Spatial and temporal patterns of pore water chemistry in the inter-tidal zone of a high energy beach

Submarine groundwater discharge (SGD) is a ubiquitous source of meteoric fresh groundwater and recirculating seawater to the coastal ocean. Due to the hidden distribution of SGD, as well as the hydraulic- and stratigraphy-driven spatial and temporal heterogeneities, one of the biggest challenges to date is the correct assessment of SGD-driven constituent fluxes. Here, we present results from a 3-dimensional seasonal sampling campaign of a shallow subterranean estuary in a high-energy, meso-tidal beach, Spiekeroog Island, Northern Germany. We determined beach topography and analyzed physico-chemical and biogeochemical parameters such as salinity, temperature, dissolved oxygen, Fe(II) and dissolved organic matter fluorescence (FDOM). Overall, the highest gradients in pore water chemistry were found in the cross-shore direction. In particular, a strong physico-chemical differentiation between the tidal high water and low water line was found and reflected relatively stable in- and exfiltrating conditions in these areas. Contrastingly, in between, the pore water compositions in the existing foreshore ridge and runnel system were very heterogeneous on a spatial and temporal scale. The reasons for this observation may be the strong morphological changes that occur throughout the entire year, which affect the exact locations and heights of the ridge and runnel structures and associated flow paths. Further, seasonal changes in temperature and inland hydraulic head, and the associated effect on microbial mediated redox reactions likely overprint these patterns. In the long-shore direction the pore water chemistry varied less than the along the cross-shore direction. Variation in long-shore direction was probably occurring due to topography changes of the ridge-runnel structure and a physical heterogeneity of the sediment, which produced non-uniform groundwater flow conditions. We conclude that on meso-tidal high energy beaches, the rapidly changing beach morphology produces zones with different approximations to steady-state conditions. Therefore, we suggest that zone-specific endmember sampling is the optimal strategy to reduce uncertainties of SGD-driven constituent fluxes

Synthesis of Indomorphan Pseudo Natural Product Inhibitors of Glucose Transporters GLUT‐1 and ‐3

Bioactive compound design based on natural product (NP) structure may be limited due to partial coverage of NP‐like chemical space and biological target space. These limitations can be overcome by combining NP‐centered strategies with fragment‐based compound design through combination of NP‐derived fragments to structurally unprecedented “pseudo natural products” (pseudo‐NPs). We describe the design, synthesis and biological evaluation of a collection of indomorphan pseudo‐NPs that combine biosynthetically unrelated indole‐ and morphan‐alkaloid fragments. Biological investigation in a cell‐based screen for modulators of glucose uptake identified the indomorphane derivative Glupin as potent inhibitor of glucose uptake. Glupin selectively targets and upregulates both, glucose transporters GLUT‐1 and GLUT‐3. Glupin suppresses glycolysis, reduces the levels of glucose‐derived metabolites and attenuates the growth of various cancer cell lines. Our findings underscore the importance of dual GLUT‐1 and GLUT‐3 inhibition to efficiently suppress tumor cell growth and the cellular rescue mechanism, which counteracts glucose scarcity

Efficacy of vitamin D3-fortified-yogurt drink on anthropometric, metabolic, inflammatory and oxidative stress biomarkers according to vitamin D receptor gene polymorphisms in type 2 diabetic patients: a study protocol for a randomized controlled clinical trial

<p>Abstract</p> <p>Background</p> <p>Development of type 2 diabetes mellitus (T2DM) is determined by the interactions of genetic and environmental factors. This study was designed to evaluate the possible role of VDR single nucleotide polymorphisms (SNPs) on different aspects of diabetic host response (anthropometric, metabolic, oxidative stress and inflammatory) to daily intake of vitamin D through fortified yogurt drink for 12 weeks.</p> <p>Methods/Design</p> <p>This study comprises two parts: (i) a case-control study; and (ii) an intervention trial. In the first part, VDR polymorphisms <it>(Taq1</it>, <it>FokI</it>, <it>Apa1</it>, <it>Bsm1</it>, and <it>Cdx2) </it>are determined in 350 T2DM patients and 350 non-diabetic subjects. In the second part, the possible effects of daily intake of two servings of vitamin D3-fortified yogurt drink (FYD; 500 IU vitamin D/250 mL) on some selected metabolic (including insulin resistance), inflammatory and oxidative stress biomarkers in 135 T2DM patients are assessed. To relate the resulted changes in the biomarkers to vitamin D replenishment, another group of diabetic patients (n = 45) are also included in the study who receive 2 servings of plain yogurt drink (PYD) a day. The primary outcome is serum level of 25(OH) D, which it is expected to be elevated only in FYD group. Secondary outcomes include improvements in glycemic, metabolic, inflammatory and oxidative stress biomarkers in FYD group compared to PYD group. Three VDR <it>FokI </it>polymorphisms are determined only in FYD group followed by comparison of changes in the biomarkers among these genotypic variants.</p> <p>Discussion</p> <p>The present study, at least in part, elucidates the discrepancies in the results of different vitamin D-diabetes studies pertaining to the genetic variations of the population. If VDR polymorphisms are found to influence the response to our intervention, then knowing distribution of VDR polymorphisms in both diabetic and non-diabetic populations can give a picture of the proportion of the community in whom up to 1000 IU/d vitamin D may not be effective enough to improve insulin resistance and related morbidities. Therefore, they should ideally receive further nutritional support according to their genotype.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01236846">NCT01236846</a></p

Spatial and Temporal Patterns of Pore Water Chemistry in the Inter-Tidal Zone of a High Energy Beach

Submarine groundwater discharge (SGD) is a ubiquitous source of meteoric fresh groundwater and recirculating seawater to the coastal ocean. Due to the hidden distribution of SGD, as well as the hydraulic- and stratigraphy-driven spatial and temporal heterogeneities, one of the biggest challenges to date is the correct assessment of SGD-driven constituent fluxes. Here, we present results from a 3-dimensional seasonal sampling campaign of a shallow subterranean estuary in a high-energy, meso-tidal beach, Spiekeroog Island, Northern Germany. We determined beach topography and analyzed physico-chemical and biogeochemical parameters such as salinity, temperature, dissolved oxygen, Fe(II) and dissolved organic matter fluorescence (FDOM). Overall, the highest gradients in pore water chemistry were found in the cross-shore direction. In particular, a strong physico-chemical differentiation between the tidal high water and low water line was found and reflected relatively stable in- and exfiltrating conditions in these areas. Contrastingly, in between, the pore water compositions in the existing foreshore ridge and runnel system were very heterogeneous on a spatial and temporal scale. The reasons for this observation may be the strong morphological changes that occur throughout the entire year, which affect the exact locations and heights of the ridge and runnel structures and associated flow paths. Further, seasonal changes in temperature and inland hydraulic head, and the associated effect on microbial mediated redox reactions likely overprint these patterns. In the long-shore direction the pore water chemistry varied less than the along the cross-shore direction. Variation in long-shore direction was probably occurring due to topography changes of the ridge-runnel structure and a physical heterogeneity of the sediment, which produced non-uniform groundwater flow conditions. We conclude that on meso-tidal high energy beaches, the rapidly changing beach morphology produces zones with different approximations to steady-state conditions. Therefore, we suggest that zone-specific endmember sampling is the optimal strategy to reduce uncertainties of SGD-driven constituent fluxes

Vitamin d status predicts 30 day mortality in hospitalised cats

Vitamin D insufficiency, defined as low serum concentrations of the major circulating form of vitamin D, 25 hydroxyvitamin D (25(OH)D), has been associated with the development of numerous infectious, inflammatory, and neoplastic disorders in humans. In addition, vitamin D insufficiency has been found to be predictive of mortality for many disorders. However, interpretation of human studies is difficult since vitamin D status is influenced by many factors, including diet, season, latitude, and exposure to UV radiation. In contrast, domesticated cats do not produce vitamin D cutaneously, and most cats are fed a commercial diet containing a relatively standard amount of vitamin D. Consequently, domesticated cats are an attractive model system in which to examine the relationship between serum 25(OH)D and health outcomes. The hypothesis of this study was that vitamin D status would predict short term, all-cause mortality in domesticated cats. Serum concentrations of 25(OH)D, together with a wide range of other clinical, hematological, and biochemical parameters, were measured in 99 consecutively hospitalised cats. Cats which died within 30 days of initial assessment had significantly lower serum 25(OH)D concentrations than cats which survived. In a linear regression model including 12 clinical variables, serum 25(OH)D concentration in the lower tertile was significantly predictive of mortality. The odds ratio of mortality within 30 days was 8.27 (95% confidence interval 2.54-31.52) for cats with a serum 25(OH)D concentration in the lower tertile. In conclusion, this study demonstrates that low serum 25(OH)D concentration status is an independent predictor of short term mortality in cats