mistakes

And I see myself reflected in all my mistakes

Ca2+/calmodulin-dependent protein kinase kinase-β acts upstream of AMP-activated protein kinase in mammalian cells

SummaryAMP-activated protein kinase (AMPK) is the downstream component of a kinase cascade that plays a pivotal role in energy homeostasis. Activation of AMPK requires phosphorylation of threonine 172 (T172) within the T loop region of the catalytic α subunit. Recently, LKB1 was shown to activate AMPK. Here we show that AMPK is also activated by Ca2+/calmodulin-dependent protein kinase kinase (CaMKK). Overexpression of CaMKKβ in mammalian cells increases AMPK activity, whereas pharmacological inhibition of CaMKK, or downregulation of CaMKKβ using RNA interference, almost completely abolishes AMPK activation. CaMKKβ isolated from rat brain or expressed in E. coli phosphorylates and activates AMPK in vitro. In yeast, CaMKKβ expression rescues a mutant strain lacking the three kinases upstream of Snf1, the yeast homolog of AMPK. These results demonstrate that AMPK is regulated by at least two upstream kinases and suggest that AMPK may play a role in Ca2+-mediated signal transduction pathways

Replenishment of selenium deficient rats with selenium results in redistribution of the selenocysteine tRNA population in a tissue specific manner

AbstractWe reported previously that the selenium status of rats influences both the steady-state levels and distributions of two selenocysteine tRNA isoacceptors and that these isoacceptors differ by a single methyl group attached to the ribosyl moiety at position 34. In this study, we demonstrate that repletion of selenium-deficient rats results in a gradual, tissue-dependent shift in the distribution of these isoacceptors. Rats fed a selenium-deficient diet possess a greater abundance of the species unmethylated on the ribosyl moiety at position 34 compared to the form methylated at this position. A redistribution of the Sec–tRNA isoacceptors occurred in tissues of selenium-supplemented rats whereby the unmethylated form gradually shifted toward the methylated form. This was true in each of four tissues examined, muscle, kidney, liver and heart, although the rate of redistribution was tissue-specific. Muscle manifested a predominance of two minor serine isoacceptors under conditions of extreme selenium-deficiency which also appeared to respond to selenium. Ribosomal binding studies revealed that one of the two additional isoacceptors decodes the serine codeword, AGU, and the second decodes the serine codeword, UCU. Interestingly, muscle and heart were the slower tissues to return to a `selenium adequate' tRNA distribution pattern

The Seasonal Flux and Fate of Dissolved Organic Carbon Through Bacterioplankton in the Western North Atlantic

The oceans teem with heterotrophic bacterioplankton that play an appreciable role in the uptake of dissolved organic carbon (DOC) derived from phytoplankton net primary production (NPP). As such, bacterioplankton carbon demand (BCD), or gross heterotrophic production, represents a major carbon pathway that influences the seasonal accumulation of DOC in the surface ocean and, subsequently, the potential vertical or horizontal export of seasonally accumulated DOC. Here, we examine the contributions of bacterioplankton and DOM to ecological and biogeochemical carbon flow pathways, including those of the microbial loop and the biological carbon pump, in the Western North Atlantic Ocean (∼39–54°N along ∼40°W) over a composite annual phytoplankton bloom cycle. Combining field observations with data collected from corresponding DOC remineralization experiments, we estimate the efficiency at which bacterioplankton utilize DOC, demonstrate seasonality in the fraction of NPP that supports BCD, and provide evidence for shifts in the bioavailability and persistence of the seasonally accumulated DOC. Our results indicate that while the portion of DOC flux through bacterioplankton relative to NPP increased as seasons transitioned from high to low productivity, there was a fraction of the DOM production that accumulated and persisted. This persistent DOM is potentially an important pool of organic carbon available for export to the deep ocean via convective mixing, thus representing an important export term of the biological carbon pump

Recent Shifts in the Occurrence, Cause, and Magnitude of Animal Mass Mortality Events

Mass mortality events (MMEs) are rapidly occurring catastrophic demographic events that punctuate background mortality levels. Individual MMEs are staggering in their observed magnitude: re- moving more than 90% of a population, resulting in the death of more than a billion individuals, or producing 700 million tons of dead biomass in a single event. Despite extensive documentation of individual MMEs, we have no understanding of the major features characterizing the occurrence and magnitude of MMEs, their causes, or trends through time. Thus, no framework exists for contextualizing MMEs in the wake of ongoing global and regional perturbations to natural systems. Here we present an analysis of 727 published MMEs from across the globe, affecting 2,407 animal populations. We show that the magnitude of MMEs has been intensifying for birds, fishes, and marine invertebrates; invariant for mammals; and decreasing for reptiles and amphibians. These shifts in magnitude proved robust when we accounted for an increase in the occurrence of MMEs since 1940. However, it remains unclear whether the increase in the occurrence of MMEs represents a true pattern or simply a perceived increase. Regardless, the increase in MMEs appears to be associated with a rise in disease emergence, biotoxicity, and events produced by multiple interacting stressors, yet temporal trends in MME causes varied among taxa and may be associated with increased de- tectability. In addition, MMEs with the largest magnitudes were those that resulted from multiple stressors, starvation, and disease. These results advance our understanding of rare demographic processes and their relationship to global and regional perturba- tions to natural systems

Project Khepri: Mining Asteroid Bennu for Water

Deep space asteroid mining presents the opportunity for the collection of critical resources required to establish a cis-lunar infrastructure. In specific, the Project Khepri team has focused on the collection of water from asteroid Bennu. This water has the potential to provide a source of clean-energy propellant as well as an essential consumable for humans or agriculture on crewed trips to the Moon or Mars. This would avoid the high costs of launching from Earth - making it a highly desirable element for the future of cis-lunar infrastructure. The OSIRIS-REx mission provided a complete survey of asteroid Bennu and is set to return regolith samples to Earth in 2023. This makes asteroid Bennu a well-understood and low-risk target that is estimated to be around 6.26% water by mass. The Khepri Project comprises a team of international students, academics, and industry subject matter experts working on the technical design, business case, and political aspects of a mission to mine asteroid Bennu for water. The research output explores the multi-year mission that the Khepri team has proposed

The Seasonal Flux and Fate of Dissolved Organic Carbon Through Bacterioplankton in the Western North Atlantic

The oceans teem with heterotrophic bacterioplankton that play an appreciable role in the uptake of dissolved organic carbon (DOC) derived from phytoplankton net primary production (NPP). As such, bacterioplankton carbon demand (BCD), or gross heterotrophic production, represents a major carbon pathway that influences the seasonal accumulation of DOC in the surface ocean and, subsequently, the potential vertical or horizontal export of seasonally accumulated DOC. Here, we examine the contributions of bacterioplankton and DOM to ecological and biogeochemical carbon flow pathways, including those of the microbial loop and the biological carbon pump, in the Western North Atlantic Ocean (∼39–54°N along ∼40°W) over a composite annual phytoplankton bloom cycle. Combining field observations with data collected from corresponding DOC remineralization experiments, we estimate the efficiency at which bacterioplankton utilize DOC, demonstrate seasonality in the fraction of NPP that supports BCD, and provide evidence for shifts in the bioavailability and persistence of the seasonally accumulated DOC. Our results indicate that while the portion of DOC flux through bacterioplankton relative to NPP increased as seasons transitioned from high to low productivity, there was a fraction of the DOM production that accumulated and persisted. This persistent DOM is potentially an important pool of organic carbon available for export to the deep ocean via convective mixing, thus representing an important export term of the biological carbon pump

Development of a Antibacterial Disc Diffusion Assay to Differentiate Fusarin C from Non-Fusarin C activity in Early Screening of Mutant Fusarium graminearum Extracts

The discovery of novel compounds with antibacterial properties continues to be critically important.3 One potential source of such compounds is the cryptic genome of fungi known to produce biologically active molecules. A kmt6 mutant of the cereal pathogen Fusarium graminearum was previously developed through a histone H3 lysine 27 methyltransferase gene knockout, and has been shown to express hundreds of additional genes compared to wild type under the same growth conditions.1 Both the kmt6 mutant and the wild type F. graminearum produce the biologically active metabolite fusarin C, shown in Figure 1, and its analogs. Activity due to fusarin C can mask any activity of non-fusarin C compounds during early screening of extracts. Using a broad panel of bacteria, two samples were tested for differentiating activity profiles. These included an ethyl acetate extract of kmt6 growth media (i.e., the “160001E” fraction), and a more purified flash column fraction containing fusarin C and its analogs (i.e., the “fusarin C isolate”). Intriguingly, both Bacillus cereus and Staphylococcus aureus were inhibited by the 160001E extract, but were not inhibited by the fusarin C isolate. This indicates that activity from the 160001E fraction is not due to fusarin C or its analogs, but rather due to non-fusarin C compounds. With these results, a panel of 5 bacteria, including both gram negative and gram positive strains, has been developed as an early screening tool to differentiate activity between fusarin C isolates and non-fusarin C compounds from kmt6 mutant F. graminearum. This will aid in the bioassay-guided fractionation of extracts exhibiting antibacterial activity due to non-fusarin C compounds and toward the important aim of identifying novel compounds with antibacterial activity

Saccharomyces cerevisiae Fermentation Products That Mitigate Foodborne Salmonella in Cattle and Poultry

Prior studies revealed that yeast fermentation products, specifically XPC™ and related products (Diamond V, Cedar Rapids, IA), serve as viable food safety tools across multiple food animal species including cattle and poultry. Providing this supplement in feed leads to reduced prevalence, load, virulence, and antibiotic resistance of foodborne pathogens such as Salmonella and Escherichia coli O157:H7. These findings are worthy of further study, especially when coupled with the enhanced growth and performance observed with these products. Mechanistically, XPC appears to modulate these effects through the immune system and gut microbiome. Herein we further investigated this product and demonstrate that XPC mediates an enhancement of immunocyte killing of Salmonella in calves fed the product. Additionally, these studies reveal that XPC reduces the lymph node infiltration, invasiveness, and antibiotic resistance of Salmonella in dairy calves fed the product-consistent with findings observed in poultry and adult beef cattle. Furthermore, the reduction in invasiveness does not lead to a rebound hyperinvasive phenotype in Salmonella obtained from XPC-fed animals. In summary, these studies suggest that XPC reduces the invasion of Salmonella and may alter various phenotypic characteristics of the pathogen

Theoretical Engineering of the Gut Micro biome for the Purpose of Creating Superior Soldiers

The purpose of this review is to highlight research raising the possibility of exploiting the host-microbiome gut axis for military purposes. Through optimizing the gut-microbiome environment it is possible to enhance nutritional access to indigestible material, provide local and systemic analgesia, enhance psychological robustness to battlefield stress, produce endogenous steroids, reduce muscle fatigue, and promote peripheral wound healing. However, this approach is still in its early stages and thus has not been explored to its full potential. The challenges that are currently preventing the practical use of gut bacteria include the following: inconsistency of clinical outcomes, transient effects requiring continuous supplementation, the type of regimen selected, the initiation and cessation of regimen, and the broader clinical studies needed to validate this research. This review is intended to shed light on the numerous and varied positive impacts such an approach could have for the military if further developed