Water formation at low temperatures by surface O2 hydrogenation II: the reaction network

Water is abundantly present in the Universe. It is the main component of interstellar ice mantles and a key ingredient for life. Water in space is mainly formed through surface reactions. Three formation routes have been proposed in the past: hydrogenation of surface O, O2, and O3. In a previous paper [Ioppolo et al., Astrophys. J., 2008, 686, 1474] we discussed an unexpected non-standard zeroth-order H2O2 production behaviour in O2 hydrogenation experiments, which suggests that the proposed reaction network is not complete, and that the reaction channels are probably more interconnected than previously thought. In this paper we aim to derive the full reaction scheme for O2 surface hydrogenation and to constrain the rates of the individual reactions. This is achieved through simultaneous H-atom and O2 deposition under ultra-high vacuum conditions for astronomically relevant temperatures. Different H/O2 ratios are used to trace different stages in the hydrogenation network. The chemical changes in the forming ice are followed by means of reflection absorption infrared spectroscopy (RAIRS). New reaction paths are revealed as compared to previous experiments. Several reaction steps prove to be much more efficient (H + O2) or less efficient (H + OH and H2 + OH) than originally thought. These are the main conclusions of this work and the extended network concluded here will have profound implications for models that describe the formation of water in space.Comment: 1 page, 1 figur

Simvastatin Restores Down-Regulated GATA-6 Expression in Pulmonary Hypertensive Rats

Vascular smooth muscle cell proliferation has been known to be predominant in vascular remodeling of pulmonary hypertensive. The GATA family proteins, a group of zinc finger transcription factors, play an important role during cell proliferation. The aim of present study was to investigate the expression of GATA-6 gene in experimental pulmonary hypertensive rats and explore the effect of regulation of GATA-6 expression by simvastatin on pulmonary vascular remodeling. The male Sprague-Dawley rats model was established with receiving pneumonectomy and monocrotaline (MCT) administration. Right pulmonary artery remodeling in these animals was compared with untreated rats or rats receiving simvastatin. The level of GATA-6 mRNA and protein expression was detected by reverse transcriptase–polymerase chain reaction (RT-PCR) and Western blotting, respectively. Pneumonectomized, MCT-treated rats had significantly increased mean pulmonary arterial pressure (mPAP), RV/(LV + S) ratio (ratio of the right ventricular to left ventricular and septum weights), vascular occlusion scores (VOSs), and percent media wall thickness on day 35, all the indices were significantly decreased after simvastatin administration in these rats. The level of GATA-6 mRNA and protein were markedly decreased in these pneumonectomy and MCT-treated rats, and they were significantly up-regulated in these rats after receiving simvastatin. These results indicate that the development and progression of pulmonary hypertension is prevented by simvastatin by up-regulating GATA-6 expression in the lung tissue

Epigenetic memory in induced pluripotent stem cells.

Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment

Chemical Kinetics and Photochemical Data for Use in Atmospheric Studies Evaluation Number 15

This is the fifteenth in a series of evaluated sets of rate constants and photochemical cross sections compiled by the NASA Panel for Data Evaluation. The data are used primarily to model stratospheric and upper tropospheric processes, with particular emphasis on the ozone layer and its possible perturbation by anthropogenic and natural phenomena. Copies of this evaluation are available in electronic form and may be printed from the following Internet URL: http://jpldataeval.jpl.nasa.gov/

The mTORC1/4E-BP pathway coordinates hemoglobin production with L-leucine availability

In multicellular organisms, the mechanisms by which diverse cell types acquire distinct amino acids and how cellular function adapts to their availability are fundamental questions in biology. We found that increased neutral essential amino acid (NEAA) uptake was a critical component of erythropoiesis. As red blood cells matured, expression of the amino acid transporter gene Lat3 increased, which increased NEAA import. Inadequate NEAA uptake by pharmacologic inhibition or RNAi-mediated knockdown of LAT3 triggered a specific reduction in hemoglobin production in zebrafish embryos and murine erythroid cells through the mTORC1 (mammalian target of rapamycin complex 1)/4E-BP (eukaryotic translation initiation factor 4E–binding protein) pathway. CRISPR-mediated deletion of members of the 4E-BP family in murine erythroid cells rendered them resistant to mTORC1 and LAT3 inhibition and restored hemoglobin production. These results identify a developmental role for LAT3 in red blood cells and demonstrate that mTORC1 serves as a homeostatic sensor that couples hemoglobin production at the translational level to sufficient uptake of NEAAs, particularly L-leucine.National Institutes of Health (U.S.) (P01 HL032262

Long-Acting Cabotegravir and Rilpivirine after Oral Induction for HIV-1 Infection.

BACKGROUND: Long-acting injectable regimens may simplify therapy for patients with human immunodeficiency virus type 1 (HIV-1) infection. METHODS: We conducted a phase 3, randomized, open-label trial in which adults with HIV-1 infection who had not previously received antiretroviral therapy were given 20 weeks of daily oral induction therapy with dolutegravir-abacavir-lamivudine. Participants who had an HIV-1 RNA level of less than 50 copies per milliliter after 16 weeks were randomly assigned (1:1) to continue the current oral therapy or switch to oral cabotegravir plus rilpivirine for 1 month followed by monthly injections of long-acting cabotegravir plus rilpivirine. The primary end point was the percentage of participants who had an HIV-1 RNA level of 50 copies per milliliter or higher at week 48 (Food and Drug Administration snapshot algorithm). RESULTS: At week 48, an HIV-1 RNA level of 50 copies per milliliter or higher was found in 6 of 283 participants (2.1%) who received long-acting therapy and in 7 of 283 (2.5%) who received oral therapy (adjusted difference, -0.4 percentage points; 95% confidence interval [CI], -2.8 to 2.1), a result that met the criterion for noninferiority for the primary end point (margin, 6 percentage points). An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 93.6% who received long-acting therapy and in 93.3% who received oral therapy (adjusted difference, 0.4 percentage points; 95% CI, -3.7 to 4.5), a result that met the criterion for noninferiority for this end point (margin, -10 percentage points). Of the participants who received long-acting therapy, 86% reported injection-site reactions (median duration, 3 days; mild or moderate severity, 99% of cases); 4 participants withdrew from the trial for injection-related reasons. Grade 3 or higher adverse events and events that met liver-related stopping criteria occurred in 11% and 2%, respectively, who received long-acting therapy and in 4% and 1% who received oral therapy. Treatment satisfaction increased after participants switched to long-acting therapy; 91% preferred long-acting therapy at week 48. CONCLUSIONS: Therapy with long-acting cabotegravir plus rilpivirine was noninferior to oral therapy with dolutegravir-abacavir-lamivudine with regard to maintaining HIV-1 suppression. Injection-site reactions were common. (Funded by ViiV Healthcare and Janssen; FLAIR ClinicalTrials.gov number, NCT02938520.)