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1.
Biol Reprod ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33524105

RESUMO

nesis but few has been functionally verified. Here, we identified one member, Rbm46 and investigated its expression and role during zebrafish reproduction. We found that is maternally provided and specifically expressed in the germ cells of gonadal tissues using in situ hybridization, RT-PCR and qRT-PCR. Utilizing TALEN (transcription activator-like effector nuclease) techniques, two independent rbm46 mutant zebrafish lines were generated. Specific disruption of rbm46 resulted in masculinization and infertility in the mutants. Although the spermatogonia appeared grossly normal, spermatogenesis was impaired and meiosis events were not observed in the mutants. The introduction of a tp53M214K mutation could not rescue the female-to-male sex-reversal phenotype, which suggests that rbm46 acts independently of p53 dependent apoptotic pathway. RNA-seq and qRT-PCR results subsequently indicate that Rbm46 might be involved in post-transcriptional regulation of functional genes essential for the germ cell development such as nanos3, dazl, sycp3 during gametogenesis. Altogether, our results firstly reveal a crucial in vivo role of rbm46 in regulating germ cell development by promoting the transition from mitosis to meiosis.

2.
Genome Biol Evol ; 13(3)2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33528489

RESUMO

As a polyphagous soil-dwelling predatory mite, Stratiolaelaps scimitus (Womersley) (Acari: Laelapidae), formerly known as Stratiolaelaps miles (Berlese), is native to the Northern hemisphere and preys on soil invertebrates, including fungus gnats, springtails, thrips nymphs, nematodes, and other species of mites. Already mass-produced and commercialized in North America, Europe, Oceania and China, S. scimitus will highly likely be introduced to other countries and regions as a biocontrol agent against edaphic pests in the near future. The introduction, however, can lead to unexpected genetic changes within populations of biological control agents, which might decrease the efficacy of pest management or increase the risks to local environments. To better understand the genetic basis of its biology and behavior, we sequenced and assembled the draft genome of S. scimitus using the PacBio Sequel platform II. We generated ∼150× (64.81 Gb) PacBio long reads with an average read length of 12.60 kb. Reads longer than 5 kb were assembled into contigs, resulting in the final assembly of 158 contigs with an N50 length of 7.66 Mb, and captured 93.1% of the BUSCO (Benchmarking Universal Single-Copy Orthologs) gene set (n = 1,066). We identified 16.39% (69.91 Mb) repetitive elements, 1,686 noncoding RNAs, and 13,305 protein-coding genes, which represented 95.8% BUSCO completeness. Combining analyses of genome family evolution and function enrichment of gene ontology and pathway, a total of 135 families experienced significant expansions, which were mainly involved in digestion, detoxification, immunity, and venom. Major expansions of the detoxification enzymes, that is, P450s and carboxylesterases, suggest a possible genetic mechanism underlying polyphagy and ecological adaptions. Our high-quality genome assembly and annotation provide new insights on the evolutionary biology, soil ecology, and biological control for predaceous mites.

3.
Nat Commun ; 12(1): 707, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514727

RESUMO

Mitochondrial complex I is central to the pathological reactive oxygen species (ROS) production that underlies cardiac ischemia-reperfusion (IR) injury. ND6-P25L mice are homoplasmic for a disease-causing mtDNA point mutation encoding the P25L substitution in the ND6 subunit of complex I. The cryo-EM structure of ND6-P25L complex I revealed subtle structural changes that facilitate rapid conversion to the "deactive" state, usually formed only after prolonged inactivity. Despite its tendency to adopt the "deactive" state, the mutant complex is fully active for NADH oxidation, but cannot generate ROS by reverse electron transfer (RET). ND6-P25L mitochondria function normally, except for their lack of RET ROS production, and ND6-P25L mice are protected against cardiac IR injury in vivo. Thus, this single point mutation in complex I, which does not affect oxidative phosphorylation but renders the complex unable to catalyse RET, demonstrates the pathological role of ROS production by RET during IR injury.


Assuntos
Complexo I de Transporte de Elétrons/ultraestrutura , Mitocôndrias/patologia , Traumatismo por Reperfusão Miocárdica/patologia , NADH Desidrogenase/genética , Espécies Reativas de Oxigênio/metabolismo , Substituição de Aminoácidos , Animais , Microscopia Crioeletrônica , DNA Mitocondrial/genética , Modelos Animais de Doenças , Resistência à Doença/genética , Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Humanos , Preparação de Coração Isolado , Leucina/genética , Masculino , Camundongos , Camundongos Transgênicos , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , Membranas Mitocondriais/patologia , Traumatismo por Reperfusão Miocárdica/genética , NAD/metabolismo , NADH Desidrogenase/metabolismo , NADH Desidrogenase/ultraestrutura , Oxirredução , Mutação Puntual , Prolina/genética
4.
Brain Behav Immun ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33412253

RESUMO

Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders in children. The orexigenic hormone ghrelin is important in neuroprotection and neurodevelopment, which may play an important role in psychopathogenesis of ADHD. This study aimed to systematically investigate the genomic and pharmacological manipulations of ghrelin functioning in ADHD-like symptoms in zebrafish models and validated the effects of ghrelin polymorphisms in human subjects with ADHD. We firstly generated ghrelinΔ/Δ zebrafish mutant, which displayed hyperactive, attention deficit-like and impulsive-like behaviors, as well as endophenotypes, mimicking human ADHD. GhrelinΔ/Δ zebrafish exhibited downregulated expression levels of wnt1, wnt3a, wnt5a that are critical for dopaminergic neuron development to possibly regulate their number and spatial organization. Pharmacological blockade of wnt signaling with XAV939 induced a reduced moving activity and less dopaminergic neurons; whereas, wnt agonist SB415286 rescued hyperactivity and dopaminergic neuron loss in ghrelinΔ/Δ zebrafish. In addition, we further identified and validated a SNP, rs696217, on orexigenic hormone preproghrelin/ghrelin (T408T, Met72Met) to be associated with a higher risk of ADHD in a case-controlled association study with 248 subjects with ADHD and 208 subjects of healthy controls. Together, our results reveal a novel endogenous role for orexigenic hormone ghrelin in ADHD, which provides insights into genetic regulation and drug screens for the identification of novel treatments of ADHD.

5.
Zootaxa ; 4894(2): zootaxa.4894.2.8, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33311087

RESUMO

A new species and a key to 10 species of the genus Lemba Huang, 1983, namely Lemba wushanensis sp. nov. is described in this paper from China. The new species is similar to L. sichuanensis Ma et al, 1994, but differs from the latter by the length of tegmen 2.7 times width in male, length of interspace of mesosternum 3.5 times width in male, posterior margin of epiproct straight; ancorae of epiphallus not inward tilt and vertical diameter 1.8 times subocular furrow in female. The type specimens are deposited in the Northwest Plateau Institute of Biology, Chinese Academy of Sciences, Xining, China.


Assuntos
Gafanhotos , Ortópteros , Distribuição Animal , Estruturas Animais , Animais , Tamanho Corporal , China , Feminino , Masculino , Tamanho do Órgão
6.
Zootaxa ; 4869(1): zootaxa.4869.1.8, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33311376

RESUMO

A new species of the genus Sulcohumpacris Yin, Yin et Cao, 2017 i.e. Sulcohumpacris wuanensis sp. nov. is described in this paper from China. The new species is similar to Sulcohumpacris hebeiensis Yin, Yin et Cao, 2017 but differs from latter by median keel of pronotum cut by hind sulcus slightly, tegmen of male cover 2/3 tympanum, length of Krauss' organ 1.8 times of width in female, apex of subgenital plate of male point, cercus of male narrow at base, lower margin of Epiphallus with large projection in the middle and hind knee of female not curved at lower margin. Type specimens are deposited in the College of Life Sciences, Hebei University, Baoding, China.


Assuntos
Ortópteros , Distribuição Animal , Estruturas Animais , Animais , Tamanho Corporal , China , Feminino , Masculino , Tamanho do Órgão
7.
Zootaxa ; 4822(1): zootaxa.4822.1.10, 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-33056307

RESUMO

The genus Sinohaplotropis Cao et Yin, 2008 is a valid genus and not a synonym of Haplotropis Saussur, 1888. A new species Sinohaplotropis amurensis sp. nov. is described in this paper from Russia. The new species is similar to Sinohaplotropis erenchuanensis Cao et Yin, 2008, but differs from latter by subgenital plate of male triangular, with large bifurcate apex in dorsal view, pronotum longer reaching first abdominal tergite, top of Kraus` organ narrow and interspace of mesosternum straight in the middle. Type specimen is deposited in the Hebei University, Baoding, Hebei, China.


Assuntos
Ortópteros , Distribuição Animal , Estruturas Animais , Animais , Tamanho Corporal , Masculino , Tamanho do Órgão , Rios , Federação Russa
8.
Biology (Basel) ; 9(9)2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32911654

RESUMO

In mammals, epidermal growth factor (EGF) plays a vital role in both pituitary physiology and pathology. However, the functional role of EGF in the regulation of pituitary hormones has rarely reported in teleost. In our study, using primary cultured grass carp pituitary cells as an in vitro model, we examined the effects of EGF on pituitary hormone secretion and gene expression as well as the post-receptor signaling mechanisms involved. Firstly, we found that EGF significantly reduced luteinizing hormone (LHß) mRNA expression via ErbB1 coupled to ERK1/2 pathway, but had no effect on LH release in grass carp pituitary cells. Secondly, the results showed that EGF was effective in up-regulating mRNA expression of growth hormone (GH), somatolactin α (SLα) and somatolactin ß (SLß) via ErbB1 and ErbB2 and subsequently coupled to MEK1/2/ERK1/2 and PI3K/Akt/mTOR pathways, respectively. However, EGF was not effective in GH release in pituitary cells. Thirdly, we found that EGF strongly induced pituitary prolactin (PRL) release and mRNA expression, which was mediated by ErbB1 and subsequent stimulation of MEK1/2/ERK1/2 and PI3K/Akt/mTOR pathways. Interestingly, subsequent study further found that neurokinin B (NKB) significantly suppressed EGF-induced PRL mRNA expression, which was mediated by neurokinin receptor (NK2R) and coupled to AC/cAMP/PKA signal pathway. These results suggested that EGF could differently regulate the pituitary hormones expression in grass carp pituitary cells.

9.
Commun Biol ; 3(1): 361, 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32647268

RESUMO

Mandarin fishes (Sinipercidae) are piscivores that feed solely on live fry. Unlike higher vertebrates, teleosts exhibit feeding behavior driven mainly by genetic responses, with no modification by learning from parents. Mandarin fishes could serve as excellent model organisms for studying feeding behavior. We report a long-read, chromosomal-scale genome assembly for Siniperca chuatsi and genome assemblies for Siniperca kneri, Siniperca scherzeri and Coreoperca whiteheadi. Positive selection analysis revealed rapid adaptive evolution of genes related to predatory feeding/aggression, growth, pyloric caeca and euryhalinity. Very few gill rakers are observed in mandarin fishes; analogously, we found that zebrafish deficient in edar had a gill raker loss phenotype and a more predatory habit, with reduced intake of zooplankton but increased intake of prey fish. Higher expression of bmp4, which could inhibit edar expression and gill raker development through binding of a Xvent-1 site upstream of edar, may cause predatory feeding in Siniperca.

10.
World J Gastroenterol ; 26(15): 1805-1819, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32351295

RESUMO

BACKGROUND: Transarterial chemoembolization (TACE) is recommended for patients with intermediate hepatocellular carcinoma (HCC) according to treatment guidelines. However, a large number of patients with advanced HCC also receive TACE in clinical practice, especially for those with liver-confined HCC and Eastern Cooperative Oncology Group score (ECOG) 1. In view of previous studies, such patients have different prognoses from advanced HCC patients with macrovascular invasion or extrahepatic spread; therefore, patients with ECOG 1 alone might be classified into the intermediate stage and benefit from TACE treatment, but a study particularly focusing on such patients and exploring the effectiveness of TACE therapy is lacking. AIM: To investigate treatment outcomes of TACE in HCC patients with ECOG 1 alone and propose a specific prognostic model. METHODS: Patients from 24 Chinese tertiary hospitals were selected in this nationwide multicenter observational study from January 2010 to May 2016. Overall survival (OS) was estimated using Kaplan-Meier curves and compared by the log-rank test. Multivariate Cox regression was used to develop the potential prognostic models. The discriminatory ability of the models was compared and validated in various patient subgroups. The individual survival prediction for six-and-twelve (6&12) criteria, defined as the algebraic sum of tumor size (cm) and tumor number, was illustrated by contour plot of 3-year survival probability and nomogram. RESULTS: A total of 792 eligible patients were included. During follow-up, median OS reached 18.9 mo [95% confidence interval (CI): 16.9-21.0]. Three independent multivariate analyses demonstrated that tumor size, tumor number, α-fetoprotein level, albumin-bilirubin grade and total bilirubin were prognostic factors of OS (P < 0.05). The previously proposed 6&12 criteria was comparable or even better than currently proposed with the highest predictive ability. In addition, the 6&12 criteria was correlated with OS in various subgroups of patients. The patients were stratified into three strata with score ≤ 6, > 6 but ≤ 12, and > 12 with different median OS of 39.8 mo (95%CI: 23.9-55.7), 21.1 mo (95%CI: 18.4-23.8) and 9.8 mo (95%CI: 8.3-11.3), respectively (P < 0.001). CONCLUSION: TACE is effective for advanced HCC patients with ECOG 1 alone, and the 6&12 criteria may help with clinical decision-making.

11.
ACS Synth Biol ; 9(6): 1450-1459, 2020 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-32383867

RESUMO

Adenosine triphosphate (ATP), the cellular energy currency, is essential for life. The ability to provide a constant supply of ATP is therefore crucial for the construction of artificial cells in synthetic biology. Here, we describe the bottom-up assembly and characterization of a minimal respiratory system that uses NADH as a fuel to produce ATP from ADP and inorganic phosphate, and is thus capable of sustaining both upstream metabolic processes that rely on NAD+, and downstream energy-demanding processes that are powered by ATP hydrolysis. A detergent-mediated approach was used to co-reconstitute respiratory mitochondrial complex I and an F-type ATP synthase into nanosized liposomes. Addition of the alternative oxidase to the resulting proteoliposomes produced a minimal artificial "organelle" that reproduces the energy-converting catalytic reactions of the mitochondrial respiratory chain: NADH oxidation, ubiquinone cycling, oxygen reduction, proton pumping, and ATP synthesis. As a proof-of-principle, we demonstrate that our nanovesicles are capable of using an NAD+-linked substrate to drive cell-free protein expression. Our nanovesicles are both efficient and durable and may be applied to sustain artificial cells in future work.

12.
Gen Comp Endocrinol ; 295: 113490, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32283058

RESUMO

Brain sex differentiation is a complex process, wherein genes and steroid hormones act to induce specific gender brain differentiation. Testosterone (T) derived from the gonads has been linked to neural circuit modeling in a sex-specific manner. Previously, we have shown that cyp17a1 knockout (KO) zebrafish have low plasma androgen levels, and display compromised male-typical mating behaviors. In this study, we demonstrated that treatment of cyp17a1 KO males with T or 11-ketotestosterone (11-KT) is sufficient to rescue mating impairment by restoring the male-typical secondary sex characters (SSCs) and mating behaviors, confirming an essential role of androgen in maintaining SSCs and mating behaviors. Brain steroid hormone analysis revealed that cyp17a1 KO fish have reduced levels of T and 11-KT. We performed RNA sequencing on brain samples of control and cyp17a1 KO male zebrafish to get insights regarding the impact of cyp17a1 KO on gene expression pattern, and to correlate it with the observed disruption of male-typical mating behaviors. Transcriptome analysis of cyp17a1 KO males showed a differential gene expression when compared to control males. In total, 358 genes were differentially regulated between control males and KO males. Important genes including brain aromatase (cyp19a1b), progesterone receptor (pgr), deiodinase (dio2), and insulin-like growth factor 1 (igf1) that are involved in brain functions, as well as androgen response genes including igf1, frem1a, elovl1a, pax3a, mmp13b, hsc70, ogg1 were regulated. RT-qPCR analysis following rescue of cyp17a1 KO with T and 11-KT further suggested that androgen-mediated signaling is disrupted in the cyp17a1 KO fish. Our results indicated that cyp17a1 KO fish have an incomplete masculinization and altered brain gene expression, which could be due to decreased androgen levels.

13.
Zootaxa ; 4731(3): zootaxa.4731.3.13, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32230305

RESUMO

The genus Xya Latreille, 1808 obtains 58 known species in the world, among them 18 species distributed in Asia and 8 species in China only i.e. Xya japonica (Haan, 1842), Xya riparia (Saussure, 1877), Xya nitobei (Shiraki, 1911), Xya apicicornis (Chopard, 1928), Xya manchurei Shiraki, 1936, Xya lehsanensis Cao et al, 2017, Xya sichuanensis Cao et al, 2018, Xya shandongensis, Zhang et al, 2018; [Latreille, 1809; Haan, 1844; Walker, 1871; Saussure, 1877, 1896; Brunner von Wattenwyl. 1893; Bolivar, 1900(1899); Shiraki,1911, 1936; Chopard, 1920, 1928, 1936, 1968; Tindale, 1928; Willemse, 1954; Bey-Bienko, 1967; Harz, 1970, 1971; Günther, 1974, 1978, 1980, 1982, 1990, 1995, 1998; Ingrisch, 1987, 2006; Baehr, 1988; Yin et al, 1996; Murai, 2005; Yin et al, 2013; Heads Hollier, 2016; Kuravova Kocarek, 2016; Cao et al, 2017; Cao et al, 2018; Zhang et al, 2018; Cigliano, et al, 2019]. In the present paper, a new species of the genus Xya Latreille, 1809 from Fujian, China is described. The new species Xya fujianensis sp. nov. is similar to Xya lehsanensis Cao et al, 2017, but differs from the latter by head black, with a yellow band along inner margin of eye; pronotum black, with a white band on the lower margin; fore wing black, with two yellow spots near base and two yellow spots near top and hind femur black with two large yellow spots on upper side. Type specimens are deposited in the College of Life Science, Leshan Normal University, Leshan 614004, China.


Assuntos
Ortópteros , Distribuição Animal , Estruturas Animais , Animais , Tamanho Corporal , China , Tamanho do Órgão
14.
Zootaxa ; 4742(2): zootaxa.4742.2.11, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32230385

RESUMO

The genus Haplotropis Saussure, 1888 belongs to family Pamphagidae, superfamily Acridioidea. It contains five species: Haplotropis brunneriana Saussure, 1888; Haplotropis xiai Ye, Shi Li 2016; Haplotropis zhuoluensis Ye, Shi Li 2016; Haplotropis aqiensis Zhang, Lin et Yin, 2018 and Haplotropis shandongensis Zhang, Yin et Liu, 2019 distributed mainly in Amur River region of Asia and China only (Saussure, 1888; Bey-Bienko et Mishchenko, 1951; Otte, 1994; Yin, Shi et Yin, 1996; Storozhenko Paik, 2011; Yin et al, 2014; Dong et al, 2015; Ye et al, 2016; Zhang et al, 2017; Zhang et al, 2018; Zhang et al, 2019; Cigliano et al, 2019). A new species Haplotropis heiheensis sp. nov. is described in this paper. The new species is similar to Haplotropis aqiensis Zhang, Lin et Yin, 2018, but differs from latter by Krauss' organ of male without ramified keel; tegmine narrower, length 2.4 times width; cercus of male gently tapering at apical half part; minimum width 1.4 times length in mesosternum and epiphallus with 36 spikes. Type specimens are deposited in the College of Plant Protection, Shandong Agricultural University, Taian, Shandong, China.


Assuntos
Ortópteros , Distribuição Animal , Estruturas Animais , Animais , Tamanho Corporal , China , Masculino , Tamanho do Órgão
15.
J Immunol ; 204(9): 2401-2415, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32188757

RESUMO

Mammalian CIITA isoforms are tightly regulated by independent promoters. These promotors are induced by IFN-γ through JAK-STAT signaling pathway. The induction of CIITA controls the expression of MHC class II (MHCII) and Ag presentation to the adaptive immune system. In the current study, to our knowledge, we first identified two independent promoters, p1 and p2, in the zebrafish (Danio rerio) that control the expression of the two variants of CIITA, CIITA variant 1 (CIITAv1), and CIITA variant 2 (CIITAv2), respectively. Moreover, although IRF1 in an IFN-γ signaling pathway induced CIITAv2, which has two ISRE motifs in its promoter, CIITAv1 expression was not induced by this signal. Further, the transcription of MHCII DAB was controlled by IRF1 via two distinct mechanisms: 1) the transcription of MHCII DAB was controlled by IRF1 indirectly through the two ISREs in p2; and 2) directly via the ISRE in MHCII DAB promoter. We also found that IRF1 associated with CIITAv1 and CIITAv2 via protein-protein interactions to synergistically drive the transcription of MHCII DAB. The IFN-γ-IRF1-CIITA-MHCII signaling cascade was functional in early life stages of CIITA-/- and IRF1-/- zebrafish. Our findings imply that the immune system develops early in fishes and that the IFN-γ signaling cascade-induced CIITA and MHCII DAB is conserved in teleost fishes and mammals.

16.
World J Gastroenterol ; 26(6): 657-669, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32103874

RESUMO

BACKGROUND: The treatment outcome of transarterial chemoembolization (TACE) in unresectable hepatocellular carcinoma (HCC) varies greatly due to the clinical heterogeneity of the patients. Therefore, several prognostic systems have been proposed for risk stratification and candidate identification for first TACE and repeated TACE (re-TACE). AIM: To investigate the correlations between prognostic systems and radiological response, compare the predictive abilities, and integrate them in sequence for outcome prediction. METHODS: This nationwide multicenter retrospective cohort consisted of 1107 unresectable HCC patients in 15 Chinese tertiary hospitals from January 2010 to May 2016. The Hepatoma Arterial-embolization Prognostic (HAP) score system and its modified versions (mHAP, mHAP2 and mHAP3), as well as the six-and-twelve criteria were compared in terms of their correlations with radiological response and overall survival (OS) prediction for first TACE. The same analyses were conducted in 912 patients receiving re-TACE to evaluate the ART (assessment for re-treatment with TACE) and ABCR (alpha-fetoprotein, Barcelona Clinic Liver Cancer, Child-Pugh and Response) systems for post re-TACE survival (PRTS). RESULTS: All the prognostic systems were correlated with radiological response achieved by first TACE, and the six-and-twelve criteria exhibited the highest correlation (Spearman R = 0.39, P = 0.026) and consistency (Kappa = 0.14, P = 0.019), with optimal performance by area under the receiver operating characteristic curve of 0.71 [95% confidence interval (CI): 0.68-0.74]. With regard to the prediction of OS, the mHAP3 system identified patients with a favorable outcome with the highest concordance (C)-index of 0.60 (95%CI: 0.57-0.62) and the best area under the receiver operating characteristic curve at any time point during follow-up; whereas, PRTS was well-predicted by the ABCR system with a C-index of 0.61 (95%CI: 0.59-0.63), rather than ART. Finally, combining the mHAP3 and ABCR systems identified candidates suitable for TACE with an improved median PRTS of 36.6 mo, compared with non-candidates with a median PRTS of 20.0 mo (log-rank test P < 0.001). CONCLUSION: Radiological response to TACE is closely associated with tumor burden, but superior prognostic prediction could be achieved with the combination of mHAP3 and ABCR in patients with unresectable liver-confined HCC.

17.
Redox Biol ; 28: 101355, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31677554

RESUMO

Nuclear prelamin A recognition factor-like (NARFL) is a human protein that participates in cytosolic iron-sulfur (Fe-S) protein biogenesis and cellular defense against oxidative stress. Previous studies of Narfl knockout mice did not reveal well the regulatory mechanisms of embryonic development mediated by Narfl because the homozygous mice die in utero. Here, we investigated the function of narfl in an established zebrafish knockout model by taking advantage of zebrafish external fertilization and ease of embryonic development examination. Our experiments showed that narfl deletion resulted in larvae lethality, subintestinal vessel (SIV) malformation and digestive organ defects in the early stages of embryonic development. Biochemical analyses and western blot revealed increased oxidative stress and upregulated hypoxia-inducible factor-1α (HIF-1α) expression in narfl-/- fish. The use of HIF-1α inhibitor 2-methoxyestradiol (2ME2) for the treatment of mutants partially rescued the SIV sprouting. These results suggest that narfl deletion causes increased oxidative stress and subintestinal vessel malformation, which further influence the development of digestive organs and might contribute to the lethality of the narfl knockout fish.


Assuntos
Trato Gastrointestinal/anormalidades , Técnicas de Inativação de Genes , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteínas com Ferro-Enxofre/genética , Neovascularização Patológica/genética , 2-Metoxiestradiol/farmacologia , Animais , Modelos Animais de Doenças , Desenvolvimento Embrionário/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento , Estresse Oxidativo , Peixe-Zebra , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
18.
J Mol Cell Biol ; 12(4): 291-304, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-31237951

RESUMO

The endocrine regulatory roles of the hypothalamic-pituitary-adrenocortical axis on anxiety-like behavior and metabolic status have been found throughout animal taxa. However, the precise effects of the balancing adrenal corticosteroid biosynthesis under the influence of adrenocorticotrophic hormone (ACTH), a pro-opiomelanocortin (POMC)-derived peptide, on animal energy expenditure and somatic growth remain unknown. POMC has also been identified as one of the candidate loci for polycystic ovary syndrome, which features hyperandrogenism and some prevalence of obesity in patients. Here we show that zebrafish lacking functional POMCa exhibit similar phenotypes of stress response and body weight gain but not obesity as observed in mammalian models. In contrast with the impaired anorexigenic signaling cascade of melanocyte-stimulating hormones and leptin, which are responsible for their obesity-prone weight gain observed in various pomc mutant mammals, analyses with our pomca mutant series indicate that ACTH is the key regulator for the phenotype with enhanced somatic growth without obesity in pomca-deficient zebrafish. Hypocortisolism associated with hyperandrogenism has been observed in the pomca-deficient zebrafish, with enhanced activation of mammalian target of rapamycin complex 1; reutilization of amino acids and fatty acid ß-oxidation are observed in the muscle tissue of the pomca-deficient fish. After reducing hyperandrogenism by crossing our pomca mutant fish with a cyp17a1-deficient background, the phenotype of enhanced somatic growth in pomca-deficient fish was no longer observed. Thus, our work also demonstrated that the role of POMCa in stress response seems to be conserved in vertebrates, whereas its effect on adipostasis is unique to teleosts.

19.
Genome Res ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831591

RESUMO

Genome editing by the well-established CRISPR/Cas9 technology has greatly facilitated our understanding of many biological processes. However, a complete whole-genome knockout for any species or model organism has rarely been achieved. Here, we performed a systematic knockout of all the genes (1333) on Chromosome 1 in zebrafish, successfully mutated 1029 genes, and generated 1039 germline-transmissible alleles corresponding to 636 genes. Meanwhile, by high-throughput bioinformatics analysis, we found that sequence features play pivotal roles in effective gRNA targeting at specific genes of interest, while the success rate of gene targeting positively correlates with GC content of the target sites. Moreover, we found that nearly one-fourth of all mutants are related to human diseases, and several representative CRISPR/Cas9-generated mutants are described here. Furthermore, we tried to identify the underlying mechanisms leading to distinct phenotypes between genetic mutants and antisense morpholino-mediated knockdown embryos. Altogether, this work has generated the first chromosome-wide collection of zebrafish genetic mutants by the CRISPR/Cas9 technology, which will serve as a valuable resource for the community, and our bioinformatics analysis also provides some useful guidance to design gene-specific gRNAs for successful gene editing.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31756961

RESUMO

The timely and secure evacuation of an urban residential community is crucial to residents' safety when emergency events happen. This is different to evacuation of office spaces or schools, emergency evacuation in residential communities must consider the pre-evacuation time. The importance of estimating evacuation time components has been recognized for approximately 40 years. However, pre-evacuation time is rarely discussed in previous community-scale emergency evacuation studies. This paper proposes a new method that estimates the pre-evacuation time, which makes the evacuation simulation in urban residential communities more realistic. This method integrates the residents' pre-evacuation behavior data obtained by surveys to explore the influencing factors of pre-evacuation time and builds a predictive model to forecast pre-evacuation times based on the Random Forest algorithm. A sensitivity analysis is also conducted to find the critical parameters in evacuation simulations. The results of evacuation simulations in different scenarios can be compared to identify potential evacuation problems. A case study in Luoshanqicun Community, Pudong New District, Shanghai, China, was conducted to demonstrate the feasibility of the proposed method. The simulation results showed that the pre-evacuation times have significant impacts on the simulation procedure, including the total evacuation time, the congestion time and the congestion degree. This study can help to gain a deeper understanding of residents' behaviors under emergencies and improve emergency managements of urban communities.


Assuntos
Planejamento em Desastres/métodos , Comportamentos Relacionados com a Saúde , Saúde da População Urbana , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Criança , Pré-Escolar , China , Emergências , Estudos de Viabilidade , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Modelos Psicológicos , Características de Residência , Fatores de Tempo , Adulto Jovem
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