Mobile Eye Tracking in Landscape Architecture: Discovering a New Application for Research on Site

This chapter presents the process of establishing a laboratory for mobile eye tracking focussing on real-world, open-space environments within the field of landscape architecture at the Osnabrück University of Applied Sciences (D) as well as the latest results from the feasibility study ‘Point de Vue’, which defines the basis for qualitative interaction analyses in landscape architecture. Eye tracking is a tool that has been used extensively in the domains of psychology, marketing, usability and user experience in remote and mobile applications, but has rarely been used in real-world open spaces because of technical limitations. To check the possibilities of mobile eye tracking as a new application in open spaces, several exploratory tests and a feasibility study with long-term experiments have been carried out in urban settings as well as in world famous parks such as ‘Grosser Garten’ in Hannover (D) and ‘Stourhead’ in Wiltshire (GB). These experiments have shown extraordinary results that enable us to use mobile eye tracking as a new tool in open space research to gain knowledge about how people act, react and interact in open-space environments. Being able to see and understand what catches one’s eye and the response to it will be a guide to better design

The cellular modifier MOAG-4/SERF drives amyloid formation through charge complementation.

While aggregation-prone proteins are known to accelerate aging and cause age-related diseases, the cellular mechanisms that drive their cytotoxicity remain unresolved. The orthologous proteins MOAG-4, SERF1A, and SERF2 have recently been identified as cellular modifiers of such proteotoxicity. Using a peptide array screening approach on human amyloidogenic proteins, we found that SERF2 interacted with protein segments enriched in negatively charged and hydrophobic, aromatic amino acids. The absence of such segments, or the neutralization of the positive charge in SERF2, prevented these interactions and abolished the amyloid-promoting activity of SERF2. In protein aggregation models in the nematode worm Caenorhabditis elegans, protein aggregation and toxicity were suppressed by mutating the endogenous locus of MOAG-4 to neutralize charge. Our data indicate that MOAG-4 and SERF2 drive protein aggregation and toxicity by interactions with negatively charged segments in aggregation-prone proteins. Such charge interactions might accelerate primary nucleation of amyloid by initiating structural changes and by decreasing colloidal stability. Our study points at charge interactions between cellular modifiers and amyloidogenic proteins as potential targets for interventions to reduce age-related protein toxicity

Variation within the Huntington's Disease Gene Influences Normal Brain Structure

Genetics of the variability of normal and diseased brain structure largely remains to be elucidated. Expansions of certain trinucleotide repeats cause neurodegenerative disorders of which Huntington's disease constitutes the most common example. Here, we test the hypothesis that variation within the IT15 gene on chromosome 4, whose expansion causes Huntington's disease, influences normal human brain structure. In 278 normal subjects, we determined CAG repeat length within the IT15 gene on chromosome 4 and analyzed high-resolution T1-weighted magnetic resonance images by the use of voxel-based morphometry. We found an increase of GM with increasing long CAG repeat and its interaction with age within the pallidum, which is involved in Huntington's disease. Our study demonstrates that a certain trinucleotide repeat influences normal brain structure in humans. This result may have important implications for the understanding of both the healthy and diseased brain

Alternative Oxidase Dependent Respiration Leads to an Increased Mitochondrial Content in Two Long-Lived Mutants of the Ageing Model Podospora anserina

The retrograde response constitutes an important signalling pathway from mitochondria to the nucleus which induces several genes to allow compensation of mitochondrial impairments. In the filamentous ascomycete Podospora anserina, an example for such a response is the induction of a nuclear-encoded and iron-dependent alternative oxidase (AOX) occurring when cytochrome-c oxidase (COX) dependent respiration is affected. Several long-lived mutants are known which predominantly or exclusively respire via AOX. Here we show that two AOX-utilising mutants, grisea and PaCox17::ble, are able to compensate partially for lowered OXPHOS efficiency resulting from AOX-dependent respiration by increasing mitochondrial content. At the physiological level this is demonstrated by an elevated oxygen consumption and increased heat production. However, in the two mutants, ATP levels do not reach WT levels. Interestingly, mutant PaCox17::ble is characterized by a highly increased release of the reactive oxygen species (ROS) hydrogen peroxide. Both grisea and PaCox17::ble contain elevated levels of mitochondrial proteins involved in quality control, i. e. LON protease and the molecular chaperone HSP60. Taken together, our work demonstrates that AOX-dependent respiration in two mutants of the ageing model P. anserina is linked to a novel mechanism involved in the retrograde response pathway, mitochondrial biogenesis, which might also play an important role for cellular maintenance in other organisms

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Activating transcription factor-3 (ATF3) functions as a tumor suppressor in colon cancer and is up-regulated upon heat-shock protein 90 (Hsp90) inhibition

In conclusion, ATF3 down-regulation in colon cancer promotes tumor growth and metastasis. Considering that blocking Hsp90 induces ATF3 expression, Hsp90 inhibition may represent a valid strategy to treat metastatic colon cancer by up-regulating this anti-metastatic transcription factor

Delaying aging and the aging-associated decline in protein homeostasis by inhibition of tryptophan degradation

Toxicity of aggregation-prone proteins is thought to play an important role in aging and age-related neurological diseases like Parkinson and Alzheimer's diseases. Here, we identify tryptophan 2,3-dioxygenase (tdo-2), the first enzyme in the kynurenine pathway of tryptophan degradation, as a metabolic regulator of age-related α-synuclein toxicity in a Caenorhabditis elegans model. Depletion of tdo-2 also suppresses toxicity of other heterologous aggregation-prone proteins, including amyloid-β and polyglutamine proteins, and endogenous metastable proteins that are sensors of normal protein homeostasis. This finding suggests that tdo-2 functions as a general regulator of protein homeostasis. Analysis of metabolite levels in C. elegans strains with mutations in enzymes that act downstream of tdo-2 indicates that this suppression of toxicity is independent of downstream metabolites in the kynurenine pathway. Depletion of tdo-2 increases tryptophan levels, and feeding worms with extra L-tryptophan also suppresses toxicity, suggesting that tdo-2 regulates proteotoxicity through tryptophan. Depletion of tdo-2 extends lifespan in these worms. Together, these results implicate tdo-2 as a metabolic switch of age-related protein homeostasis and lifespan. With TDO and Indoleamine 2,3-dioxygenase as evolutionarily conserved human orthologs of TDO-2, intervening with tryptophan metabolism may offer avenues to reducing proteotoxicity in aging and age-related diseases

Different patterns of aortic wall elasticity in patients with Marfan syndrome: a noninvasive follow-up study

OBJECTIVE: Aortic complications determine the life expectancy of most patients with Marfan syndrome. To find out whether there is heterogenous aortic involvement among patients and, if there is, to characterize aortic patterns and response to long-term beta-blocker therapy, we investigated aortic elastic properties before and during beta-blocker treatment. METHODS: In 46 patients with Marfan syndrome (age, 17.4 +/- 11.1 years) and 46 healthy control subjects, ascending and descending aortic elastic parameters were determined noninvasively before and after 39 +/- 16 months of beta-blocker treatment with atenolol. RESULTS: Aortic diameters and distensibility distinguished Marfan patients and controls with a sensitivity of 85% and a specificity of 87%. Cluster analysis revealed 4 patterns of aortic phenotypic expression: (1) reduced ascending aortic elasticity (46% of patients), (2) diminished ascending and descending aortic elasticity (17%), (3) minimal alterations of ascending and descending aortic elasticity (20%), and (4) reduced descending aortic elasticity (17%). During follow-up, aortic elastic properties improved in 21 (70%) of 30 patients and deteriorated in 9 (30%) irrespective of beta-blocker dosage. Improvement was observed in 100% of patients (n = 7; age, 5.3 +/- 4.2 years) with end-diastolic aortic root diameters between 20 and 30 mm and in 61% of patients (14/23; age, 20.5 +/- 10.0 years) with root diameters between 30 and 52 mm. CONCLUSIONS: Aortic elastic parameters distinguish between patients with Marfan syndrome and healthy controls and show the pattern of regional aortic involvement. Improvement or deterioration during follow-up can influence therapeutic decisions to prevent aortic dissection and rupture. Young age, small root diameter, and high distensibility are favorable prognostic factors