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Insoluble particles in ice cores record signatures of past climate parameters like vegetation dynamics, volcanic activity, and aridity. For some of them, the analytical detection relies on intensive bench microscopy investigation and requires dedicated sample preparation steps. Both are laborious, require in-depth knowledge, and often restrict sampling strategies. To help overcome these limitations, we present a framework based on flow imaging microscopy coupled to a deep neural network for autonomous image classification of ice core particles. We train the network to classify seven commonly found classes, namely mineral dust, felsic and mafic (basaltic) volcanic ash grains (tephra), three species of pollen (Corylus avellana, Quercus robur, Quercus suber), and contamination particles that may be introduced onto the ice core surface during core handling operations. The trained network achieves 96.8 % classification accuracy at test time. We present the system's potential and its limitations with respect to the detection of mineral dust, pollen grains, and tephra shards, using both controlled materials and real ice core samples. The methodology requires little sample material, is non-destructive, fully reproducible, and does not require any sample preparation procedures. The presented framework can bolster research in the field by cutting down processing time, supporting human-operated microscopy, and further unlocking the paleoclimate potential of ice core records by providing the opportunity to identify an array of ice core particles. Suggestions for an improved system to be deployed within a continuous flow analysis workflow are also presented. [ABSTRACT FROM AUTHOR]

Insoluble particles in ice cores record signatures of past climate parameters like vegetation, volcanic activity or aridity. Their analytical detection depends on intensive bench microscopy investigation and requires dedicated sample preparation steps. Both are laborious, require in-depth knowledge and often restrict sampling strategies. To help overcome these limitations, we present a framework based on Flow Imaging Microscopy coupled to a deep neural network for autonomous image classification of ice core particles. We train the network to classify 7 commonly found classes: mineral dust, felsic and basaltic volcanic ash (tephra), three species of pollen (Corylus avellana, Quercus robur, Quercus suber) and contamination particles that may be introduced onto the ice core surface during core handling operations. The trained network achieves 96.8 % classification accuracy at test time. We present the system’s potentials and limitations with respect to the detection of mineral dust, pollen grains and tephra shards, using both controlled materials and real ice core samples. The methodology requires little sample material, is non destructive, fully reproducible and does not require any sample preparation step. The presented framework can bolster research in the field, by cutting down processing time, supporting human-operated microscopy and further unlocking the paleoclimate potential of ice core records by providing the opportunity to identify an array of ice core particles. Suggestions for an improved system to be deployed within a continuous flow analysis workflow are also presented. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2009.05.569 Byline: Katherine Whalley, Stefanie Gogel, Sigrun Lange, Patrizia Ferretti Keywords: Chick; Development; Doublecortin; Glast; Injury; Neurogenesis; NeuN; Radial glia; Regeneration; Spinal cord; Transitin Abstract: The chick spinal cord can regenerate following injury until advanced developmental stages. It is conceivable that changes in stem/progenitor cell plasticity contribute to the loss of this capacity, which occurs around E13. We investigated the contribution of proliferation, phenotypic changes in radial glia progenitors, and neurogenesis to spinal cord regeneration. There was no early up-regulation of markers of gliogenic radial glia after injury either at E11 or E15. In contrast, increased proliferation in the grey matter and up-regulation of transitin expression following injury at E11, but not E15, suggested high levels of plasticity within the E11 spinal cord progenitor population that are lost by later stages. Changes in neural progenitors with development were also supported by a higher neurosphere forming ability at E11 than at E15. Co-labelling with doublecortin and neuron-specific markers and BrdU in spinal cord sections and dissociated cells showed that neurogenesis is an ongoing process in E11 chick spinal cords. This neurogenesis appeared to be complete by E15. Our findings demonstrate that the regeneration-competent chick spinal cord is less mature and more plastic than previously believed, which may contribute to its favourable response to injury, and suggest a role for neurogenesis in maintaining regenerative capacity. Author Affiliation: Developmental Biology Unit, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK Article History: Received 7 November 2008; Revised 26 May 2009; Accepted 27 May 2009

Exposure to environmental pollutants and endogenous metabolites that induce aryl hydrocarbon receptor (AhR) expression has been suggested to affect cognitive development and, particularly in boys, also motor function. As current knowledge is based on epidemiological and animal studies, in vitro models are needed to better understand the effects of these compounds in the human nervous system at the molecular level. Here, we investigated expression of AhR pathway components and how they are regulated by AhR ligands in human motor neurons. Motor neurons generated from human induced pluripotent stem cells (hiPSCs) were characterized at the molecular level and by electrophysiology. mRNA levels of AhR target genes, CYP1A1 and CYP1B1 (cytochromes P450 1A1/1B1), and AhR signaling components were monitored in hiPSCs and in differentiated neurons following treatment with AhR ligands, 2,3,7,8,-tetrachlodibenzo-p-dioxin (TCDD), L-kynurenine (L-Kyn), and kynurenic acid (KA), by RT-qPCR. Changes in AhR cellular localization and CYP1A1 activity in neurons treated with AhR ligands were also assessed. The neurons we generated express motor neuron-specific markers and are functional. Transcript levels of CYP1B1, AhR nuclear translocators (ARNT1 and ARNT2) and the AhR repressor (AhRR) change with neuronal differentiation, being significantly higher in neurons than hiPSCs. In contrast, CYP1A1 and AhR transcript levels are slightly lower in neurons than in hiPSCs. The response to TCDD treatment differs in hiPSCs and neurons, with only the latter showing significant CYP1A1 up-regulation. In contrast, TCDD slightly up-regulates CYP1B1 mRNA in hiPSCs, but downregulates it in neurons. Comparison of the effects of different AhR ligands on AhR and some of its target genes in neurons shows that L-Kyn and KA, but not TCDD, regulate AhR expression and differently affect CYP1A1 and CYP1B1 expression. Finally, although TCDD does not significantly affect AhR transcript levels, it induces AhR protein translocation to the nucleus and increases CYP1A1 activity. This is in contrast to L-Kyn and KA, which either do not affect or reduce, respectively, CYP1A1 activity. Expression of components of the AhR signaling pathway are regulated with neuronal differentiation and are differently affected by TCDD, suggesting that pluripotent stem cells might be less sensitive to this toxin than neurons. Crucially, AhR signaling is affected differently by TCDD and other AhR ligands in human motor neurons, suggesting that they can provide a valuable tool for assessing the impact of environmental pollutants. [ABSTRACT FROM AUTHOR]

Author(s): Aradhna Tripati (corresponding author) [1]; Jan Backman [2]; Henry Elderfield [1]; Patrizia Ferretti [1] A change in the state of Earth's ocean-climate system occurred at the end of the [...]

Olfactory ensheathing cells (OECs) are specialized glia cells of the olfactory system that support the continual regeneration of olfactory neurons throughout adulthood. Owing to their pro-regenerative properties, OECs have been transplanted in animal models of spinal cord injuries (SCI) and trialed in clinical studies on SCI patients. Although these studies have provided convincing evidence to support the continued development of OEC transplantation as a treatment option for the repair of SCI, discrepancies in the reported outcome has shown that OEC transplantation requires further improvement. Much of the variability in the reparative potential of OEC transplants is due to the variations in the cell composition of transplants between studies. As a result, the optimal cell preparation is currently a subject of debate. Here we review, the characterization as well as the effect of the cell composition of olfactory cell transplantation on therapeutic outcome in SCI. Firstly, we summarize and review the cell composition of olfactory cell preparations across the different species studied prior to transplantation. Since the purity of cells in olfactory transplants might affect the study outcome we also examine the effect of the proportions of OECs and the different cell types identified in the transplant on neuroregeneration. Finally, we consider the effect of the yield of cells on neuroregeneration by assessing the cell dose of transplants on therapeutic outcome. [ABSTRACT FROM AUTHOR]

Byline: Paul Hunt (a ), Jonathan D.W. Clarke (a)(a ), Paul Buxton (a ), Patrizia Ferretti (a ), Peter Thorogood (a ) Abstract: The extent to which the spatial organisation of craniofacial development is due to intrinsic properties of the neural crest is at present unclear. There is some experimental evidence supporting the concept of a prepattern established within crest while contiguous with the neural plate. In experiments in which the neural tube and premigratory crest are relocated within the branchial region, crest cells retain patterns of gene expression appropriate for their position of origin after migration into the branchial arches, resulting in skeletal abnormalities. But in apparent conflict with these findings, when crest is rerouted by late deletion of adjacent crest, infilling crest alters its pattern of gene expression to match its new location, and a normal facial skeleton results. In order to reconcile these findings and thus identify processes of relevance to the course of normal development, we have performed a series of neural tube and crest rotations producing a more extensive reorganisation of cephalic crest than has been previously described. Lineage analysis using DiI labelling of crest derived from the rotated hindbrain reveals that crest does not migrate into the branchial arch it would have colonised in normal development, rather it simply populates the nearest available branchial arches. We also find that crest adjacent to the grafted region contributes to a greater number of branchial arches than it would in normal development, resulting in branchial arches containing mixed cell populations not occurring in normal development. We find that after exchange of first and third arch crest by rotation of r1-7, crest alters its expression of hoxa-2 and hoxa-3 to match its new location within the embryo resulting in the reestablishment of the normal branchial arch Hox code. A facial skeleton in which all the normal components are present, with some additional ectopic first arch structures, is formed in this situation. In contrast, when second and third arch crest are exchanged by rotation of r3 to 7, ectopic Hox gene expression is stable, resulting in the persistence of an abnormal branchial arch Hox code and extensive defects in the hyoid skeleton. We suggest that the intrinsic properties of crest have an effect on the spatial organisation of structures derived from the branchial arches, but that exposure to increasingly novel environments within the branchial region or 'community effects' within mixed populations of cells can result in alterations to crest Hox code and morphogenetic fate. In both classes of operation we find that there is a tight link between the resulting branchial arch Hox code and a particular skeletal morphology. Author Affiliation: (a ) Developmental Biology Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, United Kingdom (a) Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom Article History: Received 28 May 1997; Accepted 9 January 1998

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene (HTT). Disease progression is characterized by the loss of vulnerable neuronal populations within the striatum. A consistent phenotype across HD models is disruption of nucleocytoplasmic transport and nuclear pore complex (NPC) function. Here we demonstrate that high content imaging is a suitable method for detecting mislocalization of lamin-B1, RAN and RANGAP1 in striatal neuronal cultures thus allowing a robust, unbiased, highly powered approach to assay nuclear pore deficits. Furthermore, nuclear pore deficits extended to the selectively vulnerable DARPP32 + subpopulation neurons, but not to astrocytes. Striatal neuron cultures are further affected by changes in gene and protein expression of RAN, RANGAP1 and lamin-B1. Lowering total HTT using HTT- targeted anti-sense oligonucleotides partially restored gene expression, as well as subtly reducing mislocalization of proteins involved in nucleocytoplasmic transport. This suggests that mislocalization of RAN, RANGAP1 and lamin-B1 cannot be normalized by simply reducing expression of CAG-expanded HTT in the absence of healthy HTT protein. [ABSTRACT FROM AUTHOR]

Abstract Background Although fibroblast growth factor (Fgf) signalling plays crucial roles in several developing and mature tissues, little information is currently available on expression of Fgf2 during early choroid plexus development and whether Fgf2 directly affects the behaviour of the choroid plexus epithelium (CPe). The purpose of this study was to investigate expression of Fgf2 in rodent and human developing CPe and possible function of Fgf2, using in vitro models. The application of Fgf2 to brain in vivo can affect the whole tissue, making it difficult to assess specific responses of the CPe. Methods Expression of Fgf2 was studied by immunohistochemistry in rodent and human embryonic choroid plexus. Effects of Fgf2 on growth, secretion, aggregation and gene expression was investigated using rodent CPe vesicles, a three-dimensional polarized culture model that closely mimics CPe properties in vivo, and rodent CPe monolayer cultures. Results Fgf2 was present early in development of the choroid plexus both in mouse and human, suggesting the importance of this ligand in Fgf signalling in the developing choroid plexus. Parallel analysis of Fgf2 expression and cell proliferation during CP development suggests that Fgf2 is not involved in CPe proliferation in vivo. Consistent with this observation is the failure of Fgf2 to increase proliferation in the tri-dimensional vesicle culture model. The CPe however, can respond to Fgf2 treatment, as the diameter of CPe vesicles is significantly increased by treatment with this growth factor. We show that this is due to an increase in cell aggregation during vesicle formation rather than increased secretion into the vesicle lumen. Finally, Fgf2 regulates expression of the CPe-associated transcription factors, Foxj1 and E2f5, whereas transthyretin, a marker of secretory activity, is not affected by Fgf2 treatment. Conclusion Fgf2 expression early in the development of both human and rodent choroid plexus, and its ability to modulate behaviour and gene expression in CPe, supports the view that Fgf signalling plays a role in the maintenance of integrity and function of this specialized epithelium, and that this role is conserved between rodents and humans.

During the Late Pleistocene–Holocene, the Ross Sea Ice Shelf exhibited strong spatial variability in relation to the atmospheric and oceanographic climatic variations. Despite being thoroughly investigated, the timing of the ice sheet retreat from the outer continental shelf since the Last Glacial Maximum (LGM) still remains controversial, mainly due to a lack of sediment cores with a robust chronostratigraphy. For this reason, the recent recovery of sediments containing a continuous occurrence of calcareous foraminifera provides the important opportunity to create a reliable age model and document the early deglacial phase in particular. Here we present a multiproxy study from a sediment core collected at the Hallett Ridge (1800 m of depth), where significant occurrences of calcareous planktonic and benthic foraminifera allow us to document the first evidence of the deglaciation after the LGM at about 20.2 ka. Our results suggest that the co-occurrence of large Neogloboquadrina pachyderma tests and abundant juvenile forms reflects the beginning of open-water conditions and coverage of seasonal sea ice. Our multiproxy approach based on diatoms, silicoflagellates, carbon and oxygen stable isotopes on N. pachyderma , sediment texture, and geochemistry indicates that abrupt warming occurred at approximately 17.8 ka, followed by a period of increasing biological productivity. During the Holocene, the exclusive dominance of agglutinated benthic foraminifera suggests that dissolution was the main controlling factor on calcareous test accumulation and preservation. Diatoms and silicoflagellates show that ocean conditions were variable during the middle Holocene and the beginning of the Neoglacial period at around 4 ka. In the Neoglacial, an increase in sand content testifies to a strengthening of bottom-water currents, supported by an increase in the abundance of the tycopelagic fossil diatom Paralia sulcata transported from the coastal regions, while an increase in ice-rafted debris suggests more glacial transport by icebergs. [ABSTRACT FROM AUTHOR]

The global thermohaline circulation plays a major role in regulating global climate, driven by the formation of North Atlantic Deep Water (NADW). ODP Site 1063 on the Bermuda Rise, at the interface of NADW and Southern Ocean‐sourced water, appears an ideal location to study the relationships between ocean circulation and climate. This study reports Nd isotope ratios at Site 1063 that extend to ~1 Ma. The data show Nd isotope values during portions of interglacials that are much lower than modern NADW. However, interglacial Nd isotope values at Site 607, located within the core of NADW, off the abyssal seafloor in the North Atlantic, are consistently similar to modern NADW. In contrast to glacial values, we infer that interglacial Nd isotopes at Site 1063 are not representative of NADW and do not solely record water mass mixing. We conclude that the low Ndisotope ratios reflect regional particle‐seawater exchange as a consequence of input of freshly ground bedrock from the Canadian shield, which is eroded into the North Atlantic during major ice sheet retreats. The result is a deep, thin, and regionally constrained layer of seawater tagged with this anomalous low Nd isotope signature that is unrepresentative of the Atlantic Meridional Overturning Circulation (AMOC). We suggest that a benthic nepheloid layer, whose development is linked to the behavior of a deep‐recirculating gyre system, regulated by the interaction between the Gulf Stream and the deep western boundary current, facilitates the periodic masking of the Nd isotope signature of the North Atlantic AMOC end‐member in this region at these depths. Key Points: Glacial‐interglacial changes at the deep Bermuda Rise during the Middle and early Lower Pleistocene were recorded with εNdGlacial εNd values in the deep Bermuda Rise record the AMOC, interglacial εNd values do notDynamic benthic nepheloid layers temporally mask εNd at the deep Bermuda Rise during parts of interglacials [ABSTRACT FROM AUTHOR]

The total syntheses of three C37 methyl‐alkenones with different degrees of unsaturation and of their 13C‐labelled analogues from commercially available starting materials are presented herein for the first time. These molecules are important to improve the reliability of the measurements and reconstructions of the sea surface temperature and salinity. [ABSTRACT FROM AUTHOR]

Highlights • Strongest expansion of the Mediterranean forest of the last 800,000 yr. • Maximum summer warmth in SW Iberia during the peak of the cool MIS 17. • Pronounced two-step northward shift of the westerlies centered at ∼693 ka. • Increasing arrival of moisture at northern high latitudes at the end of MIS 17. • Important contribution of the westerlies in explaining the strong 100-kyr ice cycles. Abstract The MIS 17 interglacial, ∼715–675 ka, marks the end of the Mid-Pleistocene Transition as intensified, long and asymmetrical 100-kyr ice age cycles became eminently established. Increasing arrival of moisture to the Northern Hemisphere high latitudes, resulting from the northwestward migration of the Subpolar Front and the intensification of the Norwegian Greenland Seas (NGS) convection, has been put forward to explain the emergence of this quasi-periodic 100-kyr cycle. However, testing this hypothesis is problematic with the available North Atlantic precipitation data. Here we present new pollen-based quantitative seasonal climate reconstructions from the southwestern Iberian margin that track changes in the position and intensity of the westerlies. Our data compared to changes in North Atlantic deep and surface water conditions show that MIS 17 interglacial was marked by three major changes in the direction and strength of the westerlies tightly linked to oceanographic changes. In particular, we report here for the first time a drastic two-steps northward shift of the westerlies centered at ∼693 ka that ended up with the sustained precipitation over southern European. This atmospheric reorganization was associated with northwestward migration of the Subpolar Front, strengthening of the NGS deep water formation and cooling of the western North Atlantic region. This finding points to the substantial arrival of moisture to the Northern Hemisphere high latitudes at the time of the decrease in summer energy and insolation contributing to the establishment of strong 100-kyr cycles. [ABSTRACT FROM AUTHOR]

The Mg/Ca molar ratio in foraminiferal calcite accumulated in marine sea sediments is a well-established proxy of ancient ocean temperatures. Magnesium is three orders of magnitude less abundant than Ca (0.5–10 mmol per mol), and the relationship between their ratio and sea surface temperature is exponential. Consequently, the reliability of the calculated temperature depends dramatically on the accuracy and precision of measurements, and the comparability of the results is heavily impacted by standardisation of the analytical methodology. Here, we extended the applicability of inductively coupled plasma-mass spectrometry for the determination of Mg/Ca in foraminifera, by implementing an automated on-line dual-dilution manifold combined with mixed instrumental acquisition modes (no gas-H2 reaction), and the use of on-line Sc addition as an internal standard. This allowed the independent acquisition of Mg and Ca at their optimised working concentrations under instrumental conditions that were free of significant spectral interferences. Matrix effects and instrumental drift are effectively mitigated, as supported by comparison with results from on-line isotope dilution analysis. Memory effects were minimized, and only 20 μg of calcitic material was required for analysis. Automation of the setup allowed dual dilution analysis of samples without any significant increase in preparation or analysis time. The system is easily upgradable to multiple on-line dilutions and multi-elemental ratios. The method was found to be accurate over the wide range of Mg/Ca values (from 0.8 to 5.7 mmol mol−1) present in the certified reference materials BAM-RS3, ECRM-752-1 and CMSI-1767, with repeatability in the range of 0.3–0.7% and an instrumental LOD of 0.6 nmol mol−1. Test application to five samples from the Integrated Ocean Drilling Program Site U1313 gave results consistent with literature values. [ABSTRACT FROM AUTHOR]