Uncoupling of p97 ATPase activity has a dominant negative effect on protein extraction

p97 is a highly abundant, homohexameric AAA+ ATPase that performs a variety of essential cellular functions. Characterized as a ubiquitin-selective chaperone, p97 recognizes proteins conjugated to K48-linked polyubiquitin chains and promotes their removal from chromatin and other molecular complexes. Changes in p97 expression or activity are associated with the development of cancer and several related neurodegenerative disorders. Although pathogenic p97 mutations cluster in and around p97's ATPase domains, mutant proteins display normal or elevated ATPase activity. Here, we show that one of the most common p97 mutations (R155C) retains ATPase activity, but is functionally defective. p97-R155C can be recruited to ubiquitinated substrates on chromatin, but is unable to promote substrate removal. As a result, p97-R155C acts as a dominant negative, blocking protein extraction by a similar mechanism to that observed when p97's ATPase activity is inhibited or inactivated. However, unlike ATPase-deficient proteins, p97-R155C consumes excess ATP, which can hinder high-energy processes. Together, our results shed new insight into how pathogenic mutations in p97 alter its cellular function, with implications for understanding the etiology and treatment of p97-associated diseases

Decreasing Opportunities for Low-Wage Workers: The Role of the Nondiscrimination Law for Employer-Provided Health Insurance

As of 1978, the favorable tax treatment of fringe benefits, including health insurance, has been regulated via a nondiscrimination clause such that low-wage, full-time workers must be offered health insurance (and other benefits) that are offered to higher-wage workers by the firm. Part-time workers may be excluded from coverage, however, creating incentives for firms to hire some types of workers part time to deny them coverage. We hypothesize that firms will hire fewer workers whose relative costs have increased, that is, low-wage workers. These workers will be less likely to work for firms that offer coverage, and those that do will be more likely to work part time without being eligible for the firm’s health insurance benefits. We use the 1988 and 1993 Employee Benefits Supplements to the Current Population Surveys and an employer premium imputation to examine these hypotheses. Both the descriptive and multivariate analysis are consistent with our hypotheses. We predict the probability of working for a firm that offers health insurance to decrease as premiums increase for both high- and low-wage workers. An increase in the premium is also associated with a decrease in the probability of part-time work, but an even greater decrease in the joint probability of part-time work with eligibility for health insurance.

A rural shelter in Ontario adapting to address the changing needs of women who have experienced intimate partner violence: A qualitative case study

Introduction: Intimate partner violence is a significant public health problem, with shelters offering the predominant communitybased solution. Shelters in Canada are mandated to provide a safe place, protection planning, advocacy and counseling among other services. Recently it has been noted the role of the shelter was shifting from an inpatient to outpatient model with a focus on increased integration of health and social services. This changing role of the shelter is amplified within the rural context where resources and cultural norms may be limited or incompatible with help-seeking behaviors. Women\u27s shelters located in rural settings provide services within a specific cultural context that can be at odds with the needs of women who have experienced abuse, because cultural values such as rural pride, lack of anonymity, and lack of services may inhibit access to health and social services. Methods: The purpose of this in-depth qualitative case study was to examine and explore how one rural Canadian women\u27s shelter role was changing and how the shelter was adapting to achieve the changing role. The theoretical framework utilized was a feminist intersectional lens. Qualitative interviews (averaging 60 minutes) were conducted with shelter service providers (n = 6) and women staying in the shelter or utilizing shelter services (n = 4). Throughout semi-structured interviews, data-trustworthy steps were taken including member-checking and paraphrasing to ensure data were an accurate representation of participants\u27 experiences. Inductive content analysis of all interviews and field notes was conducted independently by two researchers. Results: Analysis revealed the shelter\u27s role was changing to include filling gaps, case management, and system navigation. To achieve the changing role, relationship building, community mobilization (both education and empowerment), and redesigning delivery were implemented as adaptation strategies. Together both the changing role of the shelter and the adaptation strategies being implemented were found to be working toward a larger goal of transformation of cultural and structural norms related to violence against women. Conclusions: This study uniquely identified the specific changes to the role of one rural Canadian shelter and the adaptations strategies utilized to adapt to the changing needs of women. The changing role of the shelter and the adaptation strategies being utilized have significant implications for the health of women given the increased use of healthcare services for women who have experienced violence. Specifically, the changing role of the shelter has the potential to decrease healthcare service use while increasing the potential fit of services. Further research is required to assess the impact of the changing role of the shelter on the healthcare needs and outcomes for women who have experienced intimate partner violence

Experimental Studies of the NaCs 53Π0 and a3Σ+ States

We report high resolution measurements of 372 NaCs 53Π0(v, J) ro-vibrational level energies in the range 0 ≤ v ≤ 22. The data have been used to construct NaCs 53Π0 potential energy curves using the Rydberg–Klein-Rees and inverted perturbation approximation methods. Bound-free 53Π0(v, J) → 1(a)3Σ+ emission has also been measured, and is used to determine the repulsive wall of the 1(a)3Σ+ state and the 53Π0 → 1(a)3Σ+ relative transition dipole moment function. Hyperfine structure in the 53Π0 state has not been observed in this experiment. This null result is explained using a simple vector coupling model

Maximizing phonon thermal conductance for ballistic membranes

At low temperatures, phonon scattering can become so weak that phonon transport becomes ballistic. We calculate the ballistic phonon conductance G for membranes using elasticity theory, considering the transition from three to two dimensions. We discuss the temperature and thickness dependence and especially concentrate on the issue of material parameters. For all membrane thicknesses, the best conductors have, counter-intuitively, the lowest speed of sound.Comment: 4 pages, 4 figures, proceedings to phonons 2007 conferenc

Collisional Transfer of Population and Orientation in NaK

We report current work to study transfer of population and orientation in collisions of NaK molecules with argon and potassium atoms using polarization labeling (PL) and laser- induced fluorescence (LIF) spectroscopy. In the PL experiment, a circularly polarized pump laser excites a specific NaK A1Σ +(v 0=16, J 0 ) ← X1Σ +(v 00=0, J 0 ± 1) transition, creating an orientation (non-uniform MJ0 level distribution) in both levels. The linearly polarized probe laser is scanned over various 31Π(v, J 0±1) ← A1Σ +(v 0=16, J 0 ) transitions. The probe laser passes through a crossed linear polarizer before detection, and signal is recorded if the probe laser polarization has been modified by the vapor (which occurs when it comes into resonance with an oriented level). Using both spectroscopic methods, analysis of weak collisional satellite lines adjacent to these directly populated lines, as a function of argon buffer gas pressure and cell temperature, allows us to discern separately the effects collisions with argon atoms and potassium atoms have on the population and orientation of the molecule. In addition, code has been written which provides a theoretical analysis of the process, through a solution of the density matrix equations of motion for the system

Polarization Spectroscopy and Collisions in NaK

We report current work to study transfer of population and orientation in collisions of NaK molecules with argon and potassium atoms using polarization labeling (PL) and laser-induced fluorescence (LIF) spectroscopy. In the PL experiment, a circularly polarized pump laser excites a specific NaK A1Σ +(v=16, J) ← X1Σ +(v=0, J ± 1) transition, creating an orientation (non-uniform MJ level distribution) in both levels. The linear polarized probe laser is scanned over various 3 1Π(v=8, J 0 ± 1) ← A1Σ +(v=16, J 0 ) transitions. The probe laser passes through a crossed linear polarizer before detection, and signal is recorded if the probe laser polarization has been modified by the vapor (which occurs when it comes into resonance with an oriented level). In addition to strong direct transitions (J 0 = J), we also observe weak collisional satellite lines (J 0 = J ±n with n = 1, 2, 3, ...) indicating that orientation is transferred to adjacent rotational levels during a collision. An LIF experiment (with linear polarized pump and probe beams) gives information on the collisional transfer of population. From these data, cross sections for both processes can be determined. We experimentally distinguish collisions of NaK with argon atoms from collisions with alkali atoms

Comparing Segmentation by Time and by Motion in Visual Search: An fMRI Investigation

Abstract Brain activity was recorded while participants engaged in a difficult visual search task for a target defined by the spatial configuration of its component elements. The search displays were segmented by time (a preview then a search display), by motion, or were unsegmented. A preparatory network showed activity to the preview display, in the time but not in the motion segmentation condition. A region of the precuneus showed (i) higher activation when displays were segmented by time or by motion, and (ii) correlated activity with larger segmentation benefits behaviorally, regardless of the cue. Additionally, the results revealed that success in temporal segmentation was correlated with reduced activation in early visual areas, including V1. The results depict partially overlapping brain networks for segmentation in search by time and motion, with both cue-independent and cue-specific mechanisms.</jats:p

Resonance-like piezoelectric electron-phonon interaction in layered structures

We show that mismatch of the piezoelectric parameters between layers of multiple-quantum well structures leads to modification of the electron-phonon interaction. In particular, short-wavelength phonons propagating perpendicular to the layers with wavevector close to $2\pi n/d$, where $d$ is the period of the structure, induce a strong smoothly-varying component of the piezo-potential. As a result, they interact efficiently with 2D electrons. It is shown, that this property leads to emission of collimated quasi-monochromatic beams of high-frequency acoustic phonons from hot electrons in multiple-quantum well structures. We argue that this effect is responsible for the recently reported monochromatic transverse phonon emission from optically excited GaAs/AlAs superlattices, and provide additional experimental evidences of this.Comment: 6 pages, 7 figure

Ultrafast acoustics for imaging at the nanoscale

In this paper we present a series of experiments which show that 2-D and possibly 3-D imaging with sub-micron resolution is possible by means of ultrafast acoustic techniques. Optical pulses from a Ti:sapphire laser are used to generate picosecond acoustic pulses on one side of a ~1 mm thick Si wafer. The 1 mm distance is sufficient for the acoustic waves to diffract to the far field before they are detected by time-delayed probe pulses from the Ti:sapphire laser. The acoustic waves are either generated by a surface nanostructure or scattered from a buried nanostructure, and an image of that nanostructure is reconstructed through an analysis of the detected acoustic waves.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/58182/2/jpconf7_92_012094.pd