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1.
Insect Biochem Mol Biol ; 139: 103665, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34624466

RESUMO

The black cutworm (BCW), Agrotis ipsilon, is a worldwide polyphagous and underground pest that causes a high level of economic loss to a wide range of crops through the damage of roots. This species performs non-directed migration throughout East and Southeast Asia seasonally. Lack of a genome information has limited further studies on its unique biology and the development of novel management approaches. In this study, we present a 476 Mb de novo assembly of BCW, along with a consensus gene set of 14,801 protein-coding gene models. Quality controls show that both genome assembly and annotations are high-quality and mostly complete. We focus manual annotation and comparative genomics on gene families that related to the unique attributes of this species, such as nocturnality, long-distance migration, and host adaptation. We find that the BCW genome encodes a similar gene repertoire in various migration-related gene families to the diural migratory butterfly Danaus plexiipus, with additional copies of long wavelength opsin and two eye development-related genes. On the other hand, we find that the genomes of BCW and many other polyphagous lepidopterans encode many more gustatory receptor genes, particularly the lineage-specific expanded bitter receptor genes, than the mono- or oligo-phagous species, suggesting a common role of gustatory receptors (GRs) expansion in host range expansion. The availability of a BCW genome provides valuable resources to study the molecular mechanisms of non-directed migration in lepidopteran pests and to develop novel strategies to control migratory nocturnal pests.

2.
Insect Biochem Mol Biol ; 139: 103672, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34700022

RESUMO

The silkworm (Bombyx mori) is a domesticated and economically important insect. During the whole growth period, silkworm suffers various pathogen infection. Nearly 80% of silk cocoon crop losses are attributed to viral diseases. The circular double-stranded DNA virus Bombyx mori nuclepolyhedrovirus (BmNPV) is the major viral pathogen responsible for massive silkworm death and huge economic losses in the sericulture industry. Up to now, almost all the new strategies for developing immunity against BmNPV are in laboratory strains because of the lack of transgenic technology in industrial silkworm strains. We previously demonstrated that modification of BmNPV genome DNA with the antivirus transgenic CRISPR/Cas9 system effectively improved the resistance of laboratory silkworm strains to viral pathogens. The industrial strains are monovoltine or bivoltine. It is very difficult to break the diapause before microinjection for genetic transformation. Here, we show that the anti-BmNPV transgenic CRISPR/Cas9 system also works in the industrial silkworm strain Jingsong. In this study, we successfully broke diapause and obtained generation-skipping embryos and constructed two TG Jingsong lines. Both lines exhibited significantly enhanced immunity to BmNPV without significant changes in most of the commercially important traits. These results demonstrate that the construction of TG silkworm lines carrying a heritable immune defense system against BmNPV could be an effective strategy to enhance the resistance of industrial silkworm strains to the most devastating DNA virus. The research opened a window for genetic modification of the important strains from laboratory strains to industrial strains.

3.
Cells ; 10(9)2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34571893

RESUMO

Uric acid (UA) is the end-product in the human purine metabolism pathway. The UA that accumulates in silkworm tissues is excreted as a nitrogen waste product. Here, we first validated that Bombyx mori has a homolog of the human gene that encodes the 5'-nucleotidase (5'N) involved in purine metabolism. The B. mori gene, Bm5'N, is located upstream of other genes involved in UA metabolism in the silkworm. Disruption of Bm5'N via the CRISPR/Cas9 system resulted in decreased UA levels in the silkworm epidermis and caused a translucent skin phenotype. When Bm5'N mutant silkworms were fed with the uric acid precursor inosine, the UA levels in the epidermis increased significantly. Furthermore, the metabolomic and transcriptomic analyses of Bm5'N mutants indicated that loss of the Bm5'N affected purine metabolism and the ABC transport pathway. Taken together, these results suggest that the UA pathway is conserved between the silkworm and humans and that the Bm5'N gene plays a crucial role in the uric acid metabolism of the silkworm. Thus, the silkworm may be a suitable model for the study of UA metabolism pathways relevant to human disease.


Assuntos
5'-Nucleotidase/metabolismo , Bombyx/metabolismo , Metaboloma , Transcriptoma , Ácido Úrico/metabolismo , 5'-Nucleotidase/genética , Sequência de Aminoácidos , Animais , Bombyx/genética , Comportamento Alimentar , Humanos , Filogenia , Homologia de Sequência
4.
Cell Metab ; 33(10): 2059-2075.e10, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34536344

RESUMO

Myocardial ischemia-reperfusion (MIR) injury is a major cause of adverse outcomes of revascularization after myocardial infarction. To identify the fundamental regulator of reperfusion injury, we performed metabolomics profiling in plasma of individuals before and after revascularization and identified a marked accumulation of arachidonate 12-lipoxygenase (ALOX12)-dependent 12-HETE following revascularization. The potent induction of 12-HETE proceeded by reperfusion was conserved in post-MIR in mice, pigs, and monkeys. While genetic inhibition of Alox12 protected mouse hearts from reperfusion injury and remodeling, Alox12 overexpression exacerbated MIR injury. Remarkably, pharmacological inhibition of ALOX12 significantly reduced cardiac injury in mice, pigs, and monkeys. Unexpectedly, ALOX12 promotes cardiomyocyte injury beyond its enzymatic activity and production of 12-HETE but also by its suppression of AMPK activity via a direct interaction with its upstream kinase TAK1. Taken together, our study demonstrates that ALOX12 is a novel AMPK upstream regulator in the post-MIR heart and that it represents a conserved therapeutic target for the treatment of myocardial reperfusion injury.

5.
Zool Res ; 42(5): 637-649, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34472225

RESUMO

The insect brain is the central part of the neurosecretory system, which controls morphology, physiology, and behavior during the insect's lifecycle. Lepidoptera are holometabolous insects, and their brains develop during the larval period and metamorphosis into the adult form. As the only fully domesticated insect, the Lepidoptera silkworm Bombyx mori experienced changes in larval brain morphology and certain behaviors during the domestication process. Hormonal regulation in insects is a key factor in multiple processes. However, how juvenile hormone (JH) signals regulate brain development in Lepidoptera species, especially in the larval stage, remains elusive. We recently identified the JH receptor Methoprene tolerant 1 ( Met1) as a putative domestication gene. How artificial selection on Met1 impacts brain and behavioral domestication is another important issue addressing Darwin's theory on domestication. Here, CRISPR/Cas9-mediated knockout of Bombyx Met1 caused developmental retardation in the brain, unlike precocious pupation of the cuticle. At the whole transcriptome level, the ecdysteroid (20-hydroxyecdysone, 20E) signaling and downstream pathways were overactivated in the mutant cuticle but not in the brain. Pathways related to cell proliferation and specialization processes, such as extracellular matrix (ECM)-receptor interaction and tyrosine metabolism pathways, were suppressed in the brain. Molecular evolutionary analysis and in vitro assay identified an amino acid replacement located in a novel motif under positive selection in B. mori, which decreased transcriptional binding activity. The B. mori MET1 protein showed a changed structure and dynamic features, as well as a weakened co-expression gene network, compared with B. mandarina. Based on comparative transcriptomic analyses, we proposed a pathway downstream of JH signaling (i.e., tyrosine metabolism pathway) that likely contributed to silkworm larval brain development and domestication and highlighted the importance of the biogenic amine system in larval evolution during silkworm domestication.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Bombyx/metabolismo , Proteínas de Insetos/metabolismo , Hormônios Juvenis/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Bombyx/crescimento & desenvolvimento , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Sistemas CRISPR-Cas , Deleção de Genes , Regulação da Expressão Gênica no Desenvolvimento , Genótipo , Proteínas de Insetos/genética , Tegumento Comum/fisiologia , Larva/crescimento & desenvolvimento , Larva/metabolismo , Filogenia , Conformação Proteica
6.
Insect Biochem Mol Biol ; 138: 103638, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34428581

RESUMO

The Asian corn borer (ACB) is the most devastating pest on maize in the western Pacific region of Asia. Despite broad interests in insecticide resistance, seasonal adaptation, and larval color mimicry regarding the ACB system, lacking of reference genomic information and a powerful gene editing approach have hindered the in-depth studies of these aspects. Here we present a 455.7 Mb draft genome of ACB with 98.4% completeness. Comparative genomics analysis showed an evident expansion in gene families of gustatory receptors (105), which is related to polyphagous characteristics. Based on the comparative transcriptome analysis of resistant and susceptible ACB against Bt Cry1Ab toxin, we identified 26 genes related to Cry1Ab resistance. Additionally, transcriptomics of insects exposed to conditions of low temperature and diapause (LT) vs. room temperature and diapause (RT) provided insights into the genetic mechanisms of cold adaptation. We also successfully developed an efficient CRISPR/Cas9-based genome editing system and applied it to explore the role of color pattern genes in the ecological adaptation of ACB. Taken together, our study provides a fully annotated high-quality reference genome and efficient gene editing system to realize the potential of ACB as a study system to address important biological questions such as insecticide resistance, seasonal adaptation, and coloration. These valuable genomic resources will also benefit the development of novel strategies for maize pest management.


Assuntos
Adaptação Biológica , Genoma de Inseto , Herbivoria/genética , Mariposas/genética , Animais , Zea mays
7.
Hepatology ; 74(6): 3018-3036, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34272738

RESUMO

BACKGROUND AND AIMS: NAFLD is the most prevalent chronic liver disease worldwide, but no effective pharmacological therapeutics are available for clinical use. NASH is the more severe stage of NAFLD. During this progress, dysregulation of endoplasmic reticulum (ER)-related pathways and proteins is one of the predominant hallmarks. We aimed to reveal the role of ring finger protein 5 (RNF5), an ER-localized E3 ubiquitin-protein ligase, in NASH and to explore its underlying mechanism. APPROACH AND RESULTS: We first inspected the expression level of RNF5 and found that it was markedly decreased in livers with NASH in multiple species including humans. We then introduced adenoviruses for Rnf5 overexpression or knockdown into primary mouse hepatocytes and found that palmitic acid/oleic acid (PAOA)-induced lipid accumulation and inflammation in hepatocytes were markedly attenuated by Rnf5 overexpression but exacerbated by Rnf5 gene silencing. Hepatocyte-specific Rnf5 knockout significantly exacerbated hepatic steatosis, inflammatory response, and fibrosis in mice challenged with diet-induced NASH. Mechanistically, we identified 3-hydroxy-3-methylglutaryl CoA reductase degradation protein 1 (HRD1) as a binding partner of RNF5 by systematic interactomics analysis. RNF5 directly bound to HRD1 and promoted its lysine 48 (K48)-linked and K33-linked ubiquitination and subsequent proteasomal degradation. Furthermore, Hrd1 overexpression significantly exacerbated PAOA-induced lipid accumulation and inflammation, and short hairpin RNA-mediated Hrd1 knockdown exerted the opposite effects. Notably, Hrd1 knockdown significantly diminished PAOA-induced lipid deposition, and up-regulation of related genes resulted from Rnf5 ablation in hepatocytes. CONCLUSIONS: These data indicate that RNF5 inhibits NASH progression by targeting HRD1 in the ubiquitin-mediated proteasomal pathway. Targeting the RNF5-HRD1 axis may provide insights into the pathogenesis of NASH and pave the way for developing strategies for NASH prevention and treatment.

8.
Int J Biol Sci ; 17(9): 2205-2222, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239350

RESUMO

Purpose: This study aimed to identify the potential prognostic role of HK3 and provide clues about glycolysis and the microenvironmental characteristics of ccRCC. Methods: Based on the Cancer Genome Atlas (TCGA, n = 533) and Gene expression omnibus (GEO) (n = 127) databases, real-world (n = 377) ccRCC cohorts, and approximately 15,000 cancer samples, the prognostic value and immune implications of HK3 were identified. The functional effects of HK3 in ccRCC were analyzed in silico and in vitro. Results: The large-scale findings suggested a significantly higher HK3 expression in ccRCC tissues and the predictive efficacy of HK3 for tumor progression and a poor prognosis. Next, the subgroup survival and Cox regression analyses showed that HK3 serves as a promising and independent predictive marker for the prognosis and survival of patients with ccRCC from bioinformatic databases and real-world cohorts. Subsequently, we found that HK3 could be used to modulate glycolysis and the malignant behaviors of ccRCC cells. The comprehensive results suggested that HK3 is highly correlated with the abundance of immune cells, and specifically stimulates the infiltration of monocytes/macrophages presenting surface markers, regulates the immune checkpoint molecules PD-1 and CTLA-4 of exhaustive T cells, restrains the immune escape of tumor cells, and prompts the immune-rejection microenvironment of ccRCC. Conclusion: In conclusion, the large-scale data first revealed that HK3 could affect glycolysis, promote malignant biologic processes, and predict the aggressive progression of ccRCC. HK3 may stimulate the abundance of infiltrating monocytes/macrophages presenting surface markers and regulate the key molecular subgroups of immune checkpoint molecules of exhaustive T cells, thus inducing the microenvironmental characteristics of active anti-tumor immune responses.

9.
Hepatology ; 74(5): 2508-2525, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34231239

RESUMO

BACKGROUND AND AIMS: NAFLD is the most prevalent chronic liver disease without any Food and Drug Administration-approved pharmacological intervention in clinic. Fatty acid synthase (FASN) is one of the most attractive targets for NAFLD treatment because of its robust rate-limiting capacity to control hepatic de novo lipogenesis. However, the regulatory mechanisms of FASN in NAFLD and potential therapeutic strategies targeting FASN remain largely unknown. METHODS AND RESULTS: Through a systematic interactomics analysis of FASN-complex proteins, we screened and identified sorting nexin 8 (SNX8) as a binding partner of FASN. SNX8 directly bound to FASN and promoted FASN ubiquitination and subsequent proteasomal degradation. We further demonstrated that SNX8 mediated FASN protein degradation by recruiting the E3 ligase tripartite motif containing 28 (TRIM28) and enhancing the TRIM28-FASN interaction. Notably, Snx8 interference in hepatocytes significantly deteriorated lipid accumulation in vitro, whereas SNX8 overexpression markedly blocked hepatocyte lipid deposition. Furthermore, the aggravating effect of Snx8 deletion on NAFLD was validated in vivo as hepatic steatosis and lipogenic pathways in the liver were significantly exacerbated in Snx8-knockout mice compared to wild-type controls. Consistently, hepatocyte-specific overexpression of Snx8 in vivo markedly suppressed high-fat, high-cholesterol diet (HFHC)-induced hepatic steatosis. Notably, the protective effect of SNX8 against NAFLD was largely dependent on FASN suppression. CONCLUSIONS: These data indicate that SNX8 is a key suppressor of NAFLD that promotes FASN proteasomal degradation. Targeting the SNX8-FASN axis is a promising strategy for NAFLD prevention and treatment.

10.
Insect Sci ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34231971

RESUMO

U1 small nuclear ribonucleoproteins (U1 snRNP) associates with 5' splice sites in the form of ribonucleoprotein particles and is highly conserved among species. The physiological functions of U1 snRNP in a lepidopteran model insect Bombyx mori is mostly unknown. Here, we showed that U1 snRNP plays an important role in the development of silkworm. Knockout of U1 snRNP in silkworm showed either delayed or stationary 1st instar larva development compared with the wild-type group. U1 snRNP deletion mutants exhibited abnormal cellular phenotypes with enlarged cell nucleus, scant cytoplasm and enlarged nuclei. RNA-seq analysis revealed that genes involved in metabolic pathway, biosynthesis of secondary metabolites and steroid hormone biosynthesis were significantly affected by U1 snRNP depletion. Taken together, our study suggests that U1 snRNP homeostasis plays an important role in silkworm development.

11.
Hepatology ; 74(4): 2133-2153, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34133792

RESUMO

BACKGROUND AND AIMS: Hepatic ischemia/reperfusion (I/R) injury, a common clinical problem that occurs during liver surgical procedures, causes a large proportion of early graft failure and organ rejection cases. The identification of key regulators of hepatic I/R injury may provide potential strategies to clinically improve the prognosis of liver surgery. Here, we aimed to identify the role of tumor necrosis factor alpha-induced protein 3-interacting protein 3 (TNIP3) in hepatic I/R injury and further reveal its immanent mechanisms. APPROACH AND RESULTS: In the present study, we found that hepatocyte TNIP3 was markedly up-regulated in livers of both persons and mice subjected to I/R surgery. Hepatocyte-specific Tnip3 overexpression effectively attenuated I/R-induced liver necrosis and inflammation, but improved cell proliferation in mice, whereas TNIP3 ablation largely aggravated liver injury. This inhibitory effect of TNIP3 on hepatic I/R injury was found to be dependent on significant activation of the Hippo-YAP signaling pathway. Mechanistically, TNIP3 was found to directly interact with large tumor suppressor 2 (LATS2) and promote neuronal precursor cell-expressed developmentally down-regulated 4-mediated LATS2 ubiquitination, leading to decreased Yes-associated protein (YAP) phosphorylation at serine 112 and the activated transcription of factors downstream of YAP. Notably, adeno-associated virus delivered TNIP3 expression in the liver substantially blocked I/R injury in mice. CONCLUSIONS: TNIP3 is a regulator of hepatic I/R injury that alleviates cell death and inflammation by assisting ubiquitination and degradation of LATS2 and the resultant YAP activation.TNIP3 represents a promising therapeutic target for hepatic I/R injury to improve the prognosis of liver surgery.

12.
13.
Pest Manag Sci ; 77(7): 3588-3596, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33843144

RESUMO

BACKGROUND: Genetic manipulation of sex determination pathways in insects provides the basis for a broad range of strategies to benefit agricultural security and human health. The P-element somatic inhibitor (PSI) protein, an exon splicing silencer that promotes male-specific splicing of dsx, plays a critical role in male sexual differentiation and development. The functions of PSI have been characterized in the lepidopteran model species Bombyx mori. However, the molecular mechanism and functions of PSI in Plutella xylostella, a worldwide agricultural pest and taxonomically basal species, are still unknown. RESULTS: Here we identified PxPSI transcripts and analyzed their spatiotemporal expression pattern in P. xylostella. Multiple sequence alignment revealed that PxPSI contains four KH domains and is highly conserved in lepidopterans. We used the CRISPR-Cas9 system to generate mutations of the PxPSI genomic locus. Disruptions of PxPSI caused male-specific defects in internal and external genitals. In addition, we detected female-specific Pxdsx transcripts in PxPSI male mutants. Mutations also caused changes in expression of several sex-biased genes and induced male sterility. CONCLUSION: Our study demonstrates that PxPSI plays a key role in male sex determination in P. xylostella and suggests a potential molecular target for genetic-based pest management in lepidopteran pests. © 2021 Society of Chemical Industry.


Assuntos
Infertilidade Masculina , Mariposas , Animais , Feminino , Proteínas de Insetos/genética , Masculino , Mariposas/genética , Mutação
14.
Hepatology ; 74(3): 1319-1338, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33894019

RESUMO

BACKGROUND AND AIMS: NAFLD has become the most common liver disease worldwide but lacks a well-established pharmacological therapy. Here, we aimed to investigate the role of an E3 ligase SH3 domain-containing ring finger 2 (SH3RF2) in NAFLD and to further explore the underlying mechanisms. METHODS AND RESULTS: In this study, we found that SH3RF2 was suppressed in the setting of NAFLD across mice, monkeys, and clinical individuals. Based on a genetic interruption model, we further demonstrated that hepatocyte SH3RF2 deficiency markedly deteriorates lipid accumulation in cultured hepatocytes and diet-induced NAFLD mice. Mechanistically, SH3RF2 directly binds to ATP citrate lyase, the primary enzyme promoting cytosolic acetyl-coenzyme A production, and promotes its K48-linked ubiquitination-dependent degradation. Consistently, acetyl-coenzyme A was significantly accumulated in Sh3rf2-knockout hepatocytes and livers compared with wild-type controls, leading to enhanced de novo lipogenesis, cholesterol production, and resultant lipid deposition. CONCLUSION: SH3RF2 depletion in hepatocytes is a critical aggravator for NAFLD progression and therefore represents a promising therapeutic target for related liver diseases.

15.
Genes (Basel) ; 12(2)2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33672402

RESUMO

In insects, sex determination pathways involve three levels of master regulators: primary signals, which determine the sex; executors, which control sex-specific differentiation of tissues and organs; and transducers, which link the primary signals to the executors. The primary signals differ widely among insect species. In Diptera alone, several unrelated primary sex determiners have been identified. However, the doublesex (dsx) gene is highly conserved as the executor component across multiple insect orders. The transducer level shows an intermediate level of conservation. In many, but not all examined insects, a key transducer role is performed by transformer (tra), which controls sex-specific splicing of dsx. In Lepidoptera, studies of sex determination have focused on the lepidopteran model species Bombyx mori (the silkworm). In B. mori, the primary signal of sex determination cascade starts from Fem, a female-specific PIWI-interacting RNA, and its targeting gene Masc, which is apparently specific to and conserved among Lepidoptera. Tra has not been found in Lepidoptera. Instead, the B. mori PSI protein binds directly to dsx pre-mRNA and regulates its alternative splicing to produce male- and female-specific transcripts. Despite this basic understanding of the molecular mechanisms underlying sex determination, the links among the primary signals, transducers and executors remain largely unknown in Lepidoptera. In this review, we focus on the latest findings regarding the functions and working mechanisms of genes involved in feminization and masculinization in Lepidoptera and discuss directions for future research of sex determination in the silkworm.


Assuntos
Bombyx/genética , RNA Interferente Pequeno/genética , Processos de Determinação Sexual/genética , Diferenciação Sexual/genética , Processamento Alternativo/genética , Animais , Bombyx/crescimento & desenvolvimento , Éxons/genética , Feminino , Proteínas de Insetos/genética , Masculino , Splicing de RNA/genética
16.
Insect Sci ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33629486

RESUMO

Yolk proteins are the main source of nutrients during embryonic and early larval development in oviparous animals. Therefore, vitellogenesis is crucial for reproduction. The silkworm, Bombyx mori, is a model lepidopteran insect in which there are three yolk proteins: vitellin, 30-kDa protein, and egg-specific protein (Esp). In this study, we explored the gene function of Esp through transgenic clustered regularly interspaced palindromic repeats (CRISPR) / CRISPR-associated protein 9 technology-mediated mutations in the silkworm. We found that Esp mutation resulted in female sterility but had no effect on male fertility. Female mutants could lay eggs after mating, but the eggs were smaller and lighter colored than those laid by wild-type females. The most important finding is that the eggs laid by female mutants did not hatch. Furthermore, we observed stable inheritance of female sterility caused by Esp mutation through successive generations. Thus, Esp encodes a yolk protein that is crucial for female reproductive success and is a potential target for pest control.

17.
Sensors (Basel) ; 21(3)2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33498422

RESUMO

The fuzzy C-means clustering (FCM) algorithm is used widely in medical image segmentation and suitable for segmenting brain tumors. Therefore, an intuitionistic fuzzy C-means algorithm based on membership information transferring and similarity measurements (IFCM-MS) is proposed to segment brain tumor magnetic resonance images (MRI) in this paper. The original FCM lacks spatial information, which leads to a high noise sensitivity. To address this issue, the membership information transfer model is adopted to the IFCM-MS. Specifically, neighborhood information and the similarity of adjacent iterations are incorporated into the clustering process. Besides, FCM uses simple distance measurements to calculate the membership degree, which causes an unsatisfactory result. So, a similarity measurement method is designed in the IFCM-MS to improve the membership calculation, in which gray information and distance information are fused adaptively. In addition, the complex structure of the brain results in MRIs with uncertainty boundary tissues. To overcome this problem, an intuitive fuzzy attribute is embedded into the IFCM-MS. Experiments performed on real brain tumor images demonstrate that our IFCM-MS has low noise sensitivity and high segmentation accuracy.

18.
Hepatology ; 73(2): 586-605, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32297339

RESUMO

BACKGROUND AND AIMS: Milk fat globule-epidermal growth factor-factor 8 (MFGE8) has been shown to be a critical extracellular molecule that mediates apoptotic signaling in the pathological process of nonalcoholic fatty liver disease (NAFLD). MFGE8 is abundantly expressed in hepatocytes, but its function in the pathogenesis of NAFLD has not been characterized. APPROACH AND RESULTS: In our current study, hepatic MFGE8 showed a protective role in the pathogenesis of NAFLD. Hepatic MFGE8 deletion largely exacerbated lipid accumulation and inflammatory responses in the liver in response to overnutrition. Mechanistically, intercellular MFGE8 was shown to directly bind to apoptosis signal-regulating kinase 1 (ASK1) and to inhibit its dimerization and phosphorylation under a normal diet. However, under metabolic challenges, decreased cytoplasmic MFGE8 facilitated the dimerization and phosphorylation of ASK1 and subsequent mitogen-activated protein kinase signaling in hepatocytes. CONCLUSIONS: Hepatic MFGE8 is an endogenous inhibitor that halts the progression of hepatic steatosis and inflammation. Metabolic challenge-induced loss of intracellular MFGE8 facilitates ASK1 dimerization and phosphorylation. Therefore, maintaining hepatic MFGE8 levels may serve as an alternative strategy for the treatment of NAFLD.


Assuntos
Antígenos de Superfície/metabolismo , Fígado/patologia , Proteínas do Leite/metabolismo , Hepatopatia Gordurosa não Alcoólica/imunologia , Animais , Antígenos de Superfície/genética , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Hepatócitos , Humanos , Metabolismo dos Lipídeos/imunologia , Fígado/imunologia , MAP Quinase Quinase Quinase 5/metabolismo , Sistema de Sinalização das MAP Quinases/imunologia , Masculino , Camundongos , Camundongos Knockout , Proteínas do Leite/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Fosforilação/imunologia , Multimerização Proteica/imunologia
19.
PLoS Genet ; 16(11): e1009194, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33137136

RESUMO

Sex determination pathways are astoundingly diverse in insects. For instance, the silk moth Bombyx mori uniquely use various components of the piRNA pathway to produce the Fem signal for specification of the female fate. In this study, we identified BmGTSF1 as a novel piRNA factor which participates in B. mori sex determination. We found that BmGtsf1 has a distinct expression pattern compared to Drosophila and mouse. CRISPR/Cas9 induced mutation in BmGtsf1 resulted in partial sex reversal in genotypically female animals by shifting expression of the downstream targets BmMasc and Bmdsx to the male pattern. As levels of Fem piRNAs were substantially reduced in female mutants, we concluded that BmGtsf1 plays a critical role in the biogenesis of the feminizing signal. We also demonstrated that BmGTSF1 physically interacted with BmSIWI, a protein previously reported to be involved in female sex determination, indicating BmGTSF1 function as the cofactor of BmSIWI. BmGtsf1 mutation resulted in piRNA pathway dysregulation, including piRNA biogenesis defects and transposon derepression, suggesting BmGtsf1 is also a piRNA factor in the silkworm. Furthermore, we found that BmGtsf1 mutation leads to gametogenesis defects in both male and female. Our data suggested that BmGtsf1 is a new component involved in the sex determination pathway in B. mori.


Assuntos
Bombyx/fisiologia , Elementos de DNA Transponíveis/genética , Proteínas de Insetos/metabolismo , Proteínas Nucleares/metabolismo , Processos de Determinação Sexual/genética , Animais , Animais Geneticamente Modificados , Sistemas CRISPR-Cas/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Insetos/genética , Masculino , Mutação , Proteínas Nucleares/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo
20.
Insect Biochem Mol Biol ; 127: 103487, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33068728

RESUMO

Antimicrobial peptides (AMPs) are effective molecules produced by the innate immune system of most organisms to fend off invading microbes and regarded as promising alternatives to conventional antibiotics due to their potent antimicrobial activities. The larvae of black soldier fly (BSF), Hermetia illucens, inhabit microbe-rich environments and its insect genome encodes a broad repertoire of AMPs. In the present study, three AMPs encoded by BSF Hidefensin-1, Hidiptericin-1 and HiCG13551 were cloned, expressed and purified in a recombinant Escherichia coli expression system. In vitro, both Hidefensin-1 and Hidiptericin-1 inhibited the growth of Streptococcus pneumoniae and Escherichia coli, while HiCG13551 inhibited the growth of Staphylococcus aureus and E. coli. Transmission electron microscopy showed that Hidiptericin-1 inhibited bacterial growth through bacterial membrane lysis. We also constructed a transgenic silkworm line constitutively expressing an AMP cassette HiAMP4516 encoding all the three AMPs, and the silkworms showed an increased resistance to both gram-positive and gram-negative entomopathogenic bacteria. These results provide insights into the antibacterial activities of BSF AMPs both in vitro and in vivo and suggest a great potential of exploiting insect-derived AMPs in silkworm disease resistance breeding.


Assuntos
Antibiose/genética , Bombyx/genética , Dípteros/genética , Proteínas de Insetos/genética , Proteínas Citotóxicas Formadoras de Poros/genética , Sequência de Aminoácidos , Animais , Animais Geneticamente Modificados/genética , Animais Geneticamente Modificados/metabolismo , Bombyx/metabolismo , Dípteros/metabolismo , Escherichia coli/fisiologia , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Alinhamento de Sequência , Staphylococcus aureus/fisiologia , Streptococcus pneumoniae/fisiologia
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