Assessing the temporal scale of deep-sea mining impacts on sediment biogeochemistry

Deep-sea mining for polymetallic nodules is expected to have severe environmental impacts because not only nodules but also benthic fauna and the upper reactive sediment layer are removed through the mining operation and blanketed by resettling material from the suspended sediment plume. This study aims to provide a holistic assessment of the biogeochemical recovery after a disturbance event by applying prognostic simulations based on an updated diagenetic background model and validated against novel data on microbiological processes. It was found that the recovery strongly depends on the impact type; complete removal of the reactive surface sediment reduces benthic release of nutrients over centuries, while geochemical processes after resuspension and mixing of the surface sediment are near the pre-impact state 1 year after the disturbance. Furthermore, the geochemical impact in the DISturbance and reCOLonization (DISCOL) experiment area would be mitigated to some degree by a clay-bound Fe(II)-reaction layer, impeding the downward diffusion of oxygen, thus stabilizing the redox zonation of the sediment during transient post-impact recovery. The interdisciplinary (geochemical, numerical and biological) approach highlights the closely linked nature of benthic ecosystem functions, e.g. through bioturbation, microbial biomass and nutrient fluxes, which is also of great importance for the system recovery. It is, however, important to note that the nodule ecosystem may never recover to the pre-impact state without the essential hard substrate and will instead be dominated by different faunal communities, functions and services

A quantitative assessment of methane cycling in Hikurangi Margin sediments (New Zealand) using geophysical imaging and biogeochemical modeling

Takahe seep, located on the Opouawe Bank, Hikurangi Margin, is characterized by a well-defined subsurface seismic chimney structure ca. 80,500 m2 in area. Sub-seafloor geophysical data based on acoustic anomaly layers indicated the presence of gas hydrate and free gas layers within the chimney structure. Reaction-transport modeling was applied to porewater data from 11 gravity cores to constrain methane turnover rates and benthic methane fluxes in the upper 10 m. Model results show that methane dynamics were highly variable due to transport and dissolution of ascending gas. The dissolution of gas (up to 3761 mmol m−2 yr−1) dwarfed the rate of methanogenesis within the simulated sediment column (2.6 mmol m−2 yr−1). Dissolved methane is mainly consumed by anaerobic oxidation of methane (AOM) at the base of the sulfate reduction zone and trapped by methane hydrate formation below it, with maximum rates in the central part of the chimney (946 and 2420 mmol m−2 yr−1, respectively). A seep-wide methane budget was constrained by combining the biogeochemical model results with geophysical data and led to estimates of AOM rates, gas hydrate formation and benthic dissolved methane fluxes of 3.68 × 104 mol yr−1, 73.85 × 104 mol yr−1and 1.19 × 104 mol yr−1, respectively. A much larger flux of methane probably escapes in gaseous form through focused bubble vents. The approach of linking geochemical model results with spatial geophysical data put forward here can be applied elsewhere to improve benthic methane turnover rates from limited single spot measurements to larger spatial scales

Prohypertensive Effect of Gestational Personal Exposure to Fine Particulate Matter. Prospective Cohort Study in Non-smoking and Non-obese Pregnant Women

Exposure to fine particulate matter (PM) is a recognized risk factor for elevated blood pressure (BP) and cardiovascular disease in adults, and this prospective cohort study was undertaken to evaluate whether gestational exposure to $PM_{2.5}$ has a prohypertensive effect. We measured personal exposure to fine particulate matter ($PM_{2.5}$) by personal air monitoring in the second trimester of pregnancy among 431 women, and BP values in the third trimester were obtained from medical records of prenatal care clinics. In the general estimating equation model, the effect of $PM_{2.5}$ on BP was adjusted for relevant covariates such as maternal age, education, parity, gestational weight gain (GWG), prepregnancy BMI, environmental tobacco smoke (ETS), and blood lead level. Systolic blood pressure (SBP) increased in a linear fashion across a dosage of $PM_{2.5}$ and on average augmented by 6.1 mm Hg (95% CI, 0.6–11.6) with log unit of $PM_{2.5}$ concentration. Effects of age, maternal education, prepregnancy BMI, blood lead level, and ETS were insignificant. Women with excessive gestational weight gain (>18 kg) had higher mean SBP parameters by 5.5 mmHg (95% CI, 2.7–8.3). In contrast, multiparous women had significantly lower SBP values (coeff. = −4.2 mm Hg; 95% CI, −6.8 to −1.6). Similar analysis performed for diastolic blood pressure (DBP) has demonstrated that PM2.5 also affected DBP parameters (coeff. = 4.1; 95% CI, −0.02 to 8.2), but at the border significance level. DBP values were positively associated with the excessive GWG (coeff. = 2.3; 95% CI, 0.3–4.4) but were inversely related to parity (coeff. = −2.7; 95% CI, −4.6 to −0.73). In the observed cohort, the exposure to fine particulate matter during pregnancy was associated with increased maternal blood pressure

Lipoproteins act as vehicles for lipid antigen delivery and activation of invariant natural killer T cells

Invariant natural killer T (iNKT) cells act at the interface between lipid metabolism and immunity because of their restriction to lipid antigens presented on CD1d by antigen-presenting cells (APCs). How foreign lipid antigens are delivered to APCs remains elusive. Since lipoproteins routinely bind glycosylceramides structurally similar to lipid antigens, we hypothesized that circulating lipoproteins form complexes with foreign lipid antigens. In this study, we used 2-color fluorescence correlation spectroscopy to show, for the first time to our knowledge, stable complex formation of lipid antigens α-galactosylceramide (αGalCer), isoglobotrihexosylceramide, and OCH, a sphingosine-truncated analog of αGalCer, with VLDL and/or LDL in vitro and in vivo. We demonstrate LDL receptor–mediated (LDLR-mediated) uptake of lipoprotein-αGalCer complexes by APCs, leading to potent complex-mediated activation of iNKT cells in vitro and in vivo. Finally, LDLR-mutant PBMCs of patients with familial hypercholesterolemia showed impaired activation and proliferation of iNKT cells upon stimulation, underscoring the relevance of lipoproteins as a lipid antigen delivery system in humans. Taken together, circulating lipoproteins form complexes with lipid antigens to facilitate their transport and uptake by APCs, leading to enhanced iNKT cell activation. This study thereby reveals a potentially novel mechanism of lipid antigen delivery to APCs and provides further insight into the immunological capacities of circulating lipoproteins

PAS-positive lymphocyte vacuoles can be used as diagnostic screening test for Pompe disease

Screening of blood films for the presence of periodic acid-Schiff (PAS)-positive lymphocyte vacuoles is sometimes used to support the diagnosis of Pompe disease, but the actual diagnostic value is still unknown. We collected peripheral blood films from 65 untreated Pompe patients and 51 controls. Lymphocyte vacuolization was quantified using three methods: percentage vacuolated lymphocytes, percentage PAS-positive lymphocytes, and a PAS score depending on staining intensity. Diagnostic accuracy of the tests was assessed using receiver operating characteristic (ROC) curves. All three methods fully discerned classic infantile patients from controls. The mean values of patients with milder forms of Pompe disease were significantly higher than those of controls, but full separation was not obtained. The area under the ROC curve was 0.98 for the percentage vacuolated lymphocytes (optimal cutoff value 3; sensitivity 91%, specificity 96%) and 0.99 for the percentage PAS-positive lymphocytes and PAS score (optimal cutoff value 9; sensitivity 100%, specificity 98%). Our data indicate that PAS-stained blood films can be used as a reliable screening tool to support a diagnosis of Pompe disease. The percentage of PAS-positive lymphocytes is convenient for use in clinical practice but should always be interpreted in combination with other clinical and laboratory parameters

The pseudokinase TRIB3 controls adipocyte lipid homeostasis and proliferation in vitro and in vivo

OBJECTIVE: In vivo studies in humans and mice have implicated the pseudokinase Tribbles 3 (TRIB3) in various aspects of energy metabolism. Whilst cell-based studies indicate a role for TRIB3 in adipocyte differentiation and function, it is unclear if and how these cellular functions may contribute to overall metabolic health. METHODS: We investigated the metabolic phenotype of whole-body Trib3 knockout (Trib3KO) mice, focusing on adipocyte and adipose tissue functions. In addition, we combined lipidomics, transcriptomics, interactomics and phosphoproteomics analyses to elucidate cell-intrinsic functions of TRIB3 in pre- and mature adipocytes. RESULTS: Trib3KO mice display increased adiposity, but their insulin sensitivity remains unaltered. Trib3KO adipocytes are smaller and display higher Proliferating Cell Nuclear Antigen (PCNA) levels, indicating potential alterations in either i) proliferation-differentiation balance, ii) impaired expansion after cell division, or iii) an altered balance between lipid storage and release, or a combination thereof. Lipidome analyses suggest TRIB3 involvement in the latter two processes, as triglyceride storage is reduced and membrane composition, which can restrain cellular expansion, is altered. Integrated interactome, phosphoproteome and transcriptome analyses support a role for TRIB3 in all three cellular processes through multiple cellular pathways, including Mitogen Activated Protein Kinase- (MAPK/ERK), Protein Kinase A (PKA)-mediated signaling and Transcription Factor 7 like 2 (TCF7L2) and Beta Catenin-mediated gene expression. CONCLUSIONS: Our findings support TRIB3 playing multiple distinct regulatory roles in the cytoplasm, nucleus and mitochondria, ultimately controlling adipose tissue homeostasis, rather than affecting a single cellular pathway

Lipoproteins act as vehicles for lipid antigen delivery and activation of invariant natural killer T-cells

Invariant natural killer T (iNKT) cells act at the interface between lipid metabolism and immunity because of their restriction to lipid antigens presented on CD1d by antigen-presenting cells (APCs). How foreign lipid antigens are delivered to APCs remains elusive. Since lipoproteins routinely bind glycosylceramides structurally similar to lipid antigens, we hypothesized that circulating lipoproteins form complexes with foreign lipid antigens. In this study, we used 2-color fluorescence correlation spectroscopy to show, for the first time to our knowledge, stable complex formation of lipid antigens α-galactosylceramide (αGalCer), isoglobotrihexosylceramide, and OCH, a sphingosine-truncated analog of αGalCer, with VLDL and/or LDL in vitro and in vivo. We demonstrate LDL receptor-mediated (LDLR-mediated) uptake of lipoprotein-αGalCer complexes by APCs, leading to potent complex-mediated activation of iNKT cells in vitro and in vivo. Finally, LDLR-mutant PBMCs of patients with familial hypercholesterolemia showed impaired activation and proliferation of iNKT cells upon stimulation, underscoring the relevance of lipoproteins as a lipid antigen delivery system in humans. Taken together, circulating lipoproteins form complexes with lipid antigens to facilitate their transport and uptake by APCs, leading to enhanced iNKT cell activation. This study thereby reveals a potentially novel mechanism of lipid antigen delivery to APCs and provides further insight into the immunological capacities of circulating lipoproteins

Parameter estimation in tree graph metabolic networks

We study the glycosylation processes that convert initially toxic substrates to nutritionally valuable metabolites in the flavonoid biosynthesis pathway of tomato (Solanum lycopersicum) seedlings. To estimate the reaction rates we use ordinary differential equations (ODEs) to model the enzyme kinetics. A popular choice is to use a system of linear ODEs with constant kinetic rates or to use Michaelis–Menten kinetics. In reality, the catalytic rates, which are affected among other factors by kinetic constants and enzyme concentrations, are changing in time and with the approaches just mentioned, this phenomenon cannot be described. Another problem is that, in general these kinetic coefficients are not always identifiable. A third problem is that, it is not precisely known which enzymes are catalyzing the observed glycosylation processes. With several hundred potential gene candidates, experimental validation using purified target proteins is expensive and time consuming. We aim at reducing this task via mathematical modeling to allow for the pre-selection of most potential gene candidates. In this article we discuss a fast and relatively simple approach to estimate time varying kinetic rates, with three favorable properties: firstly, it allows for identifiable estimation of time dependent parameters in networks with a tree-like structure. Secondly, it is relatively fast compared to usually applied methods that estimate the model derivatives together with the network parameters. Thirdly, by combining the metabolite concentration data with a corresponding microarray data, it can help in detecting the genes related to the enzymatic processes. By comparing the estimated time dynamics of the catalytic rates with time series gene expression data we may assess potential candidate genes behind enzymatic reactions. As an example, we show how to apply this method to select prominent glycosyltransferase genes in tomato seedlings

Final prediction errors.

<p>The AFPE values obtained during the second thickening phase. The leftmost red star corresponds to the AFPE value of the network after the initial thinning phase. Next to this, are the sorted AFPE-values shown together with the corresponding candidate-edge added to the network for parameter estimation. Since adding any edge, not already present in this network, resulted in larger AFPE than without the addition, further thickening is impossible and we stop the iteration.</p