The NAD(P)H oxidase homolog Nox4 modulates insulin-stimulated generation of H\u3csub\u3e2\u3c/sub\u3e0\u3csub\u3e2\u3c/sub\u3e and plays an integral role in insulin signal transduction

Insulin stimulation of target cells elicits a burst of H2O2 that enhances tyrosine phosphorylation of the insulin receptor and its cellular substrate proteins as well as distal signaling events in the insulin action cascade. The molecular mechanism coupling the insulin receptor with the cellular oxidant-generating apparatus has not been elucidated. Using reverse transcription-PCR and Northern blot analyses, we found that Nox4, a homolog of gp91phox, the phagocytic NAD(P)H oxidase catalytic subunit, is prominently expressed in insulin-sensitive adipose cells. Adenovirus-mediated expression of Nox4 deletion constructs lacking NAD(P)H or FAD/NAD(P)H cofactor binding domains acted in a dominant-negative fashion in differentiated 3T3-L1 adipocytes and attenuated insulin-stimulated H2O2 generation, insulin receptor (IR) and IRS-1 tyrosine phosphorylation, activation of downstream serine kinases, and glucose uptake. Transfection of specific small interfering RNA oligonucleotides reduced Nox4 protein abundance and also inhibited the insulin signaling cascade. Overexpression of Nox4 also significantly reversed the inhibition of insulin-stimulated IR tyrosine phosphorylation induced by coexpression of PTP1B by inhibiting PTP1B catalytic activity. These data suggest that Nox4 provides a novel link between the IR and the generation of cellular reactive oxygen species that enhance insulin signal transduction, at least in part via the oxidative inhibition of cellular protein-tyrosine phosphatases (PTPases), including PTP1B, a PTPase that has been previously implicated in the regulation of insulin action

Enhanced anticancer activity of a combination of docetaxel and Aneustat (OMN54) in a patient-derived, advanced prostate cancer tissue xenograft model.

The current first-line treatment for advanced metastatic prostate cancer, i.e. docetaxel-based therapy, is only marginally effective. The aim of the present study was to determine whether such therapy can be improved by combining docetaxel with Aneustat (OMN54), a multivalent botanical drug candidate shown to have anti-prostate cancer activity in preliminary in vitro experiments, which is currently undergoing a Phase-I Clinical Trial. Human metastatic, androgen-independent C4-2 prostate cancer cells and NOD-SCID mice bearing PTEN-deficient, metastatic and PSA-secreting, patient-derived subrenal capsule LTL-313H prostate cancer tissue xenografts were treated with docetaxel and Aneustat, alone and in combination. In vitro, Aneustat markedly inhibited C4-2 cell replication in a dose-dependent manner. When Aneustat was combined with docetaxel, the growth inhibitions of the drugs were essentially additive. In vivo, however, the combination of docetaxel and Aneustat enhanced anti-tumor activity synergistically and very markedly, without inducing major host toxicity. Complete growth inhibition and shrinkage of the xenografts could be obtained with the combined drugs as distinct from the drugs on their own. Analysis of the gene expression of the xenografts using microarray indicated that docetaxel + Aneustat led to expanded anticancer activity, in particular to targeting of cancer hallmarks that were not affected by the single drugs. Our findings, obtained with a highly clinically relevant prostate cancer model, suggest, for the first time, that docetaxel-based therapy of advanced human prostate cancer may be improved by combining docetaxel with Aneustat

Factors Associated with Immunization Opinion Leadership among Men Who Have Sex with Men in Los Angeles, California

We sought to identify the characteristics of men who have sex with men (MSM) who are opinion leaders on immunization issues and to identify potential opportunities to leverage their influence for vaccine promotion within MSM communities. Using venue-based sampling, we recruited and enrolled MSM living in Los Angeles (N = 520) from December 2016 to February 2017 and evaluated characteristic differences in sociodemographic characteristics, health behaviors, and technology use among those classified as opinion leaders versus those who were not. We also asked respondents about their past receipt of meningococcal serogroups A, C, W, and Y (MenACWY) and meningococcal B (MenB) vaccines, as well as their opinions on the importance of 13 additional vaccines. Multivariable results revealed that non-Hispanic black (aOR = 2.64; 95% CI: 1.17–5.95) and other race/ethnicity (aOR = 2.98; 95% CI: 1.41–6.29) respondents, as well as those with a history of an STI other than HIV (aOR = 1.95; 95% CI: 1.10–3.48), were more likely to be opinion leaders. MenACWY (aOR = 1.92; 95% CI: 1.13–3.25) and MenB (aOR = 3.09; 95% CI: 1.77–5.41) vaccine uptake, and perceived importance for these and seven additional vaccines, were also associated with being an opinion leader. The results suggest that the co-promotion of vaccination and other health promotion initiatives via opinion leaders could be a useful strategy for increasing vaccination among MSM

Goals as Reference Points in Marathon Running: A Novel Test of Reference Dependence

In a large-scale field study of marathon runners, we test whether goals act as reference points in shaping the valuation of outcomes. Theories of reference-dependent preferences, such as Prospect Theory, imply that outcomes that are just below or just above a reference point are evaluated differently. Consistent with the Prospect Theory value function, we find that satisfaction as a function of relative performance (the difference between a runner’s finishing time goal and her actual finishing time) exhibits loss aversion and diminishing sensitivity in both predictions of and actual experienced satisfaction. However, in contrast to Prospect Theory, we observe that loss aversion is partially driven by a discontinuity or jump at the reference point. In addition, we find that a runner’s time goal as well as their previous marathon times simultaneously impact runner satisfaction, providing support for the impact of multiple reference points on satisfaction

RESPONSE OF SOYBEAN YIELD AND YIELD COMPONENTS TO PHOSPHORUS FERTILIZATION IN SOUTH DAKOTA

Increased demand for soybean [Glycine max (L.) Merrill] production for industrial, human, and animal consumption has provided many incentives for farmers and producers to increase their production. In many soils used for soybean production, phosphorus (P) becomes a major limiting factor to soybean growth and grain production. A field experiment was conducted in five locations across Eastern South Dakota in 2013 to study the response of soybean yield and yield components to phosphorus fertilizer applications. The experiment was laid out in a randomized complete block (RCB) design with four replications. The treatments consisted of five P levels 0, 20, 40, 60, and 80lb/ac of triple superphosphate. Data for yield and yield components were collect and analyzed with several statistical methods including linear mixed model approaches and Additive Model and Multiplicative Interaction effect (AMMI) methods. There was no evidence showing that P had significant impacts on grain yield and yield components. P by environment (PE) interactions were not significant for all traits except whole pod weight. Large variation in yield and yield components were attributed to environmental conditions. Plant height, 100-pod weight, and seed weight of 100- pod had positive and significant correlations with yield in three locations; Geddes, Mitchell, and Bancroft

Symbiont Consciousness: Sociocultural Embodied Augmentation of Humanity

The psychology of consciousness as explained by Vygotsky is the ability of one to focus on the inner state of being. Vygotsky’s proposition of external tools redistributing mental and external processes into internalized acts lacks the concept of embodied mediational tools existing in the current world as computational artifacts extending or augmenting human capabilities. This paper proposes sociocultural embodied augmentation theory (SEAT) as a means to explain the impact of augmenting technologies on Vygotsky’s original notion of “psychological tool,” therefore initiating an inevitable transformation of the sociocultural mind. Hence, a new social mind is posited as an evolving symbiosis between human life and artificial life that extends consciousness: a symbiont consciousness