Identification of the orphan gene Prod 1 in basal and other salamander families.

The urodele amphibians (salamanders) are the only adult tetrapods able to regenerate the limb. It is unclear if this is an ancestral property that is retained in salamanders but lost in other tetrapods or if it evolved in salamanders. The three-finger protein Prod 1 is implicated in the mechanism of newt limb regeneration, and no orthologs have been found in other vertebrates, thus providing evidence for the second viewpoint. It has also been suggested that this protein could play a role in salamander-specific aspects of limb development. There are ten families of extant salamanders, and Prod 1 has only been identified in two of them to date. It is important to determine if it is present in other families and, particularly, the basal group of two families which diverged approximately 200 MYA

TREX-DM: a low background Micromegas-based TPC for low-mass WIMP detection

Dark Matter experiments are recently focusing their detection techniques in low-mass WIMPs, which requires the use of light elements and low energy threshold. In this context, we describe the TREX-DM experiment, a low background Micromegas-based TPC for low-mass WIMP detection. Its main goal is the operation of an active detection mass $\sim$0.3 kg, with an energy threshold below 0.4 keVee and fully built with previously selected radiopure materials. This work describes the commissioning of the actual setup situated in a laboratory on surface and the updates needed for a possible physics run at the Canfranc Underground Laboratory (LSC) in 2016. A preliminary background model of TREX-DM is also presented, based on a Geant4 simulation, the simulation of the detector's response and two discrimination methods: a conservative muon/electron and one based on a neutron source. Based on this background model, TREX-DM could be competitive in the search for low-mass WIMPs. In particular it could be sensitive, e.g., to the low-mass WIMP interpretation of the DAMA/LIBRA and other hints in a conservative scenario.Comment: Proceedings of the XIV International Conference on Topics in Astroparticle and Underground Physics (TAUP 2015), 7-11 September 2015, Torino, Ital

TREX-DM: a low background Micromegas-based TPC for low mass WIMP detection

Dark Matter experiments are recently focusing their detection techniques in low-mass WIMPs, which requires the use of light elements and low energy threshold. In this context, we present the TREX-DM experiment, a low background Micromegas-based TPC for low-mass WIMP detection. Its main goal is the operation of an active detection mass $\sim$0.300 kg, with an energy threshold below 0.4 keVee and fully built with previously selected radiopure materials. This article describes the actual setup, the first results of the comissioning in Ar+2\%iC$_4$H$_{10}$ at 1.2 bar and the future updates for a possible physics run at the Canfranc Underground Laboratory in 2016. A first background model is also presented, based on Geant4 simulations and a muon/electron discrimination method. In a conservative scenario, TREX-DM could be sensitive to DAMA/LIBRA and other hints of positive WIMPs signals, with some space for improvement with a neutron/electron discrimination method or the use of other light gases.Comment: Proceedings of the 7th Symposium on Large TPCs for Low-Energy Rare Event Detectio

Commissioning of the Liquid Nitrogen Thermo-Siphon System for NASA-JSC Chamber-A

NASA's Space Environment Simulation Laboratory's (SESL) Chamber A, located at the Johnson Space Center in Houston Texas has recently implemented major enhancements of its cryogenic and vacuum systems. The new liquid nitrogen (LN2) thermo-siphon system was successfully commissioned in August of 2012. Chamber A, which has 20 K helium cryo-panels (or shrouds ) which are shielded by 80 K nitrogen shrouds, is capable of simulating a deep space environment necessary to perform ground testing of NASA s James Webb Space Telescope (JWST). Chamber A s previous system used forced flow LN2 cooling with centrifugal pumps, requiring 200,000 liters of LN2 to cool-down and consuming 180,000 liters per day of LN2 in steady operation. The LN2 system did not have the reliability required to meet the long duration test of the JWST, and the cost estimate provided in the initial approach to NASA-JSC by the sub-contractor for refurbishment of the system to meet the reliability goals was prohibitive. At NASA-JSC's request, the JLab Cryogenics Group provided alternative options in 2007, including a thermo-siphon, or natural flow system. This system, eliminated the need for pumps and used one tenth of the original control valves, relief valves, and burst disks. After the thermo-siphon approach was selected, JLab provided technical assistance in the process design, mechanical design, component specification development and commissioning oversight, while the installation and commissioning operations of the system was overseen by the Jacobs Technology/ESC group at JSC. The preliminary commissioning data indicate lower shroud temperatures, 70,000 liters to cool-down and less than 90,000 liters per day consumed in steady operation. All of the performance capabilities have exceeded the design goals. This paper will outline the comparison between the original system and the predicted results of the selected design option, and the commissioning results of thermo-siphon system

Mechanism of Action of Secreted Newt Anterior Gradient Protein

Anterior gradient (AG) proteins have a thioredoxin fold and are targeted to the secretory pathway where they may act in the ER, as well as after secretion into the extracellular space. A newt member of the family (nAG) was previously identified as interacting with the GPI-anchored salamander-specific three-finger protein called Prod1. Expression of nAG has been implicated in the nerve dependence of limb regeneration in salamanders, and nAG acted as a growth factor for cultured newt limb blastemal (progenitor) cells, but the mechanism of action was not understood. Here we show that addition of a peptide antibody to Prod1 specifically inhibit the proliferation of blastema cells, suggesting that Prod1 acts as a cell surface receptor for secreted nAG, leading to S phase entry. Mutation of the single cysteine residue in the canonical active site of nAG to alanine or serine leads to protein degradation, but addition of residues at the C terminus stabilises the secreted protein. The mutation of the cysteine residue led to no detectable activity on S phase entry in cultured newt limb blastemal cells. In addition, our phylogenetic analyses have identified a new Caudata AG protein called AG4. A comparison of the AG proteins in a cell culture assay indicates that nAG secretion is significantly higher than AGR2 or AG4, suggesting that this property may vary in different members of the family

Lowering the background level and the energy threshold of Micromegas x-ray detectors for axion searches

Axion helioscopes search for solar axions by their conversion in x-rays in the presence of high magnetic fields. The use of low background x-ray detectors is an essential component contributing to the sensitivity of these searches. In this work, we review the recent advances on Micromegas detectors used in the CERN Axion Solar Telescope (CAST) and proposed for the future International Axion Observatory (IAXO). The actual setup in CAST has achieved background levels below 10$^{-6}$ keV$^{-1}$ cm$^{-2}$ s$^{-1}$, a factor 100 lower than the first generation of Micromegas detectors. This reduction is based on active and passive shielding techniques, the selection of radiopure materials, offline discrimination techniques and the high granularity of the readout. We describe in detail the background model of the detector, based on its operation at CAST site and at the Canfranc Underground Laboratory (LSC), as well as on Geant4 simulations. The best levels currently achieved at LSC are low than 10$^{-7}$ keV$^{-1}$ cm$^{-2}$ s$^{-1}$ and show good prospects for the application of this technology in IAXO. Finally, we present some ideas and results for reducing the energy threshold of these detectors below 1 keV, using high-transparent windows, autotrigger electronics and studying the cluster shape at different energies. As a high flux of axion-like-particles is expected in this energy range, a sub-keV threshold detector could enlarge the physics case of axion helioscopes.Comment: Proceedings of 3rd International Conference on Technology and Instrumentation in Particle Physics (TIPP 2014

MTHFD1 controls DNA methylation in Arabidopsis.

DNA methylation is an epigenetic mechanism that has important functions in transcriptional silencing and is associated with repressive histone methylation (H3K9me). To further investigate silencing mechanisms, we screened a mutagenized Arabidopsis thaliana population for expression of SDCpro-GFP, redundantly controlled by DNA methyltransferases DRM2 and CMT3. Here, we identify the hypomorphic mutant mthfd1-1, carrying a mutation (R175Q) in the cytoplasmic bifunctional methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase (MTHFD1). Decreased levels of oxidized tetrahydrofolates in mthfd1-1 and lethality of loss-of-function demonstrate the essential enzymatic role of MTHFD1 in Arabidopsis. Accumulation of homocysteine and S-adenosylhomocysteine, genome-wide DNA hypomethylation, loss of H3K9me and transposon derepression indicate that S-adenosylmethionine-dependent transmethylation is inhibited in mthfd1-1. Comparative analysis of DNA methylation revealed that the CMT3 and CMT2 pathways involving positive feedback with H3K9me are mostly affected. Our work highlights the sensitivity of epigenetic networks to one-carbon metabolism due to their common S-adenosylmethionine-dependent transmethylation and has implications for human MTHFD1-associated diseases

POPDC1 scaffolds a complex of adenylyl cyclase 9 and the potassium channel TREK-1 in heart

The establishment of macromolecular complexes by scaffolding proteins is key to the local production of cAMP by anchored adenylyl cyclase (AC) and the subsequent cAMP signaling necessary for cardiac functions. We identify a novel AC scaffold, the Popeye domain-containing (POPDC) protein. The POPDC family of proteins is important for cardiac pacemaking and conduction, due in part to their cAMP-dependent binding and regulation of TREK-1 potassium channels. We show that TREK-1 binds the AC9:POPDC1 complex and copurifies in a POPDC1-dependent manner with AC9 activity in heart. Although the AC9:POPDC1 interaction is cAMP-independent, TREK-1 association with AC9 and POPDC1 is reduced upon stimulation of the β-adrenergic receptor (βAR). AC9 activity is required for βAR reduction of TREK-1 complex formation with AC9:POPDC1 and in reversing POPDC1 enhancement of TREK-1 currents. Finally, deletion of the gene-encoding AC9 (Adcy9) gives rise to bradycardia at rest and stress-induced heart rate variability, a milder phenotype than the loss of Popdc1 but similar to the loss of Kcnk2 (TREK-1). Thus, POPDC1 represents a novel adaptor for AC9 interactions with TREK-1 to regulate heart rate control