Event-related potentials reveal limited readiness to access phonetic details during word processing in dogs.

While dogs have remarkable abilities for social cognition and communication, the number of words they learn to recognize typically remains very low. The reason for this limited capacity is still unclear. We hypothesized that despite their human-like auditory abilities for analysing speech sounds, their word processing capacities might be less ready to access phonetic details. To test this, we developed procedures for non-invasive measurement of event-related potentials (ERPs) for language stimuli in awake dogs (n = 17). Dogs listened to familiar instruction words and phonetically similar and dissimilar nonsense words. We compared two different artefact cleaning procedures on the same data; they led to similar results. An early (200-300 ms; only after one of the cleaning procedures) and a late (650-800 ms; after both cleaning procedures) difference was present in the ERPs for known versus phonetically dissimilar nonsense words. There were no differences between the ERPs for known versus phonetically similar nonsense words. ERPs of dogs who heard the instructions more often also showed larger differences between instructions and dissimilar nonsense words. The study revealed not only dogs' sensitivity to known words, but also their limited capacity to access phonetic details. Future work should confirm the reported ERP correlates of word processing abilities in dogs.

Plasma carnitine ester profile in homozygous and heterozygous OCTN2 deficiency.

The carnitine ester spectrum was studied using ESI tandem mass spectrometry in a 2.5-year-old male Roma child with homozygous deletion of 844C of the SLC22A5 gene, presenting with hepatopathy and cardiomyopathy. Besides the dramatic decrease of plasma free carnitine (1.38 vs 32.7 mumol/L in controls) all plasma carnitine esters were severely decreased in the proband: the total esters were 31.4% of the controls. In three heterozygous siblings the free carnitine level was 62.3% of the normal controls, while the levels of the individual carnitine esters ranged between 15.5% and 163% (average 70.9%). The heterozygous parents exhibited the same pattern. The proband was supplemented with 50 mg/kg per day of L-carnitine oral solution. After 2 months of treatment, his hepatomegaly, elevated transaminases and the pathological cardiac ultrasound parameters normalized. The plasma free carnitine rose to 12.8 mumol/L (39% of the controls). All of the carnitine esters also increased; however, the individual esters were still 8.5-169.7% of the controls (average 55.5%). After 13 months of treatment there was a further increase in free carnitine (15.9 mumol/L) as well as in the level of the individual esters, ranging between 16.1% and 140.3% of the controls (average 66.9%). The data presented here show that, besides the dramatic decrease of free carnitine, the carnitine ester metabolism is also affected in OCTN2 deficiency; the replenishment of the pools under treatment is slow. Despite an impressive clinical improvement, the carnitine metabolism can be still seriously affected.

No influence of SLC22A4 C6607T and RUNX1 G24658C genotypic variants on the circulating carnitine ester profile in patients with rheumatoid arthritis.

OBJECTIVE: In a Japanese study, the C6607T SNP mapping to intron 1 of the SLC22A4 gene encoding the OCTN1 protein was found to be associated with rheumatoid arthritis. Similarly, a G24658C transversion in intron 6 of the gene encoding the RUNX1 transcription factor that regulates OCTN1 and also likely OCTN2 expression was also found to confer susceptibility to the disease. METHODS: We investigated the prevalence of these two SNPs by RFLP analysis in a cohort of 209 Hungarian rheumatoid arthritis patients, and 217 healthy controls. Since both the OCTN1 and OCTN2 play a central role in the transmembrane transport of carnitine, we also determined the quantitative serum carnitine ester profile by ESI tandem mass spectrometry. RESULTS: No statistically significant differences were found comparing the genotype prevalence rates between the patients and the controls for either the SLC22A4 genotypes or for the RUNX1 SNPs. There was no significant difference in the serum carnitine ester profile when the rheumatoid arthritis patients were compared with the controls; furthermore, no significant difference in the carnitine esters could be detected when genotype specific subgroups of the patients and the controls were studied. CONCLUSION: Data of the current study do not confirm the universal and population independent susceptibility role of the SLC22A4 C6607T and RUNX1 G24658C variants for rheumatoid arthritis; furthermore, the data presented here show, that there are no significant carnitine-metabolism associated functional consequences of the different genotypes evidenced by the lack of detectable differences in the carnitine ester profiles.

Functional variants of interleukin-23 receptor gene confer risk for rheumatoid arthritis but not for systemic sclerosis.

OBJECTIVES: Recently, an association was found between Crohn's disease and the interleukin-23 receptor (IL-23R) gene. Since the IL-23/IL-17 pathway is known to associate with other autoimmune diseases, including rheumatoid arthritis (RA) and systemic sclerosis (SSc), we hypothesised that IL-23R could be a shared susceptibility gene. METHODS: Groups of patients with rheumatoid arthritis (n = 412), systemic sclerosis (n = 224), Crohn's disease (n = 190) and healthy controls (n = 220) were genotyped for rs10889677 (exon-3'UTR C2370A), rs2201841, and rs1884444 variants; the first two have been shown to confer risk for Crohn's disease. RESULTS: We observed an increased prevalence of the homozygous rs10889677 AA and homozygous rs2201841 CC genotypes both in the Crohn's disease and in the RA groups as compared to the controls (12.1%, 11.9% vs 5.91%, p<0.05; and 13.2%, 13.1% vs 5.91%, p<0.05), but not in the SSc patients. Logistic regression analysis revealed that bearing these alleles represent risk for the development of rheumatoid arthritis (chi(2) = 5.58, p = 0.018, OR = 2.15, 95% CI 1.14-4.06 for rs10889677; and chi(2) = 7.45, p = 0.006, OR = 2.40, 95% CI 1.28-4.51 for rs2201841). The rs1884444 allele, which has been previously reported as neutral for development of Crohn's disease, was also found neutral for all studied groups in the present study. CONCLUSIONS: The data reported here provide direct evidence that some allelic variants or haplogroups of IL-23R represent independent risk factors for rheumatoid arthritis as well as Crohn's disease, but not for scleroderma.

Prevalence of functional haplotypes of the peptidylarginine deiminase citrullinating enzyme gene in patients with rheumatoid arthritis: no influence of the presence of anti-citrullinated peptide antibodies.

OBJECTIVE: Citrullinated peptides produced by enzymatic deimination of arginine residues in proteins by peptidylarginine deiminases are of particular interest in the pathogenesis of rheumatoid arthritis (RA). One type of citrullinated protein - the cyclic citrullinated peptide - is the target of the anti-cyclic citrullinated peptide antibody, the most sensitive and specific autoantibody in RA. The peptidylarginine deiminase type 4 (PADI4) gene, which codes one of the PADI enzyme isotypes, has genetic variants that confer susceptibility to RA in Asian, but not in European populations. METHODS: Genetic associations were examined in 214 Hungarian RA patients characterized for the presence of anti-CCP and rheumatoid factor. The patients were characterized for the existing haplotypes of the PADI4 gene (defined by the combinations of 4 exonic padi4_89: 163G/A, padi4_90: 245T/C, padi4_92: 335C/G, padi4_104: 349T/C and 2 intronic padi4_94: 17535226C/T and padi4_102: 17546809C/T variants) by the PCR-RFLP method. RESULTS: None of the PADI4 haplotypes was accumulated in RA patients. One new finding was that we also did not detect the accumulation of any haplotypes either in the anti-CCP or in the RF-positive subgroups of patients. CONCLUSION: The data presented here show that none of the naturally occurring haplotypes of the PADI4 gene conferred susceptibility to RA in an average group of Hungarian patients; this is in agreement with findings for other European populations. In addition, none of the functional PADI4 haplotypes were associated with the pathologic immune response, which was evidenced by the absence of accumulation of anti-CCP-positive subjects in the specific PADI4 haplotypes.

Prevalence and molecular characterization of human group C rotaviruses in Hungary.

BACKGROUND: Group C rotaviruses are recognized enteric pathogens of humans and animals. Human group C rotaviruses have been associated with sporadic episodes and large outbreaks of gastroenteritis in children and adults but their epidemiology and ecology are still unexplored. OBJECTIVES: To collect epidemiological data on group C rotavirus infections among children with gastroenteritis in Hungary and perform molecular characterization on the identified strains. STUDY DESIGN: Fecal samples were collected during the 2003 surveillance in Baranya County, Hungary. The presence of group C rotavirus RNA was investigated by polyacrylamide gel electrophoresis and by reverse transcription-nested polymerase chain reaction for the VP6 gene. The identified strains were further characterized by sequencing and phylogenetic analysis of the VP7, VP6, VP4, and NSP4 genes. RESULTS: Three of 472 samples (0.6%) tested positive for group C rotavirus. Two samples were selected for molecular analysis. Strains BaC 6104/03 and BaC 11549/03 displayed an overall identity of >99.8% and 99.3% at the nucleotide and amino acid level, respectively. The VP7 of the strain BaC 6104/03 was most closely related (99.5% aa) to the Nigerian strain Jajeri, while the VP4s of strains BaC 6104/03 and BaC 11549/03 were more similar (98.1% aa) to strains Belem and 208, detected in Brazil and China, respectively. CONCLUSIONS: Based on this 1-year study, we conclude that group C rotaviruses are not of epidemiological relevance in the etiology of childhood acute gastroenteritis in Hungary. The low sequence divergence between the Hungarian strains suggested that a single group C rotavirus strain circulated in this period in the study area.