Changes in biological productivity along the northwest African margin over the past 20,000 years

Author Posting. © American Geophysical Union, 2016. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 31 (2016): 185–202, doi:10.1002/2015PA002862.The intertropical convergence zone and the African monsoon system are highly sensitive to climate forcing at orbital and millennial timescales. Both systems influence the strength and direction of the trade winds along northwest Africa and thus directly impact coastal upwelling. Sediment cores from the northwest African margin record upwelling-related changes in biological productivity connected to changes in regional and hemispheric climate. We present records of 230Th-normalized biogenic opal and Corg fluxes using a meridional transect of four cores from 19°N–31°N along the northwest African margin to examine changes in paleoproductivity since the last glacial maximum. We find large changes in biogenic fluxes synchronous with changes in eolian fluxes calculated using end-member modeling, suggesting that paleoproductivity and dust fluxes were strongly coupled, likely linked by changes in wind strength. Opal and Corg fluxes increase at all sites during Heinrich Stadial 1 and the Younger Dryas, consistent with an overall intensification of the trade winds, and changes in the meridional flux gradient indicate a southward wind shift at these times. Biogenic fluxes were lowest, and the meridional flux gradients were weakest during the African Humid Period when the monsoon was invigorated due to precessional changes, with greater rainfall and weaker trade winds over northwest Africa. These results expand the spatial coverage of previous paleoproxy studies showing similar changes, and they provide support for modeling studies showing changes in wind strength and direction consistent with increased upwelling during abrupt coolings and decreased upwelling during the African Humid Period.NSF Grant Numbers: OCE-1103262, OCE-1030784, OCE-0402348; Center for Climate and Life2016-07-2

Efficient Bayesian inference for COM-Poisson regression models

COM-Poisson regression is an increasingly popular model for count data. Its main advantage is that it permits to model separately the mean and the variance of the counts, thus allowing the same covariate to affect in different ways the average level and the variability of the response variable. A key limiting factor to the use of the COM-Poisson distribution is the calculation of the normalisation constant: its accurate evaluation can be time-consuming and is not always feasible. We circumvent this problem, in the context of estimating a Bayesian COM-Poisson regression, by resorting to the exchange algorithm, an MCMC method applicable to situations where the sampling model (likelihood) can only be computed up to a normalisation constant. The algorithm requires to draw from the sampling model, which in the case of the COM-Poisson distribution can be done efficiently using rejection sampling. We illustrate the method and the benefits of using a Bayesian COM-Poisson regression model, through a simulation and two real-world data sets with different levels of dispersion

Novel chimerized IgA CD20 antibodies : Improving neutrophil activation against CD20-positive malignancies

ABSTRACT Current combination therapies elicit high response rates in B cell malignancies, often using CD20 antibodies as the backbone of therapy. However, many patients eventually relapse or develop progressive disease. Therefore, novel CD20 antibodies combining multiple effector mechanisms were generated. To study whether neutrophil-mediated destruction of B cell malignancies can be added to the arsenal of effector mechanisms, we chimerized a panel of five previously described murine CD20 antibodies to the human IgG1, IgA1 and IgA2 isotype. Of this panel, we assessed in vitro antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) and direct cell death induction capacity and studied the efficacy in two different in vivo mouse models. IgA antibodies outperformed IgG1 antibodies in neutrophil-mediated killing in vitro, both against CD20-expressing cell lines and primary patient material. In these assays, we observed loss of CD19 with both IgA and IgG antibodies. Therefore, we established a novel method to improve the assessment of B-cell depletion by CD20 antibodies by including CD24 as a stable cell marker. Subsequently, we demonstrated that only IgA antibodies were able to reduce B cell numbers in this context. Additionally, IgA antibodies showed efficacy in both an intraperitoneal tumor model with EL4 cells expressing huCD20 and in an adoptive transfer model with huCD20-expressing B cells. Taken together, we show that IgA, like IgG, can induce ADCC and CDC, but additionally triggers neutrophils to kill (malignant) B cells. We conclude that antibodies of the IgA isotype offer an attractive repertoire of effector mechanisms for the treatment of CD20-expressing malignancies.Peer reviewe

Characterization of human Fc alpha receptor transgenic mice: comparison of CD89 expression and antibody-dependent tumor killing between mouse strains

Since mice do not express a homologue of the human Fc alpha receptor (FcαRI or CD89), a transgenic mouse model was generated in four different backgrounds (C57BL/6, BALB/c, SCID and NXG) expressing the FcαRI under the endogenous human promoter. In this study, we describe previously unknown characteristics of this model, such as the integration site of the FCAR gene, the CD89 expression pattern in healthy male and female mice and in tumor-bearing mice, expression of myeloid activation markers and FcγRs and IgA/CD89-mediated tumor killing capacity. In all mouse strains, CD89 expression is highest in neutrophils, intermediate on other myeloid cells such as eosinophils and DC subsets and inducible on, among others, monocytes, macrophages and Kupffer cells. CD89 expression levels are highest in BALB/c and SCID, lower in C57BL/6 and lowest in NXG mice. Additionally, CD89 expression on myeloid cells is increased in tumor-bearing mice across all mouse strains. Using Targeted Locus Amplification, we determined that the hCD89 transgene has integrated in chromosome 4. Furthermore, we established that wildtype and hCD89 transgenic mice have a similar composition and phenotype of immune cells. Finally, IgA-mediated killing of tumor cells is most potent with neutrophils from BALB/c and C57BL/6 and less with neutrophils from SCID and NXG mice. However, when effector cells from whole blood are used, SCID and BALB/c are most efficient, since these strains have a much higher number of neutrophils. Overall, hCD89 transgenic mice provide a very powerful model to test the efficacy of IgA immunotherapy against infectious diseases and cancer

Anti-GD2 IgA kills tumors by neutrophils without antibody-associated pain in the preclinical treatment of high-risk neuroblastoma

BACKGROUND: The addition of monoclonal antibody therapy against GD2 to the treatment of high-risk neuroblastoma led to improved responses in patients. Nevertheless, administration of GD2 antibodies against neuroblastoma is associated with therapy-limiting neuropathic pain. This severe pain is evoked at least partially through complement activation on GD2-expressing sensory neurons. METHODS: To reduce pain while maintaining antitumor activity, we have reformatted the approved GD2 antibody ch14.18 into the IgA1 isotype. This novel reformatted IgA is unable to activate the complement system but efficiently activates leukocytes through the FcαRI (CD89). RESULTS: IgA GD2 did not activate the complement system in vitro nor induced pain in mice. Importantly, neutrophil-mediated killing of neuroblastoma cells is enhanced with IgA in comparison to IgG, resulting in efficient tumoricidal capacity of the antibody in vitro and in vivo. CONCLUSIONS: Our results indicate that employing IgA GD2 as a novel isotype has two major benefits: it halts antibody-induced excruciating pain and improves neutrophil-mediated lysis of neuroblastoma. Thus, we postulate that patients with high-risk neuroblastoma would strongly benefit from IgA GD2 therapy

Re-conceptualising Territorial Cohesion Through the Prism of Spatial Justice : Critical Perspectives on Academic and Policy Discourses

Peer reviewe

A novel low-cost, high-resolution camera system for measuring peat subsidence and water table dynamics

This is the final version. Available from Frontiers Media via the DOI in this record. DATA AVAILABILITY STATEMENT: The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Peatlands are highly dynamic systems, able to accumulate carbon over millennia under natural conditions, but susceptible to rapid subsidence and carbon loss when drained. Short-term, seasonal and long-term peat surface elevation changes are closely linked to key peatland attributes such as water table depth (WTD) and carbon balance, and may be measured remotely using satellite radar and LiDAR methods. However, field measurements of peat elevation change are spatially and temporally sparse, reliant on low-resolution manual subsidence pole measurements, or expensive sensor systems. Here we describe a novel, simple and low-cost image-based method for measuring peat surface motion and WTD using commercially available time-lapse cameras and image processing methods. Based on almost two years’ deployment of peat cameras across contrasting forested, burned, agricultural and oil palm plantation sites in Central Kalimantan, Indonesia, we show that the method can capture extremely high resolution (sub-mm) and high-frequency (sub-daily) changes in peat surface elevation over extended periods and under challenging environmental conditions. WTD measurements were of similar quality to commercially available pressure transducers. Results reveal dynamic peat elevation response to individual rain events, consistent with variations in WTD. Over the course of the relatively severe 2019 dry season, cameras in deep-drained peatlands recorded maximum peat shrinkage of over 8 cm, followed by partial rebound, leading to net annual subsidence of up to 5 cm. Sites with higher water tables, and where borehole irrigation was used to maintain soil moisture, had lower subsidence, suggesting potential to reduce subsidence through altered land-management. Given the established link between subsidence and CO2 emissions, these results have direct implications for the management of peatlands to reduce high current greenhouse gas (GHG) emissions. Camera-based sensors provide a simple, low-cost alternative to commercial elevation, WTD and GHG flux monitoring systems, suitable for deployment at scale, and in areas where existing approaches are impractical or unaffordable. If ground-based observations of peat motion can be linked to measured GHG fluxes and with satellite-based monitoring tools, this approach offers the potential for a large-scale peatland monitoring tool, suitable for identifying areas of active carbon loss, targeting climate change mitigation interventions, and evaluating intervention outcomes.United Kingdom Space Agency International Partnership ProgramBiotechnology and Biological Sciences Research CouncilNatural Environment Research CouncilNatural Environment Research Counci

A novel low-cost, high-resolution camera system for measuring peat subsidence and water table dynamics

Peatlands are highly dynamic systems, able to accumulate carbon over millennia under natural conditions, but susceptible to rapid subsidence and carbon loss when drained. Short-term, seasonal and long-term peat surface elevation changes are closely linked to key peatland attributes such as water table depth (WTD) and carbon balance, and may be measured remotely using satellite radar and LiDAR methods. However, field measurements of peat elevation change are spatially and temporally sparse, reliant on low-resolution manual subsidence pole measurements, or expensive sensor systems. Here we describe a novel, simple and low-cost image-based method for measuring peat surface motion and WTD using commercially available time-lapse cameras and image processing methods. Based on almost two years’ deployment of peat cameras across contrasting forested, burned, agricultural and oil palm plantation sites in Central Kalimantan, Indonesia, we show that the method can capture extremely high resolution (sub-mm) and high-frequency (sub-daily) changes in peat surface elevation over extended periods and under challenging environmental conditions. WTD measurements were of similar quality to commercially available pressure transducers. Results reveal dynamic peat elevation response to individual rain events, consistent with variations in WTD. Over the course of the relatively severe 2019 dry season, cameras in deep-drained peatlands recorded maximum peat shrinkage of over 8 cm, followed by partial rebound, leading to net annual subsidence of up to 5 cm. Sites with higher water tables, and where borehole irrigation was used to maintain soil moisture, had lower subsidence, suggesting potential to reduce subsidence through altered land-management. Given the established link between subsidence and CO2 emissions, these results have direct implications for the management of peatlands to reduce high current greenhouse gas (GHG) emissions. Camera-based sensors provide a simple, low-cost alternative to commercial elevation, WTD and GHG flux monitoring systems, suitable for deployment at scale, and in areas where existing approaches are impractical or unaffordable. If ground-based observations of peat motion can be linked to measured GHG fluxes and with satellite-based monitoring tools, this approach offers the potential for a large-scale peatland monitoring tool, suitable for identifying areas of active carbon loss, targeting climate change mitigation interventions, and evaluating intervention outcomes

Dietary intake and breast density in high-risk women: a cross-sectional study

Background Women with a family history of breast cancer may be at higher risk for breast cancer, but few previous studies evaluating diet and breast cancer have focused on such women. The objective of the present study was to determine whether diet, a modifiable risk factor, is related to breast density among women at high genetic risk for breast cancer. Methods Women with at least one first-degree or second-degree relative with breast cancer or ovarian cancer participating in the Fox Chase Cancer Center Family Risk Assessment Program completed health history and food frequency questionnaires and received standard screening mammograms. Cranial–caudal mammographic images were classified into the four Breast Imaging Reporting and Data System categories ranging from \u27entirely fatty\u27 to \u27extremely dense\u27. Logistic regression analysis using proportional odds models for polychotomous outcomes provided estimates of odds ratios for having a higher category versus a lower category of breast density. Results Among 157 high-risk women, breast density was inversely associated with vitamin D intake (odds ratio for third tertile versus first tertile, 0.5; 95% confidence interval, 0.2–1.0). In contrast, intakes above the median level for protein (odds ratio, 3.0; 95% confidence interval, 1.3–6.9) and above the median level for animal protein (odds ratio, 4.3; 95% confidence interval, 1.8–10.3) were associated with higher breast density, but only among women whose family history did not reflect a known familial cancer syndrome or a breast cancer predisposition gene. Conclusion For women with a strong family history that was not associated with known cancer syndromes, dietary factors may be associated with breast density, a strong predictor of breast cancer risk. Since women with strong family history are often very motivated to change their lifestyle habits, further studies are needed to confirm whether changes in diet will change the breast density and the subsequent onset of breast cancer in these women