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We present a case of kidney transplantation in a 28-year-old patient who received a heart transplant at 7 weeks of age due to hypoplastic left heart syndrome. The patient's renal insufficiency was the result of chronic immunosuppression and hypertension. The almost 28-year-old graft demonstrated very good function. This patient represents as one of the longest pediatric cardiac graft recipients living without any significant functional limitations. [ABSTRACT FROM AUTHOR]

Dupuytren's contracture is a condition in which fibromatosis of the palmar and digital fascia can lead to painful contractures of the hand. Common conservative treatments are of limited efficacy, while invasive options have risk of adverse effects. A 57-year-old female presented with chronic, bilateral hand pain secondary to Dupuytren's contractures. Traditional conservative treatments did not provide relief. She received a series of three botulinum toxin A injections into the palmar fascia of both hands, resulting in four months of improved hand function and pain relief. This case presents a novel treatment for Dupuytren's contracture using botulinum toxin injection. Botulinum toxin has inhibitory effects on the neuromuscular junction and pain signaling pathways to relax muscles and reduce pain. We believe its action on this patient's intrinsic hand muscles resulted in her improved hand function. Botulinum toxin injection can be considered as a treatment option for Dupuytren's contracture. [ABSTRACT FROM AUTHOR]

* Background and Aims Phosphoenolpyruvate carboxylase (PEPC) is a tightly regulated enzyme that controls carbohydrate partitioning to organic acid anions (malate, citrate) excreted in copious amounts by cluster roots of inorganic phosphate (Pi)-deprived white lupin plants. Excreted malate and citrate solubilize otherwise inaccessible sources of mineralized soil Pi for plant uptake. The aim of this study was to test the hypotheses that (1) PEPC is post-translationally activated by reversible phosphorylation in cluster roots of illuminated white lupin plants, and (2) light-dependent phosphorylation of cluster root PEPC is associated with elevated intracellular levels of sucrose and its signalling metabolite, trehalose-6-phosphate. * Methods White lupin plants were cultivated hydroponically at low Pi levels (≤1 µM) and subjected to various light/ dark pretreatments. Cluster root PEPC activity and in vivo phosphorylation status were analysed to assess the enzyme's diurnal, post-translational control in response to light and dark. Levels of various metabolites, including sucrose and trehalose-6-phosphate, were also quantified in cluster root extracts using enzymatic and spectrometric methods. * Key Results During the daytime the cluster root PEPC was activated by phosphorylation at its conserved N-terminal seryl residue. Darkness triggered a progressive reduction in PEPC phosphorylation to undetectable levels, and this was correlated with 75-80 % decreases in concentrations of sucrose and trehalose-6-phosphate. * Conclusions Reversible, light-dependent regulatory PEPC phosphorylation occurs in cluster roots of Pi-deprived white lupin plants. This likely facilitates the well-documented light- and sucrose-dependent exudation of Pi-solubilizing organic acid anions by the cluster roots. PEPC's in vivo phosphorylation status appears to be modulated by sucrose translocated from CO2-fixing leaves into the non-photosynthetic cluster roots. [ABSTRACT FROM AUTHOR]

Catalyzed hydrocarbon traps (HC traps) are being developed to provide HC control during the cold start. HC traps are made up of an adsorbent material, such as a zeolite, and a three way catalyst (precious metal based) present on the same monolith to provide trapping and oxidation functions. Traps are typically formulated with a multi-layer washcoat structure with the catalyst layer on top, and the trapping material placed under. The HC traps operate by storing (trapping) the unburned hydrocarbon molecules in the adsorbent material at a lower temperature when adsorption is favored and oxidation does not occur, and subsequently releasing these trapped HCs when the catalyst has heated sufficiently to convert the HCs to carbon dioxide and water. This paper presents the results of a modeling, laboratory and vehicle study on the performance of HC traps. First we present procedure to evaluate trap performance in the laboratory that provides the kinetic parameters for HC adsorption. A mathematical model is presented that can be used to simulate the HC trap. The feedgas to the zeolite trap on vehicle contains both HCs and water, present in the vehicle exhaust. The various HC species and water compete for adsorption on the zeolites. Lab experiments conducted on zeolites to study the competitive adsorption of various HCs and water is presented. Experiments have been conducted where different HCs and water are sequentially adsorbed on the zeolite, and TPD conducted. For modeling, Langmuir isotherm is assumed to represent the adsorption phenomena on the zeolite sites. Exothermic effects of water adsorption on acidic zeolites have been presented. Details on the experiments done to estimate the heat of adsorption of water on zeolites, and the modeling results of water adsorption on zeolites have also been provided. [ABSTRACT FROM AUTHOR]

Targeting of senescence-inducible acid phosphatases and RNases to the cell wall and vacuolar compartments appears to make a crucial contribution to efficient P remobilization networks of senescing tissues of Hakea prostrata and Arabidopsis.Despite its agronomic importance, the metabolic networks mediating phosphorus (P) remobilization during plant senescence are poorly understood. Highly efficient P remobilization (~85%) from senescing leaves and proteoid roots of harsh hakea (Hakea prostrata), a native ‘extremophile’ plant of south-western Australia, was linked with striking up-regulation of cell wall-localized and intracellular acid phosphatase (APase) and RNase activities. Non-denaturing PAGE followed by in-gel APase activity staining revealed senescence-inducible 120kDa and 60kDa intracellular APase isoforms, whereas only the 120kDa isoform was detected in corresponding cell wall fractions. Kinetic and immunological properties of the 120kDa and 60kDa APases partially purified from senescing leaves indicated that they are purple acid phosphatases (PAPs). Results obtained with cell wall-targeted hydrolases of harsh hakea were corroborated using Arabidopsis thaliana in which an ~200% increase in cell wall APase activity during leaf senescence was paralleled by accumulation of immunoreactive 55kDa AtPAP26 polypeptides. Senescing leaves of an atpap26 T-DNA insertion mutant displayed a >90% decrease in cell wall APase activity. Previous research established that senescing leaves of atpap26 plants exhibited a similar reduction in intracellular (vacuolar) APase activity, while displaying markedly impaired P remobilization efficiency and delayed senescence. It is hypothesized that up-regulation and dual targeting of PAPs and RNases to the cell wall and vacuolar compartments make a crucial contribution to highly efficient P remobilization that dominates the P metabolism of senescing tissues of harsh hakea and Arabidopsis. To the best of the authors’ knowledge, the apparent contribution of cell wall-targeted hydrolases to remobilizing key macronutrients such as P during senescence has not been previously suggested. [ABSTRACT FROM AUTHOR]

Microhomology-mediated end-joining (MMEJ) is an error-prone alternative double-strand break-repair pathway that uses sequence microhomology to recombine broken DNA. Although MMEJ has been implicated in cancer development, the mechanism of this pathway is unknown. We demonstrate that purified human DNA polymerase θ (Polθ) performs MMEJ of DNA containing 3′ single-strand DNA overhangs with ≥2 bp of homology, including DNA modeled after telomeres, and show that MMEJ is dependent on Polθ in human cells. Our data support a mechanism whereby Polθ facilitates end-joining and microhomology annealing, then uses the opposing overhang as a template in trans to stabilize the DNA synapse. Polθ exhibits a preference for DNA containing a 5′-terminal phosphate, similarly to polymerases involved in nonhomologous end-joining. Finally, we identify a conserved loop domain that is essential for MMEJ and higher-order structures of Polθ that probably promote DNA synapse formation. [ABSTRACT FROM AUTHOR]

Summary Increased protein synthesis plays an etiologic role in diverse cancers. Here, we demonstrate that METTL13 (methyltransferase-like 13) dimethylation of eEF1A (eukaryotic elongation factor 1A) lysine 55 (eEF1AK55me2) is utilized by Ras-driven cancers to increase translational output and promote tumorigenesis in vivo. METTL13-catalyzed eEF1A methylation increases eEF1A's intrinsic GTPase activity in vitro and protein production in cells. METTL13 and eEF1AK55me2 levels are upregulated in cancer and negatively correlate with pancreatic and lung cancer patient survival. METTL13 deletion and eEF1AK55me2 loss dramatically reduce Ras-driven neoplastic growth in mouse models and in patient-derived xenografts (PDXs) from primary pancreatic and lung tumors. Finally, METTL13 depletion renders PDX tumors hypersensitive to drugs that target growth-signaling pathways. Together, our work uncovers a mechanism by which lethal cancers become dependent on the METTL13-eEF1AK55me2 axis to meet their elevated protein synthesis requirement and suggests that METTL13 inhibition may constitute a targetable vulnerability of tumors driven by aberrant Ras signaling. Graphical Abstract Highlights • METTL13 is the physiologic eEF1A lysine 55 dimethyltransferase • METTL13 dimethylation of eEF1A stimulates protein synthesis in cancer cells • The METTL13-eEF1A methylation axis fuels Ras-driven tumorigenesis in vivo • METTL13 depletion sensitizes cancer cells to PI3K and mTOR pathway inhibitors Ras-driven cancers ramp up protein synthesis by increasing the GTPase activity of a translation elongation factor through a mechanism that involves METTL13-catalyzed eEF1A dimethylation [ABSTRACT FROM AUTHOR]