MRP8/14 does not contribute to dissemination or inflammation in a murine model of Lyme borreliosis

Myeloid-related protein (MRP)8 and MRP14 form a complex (MRP8/14) that is released by activated neutrophils and monocytes during infection. MRP8/14 has been shown to have bacteriostatic activity in vitro against Borrelia burgdorferi, the spirochete that causes Lyme borreliosis. Furthermore, levels of MRP8/14 have been shown to be elevated in the joints of patients with Lyme arthritis. We hypothesized that MRP8/14 has a protective effect during B. burgdorferi infection. To determine the role of MRP8/14 in the immune response to B. burgdorferi, we studied the course of B. burgdorferi infection in wildtype (wt) and mrp14^?/? mice. In addition, we studied the response of leukocytes from mice lacking MRP8/14 to B. burgdorferi ex vivo. We demonstrated similar levels of B. burgdorferi dissemination, cytokine and immunoglobulin production in infected wt and mrp14^?/? mice after 21 days. Neutrophils and monocytes lacking MRP8/14 were undiminished in their ability to become activated or phagocytose B. burgdorferi. In conclusion, we did not find a central role of MRP8/14 in the immune response against B. burgdorferi. As the levels of MRP8/14 in the serum of infected mice were low, we speculate that MRP8/14 is not released in levels great enough to influence the course of B. burgdorferi infection.     

Characterizing the functional consequences of haploinsufficiency of NELF-A (WHSC2) and SLBP identifies novel cellular phenotypes in Wolf-Hirschhorn syndrome

Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion disorder associated with the distal part of the short arm of chromosome 4 (4p16.3). Employing a unique panel of patient-derived cell lines with differing-sized 4p deletions, we provide evidence that haploinsufficiency of SLBP and/or WHSC2 (NELF-A) contributes to several novel cellular phenotypes of WHS, including delayed progression from S-phase into M-phase, reduced DNA replication in asynchronous culture and altered higher order chromatin assembly. The latter is evidenced by reduced histone-chromatin association, elevated levels of soluble chaperone-bound histone H3 and increased sensitivity to micrococcal nuclease digestion in WHS patient-derived cells. We also observed increased camptothecin-induced inhibition of DNA replication and hypersensitivity to killing. Our work provides a novel pathogenomic insight into the aetiology of WHS by describing it, for the first time, as a disorder of impaired chromatin reorganization. Delayed cell-cycle progression and impaired DNA replication likely underlie or contribute to microcephaly, pre- and postnatal growth retardation, which constitute the core clinical features of WHS.     

Differences in the Temporal Typology of Alcohol Hangover

Background

At a group level, hangover severity during the day has been described to follow an inverted U‐shaped curve, with gradually increasing severity scores that, after reaching a peak, gradually decrease toward zero. The aim of this study was to examine if and how individual drinkers' hangover severity scores vary during the day.

Methods

Data from a survey (Penning et al., 2012 ) in which 727 drinkers reported on their latest alcohol hangover were reanalyzed. The temporal pattern of each individual's hangover was first categorized as belonging to 1 of 6 types based on predefined temporal characteristics.

Results

Three dominant hangover patterns emerged as comprising more than 95% of the sample: (i) a continuous decline hangover (Severity Type 1 hangover, 54.5%), (ii) a steady state hangover (Severity Type 2 hangover, 19.1%), and (iii) an inverted U‐shaped curve hangover (Severity Type 3 hangover, 21.8%). Of these 3 patterns, Severity Type 2 hangovers are associated with significantly less alcohol consumption and with having the lowest severity scores of individual hangover symptoms. Severity Type 1 hangovers are associated with having the highest severity of individual hangover symptoms. In line with significantly lower levels of alcohol consumption, Severity Type 2 hangovers were significantly more often observed in women when compared to men. Severity Type 1 hangovers were significantly more common in men than in women. Severity Type 3 hangovers, characterized by the increased presence of gastrointestinal complaints, were equally commonly experienced in men and women.

Conclusions

This study revealed that the temporal pattern of hangover severity can follow marked interindividual variability. Three common temporal patterns were identified, which are uniquely related to the amount of alcohol consumed and the presence and severity of different individual hangover symptoms. Better understanding of individual differences in hangover typology may help to delineate mechanisms underlying alcohol hangover.     

Beetroot juice improves in overweight and slightly obese men postprandial endothelial function after consumption of a mixed meal

Background

Through effects on nitric oxide (NO) bioavailability, endothelial function is improved after the intake of beetroot juice–which is rich in inorganic nitrate-, but decreased after the intake of a meal.

Objective

The objective of this study was to examine if beetroot juice could counteract the impairment of endothelial function associated with the ingestion of a mixed meal.

Methods

Twenty healthy overweight and slightly obese men with a BMI between 28 and 35 kg/m² received in random order a mixed meal providing 56.6 g of fat with beetroot juice or a control drink. The beetroot juice (140 mL) provided approximately 500 mg dietary nitrate. Flow-mediated dilation (FMD) of the brachial artery was measured before and 2 h after meal consumption. Blood was sampled at regular intervals.

Results

Postprandial changes in serum triacylglycerol (TAG) (P = 0.69), plasma glucose (P = 0.84) and insulin (P = 0.67) concentrations were comparable between the meals. After consumption of beetroot juice, the postprandial impairment in FMD following a standardized mixed meal was improved (P = 0.030) compared with the control drink (−0.37 ± 2.92% versus −1.56 ± 2.90%). Following beetroot juice consumption, plasma concentrations of the circulating NO pool were higher at T60, T120, and T240 (P < 0.001 at all time points).

Conclusion

In healthy overweight and slightly obese men a single dose of beetroot juice attenuates the postprandial impairment of FMD following a mixed meal, possibly through increases in plasma NO concentrations.