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Mechanism-driven strategies for prevention of rheumatoid arthritis

Rheumatology & Autoimmunity 2022年第3期2卷 109-119页

作者： V.Michael Holers kristine a.kuhn M.Kristen Demoruelle Jill M.Norris Gary S.Firestein Eddie A.James William H.Robinson Jane H.Buckner Kevin D.Deane Division of Rheumatology University of Colorado School of MedicineAuroraColoradoUSA Department of Epidemiology Colorado School of Public HealthAuroraColoradoUSA Division of Rheumatology Allergy and ImmunologyUniversity of California San DiegoLa JollaCaliforniaUSA Benaroya Research Institute SeattleWashingtonUSA Division of Immunology and Rheumatology Stanford UniversityStanfordCaliforniaUSA Department of Medicine Division of RheumatologyVA Palo Alto Health Care SystemPalo AltoCaliforniaUSA

In seropositive rheumatoid arthritis(RA),the onset of clinically apparent inflammatory arthritis(IA)is typically preceded by a prolonged period of autoimmunity manifest by the presence of circulating autoantibodies that can include antibodies to citrullinated protein antigens(ACPA)and rheumatoid factor.This period before clinical IA can be designated preclinical RA in those individuals who have progressed to a clinical diagnosis of RA,and an“at‐risk”status in those who have not developed IA but exhibit predictive biomarkers of future clinical RA.With the goal of developing RA prevention strategies,studies have characterized immune phenotypes of preclinical RA/at-risk states.From these studies,a model has emerged wherein mucosal inflammation and dysbiosis may lead first to local autoantibody production,which should normally be transient,but instead is followed by a systemic spread of the autoimmunity as manifested by serum autoantibody elevations,ultimately driving the development of clinically identified joint inflammation.This model can be envisioned as the progression of disease development through serial“checkpoints”that in principle should constrain or resolve autoimmunity;however,instead,the checkpoints“fail”and clinical RA develops.Herein we review the immune processes that are likely to be present at each step and the potential therapeutic strategies that could be envisioned to delay,diminish,halt,or even reverse the progression to clinical RA.Notably,these prevention strategies could utilize existing therapies approved for clinical RA,therapies approved for other diseases that target relevant pathways in the preclinical/at-risk state,or approaches that target novel pathways.

关键词： autoimmune disease inflammation mucosa prevention rheumatoid arthritis

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Distant cousins come to ABP1’s rescue

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Science China(Life Sciences) 2024年第1期67卷 219-220页

作者： Andre kuhn Dolf Weijers Laboratory of Biochemistry Wageningen UniversityStippeneng 46708WE Wageningenthe Netherlands

There are few plant processes that are not in one way or another influenced by the auxin signaling molecule.The many roles auxin plays in plants have inspired a range of investigations towards understanding its mechanisms of action.In recent years and decades,genetic analysis in the flowering plant Arabidopsis has been immensely successful in bringing a nuclear response mechanism to light(reviewed in Weijers and Wagner,2016).This system,the nuclear auxin pathway(NAP),acts by regulating gene expression,and when its components are mutated,growth and development is strongly disturbed(Weijers and Wagner,2016).

关键词： bringing disturbed Arabidopsis

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The dual role of striatal interneurons: circuit modulation and trophic support for the basal ganglia

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Neural Regeneration Research 2024年第6期19卷 1277-1283页

作者： Elliot Wegman Marlena Wosiski-kuhn Yu Luo Department of Molecular and Cellular Biosciences University of Cincinnati 2. Department of Emergency Medicine at the School of Medicine University of Cincinnati Neuroscience Graduate Program University of Cincinnati

Striatal interneurons play a key role in modulating striatal-dependent behaviors, including motor activity and reward and emotional processing. Interneurons not only provide modulation to the basal ganglia circuitry under homeostasis but are also involved in changes to plasticity and adaptation during disease conditions such as Parkinson’s or Huntington’s disease. This review aims to summarize recent findings regarding the role of striatal cholinergic and GABAergic interneurons in providing circuit modulation to the basal ganglia in both homeostatic and disease conditions. In addition to direct circuit modulation, striatal interneurons have also been shown to provide trophic support to maintain neuron populations in adulthood. We discuss this interesting and novel role of striatal interneurons, with a focus on the maintenance of adult dopaminergic neurons from interneuronderived sonic-hedgehog.

关键词： cholinergic dopamine GABAergic interneuron levodopa-induced dyskinesia parvalbumin sonic hedgehog striatum trophic factor

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An approach of the internal friction-dependent temperature changes for conventional and pure biogenic lubricating greases

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Friction 2024年第4期12卷 780-795页

作者： Leif AHME Erik kuhn MiguelÁngel DELGADO Department of Mechanical Engineering and Production Management Hamburg University of Applied SciencesHamburg 20099Germany Department of Chemical Engineering Research in Product Technology and Chemical Processes(Pro2TecS)University of HuelvaHuelva 21071Spain

This work investigated the temperature changes inside the bulk of lubricating greases under controlled high-shear stress conditions(250-500 s-1).For this purpose,a newly developed temperature-measuring cell called Calidus was successfully tested.The temperature changes(ΔT)have been related to the greases'components(thickener,base oil-type,and composition)and the structural degradation of the lubricating greases.Furthermore,a theoretical approach was proposed for calculating the internal temperature change of lubricating greases during shear stress.All greases showed an internal temperature profile characterised by a sudden rise inΔT within the first 4 h from starting the test and subsequentΔT decay until it reaches the steady state value.Furthermore,it was found that greases C1 and C5,formulated with lithium and calcium soap,respectively,with different soap content(16.1 wt%and 9.7 wt%,respectively),but the same base castor oil,showed the highest value of the maximumΔT,c.a.3.2 K,and the most drastic drop ofΔT.These greases showed both the highest specific densities and heat capacities.In addition,they showed the lowest ratio of expended energies(Rtee),which means more structural degradation in the stressed grease.On the contrary,the grease C3,with 13 wt%of Li-soap but the lowest base oil's viscosity,showed the lowest maximumΔT and the temperature profile was characterised by a moderate variation ofΔT along the test.The biogenic grease B3 developed a low-temperature change in the group of pure bio-genic greases close to grease C3.

关键词： shear-induced structural degradation rheology temperature measurements lubricating greases density lubricating greases specific heat capacities

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Improving risk reduction potential of weather index insurance by spatially downscaling gridded climate data-a machine learning approach

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Big Earth Data 2023年第4期7卷 937-960页

作者： Sarvarbek Eltazarov Ihtiyor Bobojonov Lena.kuhn Thomas Glauben Department of Agricultural Markets Marketing and World Agricultural TradeLeibniz Institute of Agricultural Development in Transition Economies(IAMO)HalleGermany

Open-access gridded climate products have been suggested as a potential source of data for index insurance design and operation in data-limited regions.However,index insurance requires climate data with long historical records,global geographical coverage and fine spatial resolution at the same time,which is nearly impossible to satisfy,especially with open-access data.In this paper,we spatially downscaled gridded climate data(precipitation,temperature,and soil moisture)in coarse spatial resolution with globally available longterm historical records to finer spatial resolution,using satellite-based data and machine learning algorithms.We then investigated the effect of index insurance contracts based on downscaled climate data for hedging spring wheat yield.This study employed countylevel spring wheat yield data between 1982 and 2018 from 56 counties overall in Kazakhstan and Mongolia.The results showed that in the majority of cases(70%),hedging effectiveness of index insurances increases when climate data is spatially downscaled with a machine learning approach.These improvements are statistically significant(p≤0.05).Among other climate data,more improvements in hedging effectiveness were observed when the insurance design was based on downscaled temperature and precipitation data.Overall,this study highlights the reasonability and benefits of downscaling climate data for insurance design and operation.

关键词： Climate risk management risk reduction extreme weather random forest ESA parametric insurance

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Performance evaluation of high/ultra-high-degree global geopotential models over Vietnam using GNSS/leveling data

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Geodesy and Geodynamics 2023年第5期14卷 500-512页

作者： Hoa Thi Pham Sten Claessens Michael kuhn Joseph Awange School of Earth and Planetary Sciences Spatial Sciences DisciplineCurtin UniversityPerthAustralia Faculty of Surveying Mapping and Geographic InformationHanoi University of Natural Resources and EnvironmentHanoiViet Nam

The availability of many high-degree Global Geopotential Models(GGMs), namely EGM2008, EIGEN-6C4,GECO, SGG-UGM-1, SGG-UGM-2, XGM2019e_2159, and GGMPlus, challenges users regarding which model is best for Vietnam. This study, therefore, evaluates their performance by comparing them with GNSS/leveling data over Vietnam. Results show that their absolute and relative performances are largely independent of topographic conditions and geographical location and can be ranked into three classes:(1)XGM2019e_2159 has the highest accuracy,(2) the models EIGEN-6C4, GECO, SGG-UGM-1, SGG-UGM-2, and GGMPlus, have a very similar level of medium accuracy, while(3) EGM2008 is found to be the least accurate. In an absolute sense, the differences between GNSS/leveling and EGM2008-based height anomalies have a standard deviation(STD) of 0.290 ± 0.010 m, whereas, for XGM2019e_2159, this is 0.156 ± 0.006 m.All other models have STDs of(0.18-0.19) ± 0.007 m. Regarding relative performance without fitting, all GGMs have comparable accuracies for baseline length of 5-20 km, while for baselines longer than 20 km,the STD of XGM2019e_2159 is 1.5 ppm-0.5 ppm(approximately 19%-40%) lower compared with EGM2008, and 0.5 ppm-0.25 ppm(approximately 7%-36%) lower compared with EIGEN6C4, GECO,SGG-UGM-1, SGG-UGM-2, and GGMPlus. In addition, the STDs decrease significantly from 20 to 12 ppm in the range of 5-10 km, slightly from 12 to 6 ppm for 10-35 km, very slightly from 6 to 2.5 ppm for35-200 km, and then remain almost unchanged for longer baselines. After fitting, the relative accuracies of all GGMs are at the same level with negligible STD/RMSE values. Furthermore, only EGM2008 experiences significant regional differences, while other GGMs show more homogeneous spatial variation of absolute accuracy over Vietnam. These findings can contribute to the development of local quasigeoid models in Vietnam and may be helpful with the improvement of GGMs in the future.

关键词： GGM Evaluation GNSS/Leveling EGM2008 EIGEN-6C4 GECO SGG-UGM-1 SGG-UGM-2 XGM2019e_2159 GGMPlus

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Periprosthetic knee joint infection caused by Brucella melitensis which was first-osteoarticular brucellosis or osteoarthrosis:A case report

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World Journal of Clinical Cases 2023年第3期11卷 677-683页

作者： Thomas Stumpner Regina.kuhn Josef Hochreiter Reinhold Ortmaier Department of Orthopaedic Surgery Ordensklinikum Linz Barmherzige SchwesternLinz 4010Austria

BACKGROUND Brucellosis is the most common zoonosis worldwide and is endemic in the Middle East,Africa,Asia,and Latin America.However,it is uncommon in Central Europe,and periprosthetic infections caused by Brucella are therefore rare.Due to the low prevalence and nonspecific clinical presentation of the disease,accurate diagnosis can be challenging;no gold standard currently exists for treating brucellosis.CASE SUMMARY Here,we present a 68-year-old Afghan woman living in Austria with a periprosthetic knee infection caused by Brucella melitensis.The interval from total knee arthroplasty to septic loosening was five years.A profound medical history and examinations suggested that the patient had been suffering from unrecognized chronic osteoarticular brucellosis prior to total knee arthroplasty.She was successfully treated by two-stage revision surgery and combined antibiotic therapy over three months.CONCLUSION Clinicians should consider brucellosis as a possible cause of chronic arthralgia and periprosthetic infection in patients originating from countries with a high brucellosis burden.

关键词： Brucellosis Arthroplasty Infection Osteoarticular Knee Case report

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’Emulsion locks’ for the containment of hydrocarbons during surfactant flushing

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Journal of Environmental Sciences 2020年第4期32卷 98-109页

作者： kristine Lamont Alejandro GMarangoni Erica Pensini University of Guelph School of Engineering50 Stone Road EastGwelph ONNIG 2W1Canada University of Guelph Food Science Department50 Stone Road EastGuelph ONNIG 2WlCanada

Reversible double water in oil in water(W/O/W)emulsions were developed to contain subsurface hydrocarbon spills during their remediation using surfactant flushing.Double emulsions were prepared by emulsifying CaCl2 solutions in canola oil,and subsequently by emulsifying the W/O emulsions in aqueous sodium alginate solutions.The formation of double emulsions was confirmed with confocal and optical microscopy.The double emulsions reversed and gelled when mixed with the surfactants sodium dodecyl sulfate(SDS)and cocamidopropyl betaine(CPB).Gels can act as’emulsion locks’to prevent spreading of the hydrocarbon plume from the areas treated with surfactant flushing,as shown in sand column tests.Shear rheology was used to quantify the viscoelastic moduli increase(gelation)upon mixing the double emulsion with SDS and CPB.SDS was more effective than CPB in gelling the double emulsions.CPB and SDS could adsorb at the interface between water and model hydrocarbons(toluene and motor oil),lowering the interfacial tension and rigidifying the interface(as shown with a Langmuir trough).Bottle tests and optical microscopy showed that SDS and CPB produced W/O and O/W emulsions,with either toluene or motor oil and water.The emulsification of motor oil and toluene in water with SDS and CPB facilitated their flow through sand columns and their recovery.Toluene recovery from sand columns was quantitated using Gas-Chromatography MassSpectroscopy(GC-MS).The data show that SDS and CPB can be used both for surfactant flushing and to trigger the gelation of’emulsion locks’.Ethanol also gelled the emulsions at100 mL/L.

关键词： Remediation Emulsion Hydrocarbons Surfactant Rheology Langmuir trough

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A FACTOR(S) PRODUCED BY SERTOLI CELLS STIMULATES ANDROGEN BIOSYNTHESIS BY LEYDIG CELLS IN NEONATAL RATS

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Science China Chemistry 1988年第7期31卷 818-827页

作者：刘以训,kristine D. DAHL Laboratory of Reproductive Biology Institute of Zoology Academia Sinica Beijing Department of Reproductive Medicine M-025 University of California San Diego La Jolla CA 92093 USA

Using a coculture system, we have studied the local action of Sertoli cells on Leydig cell function. The results show that （ⅰ） both LH and FSH have equal potency to stimulate testosterone biosynthesis by fetal and neonatal testicular cells in an age-dependent manner, the maximum stimulation is observed between D3and D5. （ⅱ） An FSH-dependent factor（s） secreted by Sertoli cells increases the basal and/or LH-stimulated Leydig cell androgen production. （ⅲ） The Sertoli cell-stimulating factor（s） is not a steroid or other small molecule, but a heat-labile peptide.

关键词： Leydig cells Sertofi cells coculture factor testosterone production.

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Unusual presentation of gastric cancer during treatment of hairy cell leukemia:Exploring the etiological basis of this rare phenomenon

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Cancer Pathogenesis and Therapy 2023年第2期1卷 146-148页

作者： Shahan Tariq Muhammad Ammar Bin Hamid Nazia Rahman Lindsey Oleary kristine Wong Aasim Sehbai Department of Hematology/Oncology Regional Medical Center(RMC)AnnistonAL36207USA Department of Internal Medicine University of South Dakota Sanford School of MedicineSioux FallsSD57069USA Alabama College of Osteopathic Medicine DothanAL36303USA

Hairy cell leukemia(HCL)is a rare B-cell lymphoproliferative disorder.Patients typically present with cytopenia and splenomegaly.We describe the case of a 78-year-old patient with refractory HCL who acutely developed a cystic lesion on the back while receiving moxetumomab pasudotox therapy.Biopsy of the lesion revealed the presence of adenocarcinoma,which prompted a detailed evaluation resulting in a diagnosis of stage IV gastric cancer.Nevertheless,to establish any association between moxetumomab pasudotox therapy and secondary cancer development,a satisfactory number of studies need to be conducted.

关键词： Cystic lesion Gastric cancer Hairy cell leukemia

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