Abstract Background Current neuroimaging perspectives on a variety of mental disorders emphasize dysfunction of the amygdala. The neuropeptide oxytocin (OXT), a key mediator in the regulation of ...social cognition and behavior, accumulates in cerebrospinal fluid after intranasal administration in macaques and humans and modulates amygdala reactivity in both species. However, the translation of neuromodulatory OXT effects to novel treatment approaches is hampered by the absence of studies defining the most effective dose and dose-response latency for targeting the amygdala. Methods To address this highly relevant issue, a total of 116 healthy men underwent functional magnetic resonance imaging (fMRI) using a randomized, double-blind, placebo-controlled crossover study design. The experimental rationale was to systematically vary dose-test latencies (15-40, 45-70, 75-100min) and doses of OXT (12IU, 24IU, 48IU) in order to identify the most robust effects on amygdala reactivity. During fMRI, subjects completed an emotional face recognition task including stimuli with varying intensities ranging from low (highly ambiguous) to high (less ambiguous). Results Our results indicate that the OXT-induced inhibition of amygdala responses to fear was most effective in a time window between 45 and 70min after administration of a 24IU dose. Furthermore, the observed effect was most evident in subjects scoring high on measures of autistic-like traits. Behavioral response patterns suggest that OXT specifically reduced an emotional bias in the perception of ambiguous faces. Conclusion These findings provide initial evidence of the most effective dose and dose-test interval for future experimental or therapeutic regimens aimed at targeting amygdala functioning using intranasal OXT administration.ClinicalTrials.gov ID: NCT03011970. Trial Name: ‘Temporal Dynamics and Pharmacokinetics of Intranasally Administered Oxytocin’ URL: https://clinicaltrials.gov/ct2/show/NCT03011970?term=Pharmacokinetics+Oxytocin&rank=4
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The accretion of volatile-rich material from the outer Solar System represents a crucial prerequisite for Earth to develop oceans and become a habitable planet
. However, the timing of this accretion ...remains controversial
. It has been proposed that volatile elements were added to Earth by the late accretion of a late veneer consisting of carbonaceous-chondrite-like material after core formation had ceased
. This view could not be reconciled with the ruthenium (Ru) isotope composition of carbonaceous chondrites
, which is distinct from that of the modern mantle
, or of any known meteorite group
. As a possible solution, Earth's pre-late-veneer mantle could already have contained a fraction of Ru that was not fully extracted by core formation
. The presence of such pre-late-veneer Ru can only be established if its isotope composition is distinct from that of the modern mantle. Here we report the first high-precision, mass-independent Ru isotope compositions for Eoarchaean ultramafic rocks from southwest Greenland, which display a relative
Ru excess of 22 parts per million compared with the modern mantle value. This
Ru excess indicates that the source of the Eoarchaean rocks already contained a substantial fraction of Ru before the accretion of the late veneer. By 3.7 billion years ago, the mantle beneath southwest Greenland had not yet fully equilibrated with late accreted material. Otherwise, no Ru isotopic difference relative to the modern mantle would be observed. If constraints from other highly siderophile elements besides Ru are also considered
, the composition of the modern mantle can only be reconciled if the late veneer contained substantial amounts of carbonaceous-chondrite-like materials with their characteristic
Ru deficits. These data therefore relax previous constraints on the late veneer and are consistent with volatile-rich material from the outer Solar System being delivered to Earth during late accretion.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Here we present a brief, historical review of research into the mammalian middle ear structures. Most of their essential homologies were established by embryologists, notably including Reichert, ...during the 19th century. The evolutionary dimension was confirmed by finds of fossil synapsids, mainly from the Karroo of South Africa. In 1913, Ernst Gaupp was the first to present a synthesis of the available embryological and paleontological data, but a number of morphological details remained to be solved, such as the origin of the tympanic membrane. Gaupp favoured an independent origin of the eardrum in anurans, sauropsids, and mammals; we support most of his ideas. The present review emphasizes the problem of how the mammalian middle ear structures that developed at the angle of the lower jaw were transferred to the basicranium; the ontogenesis of extant marsupials provides important information on this question.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The Bushveld Complex of South Africa is underlain by a fine-grained sill complex which most workers interpret to represent the quenched parent magmas to the intrusion. The sills have unusually high ...Pt contents (up to ~ 25 ppb) and Pt/Pd ratios (average 1.50) exceeding those in most other mantle magmas globally. Unusually high Pt/Pd is also found in many Bushveld cumulates. Understanding the origin of the high Pt/Pd is important for exploration, in view of the contrasting monetary value of the metals, but also for unravelling the petrogenesis of the intrusion. Here, we review existing platinum-group element (PGE) data and present the first radiogenic W isotope data on a Bushveld rock, to evaluate a range of potential models, including PGE fractionation prior to final magma emplacement and within the Bushveld magma chamber, magma derivation from the sub-continental lithospheric mantle (SCLM), contamination of Bushveld magma with Pt-rich continental crust, and a meteoritic component in the mantle source to the magmas or in the crust with which the magmas interacted. We identify three key processes causing fractionation of metals prior to final magma emplacement and within the Bushveld chamber, namely crystallisation of Pt alloys, partial melting of cumulus sulfides triggered by flux of volatiles followed by sulfide melt percolation, and mobilisation of PGE by percolation of volatiles through the cumulate pile. The currently available W and Ru isotope data are inconsistent with derivation of the Bushveld magmas from mantle or crustal sources containing an enhanced meteoritic component relative to normal post-Hadean mantle.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
There has been an unprecedented interest in the modulatory effects of intranasal oxytocin on human social cognition and behaviour, however as yet no study has actually demonstrated that this modality ...of administration increases concentrations of the peptide in the brain as well as blood in humans. Here using combined blood and cerebrospinal fluid (CSF) sampling in subjects receiving either 24 IU of oxytocin (n = 11) or placebo (n = 4) we have shown that oxytocin levels significantly increased in both plasma and CSF. However, whereas oxytocin plasma concentrations peaked at 15 min after intranasal administration and decreased after 75 min, CSF concentrations took up to 75 min to reach a significant level. Moreover, there was no correlation (r = <0.10) between oxytocin plasma and CSF concentrations. Together, these data provide crucial insights into the plasma and CSF kinetics of intranasally administered oxytocin.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Fungal research is experiencing a new wave of methodological improvements that most probably will boost mycology as profoundly as molecular phylogeny has done during the last 15 years. Especially the ...next generation sequencing technologies can be expected to have a tremendous effect on fungal biodiversity and ecology research. In order to realise the full potential of these exciting techniques by accelerating biodiversity assessments, identification procedures of fungi need to be adapted to the emerging demands of modern large-scale ecological studies. But how should fungal species be identified in the near future? While the answer might seem trivial to most microbiologists, taxonomists working with fungi may have other views. In the present review, we will analyse the state of the art of the so-called barcoding initiatives in the light of fungi, and we will seek to evaluate emerging trends in the field. We will furthermore demonstrate that the usability of DNA barcoding as a major tool for identification of fungi largely depends on the development of high-quality sequence databases that are thoroughly curated by taxonomists and systematists.
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CEKLJ, DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Highlights ► Associations between human social and emotional behaviors and oxytocin are reviewed. ► Oxytocin has effects on social bonds, trust, learning, emotion recognition and empathy. ► Clinical ...research suggests therapeutic use for oxytocin in social and affective disorders. ► Oxytocin based treatments for autism, social phobia and schizophrenia show promise. ► Future work needs to identify oxytocin’s neural targets and neuromodulatory actions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The microbiome of the ocular surface has been characterised, but only limited information is available on a possible silent intraocular microbial colonisation in normal eyes. Therefore, we performed ...next-generation sequencing (NGS) of 16S rDNA genes in the aqueous humour. The aqueous humour was sampled from three patients during cataract surgery. Air swabs, conjunctival swabs from patients as well as from healthy donors served as controls. Following DNA extraction, the V3 and V4 hypervariable regions of the 16S rDNA gene were amplified and sequenced followed by denoising. The resulting Amplicon Sequence Variants were matched to a subset of the Ribosomal Database Project 16S database. The deduced bacterial community was then statistically analysed. The DNA content in all samples was low (0–1.49 ng/µL) but sufficient for analysis. The main phyla in the samples were Acinetobacteria (48%), Proteobacteria (26%), Firmicutes (14%), Acidobacteria (8%), and Bacteroidetes (2%). Patients’ conjunctival control samples and anterior chamber fluid showed similar patterns of bacterial species containing many waterborne species. Non-disinfected samples showed a different bacterial spectrum than the air swab samples. The data confirm the existence of an ocular surface microbiome. Meanwhile, a distinct intraocular microbiome was not discernible from the background, suggesting the absence of an intraocular microbiome in normal eyes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
ObjectiveIndirect evidence suggests that common genetic variation contributes to individual differences in antidepressant efficacy among individuals with major depressive disorder, but previous ...studies may have been underpowered to detect these effects.MethodA meta-analysis was performed on data from three genome-wide pharmacogenetic studies (the Genome-Based Therapeutic Drugs for Depression GENDEP project, the Munich Antidepressant Response Signature MARS project, and the Sequenced Treatment Alternatives to Relieve Depression STAR*D study), which included 2,256 individuals of Northern European descent with major depressive disorder, and antidepressant treatment outcomes were prospectively collected. After imputation, 1.2 million single-nucleotide polymorphisms were tested, capturing common variation for association with symptomatic improvement and remission after up to 12 weeks of antidepressant treatment.ResultsNo individual association met a genome-wide threshold for statistical significance in the primary analyses. A polygenic score derived from a meta-analysis of GENDEP and MARS participants accounted for up to approximately 1.2% of the variance in outcomes in STAR*D, suggesting a weakly concordant signal distributed over many polymorphisms. An analysis restricted to 1,354 individuals treated with citalopram (STAR*D) or escitalopram (GENDEP) identified an intergenic region on chromosome 5 associated with early improvement after 2 weeks of treatment.ConclusionsDespite increased statistical power accorded by meta-analysis, the authors identified no reliable predictors of antidepressant treatment outcome, although they did identify modest, direct evidence that common genetic variation contributes to individual differences in antidepressant response.
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