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

The Fraud Diamond: Considering the Four Elements of Fraud

Focuses on the use of the elements of the fraud diamond to prevent and detect accounting fraud. Essential traits for committing fraud; Steps in assessing fraud risk through the use of the fourth element of the diamond; Ways for auditors to prevent potential fraud

Benchmarking urine storage and collection conditions for evaluating the female urinary microbiome.

Standardized conditions for collection, preservation and storage of urine for microbiome research have not been established. We aimed to identify the effects of the use of preservative AssayAssure® (AA), and the effects of storage time and temperatures on reproducibility of urine microbiome results. We sequenced the V3-4 segment of the 16S rRNA gene to characterize the bacterial community in the urine of a cohort of women. Each woman provided a single voided urine sample, which was divided into aliquots and stored with and without AA, at three different temperatures (room temperature [RT], 4 °C, or -20 °C), and for various time periods up to 4 days. There were significant microbiome differences in urine specimens stored with and without AA at all temperatures, but the most significant differences were observed in alpha diversity (estimated number of taxa) at RT. Specimens preserved at 4 °C and -20 °C for up to 4 days with or without AA had no significant alpha diversity differences. However, significant alpha diversity differences were observed in samples stored without AA at RT. Generally, there was greater microbiome preservation with AA than without AA at all time points and temperatures, although not all results were statistically significant. Addition of AA preservative, shorter storage times, and colder temperatures are most favorable for urinary microbiome reproducibility

The Deuterium Abundance at z=0.701 towards QSO 1718+4807

We present constraints on the deuterium to hydrogen ratio (D/H) in the metal-poor gas cloud at redshift $z=0.701$ towards QSO 1718+4807. We use new Keck spectra in addition to Hubble Space Telescope (HST) and International Ultraviolet Explorer (IUE) spectra. We use an improved redshift and a lower \HI column density to model the absorption. The HST spectrum shows an asymmetric Lyman-$\alpha$ (\lya) feature which is produced by either \HI at a second velocity, or a high abundance of D. Three models with a single simple H+D component give $8 \times 10^{-5} < D/H < 57 \times 10^{-5}$ (95%), a much larger range than reported by Webb et al (1997a,b). A more sophisticated velocity distribution, or a second component is necessary for lower D/H. With two components, which could be a part of one absorbing structure, or separate clouds in a galaxy halo, we find $D/H < 50 \times 10^{-5}$. We do not know if this second component is present, but it is reasonable because 40 -- 100% of absorption systems with similar redshifts and \HI column densities have more than one component.Comment: 13 pages, 4 figures, to appear in the Astronomical Journal (Jan 1999

The Deuterium to Hydrogen Abundance Ratio Towards a Fourth QSO: HS0105+1619

We report the measurement of the primordial D/H abundance ratio towards QSO \object. The column density of the hydrogen in the $z \simeq 2.536$ Lyman limit system is high, \lnhi $= 19.422 \pm 0.009$ \cmm, allowing for the deuterium to be seen in 5 Lyman series transitions. The measured value of the D/H ratio towards QSO \object is found to be D/H$= 2.54 \pm 0.23 \times 10^{-5}$. The metallicity of the system showing D/H is found to be $\simeq 0.01$ solar, indicating that the measured D/H is the primordial D/H within the measurement errors. The gas which shows D/H is neutral, unlike previous D/H systems which were more highly ionized. Thus, the determination of the D/H ratio becomes more secure since we are measuring it in different astrophysical environments, but the error is larger because we now see more dispersion between measurements. Combined with prior measurements of D/H, the best D/H ratio is now D/H$= 3.0 \pm 0.4 \times 10^{-5}$, which is 10% lower than the previous value. The new values for the baryon to photon ratio, and baryonic matter density derived from D/H are $\eta = 5.6 \pm 0.5 \times 10^{-10}$ and \ob $=0.0205 \pm 0.0018$ respectively.Comment: Minor text and reference changes. To appear in the May 10, 2001 issue of the Astrophysical Journa

ULF waves in the low‐latitude boundary layer and their relationship to magnetospheric pulsations: A multisatellite observation

On April 30 (day 120), 1985, the magnetosphere was compressed at 0923 UT and the subsolar magnetopause remained near 7 REgeocentric for ∼2 hours, during which the four spacecraft Spacecraft Charging At High Altitude (SCATHA), GOES 5, GOES 6, and Active Magnetospheric Particle Tracer Explorers (AMPTE) CCE were all in the magnetosphere on the morning side. SCATHA was in the low-latitude boundary layer (LLBL) in the second half of this period. The interplanetary magnetic field was inferred to be northward from the characteristics of precipitating particle fluxes as observed by the low-altitude satellite Defense Meteorological Satellite Program (DMSP) F7 and also from absence of substorms. We used magnetic field and particle data from this unique interval to study ULF waves in the LLBL and their relationship to magnetic pulsations in the magnetosphere. The LLBL was identified from the properties of particles, including bidirectional field-aligned electron beams at ∼200 eV. In the boundary layer the magnetic field exhibited both a 5–10 min irregular compressional oscillation and a broadband (Δƒ/ƒ ∼ 1) primarily transverse oscillations with a mean period of ∼50 s and a left-hand sense of polarization about the mean field. The former can be observed by other satellites and is likely due to pressure variations in the solar wind, while the latter is likely due to a Kelvin-Helmholtz (K.-H.) instability occurring in the LLBL or on the magnetopause. Also, a strongly transverse ∼3-s oscillation was observed in the LLBL. The magnetospheric pulsations, which exhibited position dependent frequencies, may be explained in terms of field line resonance with a broadband source wave, that is, either the pressure-induced compressional wave or the K.-H. wave generated in or near the boundary layer

The dose of hemodialysis and patient mortality

The dose of hemodialysis and patient mortality. The relationship between the delivered dose of hemodialysis and patient mortality remains somewhat controversial. Several observational studies have shown improved patient survival with higher levels of delivered dialysis dose. However, several other unmeasured variables, changes in patient mix or medical management may have impacted on this reported difference in mortality. The current study of a U.S. national sample of 2,311 patients from 347 dialysis units estimates the relationship of delivered hemodialysis dose to mortality, with a statistical adjustment for an extensive list of comorbidity/risk factors. Additionally this study investigated the existence of a dose beyond which more dialysis does not appear to lower mortality. We estimated patient survival using proportional hazards regression techniques, adjusting for 21 patient comorbidity/risk factors with stratification for nine Census regions. The patient sample was 2,311 Medicare hemodialysis patients treated with bicarbonate dialysate as of 12/31/90 who had end-stage renal disease for at least one year. Patient follow-up ranged between 1.5 and 2.4 years. The measurement of delivered therapy was based on two alternative measures of intradialytic urea reduction, the urea reduction ratio (URR) and Kt/V (with adjustment for urea generation and ultrafiltration). Hemodialysis patient mortality showed a strong and robust inverse correlation with delivered hemodialysis dose whether measured by Kt/V or by URR. Mortality risk was lower by 7% (P = 0.001) with each 0.1 higher level of delivered Kt/V. (Expressed in terms of URR, mortality was lower by 11% with each 5 percentage point higher URR; P = 0.001). Above a URR of 70% or a Kt/V of 1.3 these data did not provide statistical evidence of further reductions in mortality. In conclusion, the delivered dose of hemodialysis therapy is an important predictor of patient mortality. In a population of dialysis patients with a very high mortality rate, it appears that increasing the level of delivered therapy offers a practical and efficient means of lowering the mortality rate. The level of hemodialysis dose measured by URR or Kt/V beyond which the mortality rate does not continue to decrease, though not well defined with this study, appears to be above current levels of typical treatment of hemodialysis patients in the U.S

Fluctuating brane in a dilatonic bulk

We consider a cosmological brane moving in a static five-dimensional bulk spacetime endowed with a scalar field whose potential is exponential. After studying various cosmological behaviours for the homogeneous background, we investigate the fluctuations of the brane that leave spacetime unaffected. A single mode embodies these fluctuations and obeys a wave equation which we study for bouncing and ever-expanding branes.Comment: 17 pages, 7 figures, revte

Census 2010 Demographic Profile: Jefferson County

This demographic profile describes characteristics of the local and state population based on results from the 2010 Census. The decennial census is an official enumeration, or count, of all residents on April 1st of the census year. The results of the census provide us with information about basic demographic characteristics of the population, including age, race, ethnicity, household composition, housing occupancy, and housing tenure