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Border Control—A Membrane-Linked Interactome of <i>Arabidopsis</i>
Jones, Alexander M.,Xuan, Yuanhu,Xu, Meng,Wang, Rui-Sheng,Ho, Cheng-Hsun,Lalonde, Sylvie,You, Chang Hun,Sardi, Maria I.,Parsa, Saman A.,Smith-Valle, Erika,Su, Tianying,Frazer, Keith A.,Pilot, Guillaum American Association for the Advancement of Scienc 2014 Science Vol.344 No.6185
<P>Cellular membranes act as signaling platforms and control solute transport. Membrane receptors, transporters, and enzymes communicate with intracellular processes through protein-protein interactions. Using a split-ubiquitin yeast two-hybrid screen that covers a test-space of 6.4 x 10(6) pairs, we identified 12,102 membrane/signaling protein interactions from Arabidopsis. Besides confirmation of expected interactions such as heterotrimeric G protein subunit interactions and aquaporin oligomerization, >99% of the interactions were previously unknown. Interactions were confirmed at a rate of 32% in orthogonal in planta split-green flourescent protein interaction assays, which was statistically indistinguishable from the confirmation rate for known interactions collected from literature (38%). Regulatory associations in membrane protein trafficking, turnover, and phosphorylation include regulation of potassium channel activity through abscisic acid signaling, transporter activity by a WNK kinase, and a brassinolide receptor kinase by trafficking-related proteins. These examples underscore the utility of the membrane/signaling protein interaction network for gene discovery and hypothesis generation in plants and other organisms.</P>
Polymorphism in the CagA EPIYA Motif Impacts Development of Gastric Cancer
Jones, K. R.,Joo, Y. M.,Jang, S.,Yoo, Y.-J.,Lee, H. S.,Chung, I.-S.,Olsen, C. H.,Whitmire, J. M.,Merrell, D. S.,Cha, J.-H. American Society for Microbiology 2009 Journal of clinical microbiology Vol.47 No.4
<P>Helicobacter pylori causes diseases ranging from gastritis to peptic ulcer disease to gastric cancer. Geographically, areas with high incidences of H. pylori infection often overlap with areas with high incidences of gastric cancer, which remains one of the leading causes of cancer-related deaths worldwide. Strains of H. pylori that carry the virulence factor cytotoxin-associated gene A (cagA) are much more likely to be associated with the development of gastric cancer. Moreover, particular C-terminal polymorphisms in CagA vary by geography and have been suggested to influence disease development. We conducted a large-scale molecular epidemiologic analysis of South Korean strains and herein report a statistical link between the East Asian CagA EPIYA-ABD genotype and the development of gastric cancer. Characterization of a subset of the Korean isolates showed that all strains from cancer patients expressed and delivered phosphorylatable CagA to host cells, whereas the presence of the cagA gene did not strictly correlate to expression and delivery of CagA in all noncancer strains.</P>
Multi-target-directed phenol–triazole ligands as therapeutic agents for Alzheimer's disease
Jones, Michael R.,Mathieu, Emilie,Dyrager, Christine,Faissner, Simon,Vaillancourt, Zavier,Korshavn, Kyle J.,Lim, Mi Hee,Ramamoorthy, Ayyalusamy,Wee Yong, V.,Tsutsui, Shigeki,Stys, Peter K.,Storr, Tim Royal Society of Chemistry 2017 Chemical Science Vol.8 No.8
<▼1><P>A series of multi-target-directed ligands are described that bind Cu, act as antioxidants, modulate Aβ peptide aggregation, and abolish Aβ toxicity in primary neurons.</P></▼1><▼2><P>Alzheimer's disease (AD) is a multifactorial disease that is characterized by the formation of intracellular neurofibrillary tangles and extracellular amyloid-β (Aβ) plaque deposits. Increased oxidative stress, metal ion dysregulation, and the formation of toxic Aβ peptide oligomers are all considered to contribute to the etiology of AD. In this work we have developed a series of ligands that are multi-target-directed in order to address several disease properties. 2-(1-(3-Hydroxypropyl)-1<I>H</I>-1,2,3-triazol-4-yl)phenol (<B>POH</B>), 2-(1-(2-morpholinoethyl)-1<I>H</I>-1,2,3-triazol-4-yl)phenol (<B>PMorph</B>), and 2-(1-(2-thiomorpholinoethyl)-1<I>H</I>-1,2,3-triazol-4-yl)phenol (<B>PTMorph</B>) have been synthesized and screened for their antioxidant capacity, Cu-binding affinity, interaction with the Aβ peptide and modulation of Aβ peptide aggregation, and the ability to limit Aβ<SUB>1–42</SUB>-induced neurotoxicity in human neuronal culture. The synthetic protocol and structural variance incorporated <I>via</I> click chemistry, highlights the influence of R-group modification on ligand-Aβ interactions and neuroprotective effects. Overall, this study demonstrates that the phenol–triazole ligand scaffold can target multiple factors associated with AD, thus warranting further therapeutic development.</P></▼2>
Jones, G.,Loeffler, D.,Calkin, D.,Chung, W. Pergamon ; Elsevier Science Ltd 2010 Biomass & bioenergy Vol.34 No.5
Mill residues from forest industries are the source for most of the current wood-based energy in the US, approximately 2.1% of the nation's energy use in 2007. Forest residues from silvicultural treatments, which include limbs, tops, and small non-commercial trees removed for various forest management objectives, represent an additional source of woody biomass for energy. We spatially analyzed collecting, grinding, and hauling forest residue biomass on a 515,900ha area in western Montana, US, to compare the total emissions of burning forest residues in a boiler for thermal energy with the alternatives of onsite disposal by pile-burning and using either natural gas or #2 distillate oil to produce the equivalent amount of useable energy. When compared to the pile-burn/fossil fuel alternatives, carbon dioxide emissions from the bioenergy alternative were approximately 60%, methane emissions were approximately 3%, and particulate emissions less than 10μm were 11% and 41%, respectively, for emission control and no-control boilers. Emissions from diesel consumption for collecting, grinding, and hauling biomass represented less than 5% of the total bioenergy emissions at an average haul distance of 136km. Across the study area, an average 21 units of bioenergy were produced for each unit of diesel energy used to collect, grind, and haul biomass. Fossil fuel energy saved by the bioenergy alternative relative to the pile-burn/fossil fuel alternatives averaged 14.7-15.2GJt<SUP>-1</SUP>of biomass.