In this study, we reveal a mechanism by which plants regulate inorganic phosphate (Pi) homeostasis to adapt to environmental changes in Pi availability. This mechanism involves the suppression of a ...ubiquitin-conjugating E2 enzyme by a specific microRNA, miR399. Upon Pi starvation, the miR399 is upregulated and its target gene, a ubiquitin-conjugating E2 enzyme, is downregulated in Arabidopsis thaliana. Accumulation of the E2 transcript is suppressed in transgenic Arabidopsis overexpressing miR399. Transgenic plants accumulated five to six times the normal Pi level in shoots and displayed Pi toxicity symptoms that were phenocopied by a loss-of-function E2 mutant. Pi toxicity was caused by increased Pi uptake and by translocation of Pi from roots to shoots and retention of Pi in the shoots. Moreover, unlike wild-type plants, in which Pi in old leaves was readily retranslocated to other developing young tissues, remobilization of Pi in miR399-overexpressing plants was impaired. These results provide evidence that miRNA controls Pi homeostasis by regulating the expression of a component of the proteolysis machinery in plants.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
We recently demonstrated that microRNA399 (miR399) controls inorganic phosphate (Pi) homeostasis by regulating the expression of UBC24 encoding a ubiquitin-conjugating E2 enzyme in Arabidopsis ...(Arabidopsis thaliana). Transgenic plants overexpressing miR399 accumulated excessive Pi in the shoots and displayed Pi toxic symptoms. In this study, we revealed that a previously identified Pi overaccumulator, pho2, is caused by a single nucleotide mutation resulting in early termination within the UBC24 gene. The level of full-length UBC24 mRNA was reduced and no UBC24 protein was detected in the pho2 mutant, whereas up-regulation of miR399 by Pi deficiency was not affected. Several characteristics of Pi toxicity in the pho2 mutant were similar to those in the miR399-overexpressing and UBC24 T-DNA knockout plants: both Pi uptake and translocation of Pi from roots to shoots increased and Pi remobilization within leaves was impaired. These phenotypes of the pho2 mutation could be rescued by introduction of a wild-type copy of UBC24. Kinetic analyses revealed that greater Pi uptake in the pho2 and miR399-overexpressing plants is due to increased Vmax. The transcript level of most PHT1 Pi transporter genes was not significantly altered, except PHT1;8 whose expression was enhanced in Pi-sufficient roots of pho2 and miR399-overexpressing compared with wild-type plants. In addition, changes in the expression of several organelle-specific Pi transporters were noticed, which may be associated with the redistribution of intracellular Pi under excess Pi. Furthermore, miR399 and UBC24 were colocalized in the vascular cylinder. This observation not only provides important insight into the interaction between miR399 and UBC24 mRNA, but also supports their systemic function in Pi translocation and remobilization.
Background
Patients with functional dyspepsia (FD) are more likely to have persistent depression, yet whether depression and antidepressant treatments are associated with subsequent risk of FD remain ...unclear.
Methods
Using population‐based insurance administrative data of Taiwan, an 11‐year historic cohort study was assembled, comparing cases aged 18 and above with the diagnosis of depressive disorder, to a propensity score‐matched sample of adults without depression. Incident FD as a primary diagnosis was ascertained. Hazard ratios of FD were calculated using Cox regression models by age, gender, other comorbidities, nonsteroidal anti‐inflammatory medications, antidepressants and antidiabetic agents.
Results
A total of 20,197 people with depressive disorder and 20,197 propensity score‐matched comparisons without depression were followed up. The incidence of FD was 1.7‐fold greater in the depressive cohort than in comparisons (12.9 versus 7.57 per 1000 person‐years), with an adjusted hazard ratio (aHR) of 2.16 (95% confidence interval (CI) 1.93~2.41). Increased risks were significant regardless of comorbidities or medication uses, the highest in the untreated depression group compared to the group without depression, with an aHR of 2.51(95% CI 2.15~2.93).
Conclusions
This population‐based study showed that patients with depressive disorder are at elevated risk of FD. Antidepressant treatment could reduce the risk of FD.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Increased prevalence of sleep disorders has been found in patients with functional dyspepsia; however, direction of causality remains unclear. Our aim was to compare the risk of incident ...functional dyspepsia between patients with and without sleep disturbance from a large population-based sample. Utilizing a nation-wide health insurance administrative dataset, we assembled an 11-year historic cohort study to compare subsequent incidence of diagnosed functional dyspepsia between adult patients with any diagnosis of sleep disturbance and age- and gender-matched controls. Hazard ratios adjusted for other relevant comorbidities and medications were calculated using Cox regression models. 45,310 patients with sleep disorder and 90,620 controls were compared. Patients with sleep apnea had a 3.3-fold (95% confidence interval: 2.82 ~ 3.89) increased hazard of functional dyspepsia compared with controls. This increased risk persisted regardless of previously diagnosed depression coexisted. Sleep disturbance was associated with an increased risk of subsequent functional dyspepsia. Potential mechanisms are discussed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Anxiety is a prevalent comorbidity in lung cancer (LC) patients associated with a decline in quality of life. Dehydroepiandrosterone (DHEA), a neuroactive steroid, levels rise in response to stress. ...Prior research on the association between DHEA and anxiety has yielded contradictory results and no study has investigated this association in LC patients.
A total of 213 patients with LC were recruited from a general hospital. Data on demographic and cancer-related variables were collected. Using the Chinese version of the Hospital Anxiety and Depression Scale (HADS), the degree of anxiety was determined. Cortisol, DHEA, and Dehydroepiandrosterone sulfate (DHEA-S) levels in saliva were measured. Adjusting for confounding variables, a multivariate regression analysis was conducted.
147 men and 66 women comprised our group with an average age of 63.75 years. After accounting for demographic and treatment-related factors, anxiety levels were significantly correlated with, post-traumatic stress symptoms (PTSSs) (β = 0.332, p < 0.001) and fatigue (β = 0.247, p = 0.02). Association between anxiety and three factors, including DHEA, PTSSs, and fatigue, was observed in patients with advanced cancer stages (III and IV) (DHEA β = 0.319, p = 0.004; PTSS β = 0.396, p = 0.001; fatigue β = 0.289, p = 0.027) and those undergoing chemotherapy (DHEA β = 0.346, p = 0.001; PTSS β = 0.407, p = 0.001; fatigue β = 0.326, p = 0.011).
The association between anxiety and DHEA remained positive in advanced cancer stages and chemotherapy patients. Further study is necessary to determine whether DHEA is a potential biomarker of anxiety in LC patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study aimed to examine the association between conduct problems and mood disorders, and to evaluate the mediating roles of personality traits in it. Adult participants (N = 309), for which ...patients with major depressive disorder (MDD) or bipolar disorder (BD), and controls without major psychiatric history were recruited. Juvenile conduct problem was defined by the items in Composite International Diagnosis Interview. We assessed personality traits of extraversion and neuroticism. Multiple mediation model was performed to investigate the intervening effect of personality traits between juvenile conduct problems and adulthood mood disorders. Participants had on average 2.7 symptoms of conduct problems, and 43.4% had conduct problems. Having more symptoms of conduct problems was associated with a higher likelihood of BD (OR = 1.20). Higher neuroticism was associated with elevated risks of both MDD and BD. There was no direct effect of binary conduct problems on the risk of BD, and showed significant total indirect effect mediated by neuroticism for BD (OR = 1.49; bias-corrected and accelerated 95% CI = 1.10-2.05), but not through extraversion. Conduct problems defined as a continuous variable had a direct effect on the risk of adult MDD (OR = 1.36; bias-corrected and accelerated 95% CI = 1.05-1.76), while had an indirect effect on the risk of BD via the mediation of neuroticism (OR = 1.08; bias-corrected and accelerated 95% CI = 1.02-1.14). Neuroticism mediates between the association of juvenile conduct problems and adult BD. This finding raises our attention to assess personality traits in individuals with juvenile conduct problems for timely intervention strategies of reducing the vulnerability for developing mood disorders.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Wild tomatoes (Solanum peruvianum) are important genomic resources for tomato research and breeding. Development of a foreign DNA-free clustered regularly interspaced short palindromic repeat ...(CRISPR)-Cas delivery system has potential to mitigate public concern about genetically modified organisms. Here, we established a DNA-free CRISPR-Cas9 genome editing system based on an optimized protoplast regeneration protocol of S. peruvianum, an important resource for tomato introgression breeding. We generated mutants for genes involved in small interfering RNAs biogenesis, RNA-DEPENDENT RNA POLYMERASE 6 (SpRDR6), and SUPPRESSOR OF GENE SILENCING 3 (SpSGS3); pathogen-related peptide precursors, PATHOGENESIS-RELATED PROTEIN-1 (SpPR-1) and PROSYSTEMIN (SpProSys); and fungal resistance (MILDEW RESISTANT LOCUS O, SpMlo1) using diploid or tetraploid protoplasts derived from in vitro-grown shoots. The ploidy level of these regenerants was not affected by PEG-Ca2+-mediated transfection, CRISPR reagents, or the target genes. By karyotyping and whole genome sequencing analysis, we confirmed that CRISPR-Cas9 editing did not introduce chromosomal changes or unintended genome editing sites. All mutated genes in both diploid and tetraploid regenerants were heritable in the next generation. spsgs3 null T0 regenerants and sprdr6 null T1 progeny had wiry, sterile phenotypes in both diploid and tetraploid lines. The sterility of the spsgs3 null mutant was partially rescued, and fruits were obtained by grafting to wild-type (WT) stock and pollination with WT pollen. The resulting seeds contained the mutated alleles. Tomato yellow leaf curl virus proliferated at higher levels in spsgs3 and sprdr6 mutants than in the WT. Therefore, this protoplast regeneration technique should greatly facilitate tomato polyploidization and enable the use of CRISPR-Cas for S. peruvianum domestication and tomato breeding.
Invasive Klebsiella pneumoniae syndrome is a significant endemic disease in Taiwan. Intestinal colonization of virulent clones that cause this phenomenon has been demonstrated in asymptomatic adults. ...Comparisons of healthy adults and children with stool K. pneumoniae colonization have rarely been reported. We aimed to evaluate the frequency and abundance of K. pneumoniae in the stool of adults and children by stool microbiota analysis.
Healthy volunteers and their children without antibiotic exposure within 3 months were recruited in a Taiwanese medical center. Stool samples were sent for gut microbiota analysis, using amplification of V3–V4 hypervariable regions of 16sRNA followed by high-throughput sequence. Rectal/stool swabs were sent for K. pneumoniae culture and identification by matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF MS).
Fifty-five adults with a mean age of 46.9 years (range, 23.1–72.1 years) and 20 children with a mean age of 2.3 years (range, 0.9–5.8) were enrolled, and 29 adults and 6 children had positive K. pneumoniae swabs. Children had lower microbiota diversity than adults, including higher abundance of phylum Actinobacteria and Proteobacteria, and lower Bacteriodetes. For genus comparison, higher abundance of Escherichia, Streptococcus, Enterococcus and Bifidobacterium were found in children, but the composite abundance of Klebsiella in adults (median: 0.0156, range: 0–0.031) and in children (median: 0.0067, range: 0–0.043) were similar. Klebsiella abundance was significantly higher in participants with positive swabs (p < 0.0001). Klebsiella-positive swabs were strongly negatively correlated with Enterobacter spp. (p < 0.0001), but no known demographic factors correlated with Klebsiella-positive swabs.
Klebsiella species are present in young children, and the abundance is similar in adults and children. Positive swabs correlate strongly with higher abundance in microbiota analysis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Purpose:
Patients with osteoporosis are at an increased risk of cardiovascular disease (CVD). Several antiosteoporosis medications have been demonstrated with the benefit of preventing osteoporosis. ...Our aim is to assess the CVD risks associated with antiosteoporosis medications using the National Health Insurance Research Database in Taiwan between 2000 and 2016.
Methods:
Among 41,102 patients of 40+ years old with newly diagnosed osteoporosis, 69.1% (N = 28,387) of patients were included in the user cohort of antiosteoporosis medicines, of whom 13, 472 developed CVD by the end of 2016, while 14,915 did not. Using the nested case–control analysis in the user cohort (88.0% women and 77.4% elderly), we applied conditional logistic regression to estimate odds ratios (ORs) of eight types of CVD for the users of denosumab, bisphosphonate, teriparatide, and hormone replacement therapy (HRT).
Results:
The adjusted ORs of overall CVDs were 0.13 (95% CI: 0.12–0.15) for denosumab users, 0.52 (95% CI: 0.45–0.61) for teriparatide users, and 0.80 (95% CI: 0.76–0.85) for bisphosphonate users. The HRT users were at higher odds of coronary artery and peripheral artery diseases, heart failure, pulmonary embolism, and deep vein thrombosis.
Conclusion:
Denosumab, teriparatide, and bisphosphonate may have more protective effects against CVD than hormone therapy. Physicians may take subsequent cardiovascular risks into account when choosing an adequate antiosteoporosis medication for patients with osteoporosis.
Psychotherapy is a learning process. Updating the prediction models of the brain may be the mechanism underlying psychotherapeutic changes. Although developed in different eras and cultures, ...dialectical behavior therapy (DBT) and Morita therapy are influenced by Zen principles, and both emphasize the acceptance of reality and suffering. This article reviews these two treatments, their common and distinct therapeutic factors, and their neuroscientific implications. Additionally, it proposes a framework that includes the predictive function of the mind, constructed emotions, mindfulness, therapeutic relationship, and changes enabled via reward predictions. Brain networks, including the Default Mode Network (DMN), amygdala, fear circuitry, and reward pathways, contribute to the constructive process of brain predictions. Both treatments target the assimilation of prediction errors, gradual reorganization of predictive models, and creation of a life with step-by-step constructive rewards. By elucidating the possible neurobiological mechanisms of these psychotherapeutic techniques, this article is expected to serve as the first step towards filling the cultural gap and creating more teaching methods based on these concepts.
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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
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