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High temperatures interfere with meiotic recombination and the subsequent progression of meiosis in plants, but few genes involved in meiotic thermotolerance have been characterized. Here, we characterize a maize (Zea mays) classic dominant male-sterile mutant Ms42, which has defects in pairing and synapsis of homologous chromosomes and DNA double-strand break (DSB) repair. Ms42 encodes a member of the heat shock protein family, HSP101, which accumulates in pollen mother cells. Analysis of the dominant Ms42 mutant and hsp101 null mutants reveals that HSP101 functions in RADIATION SENSITIVE 51 loading, DSB repair, and subsequent meiosis. Consistent with these functions, overexpression of Hsp101 in anthers results in robust microspores with enhanced heat tolerance. These results demonstrate that HSP101 mediates thermotolerance during microsporogenesis, shedding light on the genetic basis underlying the adaptation of male meiocytes to high temperatures.
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Termotolerância , Zea mays , Pareamento Cromossômico , DNA/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Meiose/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Termotolerância/genética , Zea mays/genética , Zea mays/metabolismoRESUMO
In mammals, the most remarkable T cell variations with aging are the shrinking of the naïve T cell pool and the enlargement of the memory T cell pool, which are partially caused by thymic involution. However, the mechanism underlying the relationship between T-cell changes and aging remains unclear. In this study, we find that T-cell-specific Rip1 KO mice show similar age-related T cell changes and exhibit signs of accelerated aging-like phenotypes, including inflammation, multiple age-related diseases, and a shorter lifespan. Mechanistically, Rip1-deficient T cells undergo excessive apoptosis and promote chronic inflammation. Consistent with this, blocking apoptosis by co-deletion of Fadd in Rip1-deficient T cells significantly rescues lymphopenia, the imbalance between naïve and memory T cells, and aging-like phenotypes, and prolongs life span in T-cell-specific Rip1 KO mice. These results suggest that the reduction and hyperactivation of T cells can have a significant impact on organismal health and lifespan, underscoring the importance of maintaining T cell homeostasis for healthy aging and prevention or treatment of age-related diseases.
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Senilidade Prematura , Linfócitos T , Animais , Camundongos , Envelhecimento/genética , Senilidade Prematura/genética , Apoptose , Inflamação , MamíferosRESUMO
Neuropathic pain (NPP) is a refractory pain syndrome, caused by damage or disease of the somatosensory nervous system and characterized by spontaneous pain, hyperalgesia, abnormal pain and sensory abnormality. Non-coding RNAs (ncRNAs), including microRNA (miRNA), long non-coding RNA (lncRNA), circular RNA (circRNA) and Piwi interacting RNA (piRNA), play a notable role in initiation and maintenance of NPP. In this review, we summarize the role of ncRNAs in NPP and their underlaying mechanism. Generally, ncRNAs are interacted with mRNA, protein or DNA to regulate the molecules and signals assciated with neuroinflammation, ion channels, neurotrophic factors and others, and then involved in the occurrence and development of NPP. Therefore, this review not only contributes to deepen our understanding of the pathophysiological mechanism of NPP, but also provides theoretical basis for the development of new therapy strategies for this disorder.
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Recently, the increasing demand for data-centric applications is driving the elimination of image sensing, memory and computing unit interface, thus promising for latency- and energy-strict applications. Although dedicated electronic hardware has inspired the development of in-memory computing and in-sensor computing, folding the entire signal chain into one device remains challenging. Here an in-memory sensing and computing architecture is demonstrated using ferroelectric-defined reconfigurable two-dimensional photodiode arrays. High-level cognitive computing is realized based on the multiplications of light power and photoresponsivity through the photocurrent generation process and Kirchhoff's law. The weight is stored and programmed locally by the ferroelectric domains, enabling 51 (>5 bit) distinguishable weight states with linear, symmetric and reversible manipulation characteristics. Image recognition can be performed without any external memory and computing units. The three-in-one paradigm, integrating high-level computing, weight memorization and high-performance sensing, paves the way for a computing architecture with low energy consumption, low latency and reduced hardware overhead.
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Highly enantioselective Rh-catalyzed allylic substitution of the racemic branched allylic substrates with 2-fluoromalonate was realized enabled by a novel chiral sulfoxide-imine-olefin ligand under mild reaction conditions. The utilization of CuSO4 is beneficial for improving the enantioselectivity. Notably, the chiral fluoro-containing allyl products can be employed in a selective cyclic esterification to form chiral α-fluorolactone bearing vicinal stereogenic centers.
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Although the risk of autism spectrum disorder (ASD) has been reported to be associated with interpregnancy intervals (IPIs), their association remains debatable due to inconsistent findings in existing studies. Therefore, the present study aimed to explore their association. PubMed, Embase, Web of Science, and the Cochrane Library were systematically retrieved up to May 25, 2022. An updated search was performed on May 25, 2023, to encompass recent studies. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). Our primary outcome measures were expressed as adjusted odds ratios (ORs). Given various control measures for IPI and diverse IPI thresholds in the included studies, a Bayesian network meta-analysis was performed. Eight studies were included, involving 24,865 children with ASD and 2,890,289 children without ASD. Compared to an IPI of 24 to 35 months, various IPIs were significantly associated with a higher risk of ASD (IPIs < 6 months: OR = 1.63, 95% CI 1.53-1.74, n = 5; IPIs of 6-11 months: OR = 1.50, 95% CI 1.42-1.59, n = 4; IPIs of 12-23 months: OR = 1.19, 95% CI 1.12-1.23, n = 10; IPIs of 36-59 months: OR = 0.96, 95% CI 0.94-0.99, n = 2; IPIs of 60-119 months: OR = 1.15, 95% CI 1.10-1.20, n = 4; IPIs > 120 months: OR = 1.57, 95% CI 1.43-1.72, n = 4). After adjusting confounding variables, our analysis delineated a U-shaped restricted cubic spline curve, underscoring that both substantially short (< 24 months) and excessively long IPIs (> 72 months) are significantly correlated with an increased risk of ASD. Conclusion: Our analysis indicates that both shorter and longer IPIs might predispose children to a higher risk of ASD. Optimal childbearing health and neurodevelopmental outcomes appear to be associated with a moderate IPI, specifically between 36 and 60 months. What is Known: ⢠An association between autism spectrum disorder (ASD) and interpregnancy intervals (IPIs) has been speculated in some reports. ⢠This association remains debatable due to inconsistent findings in available studies. What is New: ⢠Our study delineated a U-shaped restricted cubic spline curve, suggesting that both shorter and longer IPIs predispose children to a higher risk of ASD. ⢠Optimal childbearing health and neurodevelopmental outcomes appear to be associated with a moderate IPI, specifically between 36 and 60 months.
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Transtorno do Espectro Autista , Criança , Humanos , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/etiologia , Fatores de Risco , Intervalo entre Nascimentos , Teorema de Bayes , Metanálise em RedeRESUMO
A enantioselective tandem transformation, concerning asymmetric allylic decarboxylative addition and cyclization of N-nosylimines with vinylethylene carbonates (VECs), in the presence of [Rh(C2H4)2Cl]2, chiral sulfoxide-N-olefin tridentate ligand has been developed. The reaction of VECs with various substituted N-nosylimines proceeded smoothly under mild conditions, providing highly functionalized oxazolidine frameworks in good to high yields with good to excellent enantioselectivity.
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A hitherto unknown class of C4-symmetric Caryl-Cß (C3, C8, C13, C18) axially chiral porphyrins has been synthesized and the application of their iridium (Ir) complexes in catalytic asymmetric C(sp3)-H functionalization is documented. Cyclotetramerization of enantioenriched axially chiral 2-hydroxymethyl-3-naphthyl pyrroles under mild acidic conditions affords, after oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), the C4-symmetric α,α,α,α-atropenantiomer as an only isolable diastereomer. Both regioisomeric Ir(Por*)(CO)(Cl) complexes catalyze the carbene C-H insertion reaction affording the same enantiomer, albeit with slight difference in enantioselectivity. With the optimum Ir-complex 3 e, the 2-substituted arylacetic acid derivatives were generated from diazo compounds and cyclohexadiene in excellent yields and enantioselectivities.
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A sulfur dioxide (SO2) gas sensor based on the photoacoustic spectroscopy technology in a sulfur hexafluoride (SF6) gas matrix was demonstrated for SF6 decomposition components monitoring in the power system. A passive Q-switching laser diode (LD) pumped all-solid-state 266â nm deep-ultraviolet laser was exploited as the laser excitation source. The photoacoustic signal amplitude is linear related to the incident optical power, whereas, a random laser power jitter is inevitable since the immature laser manufacturing technology in UV spectral region. A compact laser power stabilization system was developed for better sensor performance by adopting a photodetector, a custom-made internal closed-loop feedback controller and a Bragg acousto-optic modulator (AOM). The out-power stability of 0.04% was achieved even though the original power stability was 0.41% for â¼ 2 hours. A differential two-resonator photoacoustic cell (PAC) was designed for weak photoacoustic signal detection. The special physical constants of SF6 buffer gas induced a high-Q factor of 85. A detection limit of 140 ppbv was obtained after the optimization, which corresponds to a normalized noise equivalent absorption coefficient of 3.2 × 10-9â cm-1WHz-1/2.
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The abnormal initiation of autophagy flux in neurons after ischemic stroke caused dysfunction of autophagy-lysosome, which not only led to autophagy flux blockage, but also resulted in autophagic death of neurons. However, the pathological mechanism of neuronal autophagy-lysosome dysfunction did not form a unified viewpoint until now. In this review, taking the autophagy lysosomal dysfunction of neurons as a starting point, we summarized the molecular mechanisms that led to neuronal autophagy lysosomal dysfunction after ischemic stroke, which would provide theoretical basis for the clinical treatment of ischemic stroke.
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Autofagia , AVC Isquêmico , Lisossomos , AVC Isquêmico/metabolismo , AVC Isquêmico/patologia , AVC Isquêmico/terapia , Humanos , Animais , Neurônios/metabolismo , Neurônios/patologia , Lisossomos/patologia , Reperfusão , Proteínas do Tecido Nervoso/metabolismoRESUMO
BACKGROUND: Macrophages are involved in the pathogenesis of pulmonary arterial hypertension (PAH). Caspase-8, an apical component of cell death pathways, is significantly upregulated in macrophages of PAH animal models. However, its role in PAH remains unclear. Caspase-8 plays a critical role in regulating inflammatory responses via inflammasome activation, cell death, and cytokine induction. This study investigated the mechanism of regulation of IL-1ß (interleukin 1ß) activation in macrophages by caspase-8. METHODS: A hypoxia + SU5416-induced PAH mouse model and monocrotaline-induced rat model of PAH were constructed and the role of caspase-8 was analyzed. RESULTS: Caspase-8 and cleaved-caspase-8 were significantly upregulated in the lung tissues of SU5416 and hypoxia-treated PAH mice and monocrotaline-treated rats. Pharmacological inhibition of caspase-8 alleviated PAH compared with wild-type mice, observed as a significant reduction in right ventricular systolic pressure, ratio of right ventricular wall to left ventricular wall plus ventricular septum, pulmonary vascular media thickness, and pulmonary vascular muscularization; caspase-8 ablated mice also showed significant remission. Mechanistically, increased proliferation of pulmonary arterial smooth muscle cellss is closely associated with activation of the NLRP3 (NOD [nucleotide oligomerization domain]-, LRR [leucine-rich repeat]-, and PYD [pyrin domain]-containing protein 3) inflammasome and the IL-1ß signaling pathway. Although caspase-8 did not affect extracellular matrix synthesis, it promoted inflammatory cell infiltration and pulmonary arterial smooth muscle cell proliferation via NLRP3/IL-1ß activation during the development stage of PAH. CONCLUSIONS: Taken together, our study suggests that macrophage-derived IL-1ß via caspase-8-dependent canonical inflammasome is required for macrophages to play a pathogenic role in pulmonary perivascular inflammation.
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Hipertensão Pulmonar , Animais , Caspase 1/metabolismo , Caspase 8/metabolismo , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/genética , Hipóxia/complicações , Inflamassomos/metabolismo , Inflamação/complicações , Interleucina-1beta/metabolismo , Macrófagos/metabolismo , Camundongos , Monocrotalina/toxicidade , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , RatosRESUMO
The ovipositor comprises the external genitalia of female insects, which plays an important role in the mating and ovipositing process of insects. However, it remains rudimentary of regional gene expression and physiological function in the ovipositor during structural development. Here, we analysed the basic structure and characteristics of the ovipositor in the migratory locust Locusta migratoria. RNA-seq analysis revealed the specialization of chitin metabolism, lipids synthesis and transport, tanning and cuticular protein genes in the ovipositor. Among them, two cuticle protein genes, LmCP8 and LmACP79, were identified, which are specifically expressed in the ovipositor. Functional analysis based on RNA interference showed that deficiency of LmCP8 affected the structural development of the ovipositor resulting in the retention of a large number of remaining unproduced oocysts in the ovary of the locusts. Our results provide a fundamental resource to investigate the structural development and physiological function of the ovipositor in L. migratoria.
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Locusta migratoria , Feminino , Animais , Locusta migratoria/genética , Proteínas de Insetos/metabolismo , Interferência de RNA , Insetos/metabolismoRESUMO
Anomaly detection has been applied in the various disease of medical practice, such as breast cancer, retinal, lung lesion, and skin disease. However, in real-world anomaly detection, there exist a large number of healthy samples, and but very few sick samples. To alleviate the problem of data imbalance in anomaly detection, this paper proposes an unsupervised learning method for deep anomaly detection based on an improved adversarial autoencoder, in which a module called chain of convolutional block (CCB) is employed instead of the conventional skip-connections used in adversarial autoencoder. Such CCB connections provide considerable advantages via direct connections, not only preserving both global and local information but also alleviating the problem of semantic disparity between the encoding features and the corresponding decoding features. The proposed method is thus able to capture the distribution of normal samples within both image space and latent vector space. By means of minimizing the reconstruction error within both spaces during training phase, higher reconstruction error during test phase is indicative of an anomaly. Our method is trained only on the healthy persons in order to learn the distribution of normal samples and can detect sick samples based on high deviation from the distribution of normality in an unsupervised way. Experimental results for multiple datasets from different fields demonstrate that the proposed method yields superior performance to state-of-the-art methods.
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Diagnóstico por Imagem , HumanosRESUMO
Insect wing consists of a double layer of epidermal cells that produce and secrete the dorsal and ventral cuticular components. It is important for the stability of epidermal cells during wing development and morphogenesis, but its specific gene expression and physiological function during this process remain unclear. In our previous work, a wing cuticle protein gene LmACP19 was identified in Locusta migratoria based on transcriptomic data. Here, we report on its roles in wing development and morphogenesis. LmACP19 encodes a chitin-binding protein belonging to RR-2 subfamily of CPR family, which is highly homologous to CP19-like proteins in other insect species. RT-qPCR analysis revealed that LmACP19 is highly expressed in wing pads of fifth-instar nymphs, and its encoded protein is located in two layers of epidermal cells but not in the cuticle. Suppression of LmACP19 by RNA interference led to abnormal wing pad and wing morphogenesis with curved, unclosed, and wrinkled phenotypes during nymph-to-nymph and nymph-to-adult transition, respectively. Furthermore, deficiency of LmACP19 affected arrangement of epidermal cells, resulting in apoptosis. Our results indicate that LmACP19 is indispensable for wing development and normal morphological structure by maintaining the stability of epidermal cells during L. migratoria molting.
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Locusta migratoria , Animais , Células Epidérmicas/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Locusta migratoria/genética , Morfogênese/genética , Ninfa/genética , Interferência de RNA , Asas de Animais/metabolismoRESUMO
The utilization of 6,6-dimethyl-3-((trimethylsilyl)oxy)cyclohex-2-en-1-one made from an unsymmetrical 4,4-dimethylcyclohexane-1,3-dione in iridium-catalyzed allylic enolization involving keto-enol isomerization is accomplished under mild conditions. The chemoselectivity, regioselectivity, and enantioselectivity are facilitated by the quaternary carbon and adjusting the reaction conditions. This method provides the substituted 2-(but-3-en-2-yl)-3-hydroxy-6,6-dimethylcyclohex-2-en-1-ones in good to high yields with high level of chemo-, regio-, and enantioselectivities. The chiral carbon-fluorine bond formation is induced by an adjacent chiral carbon center of the allylated 3-hydroxy-6,6-dimethylcyclohex-2-en-1-one, as well.
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Flúor , Irídio , Irídio/química , Estereoisomerismo , Catálise , Isomerismo , CarbonoRESUMO
BACKGROUND: The emulsifying, antioxidant and foaming properties of soy protein isolate hydrolysates (SPH) can be improved by the addition of gum arabic (GA). We investigated the effects of different hydrolysis conditions on the complexation of SPH and GA, and the effects of the complex on the properties of emulsions. RESULTS: Fluorescence spectroscopy showed that the addition of GA had a stronger effect on bromelain and pepsin hydrolysates than trypsin hydrolysate, and therefore had a higher binding constant (KA ) and a larger number of binding sites (n). The addition of GA could also improve protein solubility and emulsifying ability. The emulsions prepared with complexes, especially the complex of GA and SPH obtained by pepsin hydrolysis for 3 h, had a high absolute charge value, uniform particle size distribution, stable morphology, and good storage stability. After storage, the emulsification index (CI) of the emulsion only increased to 23.08%; its 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity was 24.37 ± 1.22% and its 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS+ ) free radical scavenging activity was largely retained. CONCLUSION: During long-term storage, pepsin-treated protein (especially protein treated for 3 h) and GA can form a stable emulsion with antioxidant properties. This work provides new ideas for the development of natural and safe emulsifiers that have antioxidant properties and can be stored long-term and used in the food industry. © 2022 Society of Chemical Industry.
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Acacia , Goma Arábica , Antioxidantes , Emulsões/química , Radicais Livres , Goma Arábica/química , Hidrólise , Pepsina A , Hidrolisados de Proteína/química , Proteínas de Soja , Água/químicaRESUMO
OBJECTIVE: To investigate the genotypic and hematological characteristics of ß-thalassemia patients and carriers from Henan Province of China. METHODS: Clinical data of the patients and carriers were collected. Results of routine blood test, hemoglobin electrophoresis and genetic testing were retrospectively analyzed. RESULTS: Of the 83 ß-thalassemia patients and carriers, there were 46 females and 37 males, and their mean age was 27.37 ± 14.71, ranging from 5 months to 83 years. A total of 13 types of ß-thalassemia alleles (86 alleles in total) were detected, with the most common three including ISV-II-654(C>T) (33.72%), CD41-42(-TTCT) (26.74%) and CD17(A>T) (18.60%). Five rare alleles, including CD8-9(+G), IVS-II-1(G>A), CD42(T>G), and start codons ATG>AGG and ATG>ACG were identified. Among these, HBB: c.128T>G(CD42T>G) was previously unreported in China. Fifteen ß-thalassemia genotypes were detected, which included 12 simple heterozygote genotypes (80 cases, 96.40%), 2 double heterozygote genotypes (2 cases, 2.40%) and 1 homozygote genotype (1 case, 1.20%). The main manifestations were mild microcytic hypochromic anemia and raised HbA2. Compared with those with a ß+/ßN genotype, carriers with a ß0/ßN genotype have lower mean corpuscular volume (MCV) and mean corpusular hemoglobin (MCH) but higher HbA2 (P<0.05). CONCLUSION: ß-thalassemia is not rare in Henan Province and its characteristics are different from those in high incidence areas, which deserves close attention. The newly discovered HBB: c.128T>G (CD42T>G) has enriched the spectrum of ß-thalassemia mutations in China. Above results will also facilitate genetic counseling and prenatal diagnosis of ß-thalassemia in Henan Province.
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Talassemia alfa , Talassemia beta , Adolescente , Adulto , Criança , China/epidemiologia , Feminino , Genótipo , Humanos , Masculino , Mutação , Gravidez , Estudos Retrospectivos , Adulto Jovem , Talassemia alfa/genética , Talassemia beta/diagnósticoRESUMO
Systems with non-Hermitian skin effects are very sensitive to the imposed boundary conditions and lattice size, and thus an important question is whether non-Hermitian skin effects can survive when deviating from the open boundary condition. To unveil the origin of boundary sensitivity, we present exact solutions for one-dimensional non-Hermitian models with generalized boundary conditions and study rigorously the interplay effect of lattice size and boundary terms. Besides the open boundary condition, we identify the existence of non-Hermitian skin effect when one of the boundary hopping terms vanishes. Apart from this critical line on the boundary parameter space, we find that the skin effect is fragile under any tiny boundary perturbation in the thermodynamic limit, although it can survive in a finite size system. Moreover, we demonstrate that the non-Hermitian Su-Schreieffer-Heeger model exhibits a new phase diagram in the boundary critical line, which is different from either open or periodical boundary case.
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Fucoidan oligosaccharides possesses diverse physicochemical and biological activities. Specific glycoside hydrolases are valuable tools for degrading polysaccharides to produce oligosaccharides. In this study, BcFucA, a novel fucosidase belonging to GH95 family from Bacillus cereus 2-8, was cloned into pET21a vector, expressed in E. coli BL21 (DE3) and characterized. The protein consists of 1136 amino acid residues encoded by 3411 bases and has a molecular weight of 125.35 kDa. The optimal temperature and pH of this enzyme are 50 °C and pH 4.0. In addition, this study showed that the unknown function domain (encoding Lys261-Thr681) defined as a linker is quite important for its activity. The obtained novel enzyme BcFucA will contribute to the effective degradation of fucoidan and future industrial applications.
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Bacillus cereus , Escherichia coli/genética , Proteínas Recombinantes de Fusão , alfa-L-Fucosidase , Bacillus cereus/enzimologia , Bacillus cereus/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Concentração de Íons de Hidrogênio , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Temperatura , alfa-L-Fucosidase/química , alfa-L-Fucosidase/genética , alfa-L-Fucosidase/metabolismoRESUMO
The small GTPase Ran is a member of the Ras superfamily of small GTP-binding proteins, which plays a key role in the translocation of RNA and proteins through the nuclear pore complex. In this study, the full-length cDNA sequence of LmRan gene was obtained, which consists of 648-nucleotides open reading frame (ORF) and encodes 215 amino acids. RT-qPCR results revealed that LmRan was expressed in all developmental days and tissues investigated. Injection of dsLmRan into 4th and 5th instar nymphs, resulted in a significant down-regulation of LmRan transcripts, respectively. All dsLmRan-injected nymphs died before molting. Further hematoxylin and eosin staining of the integument showed that there was no apolysis occurred after silencing LmRan. In addition, the weight of dsLmRan-injected nymphs was significantly lower than that of the control group, and the gastric caecum and midgut was severely smaller. Especiallly, the mRNA level of LmCYP302a1, LmCYP315a1 and LmCYP314a1 responsible for 20E synthesis, LmE75 and LmE74 genes involved in the 20E signaling pathway, LmGfat, LmUAP1 and LmCHT10 genes involved in chitin metabolism pathway were dramatically decreased in the dsLmRan-injected nymphs. Together, the results indicated that LmRan participate in the 20E signaling pathway, which is essential for the growth and development of locusts.