94 research outputs found
Surfactant control of gas transfer velocity along an offshore coastal transect: results from a laboratory gas exchange tank
Understanding the physical and biogeochemical controls of air–sea gas
exchange is necessary for establishing biogeochemical models for predicting
regional- and global-scale trace gas fluxes and feedbacks. To this end we
report the results of experiments designed to constrain the effect of
surfactants in the sea surface microlayer (SML) on the gas transfer velocity
(<i>k</i><sub>w</sub>; cm h<sup>−1</sup>), seasonally (2012–2013) along a 20 km
coastal transect (North East UK). We measured total surfactant activity (SA),
chromophoric dissolved organic matter (CDOM) and chlorophyll <i>a</i> (Chl <i>a</i>) in
the SML and in sub-surface water (SSW) and we evaluated corresponding
<i>k</i><sub>w</sub> values using a custom-designed air–sea gas exchange tank.
Temporal SA variability exceeded its spatial variability. Overall, SA varied
5-fold between all samples (0.08 to 0.38 mg L<sup>−1</sup> T-X-100), being
highest in the SML during summer. SML SA enrichment factors (EFs) relative to
SSW were ∼ 1.0 to 1.9, except for two values (0.75; 0.89: February
2013). The range in corresponding <i>k</i><sub>660</sub> (<i>k</i><sub>w</sub> for CO<sub>2</sub> in
seawater at 20 °C) was 6.8 to 22.0 cm h<sup>−1</sup>. The film factor
<i>R</i><sub>660</sub> (the ratio of <i>k</i><sub>660</sub> for seawater to <i>k</i><sub>660</sub> for “clean”,
i.e. surfactant-free, laboratory water) was strongly correlated with SML SA
(<i>r</i> ≥ 0.70, <i>p</i> ≤ 0.002, each <i>n</i> = 16). High SML SA typically
corresponded to <i>k</i><sub>660</sub> suppressions ∼ 14 to 51 % relative to
clean laboratory water, highlighting strong spatiotemporal gradients in gas
exchange due to varying surfactant in these coastal waters. Such variability
should be taken account of when evaluating marine trace gas sources and
sinks. Total CDOM absorbance (250 to 450 nm), the CDOM spectral slope ratio
(<i>S</i><sub>R</sub> = <i>S</i><sub>275 − 295</sub>∕<i>S</i><sub>350 − 400</sub>), the 250 : 365 nm CDOM
absorption ratio (<i>E</i><sub>2</sub> : <i>E</i><sub>3</sub>), and Chl <i>a</i> all indicated spatial
and temporal signals in the quantity and composition of organic matter in the
SML and SSW. This prompts us to hypothesise that spatiotemporal variation in
<i>R</i><sub>660</sub> and its relationship with SA is a consequence of compositional
differences in the surfactant fraction of the SML DOM pool that warrants
further investigation
Nitrous oxide emissions from the Arabian Sea: A synthesis
We computed high-resolution (1º latitude x 1º longitude) seasonal and annual nitrous oxide (N2O) concentration fields for the Arabian Sea surface layer using a database containing more than 2400 values measured between December 1977 and July 1997. N2O concentrations are highest during the southwest (SW) monsoon along the southern Indian continental shelf. Annual emissions range from 0.33 to 0.70 Tg N2O and are dominated by fluxes from coastal regions during the SW and northeast monsoons. Our revised estimate for the annual N2O flux from the Arabian Sea is much more tightly constrained than the previous consensus derived using averaged in-situ data from a smaller number of studies. However, the tendency to focus on measurements in locally restricted features in combination with insufficient seasonal data coverage leads to considerable uncertainties of the concentration fields and thus in the flux estimates, especially in the coastal zones of the northern and eastern Arabian Sea. The overall mean relative error of the annual N2O emissions from the Arabian Sea was estimated to be at least 65%
FAK regulates IL-33 expression by controlling chromatin accessibility at c-Jun motifs
Focal adhesion kinase (FAK) localizes to focal adhesions and is overexpressed in many cancers. FAK can also translocate to the nucleus, where it binds to, and regulates, several transcription factors, including MBD2, p53 and IL-33, to control gene expression by unknown mechanisms. We have used ATAC-seq to reveal that FAK controls chromatin accessibility at a subset of regulated genes. Integration of ATAC-seq and RNA-seq data showed that FAK-dependent chromatin accessibility is linked to differential gene expression, including of the FAK-regulated cytokine and transcriptional regulator interleukin-33 (Il33), which controls anti-tumor immunity. Analysis of the accessibility peaks on the Il33 gene promoter/enhancer regions revealed sequences for several transcription factors, including ETS and AP-1 motifs, and we show that c-Jun, a component of AP-1, regulates Il33 gene expression by binding to its enhancer in a FAK kinase-dependent manner. This work provides the first demonstration that FAK controls transcription via chromatin accessibility, identifying a novel mechanism by which nuclear FAK regulates biologically important gene expression
The Atlantic Ocean surface microlayer from 50°N to 50°S is ubiquitously enriched in surfactants at wind speeds up to 13 m s−1
We report the first measurements of surfactant activity (SA) in the sea surface microlayer (SML) and in subsurface waters (SSW) at the ocean basin scale, for two Atlantic Meridional Transect from cruises 50°N to 50°S during 2014 and 2015. Northern Hemisphere (NH) SA was significantly higher than Southern Hemisphere (SH) SA in the SML and in the SSW. SA enrichment factors (EF = SASML/SASSW) were also higher in the NH, for wind speeds up to ~13 m s−1, questioning a prior assertion that Atlantic Ocean wind speeds >12 m s−1 poleward of 30°N and 30°S would preclude high EFs and showing the SML to be self-sustaining with respect to SA. Our results imply that surfactants exert a control on air-sea CO2 exchange across the whole North Atlantic CO2 sink region and that the contribution made by high wind, high latitude oceans to air-sea gas exchange globally should be reexamined
Nitrous oxide emissions from the Arabian Sea: A synthesis
We computed high-resolution (1º latitude x 1º longitude) seasonal and annual nitrous oxide (N<sub>2</sub>O) concentration fields for the Arabian Sea surface layer using a database containing more than 2400 values measured between December 1977 and July 1997. N<sub>2</sub>O concentrations are highest during the southwest (SW) monsoon along the southern Indian continental shelf. Annual emissions range from 0.33 to 0.70 Tg N<sub>2</sub>O and are dominated by fluxes from coastal regions during the SW and northeast monsoons. Our revised estimate for the annual N<sub>2</sub>O flux from the Arabian Sea is much more tightly constrained than the previous consensus derived using averaged in-situ data from a smaller number of studies. However, the tendency to focus on measurements in locally restricted features in combination with insufficient seasonal data coverage leads to considerable uncertainties of the concentration fields and thus in the flux estimates, especially in the coastal zones of the northern and eastern Arabian Sea. The overall mean relative error of the annual N<sub>2</sub>O emissions from the Arabian Sea was estimated to be at least 65%
Advances in understanding of air-sea exchange and cycling of greenhouse gases in the upper ocean
\ua9 2024 University of California Press. All rights reserved. The air–sea exchange and oceanic cycling of greenhouse gases (GHG), including carbon dioxide (CO2), nitrous oxide (N2O), methane (CH4), carbon monoxide (CO), and nitrogen oxides (NOx \ubc NO \ufe NO2), are fundamental in controlling the evolution of the Earth’s atmospheric chemistry and climate. Significant advances have been made over the last 10 years in understanding, instrumentation and methods, as well as deciphering the production and consumption pathways of GHG in the upper ocean (including the surface and subsurface ocean down to approximately 1000 m). The global ocean under current conditions is now well established as a major sink for CO2, a major source for N2O and a minor source for both CH4 and CO. The importance of the ocean as a sink or source of NOx is largely unknown so far. There are still considerable uncertainties about the processes and their major drivers controlling the distributions of N2O, CH4, CO, and NOx in the upper ocean. Without having a fundamental understanding of oceanic GHG production and consumption pathways, our knowledge about the effects of ongoing major oceanic changes—warming, acidification, deoxygenation, and eutrophication—on the oceanic cycling and air–sea exchange of GHG remains rudimentary at best. We suggest that only through a comprehensive, coordinated, and interdisciplinary approach that includes data collection by global observation networks as well as joint process studies can the necessary data be generated to (1) identify the relevant microbial and phytoplankton communities, (2) quantify the rates of ocean GHG production and consumption pathways, (3) comprehend their major drivers, and (4) decipher economic and cultural implications of mitigation solutions
Advances in understanding of air–sea exchange and cycling of greenhouse gases in the upper ocean
This is the final version. Available on open access from University of California Press via the DOI in this recordThe air–sea exchange and oceanic cycling of greenhouse gases (GHG), including carbon dioxide (CO2), nitrous oxide (N2O), methane (CH4), carbon monoxide (CO), and nitrogen oxides (NOx = NO + NO2), are fundamental in controlling the evolution of the Earth’s atmospheric chemistry and climate. Significant advances have been made over the last 10 years in understanding, instrumentation and methods, as well as deciphering the production and consumption pathways of GHG in the upper ocean (including the surface and subsurface ocean down to approximately 1000 m). The global ocean under current conditions is now well established as a major sink for CO2, a major source for N2O and a minor source for both CH4 and CO. The importance of the ocean as a sink or source of NOx is largely unknown so far. There are still considerable uncertainties about the processes and their major drivers controlling the distributions of N2O, CH4, CO, and NOx in the upper ocean. Without having a fundamental understanding of oceanic GHG production and consumption pathways, our knowledge about the effects of ongoing major oceanic changes—warming, acidification, deoxygenation, and eutrophication—on the oceanic cycling and air–sea exchange of GHG remains rudimentary at best. We suggest that only through a comprehensive, coordinated, and interdisciplinary approach that includes data collection by global observation networks as well as joint process studies can the necessary data be generated to (1) identify the relevant microbial and phytoplankton communities, (2) quantify the rates of ocean GHG production and consumption pathways, (3) comprehend their major drivers, and (4) decipher economic and cultural implications of mitigation solutions.European Space AgencyConvex Seascape SurveyEuropean Union Horizon 2020U.S. National Science Foundatio
Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer
BACKGROUND & AIMS: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress, and novel therapeutic response in PC to develop a biomarkerdriven therapeutic strategy targeting DDR and replication stress in PC. METHODS: We interrogated the transcriptome, genome, proteome, and functional characteristics of 61 novel PC patient–derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient-derived xenografts and human PC organoids. RESULTS: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors, including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, cosegregates with response to platinum (P < .001) and PARP inhibitor therapy (P < .001) in vitro and in vivo. We generated a novel signature of replication stress that predicts response to ATR (P < .018) and WEE1 inhibitor (P < .029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < .001) but was not associated with DDR deficiency. CONCLUSIONS: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR-proficient PC and after platinum therapy.Stephan B. Dreyer ... Karin S. Kassahn ... et al
HNF4A and GATA6 Loss Reveals Therapeutically Actionable Subtypes in Pancreatic Cancer.
Pancreatic ductal adenocarcinoma (PDAC) can be divided into transcriptomic subtypes with two broad lineages referred to as classical (pancreatic) and squamous. We find that these two subtypes are driven by distinct metabolic phenotypes. Loss of genes that drive endodermal lineage specification, HNF4A and GATA6, switch metabolic profiles from classical (pancreatic) to predominantly squamous, with glycogen synthase kinase 3 beta (GSK3β) a key regulator of glycolysis. Pharmacological inhibition of GSK3β results in selective sensitivity in the squamous subtype; however, a subset of these squamous patient-derived cell lines (PDCLs) acquires rapid drug tolerance. Using chromatin accessibility maps, we demonstrate that the squamous subtype can be further classified using chromatin accessibility to predict responsiveness and tolerance to GSK3β inhibitors. Our findings demonstrate that distinct patterns of chromatin accessibility can be used to identify patient subgroups that are indistinguishable by gene expression profiles, highlighting the utility of chromatin-based biomarkers for patient selection in the treatment of PDAC
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