Rhamnogalacturonan lyase 1 (RGL1), as a suppressor of E3 ubiquitin ligase Arabidopsis thaliana ring zinc finger 1 (AtRZF1), is involved in dehydration response to mediate proline synthesis and pectin rhamnogalacturonan-I composition.

Proline metabolism plays a crucial role in both environmental stress responses and plant growth. However, the specific mechanism by which proline contributes to abiotic stress processes remains to be elucidated. In this study, we utilized atrzf1 (Arabidopsis thaliana ring zinc finger 1) as a parental line for T-DNA tagging mutagenesis and identified a suppressor mutant of atrzf1, designated proline content alterative 31 (pca31). The pca31 mutant suppressed the insensitivity of atrzf1 to dehydration stress during early seedling growth. Using Thermal Asymmetric Interlaced-PCR, we found that the T-DNA of pca31 was inserted into the promoter region of the At2g22620 gene, which encodes the cell wall enzyme rhamnogalacturonan lyase 1 (RGL1). Enzymatic assays indicated that RGL1 exhibited rhamnogalacturonan lyase activity, influencing cell wall pectin composition. The decrease in RGL1 gene expression suppressed the transcriptomic perturbation of the atrzf1 mutant. Silencing of the RGL1 gene in atrzf1 resulted in a sensitive phenotype similar to pca31 under osmotic stress conditions. Treatment with mannitol, salt, hydrogen peroxide, and abscisic acid induced RGL1 expression. Furthermore, we uncovered that RGL1 plays a role in modulating root growth and vascular tissue development. Molecular, physiological, and genetic experiments revealed that the positive modulation of RGL1 during abiotic stress was linked to the AtRZF1 pathway. Taken together, these findings establish that pca31 acts as a suppressor of atrzf1 in abiotic stress responses through proline and cell wall metabolisms.

Telomere dynamics and oxidative stress in Arabidopsis grown in lunar regolith simulant.

NASA envisions a future where humans establish a thriving colony on the Moon by 2050. Plants will be essential for this endeavor, but little is known about their adaptation to extraterrestrial bodies. The capacity to grow plants in lunar regolith would represent a major step towards this goal by minimizing the reliance on resources transported from Earth. Recent studies reveal that Arabidopsis thaliana can germinate and grow on genuine lunar regolith as well as on lunar regolith simulant. However, plants arrest in vegetative development and activate a variety of stress response pathways, most notably the oxidative stress response. Telomeres are hotspots for oxidative damage in the genome and a marker of fitness in many organisms. Here we examine A. thaliana growth on a lunar regolith simulant and the impact of this resource on plant physiology and on telomere dynamics, telomerase enzyme activity and genome oxidation. We report that plants successfully set seed and generate a viable second plant generation if the lunar regolith simulant is pre-washed with an antioxidant cocktail. However, plants sustain a higher degree of genome oxidation and decreased biomass relative to conventional Earth soil cultivation. Moreover, telomerase activity substantially declines and telomeres shorten in plants grown in lunar regolith simulant, implying that genome integrity may not be sustainable over the long-term. Overcoming these challenges will be an important goal in ensuring success on the lunar frontier.

Arabidopsis thaliana ubiquitin-associated protein 2 (AtUAP2) functions as an E4 ubiquitin factor and negatively modulates dehydration stress response.

E4, a ubiquitin (Ub) chain assembly factor and post-translational modification protein, plays a key role in the regulation of multiple cellular functions in plants during biotic or abiotic stress. We have more recently reported that E4 factor AtUAP1 is a negative regulator of the osmotic stress response and enhances the multi-Ub chain assembly of E3 ligase Arabidopsis thaliana RING Zinc Finger 1 (AtRZF1). To further investigate the function of other E4 Ub factors in osmotic stress, we isolated AtUAP2, an AtUAP1 homolog, which interacted with AtRZF1, using pull-down assay and bimolecular fluorescence complementation analysis. AtUAP2, a Ub-associated motif-containing protein, interacts with oligo-Ub5, -Ub6, and -Ub7 chains. The yeast functional complementation experiment revealed that AtUAP2 functions as an E4 Ub factor. In addition, AtUAP2 is localized in the cytoplasm, different from AtUAP1. The activity of AtUAP2 was relatively strongly induced in the leaf tissue of AtUAP2 promoter-ß-glucuronidase transgenic plants by abscisic acid, dehydration, and oxidative stress. atuap2 RNAi lines were more insensitive to osmotic stress condition than wild-type during the early growth of seedlings, whereas the AtUAP2-overexpressing line exhibited relatively more sensitive responses. Analyses of molecular and physiological experiments showed that AtUAP2 could negatively mediate the osmotic stress-induced signaling. Genetic studies showed that AtRZF1 mutation could suppress the dehydration-induced sensitive phenotype of the AtUAP2-overexpressing line, suggesting that AtRZF1 acts genetically downstream of AtUAP2 during osmotic stress. Taken together, our findings show that the AtRZF1-AtUAP2 complex may play important roles in the ubiquitination pathway, which controls the osmotic stress response in Arabidopsis.

Arabidopsis telomerase takes off by uncoupling enzyme activity from telomere length maintenance in space.

Spaceflight-induced changes in astronaut telomeres have garnered significant attention in recent years. While plants represent an essential component of future long-duration space travel, the impacts of spaceflight on plant telomeres and telomerase have not been examined. Here we report on the telomere dynamics of Arabidopsis thaliana grown aboard the International Space Station. We observe no changes in telomere length in space-flown Arabidopsis seedlings, despite a dramatic increase in telomerase activity (up to 150-fold in roots), as well as elevated genome oxidation. Ground-based follow up studies provide further evidence that telomerase is induced by different environmental stressors, but its activity is uncoupled from telomere length. Supporting this conclusion, genetically engineered super-telomerase lines with enhanced telomerase activity maintain wildtype telomere length. Finally, genome oxidation is inversely correlated with telomerase activity levels. We propose a redox protective capacity for Arabidopsis telomerase that may promote survivability in harsh environments.

Prognostic value of resting heart rate in predicting undiagnosed diabetes in adults: Korean National Health and Nutrition Examination Survey 2008-2018.

BACKGROUND AND AIM: Although resting heart rate (RHR) is associated with prevalence and incidence of diabetes, whether it is associated with undiagnosed diabetes is still unclear. We aimed to investigate whether the RHR is associated with the prevalence of undiagnosed diabetes in a large Korean national dataset. METHODS AND RESULTS: The Korean National Health and Nutrition Examination Survey data from 2008 to 2018 were used. After screening, 51,637 participants were included in this study. The odds ratios and 95% confidence intervals (CIs) for undiagnosed diabetes were calculated using multivariable-adjusted logistic regression analyses. Analyses showed that participants with a RHR of ≥90 bpm showed a 4.00- (95% CI: 2.77-5.77) and 3.21-times (95% CI: 2.01-5.14) higher prevalence of undiagnosed diabetes for men and women, respectively, than those with a RHR of <60 bpm. The linear dose-response analyses showed that each 10-bpm increment in RHR was associated with a 1.39- (95% CI: 1.32-1.48) and 1.28-times (95% CI: 1.19-1.37) higher prevalence of undiagnosed diabetes for men and women, respectively. In the stratified analyses, the positive association between RHR and the prevalence of undiagnosed diabetes was tended to be stronger among those who were younger (age: <40 years) and lean (BMI: <23 kg/m2). CONCLUSIONS: Elevated RHR was significantly associated with a higher prevalence of undiagnosed diabetes in Korean men and women, independent of demographic, lifestyle, and medical factors. Accordingly, the value of RHR as a clinical indicator and health marker, especially in reducing the prevalence of undiagnosed diabetes, is suggestible.

Isolation and Functional Characterization of Soybean BES1/BZR1 Homolog 3-Like 1 (GmBEH3L1) Associated with Dehydration Sensitivity and Brassinosteroid Signaling in Arabidopsis thaliana

Brassinosteroid (BR) is an important steroid hormone that regulates plant development, abscisic acid (ABA) signaling, and responses to abiotic stress. We previously demonstrated that BEH3 (BES1/BZR1 Homolog 3) of Arabidopsis thaliana regulates dehydration and ABA responses by mediating proline metabolism. Furthermore, BEH3 negatively regulates BR-mediated hypocotyl elongation in dark-grown seedlings. However, the roles of BEH3 ortholog genes in the osmotic stress response of plants have remained largely unknown. Here, GmBEH3L1 (Glycine max BEH3-Like 1), a soybean (G. max) ortholog of the BEH3 gene of A. thaliana, was isolated and functionally characterized. GmBEH3L1 is induced by ABA, dehydration, and drought conditions. The GmBEH3L1-overexpressing transgenic lines (GmBEH3L1-OE/beh3) with the beh3 mutant background have ABA- and dehydration-sensitive phenotypes during early seedling growth, implying that GmBEH3L1 is involved in both osmotic stress and ABA sensitivity as a negative regulator in A. thaliana. Consistent with these results, GmBEH3L1-OE/beh3 complemental lines exhibit decreased expression levels of ABA- or dehydration-inducible genes. Under darkness, GmBEH3L1-OE/beh3 complemental lines display a short hypocotyl length compared to the beh3 mutant, indicating that GmBEH3L1 is linked to BR signaling. Together, our data suggest that GmBEH3L1 participates negatively in ABA and dehydration responses through BR signaling.

The relationship between domain-specific physical activity and depressive symptoms in Korean adults: Analysis of the Korea National Health and Nutrition Examination Survey.

BACKGROUND: This study aimed to investigate the associations of domain-specific physical activity (PA) with the prevalence of depressive symptoms. METHODS: We analyzed data from 11,679 (5,056 men and 6,623 women) participants aged ³19 years in the Korea National Health and Nutrition Examination Survey (2016 and 2018 waves). Depressive symptoms were measured using the Korean version of the Patient Health Questionnaire-9 (PHQ-9), with a cut-off score for depression of 11. The participants were first categorized by sex, and then by their PA level in different PA domains into three different groups. We examined the correlations between domain-specific PA and depressive symptoms using logistic regression analysis after controlling for confounders. RESULTS: Total amount of PA was not associated with depressive symptoms. However, in both sexes, those high in leisure and transport PA had lower levels of depressive symptoms compared with those with no leisure and transport PA (p for trend <0.001). After adjusting for covariates, those high in work PA showed a significantly higher likelihood of having depressive symptoms both in male (OR= 2.74, 95% CI 1.56-4.82) and female participants (OR= 2.84, 95% CI 1.70-4.49), compared to those with no work PA. LIMITATION: Cross-sectional nature of the data prevents causal associations. CONCLUSIONS: Although the total amount of PA participation was not associated with depressive symptoms, domain-specific PAs were differently associated with depressive symptoms. Specifically, higher amount of work PA was significantly associated with higher prevalence of depressive symptoms; this topic deserves further attention and future investigation.

Physical activity levels, exercise preferences, and exercise barriers in Korean children and adolescents after cancer treatment.

PURPOSE: The purpose of the current study was to explore physical activity (PA) levels, exercise preferences, and perceived barriers to PA in childhood cancer survivors. METHODS: This cross-sectional study surveyed 120 childhood cancer survivors aged 8-18 years from the pediatric oncology center in South Korea between March and August 2017. The modified Exercise & Quality of Life questionnaire, Korea Youth Risk Behavior Web-based Survey, and Godin Leisure-Time Questionnaire were used to assess PA levels, preferences, and exercise barriers. RESULTS: Among 120 participants (72 boys, 48 girls) whose average age at the time of the survey was 14.57 ± 3.00 years and the average age at diagnosis was 8.22 years, the three most common diagnoses were acute leukemia (43.3%), brain tumor (13.3%), and malignant lymphoma (10.8%). Only 16 participants (5%) met the PA recommendations for children (at least 60 min of moderate PA per day). The most preferred sporting activities included soccer, basketball, strengthening exercises, badminton, dance, and taekwondo. They generally had positive attitudes toward exercise, and more than 63% of participants intended to exercise the following month. The five most prevalent perceived barriers to exercise were lack of time, poor health, reluctance to sweat, lack of exercise skills, and no exercise partners. CONCLUSIONS: While most childhood cancer survivors did not meet the PA recommendation, most of them agreed that exercise was beneficial, and they intended to participate in the exercise. Exercise and PA programs should be tailored to the personal health and preferences of childhood cancer survivors.

Arabidopsis thaliana Ubiquitin-Associated Protein 1 (AtUAP1) Interacts with redundant RING Zinc Finger 1 (AtRZF1) to Negatively Regulate Dehydration Response.

Ubiquitination, one of the most frequently occurring post-translational modifications, is essential for regulating diverse cellular processes in plants during abiotic stress. The E3 ubiquitin (Ub) ligase Arabidopsis thaliana really interesting new gene (RING) zinc finger 1 (AtRZF1) mutation is known to enhance drought tolerance in A. thaliana seedlings. To further investigate the function of AtRZF1 in osmotic stress, we isolated Ub-associated protein 1 (AtUAP1) which interacts with AtRZF1 using a yeast two-hybrid system. AtUAP1, a Ub-associated motif containing protein, increased the amount of Ub-conjugated AtRZF1. Moreover, AtUAP1 RNA interference lines were more tolerant to osmotic stress than wild type, whereas AtUAP1-overexpressing (OX) transgenic lines showed sensitive responses, including cotyledon greening, water loss, proline accumulation and changes in stress-related genes expression, indicating that AtUAP1 could negatively regulate dehydration-mediated signaling. In addition, AtUAP1-green fluorescent protein fusion protein was observed in the nuclei of root cells of transgenic seedlings. Genetic studies showed that the AtRZF1 mutation could rescue the sensitive phenotype of AtUAP1-OX lines in response to osmotic stress, suggesting that AtRZF1 was epistatic to AtUAP1 in dehydration signaling. Taken together, our findings describe a new component in the AtRZF1 ubiquitination pathway which controls the dehydration response in A. thaliana.

Adherence to nine-month isoniazid for latent tuberculosis infection in healthcare workers: a prospective study in a tertiary hospital.

Poor adherence to medication can lead to treatment failure in healthcare workers (HWCs) with latent tuberculosis infection (LTBI) who are at high risk of developing active tuberculosis. However, the factors associated with non-completion of nine-month LTBI treatment with isoniazid (9 H) have not been well studied. We investigated the completion rate and factors affecting adherence to LTBI treatment with 9 H among HCWs. A prospective cohort study of 114 HCWs who were diagnosed with LTBI by QuantiFERON-TB Gold In-Tube tests were performed in a single university hospital between June 2016 and December 2017. All patients received the 9 H LTBI treatment. At each visit, treatment adherence and development of adverse reactions to isoniazid were evaluated via a standard questionnaire. To evaluate the impact of the severity of hepatotoxicity on non-completion of LTBI treatment, we classified hepatotoxicity into two groups: severe hepatotoxicity was defined as alanine aminotransferase >3.0 times the upper normal limit (UNL) with symptoms or = 5.0 times the UNL. Mild hepatotoxicity was defined as alanine aminotransferase>UNL, but not meet the definition of severe hepatotoxicity. Overall, 71 HCWs (62.3%) completed LTBI treatment with 9 H while 43 HCWs (37.7%) discontinued their treatment. Most discontinuation (81.4%, 35/43) occurred during the first three months of treatment. There were no significant differences in age, sex, occupation, or comorbidities between the HCWs who completed and those who discontinued LTBI treatment. However, HCWs who discontinued LTBI treatment had more hepatotoxicity than those who completed treatment (44.2% vs. 11.3%, P < 0.001). Cox proportional hazard analysis revealed that hepatotoxicity is the only factor significantly associated with discontinuation of 9 H LTBI treatment (unadjusted HR = 2.89, 95% CI = 1.62-5.46). In multivariable analysis, not only severe hepatotoxicity (adjusted HR = 7.99, 95% CI = 3.05-20.94) but also mild hepatotoxicity was significantly associated with discontinuation of LTBI treatment (adjusted HR = 2.34, 95% CI = 1.05-5.21). The completion rate of 9 H LTBI treatment was 62.3% among HCWs. While age, sex, occupation, and pretreatment comorbidities were not associated with treatment completion, isoniazid-induced hepatotoxicity significantly affected adherence.

Neutrophil Gelatinase-Associated Lipocalin for Predicting Intensive Care Unit Admission and Mortality in Patients with Pneumonia.

Pneumonia is one of the most common causes of hospital admissions and mortality, and it is responsible for significant socioeconomic burden worldwide. Neutrophil gelatinase-associated lipocalin (NGAL) is a 25-kDa protein, which is involved in iron trafficking and has chemostatic and bacteriostatic effects. NGAL is also known as an early marker of many inflammatory diseases. However, little is known about the role of NGAL in the management of pneumonia. Thus, this study aimed to investigate whether plasma NGAL levels can predict intensive care unit (ICU) admission and in-hospital mortality in patients with pneumonia. This retrospective observational study included 241 adults hospitalized with pneumonia who underwent NGAL measurement. We compared the prognostic values of plasma NGAL with pneumonia severity index (PSI) for prediction of ICU admission and in-hospital mortality. Of 241 patients, 47 (19.5%) died during hospital admission. There was no significant difference between NGAL and PSI for predicting ICU admission (area under the receiver operating characteristic curve [AUC] of log NGAL vs. PSI, P > 0.999). Although log NGAL was useful in predicting in-hospital mortality, its ability was inferior to that of PSI (AUC of log NGAL vs. PSI, P = 0.008). Multivariable analysis revealed that log NGAL was significantly associated with ICU admission (adjusted odds ratio = 10.76, P < 0.001) and in-hospital mortality (adjusted odds ratio = 5.04, P = 0.004). These results suggest that plasma NGAL level is a useful biomarker for predicting ICU admission and mortality in hospitalized patients with pneumonia.

Loss of Arabidopsis Halotolerance 2-like (AHL), a 3'-phosphoadenosine-5'-phosphate phosphatase, suppresses insensitive response of Arabidopsis thaliana ring zinc finger 1 (atrzf1) mutant to abiotic stress.

KEY MESSAGE: Destruction of PAP phosphatase AHL suppresses atrzf1 phenotype in abiotic stress responses. AHL plays an intermediate role in the regulation of proline accumulation by PAP nucleotidase. Proline (Pro) metabolism is important for environmental responses, plant development, and growth. However, the role of Pro in abiotic stress process is unclear. Using atrzf1 (Arabidopsis thaliana ring zinc finger 1) mutant as a parental line for T-DNA tagging mutagenesis, we identified a suppressor mutant designated as proline content alterative 17 (pca17) that suppressed insensitivity of atrzf1 to abiotic stresses during early seedling growth. Pro content of pca17 was lower than that in both wild type (WT) and atrzf1 while complementary lines were less sensitive to abscisic acid (ABA) and abiotic stresses compared to WT. Thermal Asymmetric Interlaced (TAIL)-PCR of pca17 showed that T-DNA was inserted at site of At5g54390 (AHL for Arabidopsis Halotolerance 2-like) encoding 3'-phosphoadenosine-5'-phosphate (PAP) phosphatase. Under drought stress condition, products of sulfate metabolism such as PAP and adenosine monophosphate were significantly lower in pca17 than those in WT and atrzf1. Furthermore, pca17 showed significantly higher levels of several important drought parameters including malondialdehyde, ion leakage, and water loss than WT and atrzf1. Fluorescence signal of green fluorescent protein (GFP)-tagged AHL was quite strong in nuclei of the root and guard cells of transgenic seedlings. Additionally, AHL promoter-ß-glucuronidase (GUS) construct revealed substantial gene expression in vasculature tissues and pollen. Collectively, these findings demonstrate that pca17 acts as a dominant suppressor mutant of atrzf1 in abiotic stress response by modulating proline and sulfate metabolism.

Factors associated with non-initiation of latent tuberculosis treatment among healthcare workers with a positive interferon-gamma releasing assay.

Despite widespread use of the interferon-gamma release assay for the diagnosis of latent tuberculosis infection (LTBI), the initiation rate of and factors associated with LTBI treatment among healthcare workers (HCWs) have not been studied in depth. The aim of this study was to evaluate the initiation rate of LTBI treatment and also to identify any factors associated with non-initiation of LTBI treatment among HCWs. A retrospective cohort study of 293 HCWs with LTBI was performed at a teaching hospital in Korea. LTBI was diagnosed using QuantiFERON-TB Gold In-Tube tests (Cellestis Ltd., Carnegie, VIC, Australia). Of the 293 HCWs with LTBI, 189 HCWs (64.5%) visited an outpatient clinic for a medical consultation regarding LTBI treatment. Of these, 128 (67.7%) consented to LTBI treatment for a 43.7% LTBI treatment initiation rate. Upon multivariable analysis, having a liver disease or currently taking hepatotoxic drugs (adjusted odds ratio [OR] = 12.03, 95% confidence interval [CI] = 3.12-46.35), being a physician (adjusted OR = 14.01, 95% CI = 2.82-69.74) and other patient-related HCWs (adjusted OR = 3.58, 95% CI = 1.46-8.78), and years of employment ≥20 years (adjusted OR = 4.77, 95% CI = 1.74-13.12) were independent factors associated with the non-initiation of LTBI treatment. Upon bivariate multivariable analysis, while having a liver disease or currently taking hepatotoxic drugs (adjusted OR = 12.85, 95% CI = 3.06-55.92), being a physician (adjusted OR = 28.43, 95% CI = 4.78-169.28) and other patient-related HCWs (adjusted OR = 4.80, 95% CI = 1.56-14.74), and years of employment ≥20 years (adjusted OR = 4.55, 95% CI = 1.37-15.15) were factors associated with no outpatient clinic visit for a consultation of LTBI treatment, having a liver disease or currently taking hepatotoxic drugs (adjusted OR = 11.76, 95% CI = 2.68-51.73) and years of employment ≥20 years (adjusted OR = 5.29, 95% CI = 1.38-20.19) were factors associated with refusal of LTBI treatment after a consultation. The overall initiation rate of LTBI treatment was suboptimal in HCWs with LTBI diagnosed using an interferon-gamma releasing assay. Having a liver disease or currently taking hepatotoxic drugs, being a physician and other patient-related HCWs, and years of employment ≥20 years were associated with non-initiation of LTBI treatment.

A basic helix-loop-helix 104 (bHLH104) protein functions as a transcriptional repressor for glucose and abscisic acid signaling in Arabidopsis.

Transduction of glucose (Glc) signaling is critical for plant development, metabolism, and stress responses. However, identifying initial Glc sensing and response stimulating mechanisms in plants has been difficult due to dual functions of glucose as energy sources and signaling component. A basic Helix-Loop-Helix 104 (bHLH104) protein is a homolog of bHLH34 previously isolated from Arabidopsis that functions as a transcriptional activator of Glc and abscisic acid (ABA) responses. In this study, we characterized bHLH104 as a transcription factor that binds to the regulatory region of Arabidopsis Plasma membrane Glc-responsive Regulator (AtPGR) gene. The bHLH104 binds to 5'-AANA-3' element of the promoter region of AtPGR in vitro and represses beta-glucuronidase (GUS) activity in AtPGR promoter-GUS transgenic plants. Genetic approaches show that bHLH104 positively regulates Glc and abscisic acid (ABA) response. These results suggest that bHLH104 is involved in Glc- and ABA-mediated signaling pathway. Taken together, these findings provide evidence that bHLH104 is an important transcription regulator in plant-sensitivity to Glc and ABA signaling.

Effects of a 12-week home-based exercise program on quality of life, psychological health, and the level of physical activity in colorectal cancer survivors: a randomized controlled trial.

PURPOSE: To examine the effects of a home-based exercise program on quality of life (QOL), psychological health, and the level of physical activity (PA) in colorectal cancer survivors. METHODS: Seventy-one colorectal cancer survivors were randomized into either a home-based exercise group (N = 37) or control group (N = 34). The home-based exercise program included unsupervised walking, stationary bike, or swimming for aerobic exercise, as well as resistance exercise DVDs, a pedometer, and an exercise log. The Functional Assessment of Cancer Therapy-Colorectal, Functional Assessment of Chronic Illness Therapy-Fatigue Scale, patient health questionnaire, and Godin Leisure-Time Exercise Questionnaire were used to assess QOL, fatigue, depression, and PA levels. RESULTS: Among the 71 participants, 30 in the exercise group and 28 in the control group completed the study. The change in the QOL between the intervention and control groups was insignificant. However, QOL was significantly improved in the exercise group (QOL, p = 0.024). Sub-domain of QOL, emotional well-being, and trial outcome index-physical/functional/colorectal (p = 0.015 and p = 0.035, respectively) were improved in the exercise group. The level of PA was significantly increased after 12 weeks in the exercise group (97.0 ± 188.5 vs. 332.6 ± 306.1, p < 0.001), and the change significantly differed compared with the control group (mean change 235.6 vs. 16.3, p < 0.001). CONCLUSIONS: The home-based exercise program may improve the QOL and psychological health in colorectal cancer survivors. We have demonstrated that the home-based exercise program was effective in increasing the level of PA in colorectal cancer survivors.

PCA22 acts as a suppressor of atrzf1 to mediate proline accumulation in response to abiotic stress in Arabidopsis.

Proline metabolism is important for environmental responses, plant growth, and development. However, its precise roles in plant abiotic stress tolerance are not well understood. Mutants are valuable for the identification of new genes and for elucidating their roles in physiological mechanisms. We applied a suppressor mutation approach to identify novel genes involved in the regulation of proline metabolism in Arabidopsis. Using the atrzf1 (Arabidopsis thaliana ring zinc finger 1) mutant as a parental line for activation tagging mutagenesis, we selected several mutants with suppressed induction of proline accumulation under dehydration conditions. One of the selected mutants [proline content alterative 22 (pca22)] appeared to have reduced proline contents compared with the atrzf1 mutant under drought stress. Generally, pca22 mutant plants displayed suppressed atrzf1 insensitivity to dehydration and abscisic acid during early seedling growth. Additionally, the pca22 mutant exhibited shorter pollen tube length than wild-type (WT) and atrzf1 plants. Furthermore, PCA22-overexpressing plants were more sensitive to dehydration stress than the WT and RNAi lines. Green fluorescent protein-tagged PCA22 was localized to the cytoplasm of transgenic Arabidopsis cells. Collectively, these results suggest that pca22 acts as dominant suppressor mutant of atrzf1 in the abiotic stress response.

Arabidopsis Basic Helix-Loop-Helix 34 (bHLH34) Is Involved in Glucose Signaling through Binding to a GAGA Cis-Element.

The modulation of glucose (Glc) homeostasis and signaling is crucial for plant growth and development. Nevertheless, the molecular signaling mechanism by which a plant senses a cellular Glc level and coordinates the expression of Glc-responsive genes is still incompletely understood. Previous studies have shown that Arabidopsis thaliana plasma membrane Glc-responsive regulator (AtPGR) is a component of the Glc-responsive pathway. Here, we demonstrated that a transcription factor bHLH34 binds to 5'-GAGA-3' element of the promoter region of AtPGR in vitro, and activates beta-glucuronidase (GUS) activity upon Glc treatment in AtPGR promoter-GUS transgenic plants. Gain- and loss-of-function analyses suggested that the bHLH34 involved in the responses to not only Glc, but also abscisic acid (ABA) and salinity. These results suggest that bHLH34 functions as a transcription factor in the Glc-mediated stress responsive pathway as well as an activator of AtPGR transcription. Furthermore, genetic experiments revealed that in Glc response, the functions of bHLH34 are different from that of a bHLH104, a homolog of bHLH34. Collectively, our findings indicate that bHLH34 is a positive regulator of Glc, and may affect ABA or salinity response, whereas bHLH104 is a negative regulator and epistatic to bHLH34 in the Glc response.

Repeated Panniculitis Induced by Pegylated Interferon Alpha 2a in a Patient with Chronic Hepatitis C.

Pegylated interferon alpha (PEG-IFN-α) is widely used to treat chronic hepatitis C in combination with ribavirin. Many adverse effects of PEG-IFN-α, such as hematologic, psychologic, dermatologic, immunologic, and other abnormalities, have been reported, and some serious adverse events lead to PEG-IFN-α treatment discontinuation. For very rare adverse events such as panniculitis, there are no established guidelines on whether to continue PEG-IFN-α treatment. Published reports on panniculitis induced by PEG-IFN-α 2a are sparse. Herein we report a case of repeated occurrences of panniculitis in a patient with chronic hepatitis C, leading to treatment cessation.

Regulation of Arabidopsis thaliana plasma membrane glucose-responsive regulator (AtPGR) expression by A. thaliana storekeeper-like transcription factor, AtSTKL, modulates glucose response in Arabidopsis.

Biochemical, genetic, physiological, and molecular research in plants has demonstrated a central role of glucose (Glc) in the control of plant growth, metabolism, and development, and has revealed networks that integrate light, stresses, nutrients, and hormone signaling. Previous studies have reported that AtPGR protein as potential candidates for Glc signaling protein. In the present study, we characterized transcription factors that bind to the upstream region of the AtPGR gene isolated using the yeast one-hybrid screening with an Arabidopsis cDNA library. One of the selected genes (AtSTKL) appeared to confer elevated sensitivity to Glc response. Overexpression of AtSTKLs (AtSTKL1 and AtSTKL2) increased the sensitivity to Glc during the post-germination stages. In contrast, atstkl1 and atstkl2 antisense lines displayed reduced sensitivity to high Glc concentration during the early seedling stage. Furthermore, we showed that the two AtSTKLs bind to the 5'-GCCT-3' element of the upstream promoter region of the AtPGR gene in vitro and repress the beta-glucuronidase (GUS) activity in AtPGR promoter-GUS (P999-GUS) transgenic plants. Green fluorescent protein (GFP)-tagged AtSTKLs were localized in the nuclei of transgenic Arabidopsis cells. Collectively, these results suggest that AtSTKL1 and AtSTKL2 function both as repressors of AtPGR transcription and as novel transcription factors in the Glc signaling pathway.