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Journal articleTurner PJ, Bognanni A, Arasi S, et al., 2024,
Time to ACT-UP: update on precautionary allergen labelling (PAL)
, The World Allergy Organization Journal, Vol: 17, ISSN: 1939-4551BackgroundPrecautionary Allergen (“may contain”) Labelling (PAL) is used by industry to communicate potential risk to food-allergic individuals posed by unintended allergen presence (UAP). In 2014, the World Allergy Organization (WAO) highlighted that PAL use was increasing, but often applied inconsistently and without regulation — which reduces its usefulness to consumers with food allergy and those purchasing food for them. WAO proposed the need for a regulated, international framework to underpin application of PAL. In 2019, the World Health Organization (WHO) and the Food and Agriculture Organization (FAO) of the United Nations convened an expert consultation to address the issue of PAL, the outputs of which are now being considered by the Codex Committee on Food Labelling (CCFL).ObjectivesTo summarise the latest data to inform the application of PAL in a more systematic way, for implementation into global food standards.MethodsA non-systematic review of issues surrounding precautionary labelling and food allergens in pre-packaged products.ResultsApproximately, 100 countries around the world have legislation on the declaration of allergenic ingredients. Just a few have legislation on UAP. Given the risks that UAP entails, non-regulated PAL creates inconvenience in real life due to its unequal, difficult interpretation by patients. The attempts made so far to rationalize PAL present lights and shadows.ConclusionsAt a time when CCFL is considering the results of the FAO/WHO Expert Consultation 2020–2023, we summarise the prospects to develop an effective and homogeneous legislation at a global level, and the areas of uncertainty that might hinder international agreement on a regulated framework for PAL of food allergens.
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Journal articlePatel AH, Koysombat K, Pierret A, et al., 2024,
Kisspeptin in functional hypothalamic amenorrhea: pathophysiology and therapeutic potential
, Annals of the New York Academy of Sciences, Vol: 1540, Pages: 21-46, ISSN: 0077-8923Functional hypothalamic amenorrhea (FHA) is one of the most common causes of secondary amenorrhea, resulting in anovulation and infertility, and is a low estrogen state that increases the risk of cardiovascular disease and impairs bone health. FHA is characterized by acquired suppression of physiological pulsatile gonadotropin-releasing hormone (GnRH) release by the hypothalamus in the absence of an identifiable structural cause, resulting in a functional hypogonadotropic hypogonadism. FHA results from either decreased energy intake and/or excessive exercise, leading to low energy availability and weight loss—often in combination with psychological stress on top of a background of genetic susceptibility. The hypothalamic neuropeptide kisspeptin is a key component of the GnRH pulse generator, tightly regulating pulsatile GnRH secretion and the downstream reproductive axis. Here, we review the physiological regulation of pulsatile GnRH secretion by hypothalamic kisspeptin neurons and how their activity is modulated by signals of energy status to affect reproductive function. We explore endocrine factors contributing to the suppression of GnRH pulsatility in the pathophysiology of FHA and how hypothalamic kisspeptin neurons likely represent a final common pathway through which these factors affect GnRH pulse generation. Finally, we discuss the therapeutic potential of kisspeptin as a novel treatment for women with FHA.
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Journal articleKitandwe PK, Rogers P, Hu K, et al., 2024,
A lipid nanoparticle-formulated self-amplifying RNA rift valley fever vaccine induces a robust humoral immune response in mice
, Vaccines, Vol: 12, ISSN: 2076-393XRift Valley fever (RVF) is a mosquito-borne viral zoonosis that causes high fetal and neonatal mortality rates in ruminants and sometimes severe to fatal complications like encephalitis and hemorrhagic fever in humans. There is no licensed RVF vaccine for human use while approved livestock vaccines have suboptimal safety or efficacy. We designed self-amplifying RNA (saRNA) RVF vaccines and assessed their humoral immunogenicity in mice. Plasmid DNA encoding the Rift Valley fever virus (RVFV) medium (M) segment consensus sequence (WT consensus) and its derivatives mutated to enhance cell membrane expression of the viral surface glycoproteins n (Gn) and c (Gc) were assessed for in vitro expression. The WT consensus and best-expressing derivative (furin-T2A) were cloned into a Venezuelan equine encephalitis virus (VEEV) plasmid DNA replicon and in vitro transcribed into saRNA. The saRNA was formulated in lipid nanoparticles and its humoral immunogenicity in BALB/c mice was assessed. High quantities of dose-dependent RVFV Gn IgG antibodies were detected in the serum of all mice immunized with either WT consensus or furin-T2A saRNA RVF vaccines. Significant RVFV pseudovirus-neutralizing activity was induced in mice immunized with 1 µg or 10 µg of the WT consensus saRNA vaccine. The WT consensus saRNA RVF vaccine warrants further development.
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Journal articleZafar A, Sridhar S, Bineva-Todd G, et al., 2024,
Expanding the repertoire of GalNAc analogues for cell-specific bioorthogonal tagging of glycoproteins
, RSC Chemical Biology, Vol: 5, Pages: 1002-1009, ISSN: 2633-0679Glycosylation is a ubiquitous modification of proteins, necessitating approaches for its visualization and characterization. Bioorthogonally tagged monosaccharides have been instrumental to this end, offering a chemical view into the cell biology of glycans. Understanding the use of such monosaccharides by cellular biosynthetic pathways has expanded their applicability in cell biology, for instance through the strategy named Bio-Orthogonal Cell-specific TAgging of Glycoproteins (BOCTAG). Here, we show that the cellular use of two azide-tagged analogues of the monosaccharide N-acetylgalactosamine (GalNAzMe and GalNPrAz) can be promoted through expression of two biosynthetic enzymes. More precisely, cellular expression of the bacterial kinase NahK and the engineered human pyrophosphorylase AGX1F383A led to biosynthesis of the corresponding activated nucleotide-sugars and subsequent bioorthogonal tagging of the cellular glycoproteome. We explore the use of both sugars for BOCTAG, demonstrating the visualization of cell surface glycosylation tagged with GalNPrAz in a specific cell line in a co-culture system. Our work adds to the toolbox of glycoprotein analysis in biomedicine.
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Journal articleThenappan A, Maher TM, Yazbeck L, et al., 2024,
Competing Causes of Death in Idiopathic Pulmonary Fibrosis
, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 210, Pages: 938-940, ISSN: 1073-449X -
Conference paperHanassab S, Southern J, Olabode AV, et al., 2024,
Identifying nutritional and pharmacological targets for alleviating polycystic ovary syndrome using genomic-driven machine learning
, ASRM 2024, Publisher: Elsevier, Pages: e414-e414, ISSN: 0015-0282 -
Journal articleOcasio CA, Baggelaar MP, Sipthorp J, et al., 2024,
A palmitoyl transferase chemical-genetic system to map ZDHHC-specific S-acylation
, Nature Biotechnology, Vol: 42, Pages: 1548-1558, ISSN: 1087-0156The 23 human zinc finger Asp-His-His-Cys motif-containing (ZDHHC) S-acyltransferases catalyze long-chain S-acylation at cysteine residues across an extensive network of hundreds of proteins important for normal physiology or dysregulated in disease. Here we present a technology to directly map the protein substrates of a specific ZDHHC at the whole-proteome level, in intact cells. Structure-guided engineering of paired ZDHHC 'hole' mutants and 'bumped' chemically tagged fatty acid probes enabled probe transfer to specific protein substrates with excellent selectivity over wild-type ZDHHCs. Chemical-genetic systems were exemplified for five human ZDHHCs (3, 7, 11, 15 and 20) and applied to generate de novo ZDHHC substrate profiles, identifying >300 substrates and S-acylation sites for new functionally diverse proteins across multiple cell lines. We expect that this platform will elucidate S-acylation biology for a wide range of models and organisms.
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Journal articleEisermann J, Liang Y, Wright JJ, et al., 2024,
The effect of reactive oxygen species on respiratory complex I activity in liposomes
, Chemistry: A European Journal, Vol: 30, ISSN: 0947-6539Respiratory complex I (R-CI) is an essential enzyme in the mitochondrial electron transport chain but also a major source of reactive oxygen species (ROS), which are implicated in neurodegenerative diseases and ageing. While the mechanism of ROS production by R-CI is well-established, the feedback of ROS on R-CI activity is poorly understood. Here, we perform EPR spectroscopy on R-CI incorporated in artificial membrane vesicles to reveal that ROS (particularly hydroxyl radicals) reduce R-CI activity by making the membrane more polar and by increasing its hydrogen bonding capability. Moreover, the mechanism that we have uncovered reveals that the feedback of ROS on R-CI activity via the membrane is transient and not permanent; lipid peroxidation is negligible for the levels of ROS generated under these conditions. Our successful use of modular proteoliposome systems in conjunction with EPR spectroscopy and other biophysical techniques is a powerful approach for investigating ROS effects on other membrane proteins.
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Journal articleSuseeladevi AK, Denholm R, Retford M, et al., 2024,
COVID-19 vaccination and birth outcomes of 186,990 women vaccinated before pregnancy: an England-wide cohort study
, The Lancet Regional Health. Europe, Vol: 45, ISSN: 2666-7762BackgroundCOVID-19 vaccination in pregnancy is recommended by the World Health Organisation as effective and safe. However, there remains a lack of robust evidence to inform vaccination choices for women of childbearing potential in relation to their future pregnancies. Here we investigated the association between starting a course of COVID-19 vaccination before pregnancy and birth outcomes.MethodsWe analysed England-wide linked electronic health records for all pregnancies reaching at least 24 weeks gestation between 25th May 2021 and 28th October 2022. We estimated incidence rates and hazard ratios for birth and pregnancy outcomes by pre-pregnancy COVID-19 vaccination status.FindingsBased on 186,990 women, compared to starting a pregnancy unvaccinated, receiving COVID-19 vaccination within 12 months before pregnancy was associated with lower risks of very and extremely preterm birth and small-for-gestational age in term babies for any vaccine type (adjusted hazard ratio and 95% confidence interval: 0.74 [0.63, 0.88] and 0.94 [0.88, 1.00], respectively), and lower stillbirth risk in those receiving an mRNA vaccine (0.72 [0.52, 1.00]). Incidence of venous thromboembolism during pregnancy was higher amongst women receiving a viral-vector, but not an mRNA vaccine (1.54 [1.10, 2.16] and 1.02 [0.70, 1.50], respectively). Results were generally consistent for different dose regimens and across sensitivity analyses.InterpretationWe found evidence that pregnancies starting within 12 months from a first COVID-19 vaccination, compared to those in unvaccinated women, experienced fewer adverse birth outcomes, overall or in selected subgroups of the general population, accounting for potential confounders. An mRNA vaccine should be preferred to a viral-vector vaccine, to minimise safety issues, but where the latter is the only choice, it is still to be preferred to starting a pregnancy unvaccinated. The venous thromboembolism risk of the viral-vector vaccine was substantially l
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Journal articleHuang L, Tang WH, Attar R, et al., 2024,
Remote assessment of eczema severity via AI-powered skin image analytics: a systematic review
, Artificial Intelligence in Medicine, Vol: 156, ISSN: 0933-3657Various studies have been published on the remote assessment of eczema severity from digital camera images. Successful deployment of an accurate and robust AI-powered tool for such purposes can aid the formulation of eczema treatment plans and assist in patient monitoring. This review aims to provide an overview of the quality of published studies on this topic and to identify challenges and suggestions to improve the robustness and reliability of existing tools. We identified 25 articles from the Scopus database that aimed to assess eczema severity automatically from digital camera images by eczema area detection (n=13), which is important for prior delineation of the most relevant clinical features, and/or severity prediction (n=12). Deep learning methods (n=14) were more commonly used in recent years over conventional machine learning (n=11). A set of 20 pre-defined criteria were used for critical appraisal in this study. Study quality was hindered in many cases due to dataset challenges, with only 28% of studies reporting patient age range and 16% reporting skin phototype range. Furthermore, 52% of studies utilised solely non-public datasets and only 17% provided open-source access to code repositories, making validation of experimental results a significant challenge. In terms of algorithm design, attempts to improve model accuracy and process automation are widely reported. However, there remains limited implementation of methods for explicitly improving model trustworthiness and robustness. There is a need for a high-quality dataset with a sufficient number of bias-free images and consistent labels, as well as improved image analytics methods, to enhance the state of remote eczema severity assessment algorithms. Improving the interpretability and explainability of developed tools will further improve long-term reliability and trustworthiness.
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