CX3CR1+ interstitial dendritic cells form a contiguous network throughout the entire kidney

Dendritic cells (DCs) interface innate and adaptive immunity in nonlymphoid organs; however, the exact distribution and types of DC within the kidney are not known. We utilized CX3CR1GFP/+ mice to characterize the anatomy and phenotype of tissue-resident CX3CR1+ DCs within normal kidney. Laser-scanning confocal microscopy revealed an extensive, contiguous network of stellate-shaped CX3CR1+ DCs throughout the interstitial and mesangial spaces of the entire kidney. Intravital microscopy of the superficial cortex showed stationary interstitial CX3CR1+ DCs that continually probe the surrounding tissue environment through dendrite extensions. Flow cytometry of renal CX3CR1+ DCs showed significant coexpression of CD11c and F4/80, high major histocompatibility complex class II and FcR expression, and immature costimulatory but competent phagocytic ability indicative of tissue-resident, immature DCs ready to respond to environment cues. Thus, within the renal parenchyma, there exists little immunological privilege from the surveillance provided by renal CX3CR1+ DCs, a major constituent of the heterogeneous mononuclear phagocyte system populating normal kidney

Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing

Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS. By exploiting shared phenotypic effects between ancestries and accommodating potential effect heterogeneities, TESLA improves power over other TWAS methods. When applied to tobacco use phenotypes, TESLA identified 273 new genes, up to 55% more compared with alternative TWAS methods. These hits and subsequent fine mapping using TESLA point to target genes with biological relevance. In silico drug-repurposing analyses highlight several drugs with known efficacy, including dextromethorphan and galantamine, and new drugs such as muscle relaxants that may be repurposed for treating nicotine addiction

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol- increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

[[alternative]]第一次實驗廣泛閱讀教學教師的反思、台灣大專院校學生與一名資深教師對於廣泛閱讀的感知

碩士[[abstract]]本研究旨在探討第一次運用廣泛閱讀的教師的反思，觀察學生的反應後如何發現實際的困難，並檢討會影響學生閱讀動機的可能因素。參與者包含第一次授課的教師、兩班學生以及另一名英語授課經驗豐富教師。本研究採質性研究方法，包括研究者週誌、學生態度與動機問卷、學生訪談與觀察教師訪談。參與研究的學生分為兩組，分別為傳統廣泛閱讀與廣泛閱讀後實施相關活動。實驗十三週的廣泛閱讀後，蒐集問卷並訪談學生與觀察教師的想法。 根據質性研究結果顯示 (1)研究者發現應用廣泛閱讀實際的困難與教學者經驗有關外，參與者學生也面臨閱讀內部、外部動機的影響。(2) 問卷與訪談的結果發現，閱讀後搭配討論活動的學生動機比起傳統廣泛閱讀模式的學生高，仍有少數學生不贊同廣泛閱讀的成效，而傳統閱讀組的學生仍保有對閱讀正向的觀感。(3) 觀察教師討論參與者環境背景、年紀、時間因素、教學者經驗與困難都與研究成效相關。 此外，研究中更發現除了教師與學生的關係對學生閱讀意願具有影響力外，學生本身閱讀態度也是影響閱讀動機的因素。本研究建議沒有實際運用過廣泛閱讀的教師，需謹慎設計廣泛閱讀課程，建立良好師生關係，並與提供與學生討論閱讀觀感，提高學生對閱讀的興趣，達到真正的悅讀。[[abstract]]The study investigated a first-time ER instructor’s reflections in implementation of extensive reading, how she found the difficulties after observing students’ reflections, examined the factors that might affect students’ reading motivation, and perceptions of the ER approach. The participants consisted of a first-time ER instructor, two EFL classes, and a well-experienced EFL teacher. The current study was an action research that used qualitative data analysis, including the instructor’s weekly diary, pre- and post-reading attitudes and motivation questionnaires, students’ interview, and the teacher’s interview. The participants were divided into two groups, one of traditional extensive reading (ERG), and the other of extensive reading with post-reading activity (PRG). Questionnaires and interviews were collected after a total of 13 weeks of ER. The results of qualitative research showed that (1) I found the difficulties of applying extensive reading relating to her lack of teaching experiences, and participating students confronted reading influences from both intrinsic and extrinsic motivation, (2) PRG students gained highly motivation than ERG students, some students disagreed with the ER effects; likewise, some ERG students still held positive experiences in English reading, (3) the EFL teacher discussed learners’ background, age, time, instructor’s experiences and challenges that were connecting to the effects of the study. In addition, the study revealed that not only teacher-students relationship had great influence on reading willingness, but also individual reading attitudes was a factor affecting their motivation. The findings recommended for the teachers who have not experienced the extensive reading approach that they should design the extensive reading carefully, establish the positive relationship with students, provide opportunity to discuss reading and improve their interests, and achieve the objectives of pleasure reading.[[tableofcontents]]TABLE OF CONTENTS ABSTRACT...............................................i DEDICATION...........................................iii ACKNOWLEDGEMENTS......................................iv TABLE OF CONTENTS......................................v LIST OF TABLES.......................................vii CHAPTER 1 Introduction 1.1 Research Background and Motivation.................1 1.2 Problem Statement..................................2 1.3 Purpose of the Study...............................4 1.4 Research Questions.................................5 1.5 Significance of the Study..........................5 CHAPTER 2 Literature Review 2.1 Theoretical Background.............................7 2.1.1 The Input Hypothesis.............................7 2.1.2 The Affective Filter Hypothesis..................8 2.1.3 The Bootstrap Hypothesis.........................8 2.2 ER Program 2.2.1 The Definition of ER.............................9 2.2.2 Principles of Effective ER Program...............9 2.2.3 ER Materials....................................11 2.2.3.1 Graded Readers................................12 2.3 Empirical Evidence Yielded by Prior ER Studies 2.3.1 ER and overall language proficiency, reading proficiency...........................................14 2.3.2 ER and reading comprehension and reading and listening speed.......................................19 2.3.3 ER and reading attitude and motivation..........22 2.4 Teachers’ attitudes toward ER program.............27 2.5 Action research...................................29 2.6 Summary...........................................30 CHAPTER 3 Methodology 3.1 Aims of the study.................................31 3.2 Participants......................................31 3.2.1 Research background.............................33 3.3 Research Design Extensive reading group (ERG)........................34 Post-Reading group (PRG).............................35 3.4 Reading Materials................................36 3.5 Instruments Pre-and Post-Attitudes and Motivation Questionnaire........................................37 Students’ Reading Logs...............................39 My diary.............................................40 Student Interviews...................................40 Experienced EFL Teacher’s Interview..................41 3.6 Procedure........................................41 3.7 Data analysis....................................43 CHAPTER 4 Results and Discussion 4.1 Results of Research Question 1...................45 4.2 Results of Research Question 2...................57 4.2.1 Questionnaire Results..........................57 4.2.2 Open-Ended Results Questionnaire and Interview Results..............................................64 4.3 Results of Research Question 3...................75 4.4 Discussion.......................................82 CHAPTER 5 Conclusion 5.1 Summary of the present study.....................93 5.2 Limitations of the study.........................94 5.3 Pedagogical implications.........................96 5.4 Suggestions for future studies...................98 References..........................................100 Appendix............................................109 LIST OF TABLES Table 3-1 The differences between the original ER principles and the two group’s settings 36 Table 4-1 ERG and PRG students’ reading books amount and attendance 51 Table 4-2 ERG and PRG students’ pre- and post-reading attitudes 59 Table 4-3 ERG and PRG students’ pre-and post-reading motivation 62 Table 4-4 ERG and PRG students’ aspects towards the instructor 64 Table 4-5 ERG and PRG participants’ aspects of reading activity 64[[note]]學號: 601110439, 學年度: 10

Integrin-mediated Tyrosine Phosphorylation of Shc in T Cells Is Regulated by Protein Kinase C-dependent Phosphorylations of Lck

Integrin receptor signals are costimulatory for mitogenesis with the T-cell receptor during T-cell activation. A subset of integrin receptors can link to the adapter protein Shc and provide a mitogenic stimulus. Using a combination of genetic and pharmacological approaches, we show herein that integrin signaling to Shc in T cells requires the receptor tyrosine phosphatase CD45, the Src family kinase member Lck, and protein kinase C. Our results suggest a model in which integrin-dependent serine phosphorylation of Lck is the critical step that determines the efficiency of Shc tyrosine phosphorylation in T cells. Serine phosphorylation of Lck is dependent on PKC and is also linked to CD45 dephosphorylation. Mutants of Lck that cannot be phosphorylated on the critical serine residues do not signal efficiently to Shc and have greatly reduced kinase activity. This signaling from integrins to Lck may be an important step in the costimulation with the T-cell receptor during lymphocyte activation