Plant J. 2003 Jun;34(6):856-67. The Arabidopsis thaliana CUTA gene encodes an evolutionarily conserved copper binding chloroplast protein.
Burkhead JL, Abdel-Ghany SE, Morrill JM, Pilon-Smits EA, Pilon M.
Biology Department, Colorado State University, Room E 416, Fort Collins, CO 80523, USA.
The Arabidopsis thaliana CUTA gene encodes a 182-amino-acid-long putative precursor of a chloroplast protein with high sequence similarity to evolutionarily conserved prokaryotic proteins implicated in copper tolerance. Northern analysis indicates that AtCUTA mRNA is expressed in all major tissue types. Analysis of cDNA clones and RT-PCR with total mRNA revealed alternative splicing of AtCUTA by retention of an intron. The intron-containing mRNA encodes a truncated 156-amino-acid protein as a result of stop codons in the included intron. The sequence of AtCutAp encoded by the fully spliced transcript suggests that the precursor consists of three domains: an N-terminal chloroplast transit sequence of 70 residues, followed by a domain with prokaryotic signal-sequence-like characteristics and finally the most conserved C-terminal domain. The N-terminal chloroplast transit sequence was functional to route a passenger protein into isolated pea chloroplasts with possible sorting to the envelope. Chloroplast localization was confirmed by Western blot analysis of isolated and fractionated chloroplasts. Recombinant AtCutA protein was expressed in Escherichia coli without the N-terminal 70-amino-acid chloroplast transit sequence. This recombinant AtCutAp was routed to the bacterial periplasm of E. coli. Purified recombinant AtCutAp is tetrameric and selectively binds Cu(II) ions with an affinity comparable to that reported for mammalian prion proteins.
PMID:_12795705 [PubMed - in process]
J Neurol. 2003 Jun;250(6):688-92. The 129 codon polymorphism of the prion protein gene influences earlier cognitive performance in Down syndrome subjects.
Del Bo R, Comi GP, Giorda R, Crimi M, Locatelli F, Martinelli-Boneschi F, Pozzoli U, Castelli E, Bresolin N, Scarlato G.
Dipartimento di Scienze Neurologiche, Padiglione Ponti, I. R. C. S. S. Ospedale Maggiore Policlinico, Via F. Sforza, 35, 20122 Milan, Italy. gpcomailserver.unimi.it
Recently, a frequent prion protein gene (PRNP) polymorphism consisting of a methionine (M) for valine (V) substitution at codon 129 has been associated with cognitive impairment in elderly individuals. Down syndrome (DS) is associated with mental retardation and development of Alzheimer-like brain abnormalities. In the present study, we investigated the role of the PRNP polymorphism in 122 relatively young Italian DS patients. Allele frequencies of DS subjects did not differ from those in the general population. However, we found a significantly faster rate of decline in intellectual ability in the subgroup of DS patients carrying at least one V allele compared with the M/M DS subjects. An additive deleterious effect of apolipoprotein E epsilon 4 allele was detected after stratifying by APOE gene status. Our findings provide evidence that variability of the PRNP gene at codon 129 might contribute to accelerating the rate of earlier cognitive decline in DS subjects.
PMID:_12796830
Med Clin (Barc). 2003 May 31;120(20):761-4. [Use and validity of the 14-3-3 protein test in the diagnosis of prion diseases: a 4-year prospective study]
[Article in Spanish]
Sanchez-Valle Diaz R, Graus Ribas F, Saiz Hinarejos A.
Servicio de Neurologia. Institut Clinic de Malalties del Sistema Nervios. Instituto de Investigacion Biomedica August Pi i Sunyer (IDIBAPS). Hospital Clinic. Universidad de Barcelona. Barcelona. Espana.
BACKGROUND AND OBJECTIVES: The 14-3-3 test shows a high efficiency for the diagnosis of Creutzfeldt-Jakob disease (CJD), as long as an appropriate clinical setting exists. We analyze the evolution of the use and the validity of this test in Spain. PATIENTS AND METHOD: From January 1997 to June 2001, 1,092 samples were tested in our laboratory; 674 samples were selected for the study. Diagnoses were obtained by the referring physicians and the national CJD surveillance system according to standard criteria (results of the test were not included). RESULTS: The number of samples analyzed (% of follow-up) was: 75 (96%) in 1997, 138 (82.3%) in 1998, 197 (73%) in 1999 and 264 (59%) in 2000. The negative predictive value, sensitivity and specificity for a diagnosis of prion disease revealed stable values (95, 86 and 86%, respectively). The positive predictive value (PPV) decreased from 77% in 1997 to 51% in 2000 because of an increase of false-positive (FP) results. Up to 25% of FP might have been excluded through neuroimaging or CSF characteristics. CONCLUSIONS: The observed increase of the demand suggests that the test is used as a screening technique. In this setting, the PPV of the test decreases due to an increase of false-positive results.
PMID:_12797926 [PubMed - in process]
Mol Cell Neurosci. 2003 May;23(1):144-55. Analysis of doppel protein toxicity.
Cui T, Holme A, Sassoon J, Brown DR.
Department of Biology and Biochemistry, Bath University, UK.
The recently described doppel protein (Dpl) is a homologue of the prion protein (PrP(c)). This protein, expressed in the brains of mice that lack the expression of PrP(c), causes neuronal death as the mice age. Previous studies have suggested this neuronal damage is caused by oxidative assault and changes in the activity of NOS proteins. We investigated the toxicity of Dpl in cell culture models and showed that Dpl was toxic to neurons. This toxicity was inhibited by the expression of PrP(c) and possibly involved direct interaction between the two proteins. The mechanism of toxicity involved stimulation of nitric oxide production via activation of the nitric oxide synthases, nNOS and iNOS. This mechanism of toxicity is quite different from that of PrP(Sc) and does not require the protein to change conformation. These results provide the first evidence for the mechanism of Dpl toxicity.
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