essential and novel role of neuronal LRP4 in dendritic development and synaptogenesis in the CNS

Distinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle

Preserving skeletal muscle function is essential to maintain life quality at high age. Calorie restriction (CR) potently extends health and lifespan, but is largely unachievable in humans, making "CR mimetics" of great interest. CR targets nutrient-sensing pathways centering on mTORC1. The mTORC1 inhibitor, rapamycin, is considered a potential CR mimetic and is proven to counteract age-related muscle loss. Therefore, we tested whether rapamycin acts via similar mechanisms as CR to slow muscle aging. Here we show that long-term CR and rapamycin unexpectedly display distinct gene expression profiles in geriatric mouse skeletal muscle, despite both benefiting aging muscles. Furthermore, CR improves muscle integrity in mice with nutrient-insensitive, sustained muscle mTORC1 activity and rapamycin provides additive benefits to CR in naturally aging mouse muscles. We conclude that rapamycin and CR exert distinct, compounding effects in aging skeletal muscle, thus opening the possibility of parallel interventions to counteract muscle aging

Distinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle

As global life expectancy continues to climb, maintaining skeletal muscle function is increasingly essential to ensure a good life quality for aging populations. Calorie restriction (CR) is the most potent and reproducible intervention to extend health and lifespan, but is largely unachievable in humans. Therefore, identification of "CR mimetics" has received much attention. CR targets nutrient-sensing pathways centering on mTORC1. The mTORC1 inhibitor, rapamycin, has been proposed as a potential CR mimetic and is proven to counteract age-related muscle loss. Therefore, we tested whether rapamycin acts via similar mechanisms as CR to slow muscle aging. Contrary to our expectation, long-term CR and rapamycin-treated geriatric mice display distinct skeletal muscle gene expression profiles despite both conferring benefits to aging skeletal muscle. Furthermore, CR improved muscle integrity in a mouse with nutrient-insensitive sustained muscle mTORC1 activity and rapamycin provided additive benefits to CR in aging mouse muscles. Therefore, RM and CR exert distinct, compounding effects in aging skeletal muscle, opening the possibility of parallel interventions to counteract muscle aging