9% for ICH (95% confidence interval, CI = 94 5-97 0%) and 96 1% f

9% for ICH (95% confidence interval, CI = 94.5-97.0%) and 96.1% for SAH (95% CI = 94.8-97.0%). The coding errors observed were largely expected, with different types of stroke miscoded as ICH and SAH.\n\nConclusions: https://www.selleckchem.com/products/iwr-1-endo.html The accuracy of ICD-10 hospital discharge coding for hemorrhagic stroke was excellent. However further research is needed to find ways to further improve its accuracy.”
“Complex airway diseases represent a therapeutic challenge and require multidisciplinary input. Surgery remains the definitive modality. Minimally invasive endobron, chial techniques have resulted in symptom control and long-term

improvements. The rigid bronchoscope remains the method of choice for the treatment of both benign and malignant central airway obstruction. However, it has limited use if lesions are located in the upper lobes or lung periphery, but significant technological advances allow for effective treatments using the flexible bronchoscope. Rigid and flexible

bronchoscopes should be seen as complementary procedures and most cases require the use of both modalities.”
“High soil temperatures achieved with solarization practice used in greenhouses may prevent diseases infested from soils with soil pathogens. Physical manipulations like tillage, increasing soil water content and addition of organic residues to soil increase effectiveness of solarization by way of facilitating downward heat flux and increasing temperature in subsoil. A two-year KU-57788 research buy work assessing importance of soil tillage, soil wetting and CO2 enriched air (for simulating organic residue addition to soil) on solarization Quizartinib inhibitor was carried out in glass and plastic greenhouses (1 glass and 2 of plastic) with clay and sandy soils in Eastern Mediterranean region of Turkey. Four treatments were tested: (1) with tillage (T), (2) no tillage (NT), (3) with tillage and CO2 addition

(TCO2) and (4) no tillage and no CO2 addition (NTCO2). The CO2 enrichment of air under plastic mulch covering soil during the solarization was done using dry ice (i.e. CO2). The levels of the highest temperatures attained under different treatments during solarization period were assessed and recorded. The results showed that the highest temperature was recorded throughout the complete solarization period under the treatment with soil tillage and CO2 addition (TCO2) over all soil depths (5, 20 and 35 cm). The mean highest temperatures recorded for 30 days of solarization period did not exhibit any consistent trend in clay soils (Greenhouse 1 and 2) whereas the ranking of the treatments TCO2>T>NT>NTCO2 was maintained in sandy soil (Greenhouse 3). The highest temperature attained in Greenhouses 1 and 2, with soils of clay texture, and 3 with soil of sandy texture, at soil depths of 5, 20 and 35 cm were 55.4, 45.3 and 41.4 degrees C; 56.8, 46.6 and 42.7 degrees C; 56.6, 48.4 and 44.

However, youth with ADHD showed

However, youth with ADHD showed find more greater activation in the left dorsolateral prefrontal cortex (DLPFC) and left posterior cingulate cortex (PCC), greater functional

connectivity between the left DLPFC and left intraparietal sulcus, and reduced left DLPFC connectivity with left midcingulate cortex and PCC for the high load contrast compared to controls (p smaller than .01; k bigger than 100 voxels). Reanalysis using a more conservative statistical approach (p smaller than .001; k bigger than 100 voxels) yielded group differences in PCC activation and DLPFC-midcingulate connectivity. Conclusion: Youth with ADHD show decreased efficiency of DLPFC for high-load visuospatial working memory and greater reliance on posterior spatial attention circuits to store and update spatial 432 position than healthy control youth. Findings should be replicated in larger samples.”
“About 2000 tons of chrysotile is used annually to produce friction materials in Islamic MEK inhibitor Republic

of Iran. Approximately, 3000 workers are exposed to the asbestos fibers in the different processes of brake and clutch manufacturing. In the current study, asbestos fiber concentrations during brake and clutch manufacture were measured. This study also evaluated the fiber size and morphology distribution according to the Asbestos International Association (AIA) for standardization analytical method for asbestos.\n\nThe airborne asbestos fiber concentrations selleck chemical and its chemical composition of 92 personal samples were analyzed by phase contrast microscopy (PCM)

and scanning electron microscope (SEM) equipped with an energy-dispersive X-ray analyzer (EDX).\n\nPersonal monitoring of fiber levels demonstrated counts that ranged from 0.31 to 1.3 PCM f/ml ( 15.5-51.5 SEM f/ml). Geometric means of the asbestos concentrations were 1.3 PCM f/ml (51.5 SEM f/ml) and 0.86 PCM f/ml (42.1 SEM f/ml) according to the brake weighting and mixing and clutch mixing process, respectively. The geometrical mean concentrations were 0.63 PCM f/ml (31 SEM f/ml), which is considerably higher than threshold limit value (TLV) of the American Conference of Governmental Industrial Hygienists (ACGIH) which is 0.1 f/ml. The SEM data demonstrate that the fibrous particles consisted, approximately, of chrysotile (50%), tremolite (30%), and actinolite (20%).\n\nBased on these findings, the 50% of airborne fibers inhaled by the workers were amphiboles asbestos with fibers equal and greater than 5 mu m in length and 0.2 mu m in diameter, and thus not included in the PCM-based fiber counts. Therefore, it might be expected that workers who worked in the brake and clutch manufacture will suffer from negative health effects of exposing to the amphibole asbestos fibers. (C) 2009 Elsevier Inc. All rights reserved.

The secreted products interact with

hepatocytes and vario

The secreted products interact with

hepatocytes and various immune cells in the liver. Altered liver metabolism and determinants of insulin resistance associated with visceral adipose tissue distribution are discussed, its well as, determinants of an insulin-resistant AZD0530 clinical trial state promoted by the increased free fatty acids and cytokines delivered by visceral adipose tissue to the liver. (C) 2008 Elsevier Masson SAS. All rights reserved.”
“Coffea canephora Pierre ex Frohener is a perennial plant originated from Africa. Two main groups, Guinean and Congolese, have already been identified within this species. They correspond to main refugia in western and central Africa. In this paper we present the analysis of a region that has not yet been studied, Uganda. Two wild, one feral (once cultivated but abandoned for many years), and two cultivated populations of C. canephora from Uganda were evaluated using 24 microsatellite markers. Basic diversity, this website dissimilarity and genetic distances between individuals, genetic differentiation

between populations, and structure within populations were analysed. Expected heterozygosity was high for wild compartments (0.48 to 0.54) and for cultivated and feral ones (0.57 to 0.59), with the number of private alleles ranging from 12 for cultivated genotypes to 37 for a wild compartment. The Ugandan samples show significant population structuring. We compared the Ugandan populations with a representative sample of known genetic diversity groups within the species using 18 markers. Coffea canephora of Ugandan

origin was found to be 123 genetically different from previously identified diversity groups, implying that it forms another diversity group within the species. Given its large distribution and extremely recent domestication, C. canephora can be used to understand the effect of refugia colonization on genetic diversity.”
“Background: Elderly patients with ST-elevation myocardial infarction (STEMI) are often underrepresented in major percutaneous coronary intervention (PCI) trials. selleck Use of PCI for STEMI, and associated outcomes in patients aged >= 65 years with STEMI needed further investigation.\n\nMethods: We used the 2001-2010 United States Nationwide Inpatient Sample (NIS) database to examine the temporal trends in STEMI, use of PCI for STEMI, and outcomes among patients aged 65-79 and >= 80 years.\n\nResults: During 2001-2010, of 4,017,367 patients aged >= 65 years with acute myocardial infarction (AMI), 1,434,579 (35.7%) had STEMI. Over this period, among patients aged 65-79 and >= 80 years, STEMI decreased by 16.4% and 19%, whereas the use of PCI for STEMI increased by 33.5% and 22%, respectively (Ptrend 0.001). There was a significant decrease in age-adjusted in-hospital mortality (per 1000) in patients aged >= 80 years (150 versus 116, P-trend – 0.02) but not in patients aged 65-79 years (63 versus 59, P-trend – 0.886).

Moreover, PMA-induced IL-1 beta production was significantly redu

Moreover, PMA-induced IL-1 beta production was significantly reduced

in the presence of TLR2, selleck chemicals llc TLR4, and CD11b Abs. Rottlerin, a PKC delta-specific inhibitor, significantly reduced PMA-induced IL-1 beta production as well as CD11b, TLR2 expression, and IRAK1-JNK activation. In PKC delta wild-type overexpressing THP1 cells, IRAK1 kinase activity and IL-1 beta production were significantly augmented, whereas recombinant inactive PKCd and PKCd small interfering RNA significantly inhibited basal and PMA-induced IRAK1 activation and IL-1 beta production. Endogenous PKC delta-IRAK1 interaction was observed in quiescent cells, and this interaction was regulated by PMA. IRAK1/4 inhibitors, their small interfering RNAs, and JNK inhibitor also attenuated PMA-induced find more IL-1 beta production. NF-kappa B activation inhibitor and SN50 peptide inhibitor, however, failed to affect PMA-induced IL-1 beta production. A similar role of IRAK1 in IL-1 beta production and its regulation by PKC delta was evident in the primary human monocytes, thus signifying the importance of our finding. To our knowledge, the results obtained demonstrate for the first time that IRAK1 and PKCd functionally interact to regulate IL-1 beta production in monocytic cells. A novel mechanism of IL-1 beta production that involves TLR2, CD11b,

and the PKC delta/IRAK1/JNK/AP-1 axis is thus being proposed. The Journal of Immunology, 2011, 187: 2632-2645.”
“Adjacent segment degeneration (ASD) is considered as a long-term complication of spinal fusion procedure. 4 Numerous clinical studies have reported some factors related GSI-IX with ASD, but few could address the reason why the incidence of caudal ASD is significantly lower than that of cranial ASD. Because the pedicle of vertebral arch is closer to the superior endplate of vertebrea and its cranial intervertebral disc, there might be some possibilities of malpositions of pedicle probe or screws

into the superior vertebral endplate or disc during the procedure of posterior intervertebral fusion. A number of evidences have showed that puncture of intervertebral disc will result in disc degeneration. Thus the authors put forward the hypothesis that intraoperative malposition of pedicle probe or screws might be a cause of ASD at cranial segments. (C) 2011 Elsevier Ltd. All rights reserved.”
“Purpose: In this study, we examined the clinical application of two training methods for optimizing reading ability in patients with juvenile macular dystrophy with established eccentric preferred retinal locus and optimal use of low-vision aids.\n\nMethod: This randomized study included 36 patients with juvenile macular dystrophy (35 with Stargardt’s disease and one with Best’s disease). All patients have been using individually optimized low-vision aids.

We compared the regulation of human FUT4 gene transcription in hu

We compared the regulation of human FUT4 gene transcription in human breast cancer cells (MCF-7 and MDA-MB-231) using promoter/luciferase analyses. Using a series of promoter deletion constructs, we identified a potential regulatory site located between 0.8 and 1.6kb of the FUT4 promoter. As shown by EMSA and ChIP analyses, heat-shock factor 1 (HSF1) and Sp1are required for FUT4 promoter activity. In addition, we explored the role of HSF1 and Sp1 on cell proliferation, and found that the ERK1/2 MAPK

and PI3K/Akt signaling pathways regulate the expression of FUT4, which play a role in cell proliferation via HSF1 and Sp1. These results suggest CA4P that FUT4 is a target gene for HSF1 and Sp1 that is required for cell cycle progression in breast cancer epithelial cells. J. Cell. Biochem. 115: 168-178, 2014. (c) 2013 Wiley Periodicals, Inc.”
“Runoff generation at the hillslope scale is an important component of the hydrological cycle. Recent work has shown that a common hillslope runoff response mechanism is driven by connectivity of saturated patches in the subsurface (via filling and spilling) to a threshold initiation of lateral flow at the hillslope base. Here, we show that directed percolation theory is able to represent this key runoff process including the details of dynamical flowpath development and filling and spilling processes at the 432 soil-bedrock

interface. We then use the directed percolation model to investigate how changes in slope angle, soil depth, and subsurface microtopography influence stormflow response. We map TPCA-1 the evolving subsurface flow network under different hillslope classes and compare DZNeP mouse them to the natural system response. Our results suggest that the natural system sheds water more efficiently than randomly generated systems providing some insights into key hydrogeomorphic controls on water shedding in the environment.

(C) 2014 Elsevier B.V. All rights reserved.”
“Synthetic biology has developed numerous parts for building synthetic gene circuits. However, few parts have been described for prokaryotes to integrate two signals at a promoter in an AND fashion, i.e. the promoter is only activated in the presence of both signals. Here we present a new part for this function: a split intein T7 RNA polymerase. We divide T7 RNA polymerase into two expression domains and fuse each to a split intein. Only when both domains are expressed does the split intein mediate protein trans-splicing, yielding a full-length T7 RNA polymerase that can transcribe genes via a T7 promoter. We demonstrate an AND gate with the new part: the signal-to-background ratio is very high, resulting in an almost digital signal. This has utility for more complex circuits and so we construct a band-pass filter in Escherichia coli. The split intein approach should be widely applicable for engineering artificial gene circuit parts.

Methods: Relevant studies were identified through PubMed and Web

Methods: Relevant studies were identified through PubMed and Web of Knowledge databases, studies included were those published up until to May 2012. Study quality was assessed according to the HuGENET guidelines and Strengthening the Reporting of Genetic Association (STREGA) recommendations. Results: Random-effects meta-analysis provided evidence that carriers of DPYD IVS14+1G>A are at higher risk of 3 degrees of overall grade

toxicity, hematological toxicity, mucositis and diarrhea. In addition, a strong association was also found between carriers of the DPYD 2846T allele and overall grade 3 toxicity or grade 3 diarrhea. An inverse linear relationship find more was found in prospective studies between the odds ratio of DPYD IVS14+1G>A and the incidence of overall grade 3 toxicity, indicating an higher impact in cohorts in which the incidence of severe toxicity was lower. Conclusion: The results of this meta-analysis confirm clinical validity of DPYD IVS14+1G>A and 2846A>T as risk factors for the development of severe toxicities following fluoropyrimidine treatment. Furthermore, the sensitivity and specificity estimates obtained could be useful in establishing the cost-effectiveness of testing for

DPYD variants. Original submitted 4 March 2013; Revision submitted 17 June 2013″
“3-Nitropropionic acid (NPA) produces degeneration of striatum and some neurological disturbances MLN2238 inhibitor characteristic ALK inhibitor of Huntington’s disease in rodents and primates. We have shown that the flavonoid kaempferol largely reduced striatal damage induced by cerebral ischaemia-reperfusion in rats (Lopez-Sanchez et al. 2007). In this work, we report that intraperitoneal (i.p.) administration of kaempferol affords an efficient

protection against NPA-induced neurodegeneration in Wistar rats. We studied the effects of daily i.p. injections of 7, 14 and 21 mg of kaempferol/kg body weight during the NPA-treatment (25 mg/kg body weight/12 h i.p., for 5 days) on the neurological deficits, degeneration of rat striatum and oxidative stress markers. Intraperitoneal injections of 14-21 mg of kaempferol/kg body weight largely attenuated motor deficit and delayed mortality. The higher dose of kaempferol prevented the appearance of NPA-induced striatal lesions up to the end of treatment, as revealed by haematoxylin-eosin and TUNEL staining, and also NPA-induced oxidative stress, because it blocked the fall of reduced glutathione and the increase of protein nitrotyrosines in NPA-treated rats. It was found that striatal degeneration was associated with calpains activation and a large inactivation of creatine kinase, which were also prevented when the higher doses of kaempferol were administered.

Esta falta de preparacion es de preocupacion particular dado el r

Esta falta de preparacion es de preocupacion particular dado el rapido incremento de colecciones vivientes en el mundo desde 1950, particularmente en America del Sur y Asia, y resaltar los patrones anteriores de introduccion sera un metodo pobre para determinar riesgos futuros see more de invasion. Resumen”
“One of the visions of synthetic biology is to be able to program cells using a language that is similar to that used to program computers or robotics. For large genetic programs, keeping track of the DNA on the level of nucleotides becomes tedious and error prone, requiring a new generation of computer-aided design (CAD) software. To push the size of

projects, it is important to abstract the designer from the process of part selection and optimization. The vision is to specify genetic programs Z-DEVD-FMK solubility dmso in a higher-level language, which a genetic compiler could automatically convert into a DNA sequence. Steps towards this goal include: defining the semantics of the higher-level language, algorithms to select and assemble

parts, and biophysical methods to link DNA sequence to function. These will be coupled to graphic design interfaces and simulation packages to aid in the prediction of program dynamics, optimize genes, and scan projects for errors.”
“Purpose: Recent analyses provided evidence that human adult cerebrospinal fluid (CSF) in addition to soluble proteins also contains membrane particles that moreover carry the somatic stem cell marker CD133. The significance of CD133 as a potential marker of cellular proliferation, including neurogenesis, remains unresolved. As adult neurogenesis has been implicated to be induced by epileptic seizures this study investigated whether patients with partial epilepsy

show a varying amount of membrane-associated CD133 in CSF as compared to healthy Selleck AZD6738 adults.\n\nMethods: CSF samples of 34 partial epilepsy patients were analyzed and compared to 61 healthy controls. Following sequential centrifugation up to 200,000 g quantitative immunoblotting was performed using a mouse monoclonal antibody. Antigen-antibody complexes were detected using enhanced chemiluminescence, and visualized and quantified digitally.\n\nResults: The overall amount of membrane particle-associated CD133 was significantly increased in epilepsy patients compared to healthy controls (9.6 +/- 2.9 ng of bound CD133 antibody versus 7.4 +/- 3.8 ng; p < 0.01). There were no differences according to etiology of epilepsy (cryptogenic, neoplasia, dysplasia, ammon’s horn sclerosis, and others). Dichotomization of the patients according to temporal versus extratemporal foci revealed a significant increase of membrane particle-associated CD133 in patients with temporal lobe epilepsy (10.88 +/- 1 3.3 ng of bound CD133 antibody versus 8.35 +/- 3.48 ng; p<0.05).

Additional groups received vehicle pretreatment, switching to C8-

Additional groups received vehicle pretreatment, switching to C8-Xanthate 1, 2, 3, or 4 days after chlorpyrifos and then continuing with daily C8-Xanthate treatment until 7 days post-chlorpyrifos

treatment. Neurotoxicity was assessed at baseline (before chlorpyrifos) and then daily after chlorpyrifos, using behavioral assessments (e.g., gait score). Neurochemical assays (e.g., serum and brain chlorpyrifos) were performed at the end of study. Pretreatment with C8-Xanthate completely prevented chlorpyrifos toxicity, and delayed introduction of C8-Xanthate reduced toxicity, even when started up to 4 days after chlorpyrifos treatment. Discontinuation of C8-Xanthate treatment 7 days post-chlorpyrifos treatment did not result in the reappearance Liproxstatin-1 purchase of toxicity, tested through 10 days after chlorpyrifos treatment. These findings suggest that CYP2B selleck inhibitor inhibitor treatment, even days after chlorpyrifos exposure, and using a peripheral delivery route, may be useful as a therapeutic approach to reduce chlorpyrifos toxicity.”
“Thalassemia is a congenital hemolytic disease caused by defective globin synthesis resulting in decreased quantity of globin chains. Although the Life expectancy

of beta-thalassemia 4 patients has markedly improved over the last few years, patients still suffer from many complications of this congenital disease. The presence of a high incidence of thromboembolic events, mainly in beta-thalassemia intermedia, has led to the identification of a hypercoagulable state in these patients. In this paper, we review the molecular and cellular mechanisms leading to hypercoagulability in beta-thalassemia, with a special focus on thalassemia intermedia being the group with the highest incidence of thrombotic events as compared to other types of thalassemias. We also discuss the recommendations for thrombosis prophylaxis in these patients. (c)

2008 Elsevier Ltd. All rights reserved.”
“Oncolytic adenoviruses based on serotype 5 (Ad5) have several shortcomings, Bcl-2 phosphorylation including the downregulation of its receptor in cancer cells, high prevalence of neutralizing antibodies and hepatotoxicity. Another adenoviral serotype, Ad11, could overcome these obstacles. Here, we show that human cancer cell lines express higher levels of the Ad11 receptor CD46, resulting in much better infectivity than Ad5. Surprisingly, only 36% (9/25) of the cell lines were more sensitive to Ad11- than to Ad5-mediated cytotoxicity. Investigations revealed that it was the transcription of Ad11 E1A, not CD46 expression or virus infectivity, which determined the cell’s sensitivity to Ad11 killing.

Additionally, ex vivo studies of human brain slices from an indep

Additionally, ex vivo studies of human brain slices from an independent sample of patients who had AD were performed.\n\nSetting: Three university medical centers.\n\nPatients: Patients with mild-to-moderate AD.\n\nIntervention: Two consecutive cohorts of patients received 2 to 7 infusions of intravenous 3 Gantenerumab (60 or 200 mg) or placebo every 4 weeks. Brain slices from patients who had AD were coincubated with gantenerumab at increasing concentrations and with human microglial cells.\n\nMain Outcome Measures: Percent change in the ratio of regional carbon 11-labeled Pittsburgh Compound B retention in vivo and semiquantitative assessment of gantenerumab-induced

phagocytosis ex vivo.\n\nResults: Sixteen patients with end-of-treatment positron emission tomographic scans were included in the analysis. AZD1208 The mean (95% CI) percent change from baseline difference relative to placebo (n=4) in cortical brain amyloid level was -15.6% (95% CI, -42.7 to 11.6) for the 60-mg group (n=6) and -35.7% (95% CI, -63.5 to -7.9) for the 200-mg group (n=6). Two patients in the 200-mg group showed transient and focal areas of inflammation or vasogenic edema on magnetic resonance imaging scans at sites with the highest level of amyloid reduction. Gantenerumab induced phagocytosis of human amyloid in a dose-dependent manner ex vivo.\n\nConclusion: Gantenerumab treatment resulted in a dose-dependent reduction in brain

amyloid level, possibly through an effector cell-mediated mechanism of action.”
“Many patients have been characterized harboring a mutation in thyroid hormone receptor (TR) beta. Surprisingly XMU-MP-1 none has yet been identified carrying a mutation in TR alpha 1. To facilitate the identification of such patients,

several animal models with a mutant TR alpha 1 have been generated. While some phenotypic characteristics, such as an adult euthyroidism, are similar in the mutant mice, other aspects such as metabolism are quite variable. This review summarizes the most important consequences of a mutation in TR alpha 1 in mice focusing on the TR alpha 1-R384C mutation, and projects the 5-Fluoracil order insights from the animal models to a putative phenotype of patients with a mutated TR alpha 1.”
“Background: We performed a meta-analysis to evaluate the value of (18)FDG PET-CT for the detection of gastric cancer recurrence after surgical resection.\n\nMethods: A systematic literature search was performed in the MEDLINE and EMBASE databases. We calculated the sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for (18)FDG PET-CT. We also constructed summary receiver operating characteristic curves for (18)FDG PET-CT.\n\nResults: Eight studies (500 patients) were included. The sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of (18)FDG PET-CT were 0.86 (95% confidence interval [CI] = 0.71-0.94), 0.88 (95% CI = 0.75-0.94), 17.0 (95% CI = 3.5-14.0), and 0.16 (95% CI = 0.07-0.34), respectively.

Levodopa alone resulted in marked dyskinesia induction but little

Levodopa alone resulted in marked dyskinesia induction but little or no dyskinesia resulted from the administration of pramipexole. From clay 36, some animals were treated with a combination of levodopa (3.125-6.25 mg/kg plus carbidopa 12.5 mg/kg p.o. AZD7762 nmr BID) and pramipexole (0.1-0.2 mg/kg p.o. SID).

This improved motor disability to a greater extent than occurred with levodopa alone. Importantly, while dyskinesia was greater than that produced by pramipexole alone, the combination resulted in less intense dyskinesia than produced by levodopa alone. These results suggest that pramipexole could be administered with a reduced dose of levodopa to minimize dyskinesia in Parkinson’s disease while maintaining therapeutic efficacy. (C) 2010 Movement Disorder Society”
“Objective: To characterize downstream effectors of p300 acetyltransferase in the myocardium. Background: Acetyltransferase p300 is a central driver of the hypertrophic response to increased workload, but its biological targets and downstream effectors are incompletely known.\n\nMethods and Results: Mice expressing a myocyte-restricted transgene encoding acetyltransferase p300, previously

shown to develop spontaneous hypertrophy, were observed to undergo robust compensatory blood vessel growth together with increased angiogenic gene expression. Chromatin immunoprecipitation demonstrated binding of p300 to the enhancers of the angiogenic regulators Angpt1 and Egln3. Selleck VX809 PD-1/PD-L1 Inhibitor 3 in vitro Interestingly, p300 overexpression in vivo was also associated with relative upregulation of several members of the anti-angiogenic

miR-17 similar to 92 cluster in vivo. Confirming this finding, both miR-17-3p and miR-20a were upregulated in neonatal rat ventricular myocytes following adenoviral transduction of p300. Relative expression of most members of the 17,92 cluster was similar in all 4 cardiac chambers and in other organs, however, significant downregulation of miR-17-3p and miR-20a occurred between 1 and 8 months of age in both wt and tg mice. The decline in expression of these microRNAs was associated with increased expression of VEGFA, a validated miR-20a target. In addition, miR-20a was demonstrated to directly repress p300 expression through a consensus binding site in the p300 3′UTR. In vivo transduction of p300 resulted in repression both of p300 and of p300-induced angiogenic transcripts.\n\nConclusion: p300 drives an angiogenic transcription program during hypertrophy that is fine-tuned in part through direct repression of p300 by miR-20a.”
“Post-translational histone modifications play key roles in gene regulation, development, and differentiation, but their dynamics in living organisms remain almost completely unknown. To address this problem, we developed a genetically encoded system for tracking histone modifications by generating fluorescent modification-specific intracellular antibodies (mintbodies) that can be expressed in vivo.