Distinct iron binding property of two putative iron donors for the iron-sulfur cluster assembly: IscA and the bacterial frataxin ortholog CyaY under physiological and oxidative stress conditions

Frataxin, a small mitochondrial protein linked to the neurodegenerative disease Friedreich ataxia, has recently been proposed as an iron donor for the iron-sulfur cluster assembly. An analogous function has also been attributed to IscA, a key member of the iron-sulfur cluster assembly machinery found in bacteria, yeast, and humans. Here we have compared the iron binding property of IscA and the frataxin ortholog CyaY from Escherichia coli under physiological and oxidative stress conditions. In the presence of the thioredoxin reductase system, which emulates the intracellular redox potential, CyaY fails to bind any iron even at a 10-fold excess of iron in the incubation solution. Under the same physiologically relevant conditions, IscA efficiently recruits iron and transfers the iron for the ironsulfur cluster assembly in a proposed scaffold IscU. In the presence of hydrogen peroxide, however, IscA completely loses its iron binding activity, whereas CyaY becomes a competent iron-binding protein and attenuates the iron-mediated production of hydroxyl free radicals. Hydrogen peroxide appears to oxidize the iron binding thiol groups in IscA, thus blocking the iron binding in the protein. Once the oxidized thiol groups in IscA are re-reduced with the thioredoxin reductase system, the iron binding activity of IscA is fully restored. On the other hand, hydrogen peroxide has no effect on the iron binding carboxyl groups in CyaY, allowing the protein to bind iron under oxidative stress conditions. The results suggest that IscA is capable of recruiting intracellular iron for the iron-sulfur cluster assembly under normal physiological conditions, whereas CyaY may serve as an iron chaperon to sequester redox active free iron and alleviate cellular oxidative damage under oxidative stress conditions. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc

Developing an Older Adult Volunteer Program in a New York Chinese Community: An Evidence-Based Approach

This study reports the results of a pilot volunteer project for older Chinese immigrants and documents benefits for both volunteers and caregiver recipients. Using a social marketing approach, the volunteer project was designed as a social model to promote better health among older Chinese immigrants in New York City. The packaging of this health promotion project as a volunteer program was based on a strengths perspective. In the program, 18 older Chinese immigrants were trained to provide support and referral to family caregivers of ill relatives in the Chinese community. At 6 months, outcomes were evaluated for both volunteers and caregivers. The older volunteers perceived benefits associated with volunteering, specifically, a greater sense of well-being and satisfaction with life. In addition, the majority of volunteers felt empowered by training and volunteering (100 %), felt the skills they learned improved communication with their own families (90 %), and reported physical and emotional health benefits (61 %). At the same time, caregivers reported stress reduction following volunteer support. Findings suggest that a volunteer program model may be an effective health promotion intervention for older Chinese immigrants

Image Super-Resolution Reconstruction Based on L1/2 Sparsity

Based on image sparse representation in the shearlet domain, we proposed a L1/2 sparsity regularized unconvex variation model for image super-resolution. The L1/2 regularizer term constrains the underlying image to have a sparse representation in shearlet domain. The fidelity term restricts the consistency with the measured imaged in terms of the data degradation model. Then, the variable splitting algorithm is used to break down the model into a series of constrained optimization problems which can be solved by alternating direction method of multipliers. Experimental results demonstrate the effectiveness of the proposed method, both in its visual effects and in quantitative terms

Experimentally Engineering the Edge Termination of Graphene Nanoribbons

The edges of graphene nanoribbons (GNRs) have attracted much interest due to their potentially strong influence on GNR electronic and magnetic properties. Here we report the ability to engineer the microscopic edge termination of high quality GNRs via hydrogen plasma etching. Using a combination of high-resolution scanning tunneling microscopy and first-principles calculations, we have determined the exact atomic structure of plasma-etched GNR edges and established the chemical nature of terminating functional groups for zigzag, armchair and chiral edge orientations. We find that the edges of hydrogen-plasma-etched GNRs are generally flat, free of structural reconstructions and are terminated by hydrogen atoms with no rehybridization of the outermost carbon edge atoms. Both zigzag and chiral edges show the presence of edge states.Comment: 16+9 pages, 3+4 figure

αV Integrin Induces Multicellular Radioresistance in Human Nasopharyngeal Carcinoma via Activating SAPK/JNK Pathway

BACKGROUND:Tumor cells acquire the capacity of resistance to chemotherapy or radiotherapy via cell-matrix and cell-cell crosstalk. Integrins are the most important cell adhesion molecules, in which αV integrin mainly mediating the tight contact between tumor cells. METHODOLOGY/PRINCIPAL FINDINGS:To investigate the role of αV integrin in multi-cellular radioresistance (MCR) of human nasopharyngeal carcinoma (NPC), we performed immunohistochemistry and Western blotting to find that the expression of αV integrin in the tumor tissue of radioresistant patients is much higher than that in radiosensitive patients. In vitro, we cultured human NPC cell line CNE-2 cells as multi-cellular spheroids (MCSs) or as monolayer cells (MCs), and found that the expression of αV integrin in MCSs is significantly higher than that in MCs. MTT, flow cytometry and clonogenic survival assays showed that MCSs are less sensitive to X-ray irradiation than MCs while blocking of αV integrin in MCSs dramatically reversed their radioresistance. Furthermore, as detected by Western blotting, MCSs displayed sustained activation of the stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) pathway in presence of irradiation. Blocking of αV integrin in MCSs decreased the expression of phosphorylated JNK. Additionally, blocking of SAPK/JNK signaling pathway synergistically induced apoptosis of MCSs exposed to irradiation by increasing the expression of cleaved caspase-3. In vivo, we found that irradiation combined with αV integrin blocking treatment significantly enhanced the radiosensitivity of NPC xenografts. CONCLUSIONS:Our results indicate a novel role of αV integrin in multi-cellular radioresistance of NPCs

Ebolavirus comparative genomics

The 2014 Ebola outbreak in West Africa is the largest documented for this virus. To examine the dynamics of this genome, we compare more than 100 currently available ebolavirus genomes to each other and to other viral genomes. Based on oligomer frequency analysis, the family Filoviridae forms a distinct group from all other sequenced viral genomes. All filovirus genomes sequenced to date encode proteins with similar functions and gene order, although there is considerable divergence in sequences between the three genera Ebolavirus, Cuevavirus and Marburgvirus within the family Filoviridae. Whereas all ebolavirus genomes are quite similar (multiple sequences of the same strain are often identical), variation is most common in the intergenic regions and within specific areas of the genes encoding the glycoprotein (GP), nucleoprotein (NP) and polymerase (L). We predict regions that could contain epitope-binding sites, which might be good vaccine targets. This information, combined with glycosylation sites and experimentally determined epitopes, can identify the most promising regions for the development of therapeutic strategies.This manuscript has been authored by UT-Battelle, LLC under Contract No. DE-AC05-00OR22725 with the U.S. Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes. The Department of Energy will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan (http://energy.gov/downloads/doe-public-access-plan).Fil: Jun, Se Ran. Oak Ridge National Laboratory; Estados Unidos. University of Tennessee; Estados UnidosFil: Leuze, Michael R.. Oak Ridge National Laboratory; Estados UnidosFil: Nookaew, Intawat. Oak Ridge National Laboratory; Estados UnidosFil: Uberbacher, Edward C.. Oak Ridge National Laboratory; Estados UnidosFil: Land, Miriam. Oak Ridge National Laboratory; Estados UnidosFil: Zhang, Qian. Oak Ridge National Laboratory; Estados Unidos. University of Tennessee; Estados UnidosFil: Wanchai, Visanu. Oak Ridge National Laboratory; Estados UnidosFil: Chai, Juanjuan. Oak Ridge National Laboratory; Estados UnidosFil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; ArgentinaFil: Trolle, Thomas. Technical University of Denmark; DinamarcaFil: Lund, Ole. Technical University of Denmark; DinamarcaFil: Buzard, Gregory S.. Booze Allen Hamilton; Estados UnidosFil: Pedersen, Thomas D.. Technical University of Denmark; Dinamarca. Assays; DinamarcaFil: Wassenaar, Trudy M.. Molecular Microbiology and Genomics Consultants; AlemaniaFil: Ussery, David W.. Oak Ridge National Laboratory; Estados Unidos. University of Tennessee; Estados Unidos. Technical University of Denmark; Dinamarc

HRS1 Acts as a Negative Regulator of Abscisic Acid Signaling to Promote Timely Germination of Arabidopsis Seeds

In this work, we conducted functional analysis of Arabidopsis HRS1 gene in order to provide new insights into the mechanisms governing seed germination. Compared with wild type (WT) control, HRS1 knockout mutant (hrs1-1) exhibited significant germination delays on either normal medium or those supplemented with abscisic acid (ABA) or sodium chloride (NaCl), with the magnitude of the delay being substantially larger on the latter media. The hypersensitivity of hrs1-1 germination to ABA and NaCl required ABI3, ABI4 and ABI5, and was aggravated in the double mutant hrs1-1abi1-2 and triple mutant hrs1-1hab1-1abi1-2, indicating that HRS1 acts as a negative regulator of ABA signaling during seed germination. Consistent with this notion, HRS1 expression was found in the embryo axis, and was regulated both temporally and spatially, during seed germination. Further analysis showed that the delay of hrs1-1 germination under normal conditions was associated with reduction in the elongation of the cells located in the lower hypocotyl (LH) and transition zone (TZ) of embryo axis. Interestingly, the germination rate of hrs1-1 was more severely reduced by the inhibitor of cell elongation, and more significantly decreased by the suppressors of plasmalemma H+-ATPase activity, than that of WT control. The plasmalemma H+-ATPase activity in the germinating seeds of hrs1-1 was substantially lower than that exhibited by WT control, and fusicoccin, an activator of this pump, corrected the transient germination delay of hrs1-1. Together, our data suggest that HRS1 may be needed for suppressing ABA signaling in germinating embryo axis, which promotes the timely germination of Arabidopsis seeds probably by facilitating the proper function of plasmalemma H+-ATPase and the efficient elongation of LH and TZ cells

Interaction between Attention and Bottom-Up Saliency Mediates the Representation of Foreground and Background in an Auditory Scene

Bottom-up (stimulus-driven) and top-down (attentional) processes interact when a complex acoustic scene is parsed. Both modulate the neural representation of the target in a manner strongly correlated with behavioral performance