Developmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer

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The SGLT2 inhibitor dapagliflozin promotes systemic FFA mobilization,enhances hepatic β-oxidation,and induces ketosis

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to increase ketone bodies in patients with type 2 diabetes; however, the underlying mechanisms have not been fully elucidated. Here we examined the effect of the SGLT2 inhibitor dapagliflozin (1 mg/kg/day, formulated in a water, PEG400, ethanol, propylene glycol solution, 4 weeks) on lipid metabolism in obese Zucker rats. Fasting FFA metabolism was assessed in the anesthetized state using a [9,10-³H(N)]-palmitic acid tracer by estimating rates of plasma FFA appearance (R_a), whole-body FFA oxidation (R_ox), and nonoxidative disposal (R_st). In the liver, clearance (K_β-ox) and flux (R_β-ox) of FFA into β-oxidation were estimated using [9,10-³H]-(R)-bromopalmitate/[U-¹⁴C]palmitate tracers. As expected, dapagliflozin induced glycosuria and a robust antidiabetic effect; treatment reduced fasting plasma glucose and insulin, lowered glycated hemoglobin, and increased pancreatic insulin content compared with vehicle controls. Dapagliflozin also increased plasma FFA, R_a, R_ox, and R_st with enhanced channeling toward oxidation versus storage. In the liver, there was also enhanced channeling of FFA to β-oxidation, with increased K_β-ox, R_β-ox and tissue acetyl-CoA, compared with controls. Finally, dapagliflozin increased hepatic HMG-CoA and plasma β-hydroxybutyrate, consistent with a specific enhancement of ketogenesis. Since ketogenesis has not been directly measured, we cannot exclude an additional contribution of impaired ketone body clearance to the ketosis. In conclusion, this study provides evidence that the dapagliflozin-induced increase in plasma ketone bodies is driven by the combined action of FFA mobilization from adipose tissue and diversion of hepatic FFA toward β-oxidation.     

Evaluation of methods for extraction of bacteria from soil

Abstract Several methods for dispersion of soil were tested for possible use in procedures for extraction of bacteria. Physical cell damage on cells and efficiency in extraction of indigenous cells from soil, were investigated. Cell damage by the dispersion methods was investigated by measuring the physical cell integrity and viability of pure cultures of Escherichia coli and Bacillus subtilis , as well as soil bacteria extracted from soil, when dispersed in slurries of γ-sterilized soil. Separation of bacteria and soil particles on the basis of buoyant density was conducted with the nonionic density gradient medium Nycodenz. When slurries of γ-sterilized soil with added pure cultured cells were centrifuged (10000 × g ) over cushions of Nycodenz (1.3 g ml⁻¹), practically all the added cells were recovered in a layer on top of the cushion. This proves that a reversible attachment and cosedimentation is not an important phenomenon in this procedure. The efficiency of the different dispersion methods for the extraction of indigenous soil bacteria, was assessed after separation of dislodged and attached soil bacteria. This separation was done either on the basis of sedimentation rate by low speed centrifugation, or buoyant density by Nycodenz density gradient centrifugation. The physical dispersion by ultrasonic treatment and chemical dispersion by the use of a chelating agent together with a detergent, were inferior to physical dispersion either by Waring blender (for large volumes) or a rotating rubber pestle treatment (for smaller volumes). The physical dispersion did not appear to be destructive to the cells tested.     

Temporal,cell-specific,and tissue-preferential expression of myrosinase genes during embryo and seedling development in Sinapis alba

The expression of the genes for two types of myrosinase (EC 3.2.3.1), designated MA and MB, during embryo and seedling development was investigated in Sinapis alba L. by in-situ and RNA slot-blot analyses. The expression of MA and MB genes followed similar temporal profiles during embryogenesis, but MB mRNA was present in considerably higher amounts than MA mRNA. In the embryo, both MA and MB genes are activated in cotyledons and axis. The MB genes are preferentially expressed in the cotyledons whereas MA genes are preferentially expressed in the axis. In the developing seedling, MA mRNA was not present in the organs investigated. By contrast, MB mRNA was found in appreciable amounts in hypocotyls, cotyledons and developing leaves. The MB genes seem to be activated preferentially in tissues undergoing rapid cell division and — or cell expansion.Abbreviations DAP days after pollination - MA, MB A type, B type myrosinases in Sinapis alba Anna-Stina Höglund (Uppsala Genetic Center) is gratefully acknowledged for valuable discussion, Anders Gobl (Department of Immunology, Uppsala University) for kindly advice with the labeling of probes and Qingzhu Zhai (Department of Pharmaceutical Biosciences, Uppsala University) for help with seed harvest. This work was supported by grants from the Swedish Research Council for Forestry and Agriculture.     

Aspects of cAMP Signaling in Epileptogenesis and Seizures and Its Potential as Drug Target

Neurochemical Research - Epilepsy is one of the most common chronic neurological conditions. Today, close to 30 different medications to prevent epileptic seizures are in use; yet, far from all...     

Eutrophication and Dreissena Invasion as Drivers of Biodiversity: A Century of Change in the Mollusc Community of Oneida Lake

Changes in nutrient loading and invasive species are among the strongest human-driven disturbances in freshwater ecosystems, but our knowledge on how they affect the biodiversity of lakes is still limited. We conducted a detailed historical analysis of the mollusc community of Oneida Lake based on our comprehensive lakewide study in 2012 and previous surveys dating back to 1915. In the early 20th century, the lake had a high water clarity, with abundant macrophytes and benthic algae, and hosted the most diverse molluscan community in New York State, including 32 gastropod and 9 unionid species. By the 1960s, lake turbidity increased during a period of anthropogenic eutrophication, resulting in a 38% decline in species richness and a 95% reduction in abundance of native gastropods grazing on benthic algae. Following the invasion of Dreissena spp. in 1991 and subsequent increases in water clarity, native gastropod species richness expanded by 37% and abundance increased 20-fold by 2012. In contrast, filter-feeding unionids were unaffected by increased turbidity during the period of eutrophication but were extirpated by dreissenids. Through contrasting effects on turbidity, eutrophication and Dreissena spp. have likely driven the observed changes in native grazing gastropods by affecting the abundance of light-limited benthic algae. Given the high species richness and ecological importance of benthic grazers, monitoring and managing turbidity is important in preserving molluscan diversity.     

Impacts of rewetting on peat,hydrology and water chemical composition over 15 years in two finished peat extraction areas in Sweden

Restoration of wetlands is a high priority world-wide. Peat extraction areas can be restored by rewetting, however affecting the environment. It could be expected to turn the drained peat-cutover area from a source to a sink of most elements. This study examined effects of such rewetting on peat, hydrology and water chemistry over 15 years at two sites in Sweden; the nutrient-poor Porla peatland and the nutrient-rich Västkärr peatland. Rewetting caused minor changes to peat chemistry, but at the Västkärr site ammonium concentrations increased in superficial peat layers while nitrate decreased. In terms of hydrology, rewetting of the Porla site decreased annual runoff and both high and low discharges. Water pH at the Porla site stayed fairly stable, but at the Västkärr site pH, after an initial 4 years dip, gradually increased to higher values than before rewetting. Water colour and organic matter content were fairly stable, but slightly lower values were found after 15 years than in initial 4–5 years. The concentrations of base cations and of inorganic N were lower after rewetting, while total P was higher. However, these impacts could change from an initial phase as the wetlands in the long-term perspective develop into mires.     

Prostaglandin production by human epidermal cells in vitro: A model for studying pharmacologic inhibition of prostaglandin synthesis

An inv itro model for studying the biosynthesis of prostaglandins by isolated human epidermal cells is described. Production of prostaglandin E₂-equivalent activity over an 18-hour incubation period was measured using a radioimmunoassay. Prostaglandin production was significantly inhibited by indomethacin and aspirin in a concentration-dependent manner.