Nanoscale Dynamics of Phase Flipping in Water near its Hypothesized Liquid-Liquid Critical Point

Achieving a coherent understanding of the many thermodynamic and dynamic anomalies of water is among the most important unsolved puzzles in physics, chemistry, and biology. One hypothesized explanation imagines the existence of a line of first order phase transitions separating two liquid phases and terminating at a novel "liquid-liquid" critical point in a region of low temperature ($T \approx 250 \rm{K}$) and high pressure ($P \approx 200 \rm{MPa}$). Here we analyze a common model of water, the ST2 model, and find that the entire system flips between liquid states of high and low density. Further, we find that in the critical region crystallites melt on a time scale of nanoseconds. We perform a finite-size scaling analysis that accurately locates both the liquid-liquid coexistence line and its associated liquid-liquid critical point.Comment: 22 pages, 5 figure

Spatial Extent of Charge Repulsion Regulates Assembly Pathways for Lysozyme Amyloid Fibrils

Formation of large protein fibrils with a characteristic cross β-sheet architecture is the key indicator for a wide variety of systemic and neurodegenerative amyloid diseases. Recent experiments have strongly implicated oligomeric intermediates, transiently formed during fibril assembly, as critical contributors to cellular toxicity in amyloid diseases. At the same time, amyloid fibril assembly can proceed along different assembly pathways that might or might not involve such oligomeric intermediates. Elucidating the mechanisms that determine whether fibril formation proceeds along non-oligomeric or oligomeric pathways, therefore, is important not just for understanding amyloid fibril assembly at the molecular level but also for developing new targets for intervening with fibril formation. We have investigated fibril formation by hen egg white lysozyme, an enzyme for which human variants underlie non-neuropathic amyloidosis. Using a combination of static and dynamic light scattering, atomic force microscopy and circular dichroism, we find that amyloidogenic lysozyme monomers switch between three different assembly pathways: from monomeric to oligomeric fibril assembly and, eventually, disordered precipitation as the ionic strength of the solution increases. Fibril assembly only occurred under conditions of net repulsion among the amyloidogenic monomers while net attraction caused precipitation. The transition from monomeric to oligomeric fibril assembly, in turn, occurred as salt-mediated charge screening reduced repulsion among individual charged residues on the same monomer. We suggest a model of amyloid fibril formation in which repulsive charge interactions are a prerequisite for ordered fibril assembly. Furthermore, the spatial extent of non-specific charge screening selects between monomeric and oligomeric assembly pathways by affecting which subset of denatured states can form suitable intermolecular bonds and by altering the energetic and entropic requirements for the initial intermediates emerging along the monomeric vs. oligomeric assembly path

RIGIDITY, SENSITIVITY AND QUALITY OF ATTACHMENT - THE ROLE OF MATERNAL RIGIDITY IN THE EARLY SOCIOEMOTIONAL DEVELOPMENT OF PREMATURE-INFANTS

The associations between a mother's rigidity, her sensitivity in early (3 month) interaction and the quality of her premature infant's attachment at 13 months were investigated. Rigidity as a personality characteristic was not found to be significantly associated with sensitivity or quality of attachment. Rigid attitudes to child rearing were related to sensitivity and to the responsivity of the infant. Rigid attitudes were not related to security of attachment. Infants who were rated less responsive at 3 months, however, tended to be less securely attached, and high Attitude Rigidity in the mother increased their chances of an insecure attachment