Anxiolysis and recognition memory enhancement with long-term supplemental ascorbic acid (vitamin C) in normal rats: possible dose dependency and sex differences

To investigate a possible dose-response relationship and sex differences for anxiolytic and memory-enhancing effects of ascorbic acid (vitamin C), an adult PVG /c hooded rats were individually treated for 8 weeks with approximately 61, 114 or 160 mg/kg/ day of ascorbic acid in their drinking water. After their treatment, over 3 consecutive days they experienced a 5-min trial in an open field (OF) followed by a 5-min trial in an elevated plus maze (EPM), and then finally a 5-min novel object recognition (NOR) test in the OF. Dose-related anxiolytic effects were observed that to some extent depended on the measure of anxiety. In other words, anxiolytic effects were evident in higher frequencies of walking with 114 mg/kg and 61 mg/kg, higher frequencies of rearing and lower frequencies of grooming in the OF as well as more frequent occupation of the EPM open arms. Rats treated with 160 mg/kg explored a novel versus familiar object in the NOR test to a significantly greater extent than control rats thereby suggesting enhancement of their recognition memory. Overall, it appeared that the anxiolytic effects of ascorbic acid were more typical of the lowest dose, whereas memory enhancement appeared to be confined to the highest dose. While there were a number of significant sex differences, there was no evidence of differences between females and males in the effects of ascorbic acid

A survey of spinning test particle orbits in Kerr spacetime

We investigate the dynamics of the Papapetrou equations in Kerr spacetime. These equations provide a model for the motion of a relativistic spinning test particle orbiting a rotating (Kerr) black hole. We perform a thorough parameter space search for signs of chaotic dynamics by calculating the Lyapunov exponents for a large variety of initial conditions. We find that the Papapetrou equations admit many chaotic solutions, with the strongest chaos occurring in the case of eccentric orbits with pericenters close to the limit of stability against plunge into a maximally spinning Kerr black hole. Despite the presence of these chaotic solutions, we show that physically realistic solutions to the Papapetrou equations are not chaotic; in all cases, the chaotic solutions either do not correspond to realistic astrophysical systems, or involve a breakdown of the test-particle approximation leading to the Papapetrou equations (or both). As a result, the gravitational radiation from bodies spiraling into much more massive black holes (as detectable, for example, by LISA, the Laser Interferometer Space Antenna) should not exhibit any signs of chaos.Comment: Submitted to Phys. Rev. D. Follow-up to gr-qc/0210042. Figures are low-resolution in order to satisfy archive size constraints; a high-resolution version is available at http://www.michaelhartl.com/papers

Source of gold in Neoarchean orogenic-type deposits in the North Atlantic Craton, Greenland: Insights for a proto-source of gold in sub-seafloor

Given that gold (Au) mostly remained in the incipient Earth mantle until ca. 3.9–3.8 Ga, a “proto-source” of gold may have been present in the dominantly mafic crust precursor born through first-stage melting of the early Earth mantle. In south-westernmost Greenland, a fragment of the North Atlantic Craton is characterised by greenstone belts comprising mafic volcanic and magmatic rocks, and harzburgite cumulates that were emplaced at ca.3.0 Ga prograde amphibolite-facies metamorphic assemblages and caused local dissolution of arsenopyrite. During this retrograde tectono-metamorphic stage, in gold-rich shear zones, the Re- Os geochronometer in arsenopyrite was reset to a Neoarchean age while invisible gold was liberated and deposited as free gold with 2.66 Ga pyrite (Re-Os isochron ages). The initial Os isotope ratios of Neoarchean arsenopyrite ($^{187}$Os/$^{188}$Os$_{i}$ = 0.13 ± 0.02) and gold-bearing pyrite (0.12 ± 0.02) overlap with the estimated ($^{187}$Os/$^{188}$Os ratio of the Mesoarchean mantle (0.11 ± 0.01) and preclude contribution of radiogenic crustal Os from evolved lithologies in the accretionary arc complex, but instead, favour a local contribution in Os from basaltic rocks and serpentinised harzburgite protoliths by metamorphic fluids. Thus, the ca. 2.66 Ga lode gold mineralisation identified in the North Atlantic Craton may illustrate a gold endowment in shear zones in Earth’s stabilizing continental crust at the time of the 2.75–2.55 Ga Global Gold Event, through metamorphic upgrading of bulk gold which had originally been extracted from the Mesoarchean mantle and concentrated in hydrothermal arsenopyrite deposits in oceanic crust beneath the overall reduced Mesoarchean ocean

Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1

Considerable evidence implicates DISC1 as a susceptibility gene for multiple psychiatric diseases. DISC1 has been intensively studied at the molecular, cellular and behavioral level, but its role in regulating brain connectivity and brain network function remains unknown. Here, we utilize a set of complementary approaches to assess the functional brain network abnormalities present in mice expressing a truncated Disc1 gene (Disc1tr Hemi mice). Disc1tr Hemi mice exhibited hypometabolism in the prefrontal cortex (PFC) and reticular thalamus along with a reorganization of functional brain network connectivity that included compromised hippocampal–PFC connectivity. Altered hippocampal–PFC connectivity in Disc1tr Hemi mice was confirmed by electrophysiological analysis, with Disc1tr Hemi mice showing a reduced probability of presynaptic neurotransmitter release in the monosynaptic glutamatergic hippocampal CA1–PFC projection. Glutamate system dysfunction in Disc1tr Hemi mice was further supported by the attenuated cerebral metabolic response to the NMDA receptor (NMDAR) antagonist ketamine and decreased hippocampal expression of NMDAR subunits 2A and 2B in these animals. These data show that the Disc1 truncation in Disc1tr Hemi mice induces a range of translationally relevant endophenotypes underpinned by glutamate system dysfunction and altered brain connectivity

Mechanical heterogeneity in the bone microenvironment as characterised by atomic force microscopy

Bones are structurally heterogeneous organs with diverse functions that undergo mechanical stimuli across multiple length scales. Mechanical characterisation of the bone microenvironment is important for understanding how bones function in health and disease. Here we describe the mechanical architecture of cortical bone, the growth plate, metaphysis and marrow in fresh murine bones, probed using atomic force microscopy in physiological buffer. Both elastic and viscoelastic properties are found to be highly heterogeneous with moduli ranging over 3 to 5 orders of magnitude, both within and across regions. All regions include extremely soft areas, with moduli of a few Pascal and viscosities as low as tens Pa⋅s. Aging impacts the viscoelasticity of the bone marrow strongly but has limited effect on the other regions studied. Our approach provides the opportunity to explore the mechanical properties of complex tissues at the length scale relevant to cellular processes and how these impact on aging and disease

Rapid modification of the bone microenvironment following short-term treatment with Cabozantinib in vivo

Introduction: Bone metastasis remains incurable with treatment restricted to palliative care. Cabozantinib (CBZ) is targeted against multiple receptor tyrosine kinases involved in tumour pathobiology, including hepatocyte growth factor receptor (MET) and vascular endothelial growth factor receptor 2 (VEGFR-2). CBZ has demonstrated clinical activity in advanced prostate cancer with resolution of lesions visible on bone scans, implicating a potential role of the bone microenvironment as a mediator of CBZ effects. We characterised the effects of short-term administration of CBZ on bone in a range of in vivo models to determine how CBZ affects bone in the absence of tumour. Methods: Studies were performed in a variety of in vivo models including male and female BALB/c nude mice (age 6– 17-weeks). Animals received CBZ (30 mg/kg, 5× weekly) or sterile H2O control for 5 or 10 days. Effects on bone integrity (μCT), bone cell activity (PINP, TRAP ELISA), osteoblast and osteoclast number/mm trabecular bone surface, area of epiphyseal growth plate cartilage, megakaryocyte numbers and bone marrow composition were assessed. Effects of longer-term treatment (15-day & 6-week administration) were assessed in male NOD/SCID and beige SCID mice. Results: CBZ treatment had significant effects on the bone microenvironment, including reduced osteoclast and increased osteoblast numbers compared to control. Trabecular bone structure was altered after 8 administrations. A significant elongation of the epiphyseal growth plate, in particular the hypertrophic chondrocyte zone, was observed in all CBZ treated animals irrespective of administration schedule. Both male and female BALB/c nude mice had increased megakaryocyte numbers/mm2 tissue after 10-day CBZ treatment, in addition to vascular ectasia, reduced bone marrow cellularity and extravasation of red blood cells into the extra-vascular bone marrow. All CBZinduced effects were transient and rapidly lost following cessation of treatment. Conclusion: Short-term administration of CBZ induces rapid, reversible effects on the bone microenvironmentin vivo highlighting a potential role in mediating treatment responses

Gut microbiota composition is associated with environmental landscape in honey bees.

There is growing recognition that the gut microbial community regulates a wide variety of important functions in its animal hosts, including host health. However, the complex interactions between gut microbes and environment are still unclear. Honey bees are ecologically and economically important pollinators that host a core gut microbial community that is thought to be constant across populations. Here, we examined whether the composition of the gut microbial community of honey bees is affected by the environmental landscape the bees are exposed to. We placed honey bee colonies reared under identical conditions in two main landscape types for 6 weeks: either oilseed rape farmland or agricultural farmland distant to fields of flowering oilseed rape. The gut bacterial communities of adult bees from the colonies were then characterized and compared based on amplicon sequencing of the 16S rRNA gene. While previous studies have delineated a characteristic core set of bacteria inhabiting the honey bee gut, our results suggest that the broad environment that bees are exposed to has some influence on the relative abundance of some members of that microbial community. This includes known dominant taxa thought to have functions in nutrition and health. Our results provide evidence for an influence of landscape exposure on honey bee microbial community and highlight the potential effect of exposure to different environmental parameters, such as forage type and neonicotinoid pesticides, on key honey bee gut bacteria. This work emphasizes the complexity of the relationship between the host, its gut bacteria, and the environment and identifies target microbial taxa for functional analyses

Genetic Studies of Metabolomics Change After a Liquid Meal Illuminate Novel Pathways for Glucose and Lipid Metabolism

Humans spend the greater part of the day in a postprandial state. However, the genetic basis of postprandial blood measures is relatively uncharted territory. We examined the genetics of variation in concentrations of postprandial metabolites (t = 150 min) in response to a liquid mixed meal through genome-wide association studies (GWAS) performed in the Netherlands Epidemiology of Obesity (NEO) study (n = 5,705). The metabolite response GWAS identified an association between glucose change and rs10830963:G in the melatonin receptor 1B (beta [SE] -0.23 [0.03], P = 2.15 x 10(-19)). In addition, the ANKRD55 locus led by rs458741:C showed strong associations with extremely large VLDL (XXLVLDL) particle response (XXLVLDL total cholesterol: beta [SE] 0.17 [0.03], P = 5.76 x 10(-10); XXLVLDL cholesterol ester: beta [SE] 0.17 [0.03], P = 9.74 x 10(-10)), which also revealed strong associations with body composition and diabetes in the UK Biobank (P < 5 x 10(-8)). Furthermore, the associations between XXLVLDL response and insulinogenic index, HOMA-beta, Matsuda insulin sensitivity index, and HbA(1c) in the NEO study implied the role of chylomicron synthesis in diabetes (with false discovery rate-corrected q <0.05). To conclude, genetic studies of metabolomics change after a liquid meal illuminate novel pathways for glucose and lipid metabolism. Further studies are warranted to corroborate biological pathways of the ANKRD55 locus underlying diabetes.Functional Genomics of Systemic Disorder

Verbal working memory and functional large-scale networks in schizophrenia

The aim of this study was to test whether bilinear and nonlinear effective connectivity (EC) measures of working memory fMRI data can differentiate between patients with schizophrenia (SZ) and healthy controls (HC). We applied bilinear and nonlinear Dynamic Causal Modeling (DCM) for the analysis of verbal working memory in 16 SZ and 21 HC. The connection strengths with nonlinear modulation between the dorsolateral prefrontal cortex (DLPFC) and the ventral tegmental area/substantia nigra (VTA/SN) were evaluated. We used Bayesian Model Selection at the group and family levels to compare the optimal bilinear and nonlinear models. Bayesian Model Averaging was used to assess the connection strengths with nonlinear modulation. The DCM analyses revealed that SZ and HC used different bilinear networks despite comparable behavioral performance. In addition, the connection strengths with nonlinear modulation between the DLPFC and the VTA/SN area showed differences between SZ and HC. The adoption of different functional networks in SZ and HC indicated neurobiological alterations underlying working memory performance, including different connection strengths with nonlinear modulation between the DLPFC and the VTA/SN area. These novel findings may increase our understanding of connectivity in working memory in schizophrenia

Quantum cryptography using balanced homodyne detection

We report an experimental quantum key distribution that utilizes balanced homodyne detection, instead of photon counting, to detect weak pulses of coherent light. Although our scheme inherently has a finite error rate, it allows high-efficiency detection and quantum state measurement of the transmitted light using only conventional devices at room temperature. When the average photon number was 0.1, an error rate of 0.08 and "effective" quantum efficiency of 0.76 were obtained.Comment: Errors in the sentence citing ref.[20] are correcte