Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders:progress of experimental models based on disease pathogenesis

Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.

Exploiting fly models to investigate rare human neurological disorders

Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.

A promising approach for quantifying focal stroke modeling and assessing stroke progression:optical resolution photoacoustic microscopy photothrombosis

To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex.However,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly age-related.In this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed laser.We observed the molding process in mice of different ages and presented age-dependent vascular embolism differentiation.Moreover,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a stroke.Our imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.

The Metacognitive Strategy-Oriented Model in Primary English Listening --A Study Within the Framework of Task-based Syllabus

With the development of language teaching theories and researches, people gradually realize the importance of listening among the basic foreign language skills. Thus, how to improve the efficiency of foreign language listening teaching has long been a concern of researchers and foreign language teachers. As the beginning of English study, primary English is of significant importance for the learners＇ future language development. The study tries to put primary English listening together with metacognitive strategy and build up the metacognitive strategy-oriented model in primary English listening class in order to improve primary students＇ listening comprehension. Firstly, the thesis pointed out the disadvantages of the current primary English listening teaching. In order to make up these disadvantages, the previous studies of listening comprehension and metacognition both home and abroad are reviewed and the necessity and feasibility of the study are discussed. Finally, it is concluded that it is necessary and feasible to carry out the metacognitive strategy-oriented model in primary English class.

Reduced mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor contributes to neurodegeneration in a model of spinal and bulbar muscular atrophy pathology

Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.

A Tentative Probe into Task-based Mode of Translation Teaching

By analyzing the traditional model of E-C （English-Chinese） translation teaching, this paper points out the shortcomings of this old model, and presents a brand-new task-based approach to E-C translation teaching which takes contrastive linguistics as a base and threads with the concept of text translation.

The Enlightment on Task-based Teaching Derived from Input Hypothesis

Aiming at gradually developing and perfecting the task-based teaching method, the essay, with enlightment from the Krashen＇s Input Hypothesis, discusses some issues about input, output, activities and teacher＇s role in this method.

On the Application of Task-based Language Teaching Approach to English Phonetic Teaching

Task-based language teaching approach(TBLTA), which lays stress on "learning by doing", gained increasing popularity in English teaching in recent years. The design of phonetic teaching calls for more emphasis from English educators since it is one of the basic rounds of English teaching. This paper made a trial on the utilization of TBLTA in the English phonetic teaching context and designed a TBLTA model for English phonetic teaching based on discussions about model and merits of TBLTA.

Task-Based Approach in Language Teaching

During recent years,some notions about tasks have been considered as the major part of analysis in different teaching approaches and teachers are being more interested in the use of taskbased approach both in foreign and in second language teaching.The main goal of this article is to introduce and discuss some major principles of task-based language teaching and indicates how teachers can apply them in their curriculum.

Task-Based Approach在高职英语专业《综合英语》中的应用

Task-Based Approach(TBA:任务型教学法)不仅有利于提高学生综合运用英语的能力,而且有助于培养学生的自主学习意识与合作精神.本文介绍了任务型语言教学法运用于高职英语专业《综合英语》教学的实施原则和教学模式.

Using Task-based Instruction Approach to Make Clear Communication

Unclear,ambiguous,poor communication is one of the causes of major marine disasters.To foster the students'commu-nicative competence,the task-based instruction theory was applied in the design of English for Specific Purpose(ESP)instruction.This paper explored the procedures in task-based language teaching and applied them in ESP class in a Chinese vocational institute.

On Task-based Syllabus

Task-based syllabus (TBS) is organized around tasks. The basic theoretical foundation of TBS is Krashen's acquisition theory.from the L2 acquisition theory. The characteristic of TBS is focus of process of learning. TBS can improve communicative competence of learners, but it ignores grammar learning and teaching. The application of TBS in China is wide and the author provides an example.

Analysis of Task-based Syllabus

Task-based language teaching is very popular in the modern English teaching.It is based on the Task-based Syllabus. Task-based Syllabus focuses on the learners' communicative competence,which stresses learning by doing. From the theoretical assumption and definitions of the task,the paper analysizes the components of the task, then points out the merits and demerits of the syllabus. By this means the paper may give some tips to teachers and students when they use the tsk-based language teaching.

A Brief Introduction of Task-based Language Teaching(TBLT)

This paper presents the importance of task-based language teaching(TBLT), briefly introduces some different understanding of the definition of TBLT, and the rationale for it, analyses it's suitability and difficulties of implementing it in the classroom.

A Study on Task-based Language Teaching Syllabus Design

Task-based teaching syllabus becomes more and more popular in modern English teaching. It is widely used in the English teaching from junior to senior high school and even to collage and university education. This paper is mainly studies the relevant research on task-based teaching syllabus and offers some tips on task-based syllabus design.

A Review on Theories of Task-based Teaching

Based on several books on English teaching and learning,this paper gives a general review on task-based teaching.Firstly,it introduces the definitions of task and task-based syllabus and makes two distinctions,namely,"task"and"activity","taskbased teaching"and"communicative teaching".Then it states the notions behind the task-based teaching.Finally,it gives the notes for the application of this approach.

On the Effects of Applying Task-based Approach to Business Oral English Teaching in Higher Vocational College

A teaching experiment was conducted to investigate the feasibility and effectiveness of applying of Task-based approach(TBA) to business oral English teaching in higher vocational college.Instruments are tests and questionnaire for the experimental participants.Based on the data analysis,it can be concluded that TBA proves to be more effective especially compared with PPP approach.

Application of Task-based Approach in English Reading Classes in Senior Middle School

The traditional teaching approach is teacher-oriented,giving priority to grammar and lexical usage and neglecting the development of students’linguistic ability.The task-based approach is based on tasks and its prominent feature is"learning by doing and learning by using".By accomplishing tasks in target language,students can obtain linguistic knowledge and improve linguistic ability.This thesis is based on task-based approach,referring to English compulsory textbooks in senior middle school,exploring the application of task-based approach in intensive reading classes and providing case studies.

Application of Task-based Approach in College English Vocabulary Teaching

With the rapid development of economy and society,more and more people pay attention to English teaching.Vocabulary,the basic unit of language,is regarded as the center of language teaching by many linguists and educators.For Chinese students,vocabulary learning is also the most difficult and important problem in language learning.Unlike that in English-speaking countries,there is an absence of a foreign language environment for Chinese students,and most of their vocabulary is derived from classroom learning.Thus it is necessary to find an effective method to deal with vocabulary teaching.It analyzes college English vocabulary teaching,as college students have formed the corresponding language skills with more suitability.For a long time,students develop the habit of memorizing words repeatedly,consuming a lot of time,but the result is not satisfactory.Faced with this phenomenon,this paper analyzes the problems existing in College English vocabulary teaching and explores the reasons of the problems.Then it analyzes the application of task-based approach in college English vocabulary teaching.

An Initial Plan to Explore the Use of CALL in Task-Based Instruction in College English Writing in China

Learning for using theories has been,to a great degree,acceptable over the last few decades.Learning through doing,through using the language,through performing real life or real-life-like tasks has come to its own important occasions to achieve EFL/ESL learners' communicative goals.