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Characterization of colonic dendritic cells in normal and colitic mice

World Journal of Gastroenterology 2005年第40期11卷 6338-6347页

作者： Sheena M Cruickshank nicholas r english Peter J Felsburg Simon r Carding Institute of Molecular and Cellular Biology Antigen Presentation research Group Department of Clinical Science

AIM： recent studies demonstrating the direct involvement of dendritic cells （DC） in the activation of pathogenic T cells in animal models of inflammatory bowel disease identify DC as important antigen presenting cells in the colon. However, very little is known about the properties of colonic DC. METHODS： Using immunohistochemistry, electron microscopy and flow cytometry we have characterized and compared colonic DC in the colon of healthy animals and interleukin-2-deficient （IL2-/-） mice that develop colitis. rESULTS： In the healthy colon, DC resided within the lamina propria and in close association with the basement membrane of colonic villi. Type i myeloid （CD11c^＋, CD11b^＋, B220, CD8） DC made up the largest （40-45%） population and all DC expressed low levels of CD80, CD86, and CD40, and had high endooltic activity consistent with an immature phenotype. In colitic IL2-/- mice, colonic DC numbers increased four- to five-fold and were localized within the epithelial layer and within aggregates of T and B cells. They were also many more DC in mesenteric lymph nodes （MLN）. The majority （〉85%） of DC in the colon and MLN of IL2./ mice were type 1 myeloid, and expressed high levels of MHC class II, CD80, CD86, CD40, DEC 205, and CCr5 molecules and were of low endocytic activity consistent with mature DC. CONCLUSION： These findings demonstrate striking changes in the number, distribution and phenotype of DC in the inflamed colon. Their intimate association with lymphocytes in the colon and draining lymph nodes suggest that they may contribute directly to the ongoing inflammation in the colon.

关键词： Colonic dendritic cells Interleukin 2 Colitis

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Single and multiplexed gene repression in solventogenic Clostridium via Cas12a-based CrISPr interference

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Synthetic and Systems Biotechnology 2023年第1期8卷 148-156页

作者： rochelle Carla Joseph nicholas r.Sandoval Department of Chemical and Biomolecular Engineering Tulane UniversityNew OrleansLA70118United States

The Gram-positive,spore-forming,obligate anaerobic firmicute species that make up the Clostridium genus have broad feedstock consumption capabilities and produce value-added metabolic products,but genetic manipulation is difficult,limiting their broad ***-Cas systems have recently been applied to Clostridium species,primarily using Cas9 as a counterselection marker in conjunction with plasmid-based homologous *** interference is a method that reduces gene expression of specific genes via precision targeting of a nuclease deficient Cas effector ***,we develop a dCas12a-based CrISPr interference system for transcriptional gene repression in multiple mesophilic Clostridium *** show the Francisella novicida Cas12a-based system has a broader applicability due to the low GC content in Clostridium species compared to CrISPr Cas systems derived from other *** demonstrate>99%reduction in transcript levels of targeted genes in Clostridium acetobutylicum and>75%reduction in Clostridium *** also demonstrate multiplexed repression via use of a single synthetic CrISPr array,achieving 99%reduction in targeted gene expression and elucidating a unique metabolic profile for their reduced ***,this work builds a foundation for high throughput genetic screens without genetic editing,a key limitation in current screening methods used in the Clostridium community.

关键词： CrISPr Cas12a Clostridium CrISPri

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The challenge to improve the response of biomaterials to the physiological environment

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regenerative Biomaterials 2016年第2期3卷 67-71页

作者： nicholas A.Peppas John r.Clegg McKetta Department of Chemical Engineering College of PharmacyUniversity of Texas at Austin Department of Biomedical Engineering College of PharmacyUniversity of Texas at Austin Institute for Biomaterials Drug Delivery and Regenerative MedicineCollege of PharmacyUniversity of Texas at Austin Department of Surgery and Perioperative Care Dell Medical SchoolCollege of PharmacyUniversity of Texas at Austin Division of Pharmaceutics College of PharmacyUniversity of Texas at Austin.

New applications of biomaterials often require advanced structures containing synthetic and natural components that are tuned to provide properties unique to a specific *** discuss how structural characteristics of biomaterials,especially hydrophilic ones,can be used in conjunction with non-ideal thermodynamics to develop advanced medical *** show a number of examples of biocompatible,intelligent biomaterials that can be used for organ replacement,biosensors,precise drug delivery over days or weeks,and regenerative medicine.

关键词： drug delivery nanobiomaterials regenerative mechanism materials structure

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A comprehensive investigation on nonlinear vibration and bending characteristics of bio-inspired helicoidal laminated composite structures

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Applied Mathematics and Mechanics(english Edition) 2025年第1期46卷 81-100页

作者： S.SAUrABH r.KIrAN D.SINGH r.VAISH V.S.CHAUHAN School of Mechanical and Materials Engineering Indian Institute of Technology Mandi

Bio-inspired helicoidal composite laminates, inspired by the intricate helical structures found in nature, present a promising frontier for enhancing the mechanical properties of structural designs. Hence, this study provides a comprehensive investigation into the nonlinear free vibration and nonlinear bending behavior of bio-inspired composite plates. The inverse hyperbolic shear deformation theory(IHSDT) of plates is employed to characterize the displacement field, with the incorporation of Green-Lagrange nonlinearity. The problem is modeled using the C0finite element method(FEM), and an in-house code is developed in the MATLAB environment to solve it numerically. Various helicoidal layup configurations including helicoidal recursive(Hr), helicoidal exponential(HE), helicoidal semi-circular(HS), linear helicoidal(LH), and Fibonacci helicoidal(FH)with different layup sequences and quasi-isotropic configurations are studied. The model is validated, and parametric studies are conducted. These studies investigate the effects of layup configurations, side-to-thickness ratio, modulus ratios, boundary conditions, and loading conditions at different load amplitudes on the nonlinear vibration and nonlinear bending behaviors of bio-inspired composite plates. The results show that the laminate sequence exerts a substantial impact on both nonlinear natural frequencies and nonlinear bending behaviors. Moreover, this influence varies across different side-to-thickness ratios and boundary conditions of the bio-inspired composite plate.

关键词： finite element method (FEM) nonlinear Green-Lagrange inverse hyperbolic shear deformation theory (IHSDT) bio-inspired composite plate helicoidal O322

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Evaluation of fermentation conditions triggering increased antibacterial activity from a near-shore marine intertidal environment-associated Streptomyces species

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Synthetic and Systems Biotechnology 2017年第1期2卷 28-38页

作者： A.L.english A.Boufridi r.J.Quinn D.I.Kurtboke Genecology research Centre and Faculty of Science HealthEducation and EngineeringUniversity of the Sunshine CoastMaroochydore DCQLD4558Australia Eskitis Institute for Drug Discovery Griffith UniversityNathanQLD4111Australia

A near-shore marine intertidal environment-associated Streptomyces isolate(USC-633)from the Sunshine Coast region of Queensland,Australia,cultivated under a range of chemically defined and complex media to determine optimal parameters resulting in the secretion of diverse array of secondary metabolites with antimicrobial properties against various antibiotic resistant *** extraction,fractioning and re-testing of active metabolites resulted in persistent antibacterial activity against Escherichia coli(Migula)(ATCC 13706)and subsequent Nuclear Magnetic resonance(NMr)analysis of the active fractions confirmed the induction of metabolites different than the ones in fractions which did not display activity against the same bacterial *** findings again confirmed the value of One StraineMany Compounds(OSMAC)approach that tests a wide range of growth parameters to trigger bioactive compound secretion increasing the likelihood of finding novel therapeutic *** isolate was found to be adaptable to both marine and terrestrial conditions corresponding to its original nearshore marine intertidal *** variations in its morphology,sporulation and diffusible pigment production were observed when different growth media were used.

关键词： Marine streptomycetes Marine biodiscovery Fermentation media Antibiotics Marine natural products Pigments

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recent advances in glucose-responsive insulin delivery systems:novel hydrogels and future applications

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regenerative Biomaterials 2022年第1期9卷 1037-1045页

作者： Avha r.Mohanty Akhila ravikumar nicholas A.Peppas McKetta Department of Chemical Engineering The University of Texas at Austin200 E Dean Keeton StAustinTX 78712USA Institute for Biomaterials Drug Deliveryand Regenerative MedicineThe University of Texas at Austin107WDean Keeton StAustinTX 78712USA Department of Biomedical Engineering The University of Texas at Austin107WDean Keeton StAustinTX 78712USA Division of Molecular Pharmaceutics and Drug Delivery College of PharmacyThe University of Texas at Austin2409 University AveAustinTX 78712USA Department of Surgery and Perioperative Care Dell Medical SchoolThe University of Texas at Austin1501 Red River StAustinTX 78712USA Department of Pediatrics Dell Medical SchoolThe University of Texas at Austin1501 Red River StAustinTX 78712USA

Over the past several decades,there have been major advancements in the field of glucose sensing and insulin delivery for the treatment of type I diabetes *** introduction of closed-loop insulin delivery systems that deliver insulin in response to specific levels of glucose in the blood has shifted significantly the research in this *** systems consist of encapsulated glucose-sensitive components such as glucose oxidase or phenylboronic acid in hydrogels,microgels or *** our previous evaluation of these systems in a contribution in 2004,new systems have been *** improvements in key issues,such as consistent insulin delivery over an extended period of time have been *** this contribution,we discuss recent advancements over the last 5 years and present persisting issues in these technologies that must be overcome in order for these systems to be applicable in patients.

关键词： insulin delivery glucose control hydrogels glucose oxidase diabetes

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Plasticity in the antipredator behavior of the orange-footed sea cucumber under shifting hydrodynamic forces

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Current Zoology 2019年第6期65卷 685-695页

作者： nicholas A.W.BrOWN David r.WILSON Patrick GAGNON Department of Ocean Sciences Memorial University of NewfoundlandSt.John'sNewfoundlandA1C 5S7Canada Department of Psychology Memorial University of NewfoundlandSt.John'sNewfoundlandA1B 3X9Canada

Marine invertebrates that move too slowly to evade unfavorable environmental change may instead exhibit phenotypic plasticity,allowing them to adjust to varying *** orange-footed sea cucumber Cucumaria frondosa is a slow-moving suspension feeder that is preyed on by the purple sunstar Solaster *** sea cucumber's antipredator behavior involves changing shape and detaching from the substratum,which might increase its probability of being displaced by water motion into an unsuitable *** hypothesized that sea cucumbers'antipredator responses would be diminished under stronger hydrodynamic forces,and that behavioral strategies would be flexible so that individuals could adjust to frequent changes in water *** a natural orange-footed sea cucumber habitat,individuals lived along a pronounced hydrodynamic gradient,allowing us to measure antipredator behavior under different water flow *** placed purple sunstars in physical contact with sea cucumbers living at various points along the gradient to elicit antipredator *** then repeated this procedure in a laboratory mesocosm that generated weak and strong hydrodynamic forces similar to those observed at the field *** in the mesocosm experiment were tested in both wave conditions to determine if their antipredator behavior would change in response to sudden environmental change,as would be experienced under deteriorating sea *** responses did not covary with hydrodynamic forces in the ***,antipredator responses in the mesocosm experiment increased when individuals were transplanted from strong to weak forces and decreased when transplanted from weak to strong ***,our results indicate environmentally induced plasticity in the antipredator behavior of the orange-footed sea cucumber.

关键词： behavioral plasticity benthic invertebrate predator-prey interaction reciprocal transplant experiment Solaster endeca.wave environment

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Signaling from T cell receptors (TCrs) and chimeric antigen receptors (CArs) on T cells

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Cellular & Molecular Immunology 2020年第6期17卷 600-612页

作者： Ling Wu Qianru Wei Joanna Brzostek nicholas r.J.Gascoigne Department of Microbiology and Immunology Yong Loo Lin School of MedicineNational University of Singapore5 Science Drive 2Singapore 117545Singapore Immunology Programme Life Sciences InstituteNational University of SingaporeSingaporeSingapore

T cells react to foreign or self-antigens through T cell receptor(TCr)*** decades of research have delineated the mechanism of TCr signal transduction and its impact on T cell *** knowledge provides the foundation for chimeric antigen receptor T cell(CAr-T cell)technology,by which T cells are redirected in a major histocompatibility complex-unrestricted *** and CAr signaling plays a critical role in determining the T cell state,including exhaustion and *** its artificial nature,CArs might affect or rewire signaling differently than TCrs.A better understanding of CAr signal transduction would greatly facilitate improvements to CAr-T cell technology and advance its usefulness in clinical ***,we systematically review the knowns and unknowns of TCr and CAr signaling,from the contact of receptors and antigens,proximal signaling,immunological synapse formation,and late signaling *** through different T cell subtypes and how signaling is translated into practice are also discussed.

关键词： CAr-T TCr Signaling T cell Immunological synapse

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Themis regulates metabolic signaling and effector functions in CD4^(+) T cells by controlling NFAT nuclear translocation

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Cellular & Molecular Immunology 2021年第9期18卷 2249-2261页

作者： Mukul Prasad Joanna Brzostek Namrata Gautam renu Balyan Vasily rybakin nicholas r.J.Gascoigne Translational Immunology Programme Yong Loo Lin School of MedicineNational University of Singapore5 Science Drive 2Singapore 117545Singapore Department of Microbiology and Immunology Yong Loo Lin School of MedicineNational University of Singapore5 Science Drive 2Singapore 117545Singapore H.Lee Moffitt Cancer Center and research Institute TampaFLUSA Torque Therapeutics CambridgeMAUSA

Themis is a T cell lineage-specific molecule that is involved in TCr signal *** effects of germline Themis deletion on peripheral CD4^(+)T cell function have not been described *** this study,we found that Themis-deficient CD4^(+)T cells had poor proliferative responses,reduced cytokine production in vitro and weaker inflammatory potential,as measured by their ability to cause colitis in *** T cells are quiescent,whereas activated T cells have high metabolic *** of these metabolic demands depends upon nutrient availability and upregulation of nutrient intake channels after efficient TCr signal transduction,which leads to metabolic reprogramming in T *** tested whether defects in effector functions were caused by impaired metabolic shifts in Themis-deficient CD4^(+)T cells due to inefficient TCr signal transduction,in turn caused by the lack of *** found that upon TCr stimulation,Themis-deficient CD4^(+)T cells were unable to upregulate the expression of insulin receptor(Ir),glucose transporter(GLUT1),the neutral amino acid transporter CD98 and the mTOr pathway,as measured by c-Myc and pS6 *** analysis of activated Themis-deficient CD4^(+)T cells showed more oxidative phosphorylation(OXPHOS)than aerobic glycolysis,indicating defective metabolic ***,we found reduced NFAT translocation in Themis-deficient CD4^(+)T cells upon TCr *** previously reported ChIP-seq and rNA-seq data,we found that NFAT nuclear translocation controls Ir gene ***,our results describe an internal circuit between TCr signal transduction,NFAT nuclear translocation,and metabolic signaling in CD4^(+)T cells.

关键词： Immunometabolism NFAT nuclear translocation Insulin receptor mTOr Mitochondria

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Mapping tree canopies in urban environments using airborne laser scanning (ALS):a Vancouver case study

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Forest Ecosystems 2018年第4期5卷 429-437页

作者： Giona Matasci nicholas C.Coops David A.r.Williams Nick Page Department of Forest resource Management Unlversity of British Columbia2424Main MallVancouverBC V6T IZ4Canada Vancouver Board of Parks and recreation 2099Beach AvenueVancouverBC V6G IZ4Canada

Background: The distribution of forest vegetation within urban environments is critically important as it influences urban environmental conditions and the energy exchange through the absorption of solar radiation and modulation of evapotranspiration. It also plays an important role filtering urban water systems and reducing storm water ***: We investigate the capacity of ALS data to individually detect, map and characterize large(taller than15 m) trees within the City of Vancouver. Large trees are critical for the function and character of Vancouver’s urban forest. We used an object-based approach for individual tree detection and segmentation to determine tree locations(position of the stem), to delineate the shape of the crowns and to categorize the latter either as coniferous or ***: results indicate a detection rate of 76.6% for trees > 15 m with a positioning error of 2.11 m(stem location). Extracted tree heights possessed a rMSE of 2.60 m and a bias of-1.87 m, whereas crown diameter was derived with a rMSE of 3.85 m and a bias of-2.06 m. Missed trees are principally a result of undetected treetops occurring in dense, overlapping canopies with more accurate detection and delineation of trees in open ***: By identifying key structural trees across Vancouver’s urban forests, we can better understand their role in providing ecosystem goods and services for city residents.

关键词： Urban forest Large trees Light detection and ranging Airborne laser scanning

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