Jasmonates (JAs) are important signaling molecules in plants and play crucial roles in stress responses, secondary metabolites' regulation, plant growth and development. In this study, the promoter ...of AaAOC, which was the key gene of jasmonate biosynthetic pathway, had been cloned. GUS staining showed that AaAOC was expressed ubiquitiously in A. annua. AaAOC gene was overexpressed under control of 35S promoter. RT-Q-PCR showed that the expression levels of AaAOC were increased from 1.6- to 5.2-fold in AaAOC-overexpression transgenic A. annua. The results of GC-MS showed that the content of endogenous jasmonic acid (JA) was 2- to 4.7-fold of the control level in AaAOC-overexpression plants. HPLC showed that the contents of artemisinin, dihydroartemisinic acid and artemisinic acid were increased significantly in AaAOC-overexpression plants. RT-Q-PCR showed that the expression levels of FPS (farnesyl diphosphate synthase), CYP71AV1 (cytochrome P450 dependent hydroxylase) and DBR2 (double bond reductase 2) were increased significantly in AaAOC-overexpression plants. All data demonstrated that increased endogenous JA could significantly promote the biosynthesis of artemisinin in AaAOC-overexpression transgenic A. annua.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A greenhouse is an energy-intensive sector with substantial greenhouse gas emissions and extensive energy consumption. Energy-saving greenhouse strategies become particularly important on the premise ...of ensuring effective crop production to achieve sustainable energy development. This paper aims to deliver a comprehensive review on crucial energy-saving strategies from greenhouse design to operational stage. This contribution analyses effective energy-saving methods for greenhouse design considering greenhouse structures, ventilation and lighting systems. It details the energy-saving operation of greenhouses by summarising renewable energy technologies and integration systems, including photovoltaic modules, solar collectors, heat pumps and other integrated modules. These environment-friendly technologies achieve the purpose of environment protection and energy conservation of greenhouse. The research findings reveal that more than half of the energy is saved through appropriate greenhouse renovation. Control strategies for improving the energy efficiency of the greenhouse in aspects of monitoring system management and control algorithms have been discussed as well. The neural network combined with other control algorithms is a suitable approach to solve nonlinear control problems with a good control accuracy. In the final part, the life cycle environmental impacts and environmental footprints assessment of greenhouse is discussed. Life cycle assessment of modern integrated greenhouse is expected to be further studied. This review provides valuable insights and suggestions for the design and transformation of modern sustainable greenhouses.
•Research gaps are analysed for the energy saving strategies of greenhouse.•Up to 25% environmental impact is reduced by greenhouses with sustainable energy.•Semi-transparent PV modules save above 20% energy than traditional PV modules.•The accuracy and costs of techniques hinder optimal controls of greenhouse.•Existing studies on life cycle assessment of integrated greenhouse are insufficient.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Genetic mutations in TAR DNA-binding protein 43 (TDP-43) cause amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Importantly, TDP-43 proteinopathy, characterized by aberrant ...phosphorylation, ubiquitination, cleavage or nuclear depletion of TDP-43 in neurons and glial cells, is a common prominent pathological feature of various major neurodegenerative diseases including ALS, FTD, and Alzheimer's disease (AD). Although the pathomechanisms underlying TDP-43 proteinopathy remain elusive, pathologically relevant TDP-43 has been repeatedly shown to be present in either the inside or outside of mitochondria, and functionally involved in the regulation of mitochondrial morphology, trafficking, and function, suggesting mitochondria as likely targets of TDP-43 proteinopathy. In this review, we first describe the current knowledge of the association of TDP-43 with mitochondria. We then review in detail multiple mitochondrial pathways perturbed by pathological TDP-43, including mitochondrial fission and fusion dynamics, mitochondrial trafficking, bioenergetics, and mitochondrial quality control. Lastly, we briefly discuss how the study of TDP-43 proteinopathy and mitochondrial abnormalities may provide new avenues for neurodegeneration therapeutics.
•This review describes our current knowledge of the physical association of TDP-43 with mitochondria.•This review describes our current knowledge of mitochondrial pathways perturbed by pathological TDP-43.•This review describes our perspective of TDP-43 targeted therapeutic approaches.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary
Glandular trichomes and cuticles are both specialized structures that cover the epidermis of aerial plant organs. The former are commonly regarded as ‘biofactories’ for producing valuable ...natural products. The latter are generally considered as natural barriers for defending plants against abiotic and biotic stresses. However, the regulatory network for their formation and relationship remains largely elusive.
Here we identify a homeodomain‐leucine zipper (HD‐ZIP) IV transcription factor, AaHD8, directly promoting the expression of AaHD1 for glandular trichome initiation in Artemisia annua.
We found that AaHD8 positively regulated leaf cuticle development in A. annua via controlling the expression of cuticle‐related enzyme genes. Furthermore, AaHD8 interacted with a MIXTA‐like protein AaMIXTA1, a positive regulator of trichome initiation and cuticle development, forming a regulatory complex and leading to enhanced transcriptional activity in regulating the expression of AaHD1 and cuticle development genes.
Our results reveal a molecular mechanism by which a novel HD‐ZIP IV/MIXTA complex plays a significant role in regulating epidermal development, including glandular trichome initiation and cuticle formation.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Artemisinin, the endoperoxide sesquiterpene lactone, is an effective antimalarial drug isolated from the Chinese medicinal plant Artemisia annua L. Due to its effectiveness against ...multi-drug-resistant cerebral malaria, it becomes the essential components of the artemisinin-based combination therapies which are recommended by the World Health Organization as the preferred choice for malaria tropica treatments. To date, plant A. annua is still the main commercial source of artemisinin. Although semi-synthesis of artemisinin via artemisinic acid in yeast is feasible at present, another promising approach to reduce the price of artemisinin is using plant metabolic engineering to obtain a higher content of artemisinin in transgenic plants. In the past years, an Agrobacterium-mediated transformation system of A. annua has been established by which a number of genes related to artemisinin biosynthesis have been successfully transferred into A. annua plants. In this review, the progress on increasing artemisinin content in A. annua by transgenic approach and its future prospect are summarized and discussed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Artemisinin, also known as qinghaosu, a sesquiterpene endoperoxide lactone isolated from the Chinese medicinal plant Artemisia annua L., is the most effective antimalarial drug which has saved ...millions of lives. Due to its great antimalarial activity and low content in wild A. annua plants, researches focused on enhancing the artemisin yield in plants became a hotspot. Several families of transcription factors have been reported to participate in regulating the biosynthesis and accumulation of artemisinin. In this review, we summarize recent investigations in these fields, with emphasis on newly identified transcription factors and their functions in artemisinin biosynthesis regulation, and provide new insight for further research.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UL, UM, UPCLJ, UPUK, VKSCE, ZAGLJ, ZRSKP
Artemisia annua, commonly known as sweet wormwood or Qinghao, is a shrub native to China and has long been used for medicinal purposes. A. annua is now cultivated globally as the only natural source ...of a potent anti-malarial compound, artemisinin. Here, we report a high-quality draft assembly of the 1.74-gigabase genome of A. annua, which is highly heterozygous, rich in repetitive sequences, and contains 63 226 protein-coding genes, one of the largest numbers among the sequenced plant species. We found that, as one of a few sequenced genomes in the Asteraceae, the A. annua genome contains a large number of genes specific to this large angiosperm clade. Notably, the expansion and functional diversification of genes encoding enzymes involved in terpene biosynthesis are consistent with the evolution of the artemisinin biosynthetic pathway. We further revealed by transcriptome profiling that A. annua has evolved the sophisticated transcriptional regulatory networks underlying artemisinin biosynthesis. Based on comprehensive genomic and transcriptomic analyses we generated transgenic A. annua lines producing high levels of artemisinin, which are now ready for large-scale production and thereby will help meet the challenge of increasing global demand of artemisinin.
We report a high-quality genome assembly of Artemisia annua and genomic and transcriptomic analyses of the biosynthetic pathway of the anti-malaria sesquiterpene artemisinin and its regulation. With the help of genomic and transcriptomic information we generated trangenic A. annua lines producing high levels of artemisinin.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Neuropathologically, Alzheimer’s disease (AD) is characterized by the presence of senile plaques composed of beta‐amyloid (Aβ) and neurofibrillary tangles made of hyperphosphorylated tau. ...Aβ and p‐tau have been shown to impact endoplasmic reticulum homeostasis, DNA damage response and autophagic functions. Intriguingly, alterations in these systems have also been connected to dysfunctions in UFMylation, a ubiquitin‐like posttranslational modification. Analogous to ubiquitin, UFM1, is conjugated to substrates via a catalytic cascade involving UFM1‐specific set of E1 (UBA5), E2 (UFC1), and a complex that consists of E3 ligase (UFL1), DDRGK1 and CDK5RAP3. UFMylation is reversible, and this is mediated by UFSP2. The UFMylation pathway is essential for brain development as complete loss of function of any of its components result in severe neurodevelopmental disorders. However, alterations in UFMylation and their role in and significance for age‐related AD remains unknown.
Method
We performed Western blot and Meso Scale Discovery based ELISA to measure the protein level of UFM1, UFSP2, tau, p‐tau and other UFMylation pathway components in human post‐mortem brain. Analyses were performed with RIPA‐ and 2% SDS‐soluble fraction from frontal cortex. To validate our finding in human tissues, we knocked out UFM1 and UFSP2 in ReN cells, a neural progenitor cell model that has already been used to study AD and that can be terminally differentiated in neurons.
Result
We found a significant reduction of RIPA UFSP2, but an increase of RIPA and SDS UFM1 in AD compared to controls. Strikingly, RIPA UFSP2 had a strong negative correlation with both RIPA and SDS UFM1. Furthermore. UFM1 was significantly increased in UFSP2‐KO neurons compared to WT, mirroring the negative correlation between UFM1 and UFSP2 observed in human brain. In addition, RIPA and SDS UFM1 had a strong positive correlation with p‐tau, indicating that dysfunctional UFMylation might play an important role for disease pathogenesis.
Conclusion
Reduction of RIPA soluble UFSP2 in human AD frontal cortex might result in the abnormal accumulation of UFM1 and this might further facilitate the AD pathogenesis. Because of its role for several central AD‐relevant pathways, the UFMylation pathway might be a potential therapeutic target for AD.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
19.
Basic Science and Pathogenesis - Part 1 Yan, Tingxiang; Heckman, Michael G; Murray, Melissa E ...
Alzheimer's & dementia,
12/2023, Volume:
19 Suppl 12
Journal Article
Peer reviewed
Neuropathologically, Alzheimer's disease (AD) is characterized by the presence of senile plaques composed of beta-amyloid (Aβ) and neurofibrillary tangles made of hyperphosphorylated tau. Aβ and ...p-tau have been shown to impact endoplasmic reticulum homeostasis, DNA damage response and autophagic functions. Intriguingly, alterations in these systems have also been connected to dysfunctions in UFMylation, a ubiquitin-like posttranslational modification. Analogous to ubiquitin, UFM1, is conjugated to substrates via a catalytic cascade involving UFM1-specific set of E1 (UBA5), E2 (UFC1), and a complex that consists of E3 ligase (UFL1), DDRGK1 and CDK5RAP3. UFMylation is reversible, and this is mediated by UFSP2. The UFMylation pathway is essential for brain development as complete loss of function of any of its components result in severe neurodevelopmental disorders. However, alterations in UFMylation and their role in and significance for age-related AD remains unknown.BACKGROUNDNeuropathologically, Alzheimer's disease (AD) is characterized by the presence of senile plaques composed of beta-amyloid (Aβ) and neurofibrillary tangles made of hyperphosphorylated tau. Aβ and p-tau have been shown to impact endoplasmic reticulum homeostasis, DNA damage response and autophagic functions. Intriguingly, alterations in these systems have also been connected to dysfunctions in UFMylation, a ubiquitin-like posttranslational modification. Analogous to ubiquitin, UFM1, is conjugated to substrates via a catalytic cascade involving UFM1-specific set of E1 (UBA5), E2 (UFC1), and a complex that consists of E3 ligase (UFL1), DDRGK1 and CDK5RAP3. UFMylation is reversible, and this is mediated by UFSP2. The UFMylation pathway is essential for brain development as complete loss of function of any of its components result in severe neurodevelopmental disorders. However, alterations in UFMylation and their role in and significance for age-related AD remains unknown.We performed Western blot and Meso Scale Discovery based ELISA to measure the protein level of UFM1, UFSP2, tau, p-tau and other UFMylation pathway components in human post-mortem brain. Analyses were performed with RIPA- and 2% SDS-soluble fraction from frontal cortex. To validate our finding in human tissues, we knocked out UFM1 and UFSP2 in ReN cells, a neural progenitor cell model that has already been used to study AD and that can be terminally differentiated in neurons.METHODWe performed Western blot and Meso Scale Discovery based ELISA to measure the protein level of UFM1, UFSP2, tau, p-tau and other UFMylation pathway components in human post-mortem brain. Analyses were performed with RIPA- and 2% SDS-soluble fraction from frontal cortex. To validate our finding in human tissues, we knocked out UFM1 and UFSP2 in ReN cells, a neural progenitor cell model that has already been used to study AD and that can be terminally differentiated in neurons.We found a significant reduction of RIPA UFSP2, but an increase of RIPA and SDS UFM1 in AD compared to controls. Strikingly, RIPA UFSP2 had a strong negative correlation with both RIPA and SDS UFM1. Furthermore. UFM1 was significantly increased in UFSP2-KO neurons compared to WT, mirroring the negative correlation between UFM1 and UFSP2 observed in human brain. In addition, RIPA and SDS UFM1 had a strong positive correlation with p-tau, indicating that dysfunctional UFMylation might play an important role for disease pathogenesis.RESULTWe found a significant reduction of RIPA UFSP2, but an increase of RIPA and SDS UFM1 in AD compared to controls. Strikingly, RIPA UFSP2 had a strong negative correlation with both RIPA and SDS UFM1. Furthermore. UFM1 was significantly increased in UFSP2-KO neurons compared to WT, mirroring the negative correlation between UFM1 and UFSP2 observed in human brain. In addition, RIPA and SDS UFM1 had a strong positive correlation with p-tau, indicating that dysfunctional UFMylation might play an important role for disease pathogenesis.Reduction of RIPA soluble UFSP2 in human AD frontal cortex might result in the abnormal accumulation of UFM1 and this might further facilitate the AD pathogenesis. Because of its role for several central AD-relevant pathways, the UFMylation pathway might be a potential therapeutic target for AD.CONCLUSIONReduction of RIPA soluble UFSP2 in human AD frontal cortex might result in the abnormal accumulation of UFM1 and this might further facilitate the AD pathogenesis. Because of its role for several central AD-relevant pathways, the UFMylation pathway might be a potential therapeutic target for AD.
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FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Artemisinin, the frontline drug against malaria, is a sesquiterpenoid extracted from Artemisia annua. Light has been proposed to play an important role in the activation of artemisinin biosynthesis. ...Here, we report the basic leucine zipper transcription factor (TF) AaHY5 as a key regulator of light-induced biosynthesis of artemisinin. We show that AaHY5 transcription overlaps with that of artemisinin biosynthesis genes in response to light and in A. annua tissues. Analysis of AaHY5 overexpression and RNAi-suppression lines suggests that AaHY5 is a positive regulator of the expression of artemisinin biosynthesis genes and accumulation of artemisinin. We show that AaHY5 complements the hy5 mutant in Arabidopsis thaliana. Our data further suggest that AaHY5 interacts with AaCOP1, the ubiquitin E3 ligase CONSTITUTIVE PHOTOMORPHOGENIC1 in A. annua. In yeast one-hybrid and transient expression assays, we demonstrate that AaHY5 acts via the TF GLANDULAR TRICHOME-SPECIFIC WRKY 1 (AaGSW1) in artemisinin regulation. In summary, we present a novel regulator of artemisinin gene expression and propose a model in which AaHY5 indirectly controls artemisinin production in response to changing light conditions.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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