Block design performance in the Williams syndrome phenotype: A problem with mental imagery?

Williams syndrome (WS) is a rare genetic disorder which, among other characteristics, has a distinctive cognitive profile. Non-verbal abilities are generally poor in relation to verbal abilities, but also show varying levels of ability in relation to each other. Performance on block construction tasks represents arguably the weakest non-verbal ability in WS. In this study we examined two requirements of block construction tasks in 21 individuals with WS and 21 typically developing (TD) control individuals. The Squares task, a novel two-dimensional block construction task, manipulated patterns by segmentation and perceptual cohesiveness to investigate the first factor, processing preference (local or global), and by obliqueness to examine the second factor, the ability to use mental imagery. These two factors were investigated directly by the Children?s Embedded Figures Test (CEFT; Witkin, Oltman, Raskin & Karp, 1971) and a mental rotation task respectively. Results showed that individuals with WS did not differ from the TD group in their processing style. However, the ability to use mental imagery was significantly poorer in the WS group than the TD group. This suggests that weak performance on the block construction tasks in WS may relate to an inability to use mental imagery

Divided attention, selective attention and drawing: Processing preferences in Williams syndrome are dependent on the task administered

The visuo-spatial abilities of individuals with Williams syndrome (WS) have consistently been shown to be generally weak. These poor visuo-spatial abilities have been ascribed to a local processing bias by some [30] and conversely, to a global processing bias by others [24]. In this study, two identification versions and one drawing version of the Navon hierarchical processing task, a non-verbal task, were employed to investigate this apparent contradiction. The two identification tasks were administered to 21 individuals with WS, 21 typically developing individuals, matched by non-verbal ability, and 21 adult participants matched to the WS group by mean chronological age. The third, drawing task was administered to the WS group and the TD controls only. It was hypothesised that the WS group would show differential processing biases depending on the type of processing the task was measuring. Results from two identification versions of the Navon task measuring divided and selective attention showed that the WS group experienced equal interference from global to local as from local to global levels, and did not show an advantage of one level over another. This pattern of performance was broadly comparable to that of the control groups. The third task, a drawing version of the Navon task, revealed that individuals with WS were significantly better at drawing the local form in comparison to the global figure, whereas the typically developing control group did not show a bias towards either level. In summary, this study demonstrates that individuals with WS do not have a local or a global processing bias when asked to identify stimuli, but do show a local bias in their drawing abilities. This contrast may explain the apparently contrasting findings from previous studies

Derivation of nearest-neighbor DNA parameters in magnesium from single-molecule experiments

DNA hybridization is an essential molecular reaction in biology with many applications. The nearest-neighbor (NN) model for nucleic acids predicts DNA thermodynamics using energy values for the different base pair motifs. These values have been derived from melting experiments in monovalent and divalent salt and applied to predict melting temperatures of oligos within a few degrees. However, an improved determination of the NN energy values and their salt dependencies in magnesium is still needed for current biotechnological applications seeking high selectivity in the hybridization of synthetic DNAs. We developed a methodology based on single molecule unzipping experiments to derive accurate NN energy values and initiation factors for DNA. A new set of values in magnesium is derived, which reproduces unzipping data and improves melting temperature predictions for all available oligo lengths, in a range of temperature and salt conditions where correlation effects between the magnesium bound ions are weak. The NN salt correction parameters are shown to correlate to the GC content of the NN motifs. Our study shows the power of single-molecule force spectroscopy assays to unravel novel features of nucleic acids such as sequence-dependent salt corrections

Genetic contributions to visuospatial cognition in Williams syndrome: insights from two contrasting partial deletion patients

Background Williams syndrome (WS) is a rare neurodevelopmental disorder arising from a hemizygotic deletion of approximately 27 genes on chromosome 7, at locus 7q11.23. WS is characterised by an uneven cognitive profile, with serious deficits in visuospatial tasks in comparison to relatively proficient performance in some other cognitive domains such as language and face processing. Individuals with partial genetic deletions within the WS critical region (WSCR) have provided insights into the contribution of specific genes to this complex phenotype. However, the combinatorial effects of different genes remain elusive. Methods We report on visuospatial cognition in two individuals with contrasting partial deletions in the WSCR: one female (HR), aged 11 years 9 months, with haploinsufficiency for 24 of the WS genes (up to GTF2IRD1), and one male (JB), aged 14 years 2 months, with the three most telomeric genes within the WSCR deleted, or partially deleted. Results Our in-depth phenotyping of the visuospatial domain from table-top psychometric, and small- and large-scale experimental tasks reveal a profile in HR in line with typically developing controls, albeit with some atypical features. These data are contrasted with patient JB’s atypical profile of strengths and weaknesses across the visuospatial domain, as well as with more substantial visuospatial deficits in individuals with the full WS deletion. Conclusions Our findings point to the contribution of specific genes to spatial processing difficulties associated with WS, highlighting the multifaceted nature of spatial cognition and the divergent effects of genetic deletions within the WSCR on different components of visuospatial ability. The importance of general transcription factors at the telomeric end of the WSCR, and their combinatorial effects on the WS visuospatial phenotype are also discussed

Reliability and Validity of the PROMIS-29 Health Profile in Ankylosing Spondylitis Patients: A Cross-Sectional Study

The Patient-Reported Outcomes Measurement Information System 29-Item Health Profile (PROMIS-29) is a generic measure of health-related quality of life that is not well-studied in Ankylosing Spondylitis (AS) patients. Our objective was to investigate the reliability and validity of the PROMIS-29 in AS. About 169 consecutive AS patients were enrolled from 2017 to 2022 with 167/169 patients fully completing the PROMIS-29 in this cross-sectional study. Test-retest reliability and internal consistency was assessed using intraclass correlation coefficients (ICC) and Cronbach alpha, respectively. We studied structural validity with confirmatory factor analysis (CFA) of our hypothesized and general population models. We evaluated model fit by Chi-squared goodness-of-fit-test (χ2), comparative fit index, and root mean square error of approximation. A χ2 test was used to compare nested models. PROMIS-29 convergent validity was studied by Spearman correlation coefficients with AS-legacy measures. PROMIS-29 domains showed good test-retest reliability (intraclass correlation coefficients (ICC) \u3e 0.7) and excellent internal consistency with Cronbach alpha \u3e 0.9 in all subscales. CFA of only the general population model met our model fit cutoffs (χ2 goodness-of-fit P-value of 0.21, comparative fit index of 0.99, and root mean square error of approximation of 0.05). Furthermore, a nested χ2 test was not significantly different between our hypothesized (full) and general (reduced) model [χ2 (1) = 0.754, P \u3e .38]. AS legacy measures showed a strong correlation (rho \u3e |0.7|) with the extracted physical health factor. The PROMIS-29 demonstrated good reliability and construct validity in AS patients with the general population model. Further study is required to determine its clinical and research utility in AS patients

Cooperativity-Dependent Folding of Single-Stranded DNA

The folding of biological macromolecules is a fundamental process of which we lack a full comprehension. Mostly studied in proteins and RNA, single-stranded DNA (ssDNA) also folds, at physiological salt conditions, by forming nonspecific secondary structures that are difficult to characterize with biophysical techniques. Here, we present a helix-coil model for secondary-structure formation, where ssDNA bases are organized in two different types of domains (compact and free). The model contains two parameters: the energy gain per base in a compact domain, ε , and the cooperativity related to the interfacial energy between different domains, γ . We test the ability of the model to quantify the formation of secondary structure in ssDNA molecules mechanically stretched with optical tweezers. The model reproduces the experimental force-extension curves in ssDNA of different molecular lengths and varying sodium and magnesium concentrations. Salt-correction effects for the energy of compact domains and the interfacial energy are found to be compatible with those of DNA hybridization. The model also predicts the folding free energy and the average size of domains at zero force, finding good agreement with secondary-structure predictions by mfold. We envision the model could be further extended to investigate native folding in RNA and protein

Route knowledge and configural knowledge in typical and atypical development: a comparison of sparse and rich environments

Background: Individuals with Down syndrome (DS) and individuals with Williams syndrome (WS) have poor navigation skills, which impact their potential to become independent. Two aspects of navigation were investigated in these groups, using virtual environments (VE): route knowledge (the ability to learn the way from A to B by following a fixed sequence of turns) and configural knowledge (knowledge of the spatial relationships between places within an environment). Methods: Typically developing (TD) children aged 5 to 11 years (N = 93), individuals with DS (N = 29) and individuals with WS (N = 20) were presented with a sparse and a rich VE grid maze. Within each maze, participants were asked to learn a route from A to B and a route from A to C before being asked to find a novel shortcut from B to C. Results: Performance was broadly similar across sparse and rich mazes. The majority of participants were able to learn novel routes, with poorest performance in the DS group, but the ability to find a shortcut, our measure of configural knowledge, was limited for all three groups. That is, 59 % TD participants successfully found a shortcut, compared to 10 % participants with DS and 35 % participants with WS. Differences in the underlying mechanisms associated with route knowledge and configural knowledge and in the developmental trajectories of performance across groups were observed. Only the TD participants walked a shorter distance in the last shortcut trial compared to the first, indicative of increased configural knowledge across trials. The DS group often used an alternative strategy to get from B to C, summing the two taught routes together. Conclusions: Our findings demonstrate impaired configural knowledge in DS and in WS, with the strongest deficit in DS. This suggests that these groups rely on a rigid route knowledge based method for navigating and as a result are likely to get lost easily. Route knowledge was also impaired in both DS and WS groups and was related to different underlying processes across all three groups. These are discussed with reference to limitations in attention and/or visuo-spatial processing in the atypical groups