The Fe and Zn isotope composition of deep mantle source regions: Insights from Baffin Island picrites

Young (61 Ma) unaltered picrites from Baffin Island, northwest Canada, possess some of the highest 3He/4He (up to 50 Ra) seen on Earth, and provide a unique opportunity to study primordial mantle that has escaped subsequent chemical modification. These high-degree partial melts also record anomalously high 182W/184W ratios, but their Sr-Nd-Hf-Pb isotopic compositons (including 142Nd) are indistinguishable from those of North Atlantic mid-ocean ridge basalts. New high precision Fe and Zn stable isotope analyses of Baffin Island picrites show limited variability with δ56Fe ranging from −0.03‰ to 0.13‰ and δ66Zn varying from 0.18‰ to 0.28‰. However, a clear inflection is seen in both sets of isotope data around the composition of the parental melt (MgO = 21 wt %; δ56Fe = 0.08 ± 0.04‰; and δ66Zn = 0.24 ± 0.03‰), with two diverging trends interpreted to reflect the crystallisation of olivine and spinel in low-MgO samples and the accumulation of olivine at higher MgO. Olivine mineral separates are significantly isotopically lighter than their corresponding whole rocks (δ56Fe ≥ −0.62‰ and δ66Zn ≥ −0.22‰), with analyses of individual olivine phenocrysts having extremely variable Fe isotope compositions (δ56Fe = −0.01‰ to −0.80‰). By carrying out modelling in three-isotope space, we show that the very negative Fe isotope compositions of olivine phenocryst are the result of kinetic isotope fractionation from disequilibrium diffusional processes. An excellent correlation is observed between δ56Fe and δ66Zn, demonstrating that Zn isotopes are fractionated by the same processes as Fe in simple systems dominated by magmatic olivine. The incompatible behaviour of Cu during magmatic evolution is consistent with the sulfide-undersaturated nature of these melts. Consequently Zn behaves as a purely lithophile element, and estimates of the bulk Earth Zn isotope composition based on Baffin Island should therefore be robust. The ancient undegassed lower mantle sampled at Baffin Island possesses a δ56Fe value that is within error of previous estimates of bulk mantle δ56Fe, however, our estimate of the Baffin mantle δ66Zn (0.20 ± 0.03‰) is significantly lower than some previous estimates. Comparison of our new data with those for Archean and Proterozoic komatiites is consistent with the Fe and Zn isotope composition of the mantle remaining constant from at least 3 Ga to the present day. By focusing on large-degree partial melts (e.g. komatiites and picrites) we are potenitally biasing our record to samples that will inevitably have interacted with, entrained and melted the ambient shallow mantle during ascent. For a major element such as Fe, that will continuosly participate in melting as it rises through the mantle, the final isotopic compositon of the magama will be a weighted average of the complete melting column. Thus it is unsuprising that minimal Fe isotope variation are seen between localities. In contrast, the unique geochemical signatures (e.g. He and W) displayed by the Baffin Island picrites are inferred to solely originate from the lowermost mantle and will be continuously diluted upon magma ascent

High resolution 16S rRNA gene Next Generation Sequencing study of brain areas associated with Alzheimer’s and Parkinson’s disease

IntroductionAlzheimer’s (AD) and Parkinson’s disease (PD) are neurodegenerative conditions characterized by incremental deposition of β-amyloid (Aβ) and α-synuclein in AD and PD brain, respectively, in relatively conserved patterns. Both are associated with neuroinflammation, with a proposed microbial component for disease initiation and/or progression. Notably, Aβ and α-synuclein have been shown to possess antimicrobial properties. There is evidence for bacterial presence within the brain, including the oral pathobiont Porphyromonas gingivalis, with cognitive impairment and brain pathology being linked to periodontal (gum) disease and gut dysbiosis.MethodsHere, we use high resolution 16S rRNA PCR-based Next Generation Sequencing (16SNGS) to characterize bacterial composition in brain areas associated with the early, intermediate and late-stage of the diseases.Results and discussionThis study reveals the widespread presence of bacteria in areas of the brain associated with AD and PD pathology, with distinctly different bacterial profiles in blood and brain. Brain area profiles were overall somewhat similar, predominantly oral, with some bacteria subgingival and oronasal in origin, and relatively comparable profiles in AD and PD brain. However, brain areas associated with early disease development, such as the locus coeruleus, were substantially different in bacterial DNA content compared to areas affected later in disease etiology

Extensive crustal extraction in Earth’s early history inferred from molybdenum isotopes

Estimates of the volume of the earliest crust based on zircon ages and radiogenic isotopes remain equivocal. Stable isotope systems, such as molybdenum, have the potential to provide further constraints but remain underused due to the lack of complementarity between mantle and crustal reservoirs. Here we present molybdenum isotope data for Archaean komatiites and Phanerozoic komatiites and picrites and demonstrate that their mantle sources all possess subchondritic signatures complementary to the superchondritic continental crust. These results confirm that the present-day degree of mantle depletion was achieved by 3.5 billion years ago and that Earth has been in a steady state with respect to molybdenum recycling. Mass balance modelling shows that this early mantle depletion requires the extraction of a far greater volume of mafic-dominated protocrust than previously thought, more than twice the volume of the continental crust today, implying rapid crustal growth and destruction in the first billion years of Earth’s history

Immunologic Profiling of the Atlantic Salmon Gill by Single Nuclei Transcriptomics

ACKNOWLEDGMENTS The authors thank all of the animal staff at Kårvik havbruksstasjonen for their expert care of the research animals, and the University of Manchester Genomics Technology core facility (UK) for performing chromium 10x library preparation for snRNAseq. We also thanks the reviewers for their constructive comments on the original manuscript FUNDING AW is supported by the Tromsø forskningsstiftelse (TFS) grant awarded to DH (TFS2016DH). The Sentinel North Transdisciplinary Research Program Université Laval and UiT awarded to DH supports this work. SW is supported a grant from the Tromsø forskningsstiftelse (TFS) starter grant TFS2016SW. Experimental costs were covered by HFSP grant “Evolution of seasonal timers” RGP0030/2015 awarded to AL and DH. Storage resources were provided by the Norwegian National Infrastructure for Research Data (NIRD, project NS9055K).Peer reviewedPublisher PD

The behavior of iron and zinc stable isotopes accompanying the subduction of mafic oceanic crust: A case study from Western Alpine ophiolites

Arc lavas display elevated Fe3+/ΣFe ratios relative to MORB. One mechanism to explain this is the mobilization and transfer of oxidized or oxidizing components from the subducting slab to the mantle wedge. Here we use iron and zinc isotopes, which are fractionated upon complexation by sulfide, chloride, and carbonate ligands, to remark on the chemistry and oxidation state of fluids released during prograde metamorphism of subducted oceanic crust. We present data for metagabbros and metabasalts from the Chenaillet massif, Queyras complex, and the Zermatt-Saas ophiolite (Western European Alps), which have been metamorphosed at typical subduction zone P-T conditions and preserve their prograde metamorphic history. There is no systematic, detectable fractionation of either Fe or Zn isotopes across metamorphic facies, rather the isotope composition of the eclogites overlaps with published data for MORB. The lack of resolvable Fe isotope fractionation with increasing prograde metamorphism likely reflects the mass balance of the system, and in this scenario Fe mobility is not traceable with Fe isotopes. Given that Zn isotopes are fractionated by S-bearing and C-bearing fluids, this suggests that relatively small amounts of Zn are mobilized from the mafic lithologies in within these types of dehydration fluids. Conversely, metagabbros from the Queyras that are in proximity to metasediments display a significant Fe isotope fractionation. The covariation of δ56Fe of these samples with selected fluid mobile elements suggests the infiltration of sediment derived fluids with an isotopically light signature during subduction

Abnormal visual gain control and excitotoxicity in early-onset Parkinson's disease Drosophila models

The excitotoxic theory of Parkinson's disease (PD) hypothesises that a pathophysiological degeneration of dopaminergic neurons stems from neural hyperactivity at early stages of disease, leading to mitochondrial stress and cell death. Recent research has harnessed the visual system of Drosophila PD models to probe this hypothesis. Here, we investigate whether abnormal visual sensitivity and excitotoxicity occur in early-onset PD Drosophila models DJ-1Δ72, DJ1-Δ93, and PINK15. We used an electroretinogram to record steady state visually evoked potentials driven by temporal contrast stimuli. At 1 day of age, all early-onset PD mutants had a twofold increase in response amplitudes when compared to w- controls. Further, we found that excitotoxicity occurs in older early-onset PD models after increased neural demand is applied via visual stimulation. In an additional analysis, we used a linear discriminant analysis to test whether there were subtle variations in neural gain control that could be used to classify Drosophila into their correct age and genotype. The discriminant analysis was highly accurate, classifying Drosophila into their correct genotypic class at all age groups at 50-70% accuracy (20% chance baseline). Differences in cellular processes link to subtle alterations in neural network operation in young flies - all of which lead to the same pathogenic outcome. Our data are the first to demonstrate abnormal gain control and excitotoxicity in early-onset PD Drosophila mutants. We conclude that early-onset PD mutations may be linked to more sensitive neuronal signalling in prodromal animals that may cause the expression of PD symptomologies later in life

Immune or genetic-mediated disruption of CASPR2 causes pain hypersensitivity due to enhanced primary afferent excitability

Human autoantibodies to contactin-associated protein-like 2 (CASPR2) are often associated with neuropathic pain, and CASPR2 mutations have been linked to autism spectrum disorders, in which sensory dysfunction is increasingly recognized. Human CASPR2 autoantibodies, when injected into mice, were peripherally restricted and resulted in mechanical pain-related hypersensitivity in the absence of neural injury. We therefore investigated the mechanism by which CASPR2 modulates nociceptive function. Mice lacking CASPR2 (Cntnap2 ) demonstrated enhanced pain-related hypersensitivity to noxious mechanical stimuli, heat, and algogens. Both primary afferent excitability and subsequent nociceptive transmission within the dorsal horn were increased in Cntnap2 mice. Either immune or genetic-mediated ablation of CASPR2 enhanced the excitability of DRG neurons in a cell-autonomous fashion through regulation of Kv1 channel expression at the soma membrane. This is the first example of passive transfer of an autoimmune peripheral neuropathic pain disorder and demonstrates that CASPR2 has a key role in regulating cell-intrinsic dorsal root ganglion (DRG) neuron excitability

When are breast cancer patients at highest risk of venous thromboembolism: a cohort study using English healthcare data

Breast cancer patients are at increased risk of VTE, particularly in the peri-diagnosis period. However, no previous epidemiological studies have investigated the relative impact of breast cancer treatments in a time-dependent manner. We aimed to determine the impact of breast cancer stage, biology and treatment on the absolute and relative risks of VTE, using several recently linked data sources from England. Our cohort comprised 13,202 breast cancer patients from the Clinical Practice Research Datalink (linked to Hospital Episode Statistics and Cancer Registry data), diagnosed between 1997 and 2006 with follow-up continuing to the end of 2010. Cox regression analysis was performed to determine which demographic, treatment-related and biological factors independently affected VTE risk. Women had an annual VTE incidence of 6% whilst receiving chemotherapy which was 10.8-fold higher (95% CI, 8.2 to 14.4; absolute risk (AR) =59.6 per 1000 person-years) than women who did not receive chemotherapy. Following surgery the risk was significantly raised in the first month (HR=2.2; 95% CI 1.4 to 3.4; AR=23.5; reference group, no surgery), but it was not raised subsequent to this. Risk of VTE was noticeably higher in the 3-months following initiation of Tamoxifen compared with the risk before therapy (HR=5.5; 95% CI 2.3 to 12.7; AR=24.1), however commencement of aromatase inhibitors was not associated with VTE (HR=0.8; 95% CI 0.5 to 1.4; AR=28.3). In conclusion, women receiving chemotherapy for breast cancer have a clinically important risk of VTE, whilst an increased risk of VTE immediately following endocrine therapy is restricted to Tamoxifen

Transparent Meta-Analysis: Does Aging Spare Prospective Memory with Focal vs. Non-Focal Cues?

Background: Prospective memory (ProM) is the ability to become aware of a previously-formed plan at the right time and place. For over twenty years, researchers have been debating whether prospective memory declines with aging or whether it is spared by aging and, most recently, whether aging spares prospective memory with focal vs. non-focal cues. Two recent meta-analyses examining these claims did not include all relevant studies and ignored prevalent ceiling effects, age confounds, and did not distinguish between prospective memory subdomains (e.g., ProM proper, vigilance, habitual ProM) (see Uttl, 2008, PLoS ONE). The present meta-analysis focuses on the following questions: Does prospective memory decline with aging? Does prospective memory with focal vs. non-focal cues decline with aging? Does the size of age-related declines with focal vs. non-focal cues vary across ProM subdomains? And are age-related declines in ProM smaller than agerelated declines in retrospective memory? Methods and Findings: A meta-analysis of event-cued ProM using data visualization and modeling, robust count methods, and conventional meta-analysis techniques revealed that first, the size of age-related declines in ProM with both focal and non-focal cues are large. Second, age-related declines in ProM with focal cues are larger in ProM proper and smaller in vigilance. Third, age-related declines in ProM proper with focal cues are as large as age-related declines in recall measures of retrospective memory