Modeling of DNA binding to the condensin hinge domain using molecular dynamics simulations guided by atomic force microscopy

The condensin protein complex compacts chromatin during mitosis using its DNA-loop extrusion activity. Previous studies proposed scrunching and loop-capture models as molecular mechanisms for the loop extrusion process, both of which assume the binding of double-strand (ds) DNA to the hinge domain formed at the interface of the condensin subunits Smc2 and Smc4. However, how the hinge domain contacts dsDNA has remained unknown. Here, we conducted atomic force microscopy imaging of the budding yeast condensin holo-complex and used this data as basis for coarse-grained molecular dynamics simulations to model the hinge structure in a transient open conformation. We then simulated the dsDNA binding to open and closed hinge conformations, predicting that dsDNA binds to the outside surface when closed and to the outside and inside surfaces when open. Our simulations also suggested that the hinge can close around dsDNA bound to the inside surface. Based on these simulation results, we speculate that the conformational change of the hinge domain might be essential for the dsDNA binding regulation and play roles in condensin-mediated DNA-loop extrusion

Medaka: a promising model animal for comparative population genomics

<p>Abstract</p> <p>Background</p> <p>Within-species genome diversity has been best studied in humans. The international HapMap project has revealed a tremendous amount of single-nucleotide polymorphisms (SNPs) among humans, many of which show signals of positive selection during human evolution. In most of the cases, however, functional differences between the alleles remain experimentally unverified due to the inherent difficulty of human genetic studies. It would therefore be highly useful to have a vertebrate model with the following characteristics: (1) high within-species genetic diversity, (2) a variety of gene-manipulation protocols already developed, and (3) a completely sequenced genome. Medaka (<it>Oryzias latipes</it>) and its congeneric species, tiny fresh-water teleosts distributed broadly in East and Southeast Asia, meet these criteria.</p> <p>Findings</p> <p>Using <it>Oryzias </it>species from 27 local populations, we conducted a simple screening of nonsynonymous SNPs for 11 genes with apparent orthology between medaka and humans. We found medaka SNPs for which the same sites in human orthologs are known to be highly differentiated among the HapMap populations. Importantly, some of these SNPs show signals of positive selection.</p> <p>Conclusion</p> <p>These results indicate that medaka is a promising model system for comparative population genomics exploring the functional and adaptive significance of allelic differentiations.</p

Eye tracking in an everyday environment reveals the interpersonal distance that affords infant-parent gaze communication

親子の視線交渉が対人距離によって調節されることを解明 --親視点から探る、乳児と親の視線のやりとり--. 京都大学プレスリリース. 2019-07-24.The unique morphology of human eyes enables gaze communication at various ranges of interpersonal distance. Although gaze communication contributes to infants’ social development, little is known about how infant-parent distance affects infants’ visual experience in daily gaze communication. The present study conducted longitudinal observations of infant-parent face-to-face interactions in the home environment as 5 infants aged from 10 to 15.5 months. Using head-mounted eye trackers worn by parents, we evaluated infants’ daily visual experience of 3138 eye contact scenes recorded from the infants’ second-person perspective. The results of a hierarchical Bayesian statistical analysis suggest that certain levels of interpersonal distance afforded smooth interaction with eye contact. Eye contacts were not likely to be exchanged when the infant and parent were too close or too far apart. The number of continuing eye contacts showed an inverse U-shaped pattern with interpersonal distance, regardless of whether the eye contact was initiated by the infant or the parent. However, the interpersonal distance was larger when the infant initiated the eye contact than when the parent initiated it, suggesting that interpersonal distance affects the infant’s and parent’s social look differently. Overall, the present study indicates that interpersonal distance modulates infant-parent gaze communication

Bone marrow transplantation improves outcome in a mouse model of congenital muscular dystrophy

AbstractWe examined whether pathogenesis in dystrophin-deficient (mdx) mice and laminin-α2-deficient (dy) mice is ameliorated by bone marrow transplantation (BMT). Green fluorescent protein (GFP) mice were used as donors. In mdx mice, BMT failed to produce any significant differences in muscle pathology, although some GFP-positive fibers with restored dystrophin expression were observed. In contrast, in the dy mice, BMT led to a significant increase in lifespan and an increase in growth rate, muscle strength, and respiratory function. We conclude that BMT improved outcome in dy mice but not mdx mice

<Review>Biochemical Study on Nicotinic Acetylcholine Receptor

Nicotinic acetylcholine receptor (AChR) is a multisubunit membrane glycoprotein which functions as a ligand-triggered cation channel. Receptors from electric tissues and skeletal muscle have a molecular weight of approximately 290,000 as a monomer and are composed of four types of polypeptide chains which assemble into a heterologous α_2βγδ pentamer. We determined the carbohydrate structure of Torpedo AChR, which was the first determination for neurotransmitter receptors. About 70 % of the oligosaccharides of the AChR were of the high mannose-type, Man_9GlcNAc_2 and Man_8GlcNAc_2. These two types of oligosaccharides were distributed in all the subunits. The remaining were various kinds of complex-type oligosaccharides, existing mainly in the γ and δ subunits. The α and β subunits had only one carbohydrate chain each, while the γ and δ subunits had two and three carbohydrate chains, respectively. These glycosylation sites were identified by sequencing glycopeptides obtained by lectin-affinity chromatography. The participation of oligosaccharides in ligand-binding of AChR was examined using a newly developed binding assay. The sialic acids and high mannose-type oligosaccharides on AChR were found to be unnecessary for its ligand binding. Next we found that the β and δ subunits of Torpedo AChR were phosphorylated on their tyrosine residues. The level of the phosphorylation was enhanced by incubating the AChR-rich membrane fraction with cholinergic ligands. This suggests that cholinergic agonists physiologically regulate phosphorylation on tyrosine in vivo, which might be included in the desensitization mechanism of the receptor. We also examined the spatial relation of proteins surrounding AChR using Torpedo AChR-rich membrane fraction. Bifunctional crosslinkers revealed an intimate relation among the AChR γ subunit, 43-kD protein, and dystrophin. Finally, we found neurotoxin-binding activities in the su-pernatant fraction obtained by ultracentrifugation of a homogenate of the electric organ, which usually does not contain AChR. This new activity was different in nature from AChR, and could function as a regulator or a modulator for AChR function

Anaphylactic shock due to latex allergy

Natural rubber latex (NRL) allergy is one of the most important causes of severe anaphylaxis during medical intervention. We report a pediatric case of latex allergy with multiple surgical histories. A 12-year-old girl developed anaphylactic shock during the pyeloplasty for ureteropelvic junction restenosis. Latex gloves or medications used during the surgery were suspected to be the cause of anaphylactic shock. We diagnosed her latex allergy on the basis of the results that serum latex-specific IgE, skin prick tests of extract from NRL gloves and recombinant Hev b 6.02 solution were positive. Basophil activation test of NRL gloves was also positive, supporting the diagnosis of immediate allergic reactions caused by NRL. It was speculated that a history of multiple surgeries in infancy became a trigger of sensitization to latex in this patient. Reoperation after the diagnosis of NRL allergy was carried out in a latex-free environment and completed without any allergic symptoms. It would be necessary to perform the pre-screening of latex allergy to prevent the onset of latex allergy especially in the patients with multiple surgical histories