Are female children more vulnerable to the long-term effects of maternal depression during pregnancy?

BACKGROUND: Female fetuses are more vulnerable to high levels of maternal glucocorticoids. We examined whether exposure to prenatal maternal depression, a condition associated with high glucocorticoids, carries greater risk for depression at 12 and 18 years in girls. METHODS: Our sample comprised 7959 mothers and children from the Avon Longitudinal Study of Parents and Children following imputation for missing data. Maternal depression was assessed pre-and post-natally, and offspring depression at ages 12 and 18. We used logistic regression models to examine the relationship between exposure to prenatal and postnatal depression and offspring depression at 18 and 12 and interactions with gender. RESULTS: There was an interaction between prenatal depression and gender (P=0.027) and between postnatal depression and gender (P=0.027) for offspring depression at 18. Following adjustment in pre-natally depressed mothers, the odds ratio for offspring depression at 18 was 1.55 (95% c.i. 1.03-2.34) for girls and 0.54 (0.23-1.26) for boys. In post-natally depressed mothers, the odds ratio for offspring depression at 18 was 1.15 (0.70-1.89) in girls and 3.13 (1.52-6.45) in boys. However there was no evidence for interaction between prenatal or postnatal depression and gender (P=0.559 and 0.780 respectively) for offspring depression at 12. LIMITATIONS: As expected with this large cohort spanning over 18 years, there was loss-to-follow-up. CONCLUSIONS: This is the first evidence in humans that increased vulnerability of female fetuses to maternal stress responses during pregnancy persists into adolescence. One explanation for gender differences emerging later is more depressive symptomatology is attributed to heritable risk at 12, whereas biological processes involved in brain development at 18 may be influenced by foetal programming. If replicated, this study has potential to help understand intergenerational transmission of depression, a leading cause of morbidity worldwide

Evolution and speciation in the Eocene planktonic foraminifer Turborotalia

Marine planktonic microfossils have provided some of the best examples of evolutionary rates and patterns on multi-million-year time scales, including many instances of gradual evolution. Lineage splitting as a result of speciation has also been claimed, but all such studies have used subjective visual species discrimination, and interpretation has often been complicated by relatively small sample sizes and oceanographic complexity at the study sites. Here we analyze measurements on a collection of 10,200 individual tests of the Eocene planktonic foraminifer Turborotalia in 51 stratigraphically ordered samples from a site within the oceanographically stable tropical North Pacific gyre. We use novel multivariate statistical clustering methods to test the hypothesis that a single evolutionary species was present from 45 Ma to its extinction ca. 34 Ma. After identification of a set of biologically relevant traits, the protocol we apply does not require a prior assignment of individuals to species. We find that for most of the record, contemporaneous specimens form one morphological cluster, which we interpret as an evolving species that shows quasi-continuous but non-directional gradual evolutionary change (anagenesis). However, in the upper Eocene from ca. 36 to ca. 34 Ma there are two clusters that persistently occupy distinct areas of morphospace, from which we infer that speciation (cladogenesis) must have occurred

Associations of maternal and paternal antenatal mood with offspring anxiety disorder at age 18 years.

OBJECTIVE: Maternal antenatal depression and anxiety are associated with increased risk of childhood behavioural and emotional problems in offspring; it remains unclear to what extent this is due to a maternal biological impact on foetal development. Here, we compare associations between maternal and paternal antenatal depression and anxiety with offspring anxiety disorders, thus controlling for some genetic and shared environmental factors. METHODS: We used data from the ALSPAC population cohort including measures of antenatal parental depression and anxiety. At 18 years, offspring completed the CIS-R interview, yielding diagnoses for anxiety disorders. Results were adjusted for confounding variables including parental postnatal depression and anxiety. RESULTS: Children of women with antenatal depression (18 weeks gestation), had an increased risk of anxiety disorders at 18 years of age (11.1% vs. 6.2%; adj. OR 1.75 (1.19, 2.58); p=0.01). Children of women with antenatal anxiety had increased risk of co-morbid anxiety and depression (adj. OR 1.39 (1.06, 1.82); p=0.02). No such associations were found with paternal antenatal depression or anxiety. LIMITATIONS: There was a high attrition rate from the original cohort to the CIS-R completion at 18 years postpartum. Parental mood was only assessed together at one time point during the antenatal period. CONCLUSIONS: The differences in the association between maternal and paternal mood during pregnancy and child outcomes supports the hypothesis that foetal programming may account, at least in part, for this association. We highlight the potential opportunity for preventative intervention by optimising antenatal mental health

An internal model architecture for novelty detection: Implications for cerebellar and collicular roles in sensory processing

The cerebellum is thought to implement internal models for sensory prediction, but details of the underlying circuitry are currently obscure. We therefore investigated a specific example of internal-model based sensory prediction, namely detection of whisker contacts during whisking. Inputs from the vibrissae in rats can be affected by signals generated by whisker movement, a phenomenon also observable in whisking robots. Robot novelty-detection can be improved by adaptive noise-cancellation, in which an adaptive filter learns a forward model of the whisker plant that allows the sensory effects of whisking to be predicted and thus subtracted from the noisy sensory input. However, the forward model only uses information from an efference copy of the whisking commands. Here we show that the addition of sensory information from the whiskers allows the adaptive filter to learn a more complex internal model that performs more robustly than the forward model, particularly when the whisking-induced interference has a periodic structure. We then propose a neural equivalent of the circuitry required for adaptive novelty-detection in the robot, in which the role of the adaptive filter is carried out by the cerebellum, with the comparison of its output (an estimate of the self-induced interference) and the original vibrissal signal occurring in the superior colliculus, a structure noted for its central role in novelty detection. This proposal makes a specific prediction concerning the whisker-related functions of a region in cerebellar cortical zone A2 that in rats receives climbing fibre input from the superior colliculus (via the inferior olive). This region has not been observed in non-whisking animals such as cats and primates, and its functional role in vibrissal processing has hitherto remained mysterious. Further investigation of this system may throw light on how cerebellar-based internal models could be used in broader sensory, motor and cognitive contexts. © 2012 Anderson et al

Neurosteroid-Mediated Regulation of Brain Innate Immunity in HIV/Aids: DHEA-S Suppresses Neurovirulence

Neurosteroids are cholesterol-derived molecules synthesized within the brain, which exert trophic and protective actions. Infection by human and feline immunodeficiency viruses (HIV and FIV, respectively) causes neuroinflammation and neurodegeneration, leading to neurological deficits. Secretion of neuroinflammatory host and viral factors by glia and infiltrating leukocytes mediates the principal neuropathogenic mechanisms during, although the effect of neurosteroids on these processes is unknown. We investigated the interactions between neurosteroid mediated effects and lentivirus infection outcomes. Analyses of HIV-infected uninfected human brains disclosed a reduction in neurosteroid synthesis enzyme expression. Human neurons exposed to supernatants from HIV macrophages exhibited suppressed enzyme expression without reduced cellular viability. HIV human macrophages treated with sulfated dehydroepiandrosterone (DHEA-S) showed suppression of inflammatory gene (IL-1, IL-6, TNF-) expression. IV-infected IV) animals treated daily with 15mg/kg body weight. DHEA-S treatment reduced inflammatory gene transcripts (IL-1, TNF-, CD3, GFAP) in brain compared to vehicle-(-cyclodextrin)-treated FIV animals similar to levels found in vehicle treated FIV animals. DHEA-S treatment also increased CD4T-cell levels and prevented neurobehavioral deficits and neuronal loss among FIV animals, compared to vehicle-treated FIV animals. Reduced neuronal neuro-steroid synthesis was evident in lentivirus infections, but treatment with DHEA-S limited neuroinflammation and prevented neurobehavioral deficits. Neurosteroid-derived therapies could be effective in the treatment of virus- or inflammation-mediated neurodegeneration

Geochemical ice-core constraints on the timing and climatic impact of Aniakchak II (1628 BCE) and Thera (Minoan) volcanic eruptions

This work was supported by funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement 820047 to M.Si.), the Malcolm H. Wiener Foundation (Interdisciplinary Chronology of Civilizations Project to C.P.) and a UKRI Future Leader Fellowship (MR/S035478/1 to P.A).Decades of research have focused on establishing the exact year and climatic impact of the Minoan eruption of Thera, Greece (c.1680–1500 BCE). Ice cores offer key evidence to resolve this controversy, but attempts have been hampered by a lack of multi-volcanic event synchronization between records. In this study, Antarctic and Greenland ice-core records are synchronized using a double bipolar sulfate marker and calendar dates are assigned to each eruption revealed within the ‘Thera period’. From this global scale sequence of volcanic sulfate loading, we derive indications towards each eruption’s latitude and potential to disrupt the climate system. Ultra-fine sampling for sulfur isotopes and tephra conclusively demonstrate a colossal eruption of Alaska’s Aniakchak II as the source of stratospheric sulfate in the now precisely dated 1628 BCE ice layer. These findings end decades of speculation that Thera was responsible for the 1628 BCE event, and place Aniakchak II (52 ± 17 Tg S) and an unknown volcano at 1654 BCE (50 ± 13 Tg S) as two of the largest Northern Hemisphere sulfur injections in the last 4000 years. This opens possibilities to explore widespread climatic impacts for contemporary societies and, in pinpointing Aniakchak II, confirms that stratospheric sulfate can be globally distributed from eruptions outside the tropics. Dating options for Thera are reduced to a series of precisely dated, constrained stratospheric sulfur injection events at 1611 BCE, 1562-1555 BCE and c.1538 BCE which are all below 14 ± 5 Tg S, indicating a climatic forcing potential for Thera well below that of Tambora (1815 CE).Publisher PDFPeer reviewe

Two-neutron transfer reaction mechanisms in 12^{12}C(6^6He,4^{4}He)14^{14}C using a realistic three-body 6^{6}He model

The reaction mechanisms of the two-neutron transfer reaction $^{12}$C($^6$He,$^4$He) have been studied at 30 MeV at the TRIUMF ISAC-II facility using the SHARC charged-particle detector array. Optical potential parameters have been extracted from the analysis of the elastic scattering angular distribution. The new potential has been applied to the study of the transfer angular distribution to the 2$^+_2$ 8.32 MeV state in $^{14}$C, using a realistic 3-body $^6$He model and advanced shell model calculations for the carbon structure, allowing to calculate the relative contributions of the simultaneous and sequential two-neutron transfer. The reaction model provides a good description of the 30 MeV data set and shows that the simultaneous process is the dominant transfer mechanism. Sensitivity tests of optical potential parameters show that the final results can be considerably affected by the choice of optical potentials. A reanalysis of data measured previously at 18 MeV however, is not as well described by the same reaction model, suggesting that one needs to include higher order effects in the reaction mechanism.Comment: 9 pages, 9 figure

Characterisation of tetraspanins from Schistosoma haematobium and evaluation of their potential as novel diagnostic markers

Schistosoma haematobium is the leading cause of urogenital schistosomiasis and it is recognised as a class 1 carcinogen due to the robust association of infection with bladder cancer. In schistosomes, tetraspanins (TSPs) are abundantly present in different parasite proteomes and could be potential diagnostic candidates due to their accessibility to the host immune system. The large extracellular loops of six TSPs from the secretome (including the soluble excretory/secretory products, tegument and extracellular vesicles) of S. haematobium (Sh-TSP-2, Sh-TSP-4, Sh-TSP-5, Sh-TSP-6, Sh-TSP-18 and Sh-TSP-23) were expressed in a bacterial expression system and polyclonal antibodies were raised to the recombinant proteins to confirm the anatomical sites of expression within the parasite. Sh-TSP-2, and Sh-TSP-18 were identified on the tegument, whereas Sh-TSP-4, Sh-TSP-5, Sh-TSP-6 and Sh-TSP-23 were identified both on the tegument and internal tissues of adult parasites. The mRNAs encoding these TSPs were differentially expressed throughout all schistosome developmental stages tested. The potential diagnostic value of three of these Sh-TSPs was assessed using the urine of individuals (stratified by infection intensity) from an endemic area of Zimbabwe. The three Sh-TSPs were the targets of urine IgG responses in all cohorts, including individuals with very low levels of infection (those positive for circulating anodic antigen but negative for eggs by microscopy). This study provides new antigen candidates to immunologically diagnose S. haematobium infection, and the work presented here provides compelling evidence for the use of a biomarker signature to enhance the diagnostic capability of these tetraspanins