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Serum-circulating His-tRNA synthetase inhibits organ-targeted immune responses

Cellular & Molecular Immunology 2021年第6期18卷 1463-1475页

作者： Ryan AAdams Cátia Fernandes-Cerqueira Antonella Notarnicola Elisabeth Mertsching Zhiwen Xu Wing-Sze Lo Kathleen Ogilvie Kyle PChiang Jeanette Ampudia Sanna Rosengren Andrea Cubitt David JKing John DMendlein Xiang-Lei Yang Leslie ANangle Ingrid ELundberg per-johan jakobsson Paul Schimmel aTyr Pharma 3545 John Hopkins CourtSuite 250San DiegoCA92121USA Division of Rheumatology Department of MedicineSolnaKarolinska InstitutetKarolinska University HospitalSE-17176StockholmSweden IAS HKUST-Scripps R&D Laboratory Institute for Advanced StudyHong Kong University of Science and Technologyand Pangu BiopharmaHong KongChina The Scripps Laboratories for tRNA Synthetase Research 10650 North Torrey Pines RoadLa JollaCA92037USA The Scripps Laboratories for tRNA Synthetase Research Scripps Florida130 Scripps WayJupiterFL33458USA

His-tRNA synthetase (HARS) is targeted by autoantibodies in chronic and acute inflammatory anti-Jo-1-positive antisynthetase syndrome. The extensive activation and migration of immune cells into lung and muscle are associated with interstitial lung disease, myositis, and morbidity. It is unknown whether the sequestration of HARS is an epiphenomenon or plays a causal role in the disease. Here, we show that HARS circulates in healthy individuals, but it is largely undetectable in the serum of anti-Jo-1-positive antisynthetase syndrome patients. In cultured primary human skeletal muscle myoblasts (HSkMC), HARS is released in increasing amounts during their differentiation into myotubes. We further show that HARS regulates immune cell engagement and inhibits CD4+ and CD8+ T-cell activation. In mouse and rodent models of acute inflammatory diseases, HARS administration downregulates immune activation. In contrast, neutralization of extracellular HARS by high-titer antibody responses during tissue injury increases susceptibility to immune attack, similar to what is seen in humans with anti-Jo-1-positive disease. Collectively, these data suggest that extracellular HARS is homeostatic in normal subjects, and its sequestration contributes to the morbidity of the anti-Jo-1-positive antisynthetase syndrome.

关键词： Immunology Autoimmunity Synthetase tRNA HARS

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May Traditional Chinese Medicine Reduce the Risk of Developing Rheumatoid Arthritis?An One-armed Prospective Study

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Clinical Complementary Medicine and Pharmacology 2024年第1期4卷 10-18页

作者： Kaixin Gao Qi Liang Dongyun Li Chuanning Li Maojie Wang Xiumin Chen Qingchun Huang Zehuai Wen per-johan jakobsson Runyue Huang The Second Affiliated Hospital of Guangzhou University of Chinese Medicine(Guangdong Provincial Hospital of Chinese Medicine) Guangzhou 510006GuangdongChina The Second Clinical Medical College Guangzhou University of Chinese MedicineGuangzhou 510006GuangdongChina State Key Laboratory of Dampness Syndrome of Chinese Medicine The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120GuangdongChina Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases Guangzhou 510403GuangdongChina Guangdong-Hong Kong-Macao Joint Lab on Chinese Medicine and Immune Disease Research Guangzhou 510000GuangdongChina The key unit of methodology of clinical research The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510000GuangdongChina Rheumatology Unit Department of Medicine SolnaKarolinska InstituteKarolinska University HospitalStockholm 17177Sweden Department of Doctor-Patient Relationship The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630GuangdongChina

Background:Rheumatoid arthritis(RA)is a worldwide public health *** and prevention before the onset of rheumatic diseases is a new direction in current ***:The aim of this study was to evaluate the potential and feasibility of traditional Chinese medicine(TCM)in the prevention of ***:This was a single-armed prospective clinical *** participants were recruited from a single center in Guangdong,*** who were tested positive for anti-cyclic citrullinated peptide antibody(anti-CCP)and/or rheumatoid factor(RF),had no synovitis and never been treated with disease-modifying anti-rheumatic drugs(DMARDs),were enrolled to take the Huayu-Qiangshen-Tongbi(HQT)decoction orally twice daily,200 mL each time for 24 *** outcome was the proportion of patients who met 2010 ACR(American College of Rheumatology)/EULAR(European League Against Rheumatism)classification criteria of RA during *** outcomes included levels of anti-CCP,RF,erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),assessment of signs and symptoms,and radiographic progression by magnetic resonance imaging(MRI).Results:19 individuals were enrolled in the study,4 of which withdrew because of the epidemic of *** the observation period,3 individuals(20%)developed RA and they had longer morning stiffness(P=0.009)and more obvious synovial enhancement in MRI(P=0.041)at baseline when compared with those who did not develop *** 24 weeks of intervention,there were improvements in 28-swollen joint count(SJC28)(P=0.046),Visual Analog Scale(VAS)(P=0.019),Patient’s Global Assessment(PtGA)(P=0.019)and Physician’s Global Assessment(PGA)(P=0.031),but no statistical significance was observed in the levels of anti-CCP,RF,ESR,CRP,morning stiffness,28-tender joint count(TJC28),Health Assessment Questionnaire(HAQ)and magnetic resonance imaging(MRI)analysis(P>0.05).Conclusion:The HQT formula is safe and could improve joint symptoms and s

关键词： Rheumatoid arthritis(RA) Prevention Traditional Chinese medicine(TCM) Huayu-Qiangshen-Tongbi decoction(HQT) Clinical trial

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A system for underground road condition monitoring

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International Journal of Mining Science and Technology 2020年第3期30卷 405-411页

作者： Max Astrand Erik jakobsson Martin Lindfors John Svensson KTH Royal Institute of Technology SE-10044 StockholmSweden ABB Corporate Research SE-72226 VästeråsSweden Epiroc SE-70191ÖrebroSweden Linköping University SE-58183 LinköpingSweden Boliden Mines SE-93632 BolidenSweden

Poor road conditions in underground mine tunnels can lead to decreased production efficiency and increased wear on production vehicles. A prototype system for road condition monitoring is presented in this paper to counteract this. The system consists of three components i.e. localization, road monitoring, and scheduling. The localization of vehicles is performed using a Rao-Blackwellized extended particle filter, combining vehicle mounted sensors with signal strengths of Wi Fi access points. Two methods for road monitoring are described: a Kalman filter used together with a model of the vehicle suspension system, and a relative condition measure based on the power spectral density. Lastly, a method for taking automatic action on an ill-conditioned road segment is proposed in the form of a rescheduling *** scheduling algorithm is based on the large neighborhood search and is used to integrate road service activities in the short-term production schedule while minimizing introduced production *** system is demonstrated on experimental data collected in a Swedish underground mine.

关键词： Localization Road condition monitoring Scheduling Underground mining

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Understanding the “Horizontal Dimension” of Molecular Evolution to Annotate, Classify, and Discover Proteins with Functional Domains

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Journal of Computer Science & Technology 2010年第1期25卷 82-94页

作者： Gloria Rendon Mao-Feng Ger Ruth Kantorovitz Shreedhar Natarajan Jeffrey Tilson Eric jakobsson National Center for Supercomputing Applications University of Illinois at Urbana-Champaign Beckman Institute for Advanced Science and Technology University of Illinois at Urbana-Champaign Center for Biophysics and Computational Biology University of Illinois at Urbana-Champaign Department of Mathematics University of Illinois at Urbana-Champaign Department of Biology University of Pennsylvania Renaissance Computing Institute

Protein evolution proceeds by two distinct processes： 1） individual mutation and selection for adaptive mutations and 2） rearrangement of entire domains within proteins into novel combinations, producing new protein families that combine functional properties in ways that previously did not exist. Domain rearrangement poses a challenge to sequence alignment-based search methods, such as BLAST, in predicting homology since the methodology implicitly assumes that related proteins primarily differ from each other by individual mutations. Moreover, there is ample evidence that the evolutionary process has used （and continues to use） domains as building blocks, therefore, it seems fit to utilize computational, domain-based methods to reconstruct that process. A challenge and opportunity for computational biology is how to use knowledge of evolutionary domain recombination to characterize families of proteins whose evolutionary history includes such recombination, to discover novel proteins, and to infer protein-protein interactions. In this paper we review techniques and databases that exploit our growing knowledge of “horizontal” protein evolution, and suggest possible areas of future development. We illustrate the power of the domain-based methods and the possible directions of future development by a case history in progress aiming at facilitating a particular approach to understanding microbial pathogenicity.

关键词： domain-based discovery domain-based orthology domain interactions InterPro MEME/MAST

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Time analysis for aero-engine acoustic modes exploiting block sparsity

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Chinese Journal of Aeronautics 2024年第11期37卷 254-264页

作者： Zepeng LI Baijie QIAO Bi WEN Yuanshi LIU Xuefeng CHEN Andreas jakobsson School of Mechanical Engineering Xi’an Jiaotong UniversityXi’an 710049China AECC Sichuan Gas Turbine Establishment Mianyang 621022China Department of Mathematical Statistics Lund UniversityLund 22100Sweden

Acoustic Mode Analysis(AMA)for aero-engines can offer valuable insights for the design of silent engines as well as for fault ***,this is done in the(spatial)Fourier domain,necessitating the use of multiple uniformly spaced microphones to ensure adequate *** works show that sub-Nyquist estimation is feasible using sparse reconstruction frameworks,although such modelling generally introduces an estimation bias that has to be compensated ***,there is a growing interest in monitoring mode amplitude over continuous time,as it can offer crucial insights for diagnosing operational *** this work,we introduce a Block Orthogonal Matching Pursuit(BOMP)method for continuous time mode analysis,exploiting the underlying structural sparsity of the signal ***,the(pseudo)‘0ànorm penalty is employed to induce sparsity in the wavenumber domain,whereas a block structure is imposed as a constraint to monitor the amplitude variation in the time *** effectiveness of the BOMP is evaluated using both numerical simulations and experimental measurements,indicating the proposed method's preferable performance as compared to the classic Least Absolute Shrinkage and Selection Operator(LASSO)and Orthogonal Matching Pursuit(OMP)methods.

关键词： Block sparsity Orthogonal matching pursuit Acoustic mode analysis Acoustic testing Sparse estimate

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Exploring the Implementation of Individual Care Plans in Relation to Characteristics of Staff

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Open Journal of Nursing 2016年第8期6卷 582-590页

作者： Anna Condelius Ulf jakobsson Staffan Karlsson Department of Health Sciences Faculty of Medicine Lund University Lund Sweden Centre for Primary Health Care Research Faculty of Medicine Lund University Malm&ouml Sweden Department of Health Sciences Faculty of Medicine Lund University Lund Sweden School of Health and Welfare Halmstad University Halmstad Sweden

The aim was to explore the implementation of individual care plans in municipal elderly care in relation to characteristics of staff. Data regarding characteristics of staff were derived through a questionnaire distributed to all staff working in the care for older people, (N = 908, n = 245) in four municipalities in Sweden. The number of care plans established during a one-year period was collected through a contact person in each municipality. In total 47 individual care plans were established during the study year. Significantly more staff in the municipality that had the most number of established individual care plans agreed that there had been sufficient education (p = 0.017), sufficient time (p = 0.002) and routines established regarding individual care plans (p = 0.014) and had a significantly better job satisfaction (p = 0.001), compared to staff in the other municipalities. Implementation leaders may need to take the working conditions and the perception of available resources among staff into consideration in the on-going process of implementing individual care plans.

关键词： Aged/Aged 80 and Over Patient Care Planning Health Plan Implementation

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Detecting decreased sexual health with MDHAQ-S

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Health 2013年第6期5卷 38-47页

作者： Kristina Areskoug-Josefsson Charlotte Ekdahl Ulf jakobsson Gunvor Gard Center for Primary Health Care Research CRC Lund University Lund Sweden Department of Health Sciences Division of Physiotherapy Lund University Lund Sweden

There are instruments that measure sexual function or sexual health for persons with RA, but since sexual health is a sensitive issue, the hypothesis is that it would be easier to have a standard questionnaire that could indicate the need for communication about sexual health issues instead of an extra questionnaire with more detailed questions on sexual health. The aim of the study is to find out whether sexual health difficulties can be screened by factors included in the MDHAQ-S for persons with RA. This study explores the relation between factors included in the MDHAQ-S and the Sexual Health Questionnaire (QSH) using a mixed methods design combining quantitative and qualitative data. The MDHAQ-S covers sexual health issues, not only by using the question on sexual health, but also on other factors included in the questionnaire such as increased pain, fatigue, depression, anxiety, physical capacity, level of physiccal activity and body weight. To explore decreased sexual arousal, decreased sexual satisfaction and decreased sexual well-being, in-depth interviews must be held with persons with RA, either using a sexual health questionnaire or in a clinical interview.

关键词： Sexual Health Rheumatoid Arthritis Mixed Methods Rehabilitation Health Assessement

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Is routine blood test of value for evaluating health effects among midwives working with nitrous oxide for pain relief in delivery unit

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Health 2011年第3期3卷 162-165页

作者： G. Abascall M. johansson K. J. jakobsson 不详

Chronic workplace exposure to high nitrous oxide concentrations has been suggested to potentially be associated to negative health effects caused by the interference with the vitamin B12, methionine synthase pathway. The objective of the present study was to determine if delivery unit work place ambient air nitrous oxide exposure results in detectable hyperhomocysteinemia or signs of macrocytocis in personnel. Blood samples from thirty healthy female fulltime employees, midwives, aged 43 (range 25-62) years were studied. Routine blood test analysed for plasma homocysteine and blood status;haemoglobin, mean corpuscular volume, mean corpuscular haemoglobin concentration, blood status was analysed once before going on vacation and repeated after at least 10 days’ leave, nitrous oxide free period. Median time weighted average was 41 [10 - 547] ppm;3 out of 11 TWA measurements were above recommended100 ppm limit. Median homocysteine concentrations were 10.7 [5.6 - 16] micromol/L with reference limits of 5.0 – 15 micromol/L. Megaloblastic erythrocytes was not detected in any personnel and no changes in blood status could be detected between before and after a nitrous oxide-free period. Conclusions: One of 3 delivery units’ ambient air quality measures exceed recommended ranges. No signs of routine blood test pathology could be seen in the personnel studied.

关键词： Nitrous oxide ambient air quality TWA homocysteine megaloblastic anaemia.

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