The Association between Prenatal Psychosocial Stress and Blood Pressure in the Child at Age 5-7 Years

Objective

Prenatal maternal stress could have permanent effects on the offspring’s tissue structure and function, which may predispose to cardiovascular diseases. We investigated whether maternal psychosocial stress is a prenatal factor affecting the blood pressure (BP) of offspring.

Study Design

In the Amsterdam Born Children and their Development (ABCD) study, around gestational week 16, depressive symptoms, state-anxiety, pregnancy-related anxiety, parenting daily hassles and job strain were recorded by questionnaire. A cumulative stress score was also calculated (based on 80^th percentiles). Systolic and diastolic BP and mean arterial pressure (MAP) were measured in the offspring at age 5–7 years. Inclusion criteria were: no use of antihypertensive medication during pregnancy; singleton birth; no reported cardiovascular problems in the child (N = 2968 included).

Results

After adjustment for confounders, the single stress scales were not associated with systolic and diastolic BP, MAP and hypertension (p>0.05). The presence of 3–4 psychosocial stressors prenatally (4%) was associated with 1.5 mmHg higher systolic and diastolic BP (p = 0.046; p = 0.04) and 1.5 mmHg higher MAP in the offspring (p = 0.02) compared to no stressors (46%). The presence of 3–4 stressors did not significantly increase the risk for hypertension (OR 1.8; 95% CI 0.93.4). Associations did not differ between sexes. Bonferroni correction for multiple testing rendered all associations non-significant.

Conclusions

The presence of multiple psychosocial stressors during pregnancy was associated with higher systolic and diastolic BP and MAP in the child at age 5–7. Further investigation of maternal prenatal stress may be valuable for later life cardiovascular health.     

A Physiological Increase of Insulin in the Olfactory Bulb Decreases Detection of a Learned Aversive Odor and Abolishes Food Odor-Induced Sniffing Behavior in Rats

Insulin is involved in multiple regulatory mechanisms, including body weight and food intake, and plays a critical role in metabolic disorders such as obesity and diabetes. An increasing body of evidence indicates that insulin is also involved in the modulation of olfactory function. The olfactory bulb (OB) contains the highest level of insulin and insulin receptors (IRs) in the brain. However, a role for insulin in odor detection and sniffing behavior remains to be elucidated. Using a behavioral paradigm based on conditioned olfactory aversion (COA) to isoamyl-acetate odor, we demonstrated that an intracerebroventricular (ICV) injection of 14 mU insulin acutely decreased olfactory detection of fasted rats to the level observed in satiated animals. In addition, whereas fasted animals demonstrated an increase in respiratory frequency upon food odor detection, this effect was absent in fasted animals receiving a 14 mU insulin ICV injection as well as in satiated animals. In parallel, we showed that the OB and plasma insulin levels were increased in satiated rats compared to fasted rats, and that a 14 mU insulin ICV injection elevated the OB insulin level of fasted rats to that of satiated rats. We further quantified insulin receptors (IRs) distribution and showed that IRs are preferentially expressed in the caudal and lateral parts of the main OB, with the highest labeling found in the mitral cells, the main OB projection neurons. Together, these data suggest that insulin acts on the OB network to modulate olfactory processing and demonstrate that olfactory function is under the control of signals involved in energy homeostasis regulation and feeding behaviors.     

Characterization of aerobic granular sludge at various organic loading rates

Aerobic granular sludge was cultivated from activated sludge with two types of supports, namely bivalve shell carrier (BSC) and anaerobic granules (ANG). Granules were characterized at different organic loading rates (OLRs) ranging from 2.5 to 15 kg COD/m³ d and these granules were observed to withstand high OLRs. The physico-chemical characteristics of the aerobic granules were better than those of seed sludge. The granule formation with ANG support was found to be similar to that of non-support cultivation, i.e. formation from activated sludge only. By contrast, BSC support showed better performance in terms of faster settleability, compactness and especially resistance against organic shock loading. It also enabled self-cleaning effect by removing biofilm attached on the reactor wall during the start-up phase resulting rapid granulation process.     

Structure-based analysis of GPCR function: conformational adaptation of both agonist and receptor upon leukotriene B4 binding to recombinant BLT1

We produced the human leukotriene B(4) (LTB(4)) receptor BLT1, a G-protein-coupled receptor, in Escherichia coli with yields that are sufficient for the first structural characterization of this receptor in solution. Overexpression was achieved through codon optimization and the search for optimal refolding conditions of BLT1 recovered from inclusion bodies. The detergent-solubilized receptor displays a 3D-fold compatible with a seven transmembrane (TM) domain with ca 50% alpha-helix and an essential disulfide bridge (circular dichroism evidence); it binds LTB(4) with K(a)=7.8(+/-0.2)x10(8)M(-1) and a stoichiometric ratio of 0.98(+/-0.02). Antagonistic effects were investigated using a synthetic molecule that shares common structural features with LTB(4). We report evidence that both partners, LTB(4) and BLT1, undergo a rearrangement of their respective conformations upon complex formation: (i) a departure from planarity of the LTB(4) conjugated triene moiety; (ii) a change in the environment of Trp234 (TM-VI helix) and in the exposure of the cytoplasmic region of this transmembrane helix.     

Predicting phenotype from patterns of annotation

MOTIVATION:Predicting the outcome of specific experiments (such as the growth of a particular mutant strain in a particular medium) has the potential to allow researchers to devote resources to experiments with higher expected numbers of 'hits'. RESULTS: We use decision trees to predict phenotypes associated with Saccharomyces cerevisiae genes on the basis of Gene Ontology (GO) functional annotations from the Saccharomyces Genome Database (SGD) and other phenotypic annotations from the Yeast Phenotype Catalog at the Munich Information Center for Protein Sequences (MIPS). We assess the methodology in three ways: (1) we use cross-validation on the phenotypic annotations listed in MIPS, and show ROC curves indicating the tradeoff between true-positive rate and false-positive rate; (2) we do a literature-search for 100 of the predicted gene-phenotype associations that are not listed in MIPS, and find evidence for 43 of them; (3) we use deletion strains to experimentally assess 61 predicted gene-phenotype associations not listed in MIPS; significantly more of these deletion strains show abnormal growth than would be expected by chance.     

Dynamics of meiosis and protein kinase activities in bovine oocytes correlated to prolactin treatment and follicle size

Oocyte developmental competence depends on the size of the original follicle and is affected by compounds like prolactin. We wished to investigate nuclear and cytoplasmic maturation of bovine oocytes correlated to their origin and response to prolactin treatment, by monitoring at frequent intervals meiotic configuration of chromosomes and activity of histone H1 and MAP-kinase. Bovine ovaries were obtained from a slaughterhouse and oocytes were recovered by follicle isolation. Oocytes (n = 1,397) with a compact cumulus were selected from small (2 to 3 mm) and large (4 to 5 mm in diameter) follicles and cultured up to 28 h in TCM 199+20% bull serum with or without 50 ng/mL bovine prolactin. Four groups of oocytes were formed: originating from small or large follicles, and treated or not treated with prolactin. At the scheduled time intervals for in vitro maturation, cumulus oocyte complexes from the 4 groups were randomly selected and the oocytes were analyzed for histone H1 and MAP-kinase, and for chromatin configuration. The first meiotic division took longer to complete in oocytes from large follicles (P < 0.01). Under the influence of prolactin the meiosis was prolonged in oocytes both from small and large follicles (P < 0.05). Histone H1 and MAP-kinases started to be activated at approximately the same time, around 6 h after beginning maturation. But after this time, significantly lower levels of both kinase activities were found in oocytes treated with prolactin, especially those treated during Meiosis I (P < 0.05). Our results indicate a correlation of chromatin configuration and histone H1/MAP-kinase activities.     

Gremlin-mediated BMP antagonism induces the epithelial-mesenchymal feedback signaling controlling metanephric kidney and limb organogenesis

Epithelial-mesenchymal feedback signaling is the key to diverse organogenetic processes such as limb bud development and branching morphogenesis in kidney and lung rudiments. This study establishes that the BMP antagonist gremlin (Grem1) is essential to initiate these epithelial-mesenchymal signaling interactions during limb and metanephric kidney organogenesis. A Grem1 null mutation in the mouse generated by gene targeting causes neonatal lethality because of the lack of kidneys and lung septation defects. In early limb buds, mesenchymal Grem1 is required to establish a functional apical ectodermal ridge and the epithelial-mesenchymal feedback signaling that propagates the sonic hedgehog morphogen. Furthermore, Grem1-mediated BMP antagonism is essential to induce metanephric kidney development as initiation of ureter growth, branching and establishment of RET/GDNF feedback signaling are disrupted in Grem1-deficient embryos. As a consequence, the metanephric mesenchyme is eliminated by apoptosis, in the same way as the core mesenchymal cells of the limb bud.     

A phylogenomic study of the genus Alphavirus employing whole genome comparison

The phylogenetics of the genus Alphavirus have historically been characterized using partial gene, single gene or partial proteomic data. We have mined cDNA and amino acid sequences from GenBank for all fully sequenced and some partially sequenced alphaviruses and generated phylogenomic analyses of the genus Alphavirus genus, employing capsid encoding structural regions, non-structural coding regions and complete viral genomes. Our studies support the presence of the previously reported recombination event that produced the Western Equine Encephalitis clade, and confirm many of the patterns of geographic radiation and divergence of the multiple species. Our data suggest that the Salmon Pancreatic Disease Virus and Sleeping Disease Virus are sufficiently divergent to form a separate clade from the other alphaviruses. Also, unlike previously reported studies employing limited sequence data for correlation of phylogeny, our results indicate that the Barmah Forest Virus and Middelburg Virus appear to be members of the Semliki Forest clade. Additionally, our analysis indicates that the Southern Elephant Seal Virus is part of the Semliki Forest clade, although still phylogenetically distant from all known members of the genus Alphavirus. Finally, we demonstrate that the whole Rubella viral genome provides an ideal outgroup for phylogenomic studies of the genus Alphavirus.     

Differential modulation of interleukin-2-and interleukin-4-mediated early activation of normal human B lymphocytes by the caspase inhibitor zVAD-fmk

Caspases are a group of cysteine-related proteases that control the process of apoptosis and may also be involved in the control of lymphocyte activation. We show here that the broad-spectrum caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp (Ome)-fluoromethylketone (zVAD-fmk) prevents the proliferation of resting human B tonsilar lymphocytes mediated by the B cell mitogen SAC or the combination of anti-mu Ab and IL-2. zVAD-fmk inhibits IL-2-induced phosphorylation of the retinoblastoma protein, and cyclin D2 expression. However, neither the IL-2-mediated proliferation of cycling activated B cells nor that of lymphoma cells were inhibited by zVAD-fmk, suggesting that only the early steps of SAC- or IL-2-mediated B cell activation were sensitive to the inhibitory properties of zVAD-fmk. Our data also demonstrated that the inhibitory effect of zVAD-fmk was not observed when B cells were activated with IL-4 in the presence of either anti-mu Ab or anti-CD40 Ab. Thus, our results suggest that caspase activation is required for the IL-2-mediated entry of primary B lymphocytes into the cell cycle and show that caspase activation plays different roles in IL-2- and IL-4-mediated B cell proliferation.     

Production of tannase (tannin acyl hydrolase E.C. 3.1.1.20) by a strain of Aspergillus niger

Summary Culture of a strain of Aspergillus niger on medium containing 3 % tannic acid yielded tannase (tanin acylhydrolase), evidenced both in the culture medium and the mycelium. Fermentation in submerged culture at constant air flow gave mycelium with high tannase activity.