Synthesis of a versatile (S)-3-(hydroxymethyl)butane-1,2,4-triol building block and its application for the stereoselective synthesis of N-homoceramides

A versatile (S)-3-(hydroxymethyl)butane-1,2,4-triol building block has been synthesized starting from D-isoascorbic acid, a common food preservative. The key transformation in this approach was the introduction of branching through a high yield and fully regioselective epoxide opening. This flexible synthon has been elaborated to a new class of (dihydro-)N-homo(phyto)ceramides

The evolution of thermal performance can constrain dispersal during range shifting

Organisms can cope with changing temperature under climate change by either adapting to the temperature at which they perform best and/or by dispersing to more benign locations. The evolution of a new thermal niche during range shifting is, however, expected to be strongly constrained by genetic load because spatial sorting is known to induce fast evolution of dispersal. To broaden our understanding of this interaction, we studied the joint evolution of dispersal and thermal performance curves (TPCs) of a population during range shifting by applying an individual-based spatially explicit model. Always, TPCs adapted to the local thermal conditions. Remarkably, this adaptation coincided with an evolution of dispersal at the shifting range front being equally high or lower than at the trailing edge. This optimal strategy reduces genetic load and highlights that evolutionary dynamics during range shifting change when crucial traits such as dispersal and thermal performance jointly evolve

Synthesis of Biologically Relevant Sphingolipid Analogues

Dit doctoraatswerk maakt deel uit van een omstandig project over de synthese van biologisch relevante sfingoïd- en ceramide-analogen. In dit opzicht werden twee verschillende klassen van verbindingen gesynthetiseerd. In een eerste deel werd er geopteerd om hybride PDMP analogen the synthetiseren, die zowel op PDMP als op E-styreen analogen van natuurlijk ceramide gebaseerd zijn. Aangezien preliminaire synthetische routes die gebaseerd waren op enkelvoudige bescherming van de sfingoïd stikstof resulteerden in ongewenste cyclisatie reakties, werd er geopteerd om een dubbel bescherming in te voeren waarbij de tert-Boc beschermde amine functie en het secundare alcohol van de sfingoïd keten in een oxazolidine ring werden vastgelegd. Bijgevolg werden de gewenste E-styreen analogen uitgaande van D-serine gesynthetiseerd in 16 stappen. De synthetische route werd zodanig opgevat dat verschillende aromaten op eenvoudige wijze zullen ingevoerd kunnen worden bij verdere synthetische modificaties. Er werd eveneens toegang verkregen tot een aantal structuuranalogen die meer inzicht konden verschaffen in de sructuur-aktiviteitsrelatie van deze klasse van verbindingen. In vitro biologische evaluatie op Golgi extracten en in vivo evaluatie op HEK-293 en COS-7 cellen bracht twee gelijkwaardige verbindingen verbindingen in vergelijking met PDMP aan het licht, die verder kunnen uitgewerkt worden tot meer potente inhibitoren. In een tweede luik werd de synthese van een nieuwe klasse van homoceramiden, N-homoceramiden genaamd, uitgewerkt. Deze verbindingen bevatten een extra koolstof atoom tussen de N-acyl keten en C2 van de sfingoïd keten. Om dit te bewerkstelligen werd zowel vanuit een suiker als door middel van regioselectieve epoxide opening getracht om een cyanide in te voeren. Aangezien deze benaderingswijze niet voldeed voor de synthese van de gewenste verbindingen, werd geopteerd om de vertakking in te voeren door middel van 1,3-dithiaan. Bijgevolg werden de gewenste N-homo(dihydro)ceramiden in 20 stappen gesynthetiseerd, uitgaande van D-isoascorbinezuur, een veel gebruikt bewaarmiddel in de voedingsindustrie. De sleutelreaktie in deze benaderingswijze was de volledig regioselectieve epoxide opening met lithium 1,3-dithiaan. Daarenboven stelde een volledig regioselective Grignard reaktie ons in staat om D-ribo-homophytoceramide te synthetiseren

Tango-therapy vs physical exercise in older people with dementia; a randomized controlled trial

[EN] Background: Dementia is a growing health concern that affects millions of people worldwide. Gait and mobility disorders are often present and represent a major risk factor for falls. The purpose of this study was to investigate the effectiveness of tango-therapy in gait speed, functional mobility, balance, falls, ability to perform activities of daily living and quality of life. Methods: A randomised controlled trial with 31 participants living in a specialised dementia unit, aged 65 to 93 years old, who were randomly assigned to tango group (IG) or physical exercise group (CG). The primary outcome was gait speed and Timed Up and Go test. The secondary outcomes include the Short Physical Performance Battery, the ability to perform activities of daily living (Katz Index) and quality of life (Quality of life in Alzheimer Disease). Measurements were performed at baseline, and after one and three months of training. Results: After 3 months, IG improved gait speed (p = 0.016), implying a statistically significant difference between groups in favour of IG (p = 0.003). CG significantly worsened the time to complete the TUG (p = 0.039). Both groups declined in their ability to perform activities of daily living, being statistically significant only in the CG (p < 0.001). Conclusion: Tango interventions showed efficacy in improving gait speed and in mitigating the decline in functional mobility and ADL skill capacities. Allowing older people with dementia access to non-pharmacological interventions may be a successful strategy to prevent functional decline.SISociété de Gérontologie de l’Est, ISATIS Association and the Conférence des Financeurs de Paris

Size-dependent movement explains why bigger is better in fragmented landscapes

Body size is a fundamental trait known to allometrically scale with metabolic rate and therefore a key determinant of individual development, life history, and consequently fitness. In spatially structured environments, movement is an equally important driver of fitness. Because movement is tightly coupled with body size, we expect habitat fragmentation to induce a strong selection pressure on size variation across and within species. Changes in body size distributions are then, in turn, expected to alter food web dynamics. However, no consensus has been reached on how spatial isolation and resource growth affect consumer body size distributions. Our aim was to investigate how these two factors shape the body size distribution of consumers under scenarios of size-dependent and size-independent consumer movement by applying a mechanistic, individual-based resource-consumer model. We also assessed the consequences of altered body size distributions for important ecosystem traits such as resource abundance and consumer stability. Finally, we determined those factors that explain most variation in size distributions. We demonstrate that decreasing connectivity and resource growth select for communities (or populations) consisting of larger species (or individuals) due to strong selection for the ability to move over longer distances if the movement is size-dependent. When including size-dependent movement, intermediate levels of connectivity result in increases in local size diversity. Due to this elevated functional diversity, resource uptake is maximized at the metapopulation or metacommunity level. At these intermediate levels of connectivity, size-dependent movement explains most of the observed variation in size distributions. Interestingly, local and spatial stability of consumer biomass is lowest when isolation and resource growth are high. Finally, we highlight that size-dependent movement is of vital importance for the survival of populations or communities within highly fragmented landscapes. Our results demonstrate that considering size-dependent movement is essential to understand how habitat fragmentation and resource growth shape body size distributions-and the resulting metapopulation or metacommunity dynamics-of consumers

Intra- and inter-observer variability of computed tomographic measurements of the prostate gland in neutered dogs

The purpose of this study was to evaluate the intra- and inter-observer variability of computed tomographic measurements of linear prostate dimensions in neutered dogs without signs of prostatic disease, to determine potential associations between prostatic parameters and body weight or age and to provide reference ranges. Length, width and height of the prostate gland were measured in 62 neutered dogs with no signs of prostatic disease by three observers with different levels of training. Statistically significant positive associations were found between all prostatic parameters and body weight and between all prostatic parameters and age at castration, but not with age. Formulae allowing the calculation of the expected values for prostatic parameters based on body weight are provided [length = 15.3 + body weight (BW) × 0.3; height = 9.7 + BW × 0.16; width = 9.5 + BW × 0.2]. These may represent a useful tool for computed tomographic evaluation of the size of the prostate in neutered dogs. Subjective evaluations of the morphological appearance of the prostate gland are also provided