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1.
Artigo em Inglês | MEDLINE | ID: mdl-35412198

RESUMO

Transgenic technology is now widely used in biomedical and agricultural fields. Transgenesis is commonly achieved through random integration which might cause some uncertain consequences. The site-specific integration could avoid this disadvantage. This study aimed to screen and validate the best safe harbor (SH) locus for efficient porcine transgenesis. First, the cells carrying the EGFP reporter construct at four different SH loci (ROSA26, AAVS1, H11 and COL1A1) were achieved through CRSIPR/Cas9-mediated HDR. At the COL1A1 and ROSA26 loci, a higher mRNA and protein expression of EGFP was detected, and it was correlated with a lower level of DNA methylation of the EGFP promoter, hEF1α. A decreased H3K27me3 modification of the hEF1α promoter at the COL1A1 locus was also detected. For the safety of transgenesis at different SH locus, we found that transgenesis could relatively alter the expression of the adjacent endogenous genes, but the influence was limited. We also did not observe any off-target cleavage for the selected sgRNAs of the COL1A1 and ROSA26 loci. In conclusion, the COL1A1 and ROSA26 were confirmed to be the best two SH loci with the COL1A1 being more competitive for porcine transgenesis. This work would greatly facilitate porcine genome engineering and transgenic pig production.

2.
Ecotoxicol Environ Saf ; 230: 113105, 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34954678

RESUMO

Simazine is a triazine pesticides that typically detected in ground water and soil, and can reportedly affect reproductive health in humans and animals. However, the effect of simazine on female germ cell development remains unclear. In the present study, we observed that simazine exposure decreased oocyte maturation competence and embryonic developmental capacity. Importantly, simazine exposure disrupted microtubule stability and actin polymerization, resulting in failure of spindle assembly and migration. In addition, simazine exposure impaired mitochondrial function and cytosolic Ca2+ homeostasis in both oocyte and 2-cell embryos, thus increasing the levels of reactive oxygen species (ROS). Moreover, simazine exposure induced DNA damage and early apoptosis during oocyte maturation. Collectively, our results demonstrate that simazine exposure-induced mitochondrial dysfunction and apoptosis are major causes of poor oocytes quality.

3.
Water Res ; 207: 117803, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34741900

RESUMO

Antiviral drugs are among the most common and important classes of pharmaceuticals to treat viral infections, however their continuous emission and persistence in the receiving environment has attracted increasing attention about their potential ecological risks. Here we investigated the occurrence, fate and mass load of 9 antiviral drugs for acquired immunodeficiency syndrome and hepatitis B, in 7 wastewater treatment plants (WWTPs) with different treatment processes in Guangdong, China. Totally, 8 target antiviral drugs were detected in the WWTPs influent wastewater, effluent wastewater and sludge, with maximal concentrations up to 7624 ng/L (telbivudine), 568 ng/L (telbivudine), and 2013 ng/g wet weight (telbivudine), respectively. The removal efficiency varied widely between different antiviral drugs, with the mean aqueous removal efficiency and total removal efficiency ranging from -6.2% (nevirapine) to 100% (lamivudine) and -1.2% (nevirapine) to 100% (lamivudine), respectively. Mass balance analysis showed that their elimination was mostly attributed to the biodegradation/biotransformation. The total back-estimated usage and emission of 9 target antiviral drugs were 77.8 t/y and 13.2 t/y in Guangdong province, China, respectively. Based on the sewage epidemiology approach, the consumption and emission of antiviral drugs in seven studied WWTPs were ranged at 2.31 mg/d/1000 people (nevirapine) to 4970 mg/d/1000 people (telbivudine), and 0 (lamivudine) to 900 mg/d/1000 people (telbivudine), respectively. Preliminary risk assessment showed that the antiviral drugs of zidovudine, ritonavir, lopinavir, and telbivudine in the receiving rivers could pose high ecological risks for aquatic environment. The findings from the present study illustrate the persistence of nevirapine in WWTPs, and provide essential evidence for further study into the development of wastewater treatment technologies.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Antivirais , China , Monitoramento Ambiental , Humanos , Esgotos/análise , Eliminação de Resíduos Líquidos , Águas Residuárias/análise , Poluentes Químicos da Água/análise
4.
Materials (Basel) ; 14(20)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34683657

RESUMO

The deformation behavior of rolled Mg alloy AZ31, previously compressed along the rolling direction (RD), was numerically investigated under reverse tension. The EVPSC-TDT model was employed to study the effect of pre-strain on detwinning for 3%, 6% and 9% pre-compressed materials along the RD. A new criterion was proposed to control the exhaustion of detwinning under reverse tension. Numerical results show good agreement with the corresponding experimental data. It was demonstrated that the proposed criteria can capture the key features associated with detwinning in pre-compressed materials. Regardless of the amount of pre-compression, detwinning is activated under reverse tension, leading to low yield stress and a typical s-shaped flow curve. The inflection point reflects the exhaustion of detwinning, which is delayed when increasing the amount of pre-compression.

5.
ACS Omega ; 6(35): 22468-22477, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34514219

RESUMO

Due to serious global warming and environmental issues, the demand for clean and sustainable energy storage devices is significantly increased. Often accompanied by rapid growth of portable electronic vehicles and devices, massive electromagnetic wave pollution becomes unavoidable. To mitigate the above two issues, this mini-review summaries preparation methods and recent developments of MXene/polyaniline-based composites for their applications in electrochemical devices and electromagnetic interference shielding. Based on excellent synergistic effects between single compounds and designed hierarchical structures, MXene/polyaniline-based composites usually exhibit enhanced physical and chemical properties, showing great potentials in sustainable electrochemical properties and electromagnetic wave protections for human health as well as normal operation of precise electronic devices.

6.
Inorg Chem ; 60(15): 11032-11037, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34250806

RESUMO

A highly electronegative carboxyl-decorated anionic metal-organic framework (MOF), (Me2NH2)2[In2(THBA)2](CH3CN)9(H2O)21 (InOF; H4THBA = [1,1':4',1″-terphenyl]-2',3,3″,5,5',5″-hexacarboxylic acid), with high-density electronegative functional sites was designed and constructed. One unit cell of InOF possesses 12 negative sites that originate from the negatively charged secondary building unit [In(COO)4]- and exposed carboxyl groups on the ligand. The abundant electronegative sites can facilitate the hopping of ions in channels and thus result in highly efficient ion conductivities for various metal ions. Our results show that Li+-loaded materials have a remarkably high ion conductivity of 1.49 × 10-3 S/cm, an ion transference number of 0.78, and a relatively low activation energy of 0.19 eV. The Na+, K+, and Zn2+ ion conductivities of InOF are 7.97 × 10-4, 7.69 × 10-4, and 1.22 × 10-3 S/cm at 25 °C, respectively.

7.
Anim Biotechnol ; : 1-8, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34289783

RESUMO

This study compared and analyzed the genetic diversity and population structure of exon 2 of the DQB1 gene and 13 autosomal neutral microsatellite markers from 14 Chinese goat breeds to explore the potential evolutionary mechanism of the major histocompatibility complex (MHC). A total of 287 haplotypes were constructed from MHC-DQB1 exon 2 from 14 populations, and 82 nucleotide polymorphic sites (SNPs, 31.78%) and 172 heterozygous individuals (79.12%) were identified. The FST values of the microsatellites and MHC-DQB ranged between 0.01831-0.26907 and 0.00892-0.38871, respectively. Furthermore, 14 goat populations showed rich genetic diversity in the microsatellite loci and MHC-DQB1 exon 2. However, the population structure and phylogenetic relationship represented by the two markers were different. Positive selection and Tajima's D test results showed the occurrence of a diversified selection mechanism, which was primarily based on a positive and balancing selection in goat DQB. This study also found that the DQB sequences of bovines exhibited trans-species polymorphism (TSP) among species and families. In brief, this study indicated that positive and balancing selection played a major role in maintaining the genetic diversity of DQB, and TSP of MHC in bovines was common, which enhanced the understanding of the MHC evolution.

8.
Front Cell Dev Biol ; 9: 708980, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34295902

RESUMO

Hexestrol (HES) is a synthetic non-steroidal estrogen that was widely used illegally to boost the growth rate in livestock production and aquaculture. HES can also be transferred to humans from treated animals and the environment. HES has been shown to have an adverse effect on ovarian function and oogenesis, but the potential mechanism has not been clearly defined. To understand the potential mechanisms regarding how HES affect female ovarian function, we assessed oocyte quality by examining the critical events during oocyte maturation. We found that HES has an adverse effect on oocyte quality, indicated by the decreased capacity of oocyte maturation and early embryo development competency. Specifically, HES-exposed oocytes exhibited aberrant microtubule nucleation and spindle assembly, resulting in meiotic arrest. In addition, HES exposure disrupted mitochondrial distribution and the balance of mitochondrial fission and fusion, leading to aberrant mitochondrial membrane potential and accumulation of reactive oxygen species. Lastly, we found that HES exposure can increase cytosolic Ca2+ levels and induce DNA damage and early apoptosis. In summary, these results demonstrate that mitochondrial dysfunction and perturbation of normal mitochondrial fission and fusion dynamics could be major causes of reduced oocyte quality after HES exposure.

9.
World J Clin Cases ; 9(13): 3090-3094, 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33969095

RESUMO

BACKGROUND: Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare subtype of DEB, characterized by recurrent pruritus of the extremities, pruritus papules, nodules, and mossy-like plaques. To date, fewer than 100 cases have been reported. We report a misdiagnosed 30-year-old man with sporadic late-onset DEB-Pr who responded well to tacrolimus treatment, thereby serving as a guide to correct diagnosis and treatment. CASE SUMMARY: A 30-year-old man presented with recurrent itching plaques of 1-year duration in the left tibia that aggravated and involved both legs and the back. Examination revealed multiple symmetrical, purple, and hyperpigmented papules and nodules with surface exfoliation involving the tibia and dorsum of the neck with negative Nissl's sign, no abnormalities in the skin, mucosa, hair, or fingernail, and no local lymph node enlargement. Blisters were never reported prior to presentation. Serum immunoglobulin E level was 636 IU/mL. Clinical manifestations suggested DEB-Pr. Histological examination showed subepidermal fissure, scar tissue, and milia. Direct immunofluorescence showed no obvious abnormalities. However, we were unable to perform electron microscopy or genetic research following his choice. We treated him with topical tacrolimus. After 2 wk, the itching alleviated, and the skin lesions began to subside. No adverse reactions were observed during treatment. CONCLUSION: Topical tacrolimus is a safe treatment option for patients with DEB-Pr and can achieve continuous relief of severe itching.

11.
Front Med (Lausanne) ; 8: 693915, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35572804

RESUMO

Background: Accurate identification of molecular transmission clusters (MTCs) and understanding the dynamics of human immunodeficiency virus (HIV) transmission are necessary to develop targeted interventions to prevent HIV transmission. We evaluated the characteristics of antiretroviral therapy-naïve individuals who belonged to HIV-1 MTCs in the China-Myanmar border region to inform targeted effective HIV intervention. Methods: Phylogenetic analyses were undertaken on HIV-1 pol sequences to characterize subtypes or circulating recombinant forms and identify MTCs. MTCs were defined as those with 2 or more sequences having bootstrap support > 80% and a pairwise gene distance less than or equal to 0.03. Factors correlated with MTCs were evaluated using logistic regression analysis. The chi-square test was used to compare differences between Chinese and Burmese participants belonging to MTCs. Results: A total of 900 people had their pol gene successfully sequenced. Twenty-one MTCs were identified and included 110 individuals (12.2%). Individuals in MTCs were more likely to be Burmese [aOR = 2.24 (95% CI: 1.33, 3.79), P = 0.003], be younger [aOR = 0.34 (95% CI: 0.20, 0.58), P < 0.001 for age 26-50 vs. 25 years or younger], have a lower CD4 T cell count [aOR = 2.86 (95% CI: 1.34, 6.11), P = 0.007 for < 200 vs. 350 or greater], and have subtypes CRF07_BC or C [CRF07_BC: aOR = 7.88 (95% CI: 3.55, 17.52), P < 0.001; C: aOR = 2.38 (95% CI: 1.23, 4.62), P = 0.010 compared to CRF01_AE]. In MTCs, Burmese were younger (89.7 vs. 57.7% for age 25 years or younger), had a lower education level (41.0 vs. 8.5% for illiterate), were more likely to be infected through injection drug use (35.9 vs. 12.7%), and had a higher proportion of subtype BC (33.3 vs. 15.5%) and CRF01_AE (20.5 vs. 8.5%) compared to Chinese (P < 0.05 for all). Conclusion: Burmese participants were more likely to belong to MTCs, and most MTCs had both Burmese and Chinese participants. These data highlight the bidirectional transmission of HIV-1 frequently transmission and close relationship among immigrants in the China-Myanmar border region. Local health departments should pay more attention to HIV screening and intervention to immigrants Burmese with the characteristics of younger age, having lower CD4 T cell count and infected with HIV subtypes CRF07_ BC or C.

12.
Medicine (Baltimore) ; 99(49): e23452, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33285741

RESUMO

RATIONALE: Appendiceal intussusception is a rare disease. The definite preoperative diagnosis of appendiceal intussusception is rare and challenging. Here, we present a case of McSwain type V appendiceal intussusception in a 10-year-old boy. To our best knowledge, this is the first case report of a type V appendiceal intussusception that was preoperatively confirmed with sonography. Here, we have described in detail the ultrasound features and differential diagnosis of this rare disease. PATIENT CONCERNS: A 10-year-old boy presented with 3 days of recurrent intermittent mild abdominal pain. The result of ultrasonography suggested an ileocolic intussusception and a therapeutic air-contrast enema was requested to reduce the intussusception but failed at a local hospital. DIAGNOSES: Physical exam revealed mild tenderness in the lower right quadrant of the abdomen. However, ultrasonography showed a target-sign in cross section and a finger-like appearance in the longitudinal view. A diagnosis of McSwain type V appendiceal intussusception was made. INTERVENTIONS: The patient underwent an appendectomy after successful manual reduction on laparotomy. The appendix was successfully resected. OUTCOMES: Intraoperatively, the appendix was completely inverted in the cecum, and the preoperative sonographic findings were confirmed. During follow-up, there were no signs of recurrence. LESSONS: Pre-operatively, on ultrasound a type V appendiceal intussusception is usually misdiagnosed as an ileocolic intussusception. Radiologists must execute caution to avoid over reliance on the sonographic findings of intussusception, especially when there is a mismatch with clinical symptoms. It is especially important to accurately understand the surgical-anatomic configuration of type V appendiceal intussusception that creates a "target-sign" and a "finger-like" layout on ultrasonography.


Assuntos
Doenças do Ceco/diagnóstico , Intussuscepção/diagnóstico , Apendicectomia , Doenças do Ceco/diagnóstico por imagem , Doenças do Ceco/cirurgia , Criança , Humanos , Intussuscepção/diagnóstico por imagem , Intussuscepção/cirurgia , Masculino , Ultrassonografia
13.
Curr Biol ; 30(24): 4837-4845.e5, 2020 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-33035486

RESUMO

Progress has been made in developing the maternally inherited endosymbiotic bacterium Wolbachia as a tool for protecting humans from mosquito-borne diseases. In contrast, Wolbachia-based approaches have not yet been developed for the protection of plants from insect pests and their associated diseases, with a major challenge being the establishment of artificial Wolbachia infections expressing desired characteristics in the hemipterans that transmit the majority of plant viruses. Here, we report stable introduction of Wolbachia into the brown planthopper, Nilaparvata lugens, the most destructive rice pest that annually destroys millions of hectares of staple crops. The Wolbachia strain wStri from the small brown planthopper, Laodelphax striatellus, was transferred to this new host, where it showed high levels of cytoplasmic incompatibility, enabling rapid invasion of laboratory populations. Furthermore, wStri inhibited infection and transmission of Rice ragged stunt virus and mitigated virus-induced symptoms in rice plants, opening up the development of Wolbachia-based strategies against major agricultural pests and their transmitted pathogens. VIDEO ABSTRACT.


Assuntos
Proteção de Cultivos/métodos , Hemípteros/microbiologia , Insetos Vetores/microbiologia , Oryza/virologia , Wolbachia/patogenicidade , Animais , Estudos de Viabilidade , Hemípteros/virologia , Oryza/parasitologia , Doenças das Plantas/prevenção & controle , Doenças das Plantas/virologia , Reoviridae/patogenicidade
14.
Int J Infect Dis ; 101: 131-137, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32987184

RESUMO

BACKGROUND: Recent infection testing algorithms (RITAs) incorporating clinical information with the HIV recency assay have been proven to accurately classify recent infection. However, little evidence exists on whether RITAs would help in precisely identifying major drivers of the ongoing HIV epidemic. METHODS: HIV recency test results and clinical information were collected from 1152 newly diagnosed HIV cases between 2015 and 2017 in Dehong prefecture of Yunnan province, and the efficacy of four different RITAs in identifying risk factors for new HIV infection was compared. RESULTS: RITA 1 uses the recency test only. RITA 2 and RITA 3 combine the recency test with CD4+ T cell count and viral load (VL), respectively. RITA 4 combines both CD4+ T cell count and VL. All RITAs identified the MSM group and young people between 15 and 24 years as risk factors for incident HIV infection. RITA 3 and RITA 4 further identified the Dai ethnic minority as a risk factor, which had not been identified before when only the HIV recency test was used. CONCLUSIONS: By comparing different RITAs, we determined that greater accuracy in classifying recent HIV infection could help elucidate major drivers impacting the ongoing epidemic and thus inform targeted interventions.


Assuntos
Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Programas de Rastreamento/métodos , Adolescente , Adulto , Algoritmos , China/epidemiologia , China/etnologia , Feminino , Infecções por HIV/etnologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina/estatística & dados numéricos , Humanos , Masculino , Programas de Rastreamento/instrumentação , Pessoa de Meia-Idade , Grupos Minoritários , Testes Sorológicos , Adulto Jovem
15.
Microbiome ; 8(1): 104, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32616041

RESUMO

BACKGROUND: Host-associated microbial communities play an important role in the fitness of insect hosts. However, the factors shaping microbial communities in wild populations, including genetic background, ecological factors, and interactions among microbial species, remain largely unknown. RESULTS: Here, we surveyed microbial communities of the small brown planthopper (SBPH, Laodelphax striatellus) across 17 geographical populations in China and Japan by using 16S rRNA amplicon sequencing. Using structural equation models (SEM) and Mantel analyses, we show that variation in microbial community structure is likely associated with longitude, annual mean precipitation (Bio12), and mitochondrial DNA variation. However, a Wolbachia infection, which is spreading to northern populations of SBPH, seems to have a relatively greater role than abiotic factors in shaping microbial community structure, leading to sharp decreases in bacterial taxon diversity and abundance in host-associated microbial communities. Comparative RNA-Seq analyses between Wolbachia-infected and -uninfected strains indicate that the Wolbachia do not seem to alter the immune reaction of SBPH, although Wolbachia affected expression of metabolism genes. CONCLUSION: Together, our results identify potential factors and interactions among different microbial species in the microbial communities of SBPH, which can have effects on insect physiology, ecology, and evolution. Video Abstract.


Assuntos
Hemípteros/microbiologia , Microbiota , Wolbachia/fisiologia , Animais , China , Japão , Microbiota/genética , RNA Ribossômico 16S/genética , Wolbachia/genética
16.
J Genet ; 992020.
Artigo em Inglês | MEDLINE | ID: mdl-32661207

RESUMO

Droughtmaster is a tropical breed of beef cattle that can survive in hot climates and easily adapt to torrid environments. These traits are important in livestock breeding. In this study, we genotyped five single-nucleotide polymorphisms (SNPs) of the AHSA2 gene from 190 cattle belonging to three different breeds (Droughtmaster, Angus and Simmental) by using snapshot technology. This work aimed to identify the valuable molecular marker of heat resistance in cattle. Results showed that Droughtmaster exhibited higher expected heterozygosity and polymorphic information content compared with the two other breeds. The AHSA2-1 locus deviated from the Hardy-Weinberg equilibrium in the Droughtmaster breed (P < 0.05). Two SNPs in Droughtmaster diverged significantly from Angus and Simmental. The SNPs were identified as AHSA2-3 and AHSA2-4, which were closely linked to the three breeds based on pair-wise FST. AHSA2-4 involved a missense mutation. In summary, the GG genotypes in AHSA2-3 and AHSA2-4 may be candidate genotypes associated with heat resistance traits and may serve as valuable genetic markers for breeding of heat-tolerant beef cattle in the future.


Assuntos
Marcadores Genéticos , Técnicas de Genotipagem/métodos , Chaperonas Moleculares/genética , Polimorfismo de Nucleotídeo Único , Seleção Genética , Animais , Cruzamento , Bovinos , Genótipo , Fenótipo , Característica Quantitativa Herdável
17.
Sci Adv ; 6(14): eaaz5004, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32284983

RESUMO

Patterned cell divisions require a precisely oriented spindle that segregates chromosomes and determines the cytokinetic plane. In this study, we investigated how the meiotic spindle orients through an obligatory rotation during meiotic division in mouse oocytes. We show that spindle rotation occurs at the completion of chromosome segregation, whereby the separated chromosome clusters each define a cortical actomyosin domain that produces cytoplasmic streaming, resulting in hydrodynamic forces on the spindle. These forces are initially balanced but become unbalanced to drive spindle rotation. This force imbalance is associated with spontaneous symmetry breaking in the distribution of the Arp2/3 complex and myosin-II on the cortex, brought about by feedback loops comprising Ran guanosine triphosphatase signaling, Arp2/3 complex activity, and myosin-II contractility. The torque produced by the unbalanced hydrodynamic forces, coupled with a pivot point at the spindle midzone cortical contract, constitutes a unique mechanical system for meiotic spindle rotation.


Assuntos
Hidrodinâmica , Meiose , Oócitos/fisiologia , Fuso Acromático/metabolismo , Actinas/metabolismo , Algoritmos , Anáfase , Animais , Divisão Celular , Cromossomos , Masculino , Camundongos , Modelos Biológicos , Miosina Tipo II/metabolismo , Espermatozoides/fisiologia
18.
Int J Clin Pharmacol Ther ; 58(4): 195-197, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32068532

RESUMO

OBJECTIVE: This study aims to evaluate the clinical efficacy of ketotifen fumarate and budesonide administered as nasal sprays to treat allergic rhinitis. MATERIALS AND METHODS: A total of 96 allergic rhinitis patients, who were admitted to our hospital in recent years, were selected as research subjectes. All patients were treated with ketotifen fumarate and budesonide administered as nasal sprays. Clinical efficacy was evaluated after treatment. RESULTS: After treatment, the symptoms of nasal obstruction, nasal itching, sneezing, and runny nose significantly improved, and the score of these symptoms was significantly lower when compared to that before treatment (p < 0.05). After treatment, the eosinophils and IgE in peripheral blood of patients obviously reduced (p < 0.05). CONCLUSION: Combination treatment of allergic rhinitis using ketotifen fumarate and budesonide administered as nasal sprays has a good clinical effect in treating allergic rhinitis, which is of great significance to improve the clinical symptoms and immune function of patients. Ketotifen fumarate and budesonide have good therapeutic effects on allergic rhinitis. The combination of these two drugs can rapidly relieve allergic symptoms.


Assuntos
Budesonida/uso terapêutico , Cetotifeno/uso terapêutico , Sprays Nasais , Rinite Alérgica/tratamento farmacológico , Administração Intranasal , Humanos , Resultado do Tratamento
19.
Neuroscience ; 429: 203-212, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31962145

RESUMO

Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) have been implicated in the trafficking of postsynaptic glutamate receptors, including N-methyl-d-aspartate (NMDA)-subtype glutamate receptors (NMDARs) that are critical for nociceptive plasticity and behavioral sensitization. However, the components of SNAREs complex involved in spinal nociceptive processing remain largely unknown. Here we found that SNAP25, syntaxin4, VAMP2 and Munc18-1 were localized at postsynaptic sites and formed the complex in the superficial lamina of spinal cord dorsal horn of rats. The complex formation between these SNAREs components were accelerated after intraplantar injection of complete Freund's adjuvant (CFA), pharmacological removal of GABAergic inhibition or activation of NMDAR in intact rats. The increased SNAP25/syntaxin4/VAMP2/Munc18-1 interaction facilitated the surface delivery and synaptic accumulation of NMDAR during inflammatory pain. Disruption of the molecular interaction between SNAP25 with its SNARE partners by using a blocking peptide derived from the C-terminus of SNAP25 effectively repressed the surface and synaptic accumulation of GluN2B-containing NMDARs in CFA-injected rats. This peptide also alleviated inflammatory mechanical allodynia and thermal hypersensitivity. These data suggested that SNAREs complex assembly in spinal cord dorsal horn was involved in the inflammatory pain hypersensitivity through promoting NMDAR synaptic trafficking.


Assuntos
Corno Dorsal da Medula Espinal , Proteína 2 Associada à Membrana da Vesícula , Animais , Adjuvante de Freund/toxicidade , Hiperalgesia , Dor , Células do Corno Posterior , Ratos , Receptores de N-Metil-D-Aspartato , Medula Espinal
20.
Nat Commun ; 11(1): 277, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31937754

RESUMO

Migration of meiosis-I (MI) spindle from the cell center to a sub-cortical location is a critical step for mouse oocytes to undergo asymmetric meiotic cell division. In this study, we investigate the mechanism by which formin-2 (FMN2) orchestrates the initial movement of MI spindle. By defining protein domains responsible for targeting FMN2, we show that spindle-periphery localized FMN2 is required for spindle migration. The spindle-peripheral FMN2 nucleates short actin bundles from vesicles derived likely from the endoplasmic reticulum (ER) and concentrated in a layer outside the spindle. This layer is in turn surrounded by mitochondria. A model based on polymerizing actin filaments pushing against mitochondria, thus generating a counter force on the spindle, demonstrated an inherent ability of this system to break symmetry and evolve directional spindle motion. The model is further supported through experiments involving spatially biasing actin nucleation via optogenetics and disruption of mitochondrial distribution and dynamics.


Assuntos
Actinas/metabolismo , Meiose , Oócitos/citologia , Organelas/metabolismo , Fuso Acromático/metabolismo , Animais , Divisão Celular Assimétrica , Vesículas Citoplasmáticas/metabolismo , Retículo Endoplasmático/metabolismo , Feminino , Forminas/química , Forminas/genética , Forminas/metabolismo , Camundongos , Mitocôndrias/metabolismo , Modelos Biológicos , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Oócitos/metabolismo , Domínios Proteicos , Deleção de Sequência
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