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Aquaporins in GtoPdb v.2025.4
Get PDFAquaporins 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 \u27ammoniaporins\u27 (\u27aquaammoniaporins\u27) and \u27peroxiporins\u27, 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) [27]]. 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) [24], 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 \u27pseudotransmembrane domain\u27 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 AQP1, 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) [23] for a review]
The Lacunae in the Rome Statute for the Exercise of Universal Jurisdiction by the International Criminal Court by Anwesha Mishra
Get PDFThe issue of “universal jurisdiction” reveals a legal chasm in the applicability of the Rome Statute and have plagued the International Criminal Court with criticisms for not having the right to exercise such jurisdiction over international crimes. Universal jurisdiction can be simply defined as “the exercise of jurisdiction regardless of any other acknowledged jurisdictional relationship to a State party to the Statute”. This question of universal jurisdiction becomes especially important when currently, the Court is recently struggling to exercise jurisdiction over the crimes committed in the Philippines, in the context of their government’s "War on Drugs" campaign, due to the withdrawal of the country as a State Party to the Statute on March 17, 2019. This article provides an insight into such lacunae of the Statute in terms of adequately preparing the ICC for exercising its jurisdiction in such situations or cases
On the Margins: The Disenfranchisement of Communities in International Human Rights Law as Portrayed by Rosa Ehrenreich Brooks and Ratna Kapur by Christina Yuen
No full textThis article conducts a comparative review of the perspectives presented in Rosa Ehrenreich Brooks\u27 "Feminism and International Law: An Opportunity for Transformation" and Ratna Kapur\u27s "The (Im)Possibility of Queering International Human Rights Law”. It examines the similarities in the authors\u27 overarching understandings of the nature of the contemporary human rights system, on the one hand, and their converging views on the effectiveness of dialogue, the theoretical lenses they adopt, and their verdicts on the role of the West, on the other. Ultimately, it concludes that despite their differences in argumentation, the insights of both authors reveal that the current human rights framework does not adequately fulfil the needs and interests of women and queer individuals, serving as a stepping stone for future research as to how the system can be transformed to better serve all the individuals and groups it claims to serve.
Organocatalytic Asymmetric Synthesis of SynVesT-1, a PET Imaging Agent of the SV2A Receptor
Get PDF[18F]SynVesT-1 is a potent and selective positron emission tomography imaging agent for synaptic vesicle glycoprotein 2 (SV2A).1 SV2A is an integral transmembrane glycoprotein widely expressed in the brain. Although the exact role of SV2A has not been confirmed, it is known that SV2A participates in key vesicular processes. Furthermore, SV2A is a validated target for epilepsy and a biomarker of synaptic density.2 The established synthetic strategy to obtain [18F]SynVesT-1 involves the multistep synthesis of a racemic intermediate, requiring late-stage separation of the two enantiomers via chiral HPLC.3 Our aim was to develop an asymmetric synthetic route to access [18F]SynVesT-1.
In this work, we optimised a seven-step route to an organotin precursor of [18F]SynVesT-1 starting with a Wittig reaction of 3-bromo-5-fluorobenzaldehyde.4 This was followed by the asymmetric conjugate addition of nitromethane to the resulting cinnamaldehyde utilising the Hayashi-Jørgensen organocatalyst (Scheme 1). Subsequently, a number of standard transformations facilitated the synthesis of the organotin precursor which was then subjected to automated copper(II)-mediated fluoro-destannylation for the preparation of [18F]SynVesT-1. This work will be discussed, along with a second-generation route detailing the synthesis of a boronic ester-derived precursor to [18F]SynVesT-1.
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Evaluating the potential of cis- and trans-4-[18F]fluoro-L-proline positron emission tomography as biomarkers of active collagen biosynthesis in cardiometabolic diseases
Get PDFThe increased prevalence of obesity and its associated comorbidities has coincided with an upsurge in cardiometabolic diseases, such as heart failure with preserved ejection fraction, metabolic dysfunction-associated steatotic liver disease, and chronic kidney disease. Active tissue remodelling and fibrosis following cellular damage and inflammation, characterised by aberrant collagen deposition, is a common feature of cardiometabolic disease. Currently, there are no established probes for non-invasive whole-body imaging of active collagen biosynthesis to study the multisystem consequences of cardiometabolic diseases.
We aimed to evaluate the potential of cis¬- and trans-4-[18F]fluoro-L-proline positron emission tomography (PET) as biomarkers of active misfolded and stable triple helical collagen biosynthesis, respectively, using a preclinical Western-style diet (WD)-induced rat model of cardiometabolic diseases.
Animals fed a WD had significantly greater uptake of both cis¬- and trans-4-[18F]fluoro-L-proline in the heart compared to age-matched controls across the time course, reflecting the increased histological accumulation of collagen, a profibrotic gene expression profile, and cardiac dysfunction on echocardiography. Although histological and transcriptional alterations were also noted in the liver, there were no detectable differences in hepatic cis- and trans-4-[18F]fluoro-L-proline PET signal. We hypothesise that the organ-specific differences in relative [18F]fluoro-L-proline PET uptake reflect disease-associated perturbations to the free-proline pool. Previous reports showed that WD feeding markedly increased the proline content of plasma and liver tissue1 which could in turn alter tracer kinetics. Currently, we are developing and validating new quantification strategies for [18F]fluoro-L-proline PET studies based on amino acid blood concentrations, similar to established plasma glucose corrections in [18F]fluorodeoxyglucose PET studies2, in order to improve [18F]fluoro-L-proline PET outcome reporting.
Overall, our data suggests that the rates of active collagen biosynthesis in cardiometabolic diseases are organ-specific, likely indicating differences in susceptibility to injury and fibrosis.
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Pressure Limiting Instabilities in Tokamaks
Get PDFThe plasma pressure achievable in a tokamak fusion reactor may be limited by instabilities like the ideal ballooning mode, a pressure-driven instability that acts to degrade plasma confinement. Here we investigate the sensitivity of the shape of the magnetic flux surface to the ideal ballooning mode; in particular, we modify the parameters describing the shape of magnetic flux surfaces of the equilibrium and perform infinite-n ideal ballooning scans to assess how shaping affects proximity to marginal instability. We find that for the parameter space considered, increasing squareness and elongation could help stabilise the plasma against the ideal ballooning mode instability
The Joke of Wellington: The Duke of Wellington’s cone from folk act to brand
Get PDFThis article focusses on the Glasgow landmark, the cone on the Duke of Wellington’s statue, outside the Gallery of Modern Art (GOMA). Focussing on the history of the Duke’s cone, in the wider context of similar public interactions, it discusses how the attitude of the city (both the people and the city authorities) has developed until the practice has become an informal emblem for Glasgow
The Role of Affective Labour in Expertise: Bringing Emotions Back into Expert Practices
No full textIn recent years, a lot of scholarly attention has been devoted to how practices of digitalisation and datafication require medical professionals to work together with different stakeholders, and to how such collaborations shape expertise (Stevens, Wehrens, and de Bont 2020; Carboni et al. 2024). STS scholars have generally approached expertise as an epistemic and social endeavor, but they have tended to neglect the role affects and emotions play in its development and performance. In this paper, we provide a theoretical reflection on the relation between affective labour and expertise building upon Egher’s (2023) conceptualisation of expertise as a practical achievement realised through coordination and affective labour. Based on ethnographic fieldwork conducted in various medical settings, including digital pathology, psychiatry, and datafication in intensive care, we explore what types of affective labour are conducted in digital healthcare, by whom, and with what consequences. We show how affective labour mediates both epistemic and relational practices. We argue that different affects and emotions are mobilised in these practices, which impacts the development and effective performance of expertise.
Cyberwarfare and the challenges it poses to the international governance of armed conflict with particular reference to attribution, distinction, and self-defence.
No full textCyberwarfare is an emerging form of conflict in the 21st Century. Whether it is considered a domain, a field of weaponry, or capable of being a completely new and separate type of conflict, the international governing community must find a way to protect citizens from its potential damage. International Law may be able to do so, but there are plot holes in existing international law governing armed conflicts in relation to cyber, particularly in regards to the notions of attributability, distinction, and self-defence. This paper uses two case studies, the 2008 Russo-Georgian War and the ongoing Russia-Ukraine war to discuss the practical application of international law to cyberwarfare. This is an example of a contemporary form of conflict and how we must work to effectively acknowledge and address it