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

Near-Infrared Photometric Survey of Proto-Planetary Nebula Candidates

We present JHK' photometric measurements of 78 objects mostly consisting of proto-planetary nebula candidates. Photometric magnitudes are determined by means of imaging and aperture photometry. Unlike the observations with a photometer with a fixed-sized beam, the method of imaging photometry permits accurate derivation of photometric values because the target sources can be correctly identified and confusion with neighboring sources can be easily avoided. Of the 78 sources observed, we report 10 cases in which the source seems to have been misidentified or confused by nearby bright sources. We also present nearly two dozen cases in which the source seems to have indicated a variability which prompts a follow-up monitoring. There are also a few sources that show previously unreported extendedness. In addition, we present H band finding charts of the target sources.Comment: 3 tables, 1 figur

A pilot study comparing two weight loss maintenance interventions among low-income, mid-life women

Abstract: Background: Despite high obesity prevalence rates, few low-income midlife women participate in weight loss maintenance trials. This pilot study aims to assess the effectiveness of two weight loss maintenance interventions in this under-represented population. Methods: Low-income midlife women who completed a 16-week weight loss intervention and lost ≥ 8 lbs (3.6 kg) were eligible to enroll in one of two 12-month maintenance programs. The programs were similar in content and had the same number of total contacts, but were different in the contact modality (Phone + Face-to-Face vs. Face-to- Face Only). Two criteria were used to assess successful weight loss maintenance at 12 months: (1) retaining a loss of ≥ 5% of body weight from the start of the weight loss phase and (2) a change in body weight of < 3%, from the start to the end of the maintenance program. Outcome measures of changes in physiologic and psychosocial factors, and evaluations of process measures and program acceptability (measured at 12 months) are also reported. For categorical variables, likelihood ratio or Fisher’s Exact (for small samples) tests were used to evaluate statistically significant relationships; for continuous variables, t-tests or their equivalents were used to assess differences between means and also to identify correlates of weight loss maintenance. Results: Overall, during the 12-month maintenance period, 41% (24/58) of participants maintained a loss of ≥ 5% of initial weight and 43% (25/58) had a <3% change in weight. None of the comparisons between the two maintenance programs were statistically significant. However, improvements in blood pressure and dietary behaviors remained significant at the end of the 12-month maintenance period for participants in both programs. Participant attendance and acceptability were high for both programs. Conclusions: The effectiveness of two pilot 12-month maintenance interventions provides support for further research in weight loss maintenance among high-risk, low-income women. Trial registration ClinicalTrials.gov Identifier: NCT0028830

The impacts of social determinants of health and cardiometabolic factors on cognitive and functional aging in Colombian underserved populations

Global initiatives call for further understanding of the impact of inequity on aging across underserved populations. Previous research in low- and middle-income countries (LMICs) presents limitations in assessing combined sources of inequity and outcomes (i.e., cognition and functionality). In this study, we assessed how social determinants of health (SDH), cardiometabolic factors (CMFs), and other medical/social factors predict cognition and functionality in an aging Colombian population. We ran a cross-sectional study that combined theory- (structural equation models) and data-driven (machine learning) approaches in a population-based study (N = 23,694; M = 69.8 years) to assess the best predictors of cognition and functionality. We found that a combination of SDH and CMF accurately predicted cognition and functionality, although SDH was the stronger predictor. Cognition was predicted with the highest accuracy by SDH, followed by demographics, CMF, and other factors. A combination of SDH, age, CMF, and additional physical/psychological factors were the best predictors of functional status. Results highlight the role of inequity in predicting brain health and advancing solutions to reduce the cognitive and functional decline in LMICs.Fil: Santamaria Garcia, Hernando. Pontificia Universidad Javeriana; Colombia. Hospital Universitario San Ignacio; Colombia. University of California; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Moguilner, Sebastian Gabriel. Universidad de San Andrés; Argentina. Massachusetts General Hospital; Estados Unidos. Universidad Adolfo Ibañez; ChileFil: Rodriguez Villagra, Odir Antonio. Universidad de Costa Rica; Costa RicaFil: Botero Rodriguez, Felipe. Pontificia Universidad Javeriana; ColombiaFil: Pina Escudero, Stefanie Danielle. University of California; Estados UnidosFil: O’Donovan, Gary. Universidad Adolfo Ibañez; Chile. Universidad de los Andes; ColombiaFil: Albala, Cecilia. Universidad de Chile; ChileFil: Matallana, Diana. Fundacion Santa Fe de Bogota; Colombia. Hospital Universitario San Ignacio; Colombia. Pontificia Universidad Javeriana; ColombiaFil: Schulte, Michael. Universidad Adolfo Ibañez; ChileFil: Slachevsky, Andrea. Universidad del Desarrollo; Chile. Universidad de Chile; ChileFil: Yokoyama, Jennifer S.. University of California; Estados UnidosFil: Possin, Katherine. University of California; Estados UnidosFil: Ndhlovu, Lishomwa C.. Weill Cornell Medicine; Estados UnidosFil: Al-Rousan, Tala. University of California at San Diego; Estados UnidosFil: Corley, Michael J.. Weill Cornell Medicine; Estados UnidosFil: Kosik, Kenneth. University of California; Estados UnidosFil: Muniz Terrera, Graciela. University of Edinburgh; Reino Unido. Ohio University; Estados UnidosFil: Miranda, J. Jaime. George Institute For Global Health; Australia. Cronicas Centro de Excelencia En Enfermedades Crónicas; Perú. Universidad Peruana Cayetano Heredia; PerúFil: Ibañez, Agustin Mariano. Universidad de San Andrés; Argentina. Trinity College Dublin; Irlanda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of California; Estados Unidos. Universidad Adolfo Ibañez; Chil

A community assessment to inform a multi-level intervention to reduce CVD risk and risk disparities in a rural community

In order to complete a formative evaluation to identify community-level assets and barriers to healthy lifestyle choices, we conducted qualitative interviews, community audits, and secondary data analyses. We solicited local leaders’ perspectives regarding ‘win-ability’ of obesity prevention policy options. Participants noted that many resources were available, yet a barrier was high cost. There were more parks per capita in low-income areas, but they were of lower quality. The most winnable obesity prevention policy was incentives for use of food from local farms. Results are being used to inform an intervention to reduce CVD risk in a rural eastern North Carolina

Leishmanicidal and Immunomodulatory Activities of the Palladacycle Complex DPPE 1.1, a Potential Candidate for Treatment of Cutaneous Leishmaniasis

The present study focused on the activity of the palladacycle complex DPPE 1.1 on Leishmania (Leishmania) amazonensis. Promastigotes of L. (L.) amazonensis were destroyed in vitro by nanomolar concentrations of DPPE 1.1, whereas intracellular amastigotes were killed at drug concentrations fivefold less toxic than those harmful to macrophages. L. (L.) amazonensis-infected BALB/c mice were treated by intralesional injection of DPPE 1.1. Animals treated with 3.5 and 7.0 mg/kg of DPPE 1.1 showed a significant decrease of foot lesion sizes and a parasite load reduction of 93 and 99%, respectively, when compared to untreated controls. Furthermore, DPPE 1.1 was non-toxic to treated animals. The cathepsin B activity of L. (L.) amazonensis amastigotes was inhibited by DPPE 1.1 as demonstrated spectrofluorometrically by use of a specific fluorogenic substrate. Analysis of T-cells populations in mice treated with DPPE 1.1 and untreated controls was performed by fluorescence-activated cell sorter (FACS). IFN-γ was measured in supernatants of lymphocytes from popliteal and inguinal lymph nodes isolated from treated and untreated mice and stimulated with L. (L.) amazonensis amastigotes extract and active TGF-β was evaluated in supernatants of foot lesions; both dosages were carried out by means of a double-sandwich ELISA assay. A significant increase of TCD4+ and TCD8+ lymphocytes and IFN-γ secretion was displayed in mice treated with DPPE 1.1 compared to untreated animals, whereas a significant reduction of active TGF-β was observed in treated mice. These findings open perspectives for further investment in DPPE 1.1 as an alternative option for the chemotherapy of cutaneous leishmaniasis

LICAVAL: combination therapy in acute and maintenance treatment of bipolar disorder

<p>Abstract</p> <p>Background</p> <p>The challenge of Bipolar Disorder (BD) treatment is due to the complexity of the disease. Current guidelines represent an effort to help clinicians in their everyday practice but still have limitations, specially concerning to long term treatment. LICAVAL (e<it>fficacy and tolerability of the combination of <b>LI</b>thium and <b>CA</b>rbamazepine compared to lithium and <b>VAL</b>proic acid in the treatment of young bipolar patients</it>) study aim to evaluate acute and maintenance phase of BD treatment with two combined drugs.</p> <p>Methods</p> <p>LICAVAL is a single site, parallel group, randomized, outcome assessor blinded trial. BD I patients according to the DSM-IV-TR, in depressive, manic,/hypomanic or mixed episode, aged 18 to 35 years are eligible. After the diagnostic assessments, the patients are allocated for one of the groups of treatment (lithium + valproic acid or lithium + carbamazepine). Patients will be followed up for 8 weeks in phase I (acute treatment), 6 months in phase II (continuation treatment) and 12 months in phase III (maintenance treatment). Outcome assessors are blind to the treatment. The main outcome is the evaluation of changes in mean scores on CGI-BP-M between baseline and endpoint at the end of each phase of the study.</p> <p>Results</p> <p>LICAVAL is currently in progress, with patients in phase I, II or III. It will extended until august 2012.</p> <p>Conclusions</p> <p>Trials comparing specific treatments efficacy in BD (head to head) can show relevant information in clinical practice. Long term treatment is an issue of great important and should be evaluated carefully in more studies as long as BD is a chronic disease.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier: NCT00976794</p

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO