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1.
Plant Physiol ; 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32414897

RESUMO

The greening of etiolated seedlings is crucial for the growth and survival of plants. After reaching the soil surface and sunlight, etiolated seedlings integrate numerous environmental signals and internal cues to control the initiation and rate of greening thus to improve their survival and adaption. However, the underlying regulatory mechanisms by which light and phytohormones, such as abscisic acid (ABA), coordinately regulate greening of the etiolated seedling is still unknown. In this study, we showed that Arabidopsis thaliana DE-ETIOLATED 1 (DET1), a key negative regulator of photomorphogenesis, positively regulated light-induced greening by repressing ABA responses. Upon irradiating etiolated seedlings with light, DET1 physically interacts with FAR-RED ELONGATED HYPOCOTYL 3 (FHY3) and subsequently associates to the promoter region of the FHY3 direct downstream target ABA INSENSITIVE 5 (ABI5). Further, DET1 recruits HISTONE DEACETYLASE 6 (HDA6) to the locus of the ABI5 promoter and reduces the enrichments of H3K27ac and H3K4me3 modification, thus subsequently repressing ABI5 expression and promoting the greening of etiolated seedlings. This study reveals the physiological and molecular function of DET1 and FHY3 in the greening of seedlings and provides insights into the regulatory mechanism by which plants integrate light and ABA signals to fine-tune early seedling establishment.

2.
Aging (Albany NY) ; 122020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32452829

RESUMO

Mesenchymal stromal/stem cells (MSCs) are promising carriers in cell-based therapies against central nervous system diseases, and have been evaluated in various clinical trials in recent years. However, bone marrow-derived MSCs (BMSCs) are reportedly involved in tumorigenesis initiated by glioma stem-like cells (GSCs). We therefore established three different orthotopic models of GSC-MSC interactions in vivo using dual-color fluorescence tracing. Cell sorting and micropipetting techniques were used to obtain highly proliferative MSC monoclones from each model, and these cells were identified as transformed MSC lines 1, 2 and 3. Nineteen miRNAs were upregulated and 24 miRNAs were downregulated in all three transformed MSC lines compared to normal BMSCs. Reduced miR-146a-5p expression in the transformed MSCs was associated with their proliferation, malignant transformation and overexpression of heterogeneous nuclear ribonucleoprotein D. These findings suggest that downregulation of miR-146a-5p leads to overexpression of its target gene, heterogeneous nuclear ribonucleoprotein D, thereby promoting malignant transformation of MSCs during interactions with GSCs. Given the risk that MSCs will undergo malignant transformation in the glioma microenvironment, targeted glioma therapies employing MSCs as therapeutic carriers should be considered cautiously.

3.
Metab Brain Dis ; 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32440806

RESUMO

BACKGROUND: Our understanding of the molecular mechanisms of depression remains largely unclear. Previous studies have shown that the prefrontal cortex (PFC) is among most important brain regions that exhibits metabolic changes in depression. A comprehensive analysis based on candidate metabolites in the PFC of animal models of depression will provide valuable information for understanding the pathogenic mechanism underlying depression. METHODS: Candidate metabolites that are potentially involved in the metabolic changes of the PFC in animal models of depression were retrieved from the Metabolite Network of Depression Database. The significantly altered metabolic pathways were revealed by canonical pathway analysis, and the relationships among altered pathways were explored by pathway crosstalk analysis. Additionally, drug-associated pathways were investigated using drug-associated metabolite set enrichment analysis. The interrelationships among metabolites, proteins, and other molecules were analyzed by molecular network analysis. RESULTS: Among 88 candidate metabolites, 87 altered canonical pathways were identified, and the top five ranked pathways were tRNA charging, the endocannabinoid neuronal synapse pathway, (S)-reticuline biosynthesis II, catecholamine biosynthesis, and GABA receptor signaling. Pathway crosstalk analysis revealed that these altered pathways were grouped into three interlinked modules involved in amino acid metabolism, nervous system signaling/neurotransmitters, and nucleotide metabolism. In the drug-associated metabolite set enrichment analysis, the main enriched drug pathways were opioid-related and antibiotic-related action pathways. Furthermore, the most significantly altered molecular network was involved in amino acid metabolism, molecular transport, and small molecule biochemistry. CONCLUSIONS: This study provides important clues for the metabolic characteristics of the PFC in depression.

4.
Plant Physiol ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32366640

RESUMO

Hydrogen gas (H2) has a possible signaling role in many developmental and adaptive plant responses, including mitigating the harmful effects of cadmium (Cd) uptake from soil. We used electrophysiological and molecular approaches to understand how H2 ameliorates Cd toxicity in pak choi (Brassica chinensis). Exposure of pak choi roots to Cd resulted in a rapid increase in the intracellular H2 production. Exogenous application of hydrogen-rich water (HRW) resulted in a Cd-tolerant phenotype, with reduced net Cd uptake and accumulation. We showed that this is dependent upon the transport of calcium ions (Ca2+) across the plasma membrane and apoplastic generation of hydrogen peroxide (H2O2) by Respiratory burst oxidase homolog (BcRbohD) . The reduction in root Cd uptake associated with the application of exogenous HRW or H2O2. This reduction was abolished in the iron-regulated transporter1 (Atirt1) mutant of Arabidopsis (Arabidopsis thaliana), and pak choi pretreated with HRW showed decreased BcIRT1 transcript levels. Roots exposed to HRW had rapid Ca2+ influx and Cd-induced Ca2+ leakage was alleviated. Two Ca2+ channel blockers, gadolinium ion and lanthanum ion (Gd3+ and La3+), eliminated the HRW-induced increase in BcRbohD expression, H2O2 production and Cd2+ influx inhibition. Collectively, our results suggest that the Cd-protective effect of H2 in plants may be explained by its control of the plasma membrane-based NADPH oxidase encoded by RbohD, which operates upstream of IRT1 and regulates root Cd uptake at both transcriptional and functional levels. These findings provide a mechanistic explanation for the alleviatory role of H2 in Cd accumulation and toxicity in plants.

5.
Nat Commun ; 11(1): 1955, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32327664

RESUMO

Branching/tillering is an important parameter of plant architecture and is tightly regulated by both internal factors (such as plant hormones) and external factors (such as light conditions). How the various signaling pathways converge to coordinately regulate branching is not well understood. Here, we report that in Arabidopsis, FHY3 and FAR1, two homologous transcription factors essential for phytochrome A-mediated light signaling, and SMXL6/SMXL7/SMXL8, three key repressors of the strigolactone (SL) signaling pathway, directly interact with SPL9 and SPL15 and suppress their transcriptional activation of BRC1, a key repressor of branching, thus promoting branching. In addition, FHY3 and FAR1 also directly up-regulate the expression of SMXL6 and SMXL7 to promote branching. Simulated shade treatment reduces the accumulation of FHY3 protein, leading to increased expression of BRC1 and reduced branching. Our results establish an integrated model of light and SL coordinately regulating BRC1 expression and branching through converging at the BRC1 promoter.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32287020

RESUMO

Deep generative models have demonstrated their effectiveness in learning latent representation and modeling complex dependencies of time series. In this article, we present a smoothness-inducing sequential variational auto-encoder (VAE) (SISVAE) model for the robust estimation and anomaly detection of multidimensional time series. Our model is based on VAE, and its backbone is fulfilled by a recurrent neural network to capture latent temporal structures of time series for both the generative model and the inference model. Specifically, our model parameterizes mean and variance for each time-stamp with flexible neural networks, resulting in a nonstationary model that can work without the assumption of constant noise as commonly made by existing Markov models. However, such flexibility may cause the model fragile to anomalies. To achieve robust density estimation which can also benefit detection tasks, we propose a smoothness-inducing prior over possible estimations. The proposed prior works as a regularizer that places penalty at nonsmooth reconstructions. Our model is learned efficiently with a novel stochastic gradient variational Bayes estimator. In particular, we study two decision criteria for anomaly detection: reconstruction probability and reconstruction error. We show the effectiveness of our model on both synthetic data sets and public real-world benchmarks.

7.
Plant Cell ; 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32265265

RESUMO

The antagonistic regulation of seed germination by the phytohormone ABA and GA has been well-established. However, how these phytohormones antagonistically regulate root growth and branching (tillering in rice) remains obscure. Rice Tiller Enhancer (TE) encodes an activator of the APC/CTE E3 ubiquitin ligase complex that represses tillering but promotes seed germination. In this study, we found a dual role of GA and APC/CTE in regulating root growth. High GA levels can activate APC/CTE to promote the degradation of OsSHR1 (a key promoting factor of root growth) in the root meristem (RM) or MOC1 (a key promoting factor of tillering) in the axillary meristem (AM), leading to restricted root growth and tillering; while low GA levels can activate the role of APC/CTE in stimulating RM cell division to promote root growth. In addition, we found that moderate enhancement of ABA signaling helps to maintain the RM or AM size to sustain root growth or tillering by antagonizing GA-promoted degradation of OsSHR1 and MOC1 through the SnRK2-APC/CTE regulatory module. We conclude that APC/CTE plays a key role in regulating plant architecture by mediating the signaling cross talks between ABA and GA.

8.
Transl Oncol ; 13(5): 100770, 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32298986

RESUMO

Extranodal nasal natural killer (NK)/T cell lymphoma (ENKTCL) is a rare but highly aggressive subtype of non-Hodgkin lymphoma (NHL). Nevertheless, despite extensive research, the estimated 5-year overall survival of affected patients remains low. Therefore, new treatment strategies are needed urgently. Recent advances in immunotherapy have the potential to broaden the applications of chimeric antigen receptor-modified T (CAR-T) cells and the bispecific T-cell engaging (BiTE) antibody. Here, we screened a panel of biomarkers including the B7-H3, CD70, TIM-3, VISTA, ICAM-1, and PD-1 in NKTCL cell lines. As a result, we found for the first time that B7-H3 was highly and homogeneously expressed in these cells. Consequently, we constructed a novel anti-B7-H3/CD3 BiTE antibody and B7-H3-redirected CAR-T cells, and evaluated their efficacy against NKTCL cel lines both in vitro and in vivo. Notably, we found that both anti-B7-H3/CD3 BiTE and B7-H3-redirected CAR-T cells effectively targeted and killed NKTCL cells in vitro, and suppressed the growth of NKTCL tumors in NSG mouse models. Thus, B7-H3 might be a promising therapeutic target for treating patients with NKTCL tumors.

9.
Nat Genet ; 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32341525

RESUMO

Since the development of single-hybrid maize breeding programs in the first half of the twentieth century1, maize yields have increased over sevenfold, and much of that increase can be attributed to tolerance of increased planting density2-4. To explore the genomic basis underlying the dramatic yield increase in maize, we conducted a comprehensive analysis of the genomic and phenotypic changes associated with modern maize breeding through chronological sampling of 350 elite inbred lines representing multiple eras of germplasm from both China and the United States. We document several convergent phenotypic changes in both countries. Using genome-wide association and selection scan methods, we identify 160 loci underlying adaptive agronomic phenotypes and more than 1,800 genomic regions representing the targets of selection during modern breeding. This work demonstrates the use of the breeding-era approach for identifying breeding signatures and lays the foundation for future genomics-enabled maize breeding.

10.
Cancer Imaging ; 20(1): 28, 2020 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-32321585

RESUMO

BACKGROUND: The aim of this study was to evaluate the prognostic value of radiomics signature and nomogram based on contrast-enhanced computed tomography (CT) in patients after surgical resection of laryngeal squamous cell carcinoma (LSCC). METHODS: All patients (n = 136) were divided into the training cohort (n = 96) and validation cohort (n = 40). The LASSO regression method was performed to construct radiomics signature from CT texture features. Then a radiomics nomogram incorporating the radiomics signature and clinicopathologic factors was established to predict overall survival (OS). The validation of nomogram was evaluated by calibration curve, concordance index (C-index) and decision curve. RESULTS: Based on three selected texture features, the radiomics signature showed high C-indexes of 0.782 (95%CI: 0.656-0.909) and 0.752 (95%CI, 0.614-0.891) in the two cohorts. The radiomics nomogram had significantly better discrimination capability than cancer staging in the training cohort (C-index, 0.817 vs. 0.682; P = 0.009) and validation cohort (C-index, 0.913 vs. 0.699; P = 0.019), as well as a good agreement between predicted and actual survival in calibration curves. Decision curve analysis also suggested improved clinical utility of radiomics nomogram. CONCLUSIONS: Radiomics signature and nomogram showed favorable prediction accuracy for OS, which might facilitate the individualized risk stratification and clinical decision-making in LSCC patients.

11.
Sci Adv ; 6(14): eaaz5004, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32284983

RESUMO

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

12.
Plant Cell ; 32(5): 1464-1478, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32152179

RESUMO

The circadian clock provides a time-keeping mechanism that synchronizes various biological activities with the surrounding environment. Arabidopsis (Arabidopsis thaliana) CIRCADIAN CLOCK ASSOCIATED1 (CCA1), encoding a MYB-related transcription factor, is a key component of the core oscillator of the circadian clock, with peak expression in the morning. The molecular mechanisms regulating the light induction and rhythmic expression of CCA1 remain elusive. In this study, we show that two phytochrome signaling proteins, FAR-RED ELONGATED HYPOCOTYL3 (FHY3) and its paralog FAR-RED IMPAIRED RESPONSE1 (FAR1), are essential for the light-induced expression of CCA1 FHY3 and FAR1 directly bind to the CCA1 promoter and activate its expression, whereas PHYTOCHROME INTERACTING FACTOR5 (PIF5) directly binds to its promoter and represses its expression. Furthermore, PIF5 and TIMING OF CAB EXPRESSION1 physically interact with FHY3 and FAR1 to repress their transcriptional activation activity on CCA1 expression. These findings demonstrate that the photosensory-signaling pathway integrates with circadian oscillators to orchestrate clock gene expression. This mechanism might form the molecular basis of the regulation of the clock system by light in response to daily changes in the light environment, thus increasing plant fitness.

13.
Transl Psychiatry ; 10(1): 95, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32179735

RESUMO

Major depressive disorder (MDD) is a prevalent and debilitating psychiatric mood disorder that lacks objective laboratory-based tests to support its diagnosis. A class of microRNAs (miRNAs) has been found to be centrally involved in regulating many molecular processes fundamental to central nervous system function. Among these miRNAs, miRNA-134 (miR-134) has been reported to be related to neurogenesis and synaptic plasticity. In this study, the hypothesis that plasma miR-134 can be used to diagnose MDD was tested. Perturbation of peripheral and central miR-134 in a depressive-like rat model was also examined. By reverse-transcription quantitative PCR, miR-134 was comparatively measured in a small set of plasma samples from MDD and healthy control (HC) subjects. To determine its diagnostic efficacy, plasma miR-134 levels were assessed in 100 MDD, 50 bipolar disorder (BD), 50 schizophrenic (SCZ), and 100 HC subjects. A chronic unpredictable mild stress (CUMS) rat model was also developed to evaluate miR-134 expression in plasma, hippocampus (HIP), prefrontal cortex (PFC), and olfactory bulb. We found that plasma miR-134 was significantly downregulated in MDD subjects. Diagnostically, plasma miR-134 levels could effectively distinguish MDD from HC with 79% sensitivity and 84% specificity, while distinguishing MDD from HC, BD, and SCZ subjects with 79% sensitivity and 76.5% specificity. Congruent with these clinical findings, CUMS significantly reduced miR-134 levels in the rat plasma, HIP, and PFC. Although limited by the relatively small sample size, these results demonstrated that plasma miR-134 displays potential ability as a biomarker for MDD.

14.
PLoS One ; 15(3): e0229764, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130263

RESUMO

BACKGROUND: To investigate mosquito larval habitats and resistance to common insecticides in areas with high incidence rates of mosquito-borne diseases in Jining, Shandong Province, and to provide a scientific basis for the future prevention and control of mosquito-borne diseases and the rational use of insecticides. METHODS AND RESULTS: From June to September 2018, mosquito habitat characteristics and species compositions in Jintun town were studied through a cross-sectional survey. Larvae and pupae were collected in different habitats using the standard dipping technique. A total of 7,815 mosquitoes, comprising 7 species from 4 genera, were collected. Among them, Culex pipiens pallens (n = 5,336, 68.28%) was the local dominant species and found in all four habitats (rice paddies, irrigation channels, water containers, drainage ditches). There were 1,708 Cx. tritaeniorhynchus (21.85%), 399 Anopheles sinensis (5.11%), 213 Armigeres subalbatus (2.72%), 124 Aedes albopictus (1.59%), and 35 other (Cx. bitaeniorhynchus and Cx. halifaxii) (0.45%) mosquito samples collected. Spearman correlation analysis was employed to evaluate the relationship between larval density and the physicochemical characteristics of the breeding habitat. It was found that the larval density of Cx. tritaeniorhynchus correlated positively with water depth (r = 0.927 p = 0.003), the larval density of An. sinensis correlated positively with dissolved oxygen (DO) (r = 0.775 p = 0.041) and the larval density of Cx. p. pallens correlated positively with ammonia nitrogen (r = 0.527 p = 0.002). Resistance bioassays were carried out on the dominant populations of Cx. p. pallens: mosquitoes presented very high resistance to cypermethrin and deltamethrin, moderate resistance to dichlorvos (DDVP), and low resistance to Bacillus thuringiensis israelensis (Bti), with decreased susceptibility to propoxur. CONCLUSION: We showed that mosquito species vary across habitat type and that the mosquito larval density correlated positively with certain physicochemical characteristics in different habitats. In addition, Cx. p. pallens developed different levels of resistance to five insecticides. Vector monitoring should be strengthened after an epidemic, and further research should be conducted to scientifically prevent and kill mosquitoes.

15.
Atherosclerosis ; 297: 47-54, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32078829

RESUMO

BACKGROUND AND AIMS: Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease when aortic rupture occurs, especially for elders. There is an urgent need to understand the mechanisms of AAA formation and development at molecular level. Our previous study showed that disintegrin and metalloprotease 10 (ADAM10) played an important role in abdominal aortic aneurysm formation. In this study, we investigated the effects of another ADAM protein (ADMA9) in AAA formation. METHOD AND RESULTS: Using AngII treated human aortic smooth muscle cells (HASMCs) and human aortic endothelial cells (hAoECs) as in vitro AAA model and murine AAA model, ADAM9 was overexpressed suggesting that ADAM9 may play important roles in AAA formation. Further investigation showed that ADAM9 induced inflammation leading to increased macrophage infiltration. ADAM9 was also found to induce cell apoptosis. AKT/NF-κB pathway was activated in murine AAA. Bioinformatic analysis showed that the 3' UTR of ADMA9 was a potential target of miR-126. We investigated the potential of using miR-126 to modulate ADAM9 expression. The expression level of miR-126 was decreased and inversely correlated with the expression of ADAM9 in the in vitro AAA model. Further investigation showed that miR-126 negatively regulated gene expression of ADAM9 and suppressed the production of inflammatory cytokines. miR-126 was also found to improve cell survival and significantly reduce AAA formation in murine AAA. CONCLUSIONS: Our data revealed a link between ADAM9 and AAA formation, providing an approach to control AAA development using miR-126, possibly through modulation of the expression level of ADAM9.

16.
Plant Signal Behav ; 15(3): 1726636, 2020 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-32043408

RESUMO

Phytochrome A (phyA) is the primary photoreceptor mediating various plant responses to far-red (FR) light. The defense-related phytohorme jasmonic acid (JA) has been shown recently to play a role in regulating phyA-mediated FR signaling. However, the detailed molecular mechanisms governing phyA- and JA-mediated signaling cross talks are still not well understood. Here, we uncover a molecular cascade in which JAZ1 inactivates phyA signaling through repressing the transcriptional activity of FHY3 on FHY1 and FHL. Furthermore, we demonstrate that the expression levels of FHY1 and FHL, and some FR response genes are reduced in the coi1 mutant. These findings unveil a previously unrecognized mechanism whereby JA modulates phyA signaling through repressing the activities of FHY3 by JAZs.

17.
Medicine (Baltimore) ; 99(5): e18810, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000381

RESUMO

Complex reconstruction skills in advanced head and neck cancer (HNC) could resolve the key problem of large defects after tumor resection. We combined the anterolateral thigh free flap, fascia lata flap, and greater saphenous vein graft in the reconstruction process of salvage surgery. Seven patients suffering from advanced HNC who experienced the failure of multiple therapeutic methods were enrolled in our study between June 2017 and January 2018. They all agreed to voluntarily undergo the tumor excision and complex reconstruction procedure we developed. The total flap size ranged from 20 × 13 cm to 30 × 15 cm. The length of the greater saphenous vein graft ranged from 4 to 11 cm. The hospitalization period ranged from 7 to 33 days. All of the flaps were viable, but in 1 patient, oral flap edge infection and necrosis necessitated partial debridement on day 7 postoperatively. All donor sites were closed primarily. We report our experience with this surgical method for complex reconstruction in advanced HNC patients.


Assuntos
Fascia Lata/transplante , Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Veia Safena/transplante , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Mol Plant ; 13(3): 483-498, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32017999

RESUMO

In response to competition for light from their neighbors, shade-intolerant plants flower precociously to ensure reproductive success and survival. However, the molecular mechanisms underlying this key developmental switch are not well understood. Here, we show that a pair of Arabidopsis transcription factors essential for phytochrome A signaling, FAR-RED ELONGATED HYPOCOTYL3 (FHY3) and FAR-RED IMPAIRED RESPONSE1 (FAR1), regulate flowering time by integrating environmental light signals with the miR156-SPL module-mediated aging pathway. We found that FHY3 and FAR1 directly interact with three flowering-promoting SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors, SPL3, SPL4, and SPL5, and inhibit their binding to the promoters of several key flowering regulatory genes, including FRUITFUL (FUL), LEAFY (LFY), APETALA1 (AP1), and MIR172C, thus downregulating their transcript levels and delaying flowering. Under simulated shade conditions, levels of SPL3/4/5 proteins increase, whereas levels of FHY3 and FAR1 proteins decline, thus releasing SPL3/4/5 from FHY3/FAR1 inhibition to allow activation of FUL, LFY, AP1, and MIR172C and, consequently, early flowering. Taken together, these results unravel a novel mechanism whereby plants regulate flowering time by integrating environmental cues (such as light conditions) and an internal developmental program (the miR156-SPL module-mediated aging pathway).

19.
iScience ; 23(2): 100840, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-32004992

RESUMO

A highly efficient phosphine-catalyzed enantioselective [4 + 2] annulation of allenoates with 3-nitroindoles or 3-nitrobenzothiophenes has been developed. The protocol represents a unique dearomatization-aromatization process to access functionalized dihydrocarbazoles or dihydrodibenzothiophenes with high optical purity (up to 97% ee) under mild reaction conditions. The synthetic utility of the highly enantioselective [4 + 2] annulation enables a concise synthesis of analgesic agent.

20.
Hum Gene Ther ; 31(7-8): 440-447, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32056463

RESUMO

Regulation of gene expression by viral vectors is an effective method for researchers to explore the function of gene products in a target tissue. The choroid plexus (CP) is an important target for gene therapy of neuropsychiatric diseases such as Alzheimer's disease and major depressive disorder. However, viral tropism in CP has not been well studied as a result of limited viral vector applications. To identify CP-specific viral vectors, we intracerebroventricularly administered six different serotypes of adeno-associated virus (AAV) vectors (AAV2/1, AAV2/5, AAV2/8, AAV2/9, AAV2-BR1, and AAV2-PHP.eB) and lentivirus in adult mice. Tropism in CP was compared among these viruses. We found that AAV2/5 and AAV2/8 displayed remarkable infections in CP, while AAV2/1 infected both ependymal cells and cells in the CP. Except for the low infection intensity of AAV2/9 and lentivirus in the CP, no infection intensity was found for CP tissues injected with AAV2-BR1 or AAV2-PHP.eB. Green fluorescence protein expression in the CP after AAV2/5 infection was confirmed by Western blotting. AAV2/5-mediated tropism in epithelial cells of the CP was verified by immunostaining with transthyretin. In this study, we identified for the first time that serotype-specific AAVs 5 and 8 may be robust research tools for intracerebroventricular gene delivery.

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