Results from the Mars Phoenix Lander Robotic Arm experiment

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95618/1/jgre2693.pd

Conditions for the Long-Term Preservation of a Deep Brine Reservoir in Ceres

We propose a new internal evolution model for the dwarf planet Ceres matching the constraints on Ceres' present internal state from the Dawn mission observations. We assume an interior differentiated into a volatile-dominated crust and rocky mantle, and with remnant brines in the mantle, all consistent with inferences from the Dawn geophysical observations. Simulations indicate Ceres should preserve a warm crust until present if the crust is rich in clathrate hydrates. The temperature computed at the base of the crust exceeds 220 K for a broad range of conditions, allowing for the preservation of a small amount of brines at the base of the crust. However, a temperature ≥250 K, for which at least 1 wt.% sodium carbonate gets in solution requires a crustal abundance of clathrate hydrates greater than 55 vol.%, a situation possible for a narrow set of evolutionary scenarios

Pharmacological inhibition of Ras-transformed epithelial cell growth is linked to down-regulation of epidermal growth factor–related peptides

AbstractBackground & Aims: Posttranslational farnesylation is required for Ras activation. Farnesyl transferase inhibitors (FTIs) selectively block protein farnesylation and reduce the growth of many Ras-transformed cells in vitro and in vivo. Activated Ras transforms rat intestinal epithelial (RIE-1) cells by a mechanism distinct from NIH 3T3 fibroblasts in that an epidermal growth factor receptor (EGFR) autocrine loop contributes significantly to the Ras-transformed RIE-1 phenotype. Methods: The ability of FTIs to block growth of Ras-transformed RIE-1 cells was evaluated, and these results were correlated with decreased EGFR ligand production. Results: FTI L744,832 caused a selective, dose-dependent, reversible blockade in proliferation of H-Ras–transformed RIE-1 cells, whereas control cell lines, K-Ras–transformed cells, and activated raf-transfected RIE cells were unaffected. The growth-inhibitory effects of L744,832 correlated with loss of farnesylated H-Ras protein and a marked reduction in transforming growth factor (TGF)-α and amphiregulin expression. Inhibition of proliferation of H-Ras RIE-1 cells by L744,832 was overcome by exogenous TGF-α, and enhanced growth inhibition was achieved by EGFR blockade in combination with L744,832. Conclusions: These data suggest that one mechanism by which FTIs inhibit growth of H-Ras–transformed epithelial cells is by reducing Ras-induced EGFR ligand production.GASTROENTEROLOGY 1999;117:567-57

A Science-Based Policy for Managing Free-Roaming Cats

Free-roaming domestic cats (i.e., cats that are owned or unowned and are considered ‘at large’) are globally distributed non-native species that have marked impacts on biodiversity and human health. Despite clear scientific evidence of these impacts, free-roaming cats are either unmanaged or managed using scientifically unsupported and ineffective approaches (e.g., trap-neuter-release [TNR]) in many jurisdictions around the world. A critical first initiative for effective, science-driven management of cats must be broader political and legislative recognition of free-roaming cats as a non-native, invasive species. Designating cats as invasive is important for developing and implementing science-based management plans, which should include efforts to prevent cats from becoming free-roaming, policies focused on responsible pet ownership and banning outdoor cat feeding, and better enforcement of existing laws. Using a science-based approach is necessary for responding effectively to the politically charged and increasingly urgent issue of managing free-roaming cat populations

Participation of the PI-3K/Akt-NF-κB signaling pathways in hypoxia-induced mitogenic factor-stimulated Flk-1 expression in endothelial cells

BACKGROUND: Hypoxia-induced mitogenic factor (HIMF), a lung-specific growth factor, promotes vascular tubule formation in a matrigel plug model. We initially found that HIMF enhances vascular endothelial growth factor (VEGF) expression in lung epithelial cells. In present work, we tested whether HIMF modulates expression of fetal liver kinase-1 (Flk-1) in endothelial cells, and dissected the possible signaling pathways that link HIMF to Flk-1 upregulation. METHODS: Recombinant HIMF protein was intratracheally instilled into adult mouse lungs, Flk-1 expression was examined by immunohistochemistry and Western blot. The promoter-luciferase reporter assay and real-time RT-PCR were performed to examine the effects of HIMF on Flk-1 expression in mouse endothelial cell line SVEC 4–10. The activation of NF-kappa B (NF-κB) and phosphorylation of Akt, IKK, and IκBα were examined by luciferase assay and Western blot, respectively. RESULTS: Intratracheal instillation of HIMF protein resulted in a significant increase of Flk-1 production in lung tissues. Stimulation of SVEC 4–10 cells by HIMF resulted in increased phosphorylation of IKK and IκBα, leading to activation of NF-κB. Blocking NF-κB signaling pathway by dominant-negative mutants of IKK and IκBα suppressed HIMF-induced Flk-1 upregulation. Mutation or deletion of NF-κB binding site within Flk-1 promoter also abolished HIMF-induced Flk-1 expression in SVEC 4–10 cells. Furthermore, HIMF strongly induced phosphorylation of Akt. A dominant-negative mutant of PI-3K, Δp85, as well as PI-3K inhibitor LY294002, blocked HIMF-induced NF-κB activation and attenuated Flk-1 production. CONCLUSION: These results suggest that HIMF upregulates Flk-1 expression in endothelial cells in a PI-3K/Akt-NF-κB signaling pathway-dependent manner, and may play critical roles in pulmonary angiogenesis

Deciding Together?:Best Interests and Shared Decision-Making in Paediatric Intensive Care

In the western healthcare, shared decision making has become the orthodox approach to making healthcare choices as a way of promoting patient autonomy. Despite the fact that the autonomy paradigm is poorly suited to paediatric decision making, such an approach is enshrined in English common law. When reaching moral decisions, for instance when it is unclear whether treatment or non-treatment will serve a child’s best interests, shared decision making is particularly questionable because agreement does not ensure moral validity. With reference to current common law and focusing on intensive care practice, this paper investigates what claims shared decision making may have to legitimacy in a paediatric intensive care setting. Drawing on key texts, I suggest these identify advantages to parents and clinicians but not to the child who is the subject of the decision. Without evidence that shared decision making increases the quality of the decision that is being made, it appears that a focus on the shared nature of a decision does not cohere with the principle that the best interests of the child should remain paramount. In the face of significant pressures toward the displacement of the child’s interests in a shared decision, advantages of a shared decision to decisional quality require elucidation. Although a number of arguments of this nature may have potential, should no such advantages be demonstrable we have cause to revise our commitment to either shared decision making or the paramountcy of the child in these circumstances

Targeting Cattle-Borne Zoonoses and Cattle Pathogens Using a Novel Trypanosomatid-Based Delivery System

Trypanosomatid parasites are notorious for the human diseases they cause throughout Africa and South America. However, non-pathogenic trypanosomatids are also found worldwide, infecting a wide range of hosts. One example is Trypanosoma (Megatrypanum) theileri, a ubiquitous protozoan commensal of bovids, which is distributed globally. Exploiting knowledge of pathogenic trypanosomatids, we have developed Trypanosoma theileri as a novel vehicle to deliver vaccine antigens and other proteins to cattle. Conditions for the growth and transfection of T. theileri have been optimised and expressed heterologous proteins targeted for secretion or specific localisation at the cell interior or surface using trafficking signals from Trypanosoma brucei. In cattle, the engineered vehicle could establish in the context of a pre-existing natural T. theileri population, was maintained long-term and generated specific immune responses to an expressed Babesia antigen at protective levels. Building on several decades of basic research into trypanosomatid pathogens, Trypanosoma theileri offers significant potential to target multiple infections, including major cattle-borne zoonoses such as Escherichia coli, Salmonella spp., Brucella abortus and Mycobacterium spp. It also has the potential to deliver therapeutics to cattle, including the lytic factor that protects humans from cattle trypanosomiasis. This could alleviate poverty by protecting indigenous African cattle from African trypanosomiasis