Ultrasensitive impedimetric lectin biosensors recognising different glycan entities on serum glycoproteins were constructed. Lectins were immobilised on novel mixed self-assembled monolayer containing 11-mercaptoundecanoic acid for covalent immobilisation of lectins and betaine terminated thiol to resist non-specific interactions. Construction of biosensors based on Concanavalin A (Con A), Sambucus nigra agglutinin type I (SNA) and Ricinus communis agglutinin (RCA) on polycrystalline gold electrodes was optimised and characterised with a battery of tools including electrochemical impedance spectroscopy, various electrochemical techniques, QCM, FTIR spectroscopy, AFM, XPS and compared with a protein/lectin microarray. The lectin biosensors were able to detect glycoproteins from 1 fM (Con A), 10 fM (RCA) or 100 fM (SNA) with a linear range spanning 6 (SNA), 7 (RCA) or 8 (Con A) orders of magnitude. Furthermore, a detection limit for the Con A biosensor down to 1 aM was achieved in a sandwich configuration. A non-specific binding of proteins for the Con A biosensor was only 6.1% (probed with an oxidised invertase) of the signal towards its analyte invertase and a negligible non-specific interaction of the Con A biosensor was observed in diluted human sera (1000x), as well. The performance of the lectin biosensors was finally tested by glycoprofiling of human serum samples from healthy individuals and those having rheumatoid arthritis, which resulted in distinct glycan pattern between these two groups.

Diets containing a high proportion of fat with respect to protein plus carbohydrates are capable of inducing ketone body production in the liver, which provides an energetic alternative to glucose. Some ketogenic diets have been tested as therapeutic strategies for treating metabolic disorders related to a deficiency in glucose-driven ATP generation. However, ketone bodies are not capable of providing extra tricarboxylic acid cycle intermediates, limiting the anabolic capacity of the cell. Therefore, it is reasonable to hypothesize that supplementing a ketogenic diet with anaplerotic compounds such as triheptanoin may improve ketogenic diet effectiveness. The present study tests this hypothesis in APP/PS1 (APPswe/PS1dE9) transgenic mice, used as a model of familial Alzheimer's disease because impaired energy supply to neurons has been linked to this neurodegenerative process. Triheptanoin supplementation to a ketogenic diet for three months and starting at the age of three months reduces the memory impairment of APP/PS1 mice at the age of 6 months. The Aβ production and deposition were not significantly altered by the ketogenic diet, supplemented or not by triheptanoin. However, mice fed with triheptanoin-rich ketogenic diet have shown decreased astroglial response in the vicinity of Aβ plaques and decreased expression of the pro-inflammatory cytokine interferon-γ in astrocytes. These findings correlate with transcriptional up-regulation of the ROS detoxifying mechanisms Sirt1 and Pparg, thus linking triheptanoin with improved mitochondrial status. Present findings support the concept that ketogenic diets supplemented with anaplerotic compounds can be considered potential therapeutic strategies at early stages of Alzheimer's disease.

A computer-aided design of novel D-π-A-π-D styrylamines containing five isomeric benzobisthiazole moieties as the electron-accepting core has revealed the linear centrosymmetric benzo[1,2-d:4,5-d']bisthiazole as the most promising building block for engineering chromophores displaying high two-photon absorption (TPA) in the near-IR region, as also confirmed experimentally. The ease of synthesis of quadrupolar derivatives thereof, combined with extraordinarly high TPA action cross sections (δTPAΦf > 1500 GM), makes these heteroaromatic systems particularly attractive as diagnostic agents in 3D fluorescence imaging.