234 research outputs found

    La paleodieta de cinco especies de mamíferos herbívoros rancholabreanos de valsequillo (Puebla, México)

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    Through the use of the 13C/12C and 18O/16O isotopic relationships found at enamel and osteodentine, here it is inferred the diet and preferred habitat in which five extinct herbivore species from the Late Pleistocene of Valsequillo, Puebla, México. The horses, mammoths, and sloths showed a diet mainly based in C4, meanwhile the capybaraand gomphotheres were mixed C3/C4 feeders. The vegetation in which those animals lived was open with some trees, similar to the one proposed in other studies based in some macromammals species found in the locality.Usando las relaciones isotópicas de 13C/12C y 18O/16O presentes en el esmalte y la osteodentina, se infirió la dieta y el ambiente en el cual vivieron cinco especies extintas de herbívoros procedentes del Pleistoceno Tardío de Valsequillo, Puebla, México. Los caballos, los mamutes y el perezoso mostraban una dieta basada exclusivamente en plantas C4, mientras que el carpincho y los gonfoterios exhibían una dieta mixta C3/C4. El tipo de vegetación en el cual estos animales habitaron fue abierto con poca cobertura arbórea, misma que ha sido propuesta en otros estudios usando la presencia de algunas especies de micromamíferos encontradosen la zona

    Stratification of cancer and diabetes based on circulating levels of formate and glucose

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    Background: Serum and urine metabolites have been investigated for their use as cancer biomarkers. The specificity of candidate metabolites can be limited by the impact of other disorders on metabolite levels. In particular, the increasing incidence of obesity could become a significant confounding factor. Methods: Here we developed a multinomial classifier for the stratification of cancer, obesity and healthy phenotypes based on circulating glucose and formate levels. We quantified the classifier performance from the retrospective analysis of samples from breast cancer, lung cancer, obese individuals and healthy controls. Results: We discovered that circulating formate levels are significantly lower in breast and lung cancer patients than in healthy controls. However, the performance of a cancer classifier based on formate levels alone is limited because obese patients also have low serum formate levels. By introducing a multinomial classifier based on circulating glucose and formate levels, we were able to improve the classifier performance, reaching a true positive rate of 79% with a false positive rate of 8%. Conclusions: Circulating formate is reduced in HER2+ breast cancer, non-small cell lung cancer and highly obese patients relative to healthy controls. Further studies are required to determine the relevance of these observations in other cancer types and diseases

    Metformin Is a Direct SIRT1-Activating Compound: Computational Modeling and Experimental Validation

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    Metformin has been proposed to operate as an agonist of SIRT1, a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase that mimics most of the metabolic responses to calorie restriction. Herein, we present an in silico analysis focusing on the molecular docking and dynamic simulation of the putative interactions between metformin and SIRT1. Using eight different crystal structures of human SIRT1 protein, our computational approach was able to delineate the putative binding modes of metformin to several pockets inside and outside the central deacetylase catalytic domain. First, metformin was predicted to interact with the very same allosteric site occupied by resveratrol and other sirtuin-activating compounds (STATCs) at the amino-terminal activation domain of SIRT1. Second, metformin was predicted to interact with the NAD(+) binding site in a manner slightly different to that of SIRT1 inhibitors containing an indole ring. Third, metformin was predicted to interact with the C-terminal regulatory segment of SIRT1 bound to the NAD(+) hydrolysis product ADP-ribose, a "C-pocket"-related mechanism that appears to be essential for mechanism-based activation of SIRT1. Enzymatic assays confirmed that the net biochemical effect of metformin and other biguanides such as a phenformin was to improve the catalytic efficiency of SIRT1 operating in conditions of low NAD(+) in vitro. Forthcoming studies should confirm the mechanistic relevance of our computational insights into how the putative binding modes of metformin to SIRT1 could explain its ability to operate as a direct SIRT1 -activating compound. These findings might have important implications for understanding how metformin might confer health benefits via maintenance of SIRT1 activity during the aging process when NAD(+) levels decline

    Towards an eco-friendly coffee rust control : compilation of natural alternatives from a nutritional and antifungal perspective

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    Hemileia vastatrix (HV) is the pathogen responsible for the coffee leaf rust (CLR) disease that has spread globally. CLR causes losses of up to a billion dollars annually and affects all types of crops regardless of their production regime (organic or inorganic). Additionally, smallholders produce approximately 80% of coffee in developing countries. The condition causes losses of up to a billion dollars annually. It affects all types of crops regardless of their production regime (organic or inorganic). Approximately 80% of coffee is produced by smallholders in developing countries. Until the 90s, shaded-production systems and native varieties were encouraged; however, the rapid spread of CLR has forced farmers to migrate towards inorganic schemes, mainly due to a lack of knowledge about natural alternatives to pesticides that can be implemented to control HV. Therefore, the purpose of this article is to compile the currently existing options, emphasizing two key factors that guarantee efficient rust control: selective fungicidal activity against HV and the nutrition of coffee crops. Thus, by comprehending how these natural compounds (such as plant, bacteria, fungi, animals, or algae metabolites) impact coffee rust proliferation. Furthermore, since a various range of biochar effects contributes to the control of foliar fungal pathogens through modification of root exudates, soil properties, and nutrient availability, which influence the growth of antagonist microorganisms, we present a review of the pathogen-suppressive effects of biochar, and new control strategies suitable for organic schemes can be developed.Publisher PDFPeer reviewe

    Physical literacy in older adults: a scoping review protocol

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    Population aging is a prominent phenomenon worldwide. The increase in physical inactivity and co-morbid diseases poses a major challenge to current community health policies. Physical activity guidelines recommended for older people have not been met by this population group. For this reason, a new model, physical literacy, is being innovated and has gained global attention and has emerged as an effective and innovative active aging strategy to improve physical activity participation of this vulnerable group. However, the evidence on physical literacy in the older adult so far is brief and diffuse. Therefore, the aim was to conduct a scoping review protocol to identify and map physical literacy in older people. This scoping review protocol was based on the Joanna Briggs Institute Method. The search will be performed on Embase, IBSS ProQuest, Medline OVID, PsycINFO Ebsco, PubMed, ScienceDirect, Scopus, SPORTDiscus, Social Services Abstracts ProQuest, Sociological Abstracts ProQuest, Web of Science ISI, Wiley Online Library, Cochrane Library, and ERIC Ebsco databases. All types of studies published since 2001 in English, Spanish, and Portuguese examining physical literacy over the lifespan of older adults were included. Two independent reviewers will organize and select studies according to the objectives and questions of the scoping review. The selected publications will be organized and summarized using a checklist proposed by the PRISMA-ScR. Qualitative data analysis (thematic analysis) will be performed to identify meanings and patterns to answer the research question. The final scoping review will present the main evidence available, key concepts/definitions, research conducted, and knowledge gaps related to physical literacy in older adults, leading to strategies to improve the community health of this population, as well as health literacy

    Association Between the Use of a Mobile Health Strategy App and Biological Changes in Breast Cancer Survivors: Prospective Pre-Post Study

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    The objectives of this study were to: (1) check whether it is feasible to find changes in inflammation biomarkers through an mHealth strategy app as a delivery mechanism of an intervention to monitor energy balance; and (2) discover potential predictors of change of these markers in breast cancer survivors (BCSs). Analyzing changes in inflammatory biomarker concentrations after using the mHealth app, differences between preassessment CRP (4899.04 pg/ml; SD 1085.25) and IL-6 (87.15 pg/ml; SD 33.59) and postassessment CRP (4221.24 pg/ml; SD 911.55) and IL-6 (60.53 pg/ml; SD 36.31) showed a significant decrease in both markers, with a mean difference of –635.25 pg/ml (95% CI –935.65 to –334.85; P<.001) in CRP and –26.61 pg/ml (95% CI –42.51 to –10.71; P=.002) in IL-6. Stepwise regression analyses revealed that changes in global quality of life, as well as uMARS score and hormonal therapy, were possible predictors of change in CRP concentration after using the mHealth app. In the same way, the type of tumor removal surgery conducted, as well as changes in weight and pain score, were possible predictors of change in IL-6 concentration after using the app. In conclusion, through the results of this study, we hypothesize that there is a possible association between an mHealth energy balance monitoring strategy and biological changes in BCSs. These changes could be explained by different biopsychosocial parameters, such as the use of the application itself, quality of life, pain, type of tumor removal surgery, hormonal treatment or obesity.The study was funded by the Spanish Ministry of Economy and Competitiveness (Plan Estatal de I+D+I 2013-2016), Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI14/01627), Fondos Estructurales de la Unión Europea (FEDER), and by the Spanish Ministry of Education (FPU14/01069 and FPU17/00939)

    Constraining the pˉ/p\bar{p}/p Ratio in TeV Cosmic Rays with Observations of the Moon Shadow by HAWC

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    An indirect measurement of the antiproton flux in cosmic rays is possible as the particles undergo deflection by the geomagnetic field. This effect can be measured by studying the deficit in the flux, or shadow, created by the Moon as it absorbs cosmic rays that are headed towards the Earth. The shadow is displaced from the actual position of the Moon due to geomagnetic deflection, which is a function of the energy and charge of the cosmic rays. The displacement provides a natural tool for momentum/charge discrimination that can be used to study the composition of cosmic rays. Using 33 months of data comprising more than 80 billion cosmic rays measured by the High Altitude Water Cherenkov (HAWC) observatory, we have analyzed the Moon shadow to search for TeV antiprotons in cosmic rays. We present our first upper limits on the pˉ/p\bar{p}/p fraction, which in the absence of any direct measurements, provide the tightest available constraints of 1%\sim1\% on the antiproton fraction for energies between 1 and 10 TeV.Comment: 10 pages, 5 figures. Accepted by Physical Review

    Very high energy particle acceleration powered by the jets of the microquasar SS 433

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    SS 433 is a binary system containing a supergiant star that is overflowing its Roche lobe with matter accreting onto a compact object (either a black hole or neutron star). Two jets of ionized matter with a bulk velocity of 0.26c\sim0.26c extend from the binary, perpendicular to the line of sight, and terminate inside W50, a supernova remnant that is being distorted by the jets. SS 433 differs from other microquasars in that the accretion is believed to be super-Eddington, and the luminosity of the system is 1040\sim10^{40} erg s1^{-1}. The lobes of W50 in which the jets terminate, about 40 pc from the central source, are expected to accelerate charged particles, and indeed radio and X-ray emission consistent with electron synchrotron emission in a magnetic field have been observed. At higher energies (>100 GeV), the particle fluxes of γ\gamma rays from X-ray hotspots around SS 433 have been reported as flux upper limits. In this energy regime, it has been unclear whether the emission is dominated by electrons that are interacting with photons from the cosmic microwave background through inverse-Compton scattering or by protons interacting with the ambient gas. Here we report TeV γ\gamma-ray observations of the SS 433/W50 system where the lobes are spatially resolved. The TeV emission is localized to structures in the lobes, far from the center of the system where the jets are formed. We have measured photon energies of at least 25 TeV, and these are certainly not Doppler boosted, because of the viewing geometry. We conclude that the emission from radio to TeV energies is consistent with a single population of electrons with energies extending to at least hundreds of TeV in a magnetic field of 16\sim16~micro-Gauss.Comment: Preprint version of Nature paper. Contacts: S. BenZvi, B. Dingus, K. Fang, C.D. Rho , H. Zhang, H. Zho

    Metformin induces a fasting- and antifolate-mimicking modification of systemic host metabolism in breast cancer patients

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    Certain dietary interventions might improve the therapeutic index of cancer treatments. An alternative to the "drug plus diet" approach is the pharmacological reproduction of the metabolic traits of such diets. Here we explored the impact of adding metformin to an established therapeutic regimen on the systemic host metabolism of cancer patients. A panel of 11 serum metabolites including markers of mitochondria! function and intermediates/products of folate-dependent one-carbon metabolism were measured in paired baseline and post-treatment sera obtained from HER2-positive breast cancer patients randomized to receive either metformin combined with neoadjuvant chemotherapy and trastuzumab or an equivalent regimen without metformin. Metabolite profiles revealed a significant increase of the ketone body beta-hydroxybutyrate and of the TCA intermediate alpha-ketoglutarate in the metformin-containing arm. A significant relationship was found between the follow-up levels of homocysteine and the ability of treatment arms to achieve a pathological complete response (pCR). In the metformin-containing arm, patients with significant elevations of homocysteine tended to have a higher probability of pCR. The addition of metformin to an established anticancer therapeutic regimen causes a fasting-mimicking modification of systemic host metabolism. Circulating homocysteine could be explored as a clinical pharmacodynamic biomarker linking the antifolate-like activity of metformin and biological tumor response
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