Physics of Nuclei: Key Role of an Emergent Symmetry

We show through first-principles nuclear structure calculations that the special nature of the strong nuclear force determines highly regular patterns heretofore unrecognized in nuclei that can be tied to an emergent approximate symmetry. This symmetry is ubiquitous and mathematically tracks with a symplectic symmetry group. This, in turn, has important implications for understanding the physics of nuclei: we find that nuclei are made of only a few equilibrium shapes, deformed or not, with associated vibrations and rotations. It also opens the path for ab initio large-scale modeling of open-shell intermediate-mass nuclei without the need for renormalized interactions and effective charges

Increasing Internodal Distance in Myelinated Nerves Accelerates Nerve Conduction to a Flat Maximum

SummaryPredictions that conduction velocities are sensitive to the distance between nodes of Ranvier in myelinated axons have implications for nervous system function during growth and repair [1–3]. Internodal lengths defined by Schwann cells in hindlimb nerves, for example, can undergo a 4-fold increase during mouse development, and regenerated nerves have internodes that are uniformly short [4, 5]. Nevertheless, the influence of internodal length on conduction speed has limited experimental support. Here, we examined this problem in mice expressing a mutant version of periaxin, a protein required for Schwann cell elongation [4]. Importantly, elongation of mutant Schwann cells was retarded without significant derangements to myelination or axon caliber. In young mice with short mutant Schwann cells, nerve conduction velocity was reduced and motor function was impaired. This demonstrates a functional relationship between internodal distance and conduction speed. Moreover, as internodes lengthened during postnatal growth, conduction velocities recovered to normal values and mutant mice exhibited normal motor and sensory behavior. This restoration of function confirms a further prediction by Huxley and Stämpfli that conduction speeds should increase as internodal distances lengthen until a “flat maximum” is reached, beyond which no further gains in conduction velocity accrue [6]

A murine model of Charcot-Marie-Tooth disease 4F reveals a role for the C-terminus of periaxin in the formation and stabilization of Cajal bands

Charcot-Marie-Tooth (CMT) disease comprises up to 80 monogenic inherited neuropathies of the peripheral nervous system (PNS) that collectively result in demyelination and axon degeneration. The majority of CMT disease is primarily either dysmyelinating or demyelinating in which mutations affect the ability of Schwann cells to either assemble or stabilize peripheral nerve myelin. CMT4F is a recessive demyelinating form of the disease caused by mutations in the Periaxin (PRX) gene. Periaxin (Prx) interacts with Dystrophin Related Protein 2 (Drp2) in an adhesion complex with the laminin receptor Dystroglycan (Dag). In mice the Prx/Drp2/Dag complex assembles adhesive domains at the interface between the abaxonal surface of the myelin sheath and the cytoplasmic surface of the Schwann cell plasma membrane. Assembly of these appositions causes the formation of cytoplasmic channels called Cajal bands beneath the surface of the Schwann cell plasma membrane. Loss of either Periaxin or Drp2 disrupts the appositions and causes CMT in both mouse and man. In a mouse model of CMT4F, complete loss of Periaxin first prevents normal Schwann cell elongation resulting in abnormally short internodal distances which can reduce nerve conduction velocity, and subsequently precipitates demyelination. Distinct functional domains responsible for Periaxin homodimerization and interaction with Drp2 to form the Prx/Drp2/Dag complex have been identified at the N-terminus of Periaxin. However, CMT4F can also be caused by a mutation that results in the truncation of Periaxin at the extreme C-terminus with the loss of 391 amino acids. By modelling this in mice, we show that loss of the C-terminus of Periaxin results in a surprising reduction in Drp2. This would be predicted to cause the observed instability of both appositions and myelin, and contribute significantly to the clinical phenotype in CMT4F

Periaxin is required for hexagonal geometry and membrane organization of mature lens fibers

AbstractTransparency of the ocular lens depends on symmetric packing and membrane organization of highly elongated hexagonal fiber cells. These cells possess an extensive, well-ordered cortical cytoskeleton to maintain cell shape and to anchor membrane components. Periaxin (Prx), a PDZ domain protein involved in myelin sheath stabilization, is also a component of adhaerens plaques in lens fiber cells. Here we show that Prx is expressed in lens fibers and exhibits maturation dependent redistribution, clustering discretely at the tricellular junctions in mature fiber cells. Prx exists in a macromolecular complex with proteins involved in membrane organization including ankyrin-B, spectrin, NrCAM, filensin, ezrin and desmoyokin. Importantly, Prx knockout mouse lenses were found to be softer and more easily deformed than normal lenses, revealing disruptions in fiber cell hexagonal packing, membrane skeleton and membrane stability. These observations suggest a key role for Prx in maturation, packing, and membrane organization of lens fiber cells. Hence, there may be functional parallels between the roles of Prx in membrane stabilization of the myelin sheath and the lens fiber cell

Direct Binding of the Flexible C-Terminal Segment of Periaxin to β4 Integrin Suggests a Molecular Basis for CMT4F

The process of myelination in the nervous system requires a coordinated formation of both transient and stable supramolecular complexes. Myelin-specific proteins play key roles in these assemblies, which may link membranes to each other or connect the myelinating cell cytoskeleton to the extracellular matrix. The myelin protein periaxin is known to play an important role in linking the Schwann cell cytoskeleton to the basal lamina through membrane receptors, such as the dystroglycan complex. Mutations that truncate periaxin from the C terminus cause demyelinating peripheral neuropathy, Charcot-Marie-Tooth (CMT) disease type 4F, indicating a function for the periaxin C-terminal region in myelination. We identified the cytoplasmic domain of β4 integrin as a specific high-affinity binding partner for periaxin. The C-terminal region of periaxin remains unfolded and flexible when bound to the third fibronectin type III domain of β4 integrin. Our data suggest that periaxin is able to link the Schwann cell cytoplasm to the basal lamina through a two-pronged interaction via different membrane protein complexes, which bind close to the N and C terminus of this elongated, flexible molecule.publishedVersio

Dietitian’s Problem Solving Knowledge to Promote and Support Breastfeeding

As a result of ongoing efforts in the U.S. to promote breastfeeding as the normal way to nourish an infant, breastfeeding initiation rates are higher than they have been in decades. As the experts on food and nutrition through the lifecycle, registered dietitians (RDs) should be knowledgeable to promote and support breastfeeding. It is not well known if RDs have this knowledge. The purpose of this study was to determine the current knowledge of RDs about breastfeeding, the types of professional opportunities RDs have to promote and support breastfeeding, and the level of education RDs have to deal with breastfeeding problems. Questionnaires were sent to 353 Nebraska Dietetic Association members with a response rate of 67%. The survey included 34 general breastfeeding knowledge questions, seven advanced breastfeeding knowledge questions, and questions regarding personal and professional breastfeeding experience and preparedness to promote and support breastfeeding. Mean general knowledge score was 20.7/34 (61% correct) and mean advanced knowledge score was 4.1/7 (59% correct). Significantly higher general knowledge scores were seen for RDs who worked in community/public health programs, had attended breastfeeding conferences/seminars/workshops and those whose personal experience was their main source of practical breastfeeding information (pp\u3c0.0001 for each). Few RDs had received adequate breastfeeding education in their undergraduate courses or dietetic internships (n=16 (7%) and n=14 (6%), respectively). Only 8% (n=19) of RDs felt very prepared to support breastfeeding mothers. Twenty-four percent of participants routinely counseled breastfeeding mothers and 79% of these RDs need more training on breastfeeding problem solving. Although the RDs surveyed had some breastfeeding knowledge, they are unprepared to support mothers with breastfeeding problems. Advisers: Kaye Stanek Krogstrand and Julie A. Albrech

Impact of Clustering on the Li8 β Decay and Recoil Form Factors

We place unprecedented constraints on recoil corrections in the $\beta$ decay of $^8$Li, by identifying a strong correlation between them and the $^8$Li ground state quadrupole moment in large-scale ab initio calculations. The results are essential for improving the sensitivity of high-precision experiments that probe the weak interaction theory and test physics beyond the Standard Model (BSM). In addition, our calculations predict a $2^+$ state of the $\alpha+\alpha$ system that is energetically accessible to $\beta$ decay but has not been observed in the experimental $^8$Be energy spectrum, and has an important effect on the recoil corrections and $\beta$ decay for the $A=8$ systems. This state and an associated $0^+$ state are notoriously difficult to model due to their cluster structure and collective correlations, but become feasible for calculations in the ab initio symmetry-adapted no-core shell-model framework.Comment: Accepted versio