Regulation of Coagulation Factor XI Expression by MicroRNAs in the Human Liver

High levels of factor XI (FXI) increase the risk of thromboembolic disease. However, the genetic and environmental factors regulating FXI expression are still largely unknown. The aim of our study was to evaluate the regulation of FXI by microRNAs (miRNAs) in the human liver. In silico prediction yielded four miRNA candidates that might regulate FXI expression. HepG2 cells were transfected with miR-181a-5p, miR-23a-3p, miR-16-5p and miR-195-5p. We used mir-494, which was not predicted to bind to F11, as a negative control. Only miR-181a-5p caused a significant decrease both in FXI protein and F11 mRNA levels. In addition, transfection with a miR-181a-5p inhibitor in PLC/PRF/5 hepatic cells increased both the levels of F11 mRNA and extracellular FXI. Luciferase assays in human colon cancer cells deficient for Dicer (HCT-DK) demonstrated a direct interaction between miR-181a-5p and 3′untranslated region of F11. Additionally, F11 mRNA levels were inversely and significantly correlated with miR-181a-5p levels in 114 healthy livers, but not with miR-494. This study demonstrates that FXI expression is directly regulated by a specific miRNA, miR-181a-5p, in the human liver. Future studies are necessary to further investigate the potential consequences of miRNA dysregulation in pathologies involving FXI.     

Nickel uptake and utilization by microorganisms

Nickel is an essential nutrient for selected microorganisms where it participates in a variety of cellular processes. Many microbes are capable of sensing cellular nickel ion concentrations and taking up this nutrient via nickel-specific permeases or ATP-binding cassette-type transport systems. The metal ion is specifically incorporated into nickel-dependent enzymes, often via complex assembly processes requiring accessory proteins and additional non-protein components, in some cases accompanied by nucleotide triphosphate hydrolysis. To date, nine nickel-containing enzymes are known: urease, NiFe-hydrogenase, carbon monoxide dehydrogenase, acetyl-CoA decarbonylase/synthase, methyl coenzyme M reductase, certain superoxide dismutases, some glyoxylases, aci-reductone dioxygenase, and methylenediurease. Seven of these enzymes have been structurally characterized, revealing distinct metallocenter environments in each case.     

Global change‐driven effects on dissolved organic matter composition: Implications for food webs of northern lakes

Northern ecosystems are experiencing some of the most dramatic impacts of global change on Earth. Rising temperatures, hydrological intensification, changes in atmospheric acid deposition and associated acidification recovery, and changes in vegetative cover are resulting in fundamental changes in terrestrial–aquatic biogeochemical linkages. The effects of global change are readily observed in alterations in the supply of dissolved organic matter (DOM)—the messenger between terrestrial and lake ecosystems—with potentially profound effects on the structure and function of lakes. Northern terrestrial ecosystems contain substantial stores of organic matter and filter or funnel DOM, affecting the timing and magnitude of DOM delivery to surface waters. This terrestrial DOM is processed in streams, rivers, and lakes, ultimately shifting its composition, stoichiometry, and bioavailability. Here, we explore the potential consequences of these global change‐driven effects for lake food webs at northern latitudes. Notably, we provide evidence that increased allochthonous DOM supply to lakes is overwhelming increased autochthonous DOM supply that potentially results from earlier ice‐out and a longer growing season. Furthermore, we assess the potential implications of this shift for the nutritional quality of autotrophs in terms of their stoichiometry, fatty acid composition, toxin production, and methylmercury concentration, and therefore, contaminant transfer through the food web. We conclude that global change in northern regions leads not only to reduced primary productivity but also to nutritionally poorer lake food webs, with discernible consequences for the trophic web to fish and humans.     

Rhodospirillum sodomense,sp. nov., a Dead Sea rhodospirillum species

A new species of halophilic anoxygenic purple bacteria of the genus Rhodospirillum is described. The new organism, isolated from water/sediment of the Dead Sea, was vibrio-shaped and an obligate halophile. Growth was best at 12% NaCl, with only weak growth occurring at 6% or 21% NaCl. Growth occurred at Mg²⁺ concentrations up to 1 M but optimal growth was obtained at 0.05–0.1 M Mg²⁺. Bromide was well tolerated as an alternative anion to chloride. The new organism is an obligate phototroph, growing photoheterotrophically in media containing yeast extract and acetate or a few other organic compounds. Growth of the Dead Sea Rhodospirillum species under optimal culture conditions was slow (minimum t_d 20 h). Cells contained bacteriochlorophyll a and carotenoids of the spirilloxanthin series and mass cultures were pink in color. Absorption spectra revealed the presence of a B875 (light-harvesting I) but no B800/B850 (light-harvesting II) photopigment complex. The new organism shares a number of properties with the previously described halophilic phototrophic bacterium Rhodospirillum salinarum and was shown to be related to this phototroph by 16S rRNA sequencing. However, because of its salinity requirements, photosynthetic properties, and isolation from the Dead Sea, the new phototroph is proposed as a new species of the genus Rhodospirillum, R. sodomense.     

Modelling multilocus selection in an individual‐based,spatially‐explicit landscape genetics framework

We implemented multilocus selection in a spatially‐explicit, individual‐based framework that enables multivariate environmental gradients to drive selection in many loci as a new module for the landscape genetics programs, CDPOP and CDMetaPOP. Our module simulates multilocus selection using a linear additive model, providing a flexible platform to evaluate a wide range of genotype‐environment associations. Importantly, the module allows simulation of selection in any number of loci under the influence of any number of environmental variables. We validated the module with individual‐based selection simulations under Wright‐Fisher assumptions. We then evaluated results for simulations under a simple landscape selection model. Next, we simulated individual‐based multilocus selection across a complex selection landscape with three loci linked to three different environmental variables. Finally, we demonstrated how the program can be used to simulate multilocus selection under varying selection strengths across different levels of gene flow in a landscape genetics framework. This new module provides a valuable addition to the study of landscape genetics, allowing for explicit evaluation of the contributions and interactions between gene flow and selection‐driven processes across complex, multivariate environmental and landscape conditions.     

Land Use Compounds Habitat Losses under Projected Climate Change in a Threatened California Ecosystem

Given the rapidly growing human population in mediterranean-climate systems, land use may pose a more immediate threat to biodiversity than climate change this century, yet few studies address the relative future impacts of both drivers. We assess spatial and temporal patterns of projected 21^st century land use and climate change on California sage scrub (CSS), a plant association of considerable diversity and threatened status in the mediterranean-climate California Floristic Province. Using a species distribution modeling approach combined with spatially-explicit land use projections, we model habitat loss for 20 dominant shrub species under unlimited and no dispersal scenarios at two time intervals (early and late century) in two ecoregions in California (Central Coast and South Coast). Overall, projected climate change impacts were highly variable across CSS species and heavily dependent on dispersal assumptions. Projected anthropogenic land use drove greater relative habitat losses compared to projected climate change in many species. This pattern was only significant under assumptions of unlimited dispersal, however, where considerable climate-driven habitat gains offset some concurrent climate-driven habitat losses. Additionally, some of the habitat gained with projected climate change overlapped with projected land use. Most species showed potential northern habitat expansion and southern habitat contraction due to projected climate change, resulting in sharply contrasting patterns of impact between Central and South Coast Ecoregions. In the Central Coast, dispersal could play an important role moderating losses from both climate change and land use. In contrast, high geographic overlap in habitat losses driven by projected climate change and projected land use in the South Coast underscores the potential for compounding negative impacts of both drivers. Limiting habitat conversion may be a broadly beneficial strategy under climate change. We emphasize the importance of addressing both drivers in conservation and resource management planning.     

Granzyme B regulates antiviral CD8+ T cell responses

CTLs and NK cells use the perforin/granzyme cytotoxic pathway to kill virally infected cells and tumors. Human regulatory T cells also express functional granzymes and perforin and can induce autologous target cell death in vitro. Perforin-deficient mice die of excessive immune responses after viral challenges, implicating a potential role for this pathway in immune regulation. To further investigate the role of granzyme B in immune regulation in response to viral infections, we characterized the immune response in wild-type, granzyme B-deficient, and perforin-deficient mice infected with Sendai virus. Interestingly, granzyme B-deficient mice, and to a lesser extent perforin-deficient mice, exhibited a significant increase in the number of Ag-specific CD8(+) T cells in the lungs and draining lymph nodes of virally infected animals. This increase was not the result of failure in viral clearance because viral titers in granzyme B-deficient mice were similar to wild-type mice and significantly less than perforin-deficient mice. Regulatory T cells from WT mice expressed high levels of granzyme B in response to infection, and depletion of regulatory T cells from these mice resulted in an increase in the number of Ag-specific CD8(+) T cells, similar to that observed in granzyme B-deficient mice. Furthermore, granzyme B-deficient regulatory T cells displayed defective suppression of CD8(+) T cell proliferation in vitro. Taken together, these results suggest a role for granzyme B in the regulatory T cell compartment in immune regulation to viral infections.