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Construction of a broad-host-range Anderson promoter series and particulate methane monooxygenase promoter variants expand the methanotroph genetic toolbox

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Synthetic and Systems Biotechnology 2024年第2期9卷 250-258页

作者： Etash H.Bhat Jessica M.Henard Spencer A.Lee Dustin McHalffey Mahith S.Ravulapati Elle V.Rogers Logan Yu David Skiles Calvin A.Henard Department of Biological Sciences and biodiscovery institute University of North TexasDentonTXUSA

Methanotrophic bacteria are currently used industrially for the bioconversion of methane-rich natural gas and anaerobic digestion-derived biogas to valuable *** bacteria may also serve to mitigate the negative effects of climate change by capturing atmospheric greenhouse *** genetic tools have previously been developed for genetic and metabolic engineering of ***,the available tools for use in methanotrophs are significantly underdeveloped compared to many other industrially relevant bacteria,which hinders genetic and metabolic engineering of these *** such,expansion of the methanotroph genetic toolbox is needed to further our understanding of methanotrophy and develop biotechnologies that leverage these unique microbes for mitigation and conversion of methane to valuable ***,we determined the copy number of three broad-host-range plasmids in Methylococcus capsulatus Bath and Methylosinus trichosporium OB3b,representing phylogenetically diverse Gammaproteobacterial and Alphaproteobacterial methanotrophs,***,we show that the commonly used synthetic Anderson series promoters are functional and exhibit similar relative activity in *** and *** OB3b,but the synthetic series had limited ***,we mutagenized the native *** particulate methane monooxygenase promoter and identified variants with activity that expand the activity range of synthetic,constitutive promoters functional not only in ***,but also in Escherichia ***,the tools developed here advance the methanotroph genetic engineering toolbox and represent additional synthetic genetic parts that may have broad applicability in Pseudomonadota bacteria.

关键词： Methanotroph Methane monooxygenase Promoter Metabolic engineering Synthetic biology

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Application of neurotrophic and proangiogenic factors as therapy after peripheral nervous system injury

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Neural Regeneration Research 2022年第6期17卷 1240-1247页

作者： Kamilla Faritovna Idrisova Alina Kazymovna Zeinalova Galina Andreevna Masgutova Alexey Andreevich Bogov Jr. Cinzia Allegrucci Valeriia Yurievna Syromiatnikova Ilnur Ildusovich Salafutdinov Ekaterna Evgenievna Garanina Dina Ivanovna Andreeva Adilet Abdullaatovich Kadyrov Albert Anatolevich Rizvanov Ruslan Faridovich Masgutov institute of Fundamental Medicine and Biology Kazan Federal UniversityKazanRussia Republican Clinical Hospital KazanRussia biodiscovery institute School of Veterinary Medicine and ScienceUniversity of NottinghamNottinghamUK Department of Traumatology and Orthopedics Kazan State Medical AcademyKazanRussia

The intrinsic ability of peripheral nerves to regenerate after injury is extremely limited,especially in case of severe *** often leads to poor motor function and permanent *** approaches for the treatment of injured nerves do not provide appropriate conditions to support survival and growth of nerve *** drawback can be compensated by the use of gene therapy and cell therapy-based drugs that locally provide an increase in the key regulators of nerve growth,including neurotrophic factors and extracellular matrix *** growth factor plays its own specific angiotrophic or neurotrophic ***,growth factors are widely studied as accelerators of nerve *** noteworthy is synergy between various growth factors,that is essential for both angiogenesis and *** growth factor 2 and vascular endothelial growth factor are widely known for their proangiogenic *** the same time,fibroblast growth factor 2 and vascular endothelial growth factor stimulate neural cell growth and play an important role in neurodegenerative diseases of the peripheral nervous *** together,their neurotrophic and angiogenic properties have positive effect on the regeneration *** this review we provide an in-depth overview of the role of fibroblast growth factor 2 and vascular endothelial growth factor in the regeneration of peripheral nerves,thus demonstrating their neurotherapeutic efficacy in improving neuron survival in the peripheral nervous system.

关键词： fibroblast growth factor 2 growth factors nerve growth factor peripheral nerve injury peripheral nervous system vascular endothelial growth factor

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Targeting growth hormone function: strategies and therapeutic applications

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Signal Transduction and Targeted Therapy 2019年第1期4卷 614-624页

作者： Man Lu Jack U.Flanagan Ries J.Langley Michael P.Hay Jo K.Perry Liggins institute University of AucklandAucklandNew Zealand Auckland Cancer Society Research Centre School of Medical SciencesUniversity of AucklandAucklandNew Zealand Maurice Wilkins Centre for Molecular biodiscovery AucklandNew Zealand Department of Molecular Medicine and Pathology School of Medical SciencesUniversity of AucklandAucklandNew Zealand

Human growth hormone(GH)is a classical pituitary endocrine hormone that is essential for normal postnatal growth and has pleiotropic effects across multiple physiological *** is also expressed in extrapituitary tissues and has localized autocrine/paracrine effects at these *** adults,hypersecretion of GH causes acromegaly,and strategies that block the release of GH or that inhibit GH receptor(GHR)activation are the primary forms of medical therapy for this *** of GH has also been linked to cancer and the microvascular complications that are associated with ***,studies to investigate the therapeutic potential of GHR antagonism in these diseases have been limited,most likely due to difficulty in accessing therapeutic tools to study the pharmacology of the receptor in *** review will discuss current and emerging strategies for antagonizing GH function and the potential disease indications.

关键词： therapeutic pituitary diseases

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Orthogonal assays for the identification of inhibitors of the single-stranded nucleic acid binding protein YB-1

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Acta Pharmaceutica Sinica B 2019年第5期9卷 997-1007页

作者： Alexander J.Trevarton Yan Zhou Dehua Yang Gordon W.Rewcastle Jack U.Flanagan Antony Braithwaite Peter R.Shepherd Cristin G.Print Ming-Wei Wang Annette Lasham Department of Molecular Medicine and Pathology University of AucklandAucklandNew Zealand The National Center for Drug Screening and the CAS Key Laboratory of Receptor Research Shanghai Institute of Materia MedicaChinese Academy of Sciences(CAS)Shanghai201203China Auckland Cancer Society Research Centre AucklandNew Zealand Maurice Wilkins Centre for Molecular biodiscovery University of AucklandAucklandNew Zealand Department of Pathology Dunedin School of MedicineUniversity of OtagoDunedinNew Zealand Maurice Wilkins Centre for Molecular biodiscovery University of OtagoDunedinNew Zealand School of Pharmacy Fudan UniversityShanghai201203China

We have previously shown that high expression of the nucleic acid binding factor YB-1 is strongly associated with poor prognosis in a variety of cancer types. The 3-dimensional protein structure of YB-1 has yet to be determined and its role in transcriptional regulation remains elusive. Drug targeting of transcription factors is often thought to be difficult and there are very few published high-throughput screening approaches. YB-1 predominantly binds to single-stranded nucleic acids, adding further difficulty to drug discovery. Therefore, we have developed two novel screening assays to detect compounds that interfere with the transcriptional activation properties of YB-1, both of which may be generalizable to screen for inhibitors of other nucleic acid binding molecules. The first approach is a cell-based luciferase reporter gene assay that measures the level of activation of a fragment of the E2 F1 promoter by YB-1. The second approach is a novel application of the Alpha Screen system, to detect interference of YB-1 interaction with a single-stranded DNA binding site. These complementary assays examine YB-1 binding to two discrete nucleic acid sequences using two different luminescent signal outputs and were employed sequentially to screen 7360 small molecule compounds leading to the identification of three putative YB-1 inhibitors.

关键词： Cancer YB-1 Luciferase Alpha Screen Transcription factor Single-stranded DNA

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The complexities of proanthocyanidin biosynthesis and its regulation in plants

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Plant Communications 2023年第2期4卷 12-27页

作者： Keji Yu Yushuang Song Jinxing Lin Richard A.Dixon National Engineering Research Center of Tree Breeding and Ecological Restoration Beijing Forestry UniversityBeijing 100083China College of Biological Sciences and Biotechnology Beijing Forestry UniversityBeijing 100083China biodiscovery institute and Department of Biological Sciences University of North TexasDentonTX 76203USA Beijing Advanced Innovation Center for Tree Breeding by Molecular Design Beijing Forestry UniversityBeijing 100083China

Proanthocyanidins(PAs)are natural flavan-3-ol polymers that contribute protection to plants under biotic and abiotic stress,benefits to human health,and bitterness and astringency to food *** are also potential targets for carbon sequestration for climate *** recent years,from model species to commercial crops,research has moved closer to elucidating the flux control and channeling,subunit biosynthesis and polymerization,transport mechanisms,and regulatory networks involved in plant PA *** review extends the conventional understanding with recent findings that provide new insights to address lingering questions and focus strategies for manipulating PA traits in plants.

关键词： condensed tannin proanthocyanidin carbocation chemistry metabolic channeling non-enzymatic polymerization

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Effect of different intensities of physical activity on cardiometabolic markers and vascular and cardiac function in adult rats fed with a high-fat high-carbohydrate diet

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Journal of Sport and Health Science 2018年第1期7卷 109-119页

作者： Romeo B.Batacan Jr Mitch J.Duncan Vincent J.Dalbo Geraldine L.Buitrago Andrew S.Fenning School of Medical and Applied Sciences Central Queensland University Centre for Physical Activity Studies Central Queensland University School of Medicine & Public Health Priority Research Centre for Physical Activity and Nutrition Faculty of Health and MedicineThe University of Newcastle University Drive Clinical Biochemistry Laboratory Central Queensland University Centre for biodiscovery and Molecular Development of Therapeutics Australian Institute of Tropical Health and MedicineJames Cook University

Background: Physical activity(PA) and diet are 2 lifestyle factors that affect cardiometabolic risk. However, data on how a high-fat highcarbohydrate(HFHC) diet influences the effect of different intensities of PA on cardiometabolic health and cardiovascular function in a controlled setting are yet to be fully established. This study investigated the effect of sedentary behavior, light-intensity training(LIT), and high-intensity interval training(HIIT) on cardiometabolic markers and vascular and cardiac function in HFHC-fed adult ***: Twelve-week-old Wistar rats were randomly allocated to 4 groups(12 rats/group): control(CTL), sedentary(SED), LIT, and *** indices, glucose and lipid control, inflammatory and oxidative stress markers, vascular reactivity, and cardiac electrophysiology of the experimental groups were examined after 12 weeks of HFHC-diet feeding and PA ***: The SED group had slower cardiac conduction(p = 0.0426) and greater thoracic aortic contractile responses(p < 0.05) compared with the CTL group. The LIT group showed improved cardiac conduction compared with the SED group(p = 0.0003), and the HIIT group showed decreased mesenteric artery contractile responses compared with all other groups and improved endothelium-dependent mesenteric artery relaxation compared with the LIT group(both p < 0.05). The LIT and HIIT groups had lower visceral(p = 0.0057 for LIT, p = 0.0120 for HIIT)and epididymal fat(p < 0.0001 for LIT, p = 0.0002 for HIIT) compared with the CTL ***: LIT induced positive adaptations on fat accumulation and cardiac conduction, and HIIT induced a positive effect on fat accumulation,mesenteric artery contraction, and endothelium-dependent relaxation. No other differences were observed between groups. These findings suggest that few positive health effects can be achieved through LIT and HIIT when consuming a chronic and sustained HFHC diet.

关键词： High-intensity interval training Inflammation Light-intensity training Metabolic syndrome Oxidative stress Sedentary behavior Western diet

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Sustained adenosine release:Revealing its impact on osteogenic signalling pathways of human mesenchymal stromal cells

Engineered Regeneration

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Engineered Regeneration 2024年第2期5卷 255-268页

作者： Hadi Hajiali Jane McLaren Cristina Gonzalez-García Salah Abdelrazig Dong-Hyun Kim Matthew J.Dalby Manuel Salmerón-Sánchez Felicity R.A.J.Rose School of Pharmacy Nottingham Biodiscovery InstituteUniversity of NottinghamNottinghamUK Healthcare Technologies institute School of Chemical EngineeringUniversity of BirminghamBirminghamUK Centre for the Cellular Microenvironment University of GlasgowGlasgowUK Centre for Analytical Bioscience Advanced Materials&Healthcare Technologies DivisionSchool of PharmacyUniversity of NottinghamNottinghamUK Marine Microbiomics Program in BiologyDivision of Science and MathematicsNew York University Abu Dhabi(NYUAD)P.O.Box 129188Abu DhabiUnited Arab Emirates

Non-healing fractures,a global health concern arising from trauma,osteoporosis,and tumours,can lead to severe ***,integral to cellular energy metabolism,gains prominence in bone regeneration via adeno-sine A2 B receptor *** study introduces a controlled-release system for localized adenosine delivery,fostering human mesenchymal stromal cell(hMSC)differentiation into functional bone *** study investi-gates how the ratio of lactic acid to glycolic acid in microparticles can influence adenosine release and explores the downstream effects on gene expression and metabolic profiles of osteogenic differentiation in hMSCs cultured in growth and osteoinductive *** into adenosine-modulated signalling pathways during MSC differenti-ation,with osteogenic factors,provide a comprehensive understanding of the pathways *** gene expression and metabolic profiles unravels adenosine’s regulatory mechanisms in MSC *** adenosine release from microparticles induces mineralization,synergizing with osteogenic media supplements,showcasing the potential of adenosine for treating critical bone defects and metabolic *** study high-lights the efficacy of a polymeric microparticle-based delivery system,offering novel strategies for bone *** adenosine’s roles and associated signalling pathways advances our comprehension of molecular mech-anisms steering bone regeneration,propelling innovative biomaterial,combined with metabolites,approaches for clinical use.

关键词： Adenosine release Osteogenic signalling pathways Human mesenchymal stromal cells Bone regeneration

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Carboxylated-xyloglucan and peptide amphiphile co-assembly in wound healing

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Regenerative Biomaterials 2021年第5期8卷 75-86页

作者： Alessia Ajovalasit Carlos Redondo-Go´mez Maria Antonietta Sabatino Babatunde OOkesola Kristin Braun Alvaro Mata Clelia Dispenza Dipartimento di Ingegneria(DI) Universitadegli Studi di PalermoViale delle ScienzeEdificio 6Palermo 90128Italy School of Engineering&Materials Science Queen Mary University of LondonLondon E14NSUK institute of Bioengineering Queen Mary University of LondonLondon E14NSUK Blizard institute Barts and The London School of Medicine and DentistryThe Blizard Building4 Newark StreetLondon E12ATUK School of Pharmacy University of NottinghamNottingham NG72RDUK Department of Chemical and Environmental Engineering University of NottinghamNottingham NG72RDUK biodiscovery institute University of NottinghamNottinghamNG72RDUK Istituto di Biofisica(IBF) Consiglio Nazionale Delle Ricerche(CNR)Via U.La Malfa 153Palermo 90146Italy

Hydrogel wound dressings can play critical roles in wound healing protecting the wound from trauma or contamination and providing an ideal environment to support the growth of endogenous cells and promote wound *** work presents a self-assembling hydrogel dressing that can assist the wound repair process mimicking the hierarchical structure of skin extracellular *** this aim,the co-assembly behaviour of a carboxylated variant of xyloglucan(CXG)with a peptide amphiphile(PA-H3)has been investigated to generate hierarchical constructs with tuneable molecular composition,structure,and *** electron microscopy and circular dichroism at a low concentration shows that CXG and PA-H3 co-assemble into nanofibres by hydrophobic and electrostatic interactions and further aggregate into nanofibre bundles and *** a higher concentration,CXG and PA-H3 yield hydrogels that have been characterized for their morphology by scanning electron microscopy and for the mechanical properties by smallamplitude oscillatory shear rheological measurements and compression tests at different CXG/PAH3 ratios.A preliminary biological evaluation has been carried out both in vitro with HaCat cells and in vivo in a mouse model.

关键词： self-assembly peptide nanofiber hydrogel wound healing skin tissue engineering

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HLA-G and single nucleotide polymorphism(SNP)associations with cancer in African populations:Implications in personal medicine

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Genes & Diseases 2022年第5期9卷 1220-1233页

作者： Ismael Chatita Adolf Amany Almars Nazima Dharsee Teddy Mselle Gokce Akan Irene Jeremiah Nguma Abdolrahman S.Nateri Fatmahan Atalar Mbeya College of Health and Allied Sciences University of Dar es SalaamMbeyaP.O Box 608Tanzania Cancer Genetics&Stem Cell Group BioDiscovery InstituteDivision of Cancer and Stem CellsSchool of MedicineUniversity of NottinghamNottinghamNG72UHUK Ocean Road Cancer institute Department of OncologyDar es SalaamP.O Box 3592Tanzania Muhimbili University of Health and Allied Sciences MUHAS Genetic LaboratoryDepartment of BiochemistryDar es SalaamP.O Box 65001Tanzania Clinical Oncology Department Mbeya Zonal Referral Hospital(MZRH)Mbeya P.O Box 419Tanzania Child Health institute Department of Rare DiseasesIstanbul UniversityIstanbul 34093Turkey

The immune system plays an important role in protecting the body against *** cancer immunoediting,the immune system can recognize and keep checking the tumor cells by down-expression of some self-molecules or by increasing expression of some novel ***,the microenvironment created in the course of cancer development hampers the immune ability to recognize and destroy the transforming *** Leukocyte Antigen G(HLA-G)is emerging as immune checkpoint molecule produced more by cancer cells to weaken the immune response against ***-G is a non-classical HLA class I molecule which is normally expressed in immune privileged tissues as a soluble or membrane-bound ***-G locus is highly polymorphic in the non-coding 3′untranslated region(UTR)and in the 5′upstream regulatory region(5′URR).HLA-G expression is controlled by polymorphisms located in these regions,and several association studies between these polymorphic sites and disease predisposition,response to therapy,and/or HLA-G protein expression have been *** polymorphisms are demonstrated to modulate its expression and this is increasingly finding more significance in cancer *** review focuses on the relevance of the HLA-G gene and its polymorphisms in cancer *** highlight population genetics of HLA-G as evidence to espouse the need and importance of exploring potential utility of HLA-G in cancer diagnosis,prognosis and immunotherapy in the currently understudied African population.

关键词： African population Cancer HLA-G Immune system checkpoints MHC Single nucleotide polymorphism

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Leveraging off higher plant phylogenetic insights for antiplasmodial drug discovery

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Natural Products and Bioprospecting 2023年第1期13卷 382-399页

作者： Phanankosi Moyo Luke Invernizzi Sephora M.Mianda Wiehan Rudolph Warren A.Andayi Mingxun Wang Neil R.Crouch Vinesh J.Maharaj biodiscovery Center Department of ChemistryFaculty of Natural and Agricultural SciencesUniversity of PretoriaPrivate Bag X 20HatfieldPretoria 0028South Africa Department of Physical and Biological Sciences Murang’a University of TechnologyMurang’aKenya Computer Science and Engineering University of California Riverside900 University AveRiversideCA 92521USA Biodiversity Research and Monitoring Directorate South African National Biodiversity InstituteBerea RoadP.O.Box 52099Durban 4007South Africa School of Chemistry and Physics University of KwaZulu-NatalDurban 4041South Africa

The antimalarial drug-resistance conundrum which threatens to reverse the great strides taken to curb the malaria scourge warrants an urgent need to find novel chemical scaffolds to serve as templates for the development of new antimalarial *** represent a viable alternative source for the discovery of unique potential antiplasmodial chemical *** expedite the discovery of new antiplasmodial compounds from plants,the aim of this study was to use phylogenetic analysis to identify higher plant orders and families that can be rationally prioritised for antimalarial drug *** queried the PubMed database for publications documenting antiplasmodial properties of natural compounds isolated from higher ***,we manually collated compounds reported along with plant species of origin and relevant pharmacological *** systematically assigned antiplasmodial-associated plant species into recognised families and orders,and then computed the resistance index,selectivity index and physicochemical properties of the compounds from each taxonomic *** the generated phylogenetic trees and the biological data of each clade allowed for the identification of 3‘hot’plant orders and *** top 3 ranked plant orders were the(i)Caryophyllales,(ii)Buxales,and(iii)*** top 3 ranked plant families were the(i)Ancistrocladaceae,(ii)Simaroubaceae,and(iii)*** highly active natural compounds(IC_(50)≤1μM)isolated from these plant orders and families are structurally unique to the‘legacy’antimalarial *** study was able to identify the most prolific taxa at order and family rank that we propose be prioritised in the search for potent,safe and drug-like antimalarial molecules.

关键词： Natural products Plants Phylogenetics Malaria Drug-resistance ‘Hot’plants

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