High-Resolution Spectroscopic Study of Extremely Metal-Poor Star Candidates from the SkyMapper Survey

The SkyMapper Southern Sky Survey is carrying out a search for the most metal-poor stars in the Galaxy. It identifies candidates by way of its unique filter set that allows for estimation of stellar atmospheric parameters. The set includes a narrow filter centered on the Ca II K 3933A line, enabling a robust estimate of stellar metallicity. Promising candidates are then confirmed with spectroscopy. We present the analysis of Magellan-MIKE high-resolution spectroscopy of 122 metal-poor stars found by SkyMapper in the first two years of commissioning observations. 41 stars have [Fe/H] <= -3.0. Nine have [Fe/H] <= -3.5, with three at [Fe/H] ~ -4. A 1D LTE abundance analysis of the elements Li, C, Na, Mg, Al, Si, Ca, Sc, Ti, Cr, Mn, Co, Ni, Zn, Sr, Ba and Eu shows these stars have [X/Fe] ratios typical of other halo stars. One star with low [X/Fe] [X/Fe values appears to be "Fe-enhanced," while another star has an extremely large [Sr/Ba] ratio: >2. Only one other star is known to have a comparable value. Seven stars are "CEMP-no" stars ([C/Fe] > 0.7, [Ba/Fe] < 0). 21 stars exhibit mild r-process element enhancements (0.3 <=[Eu/Fe] < 1.0), while four stars have [Eu/Fe] >= 1.0. These results demonstrate the ability to identify extremely metal-poor stars from SkyMapper photometry, pointing to increased sample sizes and a better characterization of the metal-poor tail of the halo metallicity distribution function in the future.Comment: Minor corrections to text, missing data added to Tables 3 and 4; updated to match published version. Complete tables included in sourc

Amyloid peptides in different assembly states and related effects on isolated and cellular proteasomes

The role of amyloid-β protein (Aβ) in the pathogenesis of Alzheimer's disease (AD) has been widely investigated and amyloid aggregates are considered a major cause of neuronal dysfunction. Increasing evidence has identified a correlation between this protein and the proteasome, the cellular proteolytic machinery, in particular the ubiquitin–proteasome system. The 20S proteasome is the catalytic core of a complex, known as 26S proteasome, and is the main responsible for the clearance of misfolded and oxidized proteins. In this work we have investigated the effects of different assembly states of two major amyloid peptides, Aβ (1–40) and Aβ (1–42) on the 20S proteasome functionality and on the ubiquitin dependent pathway of protein degradation. In particular, we have tested proteasome activities after Aβ treatment on purified 20S complexes and on lysates of a human neuroblastoma cell line. Our findings show a significant decrease in proteasome activity, more evident in cell lysates than in isolated complexes, and an increased amount of ubiquitin–protein conjugates and of a known proteasome substrate (p27). Furthermore, the altered proteasome functionality is not associated with a decrease in cell viability, but is linked with increased levels of protein oxidation

Efficient and versatile manipulation of the peripheral CD4+ T-cell compartment by antigen targeting to DNGR-1/CLEC9A

DC NK lectin group receptor-1 (DNGR-1, also known as CLEC9A) is a C-type lectin receptor expressed by mouse CD8α+ DC and by their putative equivalents in human. DNGR-1 senses necrosis and regulates CD8+ T-cell cross-priming to dead-cell-associated antigens. In addition, DNGR-1 is a target for selective in vivo delivery of antigens to DC and the induction of CD8+ T-cell and Ab responses. In this study, we evaluated whether DNGR-1 targeting can be additionally used to manipulate antigen-specific CD4+ T lymphocytes. Injection of small amounts of antigen-coupled anti-DNGR-1 mAb into mice promoted MHC class II antigen presentation selectively by CD8α+ DC. In the steady state, this was sufficient to induce proliferation of antigen-specific naïve CD4+ T cells and to drive their differentiation into Foxp3+ regulatory lymphocytes. Co-administration of adjuvants prevented this induction of tolerance and promoted immunity. Notably, distinct adjuvants allowed qualitative modulation of CD4+ T-cell behavior: poly I:C induced a strong IL-12-independent Th1 response, whereas curdlan led to the priming of Th17 cells. Thus, antigen targeting to DNGR-1 is a versatile approach for inducing functionally distinct CD4+ T-cell responses. Given the restricted pattern of expression of DNGR-1 across species, this strategy could prove useful for developing immunotherapy protocols in humans

Natural polyphenols as proteasome modulators and their role as anti-cancer compounds

The purpose of this review is to discuss the effect of natural antioxidantcompounds as modulators of the 20S proteasome, a multi-enzymatic multicatalytic complex present in the cytoplasm and nucleus of eukaryotic cells and involved in several cellular activities such as cell-cycle progression, proliferation and the degradation of oxidized and damaged proteins. From this perspective, proteasome inhibition is a promising approach to anticancer therapy and such natural antioxidant effectors can be considered as potential relevant adjuvants and pharmacological models in the study of new drugs

Apoptosis induction by Bid requires unconventional ubiquitination and degradation of its N-terminal fragment

Bcl-2 family member Bid is subject to autoinhibition; in the absence of stimuli, its N-terminal region sequesters the proapoptotic Bcl-2 homology 3 (BH3) domain. Upon proteolytic cleavage in its unstructured loop, Bid is activated, although structural data reveal no apparent resulting conformational change. We found that, upon Bid cleavage, the N-terminal fragment (tBid-N) is ubiquitinated and degraded, thus freeing the BH3 domain in the C-terminal fragment (tBid-C). Ubiquitination of tBid-N is unconventional because acceptor sites are neither lysines nor the N terminus. Chemical approaches implicated thioester and hydroxyester linkage of ubiquitin and mutagenesis implicated serine and possibly threonine as acceptor residues in addition to cysteine. Acceptor sites reside predominantly but not exclusively in helix 1, which is required for ubiquitination and degradation of tBid-N. Rescue of tBid-N from degradation blocked Bid's ability to induce mitochondrial outer membrane permeability but not mitochondrial translocation of the cleaved complex. We conclude that unconventional ubiquitination and proteasome-dependent degradation of tBid-N is required to unleash the proapoptotic activity of tBid-C

Interplay between 20S proteasomes and prion proteins in scrapie disease.

Scrapie is a transmissible spongiform encephalopathy affecting the central nervous system in sheep. The key event in such neurodegeneration is the conversion of the normal prion protein (PrPC) into the pathological isoform (PrPSc). Misfolded prion proteins are normally degraded by the proteasome. This work, analyzing models of scrapie disease, describes the in vivo relationship between the proteasome and prions. We report that the disease is associated with an increase of proteasome functionality, most likely as a means of counteracting the increased levels of oxidative stress. Here, we show that prions coprecipitate with the 20S proteasome and that they colocalize within the same neuron, thus raising the possibility that PrP interacts with the proteasome in both normal and diseased brain, affecting substrate trafficking and proteasome functionality. This interaction, inducing proteasome activation, leads to different neuronal alterations and triggers apoptosis. Furthermore, testing the effects of isolated PrPC on purified 20S proteasomes, we obtain a concentration- and proteasome composition-dependent decrease in the complex activity. (C) 2009 Wiley-Liss, Inc

Using the community psychology competencies to address sexual assault on a college campus

Sexual assault on college campuses is a national issue, with a recent report from the White House estimating that 20% of women will experience a sexual assault during college.&nbsp; Students at Wichita State University formed a campus organization to bring visibility to both community psychology and address this important problem.&nbsp; The Community Psychology Association is comprised of both graduate and undergraduate students, and members utilized three community psychology competencies: ecological perspectives, information dissemination/building public awareness, and community organizing and community advocacy in their work to improve resources and campus support for this issue.&nbsp; Community Psychology Association members utilized focus groups with campus students, faculty, and staff to facilitate discussions on sexual assault, campus safety, and university and administrative accountability.&nbsp; Content analysis revealed multiple themes that were used to generate a larger campus discussion and promote change in campus policies. As a result of these activities, major changes occurred at Wichita State, including data driven programming for interventions regarding sexual assault, changes in leadership in the offices of Title IX and Student Affairs, support for a CDC grant, and overall increased organizational awareness for sexual assault survivors.&nbsp; This study highlights the importance of applying community psychology principles and concepts to research and action to ultimately have a positive and tangible impact on the local community

Using the community psychology competencies to address sexual assault on a college campus

Sexual assault on college campuses is a national issue, with a recent report from the White House estimating that 20% of women will experience a sexual assault during college.&nbsp; Students at Wichita State University formed a campus organization to bring visibility to both community psychology and address this important problem.&nbsp; The Community Psychology Association is comprised of both graduate and undergraduate students, and members utilized three community psychology competencies: ecological perspectives, information dissemination/building public awareness, and community organizing and community advocacy in their work to improve resources and campus support for this issue.&nbsp; Community Psychology Association members utilized focus groups with campus students, faculty, and staff to facilitate discussions on sexual assault, campus safety, and university and administrative accountability.&nbsp; Content analysis revealed multiple themes that were used to generate a larger campus discussion and promote change in campus policies. As a result of these activities, major changes occurred at Wichita State, including data driven programming for interventions regarding sexual assault, changes in leadership in the offices of Title IX and Student Affairs, support for a CDC grant, and overall increased organizational awareness for sexual assault survivors.&nbsp; This study highlights the importance of applying community psychology principles and concepts to research and action to ultimately have a positive and tangible impact on the local community

Wheat sprout extract-induced apoptosis in human cancer cells by proteasomes modulation.

Natural occurring modulators of proteasome functionality are extensively investigated for their implication in cancer therapy. On the basis of our previous evidences both on proteasomal inhibition by monomeric polyphenols, and on the characterization of wheat sprout hydroalcoholic extract, herein we thoroughly report on a comparative study of the effect of wheat sprout extract on both normal and tumour cells. Treatment of isolated 20S proteasomes with wheat sprout extracts induced a gradual inhibition of all proteasome activities. Next, two wheat sprout extract components were separated: a polyphenol and a protein fraction. Both components exerted an in vitro inhibitory effect on proteasome activity. HeLa tumour cells and FHs 74 Int normal cells were exposed to both fractions, resulting in different rates of proteasome inhibition, with tumour cells showing a significantly higher degree of proteasome impairment and apoptosis induction. Furthermore, a decrease in proteasome activities and in cell survival of the human plasmacytoma RPMI 8226 cell line, upon the same treatments, was observed. Collectively, our results provide additional evidences supporting the possible use of natural extracts as coadjuvants in cancer treatments

Detecting forest response to droughts with global observations of vegetation water content

Droughts in a warming climate have become more common and more extreme, making understanding forest responses to water stress increasingly pressing. Analysis of water stress in trees has long focused on water potential in xylem and leaves, which influences stomatal closure and water flow through the soil-plant-atmosphere continuum. At the same time, changes of vegetation water content (VWC) are linked to a range of tree responses, including fluxes of water and carbon, mortality, flammability, and more. Unlike water potential, which requires demanding in situ measurements, VWC can be retrieved from remote sensing measurements, particularly at microwave frequencies using radar and radiometry. Here, we highlight key frontiers through which VWC has the potential to significantly increase our understanding of forest responses to water stress. To validate remote sensing observations of VWC at landscape scale and to better relate them to data assimilation model parameters, we introduce an ecosystem-scale analog of the pressure–volume curve, the non-linear relationship between average leaf or branch water potential and water content commonly used in plant hydraulics. The sources of variability in these ecosystem-scale pressure-volume curves and their relationship to forest response to water stress are discussed. We further show to what extent diel, seasonal, and decadal dynamics of VWC reflect variations in different processes relating the tree response to water stress. VWC can also be used for inferring belowground conditions—which are difficult to impossible to observe directly. Lastly, we discuss how a dedicated geostationary spaceborne observational system for VWC, when combined with existing datasets, can capture diel and seasonal water dynamics to advance the science and applications of global forest vulnerability to future droughts