Dietary sulfur amino acid restriction upregulates DICER to confer beneficial effects

Dietary restriction (DR) improves health and prolongs lifespan in part by upregulating type III endoribonuclease DICER in adipose tissue. In this study, we aimed to specifically test which missing dietary component was responsible for DICER upregulation. Methods: We performed a nutrient screen in mouse preadipocytes and validated the results in vivo using different kinds of dietary interventions in wild type or genetically modified mice and worms, also testing the requirement of DICER on the effects of the diets. Results: We found that sulfur amino acid restriction (i.e., methionine or cysteine) is sufficient to increase Dicer mRNA expression in preadipocytes. Consistently, while DR increases DICER expression in adipose tissue of mice, this effect is blunted by supplementation of the diet with methionine, cysteine, or casein, but not with a lipid or carbohydrate source. Accordingly, dietary methionine or protein restriction mirrors the effects of DR. These changes are associated with alterations in serum adiponectin. We also found that DICER controls and is controlled by adiponectin. In mice, DICER plays a role in methionine restriction-induced upregulation of Ucpl in adipose tissue. In C. elegans, DR and a model of methionine restriction also promote DICER expression in the intestine (an analog of the adipose tissue) and prolong lifespan in a DICER-dependent manner. Conclusions: We propose an evolutionary conserved mechanism in which dietary sulfur amino acid restriction upregulates DICER levels in adipose tissue leading to beneficial health effects29124135CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP305069/2015-2; 304995/2014-288887.143923/2017-002017/01184-9; 2017/07975-8; 2017/22057-5; 2015/03292-8; 2012/07259-7; 2016/02207-0; 2010/52557-0; 2015/01316-7; 2012/50558-5; 2015/19530-5We thank Elzira Elisabeth Saviani and Emanoel Cabral for valuable technical support. We thank the National Institute of Science and Technology on Photonics Applied to Cell Biology (INFABIC) at the Universidade Estadual de Campinas to provide access to microscopes, the Caenorhabditis Genetics Center (CGC) for worms and Dr. Amy Pasquinelli for the dcr-1 RNAi clone. CGC is funded by NIH Office of Research Infrastructure Programs ( P40 OD010440 ). We thank Carmen Perrone for sharing the composition of the methionine restriction diet, for valuable discussion and for sharing samples of rats exposed to methionine restriction. This study was funded by grants of the Fundação de Amparo à Pesquisa do Estado de São Paulo ( 2017/01184-9 , 2017/07975-8 , 2017/22057-5 , 2015/03292-8 , 2012/07259-7 , 2016/02207-0 , 2010/52557-0 , 2015/01316-7 , 2012/50558-5 and 2015/19530-5 ), Conselho Nacional de Desenvolvimento Científico e Tecnológico ( 305069/2015-2 and 304995/2014-2 ) and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - German Academic Exchange Service ( PROBRAL - 88887.143923/2017-00 )

Epidemiology of Disappearing Plasmodium vivax Malaria: A Case Study in Rural Amazonia

Background: New frontier settlements across the Amazon Basin pose a major challenge for malaria elimination in Brazil. Here we describe the epidemiology of malaria during the early phases of occupation of farming settlements in Remansinho area, Brazilian Amazonia. We examine the relative contribution of low-density and asymptomatic parasitemias to the overall Plasmodium vivax burden over a period of declining transmission and discuss potential hurdles for malaria elimination in Remansinho and similar settings. Methods: Eight community-wide cross-sectional surveys, involving 584 subjects, were carried out in Remansinho over 3 years and complemented by active and passive surveillance of febrile illnesses between the surveys. We used quantitative PCR to detect low-density asexual parasitemias and gametocytemias missed by conventional microscopy. Mixed-effects multiple logistic regression models were used to characterize independent risk factors for P. vivax infection and disease. Principal Findings/Conclusions P. vivax prevalence decreased from 23.8% (March–April 2010) to 3.0% (April–May 2013), with no P. falciparum infections diagnosed after March–April 2011. Although migrants from malaria-free areas were at increased risk of malaria, their odds of having P. vivax infection and disease decreased by 2–3% with each year of residence in Amazonia. Several findings indicate that low-density and asymptomatic P. vivax parasitemias may complicate residual malaria elimination in Remansinho: (a) the proportion of subpatent infections (i.e. missed by microscopy) increased from 43.8% to 73.1% as P. vivax transmission declined; (b) most (56.6%) P. vivax infections were asymptomatic and 32.8% of them were both subpatent and asymptomatic; (c) asymptomatic parasite carriers accounted for 54.4% of the total P. vivax biomass in the host population; (d) over 90% subpatent and asymptomatic P. vivax had PCR-detectable gametocytemias; and (e) few (17.0%) asymptomatic and subpatent P. vivax infections that were left untreated progressed to clinical disease over 6 weeks of follow-up and became detectable by routine malaria surveillance

Prime Focus Spectrograph - Subaru's future -

The Prime Focus Spectrograph (PFS) of the Subaru Measurement of Images and Redshifts (SuMIRe) project has been endorsed by Japanese community as one of the main future instruments of the Subaru 8.2-meter telescope at Mauna Kea, Hawaii. This optical/near-infrared multi-fiber spectrograph targets cosmology with galaxy surveys, Galactic archaeology, and studies of galaxy/AGN evolution. Taking advantage of Subaru's wide field of view, which is further extended with the recently completed Wide Field Corrector, PFS will enable us to carry out multi-fiber spectroscopy of 2400 targets within 1.3 degree diameter. A microlens is attached at each fiber entrance for F-ratio transformation into a larger one so that difficulties of spectrograph design are eased. Fibers are accurately placed onto target positions by positioners, each of which consists of two stages of piezo-electric rotary motors, through iterations by using back-illuminated fiber position measurements with a wide-field metrology camera. Fibers then carry light to a set of four identical fast-Schmidt spectrographs with three color arms each: the wavelength ranges from 0.38 {\mu}m to 1.3 {\mu}m will be simultaneously observed with an average resolving power of 3000. Before and during the era of extremely large telescopes, PFS will provide the unique capability of obtaining spectra of 2400 cosmological/astrophysical targets simultaneously with an 8-10 meter class telescope. The PFS collaboration, led by IPMU, consists of USP/LNA in Brazil, Caltech/JPL, Princeton, & JHU in USA, LAM in France, ASIAA in Taiwan, and NAOJ/Subaru.Comment: 13 pages, 11 figures, submitted to "Ground-based and Airborne Instrumentation for Astronomy IV, Ian S. McLean, Suzanne K. Ramsay, Hideki Takami, Editors, Proc. SPIE 8446 (2012)

Avaliação do estado nutricional de agroecossistemas de café orgânico no estado de Minas Gerais.

A produção de café orgânico vem se constituindo uma tendência necessária e irreversível do agronegócio brasileiro. Essa atividade tem-se destacado como uma alternativa de renda para alguns cafeicultores, devido à crescente demanda mundial por alimentos mais saudáveis. Entretanto, grande parte das técnicas propostas pela agricultura orgânica está sendo aplicada empiricamente no cultivo de café, principalmente no Estado de Minas Gerais, maior região produtora de café do Brasil. Levando-se em consideração a baixa fertilidade natural dos solos dessa região cafeeira, bem como a elevada extração de nutrientes pelo cafeeiro, objetivou-se neste trabalho identificar possíveis fatores limitantes para a produção orgânica do cafeeiro, relacionados à fertilidade do solo e ao estado nutricional das plantas. Foram realizadas avaliações da fertilidade do solo e análise das folhas em vinte e uma lavouras orgânicas representativas do Estado de Minas Gerais. As amostras de solo foram analisadas para determinação do pH, acidez potencial e dos teores de P, K, Ca, Mg, S, Al e matéria orgânica. As amostras foliares foram analisadas para determinação dos teores de N, P, K, Ca, Mg, S, B, Cu, Fe, Mn e Zn. Com base nos padrões de interpretação para cafeeiros convencionais propostos pela literatura, estabeleceram-se as freqüências com que os caracteres analisados foram inferiores aos critérios de interpretação da fertilidade do solo e estado nutricional das plantas. A análise dos dados foi realizada por estatística descritiva. Novos trabalhos nessa nova área são necessários, visando a uma melhor interpretação da análise foliar e da fertilidade do solo, quando se trabalha com café orgânico

Technical challenges of working with extracellular vesicles

Extracellular Vesicles (EVs) are gaining interest as central players in liquid biopsies, with potential applications in diagnosis, prognosis and therapeutic guidance in most pathological conditions. These nanosized particles transmit signals determined by their protein, lipid, nucleic acid and sugar content, and the unique molecular pattern of EVs dictates the type of signal to be transmitted to recipient cells. However, their small sizes and the limited quantities that can usually be obtained from patient-derived samples pose a number of challenges to their isolation, study and characterization. These challenges and some possible options to overcome them are discussed in this review

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

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

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file