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.

Verify the Function of a Potential Growth-Regulating Gene in Marine Bivalve Using a Candidate Model Organism Mulinia lateralis

A better understanding of genetic bases of growth regulation is essential for bivalve breeding,which is helpful to improve the yield of the commercially important bivalves.While previous studies have identified some candidate genes accounting for variation in growth-related traits through genotype-phenotype association analyses,seldom of them have verified the functions of these putative,growth-related genes beyond the genomic level due to the difficulty of culturing commercial bivalves under laboratory conditions.Fortunately,dwarf surf clam Mulinia lateralis can serve as a model organism for studying marine bivalves given its short generation time,the feasibility of being grown under experimental conditions and the availability of genetic and biological information.Using dwarf surf clam as a model bivalve,we characterize E2F3,a gene that has been found to account for variation in growth in scallops by a previous genome-wide association study,and verify its function in growth regulation through RNA interference(RNAi)experiments.For the first time,E2F3 in dwarf surf clam,which is termed as MulE2F3,is characterized.The results reveal that dwarf surf clams with MulE2F3 knocked down exhibit a reduction in both shell size and soft-tissue weight,indicating the functions of MulE2F3 in positively regulating bivalve growth.More importantly,we demonstrate how dwarf surf clam can be used as a model organism to investigate gene functions in commercial bivalves,shedding light on genetic causes for variation in growth to enhance the efficiency of bivalve farming.

Fairy shrimp Branchinella kugenumaensis displays sensitivity to microplastic exposure

The increasing global concern regarding plastic pollution has prompted the research into the consequences of microplastics(MPs)on aquatic ecosystems.Fairy shrimp Branchinella kugenumaensis are freshwater planktonic organisms that have existed for 250 million years.This study aimed to uncover the harmful effects of MPs,with a particular focus on their size variations(0.1,1,and 5μm),on the fairy shrimp.We focused on how MPs could significantly affect the survival and growth of fairy shrimp.Notably,larger MPs,especially those measuring 5μm,caused higher mortality rates and hindered the growth compared to smaller ones.The impact of MPs continued even subsequent to depuration in clean water.The accumulation of MPs within the intestines of fairy shrimp resulted in intestinal blockages,disrupted excretory functions,and harmed intestinal epithelial cells.Examinations at the histological,cellular,and molecular levels showed that exposure to MPs triggered necroptosis in intestinal cells,accompanied by alterations in pathways related to transcription,translation,digestion,energy metabolism,and neurological functions.Furthermore,the effects of MPs on gene expression and pathways varied based on particle size,with larger MPs having a more significant effect and causing a strong response in xenobiotic biodegradation and metabolism pathways.We suggest that the increasing severity of MPs pollution could pose a significant threat to the survival of fairy shrimp.This study provided vital insights into the complex relationship between microplastics and aquatic organisms,and highlighted the urgent need to address the potential devastating impact of plastic pollution on freshwater ecosystems.Additionally,due to their rapid growth,strong reproductive capacity,sensitivity,and ease of cultivation,fairy shrimp hold the potential candidate to serve as a model organism for studying the effects of MPs and other pollutants on freshwater ecosystems.

Research proceedings on amphibian model organisms

Model organisms have long been important in biology and medicine due to their specific characteristics. Amphibians, especially Xenopus, play key roles in answering fundamental questions on developmental biology, regeneration, genetics, and toxicology due to their large and abundant eggs, as well as their versatile embryos, which can be readily manipulated and developed in vivo. Furthermore, amphibians have also proven to be of considerable benefit in human disease research due to their conserved cellular developmental and genomic organization. This review gives a brief introduction on the progress and limitations of these animal models in biology and human disease research, and discusses the potential and challenge of Microhyla fissipes as a new model organism.

Ciona intestinalis as an emerging model organism: its regeneration under controlled conditions and methodology for egg dechorionation

The ascidian Ciona intestinalis is a model organism of developmental and evolutionary biology and may provide orucial clues concerning two fundamental matters, namely, how chordates originated from the putative deuterostome ancestor and how advanced chordates originated from the simplest chordates. In this paper, a whole-life-span culture of C. intestinalis was conducted. Fed with the diet combination of dry Spirulina, egg yolk, Dicrateria sp., edible yeast and weaning diet for shrimp, C. intestinalis grew up to average 59 mm and matured after 60 d cultivation. This culture process could be repeated using the artificially cultured mature ascidians as material. When the fertilized eggs were maintained under 10, 15, 20, 25 ℃, they hatched within 30 h, 22 h, 16 h and 12 h 50 min respectively experiencing cleavage, blastulation, gastrulation, neurulation, tailbud stage and tadpole stage, The tadpole larvae were characterized as typical but simplified chordates because of their dorsal nerve cord, notochord and primordial brain. After 8-24 h freely swimming, the tadpole larvae settled on the substrates and metamorphosized within 1-2 d into filter feeding sessile juvenile ascidians. In addition, unfertilized eggs were successfully dechorionated in filtered seawater containing 1% Tripsin, 0.25% EDTA at pH of 10.5 within 40 min. After fertilization, the dechorionated eggs developed well and hatched at normal hatching rate. In conclusion, this paper presented feasible methodology for rearing the tadpole larvae of C. intestinalis into sexual maturity under controlled conditions and detailed observations on the embryogenesis of the laboratory cultured ascidians, which will facilitate developmental and genetic research using this model system.

Experimental and modeling study of kinetics for methane hydrate formation in a crude oil-in-water emulsion

A low-viscosity emulsion of crude oil in water can be believed to be the bulk of a flow regime in a pipeline.To differentiate which crude oil would and which would not counter the blockage of flow due to gas hydrate formation in flow channels,varying amount of crude oil in water emulsion without any other extraneous additives has undergone methane gas hydrate formation in an autoclave cell.Crude oil was able to thermodynamically inhibit the gas hydrate formation as observed from its hydrate stability zone.The normalized rate of hydrate formation in the emulsion has been calculated from an illustrative chemical affinity model,which showed a decrease in the methane consumption（decreased normalized rate constant） with an increase in the oil content in the emulsion.Fourier transform infrared spectroscopy（FTIR） of the emulsion and characteristic properties of the crude oil have been used to find the chemical component that could be pivotal in selfinhibitory characteristic of the crude oil collected from Ankleshwar,India,against a situation of clogged flow due to formation of gas hydrate and establish flow assurance.

Original Frame of Organizational Model from the Chinese Traditional Philosophy

In this paper, the studies show that the framework of the original organizational models based on the philosophy view is constructed. The driving forces are also expatiated in the paper. Matching with the time and space in which the organization exists, fitted with the extra environment, making the organization take effect and properly controlling the important potential factors for the organizations further are the four driving forces development. The supporting pillars are cooperation in the competition, communication, negotiation and proper equal culture environment. At last, the researches point out that organization is a process, while organizational model is only a tool for us to realize the world.

Strategic Focus and Business Model Organization： The Mean Field Analysis Approach

The objective of this research is to show a new methodology for modeling phenomena present in complex economic systems. The case study we analyzed is the adoption of open organization model among firms operating in a particular industry. A firm with an open system model creates and captures value taking advantage not only from the internal resource but also from external. The organization could approach to open model acquisition using different focus： external focus namely looking out of its boundary, acting and reacting to competitor innovation, costumers＇ changing, demand growth, or internal focus remaining inside its boundary improving its best capabilities ignoring what happened outside （Vagnani, Moran, ＆ Simoni, 2010）. The actors involved are firms, customers and suppliers linked together through a business to business model. The methodology is based on an Object-Oriented Analysis Field Model that allows to intuitively describe systems characterized by a large number of objects that interact, as in this case of a system composed by different organizational entities. The system simulation allows to analyze how the actors influence the acquisition and diffusion of the open organization model. This approach permits the generation of different classes of objects to represent all actors involved in the evolution of the system and to define the dynamics that determine their interaction. The solution of the model can be approximated using the Mean-Field analysis technique （Kurtz, 1978）, following the results proposed in Bobbio, Gribaudo, and Yelek （2008）. A qualitative result is illustrated in order to show the applicability of the proposed methodology and to emphasize its relevant features： flexible modeling approach, capacity of solving complex systems and output management facilities. The presented model is comprehensive and its scope is wide; it could be used to study the behavior of enterprises changing model in many different scenarios and situations. In future works quantitative results will be given, and different situations will be analyzed.

Meta-model Based Model Organization and Transformation of Design Pattern Units in MDA

To achieve the purpose of applying design patterns which are various in ldnd and constant in changing in MDA from idea and application, one way is used to solve the problem of pattern disappearance which occurs at the process of pattern instantiation, to guarantee the independence of patterns, and at the same time, to apply this process to multiple design pattems. To solve these two problons, the modeling method of design pattern traits based on meta-models is adopted, i.e., to divide the basic operations into atoms in the metamodel tier and then combine the atoms to complete design pattem units meta-models withtout business logic. After one process of conversion, the purpose of making up various pattem traits meta-model and dividing business logic and pattern logic is achieved.

AN ADSORB MODEL OF ORGANIC ACID ON BASIC ZEOLITE NAX

The adsorb model of formic acid on NaX derived from TPD was discussed. It was showed that the adsorb sites were various exposed framework O2- centers bearing different basic intensity and spatial resistance. The h-peak was attributed to O2- near S-III in supercage and l-peak to O2- near S-II in beta-cage of faujusite zeolite. The model can explain the experimental results. Meanwhile, a relative standard of basic intensity based on TPD of formic acid was founded.

Research on Model of Virtual Organization and Its Practice

This paper discusses an organizational model to be used for both conventional and virtual organizations. The model deals with variable relationships within an organization and provides a framework for overall organizational design that may include relationship among different design variables and external relationship with environment. Based on the researches of virtual organization, this paper also illustrates the new model of organization in the real world such as Beijing 2008 Olympic games and Dongfeng Automobile group.

Application of Caenorhabditis elegans in screening active ingredients of traditional Chinese medicine

People continue to recognize the important role of Chinese medicine in the treatment of diseases,and there is an urgent need to clarify the mechanism of Chinese medicine.Because of the multi-target and multi-component characteristics of traditional Chinese medicine,it is difficult to elaborate from a single perspective.As a high-quality animal model,Caenorhabditis elegans with the characteristics of small size and fast reproduction,has been widely used in traditional Chinese medicine activity experiments.In this article,Caenorhabditis elegans,as model organisms used to screen the active components of traditional Chinese medicine were reviewed.

Molecular control of memory in nematode Caenorhabditis elegans

Model invertebrate organism Caenorhabditis elegans has become an ideal model to unravel the complex processes of memory. C. elegans has three simple forms of memory： memory for thermosensation, memory for chemosensation, and memory for mechanosensation. In the form of memory for mechanosensation, short-term memory, intermediate-term memory, and long-term memory have been extensively studied. The short-term memory and intermediate-term memory may occur in the presynaptic sensory neurons, whereas the long-term memory may occur in the postsynaptic interneurons. This review will discuss the recent progress on genetic and molecular regulation of memory in C. elegans.

Analysis and Related Suggestions on the Whole Process Engineering Consulting Service Mode at Home and Abroad

This paper first introduces the basic connotation of China’s whole-process engineering consulting.Immediately,analyze the organization model,service procurement model and charging standards of foreign whole-process engineering consulting(international terminology full-life cycle engineering consultant).Second,discuss the government’s role in the development of engineering consulting from two aspects:service management and market access.Finally,combined with the above analysis,the specific problems faced in the implementation process of the whole process engineering consulting are compared.Provide relevant suggestions on how companies and individuals respond to industry development trends.

Long-term organic and inorganic fertilizations enhanced basic soil productivity in a fluvo-aquic soil

The improvement of soil productivity depends on a rational input of water and nutrients, optimal field management, and the increase of basic soil productivity（BSP）. In this study, BSP is defined as the productive capacity of a farmland soil with its own physical and chemical properties for a specific crop season under local field management. Based on 19-yr data of the long-term agronomic experiments（1989–2008） on a fluvo-aquic soil in Zhengzhou, Henan Province, China, the decision support system for agrotechnology transfer（DSSAT ver. 4.0） crop growth model was used to simulate yields by BSP of winter wheat（Triticum aestivium L.） and summer maize（Zea mays L.） to examine the relationship between BSP and soil organic carbon（SOC） under long-term fertilization. Five treatments were included：（1） no fertilization（control）,（2） nitrogen, phosphorus and potassium fertilizers（NPK）,（3） NPK plus manure（NPKM）,（4） 1.5 times of NPKM（1.5NPKM）, and（5） NPK plus straw（NPKS）. After 19 yr of treatments, the SOC stock increased 16.7, 44.2, 69.9, and 25.2% under the NPK, NPKM, 1.5NPKM, and NPKS, respectively, compared to the initial value. Among various nutrient factors affecting contribution percentage of BSP to winter wheat and summer maize, SOC was a major affecting factor for BSP in the fluvo-aquic soil. There were significant positive correlations between SOC stock and yields by BSP of winter wheat and summer maize（P〈0.01）, and yields by BSP of winter wheat and summer maize increased 154 and 132 kg ha^（–1） when SOC stock increased 1 t C ha^（–1）. Thus, increased SOC accumulation is a crucial way for increasing BSP in fluvo-aquic soil. The manure or straw combined application with chemical fertilizers significantly enhanced BSP compared to the application of chemical fertilizers alone.

HIV-1 Vpr-induced cell death in Schizosaccharomyces pombe is reminiscent of apoptosis

Human immunodeficiency virus type 1 （HIV-1） Vpr induces cell death in mammalian and fssion yeast cells, suggesting that Vpr may affect a conserved cellular process. It is unclear, however, whether Vpr-induced yeast cell death mimics Vpr-mediated apoptosis in mammalian cells. We have recently identified a number of Vpr suppressors that not only suppress Vpr-induced cell death in fission yeast, but also block Vpr-induced apoptosis in mammalian cells. These findings suggest that Vpr-induced cell death in yeast may resemble some of the apoptotic processes of mammalian cells. The goal of this study was to develop and validate a fission yeast model system for future studies of apoptosis. Similar to Vpr-induced apoptosis in mammalian cells, we show here that Vpr in fission yeast promotes phosphatidylserine externalization and induces hyperpolarization of mitochondria, leading to changes of mitochondrial membrane potential. Moreover, Vpr triggers production of reactive oxygen species （ROS）, indicating that the apoptotic-like cell death might be mediated by ROS. Interestingly, Vpr induces unique morphologic changes in mitochondria that may provide a simple marker for measuring the apoptotic-like process in fission yeast. To verify this possibility, we tested two Vpr suppressors （EF2 and Hspl6） that suppress Vpr-induced apoptosis in mammalian cells in addition to a newly identified Vpr suppressor （Skpl）. All three proteins abolished cell death mediated by Vpr and restored normal mitochondrial morphology in the yeast cells. In conclusion, Vpr-induced cell death in fission yeast resembles the mammalian apoptotic process. Fission yeast may thus potentially be used as a simple model organism for the future study of the apoptotic-like process induced by Vpr and other proapoptotic agents.

Mapping Soil Organic Carbon Stocks of Northeastern China Using Expert Knowledge and GIS-based Methods

The main aim of this paper was to calculate soil organic carbon stock(SOCS) with consideration of the pedogenetic horizons using expert knowledge and GIS-based methods in northeastern China.A novel prediction process was presented and was referred to as model-then-calculate with respect to the variable thicknesses of soil horizons(MCV).The model-then-calculate with fixed-thickness(MCF),soil profile statistics(SPS),pedological professional knowledge-based(PKB) and vegetation type-based(Veg) methods were carried out for comparison.With respect to the similar pedological information,nine common layers from topsoil to bedrock were grouped in the MCV.Validation results suggested that the MCV method generated better performance than the other methods considered.For the comparison of polygon based approaches,the Veg method generated better accuracy than both SPS and PKB,as limited soil data were incorporated.Additional prediction of the pedogenetic horizons within MCV benefitted the regional SOCS estimation and provided information for future soil classification and understanding of soil functions.The intermediate product,that is,horizon thickness maps were fluctuant enough and reflected many details in space.The linear mixed model indicated that mean annual air temperature(MAAT) was the most important predictor for the SOCS simulation.The minimal residual of the linear mixed models was achieved in the vegetation type-based model,whereas the maximal residual was fitted in the soil type-based model.About 95% of SOCS could be found in Argosols,Cambosols and Isohumosols.The largest SOCS was found in the croplands with vegetation of Triticum aestivum L.,Sorghum bicolor(L.) Moench,Glycine max(L.) Merr.,Zea mays L.and Setaria italica(L.) P.Beauv.

Factors Acquisition and Content Estimation of Farmland Soil Organic Carbon Based upon Internet of Things

Aiming at the shortage of sufficient continuous parameters for using models to estimate farmland soil organic carbon(SOC) content, an acquisition method of factors influencing farmland SOC and an estimation method of farmland SOC content with Internet of Things(IOT) are proposed in this paper. The IOT sensing device and transmission network were established in a wheat demonstration base in Yanzhou Distict of Jining City, Shandong Province, China to acquire data in real time. Using real-time data and statistics data, the dynamic changes of SOC content between October 2012 and June 2015 was simulated in the experimental area with SOC dynamic simulation model. In order to verify the estimation results, potassium dichromate external heating method was applied for measuring the SOC content. The results show that: 1) The estimated value matches the measured value in the lab very well. So the method is feasible in this paper. 2) There is a clear dynamic variation in the SOC content at 0.2 m soil depth in different growing periods of wheat. The content reached the highest level during the sowing period, and is lowest in the flowering period. 3) The SOC content at 0.2 m soil depth varies in accordance with the amount of returned straw. The larger the amount of returned straw is, the higher the SOC content.

Theory and Practice of Learning Organization ——Investigation and Thinking for the Management Committee of the Baotou Rare Earth High-tech Area

Nowadays, many countries and regions use the human resources development as the major approach in holding the initiative in competition. The Baotou Rare Earth High-tech Area implements the strategies for revitalizing the area through establishing science and education learning organization and developing the entire learning in Management Committee. In accordance with the fundamental of mathematics ＂The arithmetical mean is equal to or larger than its geometric mean to any positive real number＂, it submits ＂the theoretical model of proportional development advantage of the same element in the same level＂ in order to solve ＂the problem that a few people behind in the department block the development of the High-tech Area＂, realize every member＇s common progress and each department＇s proportional development, and finally make the effect of Rare Earth High-tech maximum by strengthening team cooperation and producing a multiplier effect.

Embedded 3D bioprinting-An emerging strategy to fabricate biomimetic&large vascularized tissue constructs

Three-dimensional bioprinting is an advanced tissue fabrication technique that allows printing complex structures with precise positioning of multiple cell types layer-by-layer.Compared to other bioprinting methods,extrusion bioprinting has several advantages to print large-sized tissue constructs and complex organ models due to large build volume.Extrusion bioprinting using sacrificial,support and embedded strategies have been successfully employed to facilitate printing of complex and hollow structures.Embedded bioprinting is a gel-in-gel approach developed to overcome the gravitational and overhanging limits of bioprinting to print large-sized constructs with a micron-scale resolution.In embedded bioprinting,deposition of bioinks into the microgel or granular support bath will be facilitated by the sol-gel transition of the support bath through needle movement inside the granular medium.This review outlines various embedded bioprinting strategies and the polymers used in the embedded systems with advantages,limitations,and efficacy in the fabrication of complex vascularized tissues or organ models with micron-scale resolution.Further,the essential requirements of support bath systems like viscoelasticity,stability,transparency and easy extraction to print human scale organs are discussed.Additionally,the organs or complex geometries like vascular constructs,heart,bone,octopus and jellyfish models printed using support bath assisted printing methods with their anatomical features are elaborated.Finally,the challenges in clinical translation and the future scope of these embedded bioprinting models to replace the native organs are envisaged.