Investigation of Hypersonic Nozzle Flow Uniformity Using NO Fluorescence

Planar laser-induced fluorescence visualisation is used to investigate nonuniformities in the flow of a hypersonic conical nozzle. Possible causes for the nonuniformity are outlined and investigated, and the problem is shown to be due to a small step at the nozzle throat. Entrainment of cold boundary layer gas is postulated as the cause of the signal nonuniformity

Perinatal fluoxetine exposure disrupts the circadian response to a phase-shifting challenge in female rats

Funding Information: This research was funded by the Dobberke foundation, grant number UPS/BP/4151 2016-27.Peer reviewedPublisher PD

High-Resolution Hydrogen-Deuterium Protection Factors from Sparse Mass Spectrometry Data Validated by Nuclear Magnetic Resonance Measurements

Experimental measurement of time-dependent spontaneous exchange of amide protons with deuterium of the solvent provides information on the structure and dynamical structural variation in proteins. Two experimental techniques are used to probe the exchange: NMR, which relies on different magnetic properties of hydrogen and deuterium, and MS, which exploits the change in mass due to deuteration. NMR provides residue-specific information, that is, the rate of exchange or, analogously, the protection factor (i.e., the unitless ratio between the rate of exchange for a completely unstructured state and the observed rate). MS provides information that is specific to peptides obtained by proteolytic digestion. The spatial resolution of HDX-MS measurements depends on the proteolytic pattern of the protein, the fragmentation method used, and the overlap between peptides. Different computational approaches have been proposed to extract residue-specific information from peptide-level HDX-MS measurements. Here, we demonstrate the advantages of a method recently proposed that exploits self-consistency and classifies the possible sets of protection factors into a finite number of alternative solutions compatible with experimental data. The degeneracy of the solutions can be reduced (or completely removed) by exploiting the additional information encoded in the shape of the isotopic envelopes. We show how sparse and noisy MS data can provide high-resolution protection factors that correlate with NMR measurements probing the same protein under the same conditions

Perinatal fluoxetine treatment and dams’ early life stress history have opposite effects on aggressive behavior while having little impact on sexual behavior of male rat offspring

Funding Information: This work was supported by the NARSAD young investigator grant from the Brain and Behavior Research Foundation (Grant No. 25206) and by the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie (Grant Agreement No. 660152).Peer reviewedPublisher PD

The Effect of Gut Microbiome Composition on Human Immune Responses: An Exploration of Interference by Helminth Infections

Background: Soil-transmitted helminths have been shown to have the immune regulatory capacity, which they use to enhance their long term survival within their host. As these parasites reside in the gastrointestinal tract, they might modulate the immune system through altering the gut bacterial composition. Although the relationships between helminth infections or the microbiome with the immune system have been studied separately, their combined interactions are largely unknown. In this study we aim to analyze the relationship between bacterial communities with cytokine response in the presence or absence of helminth infections. Results: For 66 subjects from a randomized placebo-controlled trial, stool and blood samples were available at both baseline and 21 months after starting three-monthly albendazole treatment. The stool samples were used to identify the helminth infection status and fecal microbiota composition, while whole blood samples were cultured to obtain cytokine responses to innate and adaptive stimuli. When subjects were free of helminth infection (helminth-negative), increasing proportions of Bacteroidetes was associated with lower levels of IL-10 response to LPS {estimate [95% confidence interval (CI)] −1.96 (−3.05, −0.87)}. This association was significantly diminished when subjects were helminth-infected (helminth positive) (p-value for the difference between helminth-negative versus helminth-positive was 0.002). Higher diversity was associated with greater IFN-γ responses to PHA in helminth-negative (0.95 (0.15, 1.75); versus helminth-positive [−0.07 (−0.88, 0.73), p-value = 0.056] subjects. Albendazole treatment showed no direct effect in the association between bacterial proportion and cytokine responses, although the Bacteroidetes’ effect on IL-10 responses to LPS tended downward in the albendazole-treated group [−1.74 (−4.08, 0.59)] versus placebo [−0.11 (−0.84, 0.62); p-value = 0.193]. Conclusion: We observed differences in the relationship between gut microbiome composition and immune responses, when comparing individuals infected or uninfected with geohelminths. Although these findings are part of a preliminary exploration, the data support the hypothesis that intestinal helminths may modulate immune responses, in unison with the gut microbiota. Trial Registration: ISRCTN, ISRCTN83830814. Registered 27 February 2008 — Retrospectively registered, http://www.isrctn.com/ISRCTN83830814

A mixture model with random-effects components for classifying sibling pairs

In healthy aging research, typically multiple health outcomes are measured, representing health status. The aim of this paper was to develop a model-based clustering approach to identify homogeneous sibling pairs according to their health status. Model-based clustering approaches will be considered on the basis of linear mixed effect model for the mixture components. Class memberships of siblings within pairs are allowed to be correlated, and within a class the correlation between siblings is modeled using random sibling pair effects. We propose an expectation-maximization algorithm for maximum likelihood estimation. Model performance is evaluated via simulations in terms of estimating the correct parameters, degree of agreement, and the ability to detect the correct number of clusters. The performance of our model is compared with the performance of standard modelbased clustering approaches. The methods are used to classify sibling pairs from the Leiden Longevity Study according to their health status. Our results suggest that homogeneous healthy sibling pairs are associated with a longer life span. Software is available for fitting the new models

The serotonin transporter and early life stress:Translational perspectives

The interaction between the serotonin transporter (SERT) linked polymorphic region (5-HTTLPR) and adverse early life stressing (ELS) events is associated with enhanced stress susceptibility and risk to develop mental disorders like major depression, anxiety, and aggressiveness. In particular, human short allele carriers are at increased risk. This 5-HTTLPR polymorphism is absent in the rodent SERT gene, but heterozygous SERT knockout rodents (SERT+/−) show several similarities to the human S-allele carrier, therefore creating an animal model of the human situation. Many rodent studies investigated ELS interactions in SERT knockout rodents combined with ELS. However, underlying neuromolecular mechanisms of the (mal)adaptive responses to adversity displayed by SERT rodents remain to be elucidated. Here, we provide a comprehensive review including studies describing mechanisms underlying SERT variation × ELS interactions in rodents. Alterations at the level of translation and transcription but also epigenetic alterations considerably contribute to underlying mechanisms of SERT variation × ELS interactions. In particular, SERT+/− rodents exposed to adverse early rearing environment may be of high translational and predictive value to the more stress sensitive human short-allele carrier, considering the similarity in neurochemical alterations. Therefore, SERT+/− rodents are highly relevant in research that aims to unravel the complex psychopathology of mental disorders. So far, most studies fail to show solid evidence for increased vulnerability to develop affective-like behavior after ELS in SERT+/− rodents. Several reasons may underlie these failures, e.g., (1) stressors used might not be optimal or severe enough to induce maladaptations, (2) effects in females are not sufficiently studied, and (3) few studies include both behavioral manifestations and molecular correlates of ELS-induced effects in SERT+/− rodents. Of course, one should not exclude the (although unlikely) possibility of SERT+/− rodents not being sensitive to ELS. In conclusion, future studies addressing ELS-induced effects in the SERT+/− rodents should extensively study both long-term behavioral and (epi)genetic aspects in both sexes. Finally, further research is warranted using more severe stressors in animal models. From there on, we should be able to draw solid conclusions whether the SERT+/− exposed to ELS is a suitable translational animal model for studying 5-HTTLPR polymorphism and stress interactions