1,665 research outputs found

    Aquaporins in GtoPdb v.2021.3

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    Aquaporins and aquaglyceroporins are membrane channels that allow the permeation of water and certain other small solutes across the cell membrane, or in the case of AQP6, AQP11 and AQP12A, intracellular membranes, such as vesicles and the endoplasmic reticulum membrane [16]. Since the isolation and cloning of the first aquaporin (AQP1) [20], 12 additional mammalian members of the family have been identified, although little is known about the functional properties of one of these (AQP12A; Q8IXF9) and it is thus not tabulated. The other 12 aquaporins can be broadly divided into three families: orthodox aquaporins (AQP0,-1,-2,-4,-5, -6 and -8) permeable mainly to water, but for some additional solutes [4]; aquaglyceroporins (AQP3,-7 -9 and -10), additionally permeable to glycerol and for some isoforms urea [14], and superaquaporins (AQP11 and 12) located within cells [12]. Some aquaporins also conduct ammonia and/or H2O2 giving rise to the terms 'ammoniaporins' ('aquaammoniaporins') and 'peroxiporins', respectively. Aquaporins are impermeable to protons and other inorganic and organic cations, with the possible exception of AQP1, although this is controversial [14]. One or more members of this family of proteins have been found to be expressed in almost all tissues of the body [reviewed in Yang (2017) [26]]. AQPs are involved in numerous processes that include systemic water homeostasis, adipocyte metabolism, brain oedema, cell migration and fluid secretion by epithelia. Loss of function mutations of some human AQPs, or their disruption by autoantibodies further underscore their importance [reviewed by Verkman et al. (2014) [23], Kitchen et al. (2105) [14]]. Functional AQPs exist as homotetramers that are the water conducting units wherein individual AQP subunits (each a protomer) have six TM helices and two half helices that constitute a seventh 'pseudotransmembrane domain' that surrounds a narrow water conducting channel [16]. In addition to the four pores contributed by the protomers, an additional hydrophobic pore exists within the center of the complex [16] that may mediate the transport through AQP1. Although numerous small molecule inhibitors of aquaporins, particularly APQ1, have been reported primarily from Xenopus oocyte swelling assays, the activity of most has subsequently been disputed upon retesting using assays of water transport that are less prone to various artifacts [5] and they are therefore excluded from the tables [see Tradtrantip et al. (2017) [22] for a review]

    A new method of retrieving atmospheric refractivity structure

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    This is the final version. Available on open access from Taylor & Francis via the DOI in this recordData availability statement: The radiosonde data that support the findings of this study are available in ‘Met Office (2006): Met Office high resolution radiosonde data from the UK, Gibraltar, St Helena and the Falkland Islands’, CEDA Archive at http://catalogue.ceda.ac.uk/uuid/c1e2240c353f8edeb98087e90e6d832e. (Accessed 10 May 2022).It is proposed to obtain information on atmospheric refractivity structure by measuring the angle of arrival (AoA) of radio signals routinely broadcast by commercial aircraft. The angle of arrival would be measured at hill-top sites using a simple two-element interferometer. Knowledge of the aircraft’s location (information conveniently contained within the broadcasts) and the AoA will enable the bending angle of the signals to be calculated. As measurable bending will only occur at grazing incidence, sources of signals either very close to the radio horizon, or at a similar height to the interferometer, are essential. The routine navigational data broadcasts from civil aircraft represent the ideal source. In areas of high air traffic density such as the UK, ∼ 10⁵ - 10⁶ bending angle measurements may be possible each day. Numerical weather prediction models routinely assimilate bending angles retrieved from GNSS radio occultation data, so it is anticipated that assimilation methods could be developed that are able to make good use of this new source of bending angle data. Sensitivity tests were performed to estimate the resolution of humidity retrievals assuming a target AoA accuracy of 0.01°. Simulated annealing was used to demonstrate the ability to retrieve relative humidity and mixing ratio vertical profiles using AoA measurements. It is shown that for observed AoA measurements with an accuracy of 0.01° it should be possible to retrieve relative humidity and mixing ratio vertical profiles with an accuracy of ∼ 5% and ∼ 0.5 g/kg respectively. An AoA accuracy of 0.01° should be achievable using hardware costing ∼ €10k, however further hardware development is still required.University of Exeter (College of Engineering, Mathematics and Physical Sciences)Met Offic

    Guidelines for randomized clinical trial protocol content: a systematic review

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    BACKGROUND: All randomized clinical trials (RCTs) require a protocol; however, numerous studies have highlighted protocol deficiencies. Reporting guidelines may improve the content of research reports and, if developed using robust methods, may increase the utility of reports to stakeholders. The objective of this study was to systematically identify and review RCT protocol guidelines, to assess their characteristics and methods of development, and to compare recommendations. METHODS: We conducted a systematic review of indexed literature (MEDLINE, EMBASE and the Cochrane Methodology Register from inception to September 2010; reference lists; related article features; forward citation searching) and a targeted search of supplementary sources, including a survey of major trial funding agencies in six countries. Records were eligible if they described a content guideline in English or French relevant to RCT protocols. Guidelines were excluded if they specified content for protocols for trials of specific procedures or conditions or were intended to assess trial quality. We extracted guideline characteristics and methods. Content was mapped for a subset of guidelines that described development methods or had institutional endorsement. RESULTS: Forty guidelines published in journals, books and institutional reports were included in the review; seven were specific to RCT protocols. Only eight (20%) described development methods which included informal consensus methods, pilot testing and formal validation; no guideline described all of these methods. No guideline described formal consensus methods or a systematic retrieval of empirical evidence to inform its development. The guidelines included a median of 23 concepts per guideline (interquartile range (IQR) = 14 to 34; range = 7 to 109). Among the subset of guidelines (n = 23) for which content was mapped, approximately 380 concepts were explicitly addressed (median concepts per guideline IQR = 31 (24,80); range = 16 to 150); most concepts were addressed in a minority of guidelines. CONCLUSIONS: Existing guidelines for RCT protocol content varied substantially in their recommendations. Few reports described the methods of guideline development, limiting comparisons of guideline validity. Given the importance of protocols to diverse stakeholders, we believe a systematically developed, evidence-informed guideline for clinical trial protocols is needed

    Inhibitors of Mammalian Aquaporin Water Channels

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    Aquaporins (AQPs) are water channel proteins that are essential to life, being expressed in all kingdoms. In humans, there are 13 AQPs, at least one of which is found in every organ system. The structural biology of the AQP family is well-established and many functions for AQPs have been reported in health and disease. AQP expression is linked to numerous pathologies including tumor metastasis, fluid dysregulation, and traumatic injury. The targeted modulation of AQPs therefore presents an opportunity to develop novel treatments for diverse conditions. Various techniques such as video microscopy, light scattering and fluorescence quenching have been used to test putative AQP inhibitors in both AQP-expressing mammalian cells and heterologous expression systems. The inherent variability within these methods has caused discrepancy and many molecules that are inhibitory in one experimental system (such as tetraethylammonium, acetazolamide, and anti-epileptic drugs) have no activity in others. Some heavy metal ions (that would not be suitable for therapeutic use) and the compound, TGN-020, have been shown to inhibit some AQPs. Clinical trials for neuromyelitis optica treatments using anti-AQP4 IgG are in progress. However, these antibodies have no effect on water transport. More research to standardize high-throughput assays is required to identify AQP modulators for which there is an urgent and unmet clinical need

    XTE J0111.2-7317 : a nebula-embedded X-ray binary in the SMC

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    The observed characteristics of the nebulosity surrounding the SMC High Mass X-ray Binary XTE J0111.2-7317 are examined in the context of three possible nebular types: SNR, bowshock and HII region. Observational evidence is presented which appears to support the interpretation that the nebulosity surrounding XTE J0111.2-7317 is an HII region. The source therefore appears to be a normal SMC Be X-ray binary (BeXRB) embedded in a locally enhanced ISM which it has photoionised to create an HII region. This is supported by observations of the X-ray outburst seen with BATSE and RXTE in 1998-1999. It exhibited characteristics typical of a giant or type II outburst in a BeXRB including large spin-up rates, Lx~10E38 erg/sq.cm-s, and a correlation between spin-up rate and pulsed flux. However, the temporal profile of the outburst was unusual, consisting of two similar intensity peaks, with the first peak of shorter duration than the second.Comment: Accepted for publication by MNRA
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