Tau Clearance Mechanisms and Their Possible Role in the Pathogenesis of Alzheimer Disease

One of the defining pathological features of Alzheimer disease (AD) is the intraneuronal accumulation of tau. The tau that forms these accumulations is altered both posttranslationally and conformationally, and there is now significant evidence that soluble forms of these modified tau species are the toxic entities rather than the insoluble neurofibrillary tangles. However there is still noteworthy debate concerning which specific pathological forms of tau are the contributors to neuronal dysfunction and death in AD. Given that increases in aberrant forms of tau play a role in the neurodegeneration process in AD, there is growing interest in understanding the degradative pathways that remove tau from the cell, and the selectivity of these different pathways for various forms of tau. Indeed, one can speculate that deficits in a pathway that selectively removes certain pathological forms of tau could play a pivotal role in AD. In this review we will discuss the different proteolytic and degradative machineries that may be involved in removing tau from the cell. How deficits in these different degradative pathways may contribute to abnormal accumulation of tau in AD will also be considered. In addition, the issue of the selective targeting of specific tau species to a given degradative pathway for clearance from the cell will be addressed

Extended quantum critical phase in a magnetized spin-1/2 antiferromagnetic chain

Measurements are reported of the magnetic field dependence of excitations in the quantum critical state of the spin S=1/2 linear chain Heisenberg antiferromagnet copper pyrazine dinitrate (CuPzN). The complete spectrum was measured at k_B T/J <= 0.025 for H=0 and H=8.7 Tesla where the system is ~30% magnetized. At H=0, the results are in quantitative agreement with exact calculations of the dynamic spin correlation function for a two-spinon continuum. At high magnetic field, there are multiple overlapping continua with incommensurate soft modes. The boundaries of these continua confirm long-standing predictions, and the intensities are consistent with exact diagonalization and Bethe Ansatz calculations.Comment: 4 pages, 4 figure

The myogenic response in uremic hypertension

The myogenic response in uremic hypertension.BackgroundThe constriction of resistance arteries in response to an increase in transmural pressure, the myogenic response, is thought to be an important determinant of peripheral vascular resistance and therefore of arterial blood pressure. Since raised peripheral resistance is known to occur in uremic hypertension, abnormal myogenic constriction might be responsible. We sought to assess the myogenic response of resistance arteries from the subtotal nephrectomy rat model of uremic hypertension.MethodsUremic Wistar-Kyoto (WKYU) rats, and sham-operated normotensive (WKYC) and spontaneously hypertensive (SHRC) controls were studied in parallel. Skeletal muscle arteries were mounted on a pressure myograph and allowed to develop myogenic constriction. The active internal diameter was measured at increasing lumen pressures from 20 to 200 mm Hg. Vascular smooth muscle then was relaxed in a calcium free solution containing nitroprusside, and the passive internal diameter measured at the same pressure steps. The ratio of active to passive diameter at any given pressure was used to assess the myogenic response.ResultsMyogenic constriction was not increased in either WKYU or SHRC compared to WKYC at pressures up to 180 mm Hg.ConclusionsIncreased myogenic tone is not the cause of uremic hypertension

Morphological asymmetry in mammals: genetics and homeostasis reconsidered

It has been hypothesized that developmental stability is increased at higher levels of genetic variability (heterozygosity) in animals. However, the existence of this relationship is questionable for homeotherms in general and mammals in particular. The difference between the sides of a bilateral character in an individual is a measure of fluctuating asymmetry that can be used as a measure of the developmental stability of mammals. Increased developmental stability should result in a greater degree of similarity between the right and left side of the body even though environmental variability would tend to increase the differences between right and left sides of the body. It is necessary to separate the effects of the three types of asymmetry so that an accurate estim.ate of the variance attributable to fluctuating asymmetry can be made. In addition, many early studies of asymmetry in poikilotherms used meristic characters (such as scale counts), and these types of characters are not easily studied in mammals. Mammals, because of their precise regulation of body temperature show little phenotypic effect of environmental variability, and thus may exhibit low absolute levels of asymmetry. Mammals may also be able to reduce the level of asymmetry during their prolonged intrauterine development and juvenile growth period. The literature is reviewed relative to relationships between genetic variation and asymmetry in mammals. Hypotheses are reviewed as they relate to the relationship between fluctuating asymmetry and heterozygosity observed in previous studies. Finally, recommendations are put forth regarding the design and interpretation of future research into the relationship between developmental homeostasis and genetic variability

Evolution of mammalian social structure

Social groups may be viewed as collections of individuals exhibiting nonindependent behavior and organized in a cooperative manner. The evolutionary advantage of social behavior to individuals must be measured in its relativity to other potential behaviors, the scale of competitive interactions, and under a variety of environmental and genetic constraints. A primary tenet of social evolution is that coancestry will promote the genes of related individuals. High values of coancestry, however, do not necessarily translate into evolutionary advantage unless the primary competitive interactions occur among the groups. Coancestry is affected by the breeding tactics within and rates of genetic exchange among social groups. Low rates of exchange among groups, regardless of breeding tactics, may result in high values for intragroup coancestry but may lead to inbreeding depression in progeny. Likewise, breeding tactics such as polygyny, may not impart any long-lasting evolutionary advantage if genetic exchange rates are high. The evolution of social organizations typified by different breeding and migration strategies is evaluated to determine the conditions necessary for various tactics to result in genetic contributions by individuals equal to those of monogamous mating systems. The models show that breeding and dispersal tactics have probably evolved in concert and predict that social groups which are characterized by strong gene correlations are likely to exhibit relatively low group advantage for progeny survival and breeding. There is little impetus for high gene correlations to accrue in situations where group advantage is very high relative to monogamous systems

The Bristol Hip View: Its Role in the Diagnosis and Surgical Planning and Occult Fracture Diagnosis for Proximal Femoral Fractures

Aim. To evaluate whether a modified radiographic view of the femoral neck improves the diagnosis of occult proximal femoral. Materials and Methods. Prospective study of patients presenting with clinically suspected proximal femoral fractures or who underwent traditional plain radiographic views and the Bristol hip view (a 30-degree angled projection). Six blinded independent observers assessed the images for presence of a fracture, anatomical level, and displacement. Results. 166 consecutive patients presenting with the clinical diagnosis of a proximal femoral fracture, of which 61 sustained a fracture. Six of these were deemed occult due to negative plain and had proven fractures on subsequent cross-sectional imaging. The Bristol hip view demonstrated five of these six fractures. It performed better than the traditional lateral hip view to identify the injury. The Bristol hip view predicted correctly the fracture type and displacement in all cases and missed only one of the occult fractures. Conclusion. The Bristol hip view is more sensitive and clearer than a lateral projection for patients. It adds useful diagnostic information and performs better than the traditional views in occult fractures. Its use may prevent the need for further cross sectional imaging and subsequent surgical delay

Field-driven phase transitions in a quasi-two-dimensional quantum antiferromagnet

We report magnetic susceptibility, specific heat, and neutron scattering measurements as a function of applied magnetic field and temperature to characterize the $S=1/2$ quasi-two-dimensional frustrated magnet piperazinium hexachlorodicuprate (PHCC). The experiments reveal four distinct phases. At low temperatures and fields the material forms a quantum paramagnet with a 1 meV singlet triplet gap and a magnon bandwidth of 1.7 meV. The singlet state involves multiple spin pairs some of which have negative ground state bond energies. Increasing the field at low temperatures induces three dimensional long range antiferromagnetic order at 7.5 Tesla through a continuous phase transition that can be described as magnon Bose-Einstein condensation. The phase transition to a fully polarized ferromagnetic state occurs at 37 Tesla. The ordered antiferromagnetic phase is surrounded by a renormalized classical regime. The crossover to this phase from the quantum paramagnet is marked by a distinct anomaly in the magnetic susceptibility which coincides with closure of the finite temperature singlet-triplet pseudo gap. The phase boundary between the quantum paramagnet and the Bose-Einstein condensate features a finite temperature minimum at $T=0.2$ K, which may be associated with coupling to nuclear spin or lattice degrees of freedom close to quantum criticality.Comment: Submitted to New Journal of Physic

Metrology/viewing system for next generation fusion reactors

Next generation fusion reactors require accurate measuring systems to verify sub-millimeter alignment of plasma-facing components in the reactor vessel. A metrology system capable of achieving such accuracy must be compatible with the vessel environment of high gamma radiation, high vacuum, elevated temperature, and magnetic field. This environment requires that the system must be remotely deployed. A coherent, frequency modulated laser radar system is being integrated with a remotely operated deployment system to meet these requirements. The metrology/viewing system consists of a compact laser transceiver optics module which is linked through fiber optics to the laser source and imaging units that are located outside of the harsh environment. The deployment mechanism is a telescopic-mast positioning system. This paper identifies the requirements for the International Thermonuclear Experimental Reactor metrology and viewing system, and describes a remotely operated precision ranging and surface mapping system

Unconventional ferromagnetic and spin-glass states of the reentrant spin glass Fe0.7Al0.3

Spin excitations of single crystal Fe0.7Al0.3 were investigated over a wide range in energy and reciprocal space with inelastic neutron scattering. In the ferromagnetic phase, propagating spin wave modes become paramagnon-like diffusive modes beyond a critical wave vector q0, indicating substantial disorder in the long-range ordered state. In the spin glass phase, spin dynamics is strongly q-dependent, suggesting remnant short-range spin correlations. Quantitative model for S(energy,q) in the ``ferromagnetic'' phase is determined.Comment: 4 pages, 5 figure