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Metabolomic studies in the inborn error of metabolism alkaptonuria reveal new biotransformations in tyrosine metabolism

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Genes & Diseases 2022年第4期9卷 1129-1142页

作者： Brendan P.Norman Andrew S.Davison juliette h.hughes hazel Sutherland Peter J.M.Wilson Neil G.Berry Andrew T.hughes Anna M.Milan Jonathan C.Jarvis Norman B.Roberts Lakshminarayan R.Ranganath George Bou-Gharios James A.Gallagher Institute of Life Course and Medical Sciences University of LiverpoolWilliam Henry Duncan Building6 West Derby StreetLiverpoolL78TXUK Department of Clinical Biochemistry&Metabolic Medicine Liverpool Clinical LaboratoriesRoyal Liverpool University HospitalPrescot StreetLiverpoolL78XPUK School of Sport&Exercise Sciences Liverpool John Moores UniversityTom Reilly BuildingByrom StreetLiverpoolL33AFUK Department of Chemistry University of LiverpoolCrown StreetLiverpoolL697ZDUK

Alkaptonuria (AKU) is an inherited disorder of tyrosine metabolism caused by lack of active enzyme homogentisate 1,2-dioxygenase (hGD). The primary consequence of hGD deficiency is increased circulating homogentisic acid (hGA), the main agent in the pathology of AKU disease. here we report the first metabolomic analysis of AKU homozygous hgd knockout (hgd−/−) mice to model the wider metabolic effects of hgd deletion and the implication for AKU in humans. Untargeted metabolic profiling was performed on urine from hgd−/− AKU (n = 15) and hgd+/− non-AKU control (n = 14) mice by liquid chromatography high-resolution time-of-flight mass spectrometry (Experiment 1). The metabolites showing alteration in hgd−/− were further investigated in AKU mice (n = 18) and patients from the UK National AKU Centre (n = 25) at baseline and after treatment with the hGA-lowering agent nitisinone (Experiment 2). A metabolic flux experiment was carried out after administration of 13C-labelled hGA to hgd−/−(n = 4) and hgd+/−(n = 4) mice (Experiment 3) to confirm direct association with hGA. hgd−/− mice showed the expected increase in hGA, together with unexpected alterations in tyrosine, purine and TCA-cycle pathways. Metabolites with the greatest abundance increases in hgd−/− were hGA and previously unreported sulfate and glucuronide hGA conjugates, these were decreased in mice and patients on nitisinone and shown to be products from hGA by the 13C-labelled hGA tracer. Our findings reveal that increased hGA in AKU undergoes further metabolism by mainly phase II biotransformations. The data advance our understanding of overall tyrosine metabolism, demonstrating how specific metabolic conditions can elucidate hitherto undiscovered pathways in biochemistry and metabolism.

关键词： Alkaptonuria Biotransformation Metabolism Metabolomics Mice

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Gel casting of PZT pillar arrays for high frequency ultrasonic medical imaging applications

Gel casting of PZT pillar arrays for high frequency ultrason...

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2011 World Congress on Engineering and Technology(CET 2011)

作者： h.hughes C.Meggs T.W.Button School of Metallurgy and Materials University of Birmingham

In this paper we report ultrafine PZT （lead zirconate titanate） pillar arrays for high frequency ultrasonic transducers application by gel casting fabricated using a water soluble resin as a gel *** effect of the amount of hardener addition and ceramic solids loading on the rheological properties and the effect of resin content on the mechanical strength has been *** green strengths of 36.8 MPa have been obtained from gel cast PZT green bodies with 45 vol % solids loading containing 20 wt% of epoxy resin in the premixed *** structures with lateral features down to 2 μm and aspect ratios up to 30 have been demoulded without *** PZT samples are homogenous with low porosity and also show good piezoelectric properties.

关键词： gel casting PZT ultrasonic transducer

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Reticulate spore ornamentation in Strobilomyces

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菌物学报 2011年第6期30卷 901-911页

作者： Ronald h.Petersen John Dunlap Karen W.hughes Department of Ecology and Evolutionary Biology University of TennesseeKnoxvilleTN 37996-1100USA Electron Microscope Facility Division of BiologyUniversity of TennesseeKnoxvilleTN 37996-0830USA

Reticulate spore ornamentation in Strobilomyces(Boletaceae,Basidiomycotina) is visible under light microscopy(bright field and phase contrast) up to 1,500×.While some distinctions can be made at this magnification,ontogeny and fine structure of the ornamentation cannot be *** electron microscope images,conversely,reveal significant additional structure from which the ontogenetic process can be *** numerous New and Old World collections,this paper presents evidence distinguishing reticulate ornamentation ontogeny in these disjunct populations.

关键词：网状孢子电子显微镜观察菌物学

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JAK inhibitors alter NK cell functions and may impair immunosurveillance against lymphomagenesis

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Cellular & Molecular Immunology 2020年第5期17卷 552-553页

作者： Gaetane Nocturne juliette Pascaud Bineta Ly Farhad Tahmasebi Xavier Mariette INSERM UMR 1184 Center for Immunology of Viral Infections and Autoimmune DiseasesUniversitéParis-SudUniversitéParis-SaclayLe Kremlin-BicêtreParisFrance Department of Rheumatology AP-HPHôpitaux Universitaires Paris-SudLe Kremlin-BicêtreParisFrance

An increased risk of B cell lymphomas in patients with myeloproliferative neoplasm(MPN)treated with Janus kinase(JAK)inhibitors has recently been explored.1–3 In light of contradictory results,it is highly important to assess whether JAK inhibitors might be associated with a higher risk of lymphoma,notably in patients with pre-existing B cell clones that can escape immunosurveillance after exposure to JAK *** situation is very similar to what is observed in patients with autoimmune diseases,especially rheumatoid arthritis(RA).B cell clones are present in patients with RA,and dominant BCR clones in the peripheral blood predict the onset of the disease in at-risk individuals.

关键词： lymphoma diseases immuno

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Survey of the electrostatic tractor research for reorbiting passive GEO space objects

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Astrodynamics 2018年第4期2卷 291-305页

作者： M.Bengtson K.Wilson J.hughes h.Schaub Aerospace Engineering Sciences Department University of Colorado Boulder431 UCBBoulderCO80309USA

The number of operational satellites and debris objects in the valuable geosynchronous ring has increased steadily over time such that active debris removal missions are necessary to ensure long-term stability. These objects are very large and tumbling, making any mission scenarios requiring physical contact very challenging. In the last 10 years, the concept of using an electrostatic tractor has been investigated extensively. With the electrostatic tractor concept, active charge emission is employed to simultaneously charge the tug or services vehicle, while aiming the charge exhaust onto the passive space debris object to charge it as well. The resulting electrostatic force has been explored to actuate this debris object to a disposal orbit or to detumble the object, all without physical contact. This paper provides a survey of the related research and reviews the charging concepts, the associated electrostatic force and torque modeling, and the feedback control developments, as well as the charge sensing research.

关键词： electrostatics geosynchronous orbit debris control

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Seasonal and Spatial Variations of Silicon Isotopes in Large Tropical Rivers

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地学前缘 2009年第S1期16卷 235-235页

作者： h.hughes D.Cardinal F.Sondag C.Cocquyt S.Bouillon A.V.Borges A.Pandi L.André Department of Geology and MineralogyRoyal Museum for Central Africa LMTG/OMP Université Paul Sabatier Toulouse Ⅲ/CNRS/IRD National Botanic Garden of Belgium Meise Department of Earth & Environmental SciencesKatholieke Universiteit Leuven Chemical Oceanography Unit Université de Liège Universite Mariem Ngouabi Brazzaville

We present the first large dataset of dissolved silicon isotopes signatures(δ30Si)in different tropical rivers,including the Amazon and the Congo,the two largest silicon suppliers to the world ocean.A two-year long monthly series was obtained in the Congo River upstream of the Kinshasa/Brazzaville urban *** and temporal variations in the Amazon River and its main tributaries were studied for one *** the Congo and Amazon rivers convey similar meanδ30Si signatures to the ocean （close to +0.8‰）,in the range of the few previously published data for those *** Congo River exhibits limited seasonal variations,with the exception of some largeδ30Si variations that

关键词： silicon isotopes silicon cycle weathering clay formation tropical rivers

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Does exploratory behavior or activity in a wild mouse explain susceptibility to virus infection？

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Current Zoology 2018年第5期64卷 585-592页

作者： Bram VANDEN BROECKE Benny BORREMANS Joachim MARIEN Rhodes h. MAKUNDI Apia W. MASSAWE herwig LEIRS Nelika K. hughes Evolutionary Ecology Group Department of Biology University of Antwerp Antwerp 2610 Belgium Department of Ecology and Evolutionary Biology University of California Los Angeles Los Angeles CA 90095-1606 USA and Pest Management Center Sokoine University of Agriculture Chuo Kikuu Morogoro 3110 Tanzania

Exploration and activity are often described as trade-offs between the fitness benefits of gathering information and resources, and the potential costs of increasing exposure to predators and para- sites. More exploratory individuals are predicted to have higher rates of parasitism, but this relationship has rarely been examined for virus infections in wild populations. here, we used the multimammate mouse Mastomys natalensis to investigate the relationship between exploration, activity, and infection with Morogoro virus （MORV）. We characterized individual exploratory behav- ior （open field and novel object tests） and activity （trap diversity）, and quantified the relationship between these traits and infection status using linear regression. We found that M. natalensis expresses consistent individual differences, or personality types, in exploratory behavior （repeat- ability of 0.30, 95% CI： 0.21-0.36）. In addition, we found a significant contrasting effect of age on ex- ploration and activity where juveniles display higher exploration levels than adults, but lower field- activity. There was however no statistical evidence for a behavioral syndrome between these 2 traits. Contrary to our expectations, we found no correlation between MORV infection status and exploratory behavior or activity, which suggests that these behaviors may not increase exposure probability to MORV infection. This would further imply that variation in viral infection between individuals is not affected by between-individual variation in exploration and activity.

关键词： animal personality arenavirus disease ecology exploration Mastomys natalensis Morogoro virus.

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Real-time temperature prediction of electric machines using machine learning with physically informed features

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Energy and AI 2023年第4期14卷 415-425页

作者： Ryan hughes Thomas haidinger Xiaoze Pei Christopher Vagg University of Bath UK AVL List Gmbh Austria

Accurate estimation of the internal temperatures of electric machines is critical to increasing their power density and reliability since key temperatures,such as magnet temperature,are often difficult to *** work presents a new machine learning based modelling approach,incorporating novel physically informed feature engineering,which achieves best-in-class accuracy and reduced training *** different features introduced are proportional to sources of machine losses and require no prior knowledge of the machine,hence the models are completely data *** using a standard experimental dataset shows that modelling errors can be reduced by up to 82.5%,resulting in the lowest mean squared error recorded in the literature of 2.40 K^(2).Additionally,models can be trained with less training data and have lower sensitivity to data ***-ically,it was possible to train a loss enhanced multilayer perceptron model to a mean squared errorh 90 h of training data,and an enhanced ordinary least squares model with just 60 h to the same *** inference time of the model can be 1–2 orders of magnitude faster than competing models and requires no time to optimise hyperparameters,compared to weeks or months for other state-of-the-art prediction *** results are highly important for enabling low-cost real-time temperature monitoring of electric machines to improve operational efficiency,safety,reliability,and power density.

关键词： Thermal model Real-time Electric machine Machine learning Losses

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Accuracy of two optical chlorophyll meters in predicting chemical composition and in vitro ruminal organic matter degradability of Brachiaria hybrid,Megathyrsus maximus, and Paspalum atratum

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Animal Nutrition 2017年第1期3卷 67-76页

作者： Martin P.hughes Victor Mlambo Cicero h.O.Lallo Nasreldin A.D.Basha Ignatius V.Nsahlai Paul G.A.Jennings Department of Food Production Faculty of Food and AgricultureUniversity of the West Indies Department of Animal Science School of Agricultural SciencesFaculty of AgricultureScience and TechnologyNorth-West University Open Tropical Forage-Animal Production Laboratory Department of Food ProductionFaculty of Food and AgricultureUniversity of the West Indies Department of Animal & Poultry Science School of AgriculturalEarth and Environmental SciencesCollege of AgricultureEngineering and ScienceUniversity of KwaZulu-Natal Department of Animal Nutrition Faculty of Animal Production Shampat CampusUniversity of Khartoum MARJEN Consulting Group

The objective of this study was to determine the accuracy and reliability of 2 optical chlorophyll meters:FieldScout CM 1,000 NDVI and Yara N-Tester, in predicting neutral detergent fibre(NDF), acid detergent fibre(ADF), acid detergent lignin(ADL), acid detergent insoluble nitrogen(ADIN) and in vitro ruminal organic matter degradability(IVOMD) of 3 tropical grasses. Optical chlorophyll measurements were taken at 3 stages(4, 8 and 12 weeks) of regrowth in Brachiaria hybrid, and Megathyrsus maximus and at 6 and 12 weeks of regrowth in Paspalum atratum(cv. Ubon). Optical chlorophyll measurements showed the highest correlation(r = 0.57 to 0.85) with NDF concentration. The FieldScout CM 1,000 NDVI was better than the Yara N-Tester in predicting NDF(R^2 = 0.70) and ADF(R^2 = 0.79) concentrations in Brachiaria hybrid and NDF(R^2 = 0.79) in M. maximus. Similarly, FieldScout CM 1,000 NDVI produced better estimates of 24 h IVOMD(IVOMD_(24 h)) in Brachiaria hybrid(R^2 = 0.81) and IVOMD_(48 h) in Brachiaria hybrid(R^2 = 0.65) and M. maximus(R^2 = 0.75). however, these prediction models had relatively low concordance correlation coefficients, i.e., CCC >0.90, but random errors were the main source of bias. It was,therefore, concluded that both optical chlorophyll meters were poor and unreliable predictors of ADIN and ADL concentrations. Overall, the FieldScout CM 1,000 NDVI shows potential to produce useful estimates of IVOMD_(24h) and ADF in Brachiaria hybrid and IVOMD_(48 h) and NDF concentrations in M. maximus.

关键词： Optical chlorophyll measurements Chemical composition Prediction model Tropical grass

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Description of two new species of hemiphyllodactylus(Reptilia: Gekkonidae) from karst landscapes in Yunnan, China, highlights complex conservation needs

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Zoological Research 2022年第5期43卷 767-786页

作者： Ade Prasetyo Agung Ada Chornelia L.Lee Grismer Jesse L.Grismer Evan S.h.Quah Jian-Mei Lu Kyle W.Tomlinson Alice C.hughes Landscape Ecology Group Center for Integrative ConservationXishuangbanna Tropical Botanical GardenChinese Academy of SciencesMenglunMenglaYunnan 666303China University of Chinese Academy of Sciences Beijing 101408China herpetology Laboratory Department of BiologyLa Sierra UniversityRiversideCalifornia 92515USA Institute for Tropical Biology and Conservation Universiti Malaysia SabahJalan UMSKota KinabaluSabah 88400Malaysia Lee Kong Chian Natural history Museum National University of SingaporeSingapore 117377Singapore Community Ecology and Conservation Group Center for Integrative ConservationXishuangbanna Tropical Botanical GardenChinese Academy of SciencesMenglunMenglaYunnan 666303China School of Biological Sciences University of Hong KongPokfulamHong Kong SARChina

Karst habitats are hotspots of diversity and endemism. Their naturally fragmented distributions across broad geographic landscapes have led to the complex array of smaller evolutionary ecosystems that present unique challenges from a conservation *** assessments of karst habitats have revealed that these ecosystems contain an almost unparalleled level of endemism, and many site-restricted species remain undescribed, thus posing considerable challenges for effective conservation *** rock-dwelling species, such as geckos, may be particularly prone to such isolation. In this paper, we discuss one such genus, i.e.,hemiphyllodactylus, and explore its diversity across karst landforms in Yunnan Province, southwestern China. Based on morphological and genetic data, we describe two new species of hemiphyllodactylus from karst habitats in Simao District and Yanshan County. A phylogenetic tree for hemiphyllodactylus was constructed using 1?039 base pairs(bp) of the mitochondrial NADh dehydrogenase subunit 2 gene(ND2). The Simao and Yanshan specimens can be distinguished from all other congeners within their respective subclades based on uncorrected genetic pairwise distances greater than 6.3% and 4.3%respectively, as well as significant morphological differences. The discovery and description of these two new species brings the total number of described hemiphyllodactylus species in China to 14and indicates many more undescribed species from unsurveyed karst regions await *** findings suggest that karst ecosystems in Yunnan support a higher diversity of hemiphyllodactylus than previously *** study also highlights the importance of karst ecosystems as refugia for sitespecific endemic species and the need for heightened conservation efforts.

关键词： Discovery Endemism Geckos Reptiles South China

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