Martha Washington : Gavot

https://digitalcommons.library.umaine.edu/mmb-ps/1751/thumbnail.jp

Regulation and Cytoprotective Role of Hexokinase III

Hexokinases (HKs) catalyze the first step in glucose metabolism. Of the three mammalian 100-kDa HK isoforms, HKI and II can bind to mitochondria and protect against cell death. HKIII does not bind mitochondria, and little is known about its regulation or cytoprotective effects. We studied the regulation of HKIII at the transcriptional and protein levels and investigated its role in cellular protection.We show that like HKII, HKIII expression is regulated by hypoxia, but other factors that regulate HKII expression have no effect on HKIII levels. This transcriptional regulation is partially dependent on hypoxia-inducible factor (HIF) signaling. We also demonstrate regulation at the protein level, as mutations in putative N-terminal substrate binding residues altered C-terminal catalytic activity, suggesting that HKIII activity is governed, in part, by interactions between these two domains. Overexpression of HKIII reduced oxidant-induced cell death, increased ATP levels, decreased the production of reactive oxygen species (ROS), and preserved mitochondrial membrane potential. HKIII overexpression was also associated with higher levels of transcription factors that regulate mitochondrial biogenesis, and greater total mitochondrial DNA content. Attempts to target HKIII to the mitochondria by replacing its N-terminal 32-amino-acid sequence with the mitochondrial-targeting sequence of HKII led to protein aggregation, suggesting that this region is necessary to maintain proper protein folding and solubility.These results suggest that HKIII is regulated by hypoxia and there are functional interactions between its two halves. Furthermore, HKIII exerts protective effects against oxidative stress, perhaps by increasing ATP levels, reducing oxidant-induced ROS production, preserving mitochondrial membrane potential, and increasing mitochondrial biogenesis

Going to the movies in VR: Virtual reality cinemas as alternatives to in-person co-viewing

Virtual reality cinemas offer computer-generated screening environments that resemble physical-world movie theaters for avatar-based viewers. Reflecting on virtual spectatorship in the context of social isolation, the present study investigates whether VR cinemas could provide an alternative for collective movie watching and whether they could facilitate an engaging experience similar to other, physical-world co-viewing environments. To measure these effects, we designed a behavioral experiment in which participants watched a feature film sequence either in VR or a physical screening room in the presence or absence of viewing companions. After viewing, participants' experiences—including emotional engagement, narrative empathy, presence, social experiences, and physical and mental well-being—were recorded using survey methods. We observed that VR viewing can produce an equally enjoyable film experience, as well as similar levels of emotional engagement and narrative empathy, while it leads to increased comprehension of characters' feelings and sense of narrative engagement. In addition, social viewing may mean less engagement and more distractions depending on the screening environment. We also found that even though previous virtual reality exposure negatively correlates with comfort and well-being during viewing, early adopters of technology and VR supporters are more likely to have an enjoyable and engaging film experience

Confirming the Primarily Smooth Structure of the Vega Debris Disk at Millimeter Wavelengths

Clumpy structure in the debris disk around Vega has been previously reported at millimeter wavelengths and attributed to concentrations of dust grains trapped in resonances with an unseen planet. However, recent imaging at similar wavelengths with higher sensitivity has disputed the observed structure. We present three new millimeter wavelength observations that help to resolve the puzzling and contradictory observations. We have observed the Vega system with the Submillimeter Array (SMA) at a wavelength of 880 μm and an angular resolution of 5"; with the Combined Array for Research in Millimeter-wave Astronomy (CARMA) at a wavelength of 1.3 mm and an angular resolution of 5"; and with the Green Bank Telescope (GBT) at a wavelength of 3.3 mm and angular resolution of 10". Despite high sensitivity and short baselines, we do not detect the Vega debris disk in either of the interferometric data sets (SMA and CARMA), which should be sensitive at high significance to clumpy structure based on previously reported observations. We obtain a marginal (3σ) detection of disk emission in the GBT data; the spatial distribution of the emission is not well constrained.We analyze the observations in the context of several different models, demonstrating that the observations are consistent with a smooth, broad, axisymmetric disk with inner radius 20–100 AU and width ≾50 AU. The interferometric data require that at least half of the 860 μm emission detected by previous single-dish observations with the James Clerk Maxwell Telescope be distributed axisymmetrically, ruling out strong contributions from flux concentrations on spatial scales of ≾100 AU. These observations support recent results from the Plateau de Bure Interferometer indicating that previous detections of clumpy structure in the Vega debris disk were spurious

Target Selection for the LBTI Exozodi Key Science Program

The Hunt for Observable Signatures of Terrestrial planetary Systems (HOSTS) on the Large Binocular Telescope Interferometer will survey nearby stars for faint emission arising from ~300 K dust (exozodiacal dust), and aims to determine the exozodiacal dust luminosity function. HOSTS results will enable planning for future space telescopes aimed at direct spectroscopy of habitable zone terrestrial planets, as well as greater understanding of the evolution of exozodiacal disks and planetary systems. We lay out here the considerations that lead to the final HOSTS target list. Our target selection strategy maximizes the ability of the survey to constrain the exozodi luminosity function by selecting a combination of stars selected for suitability as targets of future missions and as sensitive exozodi probes. With a survey of approximately 50 stars, we show that HOSTS can enable an understanding of the statistical distribution of warm dust around various types of stars and is robust to the effects of varying levels of survey sensitivity induced by weather conditions.Comment: accepted to ApJ

Prevalence of Kidney Disease in HIV-Infected and Uninfected Rwandan Women

Background: In the United States, HIV-related kidney disease disproportionately affects individuals of African descent; however, there are few estimates of kidney disease prevalence in Africa. We evaluated the prevalence of kidney disease among HIV-infected and uninfected Rwandan women. Methods: The Rwandan Women's Interassociation Study and Assessment prospectively enrolled 936 women. Associations with estimated glomerular filtration rate (eGFR)<60 mL/min/1.73 m$^2$ and proteinuria were assessed in separate logistic regression models. Results: Among 891 non-pregnant women with available data, 2.4% had an eGFR<60 mL/min/1.73 m$^2$ (calculated by the Modification of Diet in Renal Disease equation, MDRD eGFR) and 8.7% had proteinuria $\ge$1+. The prevalence of decreased eGFR varied markedly depending on the estimating method used, with the highest prevalence by Cockcroft-Gault. Regardless of the method used to estimate GFR, the proportion with decreased eGFR or proteinuria did not differ significantly between HIV-infected and -uninfected women in unadjusted analysis. After adjusting for age and blood pressure, HIV infection was associated with significantly higher odds of decreased MDRD eGFR but not proteinuria. Conclusion: In a well-characterized cohort of Rwandan women, HIV infection was associated with decreased MDRD eGFR. The prevalence of decreased eGFR among HIV-infected women in our study was lower than that previously reported in African-Americans and in other Central and East African HIV populations, although there was substantial variability depending on the equation used to estimate GFR. Future studies are needed to optimize GFR estimates and to determine the impact of antiretroviral therapy on kidney disease in this population

Exo-zodi Modeling for the Large Binocular Telescope Interferometer

Habitable zone dust levels are a key unknown that must be understood to ensure the success of future space missions to image Earth analogs around nearby stars. Current detection limits are several orders of magnitude above the level of the solar system's zodiacal cloud, so characterization of the brightness distribution of exo-zodi down to much fainter levels is needed. To this end, the Large Binocular Telescope Interferometer (LBTI) will detect thermal emission from habitable zone exo-zodi a few times brighter than solar system levels. Here we present a modeling framework for interpreting LBTI observations, which yields dust levels from detections and upper limits that are then converted into predictions and upper limits for the scattered light surface brightness. We apply this model to the HOSTS survey sample of nearby stars; assuming a null depth uncertainty of 10^(–4) the LBTI will be sensitive to dust a few times above the solar system level around Sun-like stars, and to even lower dust levels for more massive stars