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Sterile signals generate weaker and delayed macrophage NLRP3 inflammasome responses relative to microbial signals

cellular & Molecular Immunology 2017年第1期14卷 118-126页

作者： Jelena S Bezbradica rebecca c coll Kate Schroder Institute for Molecular Bioscience (IMB) IMB Centre for Inflammation and Disease Research and Australian Infectious Diseases Research Centre The University of Queensland Brisbane St Lucia Queensland 4072 Australia

Inflammation is the host response to microbial infection or sterile injury that aims to eliminate the insult, repair the tissue and restore homeostasis. Macrophages and the NLRP3 inflammasome are key sentinels for both types of insult. Although it is well established that the NLRP3 inflammasome is activated by microbial products and molecules released during sterile injury, it is unclear whether the responses elicited by these different types of signals are distinct. In this study, we used lipopolysaccharide and tumor necrosis factor as prototypical microbial and sterile signal 1 stimuli, respectively, to prime the NLRP3 inflammasome. We then used the bacterial toxin nigericin and a common product released from necrotic cells, ATP, as prototypical microbial and sterile signal 2 stimuli, respectively, to trigger the assembly of the NLRP3 inflammasome complex in mouse and human macrophages. We found that NLRP3 inflammasome responses were weakest when both signal 1 and signal 2 were sterile, but responses were faster and stronger when at least one of the two signals was microbial. Ultimately, the most rapid and potent responses were elicited when both signals were microbial. Together, these data suggest that microbial versus sterile signals are distinct, both kinetically and in magnitude, in their ability to generate inflammasome-dependent responses. This hierarchy of NLRP3 responses to sterile versus microbial stimuli likely reflects the urgent need for the immune system to respond rapidly to the presence of infection to halt pathogen dissemination.

关键词： inflammasome NLRP3 sterile inflammation TNF

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Ink-structing the future of vascular tissue engineering:a review of the physiological bioink design

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Bio-Design and Manufacturing 2024年第2期7卷 181-205页

作者： Judith Synofzik Sebastian Heene rebecca Jonczyk cornelia Blume Institute for Technical chemistry Leibniz University Hannover30167 HannoverGermany

Three-dimensional(3D)printing and bioprinting have come into view for a plannable and standardizable generation of implantable tissue-engineered constructs that can substitute native tissues and *** tissue-engineered structures are intended to integrate with the patient’s *** tissue engineering(TE)is relevant in TE because it supports the sustained oxygenization and nutrition of all tissue-engineered *** have a specific role,representingthenecessarymedium for printability and vascular cell *** review aims to understand the requirements for the design of vascular ***,an in-depth analysis of vascular cell interaction with their native environment must be gained.A physiological bioink suitable for a tissue-engineered vascular graft(TEVG)must not only ensure good printability but also induce cells to behave like in a native vascular vessel,including self-regenerative and growth *** review describes the general structure of vascular walls with wall-speciﬁc cell and extracellular matrix(EcM)components and biomechanical properties and ***,the physiological role of vascular EcM components for their interaction with vascular cells and the mode of interaction is *** currently available or imaginable bioinks are described from physiological matrix proteins to nonphysiologically occurring but natural chemical compounds useful for vascular *** physiological performance of these bioinks is evaluated with regard to biomechanical properties postprinting,with a view to current animal studies of 3D printed vascular ***,the main challenges for further bioink development,suitable bioink components to create a self-assembly bioink concept,and future bioprinting strategies are *** concepts are discussed in terms of their suitability to be part of a TEVG with a high potential for later clinical use.

关键词： Vascular wall histology Vascular cells Microenvironment Extracellular matrix cell–matrix interaction Bioink Printability

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Frequency of the c677T Polymorphism of MTHFR, G20210A of Prothrombin and R506Q of Factor V Leiden in Type 2 Diabetics in Abidjan

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Open Journal of Genetics 2024年第1期14卷 13-25页

作者： N’Guessan-Blao rebecca Yapo Vincent Yayo-Ayé Mireille Adjambri Eusèbe Koné-Koné Fatoumata Sawadogo Duni Hematology and General Biology Unit Faculty of Pharmaceutical and Biological Sciences Department of Biological Sciences Felix Houphouet-Boigny University Abidjan Ivory Coast Laboratory of Biology and Medical Research National Institute of Public Health (INSP) Abidjan Ivory Coast Molecular Biology Unit Center for Diagnosis and Research on AIDS and Other Infectious Diseases (CeDReS) Treichville University Hospital (CHU) Abidjan Ivory Coast

In Africa, the prevalence of diabetes is escalating and remains a concern due to the numerous complications it causes. Vascular damage associated with diabetes leads to a prothrombotic state observed in diabetic individuals. Diabetes is a complex and multifactorial disease involving genetic components. With the aim of preventing complications and contributing to an efficient management of diabetes, we investigated genes likely to lead to a risk of thrombosis, in particular the c677T of MTHFR, G20210A of prothrombin, and R506Q of factor V Leiden in type 2 diabetics in Abidjan receiving ambulatory care. A descriptive cross-sectional study was carried out on consenting type 2 diabetic patients. Mutation detection was carried out using the PcR-RFLP method employing restriction enzymes. Hemostasis tests (fibrinogen, D-dimers, fibrin monomers, and von Willebrand factor) were performed using citrate tubes on the Stage? Star Max automated system. Plasminogen activator inhibitor was assayed by ELISA method, and biochemical parameters were determined using the cOBAS c311. The study population consisted of 45 diabetic patients, 51.1% of whom presented vascular complications, mainly neuropathy. Disturbances in hemostasis parameters were observed, with 15.5% of patients showing an increase in fibrin monomers. Mutation analysis revealed an absence of factor V mutation (factor V Leiden) and of G20210A mutation of the prothrombin gene. However, 15.6% of subjects had a heterozygous c677T mutation of MTHFR, with 57% of them being anemic. The exploration of biological and genetic factors associated with thrombotic risk is of significant interest in the optimal management of African type 2 diabetics.

关键词： Type 2 Diabetes c677T of MTHFR G20210A Factor V Leiden Thrombosis

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Viral hepatitis in 2021:The challenges remaining and how we should tackle them

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World Journal of Gastroenterology 2022年第1期28卷 76-95页

作者： rebecca Dunn Aaron Wetten Stuart McPherson Mhairi c Donnelly Gastroenterology University Hospital of North TeesStockton on Tees TS198PEUnited Kingdom Liver Unit Freeman HospitalNewcastle NE77DNUnited Kingdom Translational and clinical Research Institute Newcastle UniversityNewcastle NE17RUUnited Kingdom

Viral hepatitis results in 1.4 million deaths *** World Health Organization(WHO)set an ambitious target to eliminate viral hepatitis by 2030,but significant challenges *** include inequalities in access to healthcare,reaching at risk populations and providing access to screening and effective *** around viral hepatitis persists and must be *** WHO goal of global elimination by 2030 is a worthy aim,but remains ambitious and the coronavirus 2019 pandemic undoubtedly has set back *** review article will focus on hepatitis A to E,highlighting problems that have been resolved in the field over the past decade,those that remain to be resolved and suggest directions for future problem solving and research.

关键词： Hepatitis A Hepatitis B Hepatitis c Hepatitis D Hepatitis E cOVID-19

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Estimation of mean water vapour residence time during tropical cyclones using a Lagrangian approach

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Tropical cyclone Research and Review 2022年第2期11卷 76-87页

作者： Albenis Perez-Alarcon Patricia coll-Hidalgo Jose c.Fernandez-Alvarez Raquel Nieto Luis Gimeno centro de Investigacion Marina Universidade de VigoEnvironmental Physics Laboratory(EPhysLab)OurenseSpain Departamento de Meteorología Instituto Superior de Tecnologías y Ciencias AplicadasUniversidad de La HabanaLa HabanaCuba Departamento de Meteorología Empresa Cubana de Navegacion AereaLa HabanaCuba

Tropical cyclone(Tc)-related rainfall mostly depends on the atmospheric moisture uptake from local and remote *** this study,the mean water vapour residence time(MWVRT)was computed for precipitation related to Tcs in each basin and on a global scale by applying a Lagrangian moisture source diagnostic *** to our results,the highest MWVRT was found for the Tcs over the South Indian Ocean and South Pacific Ocean basins(~3.08 days),followed by the Western North Pacific Ocean,central and East North Pacific Ocean,North Indian Ocean,and North Atlantic Ocean basins(which exhibited values of 2.98,2.94,2.85,and 2.72 days,respectively).We also found a statistically significant(pcrease in MWVRT,at a rate of~2.4 h/decade in the North Indian Ocean and~1.0 h/decade in the remaining *** average,the MWVRT decreased during the 24 h before Tcs made landfall,and the atmospheric parcels precipitated faster after evaporation when Tcs moved over land than over the *** research should focus on the relationship between global warming and MWVRT of atmospheric parcels that precipitate over Tc positions.

关键词： Tropical cyclones Water vapour residence time Lagrangian approach Tropical cyclones precipitation

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Discrete modeling of rock joints with a smooth-joint contact model

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Journal of Rock Mechanics and Geotechnical Engineering 2014年第1期6卷 1-12页

作者： c.Lambert c.coll Department of civil and Natural Resources Engineering University of CanterburyPrivate Bag 4800 Christchurch 8140 New Zealand Golder Associates Christchurch New Zealand

Structural defects such as joints or faults are inherent to almost any rock *** many situations those defects have a major impact on slope stability as they can control the possible failure *** a good estimate of their strength then becomes *** roughness of a structure is a major contributor to its strength through two different aspects,*** morphology of the surface(or the shape)and the strength of the asperities(related to the strength of the rock).In the current state of practice,roughness is assessed through idealized descriptions(Patton strength criterion)or through empirical parameters(Barton JRc).In both cases,the multi-dimensionality of the roughness is *** this study,we propose to take advantage of the latest developments in numerical ***3D photogrammetry and/or laser mapping,practitioners have access to the real morphology of an exposed *** derived triangulated surface was introduced into the DEM(discrete element method)code PFc3D to create a synthetic rock *** interaction between particles on either side of the discontinuity was described by a smooth-joint model(SJM),hence suppressing the artificial roughness introduced by the particle *** tests were then performed on the synthetic rock joint.A good correspondence between strengths predicted by the model and strengths derived from well-established techniques was obtained for thefirst *** the benefits of the methodology is the possibility offered by the model to be used in a quantitative way for shear strength estimates,to reproduce the progressive degradation of the asperities upon shearing and to analyze structures of different scales without introducing any empirical relation.

关键词： Rock joint Shear strength DEM simulations Smooth-joint model

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Akt3 promotes cancer stemness in triple-negative breast cancer through YB1-Snail/Slug signaling axis

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Genes & Diseases 2023年第2期10卷 301-306页

作者： Ye Tian Jiang Li Tsz chung cheung Vincent Tam c. Geoffrey Lau Xin Wang Y.rebecca chin Tung Biomedical Sciences centre Department of Biomedical SciencesCity University of Hong KongKowloonHong Kong SARChina Department of Neuroscience City University of Hong KongKowloonHong Kong SARChina city University of Hong Kong Shenzhen Research Institute ShenzhenGuangdong 518057China Department of Surgery The Chinese University of Hong KongShatinHong Kong SARChina

Dear Editor,Triple-negative breast cancer(TNBc)is an aggressive breast cancer subtype enriched in cancer stem cells(cScs),which is characterized by high malignancy and drug resistance.1 The PI3K/Akt signaling cascade is frequently hyperactivated in *** and non-redundant functions of the three Akt isoforms in tumorigenesis,however,have not been studied *** is noteworthy that despite a few isoform-specific substrates have been identified for Akt1 and Akt2,an Akt3-specific substrate is yet to be *** have previously shown that overexpression of Akt3,but not Akt1 or Akt2,plays an essential role in TNBc growth and therapeutic resistance of breast cancer.2 However,the role of Akt3 in TNBc cScs remains unclear.

关键词： Akt1 breast Akt3

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Gastrointestinal and liver disease in patients with schizophrenia:A narrative review

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World Journal of Gastroenterology 2022年第38期28卷 5515-5529页

作者： rebecca K Grant William M Brindle Mhairi c Donnelly Pauline M Mcconville Thomas G Stroud Lorenzo Bandieri John N Plevris The centre for Liver and Digestive Disorders Royal Infirmary of EdinburghEdinburghEH164SAUnited Kingdom General Adult Psychiatry Royal Edinburgh HospitalEdinburghEH105HFUnited Kingdom

Schizophrenia is a severe mental illness which can have a devastating impact onan individual’s quality of life. comorbidities are high amongst patients and lifeexpectancy is approximately 15 years less than the general population. Despite thewell-known increased mortality, little is known about the impact of gastrointestinaland liver disease on patients with schizophrenia. We aimed to reviewthe literature and to make recommendations regarding future care. Literaturesearches were performed on PubMed to identify studies related to gastrointestinaland liver disease in patients with schizophrenia. High rates of chronic liverdisease were reported, with Non-Alcoholic Fatty Liver Disease being of particularconcern;antipsychotics and metabolic syndrome were contributing factors. Ratesof acute liver failure were low but have been associated with antipsychotic useand paracetamol overdose. coeliac disease has historically been linked to schizophrenia;however, recent research suggests that a causal link is yet to be *** is emerging regarding the relationships between schizophrenia andpeptic ulcer disease, inflammatory bowel disease and irritable bowel syndrome;clinical vigilance regarding these conditions should be high. Patients with schizophreniapoorly engage with bowel cancer screening programmes, leading to latediagnosis and increased mortality. clozapine induced constipation is a significantissue for many patients and requires close monitoring. There is a significantburden of gastrointestinal and liver disease amongst patients with *** levels of support from all members of the medical team are essential toensure that appropriate, timely care is provided.

关键词： Schizophrenia Gastrointestinal disease Liver disease Mental health

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Reconciling concepts, theory, and empirical patterns surrounding cascade reinforcement

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current Zoology 2016年第2期62卷 131-134页

作者： rebecca c. FULLER Department of Animal Biology University of Illinois Urbana IL 61801 USA

Reinforcement is a critically important process in speciation. It has been credited with often completing speciation, and it is unique in that natural selection directly favors the evolution of reproductive isolating barriers. Reinforcement occurs when selection favors increased prezygotic isolation between two lineages in order to avoid maladaptive hybridization in areas of sympatry (Noor 1999; Servedio and Noor 2003; coyne and Orr 2004). The classic signature of reinforcement is reproductive character displacement (RcD), where prezygotic isolation is heightened between two lineages in areas of sympatry relative to areas of allopatry. Reinforcement was once considered controversial primarily due to theoretical difficulties (Felsenstein 1981; Spencer et al. 1986; reviewed in Noor 1999, and coyne and Orr, 2004). However, a wealth of empirical cases demonstrating reinforcement along with renewed theoretical treatments of the process of reinforcement (Liou and Price 1994; Kelly and Noor 1996; Servedio 2000; Kirkpatrick and Ravigne 2002) has led to the conclusion that reinforcement can and does occur in nature. One consequence of reinforcement is that—by altering reproductive isolating traits—reinforcement may also lead to prezygotic isolation among populations within species. Hence, like ecological and sexual selection, reinforcement can have incidental effects upon reproductive isolation (RI). In fact, reinforcement might be particularly likely to have such incidental effects precisely because it alters reproductive isolating traits among species in areas of sympatry.

关键词：调和加固梯级

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Associations of self-reported and device-assessed physical activity with fatigue,quality of life,and sleep quality in adults living with and beyond cancer

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Journal of Sport and Health Science 2023年第6期12卷 664-673,F0003页

作者： Phillippa Lally Natalie Ella Miller claire Lawrence rebecca J Beeken Abigail Fisher Department of Behavioural Science and Health University College LondonLondon WC1E 6BTUK Department of Psychology University of SurreyGuildford GU27XHUK Leeds Institute of Health Sciences Leeds LS29NLUK

Background Greater physical activity is associated with improved outcomes in people living with and beyond ***,most studies in exercise oncology use self-reported measures of physical *** have explored agreement between self-reported and device-based measures of physical activity in people living with and beyond *** study aimed to describe physical activity in adults affected by cancer across self-reported and device-assessed activity,to explore levels of agreement between these measures in terms of their utility for categorizing participants as meeting/not meeting physical activity guidelines,and to explore whether meeting guidelines is associated with fatigue,quality of life,and sleep *** A total of 1348 adults living with and beyond cancer from the Advancing Survivorship cancer Outcomes Trial completed a survey assessing fatigue,quality of life,sleep quality,and physical *** Godin-Shephard Leisure-Time Physical Activity Questionnaire was used to calculate a Leisure Score Index(LSI)and an estimate of moderate-to-vigorous physical activity(MVPA).Average daily steps and weekly aerobic steps were derived from pedometers worn by *** The percentage of individuals meeting physical activity guidelines was 44.3%using LSI,49.5%using MVPA,10.8%using average daily steps,and 28.5%using weekly aerobic ***(cohen'sκ)between self-reported and pedometer measures ranged from 0.13(LSI *** daily steps)to 0.60(LSI ***).After adjusting for sociodemographic and health-related covariates,meeting activity guidelines using all measures was associated with not experiencing severe fatigue(odds ratios(ORs):1.43–1.97).Meeting guidelines using MVPA was associated with no quality-of-life issues(OR=1.53).Meeting guidelines using both self-reported measures were associated with good sleep quality(ORs:1.33–1.40).conclusion Less than half of all adults affected by cancer are meeting physical activity guidelines,

关键词： cancer survivorship Fatigue Physical activity Quality of life SleepTagedAPTARAEnd

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