Synthesis,structure, antioxidant activity,and water solubility of trolox ion conjugates

The interaction of trolox with ammonia, alkylamines of different classes, and amino derivatives of heterocyclic compounds, including nitroxyl radicals and alkaloids, led to the production of ammonium salts called ion conjugates (ICs). Five ICs were characterised by X-ray diffraction. This is the first time a wide range of ICs were made from trolox with amines, and ESI-MS data demonstrated they have the potential to generate pseudomolecular [(A^?B⁺)?+?H]⁺ ions. For all obtained trolox ICs, a significant increase (1–3 orders of magnitude) in water solubility was achieved while retaining high antioxidant activity. ICs synthesised from two biologically active fragments may be used to create polyfunctional agents with varying solubility and bioavailability.     

Categorical and anti-categorical approaches to US racial/ethnic groupings: revisiting the National 2009 H1N1 Flu Survey (NHFS)

Intersectionality theory calls for the understanding of race/ethnicity, sex/gender and class as interlinked. Intersectional analysis can contribute to public health both through furthering understanding of power dynamics causing health disparities, and by pointing to heterogeneities within, and overlap between, social groups. The latter places the usefulness of social categories in public health under scrutiny. Drawing on McCall we relate the first approach to categorical and the second to anti-categorical intersectionality. Here, we juxtapose the categorical approach with traditional between-group risk calculations (e.g. odds ratios) and the anti-categorical approach with the statistical concept of discriminatory accuracy (DA), which is routinely used to evaluate disease markers in epidemiology. To demonstrate the salience of this distinction, we use the example of racial/ethnic identification and its value for predicting influenza vaccine uptake compared to other conceivable ways of organizing attention to social differentiation. We analyzed data on 56,434 adults who responded to the NHFS. We performed logistic regressions to estimate odds ratios and computed the area under the receiver operating characteristic curve (AU-ROC) to measure DA. Above age, the most informative variables were education and household poverty status, with race/ethnicity providing minor additional information. Our results show that the practical value of standard racial/ethnic categories for making inferences about vaccination status is questionable, because of the high degree of outcome variability within, and overlap between, categories. We argue that, reminiscent of potential tension between categorical and anti-categorical perspectives, between-group risk should be placed and understood in relationship to measures of DA, to avoid the lure of misguided individual-level interventions.     

Protein corona and phospholipase activity drive selective accumulation of nanomicelles in atherosclerotic plaques

ApoB-100 and Phosphatidylcholine-specific phospholipase C (PC-PLC) are important contributors to atherosclerosis development. ApoB-100 is the main structural protein of LDL, being directly associated with atherosclerosis plaque generation. PC-PLC is highly expressed in atherosclerosis lesions and contributes to their progression. We show how phosphatidylcholine-coated nanomicelles can be used for specific characterisation of atherosclerosis plaque. Results show that ApoB-100 in the protein corona of the nanomicelle targets the particles to atherosclerotic areas in apolipoprotein E^?/? mice. Furthermore, PC-PLC selectively removes the polar heads from the phospholipid coating of the nanomicelles leading to their accumulation. To fully characterise the behaviour of the nanomicelles, we developed multimodal probes using a nanoemulsion step. Hybrid imaging revealed plaque accumulation of the nanomicelles and colocalisation with PC-PLC expression and ApoB-100 in the plaque. This study shows how protein corona composition and enzyme-driven nanomaterial accumulation can be used for detection of atherosclerosis.     

Switching cell penetrating and CXCR4-binding activities of nanoscale-organized arginine-rich peptides

Arginine-rich protein motifs have been described as potent cell-penetrating peptides (CPPs) but also as rather specific ligands of the cell surface chemokine receptor CXCR4, involved in the infection by the human immunodeficiency virus (HIV). Polyarginines are commonly used to functionalize nanoscale vehicles for gene therapy and drug delivery, aimed to enhance cell penetrability of the therapeutic cargo. However, under which conditions these peptides do act as either unspecific or specific ligands is unknown. We have here explored the cell penetrability of differently charged polyarginines in two alternative presentations, namely as unassembled fusion proteins or assembled in multimeric protein nanoparticles. By this, we have observed that arginine-rich peptides switch between receptor-mediated and receptor-independent mechanisms of cell penetration. The relative weight of these activities is determined by the electrostatic charge of the construct and the oligomerization status of the nanoscale material, both regulatable by conventional protein engineering approaches.