We investigated a genetic pathway in root hair development in Arabidopsis thaliana, involving the receptor-like kinase FERONIA (FER), two guanine nucleotide exchange factors for ROPs (RopGEF4 and ...RopGEF10), and the small GTPase Rho of plants (ROPs).
Loss- and gain-of-function analyses demonstrated distinct roles of RopGEF4 and RopGEF10 such that RopGEF4 is only important for root hair elongation, while RopGEF10 mainly contributes to root hair initiation. Domain dissection by truncation and domain-swapping experiments indicated that their functional distinctions were mainly contributed by the noncatalytic domains.
Using fluorescent ratio imaging, we showed that functional loss of RopGEF4 and RopGEF10 additively reduced reactive oxygen species (ROS) production. Bimolecular fluorescence complementation experiments demonstrated that RopGEF4 and RopGEF10 had the same interaction specificity as ROPs, suggesting common downstream components.
We further showed that the promoting effects of environmental cues such as exogenous auxin and phosphate limitation on root hair development depended on FER. However, although functional loss of RopGEF4 and RopGEF10 largely abolished FER-induced ROS production, it did not compromise the responses to FER-mediated environmental cues on root hair development. Our results demonstrated that RopGEF4 and RopGEF10 are genetic components in FER-mediated, developmentally (but not environmentally) regulated, root hair growth.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Neuronal nuclei (NeuN) is a well-recognized “marker” that is detected exclusively in post-mitotic neurons and was initially identified through an immunological screen to produce neuron-specific ...antibodies. Immunostaining evidence indicates that NeuN is distributed in the nuclei of mature neurons in nearly all parts of the vertebrate nervous system. NeuN is highly conserved among species and is stably expressed during specific stages of development. Therefore, NeuN has been considered to be a reliable marker of mature neurons for the past two decades. However, this role has been challenged by recent studies indicating that NeuN staining is variable and even absent during certain diseases and specific physiological states. More importantly, despite the widespread use of the anti-NeuN antibody, the natural identity of the NeuN protein remained elusive for 17 years. NeuN was recently eventually identified as an epitope of Rbfox3, which is a novel member of the Rbfox1 family of splicing factors. This identification might provide a novel perspective on NeuN expression during both physiological and pathological conditions. This review summarizes the current progress on the biochemical identity and biological significance of NeuN and recommends caution when applying NeuN immunoreactivity as a definitive marker of mature neurons in certain diseases and specific physiological states.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Long non‐coding RNAs (lncRNAs) have emerged as new and important regulators of pathological processes including tumour development. In this study, we demonstrated that differentiation antagonizing ...non‐protein coding RNA (DANCR) was up‐regulated in lung adenocarcinoma (ADC) and that the knockdown of DANCR inhibited tumour cell proliferation, migration and invasion and restored cell apoptosis rescued; cotransfection with a miR‐496 inhibitor reversed these effects. Luciferase reporter assays showed that miR‐496 directly modulated DANCR; additionally, we used RNA‐binding protein immunoprecipitation (RIP) and RNA pull‐down assays to further confirm that the suppression of DANCR by miR‐496 was RISC‐dependent. Our study also indicated that mTOR was a target of miR‐496 and that DANCR could modulate the expression levels of mTOR by working as a competing endogenous RNA (ceRNA). Furthermore, the knockdown of DANCR reduced tumour volumes in vivo compared with those of the control group. In conclusion, this study showed that DANCR might be an oncogenic lncRNA that regulates mTOR expression through directly binding to miR‐496. DANCR may be regarded as a biomarker or therapeutic target for ADC.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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•Broflanilide shows low toxicity to zebrafish (Danio rerio).•Both CYP450 and GST significantly contribute to the detoxification of broflanilide.•Long-term exposure to broflanilide ...could lead high bioconcentration risks in D. rerio.
Broflanilide, a novel meta-diamide insecticide, shows high insecticidal activity against agricultural pests and is scheduled to be launched onto the market in 2020. However, little information about its potential toxicological effects on fish has been reported. In this study, broflanilide showed low toxicity to the zebrafish, Danio rerio, with LC50 > 10 mg L−1 at 96 h and also did not inhibit GABA-induced currents of the heteromeric Drα1β2Sγ2 GABA receptor. Broflanilide showed medium bioconcentration level with a bioconcentration factor at steady state (BCFss) of 10.02 and 69.40 in D. rerio at 2.00 mg L−1 and 0.20 mg L−1, respectively. In the elimination process, the concentration of broflanilide rapidly decreased within two days and slowly dropped below the limit of quantification after ten days. In the 2.00 mg L-1 broflanilide treatment, CYP450 activity was significantly increased up to 3.11-fold during eight days. Glutathione-S- transferase (GST) activity significantly increased by 91.44 % within four days. In conclusion, the acute toxicity of broflanilide was low, but it might induce chronic toxicity, affecting metabolism. To our knowledge, this is the first report of the toxicological effects of broflanilide on an aquatic organism, which has the potential to guide the use of broflanilide in the field.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Macrophage infiltration and polarization during lumbar intervertebral disc herniation (LDH) have attracted increased attention but their role remains unclear. To explore macrophage polarization in ...herniated nucleus pulposus (NP) tissue of patients with LDH and investigate the association between cell frequency and different clinical characteristics or symptoms, we conducted a retrospective study by analyzing NP tissue samples from 79 patients. Clinical features and symptoms, using the visual analog scale (VAS) and Oswestry disability index (ODI), were collected. The macrophage markers CD68, CCR7, CD163, and CD206; pro‐inflammatory cytokine TNF‐α; and anti‐inflammatory factor IL‐4 were analyzed by immunohistochemistry. The frequency of polarized macrophages and positivity rate of pro‐ and anti‐inflammatory cytokines showed significant differences in some of clinical characteristics. Specifically, higher CCR7+ and TNF‐α + proportions were identified in the high‐intensity zone (HIZ) and the type of extrusion and sequestration NP tissue than in non‐HIZ and protrude NP tissue. Higher CD206+ and IL‐4+ proportion were detected in Modic changes. However, no differences in gender, age, smoking status, Pfirrmann grade, analgesic use, leg pain duration, and segments were found between groups. CD68+, CCR7+, and CD206+ cell proportions, and TNF‐α and IL‐4 showed positive associations with VAS scores preoperation. Associations between ODI and the macrophages markers were weak/insignificant. Our results indicated that macrophage polarization or macrophage‐like cells contribute to LDH pathological features. Macrophage populations displaying significant associations with VAS score reflected continuous M1/M2 transition contributing to pain during LDH. These findings may contribute to enhanced/personalized pharmacological interventions for patients with LDH considering pain heterogeneity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Highlights • Molecular mechanism is still unknown for LC development in RA patients. • The COX-2/TxA2 pathway can be induced in tumour and synovial tissue. • A positive feedback loop for the ...COX-2/TxA2 pathway promotes LC growth. • Such a feedback loop may also exist in RA-FLS. • Targeting COX-2-derived TxA2 may block LC development in RA patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Recent studies suggested that activation of Uncoupling Protein 1 (UCP1) has become an appealing therapeutic strategy against obesity and diabetes. In our research, the 3D structure of UCP1 was ...constructed through homology modelling, refined through molecular dynamics simulation, and evaluated by Ramachandran plot, the molecular docking of UCP1 activators brought about the proposal of an interaction mode inside the UCP1 active site. Remarkably, Reside Lys126 formed hydrogen bond; residues Pro121, Val125, Tyr146, Tyr149 and Arg150 formed hydrophobic interaction, which are key amino acids within UCP1 site. Then a pharmacophore model was generated consisting of three hydrophobic groups, a negative center and an additional hydrophobic group. Pharmacophore‐based virutal screening of Specs database yield 5 hits. In vitro assay indicated ZINC 04660290 significantly increased the protein expression of UCP1 and decreased the fat droplet in a dose‐dependent manner. Besides, pharmacokinetic properties were predicted for those five compounds through ADME/T prediction. All of these will guide us to design new UCP1 activators for the treatment of obesity and diabetes.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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