Brain FDG PET for visualizing the relation between impaired lung function and cognitive decline in lung cancer: a preliminary study.

OBJECTIVE: Impaired lung function is associated with an increased risk for cognitive decline. F-18 fluorodeoxyglucose (FDG) PET is a well-known neurodegenerative biomarker for dementia. We investigated the association between lung and brain function using FDG PET in patients with lung cancer. METHODS: A random sub-sample of 102 patients with lung cancer and without a self-reported history of neuropsychiatric disorders were recruited and underwent both lung function tests and FDG PET scans before treatment. Lung function was analyzed as the percentage predicted value (% pred) of forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1). FDG uptake was measured as standardized uptake values (SUVs) in the frontal, parietal, temporal, and occipital cortices and cognition-related regions. Regional SUV ratios (SUVRs) were calculated by dividing the SUV in each region by the whole-brain SUV and were then evaluated against lung function indices and clinical variables. RESULTS: After excluding five patients with brain metastases, 97 patients were included in the final analysis (mean age, 67.7 ± 10.3 years). Mean FVC and mean FEV1 were 80.0% ± 15.4% and 77.6% ± 17.8%, respectively. Both FVC and FEV1 were positively correlated with SUVRs in all brain regions after adjusting the data for clinical variables. The degree of decrease in SUVRs related to lung function was not significantly different between cognition-related regions and other regions. CONCLUSION: Impaired lung function was associated with decreased glucose metabolism in all regions of the brain, indicating that cognitive decline related to decreased glucose metabolism may be due to reduced perfusion.

Endogenous level of abscisic acid down-regulated by brassinosteroids signaling via BZR1 to control the growth of Arabidopsis thaliana.

The increased level of endogenous abscisic acid (ABA) in brassinosteroid (BR)-deficient mutants, such as det2 and cyp85a1 × cyp85a2, suggests that ABA synthesis is inhibited by endogenous BRs in Arabidopsis thaliana. Expression of the ABA biosynthesis gene ABA-deficient 2 (ABA2) was negatively regulated by exogenously applied BR but up-regulated by the application of brassinazole and in det2 and cyp85a1 × cyp85a2. In addition, ABA2 expression decreased in bzr1-1D, showing that ABA biosynthesis is inhibited by BR signaling via BZR1, intermediated by ABA2, in Arabidopsis. Four cis-element sequences (E-boxes 1-4) in the putative promoter region of ABA2 were identified as BZR1 binding sites. The electrophoretic mobility shift assay and chromatin immune precipitation analysis demonstrated that BZR1 directly binds to overlapped E-boxes (E-box 3/4) in the promoter region of ABA2. The level of endogenous ABA was decreased in bzr1-1D compared to wild-type, indicating that binding of BZR1 to the ABA2 promoter inhibits ABA synthesis in Arabidopsis. Compared to wild-type, aba2-1 exhibited severely reduced growth and development. The abnormalities in aba2-1 were rescued by the application of ABA, suggesting that ABA2 expression and ABA synthesis are necessary for the normal growth and development of A. thaliana. Finally, bzr1-KO × aba2-1 exhibited inhibitory growth of primary roots compared to bzr1-KO, verifying that ABA2 is a downstream target of BZR1 in the plant. Taken together, the level of endogenous ABA is down-regulated by BR signaling via BZR1, controlling the growth of A. thaliana.

Correction: A new bioluminescent reporter system to study the biodistribution of systematically injected tumor-derived bioluminescent extracellular vesicles in mice.

[This corrects the article DOI: 10.18632/oncotarget.22493.].

Brassinosteroids signaling via BZR1 down-regulates expression of ACC oxidase 4 to control growth of Arabidopsis thaliana seedlings.

ProACO4-GUS expression and RT-PCR analysis revealed that ACO4 is predominantly expressed in shoots of Arabidopsis seedlings under light conditions. ACO4-overexpressed mutant 35S-ACO4 produced more ethylene relative to the wild-type, which resulted in reduced growth of Arabidopsis seedlings. The abnormal growth of seedlings recurred after the application of Co2+ ions, suggesting that ACO4 is a functional ACO necessary to regulate the growth and development of Arabidopsis seedlings. Exogenously-applied brassinosteroids (BRs) inhibited the expression of ACO4, and an enhanced ACO4 expression was found in det2, a BR-deficient mutant. Additionally, expression of ACO4 was decreased in bzr1-D (a BZR1-dominant mutant), implying that BR signaling negatively regulates ACO4 expression via BZR1 in Arabidopsis. In the intergenic region of ACO4, four E-boxes and a BR regulatory element (BRRE) are found. Electrophoretic mobility shift and chromatin immunoprecipitation assays showed that BZR1 binds directly to the BRRE in the putative promoter region of ACO4. By binding of BZR1 to BRRE, less ethylene was produced, which seems to regulate the growth and development of Arabidopsis seedlings.

Early-Phase 18F-Florbetaben PET as an Alternative Modality for 18F-FDG PET.

PURPOSE: Based on the possibility that early-phase florbetaben (E-FBB) brain PET can be a surrogate for brain perfusion imaging, we conducted this study to investigate the clinical utility of E-FBB PET instead of F-FDG brain PET. MATERIALS AND METHODS: This prospective study included 35 patients with clinical suspicion of cognitive decline or dementia and 5 healthy controls. Brain MRI, E-FBB PET, late-phase FBB PET, and FDG PET were acquired. The regional SUV ratios (SUVRs) were calculated by cortical surface region of interest analysis using individual MRI, and relationship between E-FBB and FDG PET was analyzed. All PET scans were scored and analyzed as per visual scoring system, which represent tracer uptake abnormality. Moreover, uptake patterns were analyzed to determine the disease. RESULTS: Among the 40 subjects, 19 were amyloid-positive and 21 were amyloid-negative on late-phase FBB PET. Cortical surface region of interest analysis conducted for comparing between E-FBB and FDG PET revealed significant correlations (P < 0.0001) for regional SUVR among all brain regions; however, the SUVR values of FDG PET were statistically higher than those of E-FBB PET. Similarly, although the visually rated scores for E-FBB and FDG PET showed significant correlation (P < 0.0001), it was considered that the tracer uptake was more severely decreased for FDG PET. The disease types, specified by E-FBB and FDG PET, were statistically correlated. CONCLUSIONS: E-FBB PET could potentially be a useful biomarker for the diagnosis of dementia in place of FDG PET. Nevertheless, the severity of the disease was more accurately determined by FDG PET.

White blood cell labeling with Technetium-99m (99mTc) using red blood cell extracellular vesicles-mimetics.

BACKGROUND: Extracellular vesicles, have gained increasing attention for their application in drug delivery. Here, we developed a novel method for radiolabeling WBCs with 99mTc using RBC-derived extracellular vesicles -mimetics (EVMs), and monitored in vivo inflammation tracking of 99mTc-WBC using gamma camera in acute inflammation mouse model. METHODS: Engineered EVMs from RBCs were produced by a one-step extrusion method. RBC-EVMs were analyzed by NTA and TEM. Cells were labeled with 99mTc by using 99mTc-RBC-EVMs. Inflammation mice model was prepared and confirmed by 18F-FDG PET/CT. 99mTc-WBCs were injected in mice, and their biodistribution was analyzed by gamma camera. FINDING: The radiochemical purity of 99mTc-RBC-EVMs was 100%. The 99mTc-labeling did't affect the size and morphology. The 99mTc in the cytoplasm of RBC-EVMs was successfully confirmed by high angle annular dark field STEM (scanning transmission electron microscope). Cells were successfully labeled with 99mTc using 99mTc-RBC-EVMs, and the counts per minute was increased in dose- and time-dependent manners. The 18F-FDG PET/CT images confirmed establishment of acute inflammation (left mouse foot). 99mTc-WBCs showed higher uptake in the inflamed foot than non-inflamed foot. INTERPRETATION: This novel method for radiolabeling WBCs using RBC-EVMs. 99mTc labeling may be a feasible method to monitor the in vivo biodistribution of cells.

Serum thyroglobulin elevation after needle aspiration of the lymph nodes: the predictive value for detecting metastasis in papillary thyroid cancer patients - a pilot study.

Ultrasonography (USG)-guided fine needle aspiration (FNA) is widely used for diagnosis of lymph node (LN) metastasis in papillary thyroid cancer (PTC). However, FNA cytology sometimes shows inconclusive results. Recently, the measurement of thyroglobulin (Tg) in FNA washout fluid (aspirate-Tg) has been widely adopted, but there are some difficulties in the preparation of the sample and standardization of the procedure. Here, we examined serum Tg after FNA as a new predictive marker for LN metastasis of PTC. We performed USG-guided FNA cytology and examined aspirate-Tg in PTC patients showing suspicious metastatic LNs during follow-up. We measured baseline serum thyroid stimulating hormone (TSH), Tg, and Tg antibody levels before FNA, and serum Tg level within an hour after FNA. We defined aspirate-Tg level above 0.9 ng/mL as positive, and a 30% increase in serum Tg level after FNA compared to the baseline as elevation of serum Tg. Twenty-two patients were included in our study. Nine patients (40.9%) showed elevation of Tg level after FNA, and the mean value of Tg elevation was 24.8 ±â€Š48.0 ng/mL. Among these 9 patients, 8 were diagnosed with PTC and 1 patient showed cellular atypia on cytopathology. All these patients showed positive aspirate-Tg. Thirteen patients (59.1%) did not show elevation of Tg level after FNA. Among these patients, 2 had PTC, 2 had cellular atypia, and 9 yielded negative results for malignancy on cytopathology. Elevation of serum Tg level after FNA might have a diagnostic role for predicting LN metastasis of PTC.

The Preventive Effect of Parotid Gland Massage on Salivary Gland Dysfunction During High-Dose Radioactive Iodine Therapy for Differentiated Thyroid Cancer: A Randomized Clinical Trial.

PURPOSE: To evaluate the preventive effect of parotid gland (PG) massage for PG damage during the I therapy, we prospectively investigated the serum amylase value and salivary gland scintigraphy (SGS) after I therapy. MATERIALS AND METHODS: One hundred patients with thyroidectomized differentiated thyroid cancer who underwent high-dose I therapy were enrolled in the clinical trial and randomized into 2 groups (PG massage group and nonmassage group). The serum amylase value was obtained before and 24 hours after I therapy, and the SGSs were also taken just before and at 8 months after the I therapy. Change in serum amylase value and SGS was compared between PG massage and nonmassage groups. RESULTS: The difference value of serum amylase was significantly lower in PG massage group than in nonmassage group (P = 0.0052). Worsening of PG function on SGS was observed in 43 (45.3%) of the 95 patients. The incidence rate of PG abnormality on F/U SGS was significantly lower in PG massage group than in nonmassage group (odds ratio, 0.3704; P = 0.0195). In the multiple regression analysis, PG massage significantly affected the abnormality on the 8-month F/U SGS (rpartial = -0.2741, P = 0.0090) after adjusting for clinical variables (age, sex, TNM stage, TSH preparation methods for the I therapy, and I dose). CONCLUSIONS: PG gland massage significantly reduced the incidence rates of salivary gland dysfunction on the 8-month F/U SGS and the level of the serological marker of salivary gland destruction after I therapy. Therefore, PG gland massage could alleviate salivary gland damage related to I therapy.

PROGNOSTIC VALUE OF LYMPH NODE UPTAKE ON PRETREATMENT F-18 FDG PET/CT IN PATIENTS WITH N1B PAPILLARY THYROID CARCINOMA.

Objective: The aim of this study was to investigate the prognostic value of metabolic characteristics of metastatic lymph node (LN) using pretreatment F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for patients with papillary thyroid carcinoma (PTC) and metastatic lateral LN (N1b). Methods: Ninety-six PTC patients (female:male = 72:24; median age, 44.5 years) with pathologic N1b who underwent pretreatment FDG PET/CT, total thyroidectomy, and radioactive iodine ablation were retrospectively reviewed. To predict responses to initial therapy and recurrence, clinicopathologic factors and metabolic parameters were reviewed, such as sex, age, tumor size, extranodal extension, number and ratio of metastatic LNs, serum thyroglobulin, and maximum standardized uptake value (SUVmax). Results: Among the 96 PTC patients, 81 (84.4%) were classified into the acceptable response (58 excellent; 23 indeterminate) and 15 (15.6%) into the incomplete response (8 biochemical incomplete; 7 structural incomplete) by the 2015 American Thyroid Association management guideline for differentiated thyroid carcinoma. The multivariate analysis showed that SUVmax of N1b (P = .018), pre-ablation stimulated thyroglobulin level (P = .006), and the ratio of metastatic LNs (P = .018) were related to incomplete response. The cutoff value of each variable was determined by receiver operating characteristic analysis. Nine (9.4%) patients experienced recurrences (median follow-up: 50 months). The Kaplan-Meier analysis revealed that SUVmax of N1b (cutoff value: 2.3; P = .025) and ratio of metastatic LNs (cutoff value: 0.218; P = .037) were significant prognostic factors for recurrence. Conclusion: High SUVmax of N1b cervical LN on pretreatment FDG PET/CT could predict incomplete responses to initial therapy and recurrence in patients with N1b PTC. Abbreviations: ATA = American Thyroid Association; DTC = well-differentiated thyroid carcinoma; FDG = F-18 fluorodeoxyglucose; IQR = interquartile range; LN = lymph node; N1b = metastatic lateral cervical lymph node; PET/CT = positron emission tomography/computed tomography; PTC = papillary thyroid carcinoma; RAI = radioactive iodine; ROC = receiver operating characteristic; SUVmax = maximum standardized uptake value; Tg = thyroglobulin; USG = ultrasonography.

A novel strategy of transferring NIS protein to cells using extracellular vesicles leads to increase in iodine uptake and cytotoxicity.

BACKGROUND: This study was designed to explore a novel approach for transferring NIS protein to cells using extracellular vesicle (EV) and enhancing iodine avidity in hepatocellular carcinoma (HCC) cells. METHODS: We transfected the HCC cells (Huh7) with NIS gene, designated as Huh7/NIS, and isolated the EVs from them. Presence of NIS protein in EVs and EV-mediated transport of NIS protein to recipient Huh7 cells were tested using Western blotting. We also examined radioiodine uptake in Huh7 cells treated with EV-Huh7/NIS. RESULTS: Successful transfer of NIS protein into Huh7 cells was confirmed by WB and microscopy. EVs showed high levels of NIS protein in them. Treatment of Huh7 cells with EV-Huh7/NIS increased the NIS protein level and enhanced 125I uptake in recipient Huh7 cells. In addition, EV-huh7/NIS pre-treatment enhanced the cytotoxicity of 131I therapy against Huh7 cells by inducing increased DNA damage/increased γH2A.X foci formation. CONCLUSION: This is the first-of-its-kind demonstration of successful transportation of the NIS protein to cells via EVs, which increased radioiodine uptake. This approach can revert radioiodine-resistant cancers into radioiodine-sensitive cancers.

Arabidopsis ACC Oxidase 1 Coordinated by Multiple Signals Mediates Ethylene Biosynthesis and Is Involved in Root Development.

Ethylene regulates numerous aspects of plant growth and development. Multiple external and internal factors coordinate ethylene production in plant tissues. Transcriptional and post-translational regulations of ACC synthases (ACSs), which are key enzymes mediating a rate-limiting step in ethylene biosynthesis have been well characterized. However, the regulation and physiological roles of ACC oxidases (ACOs) that catalyze the final step of ethylene biosynthesis are largely unknown in Arabidopsis. Here, we show that Arabidopsis ACO1 exhibits a tissue-specific expression pattern that is regulated by multiple signals, and plays roles in the lateral root development in Arabidopsis. Histochemical analysis of the ACO1 promoter indicated that ACO1 expression was largely modulated by light and plant hormones in a tissue-specific manner. We demonstrated that point mutations in two E-box motifs on the ACO1 promoter reduce the light-regulated expression patterns of ACO1. The aco1-1 mutant showed reduced ethylene production in root tips compared to wild-type. In addition, aco1-1 displayed altered lateral root formation. Our results suggest that Arabidopsis ACO1 integrates various signals into the ethylene biosynthesis that is required for ACO1's intrinsic roles in root physiology.

Risk factors for radioactive iodine-avid metastatic lymph nodes on post I-131 ablation SPECT/CT in low- or intermediate-risk groups of papillary thyroid cancer.

OBJECTIVE: Post I-131 ablation single-photon emission computed tomography (SPECT)/CT can show radioactive iodine (RAI)-avid cervical metastatic lymph nodes (mLN) in differentiated thyroid cancer. This study aimed to evaluate the incidence of RAI-avid mLN on post I-131 ablation SPECT/CT and the risk factors related to metastasis among patients with papillary thyroid cancer (PTC) in the low- or intermediate-risk groups. STUDY DESIGN AND SETTING: Among 339 patients with PTC who underwent total thyroidectomy followed by I-131 ablation, 292 (228 women, 64 men) belonging to the low- or intermediate-risk groups before I-131 ablation, and with sufficient clinical follow-up data were enrolled. The risk groups were classified based on the American Thyroid Association 2015 guideline. Each patient was followed-up for at least 24 months after the ablation (median: 30 months). The clinical, pathologic, and biochemical factors of PTC were reviewed, and their relationships to RAI-avid mLN on SPECT/CT were analyzed. RESULTS: Of the 292 patients, 61 and 231 belonged to the low-and intermediate-risk groups, respectively. Four (6.5%) patients in the low-risk group and 31 (13.0%) patients in the intermediate-risk group had RAI-avid mLN. A high preablation TSH-stimulated serum thyroglobulin (Tg) level in the low- or intermediate-risk group predicted the presence of RAI-avid mLN (cut-off = 0.5; hazard ratio (HR): 2.96; p = 0.04). In the subgroup analysis by risk group, TSH-stimulated serum Tg only predicted RAI-avid mLN in the low-risk group (cut-off = 1.0; HR: 5.3; p = 0.03). CONCLUSION: The incidence of RAI-avid mLN on postablation SPECT/CT was relatively high in both low- and intermediate-risk patients with PTC, and high preablation TSH-stimulated serum Tg level was a predictor of metastasis, especially in the low-risk group. A selective treatment approach should be considered in patients with high preablation TSH-stimulated serum Tg level.

In vivo Non-invasive Imaging of Radio-Labeled Exosome-Mimetics Derived From Red Blood Cells in Mice.

Exosomes are natural nano-sized membrane vesicles that have garnered recent interest owing to their potential as drug delivery vehicles. Though exosomes are effective drug carriers, their production and in vivo biodistribution are still not completely elucidated. We analyzed the production of exosome mimetics (EMs) from red blood cells (RBCs) and the radio-labeling of the RBC-EMs for in vivo imaging. Engineered EMs from RBCs were produced in large-scale by a one-step extrusion method, and further purified by density-gradient centrifugation. RBC-EMs were labeled with technetium-99m (99mTc). For non-invasive imaging, 99mTc (free) or 99mTc-RBC-EMs were injected in mice, and their biodistribution was analyzed by gamma camera imaging. Animals were sacrificed, and organs were collected for further biodistribution analysis. RBC-EMs have similar characteristics as the RBC exosomes but have a 130-fold higher production yield in terms of particle numbers. Radiochemical purity of 99mTc-RBC-EMs was almost 100% till 2 h reduced to 97% at 3 h. Radio-labeling did not affect the size and morphology of RBC-EMs. In contrast to free 99mTc, in vivo imaging of 99mTc-RBC-EMs in mice showed higher uptake in the liver and spleen, and no uptake in the thyroid. Ex vivo imaging confirmed the in vivo findings. Furthermore, fluorescent imaging confirmed the nuclear imaging findings. Immunofluorescent imaging revealed that the hepatic uptake of RBC-EMs was significantly mediated by kupffer cells (resident hepatic macrophages). Our results demonstrate a simple yet large-scale production method for a novel type of RBC-EMs, which can be effectively labeled with 99mTc, and feasibly monitored in vivo by nuclear imaging. The RBC-EMs may be used as in vivo drug delivery vehicles.

Prevalence and Risk Factors of Atypical Femoral Fracture Bone Scintigraphic Feature in Patients Experiencing Bisphosphonate-Related Osteonecrosis of the Jaw.

PURPOSE: Bisphosphonate (BP) is the first-line therapy for the management of osteoporosis. BP-related osteonecrosis of the jaw (BRONJ) and atypical femoral fracture (AFF) are increasingly common comorbidities in patients with osteoporosis under long-term BP treatment. The aim of this study was to evaluate the incidence and risk factors for AFF features on bone scintigraphy in patients with BRONJ. METHODS: Among total of 373 BRONJ patients treated between September 2005 and July 2014, 237 (220 women, 17 men; median age 73 years) who underwent three-phase bone scintigraphy were enrolled for this retrospective study. AFF features on bone scintigraphy and the related clinical factors were assessed. RESULTS: Among 237 patients with BRONJ, 11 (4.6%) showed AFF features on bone scintigraphy. BP medication duration (p = 0.049) correlated significantly with AFF features on bone scintigraphy in patients with BRONJ. BP intake duration of 34 months was the cutoff value for predicting the presence of AFF features on bone scintigraphy. Among the patients with BRONJ, all those with AFF features on bone scintigraphy were female patients with osteoporosis who were on oral BP medication; however, these factors were not significantly different along with AFF features on bone scintigraphy. CONCLUSION: The incidence of AFF features on bone scintigraphy was relatively high in patients with BRONJ. A careful observation of patients presenting with the AFF features on bone scintigraphy may be needed, particularly for female BRONJ patients with osteoporosis who have been on BP medication for over 34 months.

Prognostic Value of Pretreatment Metabolic PET Parameters in Cervical Cancer Patients With Metabolic Complete Response After Concurrent Chemoradiotherapy.

PURPOSE: Cervical cancer may recur after concurrent chemoradiotherapy (CCRT), even in patients with metabolic complete response (mCR) on post-CCRT F-FDG PET. We retrospectively analyzed the value of metabolic parameters, measured by pretreatment PET, as prognostic factors for predicting recurrence and death in cervical cancer patients with mCR. METHODS: In 61 patients who reached mCR on post-CCRT, metabolic PET parameters including SUVmax, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors, as well as those of the metastatic lymph nodes, were measured by pre-CCRT PET. Total MTV and total TLG were also measured from primary tumors and metastatic lymph nodes. Survival analyses for disease-free survival (DFS) and overall survival (OS) were performed. RESULTS: Eleven patients (18.0%) presented with recurrence of cervical cancer, and 12 (19.7%) died during follow-up. SUVmax, MTV, TLG of metastatic lymph nodes, and total TLG could significantly predict DFS, and nodal SUVmax could predict OS. Para-aortic lymph node metastasis also significantly correlated with both DFS and OS. In multivariate analysis, nodal SUVmax and para-aortic lymph nodes metastasis were prognostic factors for DFS, and the best predictor was nodal SUVmax. For OS, nodal MTV and para-aortic lymph node metastasis were significant prognostic factors in multivariate analysis, and the best predictor was para-aortic lymph node metastasis. CONCLUSIONS: Metabolic PET parameters, SUVmax or MTV values of metastatic lymph nodes, may be surrogate prognostic markers for recurrence or death in patients with locally advanced cervical cancer who reached mCR after definitive CCRT.

Profiling of the Major Phenolic Compounds and Their Biosynthesis Genes in Sophora flavescens Aiton.

Sophorae Radix (Sophora flavescens Aiton) has long been used in traditional medicine in East Asia due to the various biological activities of its secondary metabolites. Endogenous contents of phenolic compounds (phenolic acid, flavonol, and isoflavone) and the main bioactive compounds of Sophorae Radix were analyzed based on the qualitative HPLC analysis and evaluated in different organs and at different developmental stages. In total, 11 compounds were detected, and the composition of the roots and aerial parts (leaves, stems, and flowers) was significantly different. trans-Cinnamic acid and p-coumaric acid were observed only in the aerial parts. Large amounts of rutin and maackiain were detected in the roots. Four phenolic acid compounds (benzoic acid, caffeic acid, ferulic acid, and chlorogenic acid) and four flavonol compounds (kaempferol, catechin hydrate, epicatechin, and rutin) were higher in aerial parts than in roots. To identify putative genes involved in phenolic compounds biosynthesis, a total of 41 transcripts were investigated. Expression patterns of these selected genes, as well as the multiple isoforms for the genes, varied by organ and developmental stage, implying that they are involved in the biosynthesis of various phenolic compounds both spatially and temporally.

Remote quantification of Cochlodinium polykrikoides blooms occurring in the East Sea using geostationary ocean color imager (GOCI).

Accurate and timely quantification of widespread harmful algal bloom (HAB) distribution is crucial to respond to the natural disaster, minimize the damage, and assess the environmental impact of the event. Although various remote sensing-based quantification approaches have been proposed for HAB since the advent of the ocean color satellite sensor, there have been no algorithms that were validated with in-situ quantitative measurements for the red tide occurring in the Korean seas. Furthermore, since the geostationary ocean color imager (GOCI) became available in June 2010, an algorithm that exploits its unprecedented observation frequency (every hour during the daytime) has been highly demanded to better track the changes in spatial distribution of red tide. This study developed a novel red tide quantification algorithm for GOCI that can estimate hourly chlorophyll-a (Chl a) concentration of Cochlodinium (Margalefidinium) polykrikoides, one of the major red tide species around Korean seas. The developed algorithm has been validated using in-situ Chl a measurements collected from a cruise campaign conducted in August 2013, when a massive C. polykrikoides bloom devastated Korean coasts. The proposed algorithm produced a high correlation (R2=0.92) with in-situ Chl a measurements with robust performance also for high Chl a concentration (300mg/m3) in East Sea areas that typically have a relatively low total suspended particle concentration (<0.5mg/m3).

In vivo migration of mesenchymal stem cells to burn injury sites and their therapeutic effects in a living mouse model.

Mesenchymal stem cell (MSC)-based therapy has emerged as a promising therapeutic strategy for tissue regeneration and repair. In this study, we non-invasively monitored the tracking of MSCs toward burn injury sites using MSCs expressing firefly luciferase (Fluc) gene in living mice, and evaluated the effects of the MSCs at the injury site. Murine MSCs co-expressing Fluc and green fluorescent protein (GFP) were established using a retroviral system (referred to as MSC/Fluc). To evaluate the ability of MSC migration toward burn injury sites, cutaneous burn injury was induced in the dorsal skin of mice. MSC/Fluc was intravenously administrated into the mice model and bioluminescence imaging (BLI) was performed to monitor MSC tracking at designated time points. BLI signals of MSC/Fluc appeared in burn injury lesions at 4 days after the cell injection and then gradually decreased. Immunoblotting analysis was conducted to determine the expression of neovascularization-related genes such as TGF-ß1 and VEGF in burnt skin. The levels of TGF-ß1 and VEGF were higher in the MSC/Fluc-treated group than in the burn injury group. Our observations suggested that MSCs might assist burn wound healing and that MSCs expressing Fluc could be a useful tool for optimizing MSC-based therapeutic strategies for burn wound healing.

Function and molecular regulation of DWARF1 as a C-24 reductase in brassinosteroid biosynthesis in Arabidopsis.

DWARF1 (DWF1) is a sterol C-24 reductase that catalyses the conversion of 24-methylenecholesterol (24-MCHR) to campesterol (CR) in Arabidopsis. A loss-of-function mutant, dwf1, showed similar phenotypic abnormalities to brassinosteroid (BR)-deficient mutants. These abnormalities were reversed in the wild-type phenotype by exogenous application of castasterone (CS) and brassinolide (BL), but not dolichosterone (DS). Accumulation of DS and decreased CS were found in quantitative analysis of endogenous BRs in dwf1. The enzyme solution prepared from dwf1 was unable to convert 6-deoxoDS to 6-deoxoCS and DS to CS, as seen in either wild-type or 35S:DWF1 transgenic plants. This suggests that DWF1 has enzyme activity not only for a sterol C-24 reductase, but also for a BR C-24 reductase that catalyses C-24 reduction of 6-deoxoDS to 6-deoxoCS and of DS to CS in Arabidopsis. Overexpression of DWF1 in a BR-deficient mutant (det2 35S:DWF1) clearly rescued abnormalities found in det2, indicating that DWF1 functions in biosynthesis of active BRs in Arabidopsis. Expression of DWF1 is down-regulated by application of CS and BL and in a BR-dominant mutant, bes1-D. E-boxes in the putative promoter region of DWF1 directly bind to a BR transcription factor, BES1, implying that DWF1 expression is feedback-regulated by BR signaling via BES1. Overall, biosynthesis of 24-methylene BR is an alternative route for generating CS, which is mediated and regulated by DWF1 in Arabidopsis.

Primary Aspergillosis of the Sphenoid Sinus Observed on Bone SPECT/CT.

The bone SPECT/CT allows for precise anatomic delineation of bone activity, which can be valuable for diagnosis of nonmalignant bone diseases. We report an extremely rare case of sphenoid sinus aspergillosis, observed on bone SPECT/CT imaging, as an isolated disease in an immunocompetent individual. A 58-year-old woman with a history of plantar fasciitis was assessed for infection in the tarsal bones. Planar bone scan image revealed incidental focal lesion in skull base, which was considered to be the left sphenoid sinusitis by the bone SPECT/CT scan.