Rescuing Spanish Radiation Therapy: The Role of Leadership and Opportunity
No abstract prepared.
62 RADIOLOGY AND NUCLEAR MEDICINE↗
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Results for “RESCUE”
Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.
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Microbiome rescue: directing resilience of environmental microbial communities
Not Available
59 BASIC BIOLOGICAL SCIENCES↗
Plant photosystem II assembly: TROL2 to the rescue
Not Available
Puthiyaveetil, Sujith (ORCID:0000000175054511)↗
Methyl Vitamin B12 but not methylfolate rescues a motor neuron-like cell line from homocysteine-mediated cell death
Homocysteine is an excitatory amino acid implicated in multiple diseases including amyotrophic lateral sclerosis (ALS). Information on the toxicity of homocysteine in motor neurons is limited and few studies have examined how this toxicity can be modulated. In NSC-34D cells (a hybrid cell line derived from motor neuron-neuroblastoma), homocysteine induces apoptotic cell death in the millimolar range with a TC{sub 50} (toxic concentration at which 50% of maximal cell death is achieved) of 2.2 mM, confirmed by activation of caspase 3/7. Induction of apoptosis was independent of short-term reactive oxygen species (ROS) generation. Methyl Vitamin B12 (MeCbl) and methyl tetrahydrofolate (MTHF), used clinically to treat elevated homocysteine levels, were tested for their ability to reverse homocysteine-mediated motor neuron cell death. MeCbl in the micromolar range was able to provide neuroprotection (2 h pretreatment prior to homocysteine) and neurorescue (simultaneous exposure with homocysteine) against millimolar homocysteine with an IC{sub 50} (concentration at which 50% of maximal cell death is inhibited) of 0.6 {mu}M and 0.4 {mu}M, respectively. In contrast, MTHF (up to 10 {mu}M) had no effect on homocysteine-mediated cell death. MeCbl inhibited caspase 3/7 activation by homocysteine in a time- and dose-dependent manner, whereas MTHF had no effect. We conclude that MeCbl is effective against homocysteine-induced cell death in motor neurons in a ROS-independent manner, via a reduction in caspase activation and apoptosis. MeCbl decreases Hcy induced motor neuron death in vitro in a hybrid cell line derived from motor neuron-neuroblastoma and may play a role in the treatment of late stage ALS where HCy levels are increased in animal models of ALS.
60 APPLIED LIFE SCIENCES↗
Curcumin rescues high fat diet-induced obesity and insulin sensitivity in mice through regulating SREBP pathway
Obesity and its major co-morbidity, type 2 diabetes, have reached an alarming epidemic prevalence without an effective treatment available. It has been demonstrated that inhibition of SREBP pathway may be a useful strategy to treat obesity with type 2 diabetes. Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acid and triglyceride. In current study, we identified a small molecule, curcumin, inhibited the SREBP expression in vitro. The inhibition of SREBP by curcumin decreased the biosynthesis of cholesterol and fatty acid. In vivo, curcumin ameliorated HFD-induced body weight gain and fat accumulation in liver or adipose tissues, and improved serum lipid levels and insulin sensitivity in HFD-induced obese mice. Consistently, curcumin regulates SREBPs target genes and metabolism associated genes in liver or adipose tissues, which may directly contribute to the lower lipid level and improvement of insulin resistance. Take together, curcumin, a major active component of Curcuma longa could be a potential leading compound for development of drugs for the prevention of obesity and insulin resistance. - Highlights: • Curcumin decreases biosynthesis of cholesterol and fatty acid in vitro. • Curcumin as a SREBP inhibitor ameliorates HFD-induced obesity. • Curcumin as a SREBP inhibitor improves insulin resistance.
60 APPLIED LIFE SCIENCES↗
Compounding variants rescue the effect of a deleterious ADAMTS13 mutation in a child with severe congenital heart disease
Not Available
Katneni, Upendra K.↗
Exosomes derived from hypoxic bone marrow mesenchymal stem cells rescue OGD-induced injury in neural cells by suppressing NLRP3 inflammasome-mediated pyroptosis
Exosomes have been shown to have therapeutic potential for cerebral ischemic diseases. In this study, we investigated the neuroprotective effects of normoxic and hypoxic bone marrow mesenchymal stromal cells-derived exosomes (N-BM-MSCs-Exo and H-BM-MSCs-Exo, respectively) on oxygen-glucose deprivation (OGD) injury in mouse neuroblastoma N2a cells and rat primary cortical neurons. The proportions of dead cells in N2a and primary cortical neurons after OGD injury were significantly increased, and N-BM-MSCs-Exo (40 μg/ml) could reduce the ratios, noteworthily, the protective effects of H-BM-MSCs-Exo (40 μg/ml) were more potent. Western blotting analysis indicated that N-BM-MSCs-Exo decreased the expression of NLRP3, ASC, Caspase-1, GSDMD-N, cleaved IL-1β and IL-18 in N2a cells. However, H-BM-MSCs-Exo (40 μg/ml) was more powerful in inhibiting the expression of these proteins in comparison with N-BM-MSCs-Exo. Similar results were obtained in primary cortical neurons. Immunofluorescence assays showed that after N-BM-MSCs-Exo and H-BM-MSCs-Exo treatment, the co-localization of NLRP3, ASC, Caspase-1 and the GSDMD translocation from the nucleus to the cytoplasm and membrane after OGD injury were reduced in N2a cells and primary cortical neurons, and H-BM-MSCs-Exo had a more obvious effect. In addition, N-BM-MSCs-Exo and H-BM-MSCs-Exo significantly reduced lactate dehydrogenase (LDH) release and the IL-18 levels in cell culture medium in N2a cells and primary cortical neurons. Once again H-BM-MSCs-Exo induced these effects more potently than N-BM-MSCs-Exo. All of these results demonstrated that N-BM-MSCs-Exo and H-BM-MSCs-Exo have significant neuroprotective effects against NLRP3 inflammasome-mediated pyroptosis. H-BM-MSCs-Exo has a more pronounced protective effect than N-BM-MSCs-Exo and may be used to ameliorate the progression of cerebral ischemia and hypoxia injury in patients.
60 APPLIED LIFE SCIENCES↗
Rescuing Those Left Behind: Recovering and Characterizing Underdigested Membrane and Hydrophobic Proteins To Enhance Proteome Measurement Depth
The marine archaeon Nanoarchaeum equitans is dependent on direct physical contact with its host, the hyperthermophile Ignicoccus hospitalis. It is thought that this interaction is membrane-associated, involving a myriad of membrane-anchored proteins; proteomic efforts to better characterize this difficult to analyze interface are paramount to uncovering the mechanism of their association. By extending multienzyme digestion strategies that use sample filtration to recover underdigested proteins for reprocessing/consecutive proteolytic digestion, we applied chymotrypsin to redigest the proteinaceous material left over after initial proteolysis with trypsin of sodium dodecyl sulfate (SDS)-extracted I. hospitalis-N. equitansproteins. We show that proteins with increased hydrophobic character, including membrane proteins with multiple transmembrane helices, are enriched and recovered in the underdigested fraction. Chymotryptic reprocessing provided significant sequence coverage gains in both soluble and hydrophobic proteins alike, with the latter benefiting more so in terms of membrane protein representation. Moreover, these gains were despite a large proportion of high-quality peptide spectra remaining unassigned in the underdigested fraction suggesting high levels of protein modification on these often surface-exposed proteins. Importantly, these gains were achieved without applying extensive fractionation strategies usually required for thorough characterization of membrane-associated proteins and were facilitated by the generation of a distinct, complementary set of peptides that aid in both the identification and quantitation of this important, under-represented class of proteins.
59 BASIC BIOLOGICAL SCIENCES↗
Hydrogen Bonding Rescues Overpotential in Seven-Coordinated Ru Water Oxidation Catalysts
In this paper, we describe the synthesis, structural characterization, and redox properties of two new Ru complexes containing the dianionic potentially pentadentate [2,2':6',2"-terpyridine]-6,6"-dicarboxylate (tda 2– ) ligand that coordinates Ru at the equatorial plane and with additional pyridine or dmso acting as monondentate ligand in the axial positions: [Ru II (tda-κ-N 3 O)(py)(dmso)], 1 II and [Ru III (tda-κ-N 3 O 2 )(py)(H 2 O) ax ] + , 2 III (H 2 O) + . Complex 1 II has been characterized by single-crystal XRD in the solid state and in solution by NMR spectroscopy. The redox properties of 1 II and 2 III (H 2 O) + have been thoroughly investigated by means of cyclic voltammetry and differential pulse voltammetry. Complex 2 II (H 2 O) displays poor catalytic activity with regard to the oxidation of water to dioxygen, and its properties have been analyzed on the basis of foot of the wave analysis and catalytic Tafel plots. The activity of 2 II (H 2 O) has been compared with related water oxidation catalysts (WOCs) previously described in the literature. Despite its moderate activity, 2 II (H 2 O) constitutes the cornerstone that has triggered the rationalization of the different factors that govern overpotentials as well as efficiencies in molecular WOCs. The present work uncovers the interplay between different parameters, namely, coordination number, number of anionic groups bonded to the first-coordination sphere of the metal center, water oxidation catalysis overpotential, p K a and hydrogen bonding, and the performance of a given WOC. It thus establishes the basic principles for the design of efficient WOCs operating at low overpotentials.
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
Rescue of the Orphan Enzyme Isoguanine Deaminase
Cytosine deaminase (CDA) from Escherichia coli was shown to catalyze the deamination of isoguanine (2-oxoadenine) to xanthine. Isoguanine is an oxidation product of adenine in DNA that is mutagenic to the cell. The isoguanine deaminase activity in E. coli was partially purified by ammonium sulfate fractionation, gel filtration, and anion exchange chromatography. The active protein was identified by peptide mass fingerprint analysis as cytosine deaminase. The kinetic constants for the deamination of isoguanine at pH 7.7 are as follows: k{sub cat} = 49 s{sup -1}, K{sub m} = 72 {micro}M, and k{sub cat}/K{sub m} = 6.7 x 10{sup 5} M{sup -1} s{sup -1}. The kinetic constants for the deamination of cytosine are as follows: k{sub cat} = 45 s{sup -1}, K{sub m} = 302 {micro}M, and k{sub cat}/K{sub m} = 1.5 x 10{sup 5} M{sup -1} s{sup -1}. Under these reaction conditions, isoguanine is the better substrate for cytosine deaminase. The three-dimensional structure of CDA was determined with isoguanine in the active site.
59 BASIC BIOLOGICAL SCIENCES↗
The Designability of Protein Switches by Chemical Rescue of Structure: Mechanisms of Inactivation and Reactivation
Abstract not provided
Xia, Yan↗
Tuning Radical Relay Residues by Proton Management Rescues Protein Electron Hopping
Explore the source record for details and available documents.
Yee, Estella F.↗
Rescue of conformational dynamics in enzyme catalysis by directed evolution
Rational design and directed evolution have proved to be successful approaches to increase catalytic efficiencies of both natural and artificial enzymes. Protein dynamics is recognized as important, but due to the inherent flexibility of biological macromolecules it is often difficult to distinguish which conformational changes are directly related to function. Here, we use directed evolution on an impaired mutant of the proline isomerase CypA and identify two second-shell mutations that partially restore its catalytic activity. We show both kinetically, using NMR spectroscopy, and structurally, by room-temperature X-ray crystallography, how local perturbations propagate through a large allosteric network to facilitate conformational dynamics. The increased catalysis selected for in the evolutionary screen is correlated with an accelerated interconversion between the two catalytically essential conformational sub-states, which are both captured in the high-resolution X-ray ensembles. Our data provide a glimpse of an evolutionary trajectory and show how subtle changes can fine-tune enzyme function.
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity
Death due to sepsis remains a persistent threat to critically ill patients confined to the intensive care unit and is characterized by colonization with multi-drug-resistant healthcare-associated pathogens. Here we report that sepsis in mice caused by a defined four-member pathogen community isolated from a patient with lethal sepsis is associated with the systemic suppression of key elements of the host transcriptome required for pathogen clearance and decreased butyrate expression. More specifically, these pathogens directly suppress interferon regulatory factor 3. Fecal microbiota transplant (FMT) reverses the course of otherwise lethal sepsis by enhancing pathogen clearance via the restoration of host immunity in an interferon regulatory factor 3-dependent manner. This protective effect is linked to the expansion of butyrate-producing Bacteroidetes. Taken together these results suggest that fecal microbiota transplantation may be a treatment option in sepsis associated with immunosuppression.
59 BASIC BIOLOGICAL SCIENCES↗
Mechanism of Rad26-assisted rescue of stalled RNA polymerase II in transcription-coupled repair
Transcription-coupled repair is essential for the removal of DNA lesions from the transcribed genome. The pathway is initiated by CSB protein binding to stalled RNA polymerase II. Mutations impairing CSB function cause severe genetic disease. Yet, the ATP-dependent mechanism by which CSB powers RNA polymerase to bypass certain lesions while triggering excision of others is incompletely understood. Here we build structural models of RNA polymerase II bound to the yeast CSB ortholog Rad26 in nucleotide-free and bound states. This enables simulations and graph-theoretical analyses to define partitioning of this complex into dynamic communities and delineate how its structural elements function together to remodel DNA. We identify an allosteric pathway coupling motions of the Rad26 ATPase modules to changes in RNA polymerase and DNA to unveil a structural mechanism for CSB-assisted progression past less bulky lesions. Our models allow functional interpretation of the effects of Cockayne syndrome disease mutations.
59 BASIC BIOLOGICAL SCIENCES↗
Iron rescues glucose-mediated photosynthesis repression during lipid accumulation in the green alga Chromochloris zofingiensis
Energy status and nutrients regulate photosynthetic protein expression. The unicellular green alga Chromochloris zofingiensis switches off photosynthesis in the presence of exogenous glucose (+Glc) in a process that depends on hexokinase (HXK1). Here, we show that this response requires that cells lack sufficient iron (–Fe). Cells grown in –Fe+Glc accumulate triacylglycerol (TAG) while losing photosynthesis and thylakoid membranes. However, cells with an iron supplement (+Fe+Glc) maintain photosynthesis and thylakoids while still accumulating TAG. Proteomic analysis shows that known photosynthetic proteins are most depleted in heterotrophy, alongside hundreds of uncharacterized, conserved proteins. Photosynthesis repression is associated with enzyme and transporter regulation that redirects iron resources to (a) respiratory instead of photosynthetic complexes and (b) a ferredoxin-dependent desaturase pathway supporting TAG accumulation rather than thylakoid lipid synthesis. Combining insights from diverse organisms from green algae to vascular plants, we show how iron and trophic constraints on metabolism aid gene discovery for photosynthesis and biofuel production.
59 BASIC BIOLOGICAL SCIENCES↗