131 research outputs found

    High folic acid consumption leads to pseudo-MTHFR deficiency, altered lipid metabolism, and liver injury in mice.

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    Increased consumption of folic acid is prevalent, leading to concerns about negative consequences. The effects of folic acid on the liver, the primary organ for folate metabolism, are largely unknown. Methylenetetrahydrofolate reductase (MTHFR) provides methyl donors for S-adenosylmethionine (SAM) synthesis and methylation reactions

    Compact planar lenses based on a pinhole and an array of single mode metallic slits

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    Plasmonic lenses are based on complex combinations of nanoscale high aspect ratio slits. We show that their design can be greatly simplified, keeping similar performance while releasing technological constraints. The simplified system, called Huygens lens, consists in a central aperture surrounded by several identical single mode slits in a thin gold layer that does not rely anymore on surface plasmons. The focusing behaviour with respect to the position and number of slits is investigated, and we demonstrate the interest of this design to get compact array of lenses

    Uncovering the multifaceted roles played by neutrophils in allogeneic hematopoietic stem cell transplantation

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    Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a life-saving procedure used for the treatment of selected hematological malignancies, inborn errors of metabolism, and bone marrow failures. The role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against infection. However, recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered functions. Accordingly, neutrophils are emerging as highly versatile cells that are able to acquire different, often opposite, functional capacities depending on the microenvironment and their differentiation status. Herein, we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT, from the hematopoietic stem cell (HSC) mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC infusion. We also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versus-host disease (GVHD) prophylaxis. Finally, the potential involvement of neutrophils in alloHSCT-related complications, such as transplant-associated thrombotic microangiopathy (TA-TMA), acute and chronic GVHD, and cytomegalovirus (CMV) reactivation, is also discussed. Based on the data reviewed herein, the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial role. However, much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT

    Temporal mapping of photochemical reactions and molecular excited states with carbon specificity

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    Photochemical reactions are essential to a large number of important industrial and biological processes. A method for monitoring photochemical reaction kinetics and the dynamics of molecular excitations with spatial resolution within the active molecule would allow a rigorous exploration of the pathway and mechanism of photophysical and photochemical processes. Here we demonstrate that laser-excited muon pump-probe spin spectroscopy (photo-μSR) can temporally and spatially map these processes with a spatial resolution at the single-carbon level in a molecule with a pentacene backbone. The observed time-dependent light-induced changes of an avoided level crossing resonance demonstrate that the photochemical reactivity of a specific carbon atom is modified as a result of the presence of the excited state wavefunction. This demonstrates the sensitivity and potential of this technique in probing molecular excitations and photochemistry

    Dissecting the transcriptional networks underlying breast cancer: NR4A1 reduces the migration of normal and breast cancer cell lines

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    Introduction: Breast cancer currently accounts for more than one-quarter of all female cancers and, despite the great progress in treatment observed in the past few years, the need for identification of new gene targets that can be used for diagnosis, prognosis and therapy is evident. A previous study identified the transcription factor NR4A1 as a gene upregulated in primary breast cancer compared with normal tissue by microarray analysis and sequencing technologies. The purpose of the study was to identify the role of NR4A1 in normal mammary epithelial and breast cancer cell biology.Methods: NR4A1 expression in breast tumours was assessed by semiquantitative and real-time PCR using RNA from normal and tumour samples or breast cancer cell lines. Immunohistochemistry on tissue microarrays was performed to check NR4A1 protein expression in breast tumours. MCF-10A and 226L normal mammary epithelial cells as well as the tumour lines PMC42, ZR-75-1 and MDA-MB-231 were transduced with full-length NR4A1, and the ability of NR4A1-overexpressing cells to migrate was tested using scratch wound or transwell migration assays. Proliferation was measured using the MTT and BrdU assays, while apoptosis was determined by the Annexin V assay. The ability of the cells to adhere to extracellular matrix was tested by adhesion assays and integrin cell surface expression was measured by flow cytometry. Activation of the FAK as well as ERK1/2 and PI3K pathways was checked by western blotting.Results: Breast tissue microarray analysis showed NR4A1 expression in primary tumours, which was reduced in higher grade and metastatic tumours. Ectopic expression of NR4A1 in MCF-10A, 226L, PMC42 and ZR-75-1 cells led to reduced ability of the cells to migrate, while no differences were observed in their proliferation and apoptotic index. NR4A1 expression altered the ability of the MCF-10A cells to adhere to the extracellular matrix and affected cell surface expression of integrins.Conclusions: NR4A1 acts as an antimigratory factor in two normal mammary epithelial and two breast cancer cell lines tested. It is therefore possible that NR4A1 acts as an antimigratory factor in breast tumours, and further studies should be conducted to understand the mechanisms involved

    Peatland Initiation, Carbon Accumulation, and 2 ka Depth in the James Bay Lowland and Adjacent Regions

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    Copyright © 2014 University of Colorado at Boulder, Institute of Arctic and Alpine ResearchPeatlands surrounding Hudson and James Bays form the second largest peatland complex in the world and contain major stores of soil carbon (C). This study utilized a transect of eight ombrotrophic peat cores from remote regions of central and northern Ontario to quantify the magnitude and rate of C accumulation since peatland initiation and for the past 2000 calendar years before present (2 ka). These new data were supplemented by 17 millennially resolved chronologies from a literature review covering the Boreal Shield, Hudson Plains, and Taiga Shield bordering Hudson and James Bays. Peatlands initiated in central and northern Ontario by 7.8 ka following deglaciation and isostatic emergence of northern areas to above sea level. Total C accumulated since inception averaged 109.7 ± (std. dev.) 36.2 kg C m–2. Approximately 40% of total soil C has accumulated since 2 ka at an average apparent rate of 20.2 ± 6.9 g C m–2 yr–1. The 2 ka depths correlate significantly and positively with modern gridded climate estimates for mean annual precipitation, mean annual air temperature, growing degree-days > 0 °C, and photosynthetically active radiation integrated over days > 0 °C. There are significantly shallower depths in permafrost peatlands. Vertical peat accumulation was likely constrained by temperature, growing season length, and photosynthetically active radiation over the last 2 ka in the Hudson Bay Lowlands and surrounding regions.US National Science Foundatio

    Molecular techniques for pathogen identification and fungus detection in the environment

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    Many species of fungi can cause disease in plants, animals and humans. Accurate and robust detection and quantification of fungi is essential for diagnosis, modeling and surveillance. Also direct detection of fungi enables a deeper understanding of natural microbial communities, particularly as a great many fungi are difficult or impossible to cultivate. In the last decade, effective amplification platforms, probe development and various quantitative PCR technologies have revolutionized research on fungal detection and identification. Examples of the latest technology in fungal detection and differentiation are discussed here

    Hiding in the background: community-level patterns in invertebrate herbivory across the tundra biome

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    Invertebrate herbivores depend on external temperature for growth and metabolism. Continued warming in tundra ecosystems is proposed to result in increased invertebrate herbivory. However, empirical data about how current levels of invertebrate herbivory vary across the Arctic is limited and generally restricted to a single host plant or a small group of species, so predicting future change remains challenging. We investigated large-scale patterns of invertebrate herbivory across the tundra biome at the community level and explored how these patterns are related to long-term climatic conditions and year-of-sampling weather, habitat characteristics, and aboveground biomass production. Utilizing a standardized protocol, we collected samples from 92 plots nested within 20 tundra sites during summer 2015. We estimated the community-weighted biomass lost based on the total leaf area consumed by invertebrates for the most common plant species within each plot. Overall, invertebrate herbivory was prevalent at low intensities across the tundra, with estimates averaging 0.94% and ranging between 0.02 and 5.69% of plant biomass. Our results suggest that mid-summer temperature influences the intensity of invertebrate herbivory at the community level, consistent with the hypothesis that climate warming should increase plant losses to invertebrates in the tundra. However, most of the observed variation in herbivory was associated with other site level characteristics, indicating that other local ecological factors also play an important role. More details about the local drivers of invertebrate herbivory are necessary to predict the consequences for rapidly changing tundra ecosystems.KeywordsBackground herbivory Biomass loss Climate change Community-weighted average Invertebrate Insects Tundra </div

    Effects of climate and atmospheric nitrogen deposition on early to mid-term stage litter decomposition across biomes

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    Litter decomposition is a key process for carbon and nutrient cycling in terrestrial ecosystems and is mainly controlled by environmental conditions, substrate quantity and quality as well as microbial community abundance and composition. In particular, the effects of climate and atmospheric nitrogen (N) deposition on litter decomposition and its temporal dynamics are of significant importance, since their effects might change over the course of the decomposition process. Within the TeaComposition initiative, we incubated Green and Rooibos teas at 524 sites across nine biomes. We assessed how macroclimate and atmospheric inorganic N deposition under current and predicted scenarios (RCP 2.6, RCP 8.5) might affect litter mass loss measured after 3 and 12 months. Our study shows that the early to mid-term mass loss at the global scale was affected predominantly by litter quality (explaining 73% and 62% of the total variance after 3 and 12 months, respectively) followed by climate and N deposition. The effects of climate were not litter-specific and became increasingly significant as decomposition progressed, with MAP explaining 2% and MAT 4% of the variation after 12 months of incubation. The effect of N deposition was litter-specific, and significant only for 12-month decomposition of Rooibos tea at the global scale. However, in the temperate biome where atmospheric N deposition rates are relatively high, the 12-month mass loss of Green and Rooibos teas decreased significantly with increasing N deposition, explaining 9.5% and 1.1% of the variance, respectively. The expected changes in macroclimate and N deposition at the global scale by the end of this century are estimated to increase the 12-month mass loss of easily decomposable litter by 1.1-3.5% and of the more stable substrates by 3.8-10.6%, relative to current mass loss. In contrast, expected changes in atmospheric N deposition will decrease the mid-term mass loss of high-quality litter by 1.4-2.2% and that of low-quality litter by 0.9-1.5% in the temperate biome. Our results suggest that projected increases in N deposition may have the capacity to dampen the climate-driven increases in litter decomposition depending on the biome and decomposition stage of substrate. © Copyright © 2021 Kwon, Shibata, Kepfer-Rojas, Schmidt, Larsen, Beier, Berg, Verheyen, Lamarque, Hagedorn, Eisenhauer, Djukic and TeaComposition Network
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