Additional file 2: Figure S2a. of Genome-wide expression profiling establishes novel modulatory roles of vitamin C in THP-1 human monocytic cell line

Fold expression values for the housekeeping genes. Heat map was generated using the fold expression values for ten housekeeping genes. Figure S2b. Raw gProcessed signal intensity values for housekeeping genes. The values shown on the Y-axis (log2 scale) are the background subtracted raw intensity values. UT, untreated; AA, ascorbic acid (vit C- treatment). The numbers in sample names refer to biological replicate numbers. (DOCX 262 kb

Additional file 3: Table S1. of Genome-wide expression profiling establishes novel modulatory roles of vitamin C in THP-1 human monocytic cell line

Target gene expression of regulatory genes enriched in class ‘Regulation of gene expression’ at 8 h. (DOCX 95 kb

Multifaceted remodeling by vitamin C boosts sensitivity of Mycobacterium tuberculosis subpopulations to combination treatment by anti-tubercular drugs

Bacterial dormancy is a major impediment to the eradication of tuberculosis (TB), because currently used drugs primarily target actively replicating bacteria. Therefore, decoding of the critical survival pathways in dormant tubercle bacilli is a research priority to formulate new approaches for killing these bacteria. Employing a network-based gene expression analysis approach, we demonstrate that redox active vitamin C (vit C) triggers a multifaceted and robust adaptation response in Mycobacterium tuberculosis (Mtb) involving similar to 67% of the genome. Vit C-adapted bacteria display well-described features of dormancy, including growth stasis and progression to a viable but non-culturable (VBNC) state, loss of acid-fastness and reduction in length, dissipation of reductive stress through triglyceride (TAG) accumulation, protective response to oxidative stress, and tolerance to first line TB drugs. VBNC bacteria are reactivatable upon removal of vit C and they recover drug susceptibility properties. Vit C synergizes with pyrazinamide, a unique TB drug with sterilizing activity, to kill dormant and replicating bacteria, negating any tolerance to rifampicin and isoniazid in combination treatment in both in-vitro and intracellular infection models. Finally, the vit C multi-stress redox models described here also offer a unique opportunity for concurrent screening of compounds/combinations active against heterogeneous subpopulations of Mtb. These findings suggest a novel strategy of vit C adjunctive therapy by modulating bacterial physiology for enhanced efficacy of combination chemotherapy with existing drugs, and also possible synergies to guide new therapeutic combinations towards accelerating TB treatment

Is it true? (When) does it matter? The roles of likelihood and desirability in argument judgments and attitudes

Several theoretical perspectives either directly or indirectly specify roles for likelihood and desirability information in argument judgments and attitude formation. Some perspectives assume that argument judgments and attitudes are a function of the likelihood of the consequences or conclusions, others contend that the desirability of the consequences or conclusions underlie judgments and attitudes, and expectancy-value perspectives, (e.g., Fishbein, 1963) propose that judgments and attitudes should depend on the likelihood × desirability interaction. Construal level theory (CLT; Trope & Liberman, 2003) also suggests that both likelihood and desirability information impact argument judgments and attitudes, but the roles of each are moderated by when the outcomes are to occur. Three studies examined the sometimes-competing predictions regarding the roles of these variables by orthogonally manipulating levels of likelihood and desirability. Although likelihood and desirability both emerged as components of argument strength, and contributed to attitudes, all 3 studies showed that desirability information was more closely associated with argument strength and attitudes than was likelihood information. In Study 1a, argument strength was shown to mediate the desirability-attitude relation. The likelihood × desirability interaction did not predict attitudes in a manner consistent with expectancy-value predictions, though in some instances likelihood and desirability judgments interacted to predict attitudes and attitude change in the predicted expectancy-value pattern. Studies 1b and 2 showed that the desirability-attitude relation was best described as a cubic trend consistent with prospect theory. CLT predictions examined in Study 2 were largely unsupported. Theoretical and methodological implications are discussed.

<i>In vitro</i> binding affinity of Tfab and Tmab.

<p>*IC₅₀ values reflect concentration of Tfab required to compete 50% of saturating Tmab IgG.</p><p>Errors are standard deviations from technical triplicates.</p><p><i>In vitro</i> binding affinity of Tfab and Tmab.</p

TEM imaging of subcellular localization following <i>in vitro</i> binding of IONP-Tfab to HER2+ breast cancer cells.

<p>(<b>A</b>) At 20,000X magnification in SKBR3 cells, 30 nm IONP-Tfab localize primary to intracellular vesicles with a smaller proportion remaining bound to the cell surface (arrows). (<b>B</b>) At 20,000X magnification in BT-474 cells, 30 nm IONP-Tfab exhibit similar localization. (<b>C</b>) At 10,000X magnification in SKBR3 cells, 100 nm IONP-Tfab are mainly found in intracellular vesicles (arrows). (<b>D</b>) At 20,000X magnification in BT-474 cells, 100 nm IONP-Tfab exhibit similar localization. Scale bars are 100 nm (A, B, D) and 500 nm (C).</p

<i>In vivo</i> biodistribution of IONP.

<p>Nanoparticles (80 μg/g body mass) were systemically administered by tail vein injection in NSG mice bearing BT-474 xenograft tumors. Iron content of various tissue compartments was quantified 24 hours post injection by ICP-MS. (<b>A</b>) Tumor, (<b>B</b>) Blood, (<b>C</b>) Heart, (<b>D</b>) Lung, (<b>E</b>) Liver, (<b>F</b>) Spleen, (<b>G</b>) Kidney. Statistical significance (P<0.05) was analyzed by one way ANOVA with a Tukey multiple comparison posttest. Solid brackets with asterisk indicate groups of mice that were not significantly different from each other but were significantly different from other groups outside the bracket. Significant differences between individual groups, including exceptions to the solid brackets, are indicated by solid arrows marked with an asterisk. For the heart, non-significance between individual groups (i.e. exceptions to the solid bracket) is indicated by hatched arrows marked with “ns”. For the heart, the 100 nm maleimide IONP group was not significantly different from any other group in the panel. N = 4 to 7 per group. Statistical analyses were completed using GraphPad Prism 5 (GraphPad Software, Inc., San Diego, CA).</p

<i>In vitro</i> binding studies of IONP.

<p>(<b>A</b>) Dose response rHER2 binding curves for 30 nm IONP-Tfab (closed circles) and 30 nm IONP-Mal (open squares). (<b>B</b>) Dose response rHER2 binding curves for 100 nm IONP-Tfab (closed circles) and 100 nm IONP-Mal (open squares). (<b>C</b>) Binding of HER2+ breast cancer cells for 30 nm IONP-Tfab and 30 nm IONP-Mal, both dosed at 100 μg/ml. (<b>D</b>) Binding of HER2+ breast cancer cells for 100 nm IONP-Tfab and 100 nm IONP-Mal, both dosed at70 μg/ml. Error bars represent standard deviation.</p