678 research outputs found

    A metabolomic, geographic, and seasonal analysis of the contribution of pollen-derived adenosine to allergic sensitization

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    Background Studies on ragweed and birch pollen extracts suggested that the adenosine content is an important factor in allergic sensitization. However, exposure levels from other pollens and considerations of geographic and seasonal factors have not been evaluated. Objective This study compared the metabolite profile of pollen species important for allergic disease, specifically measured the adenosine content, and evaluated exposure to pollen-derived adenosine. Methods An NMR metabolomics approach was used to measure metabolite concentrations in twenty-six pollen extracts. Pollen count data was analyzed from five cities to model exposure. Results A principal component analysis of the various metabolites identified by NMR showed that pollen extracts could be differentiated primarily by sugar content: glucose, fructose, sucrose, and myo-inositol. In extracts of 10 mg of pollen/ml, the adenosine was highest for grasses (45 μM) followed by trees (23 μM) and weeds (19 μM). Pollen count data showed that tree pollen was typically 5–10 times the amount of other pollens. At the daily peaks of tree, grass, and weed season the pollen-derived adenosine exposure per day is likely to only be 1.1, 0.11, and 0.12 μg, respectively. Seasonal models of pollen exposure and respiration suggest that it would be a rare event limited to tree pollen season for concentrations of pollen-derived adenosine to approach physiological levels. Conclusions Sugar content and other metabolites may be useful in classifying pollens. Unless other factors create localized exposures that are very different from these models, pollen-derived adenosine is unlikely to be a major factor in allergic sensitization

    Enhanced Approaches for Identifying Amadori Products: Application to Peanut Allergens

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    The dry roasting of peanuts is suggested to influence allergic sensitization as a result of the formation of advanced glycation end products (AGEs) on peanut proteins. Identifying AGEs is technically challenging. The AGEs of a peanut allergen were probed with nano-scale liquid chromatography−electrospray ionization−mass spectrometry (nanoLC−ESI−MS) and tandem mass spectrometry (MS/MS) analyses. Amadori product ions matched to expected peptides and yielded fragments that included a loss of three waters and HCHO. As a result of the paucity of b and y ions in the MS/MS spectrum, standard search algorithms do not perform well. Reactions with isotopically labeled sugars confirmed that the peptides contained Amadori products. An algorithm was developed on the basis of information content (Shannon entropy) and the loss of water and HCHO. Results with test data show that the algorithm finds the correct spectra with high precision, reducing the time needed to manually inspect data. Computational and technical improvements allowed for better identification of the chemical differences between modified and unmodified proteins

    Structural studies of the PARP-1 BRCT domain

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    <p>Abstract</p> <p>Background</p> <p>Poly(ADP-ribose) polymerase-1 (PARP-1) is one of the first proteins localized to foci of DNA damage. Upon activation by encountering nicked DNA, the PARP-1 mediated trans-poly(ADP-ribosyl)ation of DNA binding proteins occurs, facilitating access and accumulation of DNA repair factors. PARP-1 also auto-(ADP-ribosyl)ates its central BRCT-containing domain forming part of an interaction site for the DNA repair scaffolding protein X-ray cross complementing group 1 protein (XRCC1). The co-localization of XRCC1, as well as bound DNA repair factors, to sites of DNA damage is important for cell survival and genomic integrity.</p> <p>Results</p> <p>Here we present the solution structure and biophysical characterization of the BRCT domain of rat PARP-1. The PARP-1 BRCT domain has the globular ι/β fold characteristic of BRCT domains and has a thermal melting transition of 43.0°C. In contrast to a previous characterization of this domain, we demonstrate that it is monomeric in solution using both gel-filtration chromatography and small-angle X-ray scattering. Additionally, we report that the first BRCT domain of XRCC1 does not interact significantly with the PARP-1 BRCT domain in the absence of ADP-ribosylation. Moreover, none of the interactions with other longer PARP-1 constructs which previously had been demonstrated in a pull-down assay of mammalian cell extracts were detected.</p> <p>Conclusions</p> <p>The PARP-1 BRCT domain has the conserved BRCT fold that is known to be an important protein:protein interaction module in DNA repair and cell signalling pathways. Data indicating no significant protein:protein interactions between PARP-1 and XRCC1 likely results from the absence of poly(ADP-ribose) in one or both binding partners, and further implicates a poly(ADP-ribose)-dependent mechanism for localization of XRCC1 to sites of DNA damage.</p

    The Irrigation Efficiency Trap: Rational Farm-Scale Decisions Can Lead to Poor Hydrologic Outcomes at the Basin Scale

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    Agricultural irrigation practices have changed through time as technology has enabled more efficient conveyance and application. In some agricultural regions, irrigation can contribute to incidental aquifer recharge important for groundwater return flows to streams. The Henrys Fork Snake River, Idaho (United States) overlies a portion of the Eastern Snake Plain Aquifer, where irrigated agriculture has occurred for over a century. Using irrigator interviews, aerial and satellite imagery, and statistical streamflow analysis, we document the impact of farm-scale decisions on basin-scale hydrology. Motivated to improve economic efficiency, irrigators began converting from surface to center-pivot sprinkler irrigation in the 1950s, with rapid adoption of center-pivot sprinklers through 2000. Between 1978–2000 and 2001–2022, annual surface-water diversion decreased by 311 Mm3 (23%) and annual return flow to the river decreased by 299 Mm3 over the same period. Some reaches that gained water during 1978–2000 lost water to the aquifer during the later period. We use an interdisciplinary approach to demonstrate how individual farm-scale improvements in irrigation efficiency can cumulatively affect hydrology at the landscape scale and alter groundwater-surface water relationships. Return flows are an important part of basin hydrology in irrigated landscapes and we discuss how managed and incidental aquifer recharge can be implemented to recover return flows to rivers

    Limb-state information encoded by peripheral and central somatosensory neurons:Implications for an afferent interface

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    A major issue to be addressed in the development of neural interfaces for prosthetic control is the need for somatosensory feedback. Here, we investigate two possible strategies: electrical stimulation of either dorsal root ganglia (DRG) or primary somatosensory cortex (S1). In each approach, we must determine a model that reflects the representation of limb state in terms of neural discharge. This model can then be used to design stimuli that artificially activate the nervous system to convey information about limb state to the subject. Electrically activating DRG neurons using naturalistic stimulus patterns, modeled on recordings made during passive limb movement, evoked activity in S1 that was similar to that of the original movement. We also found that S1 neural populations could accurately discriminate different patterns of DRG stimulation across a wide range of stimulus pulse-rates. In studying the neural coding in S1, we also decoded the kinematics of active limb movement using multi-electrode recordings in the monkey. Neurons having both proprioceptive and cutaneous receptive fields contributed equally to this decoding. Some neurons were most informative of limb state in the recent past, but many others appeared to signal upcoming movements suggesting that they also were modulated by an efference copy signal. Finally, we show that a monkey was able to detect stimulation through a large percentage of electrodes implanted in area 2. We discuss the design of appropriate stimulus paradigms for conveying time-varying limb state information, and the relative merits and limitations of central and peripheral approaches

    Fluctuations of the Condensate in Ideal and Interacting Bose Gases

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    We investigate the fluctuations of the condensate in the ideal and weakly interacting Bose gases confined in a box of volume V within canonical ensemble. Canonical ensemble is developed to describe the behavior of the fluctuations when different methods of approximation to the weakly interacting Bose gases are used. Research shows that the fluctuations of the condensate exhibit anomalous behavior for the interacting Bose gas confined in a box.Comment: RevTex, 4 Figs,E-mail:[email protected], corrected typo

    Intradialytic versus home based exercise training in hemodialysis patients: a randomised controlled trial

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    Background: Exercise training in hemodialysis patients improves fitness, physical function, quality of life and markers of cardiovascular disease such as arterial stiffness. The majority of trials investigating this area have used supervised exercise training during dialysis (intradialytic), which may not be feasible for some renal units. The aim of this trial is to compare the effects of supervised intradialytic with unsupervised home-based exercise training on physical function and arterial stiffness
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