New aspects of a small GTPase RAB35 in brain development and function

In eukaryotic cells,organelles in the secretory,lysosomal,and endocytic pathways actively exchange biological materials with each other through intracellular membrane trafficking,which is the process of transporting the cargo of proteins,lipids,and other molecules to appropriate compartments via transport vesicles or intermediates.These processes are strictly regulated by various small GTPases such as the RAS-like in rat brain(RAB)protein family,which is the largest subfamily of the RAS superfamily.Dysfunction of membrane trafficking affects tissue homeostasis and leads to a wide range of diseases,including neurological disorders and neurodegenerative diseases.Therefore,it is important to understand the physiological and pathological roles of RAB proteins in brain function.RAB35,a member of the RAB family,is an evolutionarily conserved protein in metazoans.A wide range of studies using cultured mammalian cells and model organisms have revealed that RAB35 mediates various processes such as cytokinesis,endocytic recycling,actin bundling,and cell migration.RAB35 is also involved in neurite outgrowth and turnover of synaptic vesicles.We generated brain-specific Rab35 knockout mice to study the physiological roles of RAB35 in brain development and function.These mice exhibited defects in anxiety-related behaviors and spatial memory.Strikingly,RAB35 is required for the precise positioning of pyramidal neurons during hippocampal development,and thereby for normal hippocampal lamination.In contrast,layer formation in the cerebral cortex occurred superficially,even in the absence of RAB35,suggesting a predominant role for RAB35 in hippocampal development rather than in cerebral cortex development.Recent studies have suggested an association between RAB35 and neurodegenerative diseases,including Parkinson's disease and Alzheimer's disease.In this review,we provide an overview of the current understanding of subcellular functions of RAB35.We also provide insights into the physiological role of RAB35 in mammalian brain development and function,and discuss the involvement of RAB35 dysfunction in neurodegenerative diseases.

Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins

Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.

Postnatal development of rat retina:a continuous observation and comparison between the organotypic retinal explant model and in vivo development

The organotypic retinal explant culture has been established for more than a decade and offers a range of unique advantages compared with in vivo experiments and cell cultures.However,the lack of systematic and continuous comparison between in vivo retinal development and the organotypic retinal explant culture makes this model controversial in postnatal retinal development studies.Thus,we aimed to verify the feasibility of using this model for postnatal retinal development studies by comparing it with the in vivo retina.In this study,we showed that postnatal retinal explants undergo normal development,and exhibit a consistent structure and timeline with retinas in vivo.Initially,we used SOX2 and PAX6 immunostaining to identify retinal progenitor cells.We then examined cell proliferation and migration by immunostaining with Ki-67 and doublecortin,respectively.Ki-67-and doublecortin-positive cells decreased in both in vivo and explants during postnatal retinogenesis,and exhibited a high degree of similarity in abundance and distribution between groups.Additionally,we used Ceh-10 homeodomain-containing homolog,glutamate-ammonia ligase(glutamine synthetase),neuronal nuclei,and ionized calcium-binding adapter molecule 1 immunostaining to examine the emergence of bipolar cells,Müller glia,mature neurons,and microglia,respectively.The timing and spatial patterns of the emergence of these cell types were remarkably consistent between in vivo and explant retinas.Our study showed that the organotypic retinal explant culture model had a high degree of consistency with the progression of in vivo early postnatal retina development.The findings confirm the accuracy and credibility of this model and support its use for long-term,systematic,and continuous observation.

Exploring the dynamics of creative tourism:A tourist-centric perspective to achieve economic sustainable development

Creative tourism is a dynamic and innovative approach to tourism,which points out the importance of people's active participation and their immersion in such experiences.In a vernacular context,it should attract people(local and tourists)attention to accomplish its main goals.Despite its rich cultural and natural assets,Kurdistan province faces several challenges that impact its tourism potential.To achieve that,the study uses quantitative approach to thoroughly analyze and evaluate the components of creative tourism in this province.The research focuses on tourists who visited the province's ten towns during the spring and summer of 2023.Data collection utilized a Likert-scale questionnaire ranging from"very good"to"very poor".The study employed a semistructured questionnaire developed through qualitative interviews alongside a researcher-made questionnaire validated by experts from the University of Kurdistan.The qualitative questionnaire achieved a high-reliability score of 93%using Cronbach's alpha coefficient.In-depth interviews and literary research were conducted to identify creative tourism components and indicators,informing the development of a quantitative questionnaire.Data analysis was performed using SPSS 20 and AMOS software to scrutinize the survey findings,providing insights into enhancing creative tourism strategies in Kurdistan province.The results reveal the varying significance of these dimensions,with the cultural dimension identified as the most crucial(factor loading:0.95),followed by the social(0.92),economic(0.88),and managerial/political dimensions(0.83).The study highlights the importance of cultural planning,community engagement,and infrastructural support in fostering creative tourism.Furthermore,it explores the impact of creative industries,such as music and arts rooted in Kurdish culture,on tourism development.Economic diversification and spatialphysical considerations are critical factors in enhancing Kurdistan's appeal as a creative tourism destination,emphasizing sustainable growth and cultural preservation.

Development Tendency in Main Fields of Reading Researches

The last few decades have witnessed the publication of a considerable amount of empirical evidence supporting what Krashen has called "the power of reading"(Krashen,1993).There is a widespread approval that reading itself leads to better reading,better vocabulary,better writing,and better control of grammar in both first and second languages.In this article,the following research areas will be discussed,which can be mainly divided into the following 20 categories.

Deformation and Development Tendency of Shiliushubao Landslide by Numerical Modeling

On the basis of analysing basic features of Shiliushubao landslide, the landslide＇s deformation and development tendency are quantitatively studied by using FLA^3D program. The results accord with monitoring results. The results are indicated that resevoir impounding accelerates the landslide＇s deformation, and the variation of reservoir water level is key factor of affecting the deformation; The landslide has the characters of pull-behind move ment according to the displacement of the landslide body gradually reducing from leading edge to trailing edge; Excavating and deloading slow down the landslide＇s deformation in the certain degree. On the basis, the deformation developmental tendency of Shiliushubao landslide is predicted by the established simulating model.

Research on Development Tendency of College Campus Environmental Landscape Design in China

At the background that existing colleges largely construct campuses,the paper has illustrated the importance,significance and function of college campus environmental landscape design,and factors affecting it.It considers that college campuses tend to be developed into green ecological campus,regional humanistic campus,and knowledge research campus.Finally,by taking the East Lake Campus of Zhejiang A & F University for example,the campus division planning and scientific achievements' application planning have been illustrated.

Foreign-Related Tax Policy and Regime and Its Tendency of Development

China’s foreign--related tax system was established and developed in theprocess of deepening the reform and opening to the outside world begin-ning in 1979. Since the Third Plenary Session of the Eleventh CentralCommittee of the Chinese Communist Party, to meet the demands of thenew situation of opening to the outside world, several laws were promul-

Reflection on Current Situation and Development Tendency of Modern Urban Landscape Design in China

After the analysis of the development situation of urban landscape planning and design, the paper has summarized characteristics of current landscape planning, design and construction; and pointed out primary problems existing in modern urban landscape planning and design. It considers that the general planning and design level of modern landscape is to be improved, landscape construction is lacked of technological innovation, urban landscape construction and eco-environment efficiency have not been unified, plant species for landscaping are not reasonable, and construction has been emphasized while management been neglected in landscape planning. Through discussing the development tendency of modern urban landscape planning and design, it highlights that it should establish an ecological landscape idea corresponding with modern urban development requirements; set a long-term target based on modern urban development requirement; achieve the combination of bio-diversity, science and art; take social, ecological and social benefit into consideration; identify humanistic theme for landscape design; and pay attention to highly integrated application of multiple disciplines.

Current status and technology development tendency of research reactors in China

The current status and development history of domestic and abroad research reactors (RRs) are mentioned.The representative RRs and their respective technology characteristics are introduced.The utilizations of China's RRs,mainly included as nuclear engineering technology,basic research applications of nuclear technology,teaching and personnel training,are explained.

An Analysis of the Development Tendency of Chinese Folk Music under the Linear Thinking Background

This paper conducts the analysis of the development tendency of Chinese folk music under the linear thinking background. Complexity thinking is to use the basic theory of complexity science, viewpoint and method to the problem of a kind of the thinking, analysis, and to explore ways, it is the general nonlinear and integrity, relational, process as the main characteristics of a modern way of the thinking. China’s traditional music has the extremely glorious history, as it has included the folk music which the working people collective wisdom condenses becomes, that but also has the writer music, the sacred music, palace music, quantity is quite rich as spreads until now work to pass through the long years elutriate that is in our country traditional culture treasure. Under this basis, this paper proposes the novel idea of the issue that will be meaningful.

GAMYB transcription factor LoMYB65 from lily plays a vital role in pollen development

Lily(Lilium spp.)is an important horticultural crop,but its use is limited due to serious pollen contamination problems.There are many studies on pollen development in model plants,but few on flower crops such as lilies.Gibberellin(GA)is a large class of hormones and plays an important role in plant vegetative growth and reproductive development.GAMYB is a group of the R2R3-MYB family upregulated by gibberellin,and plays an important role in anther development.Here,we isolated a novel GAMYB,named LoMYB65,from lily,which was closely related to the AtMYB65 and AtMYB33 in Arabidopsis.Fluorescence quantitative PCR results showed that LoMYB65 was mainly expressed in lily anthers.LoMYB65 could be activated by 288μmol·L^(-1)GA3treatment and the LoMYB65 protein was located in the nucleus and cytoplasm,and had transactivation in yeast and tobacco leaf cells.The conserved motif within 226 amino acids of the C-terminal of LoMYB65 contributed to its transactivation.Overexpression of LoMYB65 caused dwarf phenotype,unnormal tapetum development,less seeds of siliques in transgenic Arabidopsis plants,the transgenic plants showed partly male sterile.Simultaneously,silencing of LoMYB65 with VIGS(Virus Induced Gene Silencing)in lily anthers caused unnormal pollen development and reduced the pollen amount.Overexpression of LoMYB65 in Arabidopsis and silencing of LoMYB65 in lily resulted in decreased pollen counts,so we speculate that LoMYB65 may be dose-dependent.Overall,these findings suggest that LoMYB65 may play an important role in anther development and pollen formation in lily.LoMYB65 may provide a useful candidate gene for pollenless breeding of lily.

Research and Review on the Java Multi-thread Programming and Its Further Development Tendency

In this paper, we conduct research on the Java multi-thread programming and its further development tendency. Multithreading mechanisms can run several programs at the same time, make the program run effi ciency becomes higher that also can overcome the problem of basic traditional programming language design while its design is the key to the realization of the synchronous thread. Multithreading is a mechanism that allows concurrent execution of multiple instruction stream in the program, each instruction stream is called a thread, independent from each other between each other. Thread is also known as a lightweight process, it have independent execution and process control. Our research starts from the analysis of the corresponding mechanism to enhance the performance that is innovative and meaningful.

A dynamic regulation of nitrogen on floret primordia development in wheat

Nitrogen(N)fertilization is critical for spike and floret development,which affects the number of fertile florets per spike(NFFs).However,the physiological regulation of the floret development process by N fertilization is largely unknown.A high temporal-resolution investigation of floret primordia number and morphology,dry matter,and N availability was conducted under three N fertilization levels:0(N0),120(N1)and 240(N2)kg ha^(−1).Interestingly,fertile florets at anthesis stage were determined by those floret primordia with meiotic ability at booting stage:meiotic ability was a threshold that predicted whether a floret primordium became fertile or abortive florets.Because the developmental rate of the 4th floret primordium in the central spikelet was accelerated and then they acquired meiotic ability,the NFFs increased gradually as N application increased,but the increase range decreased under N2.There were no differences in spike N concentration among treatments,but leaf N concentration was increased in the N1 and N2 treatments.Correspondingly,dry matter accumulation and N content of the leaf and spike in the N1 and N2 treatments was increased as compared to N0.Clearly,optimal N fertilization increased leaf N availability and transport of assimilates to spikes,and allowed more floret primordia to acquire meiotic ability and become fertile florets,finally increasing NFFs.There was no difference in leaf N concentration between N1 and N2 treatment,whereas soil N concentration at 0–60 cm soil layers was higher in N2 than in N1 treatment,implying that there was still some N fertilization that remained unused.Therefore,improving the leaf’s ability to further use N fertilizer is vital for greater NFFs.

Status Quo,Development,Tendency,and to be Solved Problems of Pilot Boat in China

Pilot boat is the main means and essential equipment of transport during ships transferring pilot.Ensuring pilot embarking or disembarking the ship on time is important for regulating port operation and ship’s safety.However,the pilot boat is a very small number of ship’s type whether domestic or abroad.This paper discusses the issues of pilot boat to be drawn attentions and solved,and proposes some recommendations for solving the pilot boat issues.

Conventional Geothermal Systems and Unconventional Geothermal Developments: An Overview

This paper provides an overview of conventional geothermal systems and unconventional geothermal developments as a common reference is needed for discussions between energy professionals. Conventional geothermal systems have the heat, permeability and fluid, requiring only drilling down to °C, normal heat flow or decaying radiogenic granite as heat sources, and used in district heating. Medium-temperature (MT) 100°C - 190°C, and high-temperature (HT) 190°C - 374°C resources are mostly at plate boundaries, with volcanic intrusive heat source, used mostly for electricity generation. Single well capacities are °C - 500°C) and a range of depths (1 m to 20 Km), but lack permeability or fluid, thus requiring stimulations for heat extraction by conduction. HVAC is 1 - 2 m deep and shallow geothermal down to 500 m in wells, both capturing °C, with °C are either advanced by geothermal developers at <7 Km depth (Enhanced Geothermal Systems (EGS), drilling below brittle-ductile transition zones and under geothermal fields), or by the Oil & Gas industry (Advanced Geothermal Systems, heat recovery from hydrocarbon wells or reservoirs, Superhot Rock Geothermal, and millimeter-wave drilling down to 20 Km). Their primary aim is electricity generation, relying on closed-loops, but EGS uses fractures for heat exchange with earthquake risks during fracking. Unconventional approaches could be everywhere, with shallow geothermal already functional. The deeper and hotter unconventional alternatives are still experimental, overcoming costs and technological challenges to become fully commercial. Meanwhile, the conventional geothermal resources remain the most proven opportunities for investments and development.

Development and technology status of energy storage in depleted gas reservoirs

Utilizing energy storage in depleted oil and gas reservoirs can improve productivity while reducing power costs and is one of the best ways to achieve synergistic development of"Carbon Peak–Carbon Neutral"and"Underground Resource Utiliza-tion".Starting from the development of Compressed Air Energy Storage(CAES)technology,the site selection of CAES in depleted gas and oil reservoirs,the evolution mechanism of reservoir dynamic sealing,and the high-flow CAES and injection technology are summarized.It focuses on analyzing the characteristics,key equipment,reservoir construction,application scenarios and cost analysis of CAES projects,and sorting out the technical key points and existing difficulties.The devel-opment trend of CAES technology is proposed,and the future development path is scrutinized to provide reference for the research of CAES projects in depleted oil and gas reservoirs.

Development Situation and Future Tendency of Liaohe Oil Province

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BMPRⅡ^(+)neural precursor cells isolated and characterized from organotypic neurospheres:an in vitro model of human fetal spinal cord development

Roof plate secretion of bone morphogenetic proteins(BMPs)directs the cellular fate of sensory neurons during spinal cord development,including the formation of the ascending sensory columns,though their biology is not well understood.Type-ⅡBMP receptor(BMPRⅡ),the cognate receptor,is expressed by neural precursor cells during embryogenesis;however,an in vitro method of enriching BMPRⅡ^(+)human neural precursor cells(hNPCs)from the fetal spinal cord is absent.Immunofluorescence was undertaken on intact second-trimester human fetal spinal cord using antibodies to BMPRⅡand leukemia inhibitory factor(LIF).Regions of highest BMPRⅡ^(+)immunofluorescence localized to sensory columns.Parenchymal and meningeal-associated BMPRⅡ^(+)vascular cells were identified in both intact fetal spinal cord and cortex by co-positivity with vascular lineage markers,CD34/CD39.LIF immunostaining identified a population of somas concentrated in dorsal and ventral horn interneurons,mirroring the expression of LIF receptor/CD118.A combination of LIF supplementation and high-density culture maintained culture growth beyond 10 passages,while synergistically increasing the proportion of neurospheres with a stratified,cytoarchitecture.These neurospheres were characterized by BMPRⅡ^(+)/MAP2ab^(+/–)/βⅢ-tubulin^(+)/nestin^(–)/vimentin^(–)/GFAP^(–)/NeuN^(–)surface hNPCs surrounding a heterogeneous core ofβⅢ-tubulin^(+)/nestin^(+)/vimentin^(+)/GFAP^(+)/MAP2ab^(–)/NeuN^(–)multipotent precursors.Dissociated cultures from tripotential neurospheres contained neuronal(βⅢ-tubulin^(+)),astrocytic(GFAP+),and oligodendrocytic(O4+)lineage cells.Fluorescence-activated cell sorting-sorted BMPRⅡ^(+)hNPCs were MAP2ab^(+/–)/βⅢ-tubulin^(+)/GFAP^(–)/O4^(–)in culture.This is the first isolation of BMPRⅡ^(+)hNPCs identified and characterized in human fetal spinal cords.Our data show that LIF combines synergistically with high-density reaggregate cultures to support the organotypic reorganization of neurospheres,characterized by surface BMPRⅡ^(+)hNPCs.Our study has provided a new methodology for an in vitro model capable of amplifying human fetal spinal cord cell numbers for>10 passages.Investigations of the role BMPRⅡplays in spinal cord development have primarily relied upon mouse and rat models,with interpolations to human development being derived through inference.Because of significant species differences between murine biology and human,including anatomical dissimilarities in central nervous system(CNS)structure,the findings made in murine models cannot be presumed to apply to human spinal cord development.For these reasons,our human in vitro model offers a novel tool to better understand neurodevelopmental pathways,including BMP signaling,as well as spinal cord injury research and testing drug therapies.