Induced CNS expression of CXCL1 augments neurologic disease in a murine model of multiple sclerosis via enhanced neutrophil recruitment.

Increasing evidence points to an important role for neutrophils in participating in the pathogenesis of the human demyelinating disease MS and the animal model EAE. Therefore, a better understanding of the signals controlling migration of neutrophils as well as evaluating the role of these cells in demyelination is important to define cellular components that contribute to disease in MS patients. In this study, we examined the functional role of the chemokine CXCL1 in contributing to neuroinflammation and demyelination in EAE. Using transgenic mice in which expression of CXCL1 is under the control of a tetracycline-inducible promoter active within glial fibrillary acidic protein-positive cells, we have shown that sustained CXCL1 expression within the CNS increased the severity of clinical and histologic disease that was independent of an increase in the frequency of encephalitogenic Th1 and Th17 cells. Rather, disease was associated with enhanced recruitment of CD11b+ Ly6G+ neutrophils into the spinal cord. Targeting neutrophils resulted in a reduction in demyelination arguing for a role for these cells in myelin damage. Collectively, these findings emphasize that CXCL1-mediated attraction of neutrophils into the CNS augments demyelination suggesting that this signaling pathway may offer new targets for therapeutic intervention

Sea-ice response to climate change in the Bering Sea during the Mid-Pleistocene Transition

This is the final version. Available on open access from Elsevier via the DOI in this recordData availability: All data presented in this paper is available in the Supplementary Materials.Sea-ice is believed to be an important control on climatic changes through the Mid-Pleistocene Transition (MPT; 0.6–1.2 Ma). However, the low resolution/short timescale of existing reconstructions prevents a full evaluation of these dynamics. Here, diatom assemblages from the Bering Sea are used to investigate sea-ice evolution on millennial timescales. We find that sea-ice was primarily controlled by ice-sheet/sea level fluctuations that modulated warm water flow into the Bering Sea. Facilitated by an amplified Walker circulation, sea-ice expansion began at ∼1.05 Ma with a step-increase during the 900 kyr event. Maximal pack ice was simultaneous with glacial maxima, suggesting sea-ice was responding to, rather than modulating ice-sheet dynamics, as proposed by the sea-ice switch hypothesis. Significant pack ice, coupled with Bering Strait closure at 0.9 Ma, indicates that brine rejection played an integral role in the glacial expansion/deglacial collapse of intermediate waters during the MPT, regulating subarctic ocean-atmospheric exchanges of CO2.Natural Environment Research Council (NERC)British Geological Surve

Silicic acid cycling in the Bering Sea during the Mid‐Pleistocene Transition

This is the final version. Available from Wiley via the DOI in this record. Data Availability Statement: The data presented in this paper are stored in the Pangaea data repository (https://doi.pangaea.de/10.1594/ PANGAEA.933139)The rate of deep-ocean carbon burial is considered important for modulating glacial-interglacial atmospheric CO2 concentrations and global climate during the Quaternary. It has been suggested that glacial iron fertilization and increased efficiency of the biological pump in the Southern Ocean since the Mid-Pleistocene Transition (MPT) was key in lowering atmospheric pCO2 and facilitating rapid land ice accumulation. There is growing evidence that a similar mechanism may have existed in the subarctic Pacific Ocean, although this has not yet been assessed. Here, the silicon isotope composition of diatoms (δ30Sidiatom) from the Bering Sea upwelling region is used to assess the role of nutrient cycling on the subarctic Pacific biological pump during the MPT. Results show that during and after the “900 kyr event,” the high productivity green belt zone was characterized by low silicic acid utilization but high supply, coincident with the dominance of diatom resting spores. We posit that as nutrient upwelling was suppressed following pack ice growth and expansion of glacial North Pacific Intermediate Water (GNPIW), primary productivity became nitrate-limited and enhanced opal remineralization caused a relative increase in silicic acid supply. However, preferential preservation and higher cellular carbon content of diatom resting spores, as well as increased supply of iron from expanded sea ice, likely sustained the net efficiency of the Bering Sea biological pump through the MPT. Remnant iron and silicic acid may also have propagated into the lower subarctic Pacific Ocean through GNPIW, aiding a regionally efficient biological pump at 900 kyr and during post-MPT glacials.Natural Environment Research CouncilBritish Geological SurveyNatural Environment Research CouncilNatural Environment Research Counci

Reduced upwelling of nutrient and carbon-rich water in the subarctic Pacific during the Mid-Pleistocene Transition

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordReduction in atmosphericpCO2has been hypothesised as a causal mechanism for the Mid-Pleistocene Transition(MPT), which saw global cooling and increased duration of glacials between 0.6 and 1.2 Ma. Sea ice-modulatedhigh latitude upwelling and ocean-atmospheric CO2flux is considered a potential mechanism forpCO2decline,although there are no long-term nutrient upwelling records from high latitude regions to test this hypothesis.Using nitrogen isotopes and opal mass accumulation rates from 0 to 1.2 Ma, we calculate a continuous highresolution nutrient upwelling index for the Bering Sea and assess possible changes to regional CO2fluxes and tothe relative control of sea ice, sea level and glacial North Pacific Intermediate Water (GNPIW) on deep mixingand nutrient upwelling in the region. Wefind nutrient upwelling in the Bering Sea correlates with global icevolume and air temperature throughout the study interval. From ~1 Ma, and particularly during the 900 kaevent, suppressed nutrient upwelling would have lowered oceanicfluxes of CO2to the atmosphere supporting areduction in globalpCO2during the MPT. This timing is consistent with a pronounced increase in sea ice duringthe early Pleistocene and restriction offlow through the Bering Strait during glacials after ~900 ka, both ofwhich would have acted to suppress upwelling. We suggest that sea-level modulated GNPIW expansion duringglacials after 900 ka was the dominant control on subarctic Pacific upwelling strength during the mid-latePleistocene, while sea ice variability played a secondary role.Natural Environment Research Council (NERC

Assessment of bias in carbon isotope composition of organic leaf matter due to pre‐analysis milling methods

Rationale Stable isotope analysis of leaf material has many applications including assessment of plant water-use efficiency and paleoclimatology. To facilitate interpretations of small shifts in the carbon isotope composition (δ13C) of leaves, accurate and repeatable results are required. Pre-sample homogenisation is essential to ensure a representative sample is analysed, but can also introduce error. Methods We investigate how different grinding methods (freezer-milling and ball-milling) affect the carbon content and δ13C of tree leaves from a wetland in Queensland, Australia, commenting on how increased temperature, sample contamination, sample loss, or poor homogenisation may impact results. Results No alteration of leaf δ13C is observed due to different milling methods, although there may be a significant increase in %C of samples processed using ball-milling. Conclusions We suggest %C variability is possibly due to contamination from abraded plastic vials or insufficient homogenisation during ball-milling, with no significant impact on δ13C. Overall, we suggest that intermittent ball-milling may be the best solution to reduce costs, preparation time and use of liquid nitrogen, aiming to achieve complete homogenisation using the shortest possible duration of milling

Closure of the Bering Strait caused Mid-Pleistocene Transition cooling

This is the final version. Available from Springer Nature via the DOI in this record. Data availability: All data generated during this study supporting its findings are available within the paper and the supplementary information.The Mid-Pleistocene Transition (MPT) is characterised by cooling and lengthening glacial cycles from 600–1200 ka, thought to be driven by reductions in glacial CO2 in particular from ~900 ka onwards. Reduced high latitude upwelling, a process that retains CO2 within the deep ocean over glacials, could have aided drawdown but has so far not been constrained in either hemisphere over the MPT. Here, we find that reduced nutrient upwelling in the Bering Sea, and North Pacific Intermediate Water expansion, coincided with the MPT and became more persistent at ~900 ka. We propose reduced upwelling was controlled by expanding sea ice and North Pacific Intermediate Water formation, which may have been enhanced by closure of the Bering Strait. The regional extent of North Pacific Intermediate Water across the subarctic northwest Pacific would have contributed to lower atmospheric CO2 and global cooling during the MPT.Natural Environment Research Council (NERC)National Research Foundation of Kore

Factors affecting consistency and accuracy in identifying modern macroperforate planktonic foraminifera

Planktonic foraminifera are widely used in biostratigraphic, palaeoceanographic and evolutionary studies, but the strength of many study conclusions could be weakened if taxonomic identifications are not reproducible by different workers. In this study, to assess the relative importance of a range of possible reasons for among-worker disagreement in identification, 100 specimens of 26 species of macroperforate planktonic foraminifera were selected from a core-top site in the subtropical Pacific Ocean. Twenty-three scientists at different career stages – including some with only a few days experience of planktonic foraminifera – were asked to identify each specimen to species level, and to indicate their confidence in each identification. The participants were provided with a species list and had access to additional reference materials. We use generalised linear mixed-effects models to test the relevance of three sets of factors in identification accuracy: participant-level characteristics (including experience), species-level characteristics (including a participant’s knowledge of the species) and specimen-level characteristics (size, confidence in identification). The 19 less experienced scientists achieve a median accuracy of 57 %, which rises to 75 % for specimens they are confident in. For the 4 most experienced participants, overall accuracy is 79 %, rising to 93 % when they are confident. To obtain maximum comparability and ease of analysis, everyone used a standard microscope with only 35× magnification, and each specimen was studied in isolation. Consequently, these data provide a lower limit for an estimate of consistency. Importantly, participants could largely predict whether their identifications were correct or incorrect: their own assessments of specimen-level confidence and of their previous knowledge of species concepts were the strongest predictors of accuracy

Coupled climate and subarctic Pacific nutrient upwelling over the last 850,000 years

High latitude deep water upwelling has the potential to control global climate over glacial timescales through the biological pump and ocean-atmosphere CO2 exchange. However, there is currently a lack of continuous long nutrient upwelling records with which to assess this mechanism. Here we present geochemical proxy records for nutrient upwelling and glacial North Pacific Intermediate Water (GNPIW) formation in the Bering Sea over the past 850 kyr, which demonstrates that glacial periods were characterised by reduced nutrient upwelling, when global atmospheric CO2 and temperature were also lowered. We suggest that glacial expansion of sea ice in the Bering Sea, and the simultaneous expansion of low nutrient GNPIW, inhibited vertical mixing and nutrient supply across the subarctic Pacific Ocean. Our findings lend support to the suggestion that high latitude sea ice and the resultant intermediate water formation, modulated deep water upwelling and ocean-atmosphere CO2 exchange on glacial-interglacial timescales

Induced CNS expression of CXCL1 augments neurologic disease in a murine model of multiple sclerosis via enhanced neutrophil recruitment.

Increasing evidence points to an important role for neutrophils in participating in the pathogenesis of the human demyelinating disease MS and the animal model EAE. Therefore, a better understanding of the signals controlling migration of neutrophils as well as evaluating the role of these cells in demyelination is important to define cellular components that contribute to disease in MS patients. In this study, we examined the functional role of the chemokine CXCL1 in contributing to neuroinflammation and demyelination in EAE. Using transgenic mice in which expression of CXCL1 is under the control of a tetracycline-inducible promoter active within glial fibrillary acidic protein-positive cells, we have shown that sustained CXCL1 expression within the CNS increased the severity of clinical and histologic disease that was independent of an increase in the frequency of encephalitogenic Th1 and Th17 cells. Rather, disease was associated with enhanced recruitment of CD11b+ Ly6G+ neutrophils into the spinal cord. Targeting neutrophils resulted in a reduction in demyelination arguing for a role for these cells in myelin damage. Collectively, these findings emphasize that CXCL1-mediated attraction of neutrophils into the CNS augments demyelination suggesting that this signaling pathway may offer new targets for therapeutic intervention