Voice recognition and cross-modal responses to familiar speakers' voices in prosopagnosia

Recognizing the voices of people we know does not only activate "voice areas" in the temporal lobe but also extraauditory areas including the fusiform "face area" (FFA). This cross-modal effect could reflect that individual face and voice information become specifically associated when becoming acquainted with a person. Here, we addressed whether the ability to have individual face representations 1) plays a role in voice recognition and 2) is required to observe cross-modal responses to voices in face areas. We compared speaker recognition performance and neuroimaging responses during the processing of familiar and nonfamiliar speakers' voices in a developmental prosopagnosic subject (SO) with the respective findings obtained in a group of 9 control subjects. Despite scoring worse than controls on recognition of familiar speakers' voices, SO had normal cross-modal responses in the FFA and normal connectivity between FFA and the voice regions. However, she had reduced activations in areas that usually respond to familiarity with people. An indication for the malfunctioning of her FFA was reduced connectivity of the FFA to a subset of these supramodal areas. In combination these data suggest that 1) voice recognition benefits from the ability to process faces at an individual level and 2) cross-modal association of voices and faces in the brain is achieved by a sensory binding and does not depend on a top-down mechanism subsequent to successful person recognition.     

Experimental validation of data mined single nucleotide polymorphisms from several databases and consecutive dbSNP builds

Rapid development in the annotation of human genetic variation has increased the numbers of single nucleotide polymorphisms (SNPs) in candidate genes by several orders of magnitude. The selection of both useful target SNPs for disease-gene association studies and SNPs associated with the treatment response is therefore an increasingly challenging task. We describe a workflow for selecting SNPs based on their putative function and frequency in candidate genes extracted from PubMed resources. The annotation of each SNP and its frequency in a Caucasian population was assessed in several databases. Approximately 4000 SNPs were identified from an initial 233 candidate genes. In a case study, we performed actual genotyping of 1030 of these SNPs in 213 genes and obtained 710 successfully genotyped SNPs. Using the flow-chart outlined here, only 87 SNPs were monomorphic (approximately 12%). This study reports the frequency of SNPs in a Caucasian population, selected in silico, using a candidate gene approach and validated by actually genotyping 193 individuals. The selected genotypes represent a valuable set of verified candidate SNPs for pharmacogenetic studies in Caucasian populations.     

Impairment across executive functions in recurrent major depression

Depression is associated with impairment of cognitive functions, and especially executive functions (EFs). Despite the fact that most depressed patients experience recurrence of episodes, the pattern and the severity of executive impairment have not been well characterized in this group of depressed patients. We asked if and to what extent these patients were impaired on a range of neuropsychological tests measuring EFs, and also when confounding factors were adjusted for. Forty-five patients (aged 19-51 years) with moderate to severe (Hamilton score >18) recurrent major depressive disorder (DSM-IV) were compared to 50 healthy controls matched on age, education, gender and intellectual abilities. The subjects were administered a set of neuropsychological tests that assesses sub-components of EFs. The depressed patients were impaired compared to the control group on all selected tests, with a severity of impairment within -1 standard deviation from the control group mean. The group difference was statistically significant for eight of the 10 EFs that were assessed. These were measures of verbal fluency, inhibition, working memory, set-maintenance and set-shifting. The group difference was still significant for all sub-components except for set-shifting (Wisconsin Card Sorting Test) and planning (Tower of London), when additional medication and retarded psychomotor speed was adjusted for. In conclusion, the depressed subjects were mildly impaired across a wide range of EFs. This may have a negative impact on everyday functioning for this group of patients.     

Whey predominant,whey modified infant formula with protein/energy ratio of 1.8 g/100 kcal: adequate and safe for term infants from birth to four months

BACKGROUND: Protein quality of breast milk is superior to that of formula proteins. To ensure that the protein intake is sufficient, starter formulas with conventional protein composition provide a protein/energy ratio of 2.2-2.5 g per 100 kcal to infants, which is much higher than that supplied with breast milk. Several studies have shown that formula-fed infants have higher plasma or serum urea concentrations than breast-fed infants do. We tested if feeding formulas with improved protein quality and a protein content corresponding to the minimum level that is consistent with international recommendations (1.8 g/100 kcal) allows patients to achieve normal growth and plasma urea concentrations. METHODS: Healthy term infants were enrolled into the study and were either breast-fed or randomly assigned to three formula-fed groups. Formula-fed infants received either a standard formula with a protein/energy ratio of 2.2 g/100 kcal, whereas the two other groups received formulas with a protein/energy ratio of 1.8g/100 kcal differing mainly by their source of protein. Subjects received breast milk or these formulas ad libitum as the sole source of energy from birth to four months of age in a controlled blind design (except for the breast-fed group). Anthropometric measurements (body weight and length) were obtained at birth, at 30, 60, 90, and 120 days. Energy and protein intakes were calculated from three-day dietary records. Blood was collected for biochemical measurements at 30, 60, and 120 days. RESULTS: No differences were found between the four feeding groups for weight- and length-gains or for body mass indices (BMI). No differences in energy intakes between the formula-fed groups could be found, whereas protein intakes were less in infants fed the 1.8 g/100 kcal formulas. Plasma urea levels of the infants fed the 1.8 g/100 kcal formulas were closer to those found in the breast-fed infants. CONCLUSION: Improvement of the amino acid profile permits a whey predominant starter formula with 1.8 g protein per 100 kcal to meet the needs of normal term infants during the first four months of life.     

Assessment of CD8 involvement in T cell clone avidity by direct measurement of HLA-A2/Mage3 complex density using a high-affinity TCR like monoclonal antibody

Peptide affinity for MHC molecules determines the number of MHC/peptide complexes stabilized at the cell surface in in vitro tests or in vaccination protocols. We isolated a high affinity monoclonal antibody specific for the HLA-A2/Mage3 complex that enables an equilibrium binding assay to be performed on T2 cell line loaded with a range of Mage3 peptides. Binding of Mage3 to the HLA-A2 molecule can be modeled by a standard receptor-ligand interaction characterized by an affinity constant. This model enables the measurement of the affinity of other immunogenic peptides for HLA-A2 by a competition test and the calculation of the density of complexes stabilized at the T2 cell surface for all peptide concentrations. Quantification of the HLA-A2/Mage3 complexes at target cell surfaces was used to estimate the number of complexes required to reach cytotoxicity ED50 of human T cell clones sorted from an unprimed repertoire. We confirm with this antibody the direct relationship between clone avidity and TCR affinity, and the moderate contribution of the CD8 co-receptor in the reinforcement of TCR-MHC/peptide contact. Nevertheless, CD8 plays a critical role in the amplification of the specific signal to establish an efficient T cell response at low specific complex densities found in physiological situations.     

High-resolution gene copy number and expression profiling of human chromosome 22 in ovarian carcinomas

Previous low-resolution studies of chromosome 22 in ovarian carcinoma have suggested its involvement in the development of the disease. We report a high-resolution analysis of DNA copy number and gene expression of 22q in 18 ovarian carcinomas using a 22q-specific genomic microarray. We identified aberrations in 67% of the studied tumors, which displayed 3 distinct gene copy number profiles. The majority of the cases (11 of 18) demonstrated heterozygous terminal deletions of various sizes, the smallest of which was 3.5 Mb. The second profile, detected in 3 tumors, revealed the coexistence of heterozygous deletions and different patterns of low-copy-number gain that involved the proximal half of 22q. The latter finding has not been reported previously in ovarian carcinoma. One case displayed a continuous deletion encompassing the entire 22q, consistent with monosomy 22. Furthermore, we compared the results with the available data on these tumors by using cDNA microarrays to define the degree of correlation between abnormalities at the DNA level and variation in mRNA expression. By a comparison with the expression data, we were able to identify 21 deleted genes showing low mRNA levels and 12 amplified genes displaying elevated gene expression, several of which play roles in cell cycle control and the induction of apoptosis. Our results indicated significant correlation between DNA copy number aberrations and variation in mRNA expression. We also identified several regions and candidate genes on 22q that should be studied further to determine their role in the development of ovarian cancer.