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SARS-CoV-2 spike variants differ in their allosteric responses to linoleic acid

Journal of Molecular Cell Biology 2023年第3期15卷 55-66页

作者： A.Sofia F.Oliveira deborah K.Shoemark andrew d.davidson Imre Berger Christiane Schaffitzel Adrian J.Mulholland School of Chemistry Centre for Computational ChemistryUniversity of BristolBristol BS81TSUK School of Chemistry University of BristolBristol BS81TSUK School of Biochemistry University of BristolBristol BS81TDUK School of Cellular and Molecular Medicine University of BristolUniversity WalkBristol BS81TDUK School of Chemistry Max Planck Bristol Centre for Minimal BiologyBristol BS81TSUK

The SARS-CoV-2 spike protein contains a functionally important fatty acid(FA)binding site,which is also found in some other coronaviruses,***-CoV and *** occupancy of the FA site by linoleic acid(LA)reduces infectivity by‘locking’the spike in a less infectious ***,we use dynamical-nonequilibrium molecular dynamics(d-NEMd)simulations to compare the allosteric responses of spike variants to LA removal.d-NEMd simulations show that the FA site is coupled to other functional regions of the protein,*** receptor-binding motif(RBM),N-terminal domain(NTd),furin cleavage site,and regions surrounding the fusion peptide.d-NEMd simulations also identify the allosteric networks connecting the FA site to these functional *** comparison between the wild-type spike and four variants(Alpha,delta,delta plus,and Omicron BA.1)shows that the variants differ significantly in their responses to LA *** allosteric connections to the FA site on Alpha are generally similar to those on the wild-type protein,with the exception of the RBM and the S71–R78 region,which show a weaker link to the FA *** contrast,Omicron is the most different variant,exhibiting significant differences in the RBM,NTd,V622–L629,and furin cleavage *** differences in the allosteric modulation may be of functional relevance,potentially affecting transmissibility and *** comparison of the effects of LA on SARS-CoV-2 variants,including emerging variants,is warranted.

关键词： SARS-CoV-2 spike allosteric modulation d-NEMd simulations fatty acid binding site SARS-CoV-2 variants

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Review of pharmacological inhibition of thyroid cancer metabolism

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Journal of Cancer Metastasis and Treatment 2021年第1期7卷 640-658页

作者： Cole d.davidson Frances E.Carr department of Pharmacology Larner College of MedicineBurlingtonVT 05405USA University of Vermont Cancer Center BurlingtonVT 05405USA

Thyroid cancer(TC)is the most common malignancy of the endocrine system and has been rapidly increasing in incidence over the past few *** TCs metastasize quickly and often levy poor prognoses,as they are frequently resistant to first-line treatment *** diagnosed with aggressive,dedifferentiated TC have a prognosis of under a year with the most current treatment *** many cancers,TCs also exhibit altered cell metabolism,which enhances the cell’s ability to generate energy,protect against reactive oxygen species,and synthesize macromolecules such as lipids,proteins,and nucleotides for *** and enzyme profiling of TC tissues and cell lines have uncovered several dysregulated metabolic pathways such as glycolysis,the pentose phosphate pathway,glutamine metabolism,and pyrimidine *** aberrations are most often due to overexpression of rate-limiting enzymes or metabolite *** pathways pose attractive therapeutic targets in aggressive TC and may serve to work in tandem with standard therapeutics such as kinase inhibitors depending on the genetic,metabolic,and signaling backgrounds of individual *** studies are needed to clearly delineate altered metabolic targets across TC subtypes for implementing therapeutic metabolic inhibitors that have shown success in other aggressive tumors.

关键词： Thyroid cancer tumor metabolism metabolic inhibitors Warburg effect cell signaling

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Are there sex-based disparities in cataract surgery?

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 137-143页

作者： Matthew d.Geiger Anne M.Lynch Alan G.Palestine Nathan C.Grove Karen L.Christopher Richard S.davidson Michael J.Taravella Naresh Mandava Jennifer L.Patnaik department of Ophthalmology University of Colorado School of MedicineAuroraCO 80045USA

AIM:To investigate sex-based differences in the occurrence of intra-operative and post-operative complications and associated visual outcomes following cataract ***:This was a retrospective study of patients who had phacoemulsification cataract surgery at the University of Colorado School of *** collected included the patient’s health history,ocular comorbidities,operative and post-operative complications,and the post-operative best corrected visual acuity(BCVA).The data were analyzed using univariate and multivariable logistic regression with generalized estimating equations to account for the correlation of some patients having two eyes included in the ***:A total of 11977 eyes from 7253 patients were included in the *** comorbidities differed by sex,with males having significantly higher percentages of traumatic cataracts(males 0.7%vs females 0.1%),prior ocular surgery(6.7%vs 5.5%),and mature cataracts(2.8%vs 1.9%).Conversely,females had significantly higher rates of pseudoexfoliation(2.0%vs 3.2%).In unadjusted analysis,males had higher rates of posterior capsular rupture(0.8%vs 0.4%)and vitreous loss(1.0%vs 0.6%),but this difference was not significant after adjustment for *** had a significantly increased risk of post-operative retinal detachment,but in multivariable analysis this was no longer *** were significantly less likely to undergo post-operative neodymium-doped yttrium aluminum garnet(Nd:YAG)laser capsulotomy for posterior capsule opacification(OR=0.8,95%CI=0.7-0.9,P=0.0005).The BCVA was slightly worse for males pre-operatively;but post-operatively,both sexes exhibited similar visual acuity of Snellen equivalent 20/***:The study finds that in a cohort of patients presenting for cataract surgery,sex differences exist in pre-operative comorbidities and surgical characteristics that contribute to higher rates of some complications for ***,observed surgical complicatio

关键词： cataract surgery sex-based disparity phacoemulsification outcomes

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Low-loss and polarization insensitive 32×4 optical switch for ROAdM applications

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Light(Science & Applications) 2024年第5期13卷 875-884页

作者： Xiaotian Zhu Xiang Wang Yanlu Huang Liyan Wu Chunfei Zhao Mingzhu Xiao Luyi Wang Roy davidson Yanni Ou Brent E.Little Sai T.Chu department of Physics City University of Hong KongTat Chee AvenueHong KongChina. QXP Technologies Inc. NO.15th Shanglinyuan 1st RoadXi’anShaanxi 710119China. State Key Laboratory of Information of Photonics and Optical Communications School of Electronic EngineeringBeijing University of Posts and TelecommunicationsBeijing 100876China

Integrated switches play a crucial role in the development of reconfigurable optical add-drop multiplexers(ROAdMs)that have greater flexibility and compactness,ultimately leading to robust single-chip *** decades of research on switches with various structures and platforms,achieving a balance between dense integration,low insertion loss(IL),and polarization-dependent loss(PdL)remains a significant *** this paper,we propose and demonstrate a 32×4 optical switch using high-index doped silica glass(HdSG)for ROAdM *** switch is designed to route any of the 32 inputs to the express ports or drop any channels from 32 inputs to the target 4 drop ports or add any of the 4 ports to any of the 32 express *** switch comprises 188 MachZehnder Interferometer(MZI)type switch elements,88 optical vias for the 44 optical bridges,and 618 waveguidewaveguide crossings with three-dimensional(3d)*** 1550 nm,the fiber-to-fiber loss for each express channel is below 2 dB,and across the C and L bands,below 3 *** each input channel to all 4 drop/add channels at 1550 nm,the loss is less than 3.5 dB and less than 5 dB across the C and L *** PdLs for all express and input channels to the 4 drop/add channels are below 0.3 dB over the C band,and the crosstalk is under−50 dB for both the C and L bands.

关键词： polarization ROAdM optical

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Gastroenterology service in a teaching hospital in rural New Zealand, 1991-2003

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World Journal of Gastroenterology 2009年第5期15卷 583-590页

作者： Michael Schultz andrew davidson Sarah donald Bogna Targonska Angus Turnbull Susan Weggery Vicki Livingstone John d dockerty department of Medical and Surgical Sciences University of Otago PO Box 913 Dunedin New Zealand and Department of Gastroenterology Dunedin Public Hospital Otago District Health Board Dunedin New Zealand dunedin School of Medicine University of Otago Dunedin New Zealand department of Preventive and Social Medicine University of Otago Dunedin New Zealand

AIM: To retrospectively collect inpatient and outpatient data and to assess the use of endoscopic procedures during the years 1991, 1997 and 2003 to analyse for trends. METHOdS: This retrospective survey was conducted in a University-associated Gastroenterology Unit offering secondary and tertiary health care services for a population of approximately 182 000 people in Southern New Zealand. data collected included patient contacts (inand outpatients), gastroscopic and colonoscopic investigations. RESULTS: We observed a significant increase in the absolute numbers of patient contacts over the years (1991: 2308 vs 1997: 2022 vs 2003: 2783, P disease, other diseases of the colon, anus and rectum and iron studies related disorders decreasing significantly but liver disease and constipation increasing linearly over time. The use of endoscopy services remained relatively stable but colonoscopic investigations for a positive family history of colorectal cancer increased significantly while more gastroscopies were performed for unexplained anaemia. CONCLUSION: The whole spectrum of gastroenterology contacts was studied. A substantial proportion of colonoscopies and outpatient consultations were undertaken to screen for colorectal cancer. This proportion is likely to grow further. Our fi ndings have implications for the recruitment and training of the next generation of gastroenterologists.

关键词： Colonoscopy Colorectal cancer diseasetrends Endoscopy Gastroenterology Hepatitis Inflammatory bowel disease Recruitment Workforce

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Current protective strategies in liver surgery

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World Journal of Gastroenterology 2010年第48期16卷 6098-6103页

作者： Kurinchi S Gurusamy Hector d Gonzalez Brian R davidson HPB and Liver Transplantation Royal Free CampusUniversity College London Medical SchoolRoyal Free Hospital

during liver resection surgery for cancer or liver transplantation,the liver is subject to ischaemia (reduction in blood flow) followed by reperfusion (restoration of blood flow),which results in liver injury [ischemiareperfusion (IR) or IR injury]. Modulation of IR injury can be achieved in various ways. These include hypothermia,ischaemic preconditioning (IPC) (brief cycles of ischaemia followed by reperfusion of the organ before the prolonged period of ischaemia i.e. a conditioning response),ischaemic postconditioning (conditioning after the prolonged period of ischaemia but before the reperfusion),pharmacological agents to decrease IR injury,genetic modulation of IR injury,and machine perfusion (pulsatile perfusion). Hypothermia decreases the metabolic functions and the oxygen consumption of organs. Static cold storage in University of Wisconsin solution reduces IR injury and has prolonged organ storage and improved the function of transplanted grafts. There is currently no evidence for any clinical advantage in the use of alternate solutions for static cold storage. Although experimental data from animal models suggest that IPC,ischaemic postconditioning,various pharma-cological agents,gene therapy,and machine perfusion decrease IR injury,none of these interventions can be recommended in clinical practice. This is because of the lack of randomized controlled trials assessing the safety and efficacy of ischaemic postconditioning,gene therapy,and machine perfusion. Randomized controlled trials and systematic reviews of randomized controlled trials assessing the safety and efficacy of IPC and various pharmacological agents have demonstrated biochemical or histological improvements but this has not translated to clinical benefit. Further well designed randomized controlled trials are necessary to assess the various new protective strategies in liver resection.

关键词： Liver Hepatectomy Liver transplantation Ischemia-reperfusion injury Hypothermia Ischaemic preconditioning

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An arthropod community beyond the dry limit of plant life

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Journal of Arid Land 2021年第6期13卷 629-638页

作者： Benjamin davidson Elli GRONER Arava Institute for Environmental Studies D.N.Eilot 88840Israel Vassar College PoughkeepsieNew York 12604United States of America dead Sea and Arava Science Center Mitzpe Ramon 8060000Israel Ben Gurion University Eilat 88556Israel

Water availability,which enables plant growth and animal activity,regulates dryland ecosystem *** hyper-arid ecosystems,rain cannot support vascular plant ***,hyper-arid vegetation is restricted to the lower topography,where runoff ***,food resources originating from areas of dense vegetation are dispersed across the desert floor,enabling animal life in areas lacking vascular plant ***,certain regions,such as the hyper-arid upper topography,may be devoid of plant-derived food *** present study examined arthropod activity in the upper topography of a hyper-arid desert,in comparison with arthropod activity in the lower *** traps were utilized to compare arthropod activity along unvegetated ridges with activity in parallel,vegetated ***,the study revealed dense arthropod communities in the barren upper *** collected in the upper topography represented 26%of total arthropod *** addition,the overlap between arthropod identity in the ridges and wadis(i.e.,riverbeds)was low,and certain arthropods were strongly affiliated with the *** upper topographic communities included high numbers of silverfish(Zygentoma:Lepismatidae),malachite beetles(Psiloderes),and predatory mites(Acari:Anystidae),and these arthropods were present at various life *** remains unclear how arthropod communities can persist in the unvegetated upper topography of the hyper-arid study *** results raise the possibility that other food sources,independent from vascular plants,may play a significant role in the life history of hyper-arid arthropods.

关键词： hyper-arid area spatial distribution topography silverfish Tenebrionidae desert

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Gas flow in rotary kilns

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Particuology 2010年第6期8卷 613-616页

作者： Patrick R.davies Michael J.S.Norton d.Ian Wilson John F.davidson david M.Scott department of Chemical Engineering and Biotechnology University of CambridgePembroke StreetCambridgeCB2 3RAUK

This paper describes an experimental investigation on the flow characteristics within a rotating cylinder containing a rolling bed of sand. The axis of the cylinder was horizontal and there was no axial bulk flow of particles. The velocity field of the gas flowing through the cylinder was measured by hot-wire anemometry. The measurements indicate that the velocity field is asymmetric with respect to a diameter perpendicular to the granular bed. CFd calculations confirm this finding. The gas velocity profiles are crucial in determining heat transfer from gas to solid.

关键词： Rotating cylinderVelocity profile

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Two-dimensional atomically thin Pt layers on MXenes: The role of electronic effects during catalytic dehydrogenation of ethane and propane

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Nano Research 2024年第3期17卷 1251-1258页

作者： Zhe Li Tobias K.Misicko Fan Yang Xiaopeng Liu Zhenwei Wu Xiaoyang Gao Tao Ma Jeffrey T.Miller daniela S.Mainardi Collin d.Wick Zhenhua Zeng Yang Xiao Yue Wu department of Chemical and Biological Engineering Iowa State University618 Bissell RoadAmesIA 50011USA Institute for Micromanufacturing Louisiana Tech University505 Tech DriveRustonLA 71272USA davidson School of Chemical Engineering Purdue University480 Stadium Mall DriveWest LafayetteIN 47907USA Michigan Center for Materials Characterization University of Michigan2800 Plymouth RdAnn Arbor MI 48109USA College of Engineering and Science Louisiana Tech UniversityRustonLA 71272USA

Atomically thin Pt nanolayers were synthesized on the surface of Mo2TiC2 MXenes and used for the catalytic dehydrogenation of ethane and propane into ethylene and propylene,two important chemicals for the petrochemical *** compared with Pt nanoparticles,the atomically thin Pt nanolayer catalyst showed superior coke-resistance(no deactivation for 24 h),high activity(turnover frequencies(TOFs)of 0.4–1.2 s^(-1)),and selectivity(>95%)toward ethylene and *** unique Pt nanolayer has a similar geometric surface to Pt nanoparticles,enabling the investigations of the electronic effect on the catalytic performance,where the geometric effect is *** is found that the electronic effect plays a critical role in dehydrogenative product selectivity and catalyst *** metal–support interaction is found dependent on the substrate and metal components,providing wide opportunities to explore high-performance MXene-supported metallic catalysts.

关键词： MXene catalysis alkane dehydrogenation nanolayers

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玻璃和熔体包裹体中水含量的拉曼光谱定量测定方面的进展评述

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岩石学报 2007年第1期23卷 15-20页

作者： Rainer THOMAS Paul davidson GeoForschungsZentrum Potsdam Telegrafenberg B120D-14473 PotsdamGermany ARC Centre of ExceUence in Ore deposits University of TasmaniaHobart 7001Australia

This paper is focused on the progress in the determination of water in glasses and melt inclusions with Raman *** the presented'Comparator Technique'the water content of a sample is determined by simple comparison with a known standard.A calibration curve is not ***,with this technique the water concentration in silicate melt inclusions can be determined without exposing the inclusions for *** is very important for extremely water-rich melt inclusions,which would loose H_2O on exposure.

关键词：玻璃熔体包裹体水含量拉曼光谱定量测定研究进展

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