Association between Sensory Processing by Children with High Functioning Autism Spectrum Disorder and their Daily Routines

Background: Children diagnosed with autism spectrum disorder exhibit persistent deficits in social communication and social interaction accompanied by restricted, repetitive patterns of behavior, interests, or activities. Those with normal intelligence are considered to have high functioning autism spectrum disorder (HFASD). Method: The study participants were 20 children with HFASD aged 5 to 7 years old attending mainstream educational programs and their parents (study group) and 30 typically-developing age-matched children from the same socio-economic background and their parents (control group). Parents from both groups completed the Short Sensory Profile to investigate their children’s sensory processing and the presence of Sensory Processing Disorder. Children and parents from both groups were administered the Make My Day (MMD) to obtain information regarding the children’s participation and performance in daily activities. Results: The study group had significantly more sensory difficulties, which correlated with restricted daily routines, compared with the control group. SPD significantly predicted the quality and independence of the performance of daily activities by children with HFASD as measured by the MMD. Conclusions: SPD may be a worthwhile therapeutic target for therapists seeking to improve participation in and performance of daily activities, as identified by the MMD, among children with HFASD

Digital Museum of Retinal Ganglion Cells with Dense Anatomy and Physiology

When 3D electron microscopy and calcium imaging are used to investigate the structure and function of neural circuits, the resulting datasets pose new challenges of visualization and interpretation. Here, we present a new kind of digital resource that encompasses almost 400 ganglion cells from a single patch of mouse retina. An online "museum" provides a 3D interactive view of each cell's anatomy, as well as graphs of its visual responses. The resource reveals two aspects of the retina's inner plexiform layer: an arbor segregation principle governing structure along the light axis and a density conservation principle governing structure in the tangential plane. Structure is related to visual function; ganglion cells with arbors near the layer of ganglion cell somas are more sustained in their visual responses on average. Our methods are potentially applicable to dense maps of neuronal anatomy and physiology in other parts of the nervous system

TstI, a Type II restriction–modification protein with DNA recognition, cleavage and methylation functions in a single polypeptide

Type II restriction–modification systems cleave and methylate DNA at specific sequences. However, the Type IIB systems look more like Type I than conven-tional Type II schemes as they employ the same pro-tein for both restriction and modification and for DNA recognition. Several Type IIB proteins, including the archetype BcgI, are assemblies of two polypeptides: one with endonuclease and methyltransferase roles, another for DNA recognition. Conversely, some IIB proteins express all three functions from separate segments of a single polypeptide. This study anal-ysed one such single-chain protein, TstI. Compar-ison with BcgI showed that the one- and the two-polypeptide systems differ markedly. Unlike the het-erologous assembly of BcgI, TstI forms a homote-tramer. The tetramer bridges two recognition sites before eventually cutting the DNA in both strands on both sides of the sites, but at each site the first double-strand break is made long before the second. In contrast, BcgI cuts all eight target bonds at two sites in a single step. TstI also differs from BcgI in either methylating or cleaving unmodified sites at similar rates. The site may thus be modified before TstI can make the second double-strand break. TstI MTase acts best at hemi-methylated sites

Csy4 relies on an unusual catalytic dyad to position and cleave CRISPR RNA

CRISPR-Cas adaptive immune systems protect prokaryotes against foreign genetic elements. crRNAs derived from CRISPR loci base pair with complementary nucleic acids, leading to their destruction. In Pseudomonas aeruginosa, crRNA biogenesis requires the endoribonuclease Csy4, which binds and cleaves the repetitive sequence of the CRISPR transcript. Biochemical assays and three co-crystal structures of wild-type and mutant Csy4/RNA complexes reveal a substrate positioning and cleavage mechanism in which a histidine deprotonates the ribosyl 2′-hydroxyl pinned in place by a serine, leading to nucleophilic attack on the scissile phosphate. The active site catalytic dyad lacks a general acid to protonate the leaving group and positively charged residues to stabilize the transition state, explaining why the observed catalytic rate constant is ∼10(4)-fold slower than that of RNase A. We show that this RNA cleavage step is essential for assembly of the Csy protein-crRNA complex that facilitates target recognition. Considering that Csy4 recognizes a single cellular substrate and sequesters the cleavage product, evolutionary pressure has likely selected for substrate specificity and high-affinity crRNA interactions at the expense of rapid cleavage kinetics