Oligodendrocytes in central nervous system diseases:the effect of cytokine regulation

Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular functions such as migration, survival, proliferation, and differentiation. Oligodendrocytes are the myelin-forming cells in the central nervous system and play critical roles in the conduction of action potentials, supply of metabolic components for axons, and other functions. Emerging evidence suggests that both oligodendrocytes and oligodendrocyte precursor cells are vulnerable to cytokines released under pathological conditions. This review mainly summarizes the effects of cytokines on oligodendrocyte lineage cells in central nervous system diseases. A comprehensive understanding of the effects of cytokines on oligodendrocyte lineage cells contributes to our understanding of central nervous system diseases and offers insights into treatment strategies.

SiRAP2-12,a Positive Regulatory Factor,Effectively Improves the Waterlogging Tolerance of Foxtail Millet(Setaria italica)

Foxtail millet(Setaria italica)growth was inhibited because of waterlogging stress,which has caused yield reduc-tion.ERF family plays an important role to plant adversity tolerance.In our study,we obtained 19,819 differential expressed genes(DEGs)between the two treatments based on the RNA-seq sequencing of foxtail millet of water-logging stress.Furthermore,a total of 28 ERF family members were obtained,which have a complete open read-ing frame.We studied the evolution and function of SiERF family and how they affected the waterlogging tolerance.It was found that SiERF1A/B/C(GenBank ID:OR775217,OR775219,OR775218)and SiRAP2-12(GenBank ID:OR775216)have similar functions to the known waterlogging tolerance genes of other plants.Among them,the SiRAP2-12 expression was obviously significantly up-regulated in foxtail millet after 5d water-logging stress.After SiRAP2-12 was silenced,the activity of defense enzymes in millet decreased significantly.In details,superoxide dismutase(SOD),catalase(CAT)and peroxidase(POD),the osmotic regulator proline(Pro),and the activity of the anaerobic respiratory enzyme alcohol dehydrogenase(ADH)content were decreased by 78.61%,29.52%,79.95%,19.41%and 54.77%,respectively.In contrast,the relative electrical conductivity contents(REC),malondialdehyde(MDA),and hydrogen peroxide(H_(2)O_(2))of the foxtail millet subjected to virus-induced gene silencing clearly increased by 1.03-fold,36.09%,and 15.21%,respectively.The content of sodium(Na^(+))in the SiRAP2-12-silenced foxtail millet also increased,but that of potassium(K^(+))decreased.Interestingly,we found that ethylene content was significantly reduced.Further,the SiAOC1 expression,an essential gene for ethylene synthesis,was inhibited in SiRAP2-12-silenced foxtail millet after waterlogging stress.Taken together,we hypothesized that SiRAP2-12 might be a positive regulator of millet tolerance to waterlogging stress.

Hierarchically Structured Nb_(2)O_5 Microflowers with Enhanced Capacity and Fast-Charging Capability for Flexible Planar Sodium Ion Micro-Supercapacitors

Planar Na ion micro-supercapacitors(NIMSCs) that offer both high energy density and power density are deemed to a promising class of miniaturized power sources for wearable and portable microelectron-ics. Nevertheless, the development of NIMSCs are hugely impeded by the low capacity and sluggish Na ion kinetics in the negative electrode.Herein, we demonstrate a novel carbon-coated Nb_(2)O_5 microflower with a hierarchical structure composed of vertically intercrossed and porous nanosheets, boosting Na ion storage performance. The unique structural merits, including uniform carbon coating, ultrathin nanosheets and abun-dant pores, endow the Nb_(2)O_5 microflower with highly reversible Na ion storage capacity of 245 mAh g^(-1) at 0.25 C and excellent rate capability.Benefiting from high capacity and fast charging of Nb_(2)O_5 microflower, the planar NIMSCs consisted of Nb_(2)O_5 negative electrode and activated car-bon positive electrode deliver high areal energy density of 60.7 μWh cm^(-2),considerable voltage window of 3.5 V and extraordinary cyclability. Therefore, this work exploits a structural design strategy towards electrode materials for application in NIMSCs, holding great promise for flexible microelectronics.

TTYH2,a human homologue of the Drosophila melanogaster gene tweety,is up-regulated in colon carcinoma and involved in cell proliferation and cell aggregation

AIM: To investigate the expression patterns of TTYH2 in the human colon cancer and colon cancer cell lines and to evaluate the inhibitory effect of small interfering RNA (siRNA) on the expression of TTYH2 in colon cancer cell lines.METHODS: We investigated the expression patterns of TTYH2 in colon cancer, adjacent non-tumorous colon mucosa, and cancer cell lines (DLD-1, caco-2, and Lovo) by RT-PCR. Furthermore, a siRNA plasmid expression vector against TTYH2 was constructed and transfected into DLD-1 and Caco-2 with LipofectamineTM 2000. The down regulation of TTYH2 expression was detected by RT-PCR and the role of siRNA in inducing cell proliferation and cell aggregation was evaluated by MTT and aggregation assay.RESULTS: TTYH2 gene expression in colon cancer tissue was significantly up-regulated compared with normal colonic mucosa (1.23 ± 0.404 vs 0.655 ± 0.373, P = 0.0103). Colon cancer derived cell lines including DLD-1, Caco-2, and Lovo also expressed high levels of TTYH2. In contrast, transfection with siRNA-TTYH2 signifi cantly inhibited both proliferation and scattering of these cancer cell lines.CONCLUSION: The present work demonstrates, for the fi rst time, that the TTYH2 gene expression is signifi cantly up-regulated in colon cancer. The TTYH2 gene may play an important role in regulating both proliferating andmetastatic potentials of colorectal cancer.

Fingolimod protects against neurovascular unit injury in a rat model of focal cerebral ischemia/reperfusion injury

Recent research on the underlying mechanisms of cerebral ischemia indicates that the neurovascular unit can be used as a novel subject for general surveys of neuronal damage and protein mechanisms.Fingolimod(FTY-720)is a newly developed immunosuppressant isolated from Cordyceps sinensis that exhibits a wide range of biological activities,and has recently attracted much attention for the treatment of ischemic cerebrovascular diseases.In the current research,the role of FTY-720 and its possible mechanisms were assessed from an neurovascular unit perspective using a rat cerebral ischemia model.Our results revealed that FTY-720 markedly decreased infarct volume,promoted neurological function recovery,and weakened the blood-brain barrier permeability of ischemic rats.The protective roles of FTY-720 in ischemic stroke are ascribed to a combination of sphingosin-1-phosphate receptor-1 and reduced expression of sphingosin-1-phosphate receptor-1 in microvessels and reduction of interleukin-17A protein levels.These findings indicate that FTY-720 has promise as a new therapy for neurovascular protection and functional recovery after ischemic stroke.

Asymmetric migration dynamics of the tropical Asian and Australasian floras

The tropical Asian and Australasian floras have a close relationship,and is a vital distribution pattern of seed plants worldwide.As estimated,more than 81 families and 225 genera of seed plants distributed between tropical Asia and Australasia.However,the evolutionary dynamics of two floras were still vague.Here,a total of 29 plant lineages,represented the main clades of seed plants and different habits,were selected to investigate the biotic interchange between tropical Asia and Australasia by integrated dated phylogenies,biogeography,and ancestral state reconstructions.Our statistics indicated that 68 migrations have occurred between tropical Asia and Australasia since the middle Eocene except terminal migrations,and the migration events from tropical Asia to Australasia is more than 2 times of the reverse.Only 12 migrations occurred before 15 Ma,whereas the remaining56 migrations occurred after 15 Ma.Maximal number of potential dispersal events(MDE) analysis also shows obvious asymmetry,with southward migration as the main feature,and indicates the climax of bi-directional migrations occurred after 15 Ma.We speculate that the formation of island chains after the Australian-Sundaland collision and climate changes have driven seed plant migrations since the middle Miocene.Furthermore,biotic dispersal and stable habitat may be crucial for floristic interchange between tropical Asia and Australasia.

Effects of diet shift on the gut microbiota of the critically endangered Siberian Crane

Wetlands worldwide have suffered from serious degradation and transformation,leading to waterbirds increasingly dependent on agricultural fields for feeding.Although gut microbiota is an essential component of host health,the impacts of agricultural feeding on gut microbial community and pathogen transmission remain poorly understood.To fill this knowledge gap,we used 16S rRNA sequencing to characterize the fecal bacterial community of the Siberian Crane(Grus leucogeranus),a Critically Endangered species,that recently has shifted its foraging from largely Vallisneria tubers in Poyang Lake natural wetlands to crops(i.e.,rice seeds and lotus rhizomes) in agricultural fields.We compared the bacterial communities between tuber foraging cranes and crop foraging cranes.Our results indicate that diet shift greatly modified the gut microbiota diversity,composition and function.Crop foraging cranes had higher microbiota diversity than tuber foraging cranes.The alteration in microbiota composition and function were correlated with change in food nutrition.Tuber(i.e.,high in fiber)foraging cranes were enriched in Clostridiaceae with fiber digestion ability,and crop(i.e.,high in carbohydrate)foraging cranes were enriched in bacterial taxa and functions related to carbohydrate metabolism.The flexibility of gut microbiota might enhance Siberian Cranes’ ability to adapt to novel diet and environment.However,many enriched families in crop foraging cranes were pathogenic bacteria,which might increase the susceptibility of cranes to pathogenic infection.Special caution should be taken to agricultural feeding waterbirds in Asia,where the widespread poultry-keeping in over-harvested rice fields might increase the transmission probability of pathogenetic bacteria among wild birds,domestic poultry and humans.

Characteristics and expression of the TCP transcription factors family in Allium senescens reveal its potential roles in drought stress responses

Allium senescens,is an important economic and ecological grassland plant with drought-resistant characteristics.A TCP protein transcription factor is important in the regulation of plant development and adverse responses.However,the mechanism by which TCP transcription functions in drought resistance in Allium senescens is still not clear.Here,we obtained a total of 190,305 transcripts with 115,562 single gene clusters based on RNA-Seq sequencing of Allium senescens under drought stress.The total number of bases was 97,195,096 bp,and the average length was 841.06 bp.Furthermore,we found that there were eight genes of the TCP family that showed an upregulated expression trend under drought stress in Allium senescens.We carried out an investigation to determine the evolution and function of the AsTCP family and how they produce an effect in drought resistance.The 14 AsTCP genes were confirmed and divided into class I and class II containing CIN and CYC/TBI subfamilies,respectively.We also found that the expression of AsTCP17 was remarkably upregulated with drought treatment.Besides,the transformation of AsTCP17 in Arabidopsis revealed that the protective enzymes,namely polyphenol oxidase(POD)and superoxide dismutase(SOD),were increased by 0.4 and 0.8 times,respectively.Chlorophyll content was also increased,while the H2O2 and malondialdehyde(MDA)contents were decreased.Staining assays with 3,3′-diaminobenzidine(DAB)also suggested that the AsTCP17 downregulates reactive oxygen species(ROS)accumulation.In addition,overexpression of the AsTCP17 affected the accumulation of drought-related hormones in plants,and the synthesis of ABA.The expression of AtSVP and AtNCED3,related ABA synthesis pathway genes,indicated that the level of expression of AtSVP and AtNCED3 was obviously enhanced,with the overexpression of line 6 showing a 20.6-fold and 7.0-fold increase,respectively.Taken together,our findings systematically analyze the AsTCPs family at the transcriptome expression level in Allium senescens,and we also demonstrated that AsTCP17 protein,as a positive regulator,was involved in drought resistance of Allium senescens.In addition,our research contributes to the comprehensive understanding of the drought stress defense mechanism in herbaceous plants.

The genome of okra (Abelmoschus esculentus) provides insights into its genome evolution and high nutrient content

Okra(Abelmoschus esculentus)is an important vegetable crop with high nutritional value.However,the mechanism underlying its high nutrient content remains poorly understood.Here,we present a chromosome-scale genome of okra with a size of 1.19 Gb.Comparative genomics analysis revealed the phylogenetic status of A.esculentus,as well as whole-genome duplication(WGD)events that have occurred widely across the Malvaceae species.We found that okra has experienced three additional WGDs compared with the diploid cotton Gossypium raimondii,resulting in a large chromosome number(2n=130).After three WGDs,okra has undergone extensive genomic deletions and retained substantial numbers of genes related to secondary metabolite biosynthesis and environmental adaptation,resulting in significant differences between okra and G.raimondii in the gene families related to cellulose synthesis.Combining transcriptomic and metabolomic analysis,we revealed the relationship between gene expression and metabolite content change across different okra developmental stages.Furthermore,the sinapic acid/S-lignin biosynthesis-related gene families have experienced remarkable expansion in okra,and the expression of key enzymes involved in the sinapic acid/S-lignin biosynthesis pathway vary greatly across developmental periods,which partially explains the differences in metabolite content across the different stages.Our study gains insights into the comprehensive evolutionary history of Malvaceae species and the genetic basis that underlies the nutrient content changes in okra,which will facilitate the functional study and genetic improvement of okra varieties.

Realization of homogeneous dielectric barrier discharge in atmospheric pressure argon and the effect of beads on its characteristics

This paper describes the realization of a homogeneous dielectric barrier discharge(DBD)in argon at atmospheric pressure.The effect of the morphology of the dielectric surface(especially the dielectric surface covered by hollow ceramic beads(99%Al_(2)O_(3))with different diameters)on discharge is investigated.With different dielectrics,the argon DBD presents two discharge modes:a filamentary mode and a homogeneous mode.Fast photography shows that the filamentary mode operates in a streamer discharge,and the homogeneous mode operates in a Townsend discharge regime.It is found that a homogeneous discharge can be generated within a certain voltage range.The voltage amplitude range decreases,and the breakdown voltage increases with the increase in the mean diameter of the ceramic beads.Waveforms of the total current and optical emission signal present stochastic pulses per half voltage cycle for the filamentary mode,whereas there is one single hump per half voltage cycle for the homogeneous mode.In the homogeneous mode,the intensity of the optical emission decreases with the mean diameter of the ceramic beads.The optical emission spectrum is mainly composed of atomic lines of argon and the second positive system of molecular nitrogen.It reveals that the electron density decreases with the increasing mean diameter of the ceramic beads.The vibrational temperature increases with the increasing mean diameter of the ceramic beads.It is believed that a large number of microdischarges are formed,and smaller ceramic beads have a larger activation surface area and more point discharge.Electrons liberated in the shallow well and electrons generated from microdischarges can increase the secondary electron emission coefficient of the cathode and provide initial electrons for discharge continuously.Therefore,the breakdown electric field is reduced,which contributes to easier generation of homogeneous discharge.This is confirmed by the simulation results.

Comparative transcriptome analysis provides insights into the molecular mechanism of the anti-nematode role of Arachis hypogaea(Fabales:Fabaceae)against Meloidogyne incognita(Tylenchida:Heteroderidae)

Background:Plant root-knot nematode(RKN)disease is a serious threat to agricultural production across the world.Meloidogyne incognita is the most prominent pathogen to the vegetables and cash crops cultivated.Arachis hypogaea can effectively inhibit M.incognita,but the underlying defense mechanism is still unclear.Methods:In our study,the chemotaxis and infestation of the second-stage juveniles(J2s)of M.incognita to A.hypogaea root tips were observed by the Pluronic F-127 system and stained with sodium hypochlorite acid fuchsin,respectively.The transcriptome data of A.hypogaea roots with non-infected or infected by J2s were analyzed.Results:The J2s could approach and infect inside of A.hypogaea root tips,and the chemotactic migration rate and infestation rate were 20.72%and 22.50%,respectively.Differential gene expression and pathway enrichment analyses revealed ubiquinone and other terpenoid-quinone biosynthesis pathway,plant hormone signal transduction pathway,and phenylpropanoid biosynthesis pathway in A.hypogaea roots responded to the infestation of M.incognita.Furthermore,the AhHPT gene,encoding homogentisate phytyltransferase,was considered to be an ideal candidate gene due to its higher expression based on the transcriptome data and quantitative real-time PCR analysis.Conclusion:Therefore,the key gene AhHPT might be involved in the A.hypogaea against M.incognita.These findings lay a foundation for revealing the molecular mechanism of A.hypogaea resistance to M.incognita and also provide a prerequisite for further gene function verification,aiming at RKN-resistant molecular breeding.

Efficient Improvement of Nutritional Content in Rice Grains by Precise Base Editing of OsROS1

Aleurone forms the outermost layer of the rice endosperm and plays a critical role in apoplastic nutrient uptake during endosperm development.Thickening the aleurone layer has been proposed to significantly increase the nutrient content of rice grains.In this study,we used a CRISPR/Cas9-mediated precise base editing method to target OsROS1,a gene associated with aleurone thickness,in the background of the japonica glutinous rice cultivar Zhennuo 19。

Comparative genomics of widespread and narrow-range white-bellied rats in the Niviventer niviventer species complex sheds light on invasive rodent success

Widespread species that inhabit diverse environments possess large population sizes and exhibit a high capacity for environmental adaptation,thus enabling range expansion.In contrast,narrow-range species are confined to restricted geographical areas and are ecologically adapted to narrow environmental conditions,thus limiting their ability to expand into novel environments.However,the genomic mechanisms underlying the differentiation between closely related species with varying distribution ranges remain poorly understood.The Niviventer niviventer species complex(NNSC),consisting of highly abundant wild rats in Southeast Asia and China,offers an excellent opportunity to investigate these questions due to the presence of both widespread and narrow-range species that are phylogenetically closely related.In the present study,we combined ecological niche modeling with phylogenetic analysis,which suggested that sister species cannot be both widespread and dominant within the same geographical region.Moreover,by assessing heterozygosity,linkage disequilibrium decay,and Tajima's D analysis,we found that widespread species exhibited higher genetic diversity than narrow-range species.In addition,by exploring the“genomic islands of speciation”,we identified 13 genes in highly divergent regions that were shared by the two widespread species,distinguishing them from their narrow-range counterparts.Functional annotation analysis indicated that these genes are involved in nervous system development and regulation.The adaptive evolution of these genes likely played an important role in the speciation of these widespread species.

Pediatric GNAO1 encephalopathies:from molecular etiology of the disease to drug discovery

Gao is the major G protein in neurons,where it transduces signals from numerous G proteincoupled receptors(GPCRs)such as D2 dopamine,μ-opioid,M2 muscarinic,or α2-adrenergic receptors.In 2013,the first mutations in GNAO1,the gene encoding Gao,were described in pediatric patients with encephalopathies(Nakamura et al.,2013),suffering from movementdisorders,epileptic seizures。

Anticancer therapeutic strategies for targeting mutant p53-Y220C

The tumor suppressor p53 is a transcription factor with a powerful antitumor activity that is controlled by its negative regulator murine double minute 2(MDM2,also termed HDM2 in humans)through a feedback mechanism.At the same time,TP53 is the most frequently mutated gene in human cancers.Mutant p53 proteins lose wild-type p53 tumor suppression functions but acquire new oncogenic properties,among which are deregulating cell proliferation,increasing chemoresistance,disrupting tissue architecture,and promoting migration,invasion and metastasis as well as several other pro-oncogenic activities.The oncogenic p53 mutation Y220C creates an extended surface crevice in the DNA-binding domain destabilizing p53 and causing its denaturation and aggregation.This cavity accommodates stabilizing small molecules that have therapeutic values.The development of suitable small-molecule stabilizers is one of the therapeutic strategies for reactivating the Y220C mutant protein.In this review,we summarize approaches that target p53-Y220C,including reactivating this mutation with small molecules that bind Y220C to the hydrophobic pocket and developing immunotherapies as the goal for the near future,which target tumor cells that express the p53-Y220C neoantigen.

Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

Plasma DNA methylation of Wnt antagonists predicts recurrence of esophageal squamous cell carcinoma

AIM:To detect the effects of plasma DNA methylation of Wnt antagonists/inhibitors on recurrence of esophageal squamous cell carcinoma(ESCC).METHODS:We used methylation-specific polymerase chain reaction to detect hypermethylation of the promoter of four Wnt antagonists/inhibitors(SFRP-1,WIF-1,DKK-3 and RUNX3) using DNA from the plasma of ESCC patients(n = 81) and analyzed the association between promoter hypermethylation of Wnt pathway modulator genes and the two-year recurrence of ESCC.RESULTS:Hypermethylation of SFRP-1,DKK-3 and RUNX-3 was significantly associated with an increased risk of ESCC recurrence(P = 0.001,0.003 and 0.001 for SFRP-1,DKK-3 and RUNX3,respectively).Patients carrying two to three methylated genes had a significantly elevated risk of recurrence compared with those not carrying methylated genes(odds ratio = 15.69,95% confidential interval:2.97-83).The area under the receiver operating characteristic curve(AUC) was 77.1 for ESCC recurrence prediction(sensitivity = 66.67 and specificity = 83.3).When combining methylated genes and the clinical stage,the AUC was 83.69,with a sensitivity of 76.19 and a specificity of 83.3.CONCLUSION:The status of promoter hypermethylation of Wnt antagonists/inhibitors in plasma may serve as a non-invasive prognostic biomarker for ESCC.

From leaf to whole-plant water use efficiency(WUE)in complex canopies:Limitations of leaf WUE as a selection target

Plant water use efficiency(WUE) is becoming a key issue in semiarid areas, where crop production relies on the use of large volumes of water. Improving WUE is necessary for securing environmental sustainability of food production in these areas. Given that climate change predictions include increases in temperature and drought in semiarid regions,improving crop WUE is mandatory for global food production. WUE is commonly measured at the leaf level, because portable equipment for measuring leaf gas exchange rates facilitates the simultaneous measurement of photosynthesis and transpiration. However,when those measurements are compared with daily integrals or whole-plant estimates of WUE, the two sometimes do not agree. Scaling up from single-leaf to whole-plant WUE was tested in grapevines in different experiments by comparison of daily integrals of instantaneous water use efficiency [ratio between CO2assimilation(AN) and transpiration(E); AN/E] with midday AN/E measurements, showing a low correlation, being worse with increasing water stress. We sought to evaluate the importance of spatial and temporal variation in carbon and water balances at the leaf and plant levels. The leaf position(governing average light interception) in the canopy showed a marked effect on instantaneous and daily integrals of leaf WUE. Night transpiration and respiration rates were also evaluated, as well as respiration contributions to total carbon balance. Two main components were identified as filling the gap between leaf and whole plant WUE: the large effect of leaf position on daily carbon gain and water loss and the large flux of carbon losses by dark respiration. These results show that WUE evaluation among genotypes or treatments needs to be revised.

Transformation of human amniotic epithelial cells into neuron-like cells in the microenvironment of traumatic brain injury in vivo and in vitro

Survival and differentiation of transplanted cells is closely related to the local microenvironment.The present study cultured human amniotic epithelial cells（HAECs） in a simulated microenvironment in vitro comprising RPMI 1640 culture medium and the solution extracted from injured brain tissues.Some HAECs were round,triangular in form or irregularly shaped,with extended neuron-like processes;some of the processes were interconnected,representing neuron-like morphology and some HAECs were microtubule-associated protein 2-positive.HAECs survived for at least 4 weeks following transplantation into the center and edges of the trauma focus with traumatic brain injury,and were microtubule-associated protein 2-positive.Moreover,the motor function of rat hind limbs was significantly improved.

Molecular cloning, sequence analysis, and cadmium stress-rated expression changes of BTG1 in freshwater pearl mussel(Hyriopsis schlegelii)

The B cells translocation gene 1 （BTG1） is a member of the BTG/TOB family of anti-proliferative genes, which have recently emerged as important regulators of cell growth and differentiation among vertebrates. Here, for the first time we cloned the full-length eDNA sequence of Hyriopsis schlegelii （Hs-BTG1）, an economically important freshwater shellfish and potential indicator of environmental heavy metal pollution, for the first time. Using rapid amplification of eDNA ends （RACE） together with splicing the EST sequence from a haemocyte eDNA library, we found that Hs-BTG1 contains a 525 bp open reading frame （ORF） encoding a 174 amino-acid polypeptide, a 306 bp 5＇ untranslated region （5＇ UTR）, and a 571 bp 3＇ UTR with a Poly（A） tail as well as a transcription termination signal （AATAAA）. Homologne searching against GenBank revealed that Hs-BTG1 was closest to Crassostrea gigas BTG1, sharing 50.57% of protein identities. Hs-BTG1 also shares some typical features of the BTG/TOB family, possessing two well-conserved A and B boxes. Clustering analysis of Hs-BTG1 and other known BTGs showed that Hs-BTG1 was also closely related to BTG1 of C. gigas from the invertebrate BTG1 clade. Function prediction via homology modeling showed that both Hs-BTG1 and C. gigas BTG1 share a similar three-dimensional structure with Homo sapiens BTG1. Tissue-specific expression analysis of the Hs-BTG1 via real-time PCR showed that the transcripts were constitutively expressed, with the highest levels in the hepatopancreas and gills, and the lowest in both haemocyte and muscle tissue. Expression levels of Hs-BTG1 in hepatopancreas （2.03-fold）, mantle （2.07-fold）, kidney （2.2-fold） and haemocyte （2.5-fold） were enhanced by cadmium （Cd2＋） stress, suggesting that Hs-BTG 1 may have played a significant role in H, schlegelii adaptation to adverse environmental conditions.