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A series of racemic aryl-substituted phenylalanines was synthesized and evaluated in vitro at recombinant rat GluA1-3, at GluK1-3, and at native AMPA receptors. The individual enantiomers of two target compounds, (RS)-2-amino-3-(3,4-dichloro-5-(5-hydroxypyridin-3-yl)phenyl)propanoic acid 37 and (RS)-2-amino-3-(3'-hydroxybiphenyl-3-yl)propanoic acid 38, were characterized. (S)-37 and (R)-38 were id

The α4β2 subtype of the nicotinic acetylcholine receptor has been pursued as a drug target for treatment of psychiatric and neurodegenerative disorders and smoking cessation aids for decades. Still, a thorough understanding of structure-function relationships of α4β2 agonists is lacking. Using binding experiments, electrophysiology and x-ray crystallography we have investigated a consecutive serie

Positive allosteric modulators of the ionotropic glutamate receptor-2 (GluA2) are promising compounds for the treatment of cognitive disorders, e.g. Alzheimer's disease. These modulators bind within the dimer interface of the LBD (ligand-binding domain) and stabilize the agonist-bound conformation slowing receptor desensitization and/or deactivation. In the present study, we employ isothermal titr

Snuff lesions were induced in 30 rats. Ten of the snuff-exposed rats were killed immediately after 13 months snuff exposure, as were the 10 control animals. Ten rats were killed 1 month and 10 rats 4 months after the snuff administration had ceased. The rats exposed to snuff for 13 months exhibited hyperplastic, hyperorthokeratotic epithelium with focal mild atypia, focal ulcerations and marked su

Lower-limb amputation was performed on 261 patients from a catchment population of 232,500 in 1984-1986, and 253 of the amputees were retrospectively followed up. In 241 cases amputation was performed because of threatening or manifest gangrene, 95 of them without preceding consultation with vascular surgeons. In 19 cases amputation followed thromboembolectomy. Of the 127 patients seen by vascular

An integrated approach is presented in this study to design electrical hubs combining optimization, multi-criterion assessment and decision making. Levelized Energy Cost (LEC), Initial Capital Cost (ICC), Grid Integration Level (GI), Levelized CO2 emission (LCO2), utilization of renewable energy, flexibility of the system, loss of load probability (LOLP) are considered as criteria used to assess t

Parasite proteases play key roles in several fundamental steps of the Plasmodium life cycle, including haemoglobin degradation, host cell invasion and parasite egress. Plasmodium exit from infected host cells appears to be mediated by a class of papain-like cysteine proteases called 'serine repeat antigens' (SERAs). A SERA subfamily, represented by Plasmodium falciparum SERA5, contains an atypical

Cysteine proteases mediate liberation of Plasmodium berghei merozoites from infected hepatocytes. In an attempt to identify the responsible parasite proteases, we screened the genome of P. berghei for cysteine protease-encoding genes. RT-PCR analyses revealed that transcription of four out of five P. berghei serine repeat antigen (PbSERA) genes was strongly upregulated in late liver stages briefly

Plasmodium berghei is the causative agent of rodent malaria and is widely used as a model system to study the liver stage of Plasmodium parasites. The entry of P. berghei sporozoites into hepatocytes has extensively been studied, but little is known about parasite-host interaction during later developmental stages of the intracellular parasite. Growth of the parasite far beyond the normal size of