The secondary structure of apolipoprotein A-I on 9.6-nm reconstituted high-density lipoprotein determined by EPR spectroscopy.

Apolipoprotein A-I (ApoA-I) is the major protein component of high-density lipoprotein (HDL), and is critical for maintenance of cholesterol homeostasis. During reverse cholesterol transport, HDL transitions between an array of subclasses, differing in size and composition. This process requires ApoA-I to adapt to changes in the shape of the HDL particle, transiting from an apolipoprotein to a myriad of HDL subclass-specific conformations. Changes in ApoA-I structure cause alterations in HDL-specific enzyme and receptor-binding properties, and thereby direct the HDL particle through the reverse cholesterol transport pathway. In this study, we used site-directed spin label spectroscopy to examine the conformational details of the ApoA-I central domain on HDL. The motional dynamics and accessibility to hydrophobic/hydrophilic relaxation agents of ApoA-I residues 99-163 on 9.6-nm reconstituted HDL was analyzed by EPR. In previous analyses, we examined residues 6-98 and 164-238 (of ApoA-I's 243 residues), and combining these findings with the current results, we have generated a full-length map of the backbone structure of reconstituted HDL-associated ApoA-I. Remarkably, given that the majority of ApoA-I's length is composed of amphipathic helices, we have identified nonhelical residues, specifically the presence of a β-strand (residues 149-157). The significance of these nonhelical residues is discussed, along with the other features, in the context of ApoA-I function in contrast to recent models derived by other methods

Consumption of garlic affects hedonic perception of axillary body odour

Beneficial health properties of garlic, as well as its most common adverse effect – distinctive breath odour – are well-known. In contrast, analogous research on the effect of garlic on axillary odour is currently missing. Here, in three studies varying in the amount and nature of garlic provided (raw garlic in study 1 and 2, garlic capsules in study 3), we tested the effect of garlic consumption on the quality of axillary odour. A balanced within-subject experimental design was used. In total, 42 male odour donors were allocated to either a “garlic” or “non-garlic” condition, after which they wore axillary pads for 12h to collect body odour. One week later, the conditions were reversed. Odour samples were then judged for their pleasantness, attractiveness, masculinity and intensity by 82 women. We foundnosignificant differences in ratings of any characteristics in study 1. However, the odour of donors after an increased garlic dosage was assessed as significantly more pleasant, attractive and less intense (study 2), and more attractive and less intense in study 3. Our results indicate that garlic consumption may have positive effects on perceived body odour hedonicity, perhaps due to its health effects (e.g.,antioxidantproperties,antimicrobialactivity)

Effect of biological relatedness on perfume selection for others: Preliminary evidence

People tend to choose perfumes to complement their body odour. As kin share some body odour qualities, their ability to select complementary perfumes for relatives might be higher compared to selection for non-relatives. We tested this in two studies, comparing selection of a perfume for a target man by himself and by either a familiar but unrelated individual (girlfriend; Study 1) or a relative (sister; Study 2). Target men applied the two perfumes (own/other’s choice) to their axillae and then wore cotton pads for 12h. Collected perfume-body odour blends and perfumes alone were assessed by rater panels. In Study 1, the blends were rated as nominally more pleasant when body odours were mixed with the perfumes selected by girlfriends compared to those selected by target men themselves. In Study 2, body odours mixed with perfumes selected by sisters were rated significantly more attractive than those mixed with perfumes selected by target men. No significant differences were found for attractiveness and pleasantness ratings when perfumes were rated alone, suggesting that it was the resulting blends that were uniquely different. Our results indicate that sisters might be particularly tuned to select suitable perfumes for their siblings

Human Body Odour Composites Are Not Perceived More Positively than the Individual Samples

It is well established that composite facial images are perceived as more attractive compared with individual images, suggesting a preference for heterozygosity. Similarly, there is evidence that preferences for body odours might be linked to heterozygosity. Here, we tested whether blending individual body odours into composites would follow a similar pattern as observed in the perception of faces. We collected axillary odour samples from 38 individuals, which were subsequently assessed individually and as composites of two (N=19) or four (N=9) body odours regarding their pleasantness, attractiveness and intensity. We found no significant differences between mean ratings of individual odour samples or composites of two or four odour samples. Our results indicate that, in contrast to faces, composite body odours are not rated as more attractive. Composite body odours retain similar hedonic perceptual qualities as individual odours, thus highlighting differences in visual and chemosensory perceptual mechanisms

Postprandial apoE isoform and conformational changes associated with VLDL lipolysis products modulate monocyte inflammation.

ObjectivePostprandial hyperlipemia, characterized by increased circulating very low-density lipoproteins (VLDL) and circulating lipopolysaccharide (LPS), has been proposed as a mechanism of vascular injury. Our goal was to examine the interactions between postprandial lipoproteins, LPS, and apoE3 and apoE4 on monocyte activation.Methods and resultsWe showed that apoE3 complexed to phospholipid vesicles attenuates LPS-induced THP-1 monocyte cytokine expression, while apoE4 increases expression. ELISA revealed that apoE3 binds to LPS with higher affinity than apoE4. Electron paramagnetic resonance (EPR) spectroscopy of site-directed spin labels placed on specific amino acids of apoE3 showed that LPS interferes with conformational changes normally associated with lipid binding. Specifically, compared to apoE4, apoE bearing the E3-like R112→Ser mutation displays increased self association when exposed to LPS, consistent with a stronger apoE3-LPS interaction. Additionally, lipolysis of fasting VLDL from normal human donors attenuated LPS-induced TNFα secretion from monocytes to a greater extent than postprandial VLDL, an effect partially reversed by blocking apoE. This effect was reproduced using fasting VLDL lipolysis products from e3/e3 donors, but not from e4/e4 subjects, suggesting that apoE3 on fasting VLDL prevents LPS-induced inflammation more readily than apoE4.ConclusionPostprandial apoE isoform and conformational changes associated with VLDL dramatically modulate vascular inflammation

Airway exposure to multi-walled carbon nanotubes disrupts the female reproductive cycle without affecting pregnancy outcomes in mice

Abstract Background The use of multiwalled carbon nanotubes (MWCNT) is increasing due to a growing use in a variety of products across several industries. Thus, occupational exposure is also of increasing concern, particularly since airway exposure to MWCNTs can induce sustained pulmonary acute phase response and inflammation in experimental animals, which may affect female reproduction. This proof-of-principle study therefore aimed to investigate if lung exposure by intratracheal instillation of the MWCNT NM-400 would affect the estrous cycle and reproductive function in female mice. Results Estrous cycle regularity was investigated by comparing vaginal smears before and after exposure to 67 μg of NM-400, whereas reproductive function was analyzed by measuring time to delivery of litters after instillation of 2, 18 or 67 μg of NM-400. Compared to normal estrous cycling determined prior to exposure, exposure to MWCNT significantly prolonged the estrous cycle during which exposure took place, but significantly shortened the estrous cycle immediately after the exposed cycle. No consistent effects were seen on time to delivery of litter or other gestational or litter parameters, such as litter size, sex ratio, implantations and implantation loss. Conclusion Lung exposure to MWCNT interfered with estrous cycling. Effects caused by MWCNTs depended on the time of exposure: the estrous stage was particularly sensitive to exposure, as animals exposed during this stage showed a higher incidence of irregular cycling after exposure. Our data indicates that MWCNT exposure may interfere with events leading to ovulation

Autologous, lentivirus-modified, T-rapa cell “micropharmacies” for lysosomal storage disorders

T cells are the current choice for many cell therapy applications. They are relatively easy to access, expand in culture, and genetically modify. Rapamycin-conditioning ex vivo reprograms T cells, increasing their memory properties and capacity for survival, while reducing inflammatory potential and the amount of preparative conditioning required for engraftment. Rapamycin-conditioned T cells have been tested in patients and deemed to be safe to administer in numerous settings, with reduced occurrence of infusion-related adverse events. We demonstrate that ex vivo lentivirus-modified, rapamycin-conditioned CD4+ T cells can also act as next-generation cellular delivery vehicles—that is, “micropharmacies”—to disseminate corrective enzymes for multiple lysosomal storage disorders. We evaluated the therapeutic potential of this treatment platform for Fabry, Gaucher, Farber, and Pompe diseases in vitro and in vivo. For example, such micropharmacies expressing α-galactosidase A for treatment of Fabry disease were transplanted in mice where they provided functional enzyme in key affected tissues such as kidney and heart, facilitating clearance of pathogenic substrate after a single administration

The effect of complete caloric intake restriction on human body odour quality

Previous studies on various vertebrates have shown that quantity and quality of food intake affect odour attractiveness as perceived by potential mates. In humans, the quality of body odour is similarly affected by ingested foods, such as by variation in meat and garlic intake. Nevertheless, it is not known whether quantity of food has an impact on human body odour attractiveness. Thus, here we tested how 48 h of complete caloric intake restriction affects the hedonic quality of human axillary odour. Odour samples (cotton pads fixed in both armpits and worn for 12 h) were obtained from healthy female donors across three conditions: i) during their habitual food regime; ii) after 48 h of complete caloric intake restriction (drinking water was provided), and iii) 72 h after restoration of caloric intake. Axillary samples were assessed by male raters regarding their pleasantness, attractiveness, femininity, and intensity. We also collected blood samples to assess physiological changes due to dietary restriction (e.g., glucose, sodium, albumin, and triacylglyceride assays) and anthropometric measurements at the same intervals as body odour samples. We found no differences in pleasantness, attractiveness and intensity between the odour samples collected at baseline and during complete caloric intake restriction. Interestingly, we found that body odours were rated more pleasant, more attractive and less intense after restoration of food intake as compared to the baseline and during caloric restriction. Our results suggest that restoration of food intake positively influences hedonic quality of human body odour which might thus provide cues to current fitness status and metabolic efficiency