335 research outputs found

    Biological functions of carbohydrate ABH blood group determinants

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    The ABH blood group determinants are carbohydrates found in different human cells and tissues. The modulation in their expression in the course of ontogenesis, as well as the studies on their subcellular localization, impose a discussion on the role of ABH antigens as molecules participating in cell interactions, contact inhibition, adhesion and metastases. It is supposed that they are also involved in cellular differentiation during human embryogenesis. The described association between blood groups and disease and the de novo acquisition of blood group determinants support the idea that ABH antigens are related to pathological processes. The modulation in blood group antigen expression observed in several tumors demands a clarification of their diagnostic and prognostic value as tumor-associated markers.Biomedical Reviews 1994; 10: 55-63

    Between a hygiene rock and a hygienic hard place:Avoiding SARS-CoV-2 while needing environmental exposures for immunity

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    Suboptimal understanding of concepts related to hygiene by the general public, clinicians and researchers is a persistent problem in health and medicine. Although hygiene is necessary to slow or prevent deadly pandemics of infectious disease such as coronavirus disease 2019 (COVID-19), hygiene can have unwanted effects. In particular, some aspects of hygiene cause a loss of biodiversity from the human body, characterized by the almost complete removal of intestinal worms (helminths) and protists. Research spanning more than half a century documents that this loss of biodiversity results in an increased propensity for autoimmune disease, allergic disorders, probably neuropsychiatric problems and adverse reactions to infectious agents. The differences in immune function between communities with and communities without helminths have become so pronounced that the reduced lethality of severe acute respiratory syndrome coronavirus 2 in low-income countries compared to high-income countries was predicted early in the COVID-19 pandemic. This prediction, based on the maladaptive immune responses observed in many cases of COVID-19 in high-income countries, is now supported by emerging data from low-income countries. Herein, hygiene is subdivided into components involving personal choice versus components instituted by community wide systems such as sewage treatment facilities and water treatment plants. The different effects of personal hygiene and systems hygiene are described, and appropriate measures to alleviate the adverse effects of hygiene without losing the benefits of hygiene are discussed. Finally, text boxes are provided to function as stand-alone, public-domain handouts with the goal of informing the public about hygiene and suggesting solutions for biomedical researchers and policy makers. Lay Summary: Hygiene related to sewer systems and other technology can have adverse effects on immune function, and is distinct from personal hygiene practices such as hand washing and social distancing. Dealing with the drawbacks of hygiene must be undertaken without compromising the protection from infectious disease imposed by hygiene

    Ethnicity associated microbial and metabonomic profiling in newly diagnosed ulcerative colitis

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    Introduction: Ulcerative colitis (UC) differs across geography and ethnic groups. Gut microbial diversity plays a pivotal role in disease pathogenesis and differs across ethnic groups. The functional diversity in microbial-driven metabolites may have a pathophysiologic role and offer new therapeutic avenues. Methods: Demographics and clinical data were recorded from newly diagnosed UC patients. Blood, urine and faecal samples were collected at three time points over one year. Bacterial content was analysed by 16S rRNA sequencing. Bile acid profiles and polar molecules in three biofluids were measured using liquid-chromatography mass spectrometry (HILIC) and nuclear magnetic resonance spectroscopy. Results: We studied 42 patients with a new diagnosis of UC (27 South Asians; 15 Caucasians) with 261 biosamples. There were significant differences in relative abundance of bacteria at the phylum, genus and species level. Relative concentrations of urinary metabolites in South Asians were significantly lower for hippurate (positive correlation for Ruminococcus) and 4-cresol sulfate (Clostridia) (p<0.001) with higher concentrations of lactate (negative correlation for Bifidobacteriaceae). Faecal conjugated and primary conjugated bile acids concentrations were significantly higher in South Asians (p=0.02 and p=0.03 respectively). Results were unaffected by diet, phenotype, disease severity and ongoing therapy. Comparison of time points at diagnosis and at 1 year did not reveal changes in microbial and metabolic profile. Conclusion: Ethnic-related microbial metabolite associations were observed in South Asians with UC. This suggests a predisposition to UC may be influenced by environmental factors reflected in a distinct gene-environment interaction. The variations may serve as markers to identify risk factors for UC and modified to enhance therapeutic response

    The electrical structure of the central Pacific upper mantle constrained by the NoMelt experiment

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    Author Posting. © American Geophysical Union, 2015. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry, Geophysics, Geosystems 16 (2015): 1115–1132, doi:10.1002/2014GC005709.The NoMelt experiment imaged the mantle beneath 70 Ma Pacific seafloor with the aim of understanding the transition from the lithosphere to the underlying convecting asthenosphere. Seafloor magnetotelluric data from four stations were analyzed using 2-D regularized inverse modeling. The preferred electrical model for the region contains an 80 km thick resistive (>103 Ωm) lithosphere with a less resistive (∼50 Ωm) underlying asthenosphere. The preferred model is isotropic and lacks a highly conductive (≤10 Ωm) layer under the resistive lithosphere that would be indicative of partial melt. We first examine temperature profiles that are consistent with the observed conductivity profile. Our profile is consistent with a mantle adiabat ranging from 0.3 to 0.5°C/km. A choice of the higher adiabatic gradient means that the observed conductivity can be explained solely by temperature. In contrast, a 0.3°C/km adiabat requires an additional mechanism to explain the observed conductivity profile. Of the plausible mechanisms, H2O, in the form of hydrogen dissolved in olivine, is the most likely explanation for this additional conductivity. Our profile is consistent with a mostly dry lithosphere to 80 km depth, with bulk H2O contents increasing to between 25 and 400 ppm by weight in the asthenosphere with specific values dependent on the choice of laboratory data set of hydrous olivine conductivity and the value of mantle oxygen fugacity. The estimated H2O contents support the theory that the rheological lithosphere is a result of dehydration during melting at a mid-ocean ridge with the asthenosphere remaining partially hydrated and weakened as a result.Funding for the NoMELT experiment was provided by the National Science Foundation through the following grant numbers: OCE-0927172, OCE-0928270, OCE-1459649, and OCE-0928663.2015-10-1

    Disruption of Astrocyte STAT3 Signaling Decreases Mitochondrial Function and Increases Oxidative Stress In Vitro

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    Astrocytes exert a wide variety of functions in health and disease and respond to a wide range of signaling pathways, including members of the Janus-kinase signal transducers and activators of transcription (Jak-STAT) family. We have recently shown that STAT3 is an important regulator of astrocyte reactivity after spinal cord injury in vivo[1].Here, we used both a conditional gene deletion strategy that targets the deletion of STAT3 selectively to astrocytes (STAT3-CKO), and a pharmacological inhibitor of JAK-2, AG490, in cultured astrocytes in vitro, to investigate potential functions and molecules influenced by STAT3 signaling in relation to mitochondrial function and oxidative stress. Our findings show that the absence of STAT3 signaling in astrocytes leads to (i) increased production of superoxide anion and other reactive oxygen species and decreased level of glutathione, (ii) decreased mitochondrial membrane potential and decreased ATP production, and (iii) decreased rate of cell proliferation. Many of the differences observed in STAT3-CKO astrocytes were distinctly altered by exposure to rotenone, suggesting a role for complex I of the mitochondrial electron transport chain. Gene expression microarray studies identified numerous changes in STAT3-CKO cells that may have contributed to the identified deficits in cell function.Taken together, these STAT3-dependent alterations in cell function and gene expression have relevance to both reactive gliosis and to the support and protection of surrounding cells in neural tissue

    Volatile Content of 4-Vesta: Evidence from Unequilibrated Eucrites

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    Eucrites are a class of basaltic meteorites that, along with the howardites and diogenites, likely derive from the asteroid 4-Vesta. This asteroid is depleted in moderately volatile elements relative to the Earth and carbonaceous chondrites. Extrapolation of this depletion trend predicts that bulk silicate 4-Vesta (BSV) contains at most 250-1000 g/g H2O, which is approximately a factor of two lower than the H2O content of Earth. To obtain more accurate H2O and F estimates for BSV, we examined four unequilibrated antarctic meteorites, Yamato(Y)-793548, Y-82210, Y-75011, and Y-74450, by EPMA and SIMS. Pyroxenes contain MgO-rich cores and FeO-rich rims, consistent with primary magmatic zoning. Volatile concentrations generally follow patterns expected for growth zoning with lower values in the cores and higher in the rims. These features indicate that thermal metamorphism and other post-crystallization processes did not significantly perturb the volatile contents of these unequilibrated eucrite pyroxenes. We used these data to derive best estimates for the BSV H2O and F content based on experimentally determined pyroxene-melt partition coefficients and models for magma generation on Vesta. In addition, we measured D/H in the early crystallizing pyroxenes and late crystallzing apatites. We find that the D/H of pyroxene and apatite are within error of one another as well as previous measurements of apatite in equilibrated eucrites. These results imply that degassing was minimal or did not fractionate D/H. Degassing may have been limited if eucrites were shallowly emplaced sills or dykes, or the total H2O content of the magmas was too low for vapor saturation. An alternative mechanism for limited D/H fractionation is that degassing did occur, but the H2/H2O of the exsolved vapor was approximately 15:85, as predicted from experiments

    Terrestrial exposure of a fresh Martian meteorite causes rapid changes in hydrogen isotopes and water concentrations

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    Determining the hydrogen isotopic compositions and H2O contents of meteorites and their components is important for addressing key cosmochemical questions about the abundance and source(s) of water in planetary bodies. However, deconvolving the effects of terrestrial contamination from the indigenous hydrogen isotopic compositions of these extraterrestrial materials is not trivial, because chondrites and some achondrites show only small deviations from terrestrial values such that even minor contamination can mask the indigenous values. Here we assess the effects of terrestrial weathering and contamination on the hydrogen isotope ratios and H2O contents of meteoritic minerals through monitored terrestrial weathering of Tissint, a recent Martian fall. Our findings reveal the rapidity with which this weathering affects nominally anhydrous phases in extraterrestrial materials, which illustrates the necessity of sampling the interiors of even relatively fresh meteorite falls and underlines the importance of sample return missions

    H and Cl isotope characteristics of indigenous and late hydrothermal fluids on the differentiated asteroidal parent body of Grave Nunataks 06128

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    The paired achondrites Graves Nunataks (GRA) 06128 and 06129 are samples of an asteroid that underwent partial melting within a few million years after the start of Solar System formation. In order to better constrain the origin and processing of volatiles in the early Solar System, we have investigated the abundance of H, F and Cl and the isotopic composition of H and Cl in phosphates in GRA 06128 using secondary ion mass spectrometry. Indigenous H in GRA 06128, as recorded in magmatic merrillite, is characterised by an average δD of ca. -152 ± 330‰, which is broadly similar to estimates of the H isotope composition of indigenous H in other differentiated asteroidal and planetary bodies such as Mars, the Moon and the angrite and eucrite meteorite parent bodies. The merrillite data thus suggest that early accretion of locally-derived volatiles was widespread for the bodies currently populating the asteroid belt. Apatite formed at the expense of merrillite around 100 million years after the differentiation of the GRA 06128/9 parent body, during hydrothermal alteration, which was probably triggered by an impact event. Apatite in GRA 06128 contains 5.4-5.7 wt.% Cl, 0.6-0.8 wt.% F, and ~20 to 60 ppm H2O, which is similar to the H2O abundance in merrillite from which apatite formed. The apatite δD values range between around +100‰ and +2000‰ and are inversely correlated with apatite H2O contents. The Cl isotope composition of apatite appears to be homogeneous across various grains, with an average δ37 Cl value of 3.2 ± 0.7‰. A possible scenario to account for the apatite chemical and isotopic characteristics involves interaction of GRA 06128/9 with fumarole-like fluids derived from D- and HCl-rich ices delivered to the GRA 06128/9 parent-body by an ice-rich impactor
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