1.Inhibition of GABA synthesis in the prefrontal cortex increases locomotor activity but does not affect attention in the 5-choice serial reaction time task.
Asinof SK1, Paine TA. Neuropharmacology. 2013 Feb;65:39-47. doi: 10.1016/j.neuropharm.2012.09.009. Epub 2012 Sep 26.
Attention deficits are a core cognitive symptom of schizophrenia; the neuropathology underlying these deficits is not known. Attention is regulated, at least in part, by the prefrontal cortex (PFC), a brain area in which pathology of γ-aminobutyric acid (GABA) neurons has been consistently observed in post-mortem analysis of the brains of people with schizophrenia. Specifically, expression of the 67-kD isoform of the GABA synthesis enzyme glutamic acid decarboxylase (GAD67) is reduced in parvalbumin-containing fast-spiking GABA interneurons. Thus it is hypothesized that reduced cortical GABA synthesis and release may contribute to the attention deficits in schizophrenia. Here the effect of reducing cortical GABA synthesis with l-allylglycine (LAG) on attention was tested using three different versions of the 5-choice serial reaction time task (5CSRTT). Because 5CSRTT performance can be affected by locomotor activity, we also measured this behavior in an open field.
2.Effects of disrupting medial prefrontal cortex GABA transmission on decision-making in a rodent gambling task.
Paine TA1, O'Hara A, Plaut B, Lowes DC. Psychopharmacology (Berl). 2015 May;232(10):1755-65. doi: 10.1007/s00213-014-3816-7. Epub 2014 Nov 26.
RATIONALE: Decision-making is a complex cognitive process that is mediated, in part, by subregions of the medial prefrontal cortex (PFC). Decision-making is impaired in a number of psychiatric conditions including schizophrenia. Notably, people with schizophrenia exhibit reductions in GABA function in the same PFC areas that are implicated in decision-making. For example, expression of the GABA-synthesizing enzyme GAD67 is reduced in the dorsolateral PFC of people with schizophrenia.
3.Stimuli-responsivity of secondary structures of glycopolypeptides derived from poly(L-glutamate-co-allylglycine).
Krannig KS1, Sun J, Schlaad H. Biomacromolecules. 2014 Mar 10;15(3):978-84. doi: 10.1021/bm401883p. Epub 2014 Feb 14.
Copolypeptides containing L-glutamate and various amounts of either D-/DL-/L-allylglycine or D-/DL-/L-(3-(β-D-glucopyranosyl)thio)propylglycine defect units were studied by circular dichroism (CD) and infrared (FT-IR) spectroscopy according to their secondary structures in dependence of pH and temperature. All samples adopt random coil conformation at high pH and α-helix at low pH without evidence for β-sheet formation. Folding into the α-helix structure is strongly affected by the number and configuration of allylglycine defects (which intrinsically stabilize β-sheets). Helix folding is facilitated upon the attachment of D-glucopyranose to the L- (but not the D-) allylglycine units, which is attributed to a different secondary structure preference of the L-(3-(β-D-glucopyranosyl)thio)propylglycine (L: random coil; D: β-sheet) and a majority rule effect.
4.Assembly mechanism of [Fe2S2] cluster in ferredoxin from Acidithiobacillus ferrooxidans.
Chen Q1, Mo H, Tang L, Du J, Qin F, Zeng J. J Microbiol Biotechnol. 2011 Feb;21(2):124-8.
Ferredoxin is a typical iron-sulfur protein that is ubiquitous in biological redox systems. This study investigates the in vitro assembly of a [Fe2S2] cluster in the ferredoxin from Acidithiobacillus ferrooxidans in the presence of three scaffold proteins: IscA, IscS, and IscU. The spectra and MALDI-TOF MS results for the reconstituted ferredoxin confirm that the iron-sulfur cluster was correctly assembled in the protein. The inactivation of cysteine desulfurase by L-allylglycine completely blocked any [Fe2S2] cluster assembly in the ferredoxin in E. coli, confirming that cysteine desulfurase is an essential component for iron-sulfur cluster assembly. The present results also provide strong evidence that [Fe2S2] cluster assembly in ferredoxin follows the AUS pathway.
