Soybean Calmodulin-Binding Transcription Activators, GmCAMTA2 and GmCAMTA8, Coordinate the Circadian Regulation of Developmental Processes and Drought Stress Responses.

The calmodulin-binding transcription activators (CAMTAs) mediate transcriptional regulation of development, growth, and responses to various environmental stresses in plants. To understand the biological roles of soybean CAMTA (GmCAMTA) family members in response to abiotic stresses, we characterized expression patterns of 15 GmCAMTA genes in response to various abiotic stresses. The GmCAMTA genes exhibited distinct circadian regulation expression patterns and were differently expressed in response to salt, drought, and cold stresses. Interestingly, the expression levels of GmCAMTA2, GmCAMTA8, and GmCAMTA12 were higher in stem tissue than in other soybean tissues. To determine the roles of GmCAMTAs in the regulation of developmental processes and stress responses, we isolated GmCAMTA2 and GmCAMTA8 cDNAs from soybean and generated Arabidopsis overexpressing transgenic plants. The GmCAMTA2-OX and GmCAMTA8-OX plants showed hypersensitivity to drought stress. The water in the leaves of GmCAMTA2-OX and GmCAMTA8-OX plants was lost faster than that in wild-type (WT) plants under drought-stress conditions. In addition, stress-responsive genes were down-regulated in the GmCAMTA2-OX and GmCAMTA8-OX plants under drought stress conditions compared to WT plants. Our results suggest that GmCAMTA2 and GmCAMTA8 genes are regulated by circadian rhythms and function as negative regulators in development and drought stress responses.

Microtubule Dynamics Plays a Vital Role in Plant Adaptation and Tolerance to Salt Stress.

Although recent studies suggest that the plant cytoskeleton is associated with plant stress responses, such as salt, cold, and drought, the molecular mechanism underlying microtubule function in plant salt stress response remains unclear. We performed a comparative proteomic analysis between control suspension-cultured cells (A0) and salt-adapted cells (A120) established from Arabidopsis root callus to investigate plant adaptation mechanisms to long-term salt stress. We identified 50 differentially expressed proteins (45 up- and 5 down-regulated proteins) in A120 cells compared with A0 cells. Gene ontology enrichment and protein network analyses indicated that differentially expressed proteins in A120 cells were strongly associated with cell structure-associated clusters, including cytoskeleton and cell wall biogenesis. Gene expression analysis revealed that expressions of cytoskeleton-related genes, such as FBA8, TUB3, TUB4, TUB7, TUB9, and ACT7, and a cell wall biogenesis-related gene, CCoAOMT1, were induced in salt-adapted A120 cells. Moreover, the loss-of-function mutant of Arabidopsis TUB9 gene, tub9, showed a hypersensitive phenotype to salt stress. Consistent overexpression of Arabidopsis TUB9 gene in rice transgenic plants enhanced tolerance to salt stress. Our results suggest that microtubules play crucial roles in plant adaptation and tolerance to salt stress. The modulation of microtubule-related gene expression can be an effective strategy for developing salt-tolerant crops.

High-Temperature Conditions Promote Soybean Flowering through the Transcriptional Reprograming of Flowering Genes in the Photoperiod Pathway.

Global warming has an impact on crop growth and development. Flowering time is particularly sensitive to environmental factors such as day length and temperature. In this study, we investigated the effects of global warming on flowering using an open-top Climatron chamber, which has a higher temperature and CO2 concentration than in the field. Two different soybean cultivars, Williams 82 and IT153414, which exhibited different flowering times, were promoted flowering in the open-top Climatron chamber than in the field. We more specifically examined the expression patterns of soybean flowering genes on the molecular level under high-temperature conditions. The elevated temperature induced the expression of soybean floral activators, GmFT2a and GmFT5a as well as a set of GmCOL genes. In contrast, it suppressed floral repressors, E1 and E2 homologs. Moreover, high-temperature conditions affected the expression of these flowering genes in a day length-independent manner. Taken together, our data suggest that soybean plants properly respond and adapt to changing environments by modulating the expression of a set of flowering genes in the photoperiod pathway for the successful production of seeds and offspring.

Maternal high-fructose intake induces hypertension through activating histone codes on the (pro)renin receptor promoter.

High-fructose intake induces hypertension via the renal expression of (pro)renin receptor (PRR) that stimulates the expression of sodium/hydrogen exchanger 3, Na/K/2Cl cotransporter 2, and genes of the intrarenal renin-angiotensin system. We hypothesize that maternal high-fructose intake induces hypertension in subsequent generation offspring through activating histone codes on the PRR promoter. Mice dams were offered 20% fructose solution during pregnancy and lactation, while the subsequent 1st to 4th generation offspring were raised without fructose. Blood pressure was measured via tail-cuff method. The mRNA and protein expression were determined using quantitative real-time polymerase chain reaction and western blotting, respectively. Histone modification was evaluated using a chromatin immunoprecipitation assay. Maternal high-fructose intake statistically significantly increased blood pressure in the 1st and 2nd generations of offspring compared to the control group. Expression levels of sodium transporters and PRR were increased in the kidneys of the 1st to 3rd generation offspring. Increased enrichment of active histone codes such as H3Ac and H3K4me2 but decreased enrichment of repressive histone codes such as H3K9me3 and H3K27me3 on the PRR promoter were observed in the 1st to 3rd not the 4th generation. Moreover, there was increased the mRNA expression for histone acetyltransferase and methyl transferases for H3K4 in the 1st and 2nd generation offspring compared to the control group. This study implicates that maternal high-fructose intake induces hypertension in multigenerational offspring through activating histone codes on the PRR promoter.

Tracheophytes Contain Conserved Orthologs of a Basic Helix-Loop-Helix Transcription Factor That Modulate ROOT HAIR SPECIFIC Genes.

ROOT HAIR SPECIFIC (RHS) genes, which contain the root hair-specific cis-element (RHE) in their regulatory regions, function in root hair morphogenesis. Here, we demonstrate that an Arabidopsis thaliana basic helix-loop-helix transcription factor, ROOT HAIR DEFECTVE SIX-LIKE4 (RSL4), directly binds to the RHE in vitro and in vivo, upregulates RHS genes, and stimulates root hair formation in Arabidopsis. Orthologs of RSL4 from a eudicot (poplar [Populus trichocarpa]), a monocot (rice [Oryza sativa]), and a lycophyte (Selaginella moellendorffii) each restored root hair growth in the Arabidopsis rsl4 mutant. In addition, the rice and S. moellendorffii RSL4 orthologs bound to the RHE in in vitro and in vivo assays. The RSL4 orthologous genes contain RHEs in their promoter regions, and RSL4 was able to bind to its own RHEs in vivo and amplify its own expression. This process likely provides a positive feedback loop for sustainable root hair growth. When RSL4 and its orthologs were expressed in cells in non-root-hair positions, they induced ectopic root hair growth, indicating that these genes are sufficient to specify root hair formation. Our results suggest that RSL4 mediates root hair formation by regulating RHS genes and that this mechanism is conserved throughout the tracheophyte (vascular plant) lineage.

Micropuncture Access Set Use During Implantation of Totally Implantable Venous Access Device May Reduce Upper Extremity DVT Incidence Among Patients Undergoing Chemotherapy for Colorectal Cancer.

BACKGROUND: The aim of this study was to compare the perioperative outcomes when using a micropuncture access set (MS) to those when using a conventional puncture set (CS) for implantation of totally implantable venous access device (TAVID). METHODS: A total of 314 patients undergoing chemotherapy for colorectal cancer were included between June 2015 and July 2018. Of these, 123 (39.2%) received TAVID implantation using MS and 191 patients (60.8%) received TAVID using CS. Perioperative outcomes and complications were compared between both groups. RESULTS: Baseline characteristics, including body mass index, American Society of Anesthesiologists score, cardiovascular disease, diabetes mellitus, and hyperlipidemia, were not significantly different between the groups. Postoperative complications occurred in 25 patients (8.0%), and the rate and incidence of venous thrombosis were significantly higher in the CS group. There were no significant differences between the groups in other complications such as the rate of port site infection, deep vein thrombosis, obstruction, catheter dislocation, and skin complications (exposure). No incidence of catheter infection, port rotation, intraoperative bleeding, or pneumothorax was observed in this cohort. CONCLUSIONS: MS is a safe and feasible procedure and results in less thrombosis. MS may play an important role in improving outcomes for the implantation of TAVID.

Physiological impact on layer chickens fed corn distiller's dried grains with solubles naturally contaminated with deoxynivalenol.

OBJECTIVE: An experiment was conducted to investigate the response of laying hens fed corn distiller's dried grains with solubles (DDGS) that are naturally contaminated with deoxynivalenol (DON). METHODS: One hundred and sixty 52-week-old Lohmann Brown Lite hens were randomly allotted to five dietary treatments with 8 replicates per treatment. The dietary treatments were formulated to provide a range of corn DDGS contaminated with DON from 0% to 20% (i.e., 5% scale of increment). All laying hens were subjected to the same management practices in a controlled environment. Body weight, feed intake and egg production were measured biweekly for the entire 8-week experiment. The egg quality was measured biweekly for 8 weeks. On weeks 4 and 8, visceral organ weights, blood metabolites, intestinal morphology, and blood cytokine concentrations were measured. RESULTS: The inclusion of corn DDGS contaminated with DON in the diet did not alter (p> 0.05) the body weight, feed intake, hen-day egg production, egg mass and feed efficiency of the laying hens. No difference was found (p>0.05) in the egg quality of hens that were fed the dietary treatments. Furthermore, hens that were fed a diet containing corn DDGS contaminated with DON showed no change (p>0.05) in the visceral organ weights, the blood metabolites, and the cytokine concentrations. The crypt depth increased (p<0.05) as the amount of corn DDGS contaminated with DON increased. Proportionately, the villus height to crypt depth ratio of the laying hens decreased (p<0.05) with the increasing level of corn DDGS contaminated with DON in the diet. CONCLUSION: The inclusion of corn DDGS contaminated with DON up to 20% in layer diets did not cause changes in egg production performance and egg quality, which indicates that DON is less toxic at the concentration of 1.00 mg DON/kg.

Effect of calcium stearoyl-2 lactylate and lipase supplementation on growth performance, gut health, and nutrient digestibility of broiler chickens.

OBJECTIVE: To evaluate calcium stearoyl-2 lactylate (CSL) performance as an exogenous emulsifier together with lipase for broiler diets. METHODS: In total, 252 one-day-old Ross 308 broiler chickens were allocated in a completely randomized design to give 6 replications per treatment with 7 birds in each cage. There were six dietary treatments representing a 2×3 factorial arrangement consisted of two energy levels (standard energy [positive control, PC] and -100 kcal/kg of the requirement level [negative control, NC]) and three dietary treatments (without additives [CON], CON+CSL [CSL], and CON+CSL+lipase [CSL-Lipase]). Corn and soybean meal-based experimental diets containing vegetable oil were formulated. Growth performance, blood parameters, visceral organ weights, ileal morphology, nutrient digestibility, and cytokine gene expression were measured. RESULTS: Birds fed a diet including CSL increased (p<0.05) lipase level in blood compared to birds fed a diet including CSL-Lipase on day 21. Similarly, higher (p<0.05) liver weight was observed in birds fed a diet including either CSL or CSL-Lipase on day 21. Birds fed NC diet with CSL improved (p<0.05) nutrient digestibility compared to the NC diet on day 21. However, birds fed a diet supplemented with CSL or CSL-Lipase did not affect (p>0.05) the weight gain, feed efficiency, ileal morphology, and cytokine concentrations during the experiment period, regardless of dietary energy levels. CONCLUSION: Our results indicated that CSL has a role in improving nutrient digestibility in young birds when supplemented to a corn-soybean meal based broiler diet.

Metabolic Adjustment of Arabidopsis Root Suspension Cells During Adaptation to Salt Stress and Mitotic Stress Memory.

Sessile plants reprogram their metabolic and developmental processes during adaptation to prolonged environmental stresses. To understand the molecular mechanisms underlying adaptation of plant cells to saline stress, we established callus suspension cell cultures from Arabidopsis roots adapted to high salt for an extended period of time. Adapted cells exhibit enhanced salt tolerance compared with control cells. Moreover, acquired salt tolerance is maintained even after the stress is relieved, indicating the existence of a memory of acquired salt tolerance during mitotic cell divisions, known as mitotic stress memory. Metabolite profiling using 1H-nuclear magnetic resonance (NMR) spectroscopy revealed metabolic discrimination between control, salt-adapted and stress-memory cells. Compared with control cells, salt-adapted cells accumulated higher levels of sugars, amino acids and intermediary metabolites in the shikimate pathway, such as coniferin. Moreover, adapted cells acquired thicker cell walls with higher lignin contents, suggesting the importance of adjustments of physical properties during adaptation to elevated saline conditions. When stress-memory cells were reverted to normal growth conditions, the levels of metabolites again readjusted. Whereas most of the metabolic changes reverted to levels intermediate between salt-adapted and control cells, the amounts of sugars, alanine, γ-aminobutyric acid and acetate further increased in stress-memory cells, supporting a view of their roles in mitotic stress memory. Our results provide insights into the metabolic adjustment of plant root cells during adaptation to saline conditions as well as pointing to the function of mitotic memory in acquired salt tolerance.

Chest Trauma Scoring Systems for Predicting Respiratory Complications in Isolated Rib Fracture.

BACKGROUND: We retrospectively compared chest trauma scoring systems in patients with rib fractures without major extrathoracic injury for predicting respiratory complications. We also evaluated the predictive power according to the presence or absence of pulmonary contusion. MATERIALS AND METHODS: Data from 177 patients with isolated rib fractures were included (December 2013 to April 2018). The primary outcome was respiratory complications (pneumonia, respiratory failure, or empyema). The Abbreviated Injury Scale (AIS), Thoracic Trauma Severity Score (TTSS), Chest Trauma Score (CTS), Rib Fracture Score (RFS), and RibScore were evaluated using univariate and receiver operating characteristic (ROC) analyses to determine their predictive value for pulmonary complications. We divided patients into two groups according to the presence or absence of pulmonary contusion, and constructed ROC curves for both groups. RESULTS: Twenty-eight patients (15.8%) had ≥1 respiratory complication, with significantly higher numbers of standard, segmental, and displaced rib fractures as well as significantly higher TTSS, CTS, RFS, and AIS scores. In all patients, the TTSS (0.723, 95% confidence interval [CI] 0.651-0.788) showed the highest area under the ROC curve (AUROC), followed by the CTS, RFS, AIS, and RibScore. In patients with pulmonary contusion, TTSS also showed the highest AUROC (0.704, 95% CI 0.613-0.784). In patients without pulmonary contusion, RFS showed the highest AUROC (0.759, 95% CI 0.630-0.861). CONCLUSIONS: TTSS was the most useful system for predicting respiratory complications in isolated rib fracture patients with pulmonary contusion. By contrast, RFS was the most useful in patients without pulmonary contusion.

Concise approach for screening long non-coding RNAs functionally linked to human breast cancer associated genes.

Cancer research studies using next-generation sequencing have revealed a number of genes of which aberrant expression is associated with various cancers. Recently, long non-coding RNA (lncRNA) has been highlighted due to its tissue-specific expression and cell cancerization functions, such as the regulation of key tumor suppressors. In this study, we suggest a very efficient approach to survey lncRNAs putatively associated with breast cancer. We targeted lncRNAs linked with breast cancer associated genes (BCAGs) and analyzed their expression pattern in human breast cancer cell lines. A total of 337 BCAGs were retrieved from literature review and the existence of 121 lncRNAs were identified from the 15 kb up- and downstream regions of the list of genes. Twenty lncRNAs' expression were detectable in human breast cancer cell lines with different expression patterns. Interestingly, the expression of three lncRNAs, two up-regulated (RAD51C v.4, LOC105371849) and one down-regulated (LOC102724064), were closely correlated with adjacent BCAGs (RAD51C, HEATR6 and BRMS1) in breast cancer cell lines. We thus demonstrated association between the lncRNA and its adjacent BCAG using LOC105371849-HEATR6, of which the function and regulation in breast cancer are still unknown. Knockdown of LOC105371849 by siRNA decreased the expression of HEATR6 mRNA in the MCF7 human breast cancer cell line. In conclusion, this study provides a better understanding about the biological roles of lncRNAs in breast cancer and may be useful in the investigation of proper targets for diagnostic and/or therapeutic breast cancer markers using public databases.

Upregulation of C/EBPß and TSC2 by an HDAC inhibitor CG200745 protects heart from DOCA-induced hypertrophy.

Histone deacetylases (HDACs) are a vast family divided into four major classes: class I (1, 2, 3, and 8), class II (4, 5, 6, 7, 9 and 10), class III (sirtuin family) and class IV (HDAC11). HDAC inhibition attenuates cardiac hypertrophy through suppression of the mechanistic target of rapamycin complex1 (mTORC1) signaling. HDAC inhibitors upregulate the expression of tuberous sclerosis complex 2 (TSC2), an mTORC1 inhibitor. However, the molecular mechanism underlying HDAC inhibitor-mediated upregulation of TSC2 is unclear. We hypothesized that an HDAC inhibitor, CG200745 (CG), ameliorates cardiac hypertrophy through the inhibition of mTORC1 signaling by upregulating of the CCAAT/enhancer-binding protein-ß (C/EBP-ß)/TSC2 pathway. To establish a cardiac hypertrophy model, deoxycorticosterone acetate (DOCA, 40 mg/kg/wk) was subcutaneously injected for 4 weeks into Sprague-Dawley rats. All rats were unilaterally nephrectomized and had free access to drinking water containing 1% NaCl with or without CG of different concentrations. The expression level of TSC2 and C/EBP-ß was measured by quantitative real-time PCR (qRT-PCR) and western blot analysis. Acetylation of C/EBP-ß was analyzed by immunoprecipitation. The recruitment of C/EBP-ß and polymerase II (Pol II) on TSC2 promoter region was analyzed by chromatin immunoprecipitation (ChIP). CG treatment increased the expression of TSC2. In addition, CG treated rats showed an increased in the expression and acetylation of C/EBP-ß, owing to the increase in the recruitment of C/EBP-ß and Pol II at Tsc2 gene promoter. Thus, CG ameliorates cardiac hypertrophy through the inhibition of mTORC1 signaling via upregulation of the C/EBP-ß/TSC2 pathway in DOCA-induced hypertensive rats.

Histone deacetylase inhibition ameliorates hypertension and hyperglycemia in a model of Cushing's syndrome.

Cushing's syndrome (CS) caused by hypercortisolism is occasionally accompanied by metabolic disorders such as hypertension, diabetes mellitus (DM), dyslipidemia, and central obesity. Thus morbidity and mortality, observed in cardiovascular disease, are elevated in patients with CS. We hypothesized that HDAC inhibition (HDACi) decreased transcriptional activity of glucocorticoid receptor (GR), which ameliorates hypertension and hyperglycemia in patients with CS. To establish an animal model of hypercortisolism, Sprague-Dawley rats were infused with adrenocorticotropic hormone (ACTH, 40 ng/day) or dexamethasone (Dex, 10 µg/day) via osmotic minipumps for 4 wk. Expression of GR target genes was determined by quantitative real-time PCR (qRT-PCR). GR enrichment on specific loci, and across the whole genome, was analyzed by chromatin immunoprecipitation (ChIP) and ChIPseq, respectively. HDACi decreased blood pressure and expression of ion regulators in the kidneys of ACTH-infused rats. Additionally, HDACi reduced deposition of polysaccharide, fasting blood glucose level, glucose intolerance, and expression of gluconeogenesis genes in the livers and kidneys of ACTH- and Dex-infused rats. Among class I HDACs, HDAC1 and HDAC3 interacted with GR. HDAC1 knockdown resulted in increased level of acetylation and decreased transcriptional activity of GR. GR recruitment on the promoters of 2,754 genes, which include ion transporters, channels, and gluconeogenic genes, was significantly decreased by MS-275, a class I HDAC inhibitor. These results indicate that HDACi ameliorates hypertension and hyperglycemia in a model of CS by decreasing the transcriptional activity of GR via elevating its level of acetylation.

Repression of Transcriptional Activity of Forkhead Box O1 by Histone Deacetylase Inhibitors Ameliorates Hyperglycemia in Type 2 Diabetic Rats.

Type 2 diabetes mellitus (T2DM) is a chronic disease manifested by hyperglycemia. It is essential to effectively control hyperglycemia to prevent complications of T2DM. Here, we hypothesize that repression of transcriptional activity of forkhead box O1 (FoxO1) via histone deacetylase inhibitors (HDACi) ameliorates hyperglycemia in T2DM rats. METHODS: Male Long-Evans Tokushima Otsuka (LETO) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats aged 14 weeks were administered sodium valproate (VPA, 0.71% w/v) dissolved in water for 20 weeks. Electrophoretic mobility shift assay (EMSA) and luciferase assay were performed for elucidation of transcriptional regulation through acetylation of FoxO1 by HDACi. RESULTS: VPA attenuated blood glucose levels in accordance with a decrease in the expression of gluconeogenic genes in hyperglycemic OLETF rats. It has been shown that HDAC class I-specific and HDAC class IIa-specific inhibitors, as well as pan-HDAC inhibitors decrease FoxO1 enrichment at the cis-element of target gene promoters. Mutations in FoxO1 prevent its acetylation, thereby increasing its transcriptional activity. HDAC3 and HDAC4 interact with FoxO1, and knockdown of HDAC3, HDAC4, or their combination increases FoxO1 acetylation, thereby decreasing the expression of gluconeogenic genes. CONCLUSIONS: These results indicate that HDACi attenuates the transcriptional activity of FoxO1 by impeding deacetylation, thereby ameliorating hyperglycemia in T2DM rats.

Histone deacetylase inhibition attenuates hepatic steatosis in rats with experimental Cushing's syndrome.

Cushing's syndrome (CS) is a collection of symptoms caused by prolonged exposure to excess cortisol. Chronically elevated glucocorticoid (GC) levels contribute to hepatic steatosis. We hypothesized that histone deacetylase inhibitors (HDACi) could attenuate hepatic steatosis through glucocorticoid receptor (GR) acetylation in experimental CS. To induce CS, we administered adrenocorticotropic hormone (ACTH; 40 ng/kg/day) to Sprague-Dawley rats by subcutaneous infusion with osmotic mini-pumps. We administered the HDACi, sodium valproate (VPA; 0.71% w/v), in the drinking water. Treatment with the HDACi decreased steatosis and the expression of lipogenic genes in the livers of CS rats. The enrichment of GR at the promoters of the lipogenic genes, such as acetyl-CoA carboxylase (Acc), fatty acid synthase (Fasn), and sterol regulatory element binding protein 1c (Srebp1c), was markedly decreased by VPA. Pan-HDACi and an HDAC class I-specific inhibitor, but not an HDAC class II a-specific inhibitor, attenuated dexamethasone (DEX)-induced lipogenesis in HepG2 cells. The transcriptional activity of Fasn was decreased by pretreatment with VPA. In addition, pretreatment with VPA decreased DEX-induced binding of GR to the glucocorticoid response element (GRE). Treatment with VPA increased the acetylation of GR in ACTH-infused rats and DEX-induced HepG2 cells. Taken together, these results indicate that HDAC inhibition attenuates hepatic steatosis hrough GR acetylation in experimental CS.

Inducible HGF-secreting Human Umbilical Cord Blood-derived MSCs Produced via TALEN-mediated Genome Editing Promoted Angiogenesis.

Mesenchymal stem cells (MSCs) promote therapeutic angiogenesis to cure serious vascular disorders. However, their survival period and cytokine-secretory capacity are limited. Although hepatocyte growth factor (HGF) can accelerate the rate of angiogenesis, recombinant HGF is limited because of its very short half-life (<3-5 minutes). Thus, continuous treatment with HGF is required to obtain an effective therapeutic response. To overcome these limitations, we produced genome-edited MSCs that secreted HGF upon drug-specific induction. The inducible HGF expression cassette was integrated into a safe harbor site in an MSC chromosome using the TALEN system, resulting in the production of TetOn-HGF/human umbilical cord blood-derived (hUCB)-MSCs. Functional assessment of the TetOn-HGF/hUCB-MSCs showed that they had enhanced mobility upon the induction of HGF expression. Moreover, long-term exposure by doxycycline (Dox)-treated TetOn-HGF/hUCB-MSCs enhanced the anti-apoptotic responses of genome-edited MSCs subjected to oxidative stress and improved the tube-formation ability. Furthermore, TetOn-HGF/hUCB-MSCs encapsulated by arginine-glycine-aspartic acid (RGD)-alginate microgel induced to express HGF improved in vivo angiogenesis in a mouse hindlimb ischemia model. This study showed that the inducible HGF-expressing hUCB-MSCs are competent to continuously express and secrete HGF in a controlled manner. Thus, the MSCs that express HGF in an inducible manner are a useful therapeutic modality for the treatment of vascular diseases requiring angiogenesis.

Highly Sensitive and Stretchable Multidimensional Strain Sensor with Prestrained Anisotropic Metal Nanowire Percolation Networks.

To overcome the limitation of the conventional single axis-strain sensor, we demonstrate a multidimensional strain sensor composed of two layers of prestrained silver nanowire percolation network with decoupled and polarized electrical response in principal and perpendicular directional strain. The information on strain vector is successfully measured up to 35% maximum strain with large gauge factor (>20). The potential of the proposed sensor as a versatile wearable device has been further confirmed.

Histone deacetylase inhibition attenuates transcriptional activity of mineralocorticoid receptor through its acetylation and prevents development of hypertension.

RATIONALE: Inhibition of histone deacetylases (HDACs) results in attenuated development of hypertension in deoxycorticosterone acetate-induced hypertensive rats and spontaneously hypertensive rats. However, the molecular mechanism remains elusive. OBJECTIVE: We hypothesized that HDAC inhibition attenuates transcriptional activity of mineralocorticoid receptor (MR) through its acetylation and prevents development of hypertension in deoxycorticosterone acetate-induced hypertensive rats. METHODS AND RESULTS: Expression of MR target genes was measured by quantitative real-time polymerase chain reaction. Recruitment of MR and RNA polymerase II on promoters of target genes was analyzed by chromatin immunoprecipitation assay. Live cell imaging was performed for visualization of nuclear translocation of MR. MR acetylation was determined by Western blot with anti-acetyl-lysine antibody after immunoprecipitation with anti-MR antibody. Transcriptional activity of MR was determined by luciferase assay. For establishment of a hyperaldosteronism animal, Sprague-Dawley rats underwent uninephrectomy and received subcutaneous injection of 40 mg/kg per week of deoxycorticosterone acetate and drinking water containing 1% NaCl. Treatment with a HDAC class I inhibitor resulted in reduced expression of MR target genes in accordance with reduced recruitment of MR and RNA polymerase II on promoters of target genes. HDAC inhibition promoted MR acetylation, leading to decreased transcriptional activity of MR. Knockdown or inhibition of HDAC3 resulted in reduced expression of MR target genes induced by mineralocorticoids. CONCLUSIONS: These results indicate that HDAC inhibition attenuates transcriptional activity of MR through its acetylation and prevents development of hypertension in deoxycorticosterone acetate-induced hypertensive rats.

The historical Coffin-Lowry syndrome family revisited: identification of two novel mutations of RPS6KA3 in three male patients.

Coffin-Lowry syndrome (CLS) is a rare X-linked dominant disorder characterized by intellectual disability, craniofacial abnormalities, short stature, tapering fingers, hypotonia, and skeletal malformations. CLS is caused by mutations in the Ribosomal Protein S6 Kinase, 90 kDa, Polypeptide 3 (RPS6KA3) gene located at Xp22.12, which encodes Ribosomal S6 Kinase 2 (RSK2). Here we analyzed RPS6KA3 in three unrelated CLS patients including one from the historical Coffin-Lowry syndrome family and found two novel mutations. To date, over 140 mutations in RPS6KA3 have been reported. However, the etiology of the very first familial case, which was described in 1971 by Lowry with detailed phenotype and coined the term CLS, has remained unknown. More than 40 years after the report, we succeeded in identifying deposited fibroblast cells from one patient of this historic family and found a novel heterozygous 216 bp in-frame deletion, encompassing exons 15 and 16 of RPS6KA3. Drop episodes in CLS patients were reported to be associated with truncating mutations deleting the C-terminal kinase domain (KD), and only one missense mutation and one single basepair duplication involving the C-terminal KD of RSK2 in the patients with drop episode have been reported thus far. Here we report the first in-frame deletion in C-terminal KD of RPS6KA3 in a CLS patient with drop episodes.

Application of rapid milling technology for fabrication of SiC nanoparticles.

SiC nanoparticles were successfully fabricated by a high energy ball milling method, so that can be used in the printed electronics to make SiC thin film patterns. Here we utilized the waste of Si sludge for making the SiC nanoparticles. In order to achieve uniform thin film from the nanoparticle ink, fine sized SiC nanoparticles less than 100 nm has to be uniformly dispersed. In this study, we employed the ultra apex milling (UAM) system for particle comminution and dispersion. We investigated the effects of milling parameters, e.g., size of ZrO2 bead and milling time. The size of the SiC particles reached about 103 nm after 4 hours of UAM, when the ZrO2 beads of 50 microm were used. Then SiC ink was formulated with organic solvents and a dispersing agent. A specially designed pattern was printed by an ink-jet printer for evaluating the feasibility of the SiC nanoparticle inks.