Effects of stimulus duration on audio-visual synchrony perception

The integration of visual and auditory inputs in the human brain occurs only if the components are perceived in temporal proximity, that is, when the intermodal time difference falls within the so-called subjective synchrony range. We used the midpoint of this range to estimate the point of subjective simultaneity (PSS). We measured the PSS for audio-visual (AV) stimuli in a synchrony judgment task, in which subjects had to judge a given AV stimulus using three response categories (audio first, synchronous, video first). The relevant stimulus manipulation was the duration of the auditory and visual components. Results for unimodal auditory and visual stimuli have shown that the perceived onset shifts to relatively later positions with increasing stimulus duration. These unimodal shifts should be reflected in changing PSS values, when AV stimuli with different durations of the auditory and visual components are used. The results for 17 subjects showed indeed a significant shift of the PSS for different duration combinations of the stimulus components. Because the shifts were approximately equal for duration changes in either of the components, no net shift of the PSS was observed as long as the durations of the two components were equal. This result indicates the need to appropriately account for unimodal timing effects when quantifying intermodal synchrony perceptio

MITOCHONDRIAL OXODICARBOXYLATE CARRIER DEFICIENCY: METABOLIC MODELLING IDENTIFIES DISEASE MECHANISM

Members of the mitochondrial carrier family (SLC25) transport nucleotides, keto acids, amino acids, fatty acids, co-factors and inorganic ions across the mitochondrial inner membrane. Several inherited diseases with very variable clinical presentations are associated with dysfunctional mitochondrial carriers. We report a patient with childhood-onset spinal muscular atrophy and mitochondrial myopathy caused by a homozygous mutation in SLC25A21, encoding the mitochondrial oxodicarboxylate carrier (ODC). The mutation renders the carrier dysfunctional and, consequently, 2-oxoadipate cannot be imported into the mitochondrial matrix. Computer modelling of the metabolic defect caused by the mutation predicted that the impaired transport leads to accumulation of 2-oxoadipate, pipecolic acid and the known neurotoxin quinolinic acid, which were precisely confirmed by targeted metabolomics in serum and urine. Exposure of 2-oxoadipate and quinolinic acid reduced the level of mitochondrial complexes in SH-SY5Y cells in-vitro suggesting a possible pathomechanism. Here we demonstrate that 2-oxoadipate and quinolinic acid are toxic for spinal motor neurons and their increased levels may contribute to neuropathy

Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis-1 like phenotype

We report germline loss- of- function mutations in SPRED1 in a newly identified autosomal dominant human disorder. SPRED1 is a member of the SPROUTY/ SPRED family(1) of proteins that act as negative regulators of RAS- RAF interaction and mitogen-activated protein kinase ( MAPK) signaling(2). The clinical features of the reported disorder resemble those of neurofibromatosis type 1 and consist of multiple cafe - au- lait spots, axillary freckling and macrocephaly. Melanocytes from a cafe - au- lait spot showed, in addition to the germline SPRED1 mutation, an acquired somatic mutation in the wild- type SPRED1 allele, indicating that complete SPRED1 inactivation is needed to generate a cafe - au- lait spot in this syndrome. This disorder is yet another member of the recently characterized group of phenotypically overlapping syndromes caused by mutations in the genes encoding key components of the RAS- MAPK pathway(3,4). To our knowledge, this is the first report of mutations in the SPRY ( SPROUTY)/ SPRED family of genes in human disease