•PIFs have diverged to regulate various aspects of plant life cycles.•PIF is conserved from seed plants to liverwort.•Tomato PIF1a regulates carotenoid synthesis in fruits.•Liverwort PIF regulates ...gemma germination and LHCB and POR mRNA expression.•The phy–PIF regulon emerged early in land plant evolution.
Phytochromes are red and far-red light photoreceptors that regulate the responses of plants to light throughout their life cycles. Phytochromes do this in part by inhibiting the function of a group of basic helix-loop-helix transcription factors called phytochrome-interacting factors (PIFs). Arabidopsis has eight PIFs that function sometimes redundantly and sometimes distinctively depending on their expression patterns and protein stability, as well as on variations in the promoters they target in vivo. PIF-like proteins exist in other seed plants and non-vascular plants where they also regulate light responses. The mechanism by which phytochrome regulates light responses by promoting the degradation of the PIFs is conserved in liverwort, suggesting it must have evolved some time before the last common ancestor shared by seed plants and non-vascular plants.
Inappropriate information on a deadly and rare disease can make people vulnerable to problematic decisions, leading to irreversible bad outcomes. This study explored online information exchanges on ...pancreatic cancer. We collected 35,596 questions and 83,888 answers related to pancreatic cancer from January 1, 2003 to May 31, 2020, from Naver, the most popular Korean web portal. We also collected 8495 news articles related to pancreatic cancer during the same period. The study methods employed were structural topic modeling, keyword frequency analysis, and qualitative coding of medical professionals. The number of questions and news articles increased over time. In Naver's questions, topics on symptoms and diagnostic tests regarding pancreatic cancer increased in proportion. The news topics on new technologies related to pancreatic cancer from various companies increased as well. The use of words related to back pain-which is not an important early symptom in pancreatic cancer-and biomarker tests using blood increased over time in Naver's questions. Based on 100 question samples related to symptoms and diagnostic tests and an analysis of the threaded answers' appropriateness, there was considerable misinformation and commercialized information in both categories.
Antidepressants are extensively used to treat the symptoms of depression in humans, and the environmentally discharged drugs potentially threaten aquatic organisms. In this study, the acute toxic ...effects of fluoxetine (FLX) were investigated in two aquatic organisms, the freshwater polyp (Hydra magnipapillata) and Javanese medaka (Oryzias javanicus). The median lethal concentration (LC50) of FLX in H. magnipapillata was 3.678, 3.082, and 2.901 mg/L after 24, 48, and 72 h, respectively. Morphological observations of the FLX-exposed H. magnipapillata showed that 1.5 mg/L FLX induced the contraction of the tentacles and body column. The LC50 of FLX in O. javanicus was 2.046, 1.936, 1.532, and 1.237 mg/L after 24, 48, 72, and 96 h, respectively. Observation of the behavior of the FLX-exposed fish showed that FLX reduced their swimming performance at a minimum concentration of 10 µg/L. The half-maximal effective concentration (EC50) of FLX for swimming behavior in O. javanicus was 0.135, 0.108, and 0.011 mg/L after 12, 24, and 96 h, respectively. Transcriptomic analyses indicated that FLX affects various physiological and metabolic processes in both species. FLX exposure induced oxidative stress, reproductive deficiency, abnormal pattern formation, DNA damage, and neurotransmission disturbance in H. magnipapillata, whereas it adversely affected O. javanicus by inducing oxidative stress, DNA damage, endoplasmic reticulum stress, and mRNA instability. Neurotransmission-based behavioral changes and endocrine disruption were strongly suspected in the FLX-exposed fish. These results suggest that FLX affects the behavior and metabolic regulation of aquatic organisms.
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•Acute fluoxetine exposure induces lethal effects on hydra and fish.•Fluoxetine induces contraction of the tentacles and body column in hydra.•Fluoxetine reduces swimming activities in fish.•Fluoxetine interferes neuropeptides secretion and neurotransmission associated with body contraction in hydra.•Fluoxetine interferes behavior, circadian rhythm and neurotransmission associated with reduced swimming activities in fish.
Floral transition from the vegetative to the reproductive stages is precisely regulated by both environmental and endogenous signals. Among these signals, photoperiod is one of the most important ...environmental factors for onset of flowering. A florigen, FLOWERING LOCUS T ( FT ) in Arabidopsis , has thought to be a major hub in the photoperiod-dependent flowering time regulation. Expression levels of FT likely correlates with potence of flowering. Under long days (LD), FT is mainly synthesized in leaves, and FT protein moves to shoot apical meristem (SAM) where it functions and in turns induces flowering. Recently, it has been reported that Arabidopsis grown under natural LD condition flowers earlier than that grown under laboratory LD condition, in which a red (R)/far-red (FR) ratio of light sources determines FT expression levels. Additionally, FT expression profile changes in response to combinatorial effects of FR light and photoperiod. FT orthologs exist in most of plants and functions are thought to be conserved. Although molecular mechanisms underlying photoperiodic transcriptional regulation of FT orthologs have been studied in several plants, such as rice, however, dynamics in expression profiles of FT orthologs have been less spotlighted. This review aims to revisit previously reported but overlooked expression information of FT orthologs from various plant species and classify these genes depending on the expression profiles. Plants, in general, could be classified into three groups depending on their photoperiodic flowering responses. Thus, we discuss relationship between photoperiodic responsiveness and expression of FT orthologs. Additionally, we also highlight the expression profiles of FT orthologs depending on their activities in flowering. Comparative analyses of diverse plant species will help to gain insight into molecular mechanisms for flowering in nature, and this can be utilized in the future for crop engineering to improve yield by controlling flowering time.
Seeds monitor the environment to germinate at the proper time, but different species respond differently to environmental conditions, particularly light and temperature. In Arabidopsis thaliana, ...light promotes germination but high temperature suppresses germination. We previously reported that light promotes germination by repressing SOMNUS (SOM). Here, we examined whether high temperature also regulates germination through SOM and found that high temperature activates SOM expression. Consistent with this, som mutants germinated more frequently than the wild type at high temperature. The induction of SOM mRNA at high temperature required abscisic acid (ABA) and gibberellic acid biosynthesis, and ABA-INSENSITME3 (ABI3), ABI5, and DELLAs positively regulated SOM expression. Chromatin immunoprecipitation assays indicated that ABI3, ABI5, and DELLAs all target the SOM promoter. At the protein level, ABI3, ABI5, and DELLAs all interact with each other, suggesting that they form a complex on the SOM promoter to activate SOM expression at high temperature. We found that high-temperature-inducible genes frequently have RY motifs and ÁÂÁ-responsive elements in their promoters, some of which are targeted by ABI3, ABI5, and DELLAs in vivo. Taken together, our data indicate that ABI3, ABI5, and DELLAs mediate high-temperature signaling to activate the expression of SOM and other high-temperature-inducible genes, thereby inhibiting seed germination.
Seed dormancy, a seed status that prohibits germination even in the presence of inductive germination signals, is a poorly understood process. To identify molecular components that regulate seed ...dormancy, we screened T-DNA insertion lines and identified a mutant designated honsu (hon). HON loss-of-function mutants display deep seed dormancy, whereas HON-overexpressing lines display shallow seed dormancy. HON encodes a seed-specific group A phosphatase 2C (PP2C) and is one of the major negative regulators of seed dormancy among group A PP2Cs. Like other PP2C family members, HON interacts with PYR1/RCAR11 in the presence of ABA. Our analysis indicates that HON inhibits ABA signaling and activates gibberellic acid signaling, and both of these conditions must be satisfied to promote the release of seed dormancy. However, HON mRNA levels are increased in mutants displaying deep seed dormancy or under conditions that deepen seed dormancy, and decreased in mutants displaying shallow seed dormancy or under conditions that promote the release of seed dormancy. Taken together, our results indicate that the expression of HON mRNA is homeostatically regulated by seed dormancy.
Amyloid beta (Aβ) peptide, one of the most important pathogenic traits of Alzheimer's disease (AD), invokes a cascade of oxidative damage and eventually leads to neuronal death. In the present study, ...baicalein, wogonin, and oroxylin A, main active flavones in
, were evaluated for their neuroprotective effects against Aβ
-stimulated damage. All tested compounds decreased Aβ
-induced ROS generation and cell cycle arrest. In particular, baicalein exhibited the strongest antioxidant activity. In addition, these compounds suppressed apoptosis by attenuating mitochondrial dysfunction such as loss of membrane potential, Ca
accumulation and Bax/Bcl-2 ratio. Furthermore, all tested flavones inhibited the expression of iNOS and COX-2, which resulted in suppressing inflammatory cytokines including TNF-α, NO, and PGE
. Noticeably, all compounds exhibited the anti-inflammatory effects through downregulating NF-κB/MAPK pathway. Especially, oroxylin A was effective against both p65 and IκBα, while wogonin and baicalein were suppressed phospho-p65 and phospho-IκBα, respectively. Taken together, baicalein, wogonin, and oroxylin A can effectively relieve Aβ
-stimulated neuronal apoptosis and inflammation in PC12 cells via downregulating NF-κB/MAPK signaling pathway.
A biosimilar is a biological medicinal product that contains a version of the active substance of an already authorized original biological medicinal product. Biosimilarity to the reference product ...(RP) in terms of quality characteristics, such as physicochemical and biological properties, safety, and efficacy, based on a comprehensive comparability exercise needs to be established. SB2 (Flixabi® and Renflexis®) is a biosimilar to Remicade® (infliximab). The development of SB2 was performed in accordance with relevant guidelines of the International Conference on Harmonisation, the European Medicines Agency, and the United States Food and Drug Administration. To determine whether critical quality attributes meet quality standards, an extensive characterization test was performed with more than 80 lots of EU- and US-sourced RP. The physicochemical characterization study results revealed that SB2 was similar to the RP. Although a few differences in physicochemical attributes were observed, the evidence from the related literature, structure-activity relationship studies, and comparative biological assays showed that these differences were unlikely to be clinically meaningful. The biological characterization results showed that SB2 was similar to the RP in terms of tumor necrosis factor-α (TNF-α) binding and TNF-α neutralization activities as a main mode of action. SB2 was also similar in Fc-related biological activities including antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, neonatal Fc receptor binding, C1q binding, and Fc gamma receptor binding activities. These analytical findings support that SB2 is similar to the RP and also provide confidence of biosimilarity in terms of clinical safety and efficacy.
Bioluminescence is a powerful biological signal that scientists have repurposed as a reporter for gene expression in plants and animals. However, there are downsides associated with the need to ...provide a substrate to these reporters, including its high cost and non-uniform tissue penetration. In this work we reconstitute a fungal bioluminescence pathway (FBP)
using a composable toolbox of parts. We demonstrate that the FBP can create luminescence across various tissues in a broad range of plants without external substrate addition. We also show how our toolbox can be used to deploy the FBP
to build auto-luminescent reporters for the study of gene-expression and hormone fluxes. A low-cost imaging platform for gene expression profiling is also described. These experiments lay the groundwork for future construction of programmable auto-luminescent plant traits, such as light driven plant-pollinator interactions or light emitting plant-based sensors.
This study analyzed the sex difference in the effect of smoking exposure on lung cancer in terms of absolute and relative risks despite the increasing lung cancer incidence in Asian female never ...smokers. A retrospective cohort study was conducted on individuals aged 40-79 years who participated in the national health screening program in 2007 and 2008 with linkage to the Korea Central Cancer Registry records. We evaluated sex differences in the age-standardized incidence rate (ASR) of lung cancer by smoking history and the hazard ratio (HR) after adjusting for potential confounders. ASRs for male and female never smokers were 92.5 and 38.3 per 100,000 person-years, respectively (rate ratio (RR) = 2.4; 95% confidence interval (CI) = 2.3-2.5). ASRs for male and female current smokers with a 30 pack-year smoking history were 305.3 and 188.4 per 100,000 person-years, respectively (RR = 1.6; 95% CI = 1.3-2.0). Smoking was significantly associated with lung cancer risk for both sexes. HRs for former smokers versus never smokers were 1.27 (95% CI = 1.23-1.33) for men and 1.43 (95% CI = 1.16-1.81) for women. HRs for current smokers versus never smokers were 2.71 (95% CI = 2.63-2.79) for men and 2.70 (95% CI = 2.48-2.94) for women. HRs for lung cancer increased similarly in both men and women according to smoking status. However, among Korean individuals with comparable smoking statuses, lung cancer incidence is higher in men than in women. Sex should be considered in combination with smoking history in the selection of a lung cancer screening target population.
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