Maternal stress, child behavior and the promotive role of older siblings

Abstract Background: In the first years of their lives, children develop the cognitive, social and emotional skills that will provide the foundations for their lifelong health and achievements. To increase their life prospects and reduce the long-term effects of early aversive conditions, it is therefore crucial to understand the risk factors that negatively affect child development and the factors that are instead beneficial. In this study, we tested (i) the effects of different social and environmental stressors on maternal stress levels, (ii) the dynamic relationship between maternal stress and child behavior problems during development, and (iii) the potential promotive (i.e. main) or protective (i.e. buffering) effect of siblings on child behavior problems during development.Methods: We used longitudinal data from 373 mother–child pairs (188 daughters, 185 sons) from pregnancy until 10 years of age. We assessed maternal stress and child behavior problems (internalizing and externalizing) with vali-dated questionnaires, and then used linear mixed models, generalized linear mixed models and longitudinal cross-lagged models to analyze the data.Results: Our results showed that higher maternal stress levels were predicted by socio-environmental stressors (i.e. the lack of sufficient social areas in the neighborhood). Moreover, prenatal maternal stress reliably predicted the occurrence of behavior problems during childhood. Finally, the presence of older siblings had a promotive function, by reducing the likelihood that children developed externalizing problems.Conclusions: Overall, our results confirm the negative effects that maternal stress during pregnancy may have on the offspring, and suggest an important main effect of older siblings in promoting a positive child development

Identifying atypical travel patterns for improved medium-term mobility prediction

This is the author accepted manuscript. The final version is available from IEEE via the DOI in this recordDuring the last decades, concepts of Intelligent Transportation Systems (ITS) were continuously adapted and improved based on new insights into human travel behavior. Drivers for improvements are the quantity and quality of available mobility data, which increased significantly in recent years. Based on travel behavior, literature proposes a large number of different solutions for next step or future location prediction. However a holistic spatio-temporal prediction, which could further improve the quality of ITS, creates a more complex task. The prediction of medium-term mobility for one to seven days is challenging in particular for atypical travel behavior, since the weekdays’ order delivers no reliable indication for the next day’s travel behavior. With our contribution, we explore the benefits of various prediction approaches for medium-term mobility prediction and combine them dynamically to predict individual mobility behavior for a period of one week. The derived framework utilizes an exhaustive search approach to benefit from a machine learning based clustering method on location data. In conjunction with an Artificial Neural Network, the prediction framework is robust against prediction errors created by atypical behavior. With two data sets consisting of smartphone and vehicle data, we demonstrate the framework’s real-world applicability. We show that clustering an individual’s historical movement data can improve the prediction accuracy of different prediction methods that will be explained in detail and illustrate the interrelation of entropy and prediction accuracy.University of Exete

Disruption of the plant-specific CFS1 gene impairs autophagosome turnover and triggers EDS1-dependent cell death

Cell death, autophagy and endosomal sorting contribute to many physiological, developmental and immunological processes in plants. They are mechanistically interconnected and interdependent, but the molecular basis of their mutual regulation has only begun to emerge in plants. Here, we describe the identification and molecular characterization of CELL DEATH RELATED ENDOSOMAL FYVE/SYLF PROTEIN 1 (CFS1). The CFS1 protein interacts with the ENDOSOMAL SORTING COMPLEX REQUIRED FOR TRANSPORT I (ESCRT-I) component ELCH (ELC) and is localized at ESCRT-I-positive late endosomes likely through its PI3P and actin binding SH3YL1 Ysc84/Lsb4p Lsb3p plant FYVE (SYLF) domain. Mutant alleles of cfs1 exhibit auto-immune phenotypes including spontaneous lesions that show characteristics of hypersensitive response (HR). Autoimmunity in cfs1 is dependent on ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1)-mediated effector-triggered immunity (ETI) but independent from salicylic acid. Additionally, cfs1 mutants accumulate the autophagy markers ATG8 and NBR1 independently from EDS1. We hypothesize that CFS1 acts at the intersection of autophagosomes and endosomes and contributes to cellular homeostasis by mediating autophagosome turnover

Quantification of glyphosate and aminomethylphosphonic acid from microbiome reactor fluids

Rationale: Glyphosate is one of the most widely used herbicides and it is suspected to affect the intestinal microbiota through inhibition of aromatic amino acid synthesis via the shikimate pathway.In vitromicrobiome bioreactors are increasingly used as model systems to investigate effects on intestinal microbiota and consequently methods for the quantitation of glyphosate and its degradation product aminomethylphosphonic acid (AMPA) in microbiome model systems are required. Methods: An optimized protocol enables the analysis of both glyphosate and AMPA by simple extraction with methanol:acetonitrile:water (2:3:1) without further enrichment steps. Glyphosate and AMPA are separated by liquid chromatography on an amide column and identified and quantified with a targeted tandem mass spectrometry method using a QTRAP 5500 system (AB Sciex). Results: Our method has a limit of detection (LOD) in extracted water samples of <2 ng/mL for both glyphosate and AMPA. In complex intestinal medium, the LOD is 2 and 5 ng/mL for glyphosate and AMPA, respectively. These LODs allow for measurement at exposure-relevant concentrations. Glyphosate levels in a bioreactor model of porcine colon were determined and consequently it was verified whether AMPA was produced by porcine gut microbiota. Conclusions: The method presented here allows quantitation of glyphosate and AMPA in complex bioreactor fluids and thus enables studies of the impact of glyphosate and its metabolism on intestinal microbiota. In addition, the extraction protocol is compatible with an untargeted metabolomics analysis, thus allowing one to look for other perturbations caused by glyphosate in the same sample

The Activation of Mucosal-Associated Invariant T (MAIT) Cells Is Affected by Microbial Diversity and Riboflavin Utilization in vitro

Recent research has demonstrated that MAIT cells are activated by individual bacterial or yeasts species that possess the riboflavin biosynthesis pathway. However, little is known about the MAIT cell activating potential of microbial communities and the contribution of individual community members. Here, we analyze the MAIT cell activating potential of a human intestinal model community (SIHUMIx) as well as intestinal microbiota after bioreactor cultivation. We determined the contribution of individual SIHUMIx community members to the MAIT cell activating potential and investigated whether microbial stress can influence their MAIT cell activating potential. The MAIT cell activating potential of SIHUMIx was directly related to the relative species abundances in the community. We therefore suggest an additive relationship between the species abundances and their MAIT cell activating potential. In diverse microbial communities, we found that a low MAIT cell activating potential was associated with high microbial diversity and a high level of riboflavin demand and vice versa. We suggest that microbial diversity might affect MAIT cell activation via riboflavin utilization within the community. Microbial acid stress significantly reduced the MAIT cell activating potential of SIHUMIx by impairing riboflavin availability through increasing the riboflavin demand.We show that MAIT cells can perceive microbial stress due to changes in riboflavin utilization and that riboflavin availability might also play a central role for the MAIT cell activating potential of diverse microbiota

Search for corannulene (C20H10) in the Red Rectangle

Polycyclic Aromatic Hydrocarbons (PAHs) are widely accepted as the carriers of the Aromatic Infrared Bands (AIBs), but an unambiguous identification of any specific interstellar PAH is still missing. For polar PAHs, pure rotational transitions can be used as spectral fingerprints for identification. Combining dedicated experiments, detailed simulations and observations, we explore d the mm wavelength domain to search for specific rotational transitions of corannulene (C20H10). We performed high-resolution spectroscopic measurements and a simulation of the emission spectrum of ultraviolet-excited C20H10 in the environment of the Red Rectangle (RR), calculating its synthetic rotational spectrum. Based on these results, we conducted a first observational campaign at the IRAM 30-m telescope towards this source to search for several high-J rotational transitions of C20H10. The laboratory detection of the J = 112 ← 111 transition of corannulene showed that no centrifugal splitting is present up to this line. Observations with the IRAM 30-m telescope towards the RR do not show any corannulene emission at any of the observed frequencies, down to a rms noise level of Tmb= 8 mK for the J =135 → 134 transition at 137.615 GHz. Comparing the noise level with the synthetic spectrum, we are able to estimate an upper limit to the fraction of carbon locked in corannulene of about 1.0 × 10−5 relative to the total abundance of carbon in PAHs. The sensitivity achieved in this work shows that radio spectroscopy can be a powerful tool to search for polar PAHs. We compare this upper limit with models for the PAH size distribution, emphasizing that small PAHs are much less abundant than predicted. We show that this cannot be explained by destruction but is more likely related to the chemistry of their formation in the environment of the R

Maternal and child cytokine relationship in early life is not altered by cytokine gene polymorphisms

The development of immune responses is influenced by the interaction between environmental and genetic factors. Our previous study showed a close association between maternal and young infant’s cytokine responses. The question is how this association evolves over time and the contribution of genetic polymorphisms to this association. Five cytokines in mitogen-stimulated whole blood culture were measured from pregnant mothers and their children aged 2, 5, 12, 24 and 48 months. Cytokine gene polymorphisms were determined in both mothers and children. High production of maternal interleukin (IL)-10, tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) was significantly associated with higher levels of the corresponding cytokines in their children at 2 months (T2), but the association decreased over time. Maternal single-nucleotide polymorphism (SNP) in IFN-γ gene, rs3181032, was found to be associated with child’s IFN-γ levels at T2 only, whereas maternal IL-10 rs4579758 and child’s TNF-α rs13215091 were associated with child’s corresponding cytokines at later ages but not at T2. In the final models including the gene polymorphisms, maternal cytokines were still the strongest determinant of child cytokines. Maternal cytokine during pregnancy, which could be a proxy for child’s environmental factors, showed its highest impact at early age, with no or little influence from genetic factors

Cardiac-Oxidized Antigens Are Targets of Immune Recognition by Antibodies and Potential Molecular Determinants in Chagas Disease Pathogenesis

Trypanosoma cruzi elicits reactive oxygen species (ROS) of inflammatory and mitochondrial origin in infected hosts. In this study, we examined ROS-induced oxidative modifications in the heart and determined whether the resultant oxidized cardiac proteins are targets of immune response and of pathological significance in Chagas disease. Heart biopsies from chagasic mice, rats and human patients exhibited, when compared to those from normal controls, a substantial increase in protein 4-hydroxynonenal (4-HNE), malondialdehyde (MDA), carbonyl, and 3-nitrotyrosine (3-NT) adducts. To evaluate whether oxidized proteins gain antigenic properties, heart homogenates or isolated cardiomyocytes were oxidized in vitro and one- or two-dimensional gel electrophoresis (2D-GE)/Western blotting (WB) was performed to investigate the proteomic oxidative changes and recognition of oxidized proteins by sera antibodies in chagasic rodents (mice, rats) and human patients. Human cardiomyocytes exhibited LD50 sensitivity to 30 µM 4-HNE and 100 µM H2O2 at 6 h and 12 h, respectively. In vitro oxidation with 4-HNE or H2O2 resulted in a substantial increase in 4-HNE- and carbonyl-modified proteins that correlated with increased recognition of cardiac (cardiomyocytes) proteins by sera antibodies of chagasic rodents and human patients. 2D-GE/Western blotting followed by MALDI-TOF-MS/MS analysis to identify cardiac proteins that were oxidized and recognized by human chagasic sera yielded 82 unique proteins. We validated the 2D-GE results by enzyme-linked immunosorbent assay (ELISA) and WB and demonstrated that oxidation of recombinant titin enhanced its immunogenicity and recognition by sera antibodies from chagasic hosts (rats and humans). Treatment of infected rats with phenyl-α-tert-butyl nitrone (PBN, antioxidant) resulted in normalized immune detection of cardiac proteins associated with control of cardiac pathology and preservation of heart contractile function in chagasic rats. We conclude that ROS-induced, cardiac-oxidized antigens are targets of immune recognition by antibodies and molecular determinants for pathogenesis during Chagas disease

Search for corannulene (C20H10) in the Red Rectangle

Polycyclic Aromatic Hydrocarbons (PAHs) are widely accepted as the carriers of the Aromatic Infrared Bands (AIBs), but an unambiguous identification of any specific interstellar PAH is still missing. For polar PAHs, pure rotational transitions can be used as fingerprints for identification. Combining dedicated experiments, detailed simulations and observations, we explored the mm domain to search for specific rotational transitions of corannulene (C20H10). We performed high-resolution spectroscopic measurements and a simulation of the emission spectrum of UV-excited C20H10 in the environment of the Red Rectangle, calculating its synthetic rotational spectrum. Based on these results, we conducted a first observational campaign at the IRAM 30m telescope towards this source to search for several high-J rotational transitions of (C20H10). The laboratory detection of the J = 112 <- 111 transition of corannulene showed that no centrifugal splitting is present up to this line. Observations with the IRAM 30m telescope towards the Red Rectangle do not show any corannulene emission at any of the observed frequencies, down to a rms noise level of Tmb = 8 mK for the J =135 -> 134 transition at 137.615 GHz. Comparing the noise level with the synthetic spectrum, we are able to estimate an upper limit to the fraction of carbon locked in corannulene of about 1.0x10(-5) relative to the total abundance of carbon in PAHs. The sensitivity achieved shows that radio spectroscopy can be a powerful tool to search for polar PAHs. We compare this upper limit with models for the PAH size distribution, emphasising that small PAHs are much less abundant than predicted. We show that this cannot be explained by destruction but is more likely related to the chemistry of their formation in the environment of the Red Rectangle.Comment: 8 pages, 7 figures, 2 tables, accepted for publication in MNRA