Pseudospin Dynamics of the One-Dimensional S = ½ XY System PrCl3 Studied by Electronic Raman Scattering

Direct confirmation of the one-dimensional S = ½ XY character of the interactions between the pseudospins of the Pr3+ ions in PrCl3 is obtained through a study of the pseudospin dynamics by means of electronic Raman scattering, with and without a magnetic field. This is concluded from an analytic calculation of the spectral moments and from a numerical finite-chain calculation of the line shapes, both of which are in excellent agreement with the experimental data

Molecular and pharmacological characterization of native cortical γ- aminobutyric acids receptors containing both α1 and α3 subunits

We have investigated the existence, molecular composition, and benzodiazepine binding properties of native cortical α1-α3 γ- aminobutyric acid(A) (GABA(A)) receptors using subunit-specific antibodies. The co-existence of α1 and α3 subunits in native GABA(A) receptors was demonstrated by immunoblot analysis of the anti-α1- or anti-α3- immunopurified receptors and by immunoprecipitation experiments of the [3H]zolpidem binding activity. Furthermore, immunodepletion experiments indicated that the α1-α3 GABA(A) receptors represented 54.7 ± 5.0 and 23.6 ± 3.3% of the α3 and α1 populations, respectively. Therefore, α1 and α3 subunits are associated in the same native GABA(A) receptor complex, but, on the other hand, these α1-α3 GABA(A) receptors from the cortex constitute a large proportion of the total α3 population and a relatively minor component of the α1 population. The pharmacological analysis of the α1- or α3-immunopurified receptors demonstrated the presence of two different benzodiazepine binding sites in each receptor population with high (type I binding sites) and low (type II binding sites) affinities for zolpidem and Cl 218,872. These results indicate the existence of native GABA(A) receptors possessing both α1 and α3 subunits, with α1 and α3 subunits expressing their characteristic benzodiazepine pharmacology. The molecular characterization of the anti-α1-anti-α3 double-Immunopurified receptors demonstrated the presence of stoichiometric amounts of α1 and α3 subunits, associated with α(2/3), and γ2 subunits. The pharmacological analysis of α1-α3 GABA(A) receptors demonstrated that, despite the fact that each α subunit retained its benzodiazepine binding properties, the relative proportion between type I and II binding sites or between 51- and 59-61-kDa [3H]Ro15-4513-photolabeled peptides was 70:30. Therefore, the α1 subunit is pharmacologically predominant over the α3 subunit. These results indicate the existence of active and nonactive α subunits in the native α1-α3 GABA(A) receptors from rat corte

Application of Enzymes in Industrial Organic Synthesis

Aminopeptidase- and amidase-based methods for the production of enantiomerically pure amino acids, intermediates for pharmaceuticals and agrochemicals, are discussed. Furthermore, enzymatic syntheses of the dipeptide sweetener aspartame and semisynthetic antibiotics (such as ampicillin, amoxicillin, cephalexin, and cefadroxil) are highlighted

GMP manufacturing of Vvax001, a therapeutic anti-HPV vaccine based on recombinant viral particles

Therapeutic vaccination is being explored as a treatment strategy for the treatment of patients with primary or metastatic tumours. We developed a vaccine targeted to Human papillomavirus (HPV)-induced tumours based on recombinant Semliki Forest virus (rSFV) encoding a fusion protein of the E6 and E7 proteins of HPV type 16. To enable a phase I clinical trial with this vaccine, Vvax001, a Good Manufacturing Practice (GMP)-compliant manufacturing process was set up and clinical material was produced. Upstream production of the clinical material resulted in viral titers from 2.4 × 107 to 1.3 × 109 infectious particles/ mL in the harvest. The total volume of 6.0 liter crude virus was purified in 13 consecutive downstream purification runs. The mean titer after purification was 4.0 × 108 infectious particles/ mL and the mean recovery was 19%. Finally, clinical material was filled at a target concentration of 1.25 × 108 infectious particles/mL. Release testing included tests for viral titer and virus identity, biological activity, sterility, bacterial endotoxins, adventitious viruses and absence of replication competent virus. The product complied with all specifications and was released for use as an investigational medicinal product. This is the first GMP production process developed for a SFV-based therapeutic vaccine. The vaccine, Vvax001 is targeted to HPV and has shown promising results in preclinical studies. The GMP-produced Vvax001 material met the quality criteria and was of sufficient quantity to enable assessment of its immunogenicity, safety and efficacy in a clinical setting

Inhibitors of GlyT1 Affect Glycine Transport via Discrete Binding Sites

ABSTRACT In the forebrain, synaptic glycine concentrations are regulated through the glycine transporter GlyT1. Because glycine is a coagonist of the N-methyl-D-aspartate (NMDA) receptor (NMDAR), which has been implicated in schizophrenia, inhibition of GlyT1 is thought to provide an option for the treatment of schizophrenia

Increasing foraging times with appetitive and consummatory foraging enrichment in grey parrots (Psittacus erithacus)

Foraging enrichment is considered one of the most effective ways to enhance expression of species-typical behaviours and prevent the development of abnormal (repetitive) behaviours in captive animals. However, foraging enrichments for parrots have thus far not been able to approximate natural foraging time budgets nor completely eliminate abnormal behaviours such as feather damaging behaviour. This might be related to the design of currently available foraging enrichments, which generally stimulate a subset of foraging activities rather than foraging behaviour in its entirity. We therefore designed a two-component foraging enrichment that addressed both the appetitive and consummatory phases of foraging. To evaluate whether foraging times would approximate those in the wild (4–8 h/day), we studied the effect of the separate and combined components on foraging behaviour in 12 healthy grey parrots (Psittacus erithacus) using a balanced cross-over design. Parrots were provided food by means of the appetitive (APP), consummatory (CONS), and combined (APP+CONS) component(s) of the foraging enrichment, and in a food trough that served as a control (CTRL; no enrichment) for 30 days per test condition. The time spent on foraging was evaluated on days 2, 14 and 30 in all four test conditions using continuous focal sampling. Each of the single components (APP or CONS) increased daily foraging times from 2 to 3 h per day (CTRL: 121 ± 16 min/24 h, APP: 176 ± 31 min/24 h, CONS: 194 ± 26 min/24 h), while the combined enrichment doubled daily foraging times (APP+CONS: 234 ± 42 min/24 h), thereby approaching natural foraging time budgets. Foraging times remained steady over the 30 days, indicating no habituation or change in use of the enrichments throughout this period. These results demonstrate the importance of providing both appetitive and consummatory activities to generate effective foraging opportunities for parrots. Such a bottom-up approach could be beneficial for other (parrot) species as well