Violent Deaths of Iraqi Civilians, 2003–2008: Analysis by Perpetrator, Weapon, Time, and Location

Madelyn Hsiao-Rei Hicks and colleagues provide a detailed analysis of Iraqi civilian violent deaths during 2003-2008 of the Iraq war and show that of 92,614 deaths, unknown perpetrators caused 74% of deaths, Coalition forces 12%, and Anti-Coalition forces 11%

Crystal Structures of DNA Intercalating Agents Dipyrido[3,2-f:2′,3′-h]quinoxaline (dpq), (Benzo[<i>i</i>]dipyrido[3,2-a:2′,3′c]phenazine (dppn), and [Ir(ppy)₂(dppn)][PF₆] (Where Hppy = 2-Phenylpyridine)

Pyrazino-phenanthroline ligands are commonly used with transition metals as DNA intercalation agents. Herein, we report the characterization of two commonly utilized pyrazino-phenanthroline ligands, dipyrido[3,2-f:2′,3′-h]quinoxaline (dpq) and (benzo[i]dipyrido[3,2-a:2′,3′c]phenazine (dppn), by single-crystal X-ray diffraction. Additionally, the characterization of [Ir(ppy)2(dppn)][PF6], where Hppy = 2-phenylpyridine, by single-crystal X-ray diffraction is described. Both the dpq and dppn ligands crystallize as chloroform solvates where the chloroform molecule occupies the equivalent binding pocket of a metal in metal complexes of these ligands. These pyrazino-phenanthrolines are largely planar, with the dppn ligand displaying a slight twist. When the dppn ligand is coordinated to iridium(III), the dppn ligand on the resulting complex displays a significant degree of bending along the longitudinal direction of the ligand. This iridium (III) complex crystallizes as a CH2Cl2 and Et2O solvate and due to the volatility of these solvents these crystals are only stable for a few seconds outside of the mother liquor. The structures of the free ligands and the [Ir(ppy)2(dppn)][PF6] complex all display extensive π stacking interactions

Genome-wide miRNA response to anacardic acid in breast cancer cells.

MicroRNAs are biomarkers and potential therapeutic targets for breast cancer. Anacardic acid (AnAc) is a dietary phenolic lipid that inhibits both MCF-7 estrogen receptor α (ERα) positive and MDA-MB-231 triple negative breast cancer (TNBC) cell proliferation with IC50s of 13.5 and 35 μM, respectively. To identify potential mediators of AnAc action in breast cancer, we profiled the genome-wide microRNA transcriptome (microRNAome) in these two cell lines altered by the AnAc 24:1n5 congener. Whole genome expression profiling (RNA-seq) and subsequent network analysis in MetaCore Gene Ontology (GO) algorithm was used to characterize the biological pathways altered by AnAc. In MCF-7 cells, 69 AnAc-responsive miRNAs were identified, e.g., increased let-7a and reduced miR-584. Fewer, i.e., 37 AnAc-responsive miRNAs were identified in MDA-MB-231 cells, e.g., decreased miR-23b and increased miR-1257. Only two miRNAs were increased by AnAc in both cell lines: miR-612 and miR-20b; however, opposite miRNA arm preference was noted: miR-20b-3p and miR-20b-5p were upregulated in MCF-7 and MDA-MB-231, respectively. miR-20b-5p target EFNB2 transcript levels were reduced by AnAc in MDA-MB-231 cells. AnAc reduced miR-378g that targets VIM (vimentin) and VIM mRNA transcript expression was increased in AnAc-treated MCF-7 cells, suggesting a reciprocal relationship. The top three enriched GO terms for AnAc-treated MCF-7 cells were B cell receptor signaling pathway and ribosomal large subunit biogenesis and S-adenosylmethionine metabolic process for AnAc-treated MDA-MB-231 cells. The pathways modulated by these AnAc-regulated miRNAs suggest that key nodal molecules, e.g., Cyclin D1, MYC, c-FOS, PPARγ, and SIN3, are targets of AnAc activity

miRNAs downregulated by AnAc in MDA-MB-231 cells.

<p>The genomic location of each miRNA was identified in miRAD <a href="http://bmi.ana.med.uni-muenchen.de/miriad/" target="_blank">http://bmi.ana.med.uni-muenchen.de/miriad/</a> [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184471#pone.0184471.ref034" target="_blank">34</a>]. Verified targets are those experimentally validated targets of the indicated miRNA as demonstrated by 3’-UTR luciferase reporter assay. Since many publications do not include whether the 5p or 3p arm of the miRNA was studied, if the sequence of the miRNA was provided, it was searched in miRBase.org to identify which arm was used in the target gene 3’-UTR luciferase reporter assay.</p

miRNAs upregulated by AnAc in both MCF-7 and MDA-MB-231 cells.

<p>The genomic location of each miRNA was identified in miRAD <a href="http://bmi.ana.med.uni-muenchen.de/miriad/" target="_blank">http://bmi.ana.med.uni-muenchen.de/miriad/</a> [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184471#pone.0184471.ref034" target="_blank">34</a>]. Verified targets are those experimentally validated targets of the indicated miRNA as demonstrated by 3’-UTR luciferase reporter assay. Since many publications do not include whether the 5p or 3p arm of the miRNA was studied, if the sequence of the miRNA was provided, it was searched in miRBase.org to identify which arm was used in the target gene 3’-UTR luciferase reporter assay.</p

Enrichment analysis of miRNA-seq data.

<p>Differentially expressed genes were identified in pairwise comparisons: MCF-7 AnAc vs. MDA-MB-231 AnAc using the tuxedo suite of programs including cufflink-cuffdiff2. The Venn diagrams show the number of common and differentially expressed genes significantly downregulated (A) and upregulated (B). Pathway analysis was performed using GeneGo Pathways Software (MetaCoreTM). The pathways identified for each comparison are listed in the order provided by MetaCoreTM analysis.</p

Heat map of miRNAs significantly altered in AnAc-treated MCF-7 and MDA-MB-231 cells.

<p>miRNAs significantly affected by AnAc were analyzed using Partek Genomic Suite^™ to generate the heat map.</p

Resistance exercise protects mice from protein-induced fat accretion

Low-protein (LP) diets extend the lifespan of diverse species and are associated with improved metabolic health in both rodents and humans. Paradoxically, many athletes and bodybuilders consume high-protein (HP) diets and protein supplements, yet are both fit and metabolically healthy. Here, we examine this paradox using weight pulling, a validated progressive resistance exercise training regimen, in mice fed either an LP diet or an isocaloric HP diet. We find that despite having lower food consumption than the LP group, HP-fed mice gain significantly more fat mass than LP-fed mice when not exercising, while weight pulling protected HP-fed mice from this excess fat accretion. The HP diet augmented exercise-induced hypertrophy of the forearm flexor complex, and weight pulling ability increased more rapidly in the exercised HP-fed mice. Surprisingly, exercise did not protect from HP-induced changes in glycemic control. Our results confirm that HP diets can augment muscle hypertrophy and accelerate strength gain induced by resistance exercise without negative effects on fat mass, and also demonstrate that LP diets may be advantageous in the sedentary. Our results highlight the need to consider both dietary composition and activity, not simply calories, when taking a precision nutrition approach to health

miRNAs upregulated by AnAc in MDA-MB-231 cells.

<p>The genomic location of each miRNA was identified in miRAD <a href="http://bmi.ana.med.uni-muenchen.de/miriad/" target="_blank">http://bmi.ana.med.uni-muenchen.de/miriad/</a> [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184471#pone.0184471.ref034" target="_blank">34</a>]. Verified targets are those experimentally validated targets of the indicated miRNA as demonstrated by 3’-UTR luciferase reporter assay. Since many publications do not include whether the 5p or 3p arm of the miRNA was studied, if the sequence of the miRNA was provided, it was searched in miRBase.org to identify which arm was used in the target gene 3’-UTR luciferase reporter assay.</p

miRNAs upregulated by AnAc MCF-7 cells.

<p>The genomic location of each miRNA was identified in miRAD <a href="http://bmi.ana.med.uni-muenchen.de/miriad/" target="_blank">http://bmi.ana.med.uni-muenchen.de/miriad/</a> [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184471#pone.0184471.ref034" target="_blank">34</a>]. Verified targets are those experimentally validated targets of the indicated miRNA as demonstrated by 3’-UTR luciferase reporter assay in the cited reference. Since many publications do not include whether the 5p or 3p arm of the miRNA was studied, if the sequence of the miRNA was provided, it was searched in miRBase.org to identify which arm was used in the target gene 3’-UTR luciferase reporter assay.</p