Analysis of Diffusion of Ras2 in Saccharomyces cerevisiae Using Fluorescence Recovery after Photobleaching

Binding, lateral diffusion and exchange are fundamental dynamic processes involved in protein association with cellular membranes. In this study, we developed numerical simulations of lateral diffusion and exchange of fluorophores in membranes with arbitrary bleach geometry and exchange of the membrane localized fluorophore with the cytosol during Fluorescence Recovery after Photobleaching (FRAP) experiments. The model simulations were used to design FRAP experiments with varying bleach region sizes on plasma-membrane localized wild type GFP-Ras2 with a dual lipid anchor and mutant GFP-Ras2C318S with a single lipid anchor in live yeast cells to investigate diffusional mobility and the presence of any exchange processes operating in the time scale of our experiments. Model parameters estimated using data from FRAP experiments with a 1 micron x 1 micron bleach region-of-interest (ROI) and a 0.5 micron x 0.5 micron bleach ROI showed that GFP-Ras2, single or dual lipid modified, diffuses as single species with no evidence of exchange with a cytoplasmic pool. This is the first report of Ras2 mobility in yeast plasma membrane. The methods developed in this study are generally applicable for studying diffusion and exchange of membrane associated fluorophores using FRAP on commercial confocal laser scanning microscopes.Comment: Accepted for publication in Physical Biology (2010). 28 pages, 7 figures, 3 table

Immunohistochemical localization of collagen types I and VI in human skin wounds

A total of 74 human skin wounds were investigated and collagen types I and VI were localized in the wound area by immunohistochemistry. Collagen type I appeared in the form of ramifying string-like structures after approximately 5–6 days, but positive reactions in the form of a spot-like staining around isolated fibroblasts also occurred in a skin wound aged 4 days. Collagen VI was detectable after a post-infliction interval of at least 3 days showing a strongly positive reacting network associated with fibroblasts in the wound area. Both collagens appeared almost constantly after a wound age of 6–7 clays and could also be found in wounds aged a few months. Therefore, although a positive reaction for collagen type I in the form of string-like and ramifying structures around wound fibroblasts indicates a wound age of at least 5–6 days, a spot-like positive staining for collagen type I cannot exclude a wound age of at least 4 days. A positive staining for collagen type VI represents a post-infliction time of 3 days or more. The almost constant appearance of these collagen types suggests that negative results in a sufficient number of specimens indicate a wound age of less than 6–7 days, but cannot completely exclude longer post-infliction intervals. Since collagen type I and VI are also found in the granulation/scar tissue of lesions with advanced wound age, the immunohistochemical analysis of these proteins provides no further information for an age determination of older skin wounds

Pan-STARRS1 Discovery of Two Ultra-Luminous Supernovae at z ~ 0.9

We present the discovery of two ultra-luminous supernovae (SNe) at z ~ 0.9 with the Pan-STARRS1 Medium-Deep Survey. These SNe, PS1-10ky and PS1-10awh, are amongst the most luminous SNe ever discovered, comparable to the unusual transients SN 2005ap and SCP 06F6. Like SN 2005ap and SCP 06F6, they show characteristic high luminosities (M_bol ~ -22.5 mag), blue spectra with a few broad absorption lines, and no evidence for H or He. We have constructed a full multi-color light curve sensitive to the peak of the spectral energy distribution in the rest-frame ultraviolet, and we have obtained time-series spectroscopy for these SNe. Given the similarities between the SNe, we combine their light curves to estimate a total radiated energy over the course of explosion of (0.9-1.4) x 10^51 erg. We find photospheric velocities of 12,000-19,000 km/s with no evidence for deceleration measured across ~3 rest-frame weeks around light-curve peak, consistent with the expansion of an optically-thick massive shell of material. We show that, consistent with findings for other ultra-luminous SNe in this class, radioactive decay is not sufficient to power PS1-10ky, and we discuss two plausible origins for these events: the initial spin-down of a newborn magnetar in a core-collapse SN, or SN shock breakout from the dense circumstellar wind surrounding a Wolf-Rayet star.Comment: Re-Submitted to Ap

Mapping the multicausality of Alzheimer's disease through group model building

Alzheimer's disease (AD) is a complex, multicausal disorder involving several spatiotemporal scales and scientific domains. While many studies focus on specific parts of this system, the complexity of AD is rarely studied as a whole. In this work, we apply systems thinking to map out known causal mechanisms and risk factors ranging from intracellular to psychosocial scales in sporadic AD. We report on the first systemic causal loop diagram (CLD) for AD, which is the result of an interdisciplinary group model building (GMB) process. The GMB was based on the input of experts from multiple domains and all proposed mechanisms were supported by scientific literature. The CLD elucidates interaction and feedback mechanisms that contribute to cognitive decline from midlife onward as described by the experts. As an immediate outcome, we observed several non-trivial reinforcing feedback loops involving factors at multiple spatial scales, which are rarely considered within the same theoretical framework. We also observed high centrality for modifiable risk factors such as social relationships and physical activity, which suggests they may be promising leverage points for interventions. This illustrates how a CLD from an interdisciplinary GMB process may lead to novel insights into complex disorders. Furthermore, the CLD is the first step in the development of a computational model for simulating the effects of risk factors on AD.Neuro Imaging Researc

Cosmological Constraints from Galaxy Clusters in the 2500 square-degree SPT-SZ Survey

(abridged) We present cosmological constraints obtained from galaxy clusters identified by their Sunyaev-Zel'dovich effect signature in the 2500 square degree South Pole Telescope Sunyaev Zel'dovich survey. We consider the 377 cluster candidates identified at z>0.25 with a detection significance greater than five, corresponding to the 95% purity threshold for the survey. We compute constraints on cosmological models using the measured cluster abundance as a function of mass and redshift. We include additional constraints from multi-wavelength observations, including Chandra X-ray data for 82 clusters and a weak lensing-based prior on the normalization of the mass-observable scaling relations. Assuming a LCDM cosmology, where the species-summed neutrino mass has the minimum allowed value (mnu = 0.06 eV) from neutrino oscillation experiments, we combine the cluster data with a prior on H0 and find sigma_8 = 0.797+-0.031 and Omega_m = 0.289+-0.042, with the parameter combination sigma_8(Omega_m/0.27)^0.3 = 0.784+-0.039. These results are in good agreement with constraints from the CMB from SPT, WMAP, and Planck, as well as with constraints from other cluster datasets. Adding mnu as a free parameter, we find mnu = 0.14+-0.08 eV when combining the SPT cluster data with Planck CMB data and BAO data, consistent with the minimum allowed value. Finally, we consider a cosmology where mnu and N_eff are fixed to the LCDM values, but the dark energy equation of state parameter w is free. Using the SPT cluster data in combination with an H0 prior, we measure w = -1.28+-0.31, a constraint consistent with the LCDM cosmological model and derived from the combination of growth of structure and geometry. When combined with primarily geometrical constraints from Planck CMB, H0, BAO and SNe, adding the SPT cluster data improves the w constraint from the geometrical data alone by 14%, to w = -1.023+-0.042

Dietary patterns are related to cognitive functioning in elderly enriched with individuals at increased risk for Alzheimer's disease

PURPOSE: To investigate cross-sectional associations between dietary patterns and cognitive functioning in elderly free of dementia. METHODS: Data of 389 participants from the German DELCODE study (52% female, 69 ± 6 years, mean Mini Mental State Score 29 ± 1) were included. The sample was enriched with elderly at increased risk for Alzheimer's disease (AD) by including participants with subjective cognitive decline, mild cognitive impairment (MCI) and siblings of AD patients. Mediterranean and MIND diets were derived from 148 Food Frequency Questionnaire items, and data-driven patterns by principal component analysis (PCA) of 39 food groups. Associations between dietary patterns and five cognitive domain scores were analyzed with linear regression analyses adjusted for demographics (model 1), and additionally for energy intake, BMI, other lifestyle variables and APOe4-status (model 2). For PCA-derived dietary components, final model 3 included all other dietary components. RESULTS: In fully adjusted models, adherence to Mediterranean and MIND diet was associated with better memory. The 'alcoholic beverages' PCA component was positively associated with most cognitive domains. Exclusion of MCI subjects (n = 60) revealed that Mediterranean and MIND diet were also related to language functions; associations with the alcoholic beverages component were attenuated, but most remained significant. CONCLUSION: In line with data from elderly population samples, Mediterranean and MIND diet and some data-derived dietary patterns were related to memory and language function. Longitudinal data are needed to draw conclusions on the putative effect of nutrition on the rate of cognitive decline, and on the potential of dietary interventions in groups at increased risk for AD

Supermassive Black Holes in Galactic Nuclei: Past, Present and Future Research

This review discusses the current status of supermassive black hole research, as seen from a purely observational standpoint. Since the early '90s, rapid technological advances, most notably the launch of the Hubble Space Telescope, the commissioning of the VLBA and improvements in near-infrared speckle imaging techniques, have not only given us incontrovertible proof of the existence of supermassive black holes, but have unveiled fundamental connections between the mass of the central singularity and the global properties of the host galaxy. It is thanks to these observations that we are now, for the first time, in a position to understand the origin, evolution and cosmic relevance of these fascinating objects.Comment: Invited Review, 114 pages. Because of space requirements, this version contains low resolution figures. The full resolution version can be downloaded from http://www.physics.rutgers.edu/~lff/publications.htm

Parental longevity correlates with offspring’s optimism in two cohorts of community-dwelling older subjects

Dispositional optimism and other positive personality traits have been associated with longevity. Using a familial approach, we investigated the relationship between parental longevity and offspring’s dispositional optimism among community-dwelling older subjects. Parental age of death was assessed using structured questionnaires in two different population-based samples: the Leiden Longevity Study (n = 1,252, 52.2% female, mean age 66 years, SD = 4) and the Alpha Omega Trial (n = 769, 22.8% female, mean age 69 years, SD = 6). Adult offspring’s dispositional optimism was assessed with the Life Orientation Test—Revised (LOT-R). The association between parental age of death and levels of optimism in the offspring was analysed using linear regression analysis within each sample and a meta-analysis for the overall effect. In both samples, the parental mean age of death was positively associated with optimism scores of the offspring. The association remained significant after adjustment for age, gender, living arrangement, body mass index, smoking status, education and self-rated health of the offspring. The pooled B coefficient (increase in LOT-R score per 10-year increase in parental mean age of death) was 0.30 (SE = 0.08, p < 0.001). In conclusion, parental longevity was positively associated with optimism in adult offspring, suggesting a partial linked heritability of longevity and optimism