University of Siena

About: University of Siena is a education organization based out in Siena, Italy. It is known for research contribution in the topics: Population & Cancer. The organization has 12179 authors who have published 33334 publications receiving 1008287 citations. The organization is also known as: Università degli studi di Siena & Universita degli studi di Siena.

Functional implications of the spectrum of mutations found in 234 cases with X-linked juvenile retinoschisis (XLRS)

Abstract: X-linked retinoschisis (XLRS) is the most common cause of juvenile macular degeneration in males, resulting in vision loss early in life The gene involved in XLRS was identified recently It encodes a protein with a disoidin domain, suggested to be involved in cell-cell interactions We have screened the gene for mutations in 234 familial and sporadic retinoschisis cases and identified 82 different mutations in 214 (91%) Thirty one mutations were found more than once, ie 2-10 times, with the exception of the 214G→A mutation which was found in 34 apparently unrelated cases The origin of the patients, the linkage data and the site of the mutations (mainly CG dinucleotides) indicate that most recurrent mutations had independent origins and thus suggest the existence of a significant new mutation rate in XLRS1 The mutations identified cover the entire spectrum, from small intra-genic deletions (7%), to nonsense (6%), missense (75%), small frameshifting insertions/deletions (6%) and splice site mutations (6%) Since, regardless of the mutation type, no females with a typical RS phenotype were identified, RS seems to be caused by loss-of-function mutations only Mutations occurred non-randomly, with hotspots at several CG dinudeotides and a C6 stretch Exons 1-3 contained few, mainly translation-truncating mutations, arguing against an important functional role for this segment of the protein Exons 4-6, encoding the discoidin domain, contained most, mainly missense mutations An alignment of 32 discoidin domain proteins was constructed to reveal the consensus sequence and to deduce the functional importance of the missense mutations identified The mutation analysis revealed a high preponderance of mutations involving or creating cysteine residues, pointing to sites important for the tertiary folding and/or protein function, and highlights several amino acids which may be involved in XLRS1-specific protein-protein interactions Despite the enormous mutation heterogeneity, patients have relatively uniform clinical manifestations although with great intra-familial variation in age at onset and progression

Blood oxygenation level dependent contrast resting state networks are relevant to functional activity in the neocortical sensorimotor system.

Abstract: The relevance of correlations between blood oxygenation level dependent (BOLD) signal changes across the brain acquired at rest (resting state networks, or RSN) to functional networks was tested using two quantitative criteria: (1) the localisation of major RSN correlation clusters and the task-related maxima defined in BOLD fMRI signal changes from the same subjects; and (2) the relative hemispheric lateralisation (LI) of BOLD fMRI signal changes in sensorimotor cortex RSN were defined on the basis of signal changes correlated with that of a "seed" voxel in the primary sensorimotor cortex We found a generally close spatial correspondence between clusters of correlated BOLD signal change in RSN and activation maxima associated with hand movement Conventional BOLD fMRI during active hand movement showed the expected wide variation in relative hemispheric lateralisation of LI for sensorimotor cortex across the subjects There was a good correlation between LIs for the active hand movement task and the RSN (r=074, p<0001) The RSN thus define anatomically relevant regions of motor cortex and change with functionally relevant variations in hemispheric lateralisation of sensorimotor cortical interactions with hand movement

Age-Related Functional Changes of Prefrontal Cortex in Long-Term Memory: A Repetitive Transcranial Magnetic Stimulation Study

Abstract: Neuroimaging findings suggest that the lateralization of prefrontal cortex activation associated with episodic memory performance is reduced by aging. It is still a matter of debate whether this loss of asymmetry during encoding and retrieval reflects compensatory mechanisms or de-differentiation processes. We addressed this issue by the transient interference produced by repetitive transcranial magnetic stimulation (rTMS), which directly assesses causal relationships between performance and stimulated regions. We compared the effects of rTMS (a rapid-rate train occurring simultaneously to the presentation of memoranda) applied to the left or right dorsolateral prefrontal cortex (DLPFC) on visuospatial recognition memory in 66 healthy subjects divided in two classes of age ( 50 years). In young subjects, rTMS of the right DLPFC interfered with retrieval more than left DLPFC stimulation. The asymmetry of the effect progressively vanished with aging, as indicated by bilateral interference effects on recognition performance. Conversely, the predominance of left DLPFC effect during encoding was not abolished in elders, thus probing its causal role for encoding along the life span. Findings confirm that the neural correlates of retrieval modify along aging, suggesting that the bilateral engagement of the DLPFC has a compensatory role on the elders' episodic memory performance.