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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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Evidence for the involvement of NOD2 in regulating colonic epithelial cell growth and survival

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World Journal of Gastroenterology 2008年第38期14卷 5834-5841页

作者： sheena m cruickshank Louise Wakenshaw John Cardone Peter D Howdle Peter J murray Simon R Carding molecular and Cellular Biology University of Leeds Leeds LS2 9JT United Kingdom Faculty of Life Sciences University of Manchester Manchester M13 9PT United Kingdom Institute of molecular and Cellular Biology University of Leeds Leeds LS2 9JT United Kingdom The Institute of Food Research Norwich Research Park Norwich NR4 7UA United Kingdom Institute of molecular and Cellular Biology University of Leeds Leeds LS2 9JT United Kingdom Section of medicine Surgery & Anaesthesia Leeds Institute of Molecular Medicine University of Leeds Leeds LS2 9JT United Kingdom Department of Infectious Diseases St. Jude Children's Research Hospital Memphis TN 38105 United States

AIm: To investigate the function of NOD2 in colonic epithelial cells (CEC). mETHODS: A combination of in vivo and in vitro analyses of epithelial cell turnover in the presence and absence of a functional NOD2 protein and, in response to enteric Salmonella typhimurium infection, were used. shRNA interference was also used to investigate the consequences of knocking down NOD2 gene expression on the growth and survival of colorectal carcinoma cell lines. RESULTS:In the colonic mucosa the highest levels of NOD2 expression were in proliferating crypt epithelial cells. muramyl dipeptide (mDP), that is recognized by NOD2, promoted CEC growth in vitro . By contrast,the growth of NOD2-deficient CECs was impaired. In vivo CEC proliferation was also reduced and apoptosis increased in Nod2-/- mice, which were also evident following enteric Salmonella infection. Furthermore, neutralization of NOD2 mRNA expression in human colonic carcinoma cells by shRNA interference resulted in decreased survival due to increased levels of apoptosis. CONCLUSION: These findings are consistent with the involvement of NOD2 protein in promoting CEC growth and survival. Defects in proliferation by CECs in cases of CD may contribute to the underlying pathology of disrupted intestinal homeostasis and excessive inflammation.

关键词： Colon Epithelial cells NOD2 Growth

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Heterogeneity across the murine small and large intestine

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World Journal of Gastroenterology 2014年第41期20卷 15216-15232页

作者： Rowann Bowcutt Ruth Forman maria Glymenaki Simon Richard Carding Kathryn Jane Else sheena margaret cruickshank Faculty of Life Sciences University of Manchester Department of microbiology New York University Gut Health and Food Safety Research Programme Institute of Food Research and the Norwich Medical SchoolUniversity of East Anglia

The small and large intestine of the gastrointestinal tract(GIT) have evolved to have discrete functions with distinct anatomies and immune cell *** importance of these differences is underlined when considering that different pathogens have uniquely adapted to live in each region of the ***,different regions of the GIT are also associated with differences in susceptibility to diseases such as cancer and chronic *** large and small intestine,given their anatomical and functional differences,should be seen as two separate immunological ***,this distinction is often ignored with findings from one area of the GIT being inappropriately extrapolated to the *** largely on the murine small and large intestine,this review addresses the literature relating to the immunology and biology of the two sites,drawing comparisons between them and clarifying similarities and *** also highlight the gaps in our understanding and where further research is needed.

关键词： Large intestine Small intestine Epithelial Immune microbial

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An efficient permutation approach for SbPN-based symmetric block ciphers

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Cybersecurity 2024年第2期7卷 113-130页

作者： mir Nazish m.Tariq Banday Insha Syed sheena Banday Department of Electronics and Instrumentation Technology University ofKashmirSrinagar 190006India

It is challenging to devise lightweight cryptographic primitives efficient in both hardware and software that can provide an optimum level of security to diverse Internet of Things applications running on low-end constrained ***,an effcient hardware design approach that requires some specific hardware resource may not be effcient if implemented in *** bit Permutation Network based ciphers such as PRESENT and GIFT are effcient,lightweight cryptographic hardware design *** ciphers introduce confusion and diffu-sion by employing a 4×4 static substitution box and bit *** bit-wise permutation is realised by sim-ple rerouting,which is most cost-effective to implement in hardware,resulting in negligible power ***,this method is highly resource-consuming in software,particularly for large block-sized ciphers,with each single-bit permutation requiring multiple *** paper proposes a novel software-based design approach for permutation operation in Substitution bit Permutation Network based ciphers using a bit-banding *** conventional permutation using bit rotation and the proposed approach have been implemented,analysed and compared for GIFT and PRESENT ciphers on ARm Cortex-m3-based LPC1768 development platform with KEIL mDK used as an Integrated Development *** real-time performance comparison between conven-tional and the proposed approaches in terms of memory(RAm/ROm)footprint,power,energy and execution time has been carried out using ULINKpro and ULINKplus debug adapters for various code and speed optimisation *** proposed approach substantially reduces execution time,energy and power consumption for both PRE-SENT and GIFT ciphers,thus demonstrating the effciency of the proposed method for Substitution bit Permutation Network based symmetric block ciphers.

关键词： Lightweight cryptography PRESENT GIFT SbPN Cortex-m LPC1768 Bit-band memory

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The complicated life of a physician-soldier: medical readiness training exercises &the problem of dual loyalties

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Journal of Biomedical Science and Engineering 2013年第10期6卷 8-18页

作者： sheena m. Eagan Chamberlin Institute for the medical Humanities University of Texas Medical Branch Galveston USA

While physicians are generally understood as owing moral obligation to the health and well being of their individual patients, military health professionals can face ethical tensions between responsibilities to individual patients and responsibilities to the military mission. The conflicting obligations of the two roles held by the physician-soldier are often referred to as the problem of dual loyalties and have long been a topic of debate. This paper seeks to enrich the dualloyalties debate by examining the embedded case study of medical civilian assistance programs. These programs represent the use of medicine within the military for strategic goals. Thus, a physician is expected to meet his obligation to his role as a soldier while also practicing medicine. These programs involve obligations inherent in both roles of the physician-soldier and thusly they serve as excellent exemplars for the problem of dual loyalties at an institutional level. This paper focuses on medical Readiness Training Exercises (mEDRETEs). These programs are short-term, generally taking place in low-income nations in order to accomplish strategic goals including training opportunities for military medical professionals that are not possible on the home front. This form of temporary program raises ethical concerns regarding the exploitation of vulnerable populations and the value of what is termed “parachute medicine”. The short-term nature of these interventions makes long-term treatment and follow-up impossible, begging the question as to whether this peak and trough approach to foreign civilian aid is of any use. Physicians are generally understood as having obligations towards the well being of the patient, which these programs do not necessarily prioritize. Rather, the programmatic intent is military, with political and strategic aims of furthering international relations, increasing US military global presence and providing austere and tropical training opportunities for military healt

关键词： military medicine Dual Loyalty medical Ethics History of medicine military History military Ethics mEDRETEs Civic Action

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Assessing impact of climate change on forest cover type shifts in Western Himalayan Eco-region

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Journal of Forestry Research 2012年第1期23卷 75-80页

作者： P.K.Joshi Asha Rawat sheena Narula Vinay Sinha Department of Natural Resources TERI UniversityNew Delhi 110070India

Climate is a critical factor affecting forest ecosystems and their capacity to produce goods and services. Effects of climate change on forests depend on ecosystem-specific factors including dimensions of climate （temperature, precipitation, drought, wind etc.）. Available infor- mation is not sufficient to support a quantitative assessment of the eco- logical, social and economic consequences. The present study assessed shifts in forest cover types of Western Himalayan Eco-region （700-4 500 m）. 100 randomly selected samples （75 for training and 25 for testing the model）, genetic algorithm of rule set parameters and climatic envelopes were used to assess the distribution of five prominent forest cover types （Temperate evergreen, Tropical semi-evergreen, Temperate conifer, Sub- tropical conifer, and Tropical moist deciduous forests）. modelling was conducted for four different scenarios, current scenario, changed precipi- tation （8% increase）, changed temperature （1.07℃ increase）, and both changed temperature and precipitation. On increasing precipitation a downward shift in the temperate evergreen and tropical semi-evergreen was observed, while sub-tropical conifer and tropical moist-deciduous forests showed a slight upward shift and temperate conifer showed ＇no shift. On increasing temperatm＇e, an upward shift in all forest types was observed except sub-tropical conifer forests without significant changes. When both temperature and precipitation were changed, the actual dis- tribution was maintained and slight upward shift was observed in all the forest types except sub-tropical conifer. It is important to understand the likely impacts of the projected climate change on the forest ecosystems, so that better management and conservation strategies can be adopted for the biodiversity and forest dependent community. Knowledge of impact mechanisms also enables identification and mitigation of some of the conditions that increase vulnerability to climate change in the fore

关键词： Climate change forest cover types shift western Himalaya genetic algorithm

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Foliar spraying of chlorpyrifos induces morphometric changes in Glycine max(L.)and shifts native soil microbiome

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Emerging Contaminants 2024年第3期10卷 86-102页

作者： Aman Raj muneer Ahmad malla Ashwani Kumar Pramod Kumar Khare sheena Kumari metagenomics and Secretomics Research Laboratory Department of BotanyDr.Harisingh Gour University(A Central University)Sagar470003M.P.India Institute for Water and Wastewater Technology Durban University of TechnologyDurban4001South Africa metagenomics and Secretomics Research Laboratory Department of BotanyUniversity of Allahabad(A Central University)Prayagraj211002U.P.India Department of Botany Ecology laboratoryDr.Harisingh Gour Vishwavidyalaya(A Central University)SagarMadhya Pradesh470003India

Pesticide usage alters plant growth,and development and disturbs native soil *** present study was carried out to evaluate the effect of Chlorpyrifos(CP-20%EC)on the growth and development of soybean(Glycine max),soil fertility,and soil *** conducted a pot experiment to assess the impact of different concentrations of chlorpyrifos;recommended dose(RD)and higher dose rates(2×and 4×RD).Chlorpyrifos application significantly altered the growth parameters in soybean(pmpared to RD and Control *** at these concentrations(2×and 4×RD),significant reduction in fresh shoot weight(0.86±0.008;0.66±0.002,pmpared to the RD and control ***,a significant increase in root and shoot morphometric parameters was observed in RD compared to control(pmical properties such as pH(8.51±0.82),moisture content(33.73±0.04),and electrical conductivity(3.44±0.03)were higher in CP-treated soils compared to ***,nutrient content such as nitrogen,carbon,and hydrogen were significantly reduced in treated soils compared to *** analysis showed higher concentrations of As,Cd,and Pb in CP-treated soil(8.7 mg/g,0.254 mg/g,and 16.477 mg/g,respectively)compared to untreated soil(8.09 mg/g,0.228 mg/g,and 15.25 mg/g,respectively).We also assessed soil metabolic activity and diversity using Community-level Physiological Profiling(CLPP).CP-treated soil exhibited significantly lesser microbial diversity,with lesser metabolic *** analysis revealed a shift in bacterial community composition,with Pseudomonadota and Bacteroidota dominating CP-treated s

关键词： Chlorpyrifos Glycine max Proline metabolic activity CLPP metagenomics Bacterial microbiome

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Focused transcription from the human CR2/CD21 core promoter is regulated by synergistic activity of TATA and Initiator elements in mature B cells

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Cellular & molecular Immunology 2016年第1期13卷 119-131页

作者： Rhonda L Taylor mark N cruickshank mahdad Karimi Han Leng Ng Elizabeth Quail Kenneth m Kaufman John B Harley Lawrence J Abraham Betty P Tsao Susan A Boackle Daniela Ulgiati School of Pathology and Laboratory medicine Centre for Genetic Origins of Health and Disease The University of Western Australia Crawley WA Australia Biochemistry and molecular Biology School of Chemistry and Biochemistry The University of Western Australia Crawley WA Australia Telethon Kids Institute The University of Western Australia Crawley WA Australia Cincinnati Children's Hospital medical Center Cincinnati OH USA US Department of Veterans Affairs medical Center Cincinnati OH USA Division of Rheumatology Department of Medicine University of California at Los Angeles Los Angeles CA USA Division of Rheumatology University of Colorado School of Medicine Aurora CO USA

Complement receptor 2 （CR2/CD21） is predominantly expressed on the surface of mature B cells where it forms part of a coreceptor complex that functions, in part, to modulate B-cell receptor signal strength. CR2/CD21 expression is tightly regulated throughout B-cell development such that CR2/CD21 cannot be detected on pre-B or terminally differentiated plasma cells. CR2/CD21 expression is upregulated at B-cell maturation and can be induced by IL-4 and CD40 signaling pathways. We have previously characterized elements in the proximal promoter and first intron of CR2/CD21 that are involved in regulating basal and tissue-specific expression. We now extend these analyses to the CR2/CD21 core promoter. We show that in mature B cells, CR2/~D21 transcription proceeds from a focused TSS regulated by a non-consensus TATA box, an initiator element and a downstream promoter element. Furthermore, occupancy of the general transcriptional machinery in pre-B versus mature B-cell lines correlate with CR2/CD21 expression level and indicate that promoter accessibility must switch from inactive to active during the transitional B-cell window.

关键词： B cells core promoter CR2/CD21 molecular biology transcription factor

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β受体阻滞剂在降压治疗中的作用

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中华高血压杂志 2011年第1期19卷 29-30页

作者：郭文俊 John m.cruickshank 德国默克雪兰诺有限公司北京100022 英国伯明翰综合医院全科医学科

β受体阻滞剂是否真的不能作为一线降压药物使用,本文作者认为下列情况β受体阻滞剂是首选药物。

关键词： β受体阻滞剂降压治疗药物使用首选药物

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Δ<sup>9</sup>-Tetrahydrocannabinol Produced Positive Place Preference in mice without Significant <i>Ex-Vivo</i>Effect on Hepatic Arylamine N-Acetyltransferase Activity: Implications for Its Addictive Liability and Absence of Effect on Xenobiotic metabolism

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Journal of Behavioral and Brain Science 2021年第8期11卷 179-192页

作者： Lauriann Young Karen Thaxter Danielle Campbell sheena Francis Nicola Laurieri Rupika Delgoda Physiology Section Department of Basic Medical Sciences The University of the West Indies (UWI) Mona Campus Kingston Jamaica Natural Products Institute The University of the West Indies (UWI) Mona Campus Kingston Jamaica Department of Pharmacology Oxford University Oxford England UK

Aim: Δ9-Tetrahydrocannabinol (Δ9-THC) is a potentially addictive cannabinoid. Its impact on the activity of liver arylamine N-Acetyltransferase (NAT) has not been reported. This study investigated the rewarding effects of Δ9-THC in mice and whether Δ9-THC had any impact ex-vivo and in-vitro on NAT activity. methods: Thirty-six Swiss albinomice randomly assigned to six groups (n = 6) completed a biased, 8-week Conditioned Place Preference (CPP) paradigm. mice exhibiting ~80% preference for the black chamber at pre-conditioning were selected. Treatment groups were administered Δ9-THC (0.10, 0.50 or 2.0 mg/kg/mL, ip) or amphetamine (AmP, 5.0 mg/kg/mL, ip);while untreated groups (controls) received vehicle solutions (coconut oil or 0.9% saline). Entries and time spent in the white, drug-paired chamber during a 15-min post-conditioning exploration of the CPP apparatus were compared with the pre-conditioning exploratory scores. Livers from Δ9-THC treated and untreated mice were excised and NAT enzyme activity determined ex-vivo using a spectrophotometric assay with p-anisidine as substrate. The impact of varying concentrations of Δ9-THC (0.00 - 162 μm) on the activities of NAT from untreated mice livers were also investigated in-vitro. Results: Δ9-THC treated mice entered and spent significantly more time in the drug-paired CPP chamber (p ≤ 0.05) at post-conditioning vs pre-conditioning (F = 11.22). mice treated with 2.0 mg/kg Δ9-THC made significantly more entries into the drug-paired chamber (p ≤ 0.05) as compared with their vehicle controls. AmP-treated mice displayed significant (p me spent in the drug-paired chamber at post-conditioning (positive place preference). In-vitro NAT evaluations revealed a dose-dependent inhibitory impact of Δ9-THC on NAT

关键词： Cannabis marijuana Conditioned Place Preference Addiction Drug Reward

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