Summary
Small interfering RNAs (siRNAs) are responsible for establishing and maintaining DNA methylation through the RNA‐directed DNA methylation (RdDM) pathway in plants. Although siRNA biogenesis ...is well known, it is relatively unclear about how the process is regulated. By a forward genetic screen in Arabidopsis thaliana, we identified a mutant defective in NOT1 and demonstrated that NOT1 is required for transcriptional silencing at RdDM target genomic loci. We demonstrated that NOT1 is required for Pol IV‐dependent siRNA accumulation and DNA methylation at a subset of RdDM target genomic loci. Furthermore, we revealed that NOT1 is a constituent of a multi‐subunit CCR4‐NOT deadenylase complex by immunoprecipitation combined with mass spectrometry and demonstrated that the CCR4‐NOT components can function as a whole to mediate chromatin silencing. Therefore, our work establishes that the CCR4‐NOT complex regulates the biogenesis of Pol IV‐dependent siRNAs, and hence facilitates DNA methylation and transcriptional silencing in Arabidopsis.
Significance Statement
The study identifies a mutant defective in NOT1 by a forward genetic screen and demonstrates that NOT1 is required for Pol IV‐dependent siRNA accumulation and DNA methylation and thereby facilitate chromatin silencing at a subset of RdDM target genomic loci. Because NOT1 is the largest subunit of the CCR4‐NOT complex responsible for mRNA deadenylation, the study reveals a potential role for RNA deadenylation in siRNA production.
Summary
Diabetes mellitus may be a risk factor of HCC development in chronic hepatitis B infected patients and affect the all‐cause mortality. This study aimed to examine whether DM was associated ...with the development of HCC with CHB and affected the all‐cause mortality. A total of 2966 CHB patients newly diagnosed with DM in 2000 were retrieved from the Longitudinal Cohort of Diabetes Patients database and used propensity scores matching based on age, sex‐gender, alcohol‐related liver disease and baseline liver cirrhosis to compare with the non‐DM patients from the Taiwanese National Health Insurance Research Database. The CHB patients with DM compared to the non‐DM had significantly increased (3.3%) risk for HCC development and significantly increased (2.8%) risk of HCC‐related mortality. Interestingly, the all‐cause mortality was significantly higher in the DM cohort (16.9%) compared to the non‐DM cohort (8.2%). In a multivariable transition‐specific Cox model to investigate the adjusted hazard ratio of CHB patients with DM or non‐DM during the transitions from start to HCC was 1.35; 95% CI (1.16‐1.57) and from HCC to death was 1.31; 95% CI (1.06‐1.62). All‐cause mortality between CHB patients with DM or non‐DM during the transitions from start to death was 2.32; 95% CI (1.84‐2.92). Taken together, DM is an independent risk factor associated with increasing disease development of HCC, HCC‐related mortality and all‐cause mortality in CHB patients. This study may provide a clinical strategy for strict DM control in order to reduce the risk of disease development in CHB patients.
Mosquitoes act as vectors for many life-threatening diseases, including malaria, dengue fever, and Zika virus infection. Management of mosquitoes mainly relies on synthetic insecticides, which ...usually result in the rapid development of resistance; therefore, alternative mosquito control strategies are urgently needed. This study characterized the major component of essential oils (EOs) derived from the vegetative parts of four herbal plants and their larvicidal activity toward important mosquito vectors. The EOs were extracted by hydro-distillation and subjected to gas chromatography–mass spectrometry (GC–MS) analysis and a larvicidal activity assay toward Aedes aegypti, Ae. albopictus and Culex quinquefasciatus. In total, 14, 11, 11 and 9 compounds were identified from the EOs of Plectranthus amboinicus, Mentha requienii, Vitex rotundifolia and Crossostephium chinense, respectively. The EOs derived from four herbal plants exhibited remarkable larvicidal activity against the three mosquito species. In particular, the EOs of P. amboinicus showed the highest larvicidal activity, and the larvae of Cx. quinquefasciatus were more sensitive to the P. amboinicus EOs than that of Ae. Aegypti. Although carvacrol (61.53%) was the predominant constituent of the P. amboinicus EOs, its precursors, γ-terpinene (8.51%) and p-cymene (9.42%), exhibited the most larvicidal activity toward Ae. aegypti and Cx. quinquefasciatus. However, ß-caryophyllene (12.79%) might be the major component responsible for the differential toxicity of the P. amboinicus EOs, as indicated by the significant differences in its LC₅₀ values toward both mosquitoes. Information from these studies will benefit the incorporation of EOs into integrated vector management.
Sea container has been identified as a major pathway for the unintended entry and spread of alien ant species. In Japan, red imported fire ants,
Solenopsis invicta
Buren (Hymenoptera: Formicidae), ...which are among the most harmful alien ants, were first detected in a shipping container from China in May 2017, and the invasion into Japan via the trade pathway is still continuing. To prevent containers contaminated with
S. invicta
and its establishment in Japan, control measures, such as repellents, are urgently required. The present study is the first to evaluate repellency of microencapsulated allyl isothiocyanate (AITC) against
S. invicta
, as a preliminary step to use the innovative equipment for invasive species management in sea containers. In a field in Taiwan heavily infested with
S. invicta
, a repellent test of microencapsulated AITC using bait traps showed that the equipment completely prevents
S. invicta
from accessing the bait. Due to its volatility and irritancy, AITC, a safe natural repellant in wasabi (
Eutrema japonicum
(Miq.) Kiudz), has not been used for pest management in containerized cargo. However, the encapsulation of AITC solves this problem by allowing controlled vapor release. Microencapsulated AITC has considerable potential as an effective measure to stop the spread of
S. invicta
through global trade.
Many important cell-to-cell communication events in multicellular organisms are mediated by peptides, but only a few peptides have been identified in plants. In an attempt to address the difficulties ...in identifying plant signaling peptides, we developed a novel peptidomics approach and used this approach to discover defense signaling peptides in plants. In addition to the canonical peptide systemin, several novel peptides were confidently identified in tomato (Solanum lycopersicum) and quantified to be induced by both wounding and methyl jasmonate (MeJA). A wounding or wounding plus MeJA-induced peptide derived from the pathogenesis-related protein 1 (PR-1) family was found to induce significant antipathogen and minor antiherbivore responses in tomato. This study highlights a role for PR-1 in immune signaling and suggests the potential application of plant endogenous peptides in efforts to defeat biological threats in crop production. As PR-1 is highly conserved across many organisms and the putative peptide from At-PR1 was also found to be bioactive in Arabidopsis thaliana, our results suggest that this peptide may be useful for enhancing resistance to stress in other plant species.
The red imported fire ant (RIFA) is one of the most detrimental invasive species, threatening native ecosystems, human health and economic activities worldwide. In the quarantine zone of Taiwan, RIFA ...re‐infestation frequently occurs despite the intensive application of synthetic pesticides, making its control costly and ineffective. Thus, there is an urgent need to identify eco‐friendly and sustainable alternatives for controlling RIFA populations. This study examined the efficacy and feasibility of planting herbal species for RIFA control. Five herbal species, Tagetes lemmonii, Armoracia rusticana, Cymbopogon citratus, Cymbopogon nardus and Chrysopogon zizanioides, were grown in a RIFA‐infested field with local weeds as controls. Bait and pitfall traps and RIFA‐intruded plants were used to compare the ant activity in the control fields and those containing herbal plants. We further evaluated the RIFA repellent activity of the five herbal plants and their basal soil through digging bioassays. Generally, the field surveys showed more ants and intruded plants in the control than the herbal groups; however, the significance varied based on the trap type and plant species. The digging bioassays demonstrated that the aboveground parts of T. lemmonii, C. nardus, C. citratus and the belowground parts of T. lemmonii, C. citratus and C. zizanioides effectively repelled RIFA. The basal soil of T. lemmonii, C. citratus and C. nardus also exhibited deterrent activity towards RIFA. Our results demonstrated that herbal plants are eco‐friendly, sustainable alternatives for controlling and preventing RIFA infestation in severe infested and non‐infested areas.
Hepatic encephalopathy (HE) implies high morbidity and mortality. The assessment of covert HE (CHE) i.e. minimal HE (MHE) plus grade 1 HE is often neglected in Taiwan. Therefore, the aim was to ...investigate the potential of the animal naming test (ANT
1
and simplified ANT
1
(S-ANT
1)
) for assessing CHE in Chinese-speaking regions, specifically Taiwan.
A prospective cohort study was conducted, comprising 65 cirrhotic patients and 29 healthy controls (relatives of the patients). Patients were followed up every three months and censored after two years or until death. Hospitalization for overt HE (OHE) and mortality were considered. All subjects underwent ANT
1
, psychometric HE score (PHES), and mini-mental state examination (MMSE). The patients underwent an electroencephalogram (EEG) to detect slowing indicative of MHE. Cut-off values for ANT
1
and S-ANT
1
were assessed by ROC analysis and Youden's index, considering CHE as a reference. The prognostic values for OHE and OHE-free survival were assessed.
Preliminary analysis confirmed that PHES ≤-4 is a good discriminant point for abnormal results. CHE was found in 29 patients: 9 had MHE (PHES ≤ -4 or altered EEG) and 20 had grade 1 HE. ANT
1
and S-ANT
1
were found to have diagnostic values for CHE: AUC = 0.807, 0.786; cut off: 18 and 19, respectively. ANT
1
and S-ANT
1
were found to have prognostic value for OHE, number of hospitalization episodes for OHE, and OHE recurrence-free survival.
ANT
1
shows promise as a tool for CHE detection, quantification, and follow-up in Taiwan and other Chinese-speaking regions.
Key messages
The animal naming test (ANT
1
) is a simple and valid semantic fluency test that can be easily performed in outpatient or bedside settings in one minute and can also be used as a tool for covert hepatic encephalopathy (CHE) detection, quantification, and follow-up in Taiwan, other Chinese-speaking regions, and many other countries.
The diagnostic value of ANT
1
and S-ANT
1
for CHE were found to be significant, with area under the receiver operating characteristic curve (AUROC) values of 0.807 and 0.786 respectively, and cut-off scores of 18 and 19.
ANT
1
and S-ANT
1
have prognostic value for the first breakthrough of overt hepatic encephalopathy (OHE), number of hospitalization episodes for OHE, and OHE recurrence-free survival, independent of the MELD score.
Abstract Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a CAG trinucleotide expansion in the Huntingtin (Htt) gene. The resultant mutant Htt protein (mHtt) ...forms aggregates in the brain (e.g., cortex and striatum), and causes devastating neuronal degeneration. Transcriptional dysfunction caused by mHtt is critical for HD. We recently demonstrated that a crucial transcription factor peroxisome proliferator-activated receptor-γ (PPARγ) played a major function in the energy homeostasis observed in HD and that PPARγ is a potentially neuroprotective target for this disease. We report here that the transcript level of PPARγ was markedly downregulated in the cortex of a transgenic mouse model of HD (R6/2). Treatment of R6/2 mice with an agonist of PPARγ (thiazolidinedione, TZD) resulted in a beneficial effect on PPARγ. By reducing Htt aggregates and thereby ameliorating the recruitment of PPARγ into Htt aggregates, TZD treatment also elevated the availability of PPARγ level and subsequently normalized the expression of downstream genes (including PGC-1α and several mitochondrial genes) in the cortex. The above protective effects appeared to be exerted by a direct activation of the PPARγ agonist (rosiglitazone) because rosiglitazone protected a neuroblastoma cell line (N2A) from mHtt-evoked mitochondrial deficiency. Our results reveal that TZD and rosiglitazone may play a protective role in HD, and support the view that PPARγ is a potential therapeutic target in HD.
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