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The Low Energy Relativistic Heavy Ion Collider (RHIC) electron Cooler (LEReC) is designed to deliver a 1.6 MeV to 2.6 MeV electron beam, with rms dp/p less than 5e-4. The superconducting radiofrequency (SRF) Booster Cavity is the major accelerating component in LEReC. It is a 0.4 cell cavity operating at 2 K, providing a maximum energy gain of 2.2 MeV. It is modified from an experimental Energy Recovery Linac (ERL) photocathode gun, and thus has fundamental power couplers (FPCs), pickup (PU) couplers (field probes) and HOM coupler close to each other on the same side of the cavity. Direct capacitive coupling between the FPC and PU, called the crosstalk effect, combined with microphonic detuning, can induce closed loop voltage fluctuations that exceed the total energy spread requirement of LEReC. The crosstalk effect in this cavity is modelled, simulated, and measured, and a correction method is proposed and demonstrated to suppress the voltage fluctuation so that energy spread requirement can be met. [ABSTRACT FROM AUTHOR]

Fenton's reagent and sawdust were used on the dewaterability of the raw oily sludge in this study. The result shows that the combination of the two treatment processes is favorable, although the application of Fenton's reagent only is not so good. The capillary suction time (CST) and specific resistance to filtration (SRF) were used to evaluate the effect of dewaterability of the raw oily sludge, and the CST and SRF values are reduced from 1,760 s and 13.8 × 10 m/kg to 185 s and 1.5 × 10 m/kg, respectively. The dry matter contents of sludge cakes and properties of the supernatant all gained when using only the Fenton's reagent and when using the combined treatment with Fenton's reagent and sawdust respectively were investigated. The results indicate that the oily sludge is more suitable for further treatment after combined process with Fenton's reagent and sawdust. [ABSTRACT FROM AUTHOR]

Stereo methods always require a matching function for assessing the likelihood of two pixels being in correspondence. Such functions, commonly referred as matching costs, measure the photo-similarity (or dissimilarity) between image regions centered in putative matches. This article proposes a new family of stereo cost functions that measure symmetry instead of photo-similarity for associating pixels across views. We start by observing that, given two stereo views and an arbitrary virtual plane passing in-between the cameras, it is possible to render image signals that are either symmetric or anti-symmetric with respect to the contour where the virtual plane meets the scene. The fact is investigated in detail and used as cornerstone to develop a new stereo framework that relies in symmetry cues for solving the data association problem. Extensive experiments in dense stereo show that our symmetry-based cost functions compare favorably against the best performing photo-similarity matching costs. In addition, we investigate the possibility of accomplishing Stereo Rangefinding that consists in using passive stereo to exclusively recover depth along a pre-defined scan plane. Thorough experiments provide evidence that stereo from induced symmetry is specially well suited for this purpose. [ABSTRACT FROM AUTHOR]

Abstract: The intercalated disc (ID) is a major component of the cell–cell contact structures of cardiomyocytes and has been recognized as a hot spot for cardiomyopathy. We have previously identified Myozap as a novel cardiac-enriched ID protein, which interacts with several other ID proteins and is involved in RhoA/SRF signaling in vitro. To now study its potential role in vivo we generated a mouse model with cardiac overexpression of Myozap. Transgenic (Tg) mice developed cardiomyopathy with hypertrophy and LV dilation. Consistently, these mice displayed upregulation of the hypertrophy-associated and SRF-dependent gene expression. Pressure overload (transverse aortic constriction, TAC) caused exaggerated cardiac hypertrophy, further loss of contractility and LV dilation. Similarly, a physiological stimulus (voluntary running) also led to significant LV dysfunction. On the ultrastructural level, Myozap-Tg mouse hearts exhibited massive protein aggregates composed of Myozap, desmoplakin and other ID proteins. This aggregate-associated pathology closely resembled the alterations observed in desmin-related cardiomyopathy. Interestingly, desmin was not detectable in the aggregates, yet was largely displaced from the ID. Molecular analyses revealed induction of autophagy and dysregulation of the unfolded protein response (UPR), associated with apoptosis. Taken together, cardiac overexpression of Myozap leads to cardiomyopathy, mediated, at least in part by induction of Rho-dependent SRF signaling in vivo. Surprisingly, this phenotype was also accompanied by protein aggregates in cardiomyocytes, UPR alteration, accelerated autophagy and apoptosis. Thus, this mouse model may also offer additional insight into the pathogenesis of protein-aggregate-associated cardiomyopathies and represents a new candidate gene itself. [Copyright &y& Elsevier]

ILC machine - International Liner Collider, is one of two accelerators e+e- just under design and advanced consideration to be built with final energy of colliding electron and positron beams over 1 TeV. An alternative project to ILC is CLIC in CERN The ILC machine is an important complementary addition for the research potential of the LHC accelerator complex. The required length of ILC is minimally 30 km, but some versions of the TDR estimates mention nearly 50km. Superconducting RF linacs will be built using well established 1,3 GHz TESLA technology using ultrapure niobium or Nb3Sn resonant microwave cavities of RRR class, of ultimate finesse, working with gradients over 35MV/m, while some versions of the design mention ultimate confinement as high as 50MV/m. Several teams from Poland (Kraków. Warszawa, Wrocław - IFJ-PAN, AGH, UJ, NCBJ, UW, PW, PWr, INT-PAN) participate in the global design effort for this machine - including detectors, cryogenics, and SRF systems. Now it seems that the ILC machine will be built in Japan, during the period of 2016-2026. If true, Japan will turn to a world super-power in accelerator technology no.3 after CERN and USA. The paper summarizes the state-ofthe- art of technical and administration activities around the immense ILC and CLIC machines, with emphasis on potential participation of Polish teams in the global effort of newly established LCC - The Linear Collider Consortium. [ABSTRACT FROM AUTHOR]

The transcription factor SRF (serum response factor) recruits two families of coactivators, the MRTFs (myocardin-related transcription factors) and the TCFs (ternary complex factors), to couple gene transcription to growth factor signaling. Here we investigated the role of the SRF network in the immediate transcriptional response of fibroblasts to serum stimulation. SRF recruited its cofactors in a gene-specific manner, and virtually all MRTF binding was directed by SRF. Much of SRF DNA binding was serum-inducible, reflecting a requirement for MRTF-SRF complex formation in nucleosome displacement. We identified 960 serum-responsive SRF target genes, which were mostly MRTF-controlled, as assessed by MRTF chromatin immunoprecipitation (ChIP) combined with deep sequencing (ChIP-seq) and/or sensitivity to MRTF-linked signals. MRTF activation facilitates RNA polymerase II (Pol II) recruitment or promoter escape according to gene context. MRTF targets encode regulators of the cytoskeleton, transcription, and cell growth, underpinning the role of SRF in cytoskeletal dynamics and mechanosensing. Finally, we show that specific activation of either MRTFs or TCFs can reset the circadian clock. [ABSTRACT FROM AUTHOR]

The genetic mechanisms driving normal brain development remain largely unknown. We performed genomic and immunohistochemical characterization of a novel, fatal human phenotype including extreme microcephaly with cerebral growth arrest at 14-18 weeks gestation in three full sisters born to healthy, non-consanguineous parents. Analysis of index cases and parents included familial exome sequencing, karyotyping, and genome-wide single nucleotide polymorphism ( SNP) array. From proband, control and unrelated microcephalic fetal cortical tissue, we compared gene expression of RNA and targeted immunohistochemistry. Each daughter was homozygous for a rare, non-synonymous, deleterious variant in the MKL2 gene and heterozygous for a private 185 kb deletion on the paternal allele, upstream and in cis with his MKL2 variant allele, eliminating 24 CArG transcription factor binding sites and MIR4718. MKL1 was underexpressed in probands. Dysfunction of MKL2 and its transcriptional coactivation partner, serum response factor ( SRF), was supported by a decrease in gene and protein expression of PCTAIRE1, a downstream target of MKL2: SRF heterodimer transcriptional activation, previously shown to result in severe microcephaly in murine models. While disruption of the MKL2: SRF axis has been associated with severe microcephaly and disordered brain development in multiple model systems, the role of this transcription factor complex has not been previously demonstrated in human brain development. [ABSTRACT FROM AUTHOR]

Background Serum response factor (SRF) is a widely expressed transcription factor involved in multiple regulatory programs. It is believed that SRF can toggle between disparate programs of gene expression through association with different cofactors. However, the direct evidence as to how these factors function on a genome-wide level is still lacking. Results In the present study, I explored the functions of SRF and its representative cofactors, megakaryoblastic leukemia 1/2 (MKL1/2) and ETS-domain protein 4 (ELK4), during fungal infection challenge in macrophages. The knockdown study, combined with gene expression array analysis, revealed that MKL1/2 regulated SRF-dependent genes were related to actin cytoskeleton organization, while ELK4 regulated SRF-dependent genes were related to external stimulus responses. Subsequent chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-seq) suggested that many of these regulations were mediated directly in cis. Conclusions I conclude that SRF utilizes MKL1/2 to fulfill steady state cellular functions, including cytoskeletal organization, and utilizes ELK4 to facilitate acute responses to external infection. Together, these findings indicate that SRF, along with its two cofactors, are important players in both cellular homeostasis and stress responses in macrophages. [ABSTRACT FROM AUTHOR]

Increased angiogenesis, inflammation, and proliferation are hallmarks of diseased tissues, and in vivo models of these disease phenotypes can provide insight into disease pathology. Dstncorn1 mice, deficient for the actin depolymerizing factor destrin (DSTN), display an increase of serum response factor (SRF) that results in epithelial hyperproliferation, inflammation, and neovascularization in the cornea. Previous work demonstrated that conditional ablation of Srf from the corneal epithelium of Dstncorn1 mice returns the cornea to a wild-type (WT) like state. This result implicated SRF as a major regulator of genes that contributes to abnormal phenotypes in Dstncorn1 cornea. The purpose of this study is to identify gene networks that are affected by increased expression of Srf in the Dstncorn1 cornea. Microarray analysis led to characterization of gene expression changes that occur when conditional knockout of Srf rescues mutant phenotypes in the cornea of Dstncorn1 mice. Comparison of gene expression values from WT, Dstncorn1 mutant, and Dstncorn1 rescued cornea identified >400 differentially expressed genes that are downstream from SRF. Srf ablation had a significant effect on genes associated with epithelial cell-cell junctions and regulation of actin dynamics. The majority of genes affected by SRF are downregulated in the Dstncorn1 mutant cornea, suggesting that increased SRF negatively affects transcription of SRF gene targets. ChIP-seq analysis on Dstncorn1 mutant and WT tissue revealed that, despite being present in higher abundance, SRF binding is significantly decreased in the Dstncorn1 mutant cornea. This study uses a unique model combining genetic and genomic approaches to identify genes that are regulated by SRF. These findings expand current understanding of the role of SRF in both normal and abnormal tissue homeostasis. [ABSTRACT FROM AUTHOR]

Actin cytoskeleton is one of the main targets of rho GTPases, which act as molecular switches on many signaling pathways. During the past decade, actin has emerged as an important regulator of gene expression. Nuclear actin plays a key role in transcription, chromatin remodeling, and pre-mRNA processing. In addition, the "status" of the actin cytoskeleton is used as a signaling intermediate by at least the MKL1-SrF and Hippo-pathways, which culminate in the transcriptional regulation of cytoskeletal and growth-promoting genes, respectively. Rho GTPases may therefore regulate gene expression by controlling either cytoplasmic or nuclear actin dynamics. although the regulation of nuclear actin polymerization is still poorly understood, many actin-binding proteins, which are downstream effectors of Rho, are found in the nuclear compartment. In this review, we discuss the possible mechanisms and key proteins that may mediate the transcriptional regulation by Rho GTPases through actin. [ABSTRACT FROM AUTHOR]

Compared to the cytoplasmic F-actin abundance in cells, nuclear F-actin levels are generally quite low. However, nuclear actin is present in certain cell types including oocytes and under certain cellular conditions including stress or serum stimulation. Currently, the architecture and polymerization status of nuclear actin networks has not been analyzed in great detail. In this study, we investigated the architecture and functions of such nuclear actin networks. We generated nuclear actin polymers by overexpression of actin proteins fused to a nuclear localization signal (NLS). Raising nuclear abundance of a NLS wild-type actin, we observed phalloidin- and LifeAct-positive actin bundles forming a nuclear cytoskeletal network consisting of curved F-actin. In contrast, a polymer-stabilizing actin mutant (NLS-G15S-actin) deficient in interacting with the actin-binding protein cofilin generated a nuclear actin network reminiscent of straight stress fiber-like microfilaments in the cytoplasm. We provide a first electron microscopic description of such nuclear actin polymers suggesting bundling of actin filaments. Employing different cell types from various species including neurons, we show that the morphology of and potential to generate nuclear actin are conserved. Finally, we demonstrate that nuclear actin affects cell function including morphology, serum response factor-mediated gene expression, and herpes simplex virus infection. Our data suggest that actin is able to form filamentous structures inside the nucleus, which share architectural and functional similarities with the cytoplasmic F-actin. [ABSTRACT FROM AUTHOR]

Tobacco smoking is a risk factor for many diseases, and nicotine is a major component of tobacco. Our previous work revealed that nicotine can induce myocardial fibrosis. This study aimed to investigate whether nicotine can induce cardiomyocyte apoptosis and to explore the mechanisms involved. Cardiomyocytes were exposed to different nicotine concentrations for 48 h. MTT assay showed that the viability of cardiomyocytes was significantly inhibited by nicotine in a dose- and time-dependent manner. Loss of mitochondrial membrane potential, nuclear and DNA defragmentation determined by TUNEL and ELISA assays, and morphological alterations all revealed the pro-apoptotic property of nicotine. Meanwhile, miR-133, a muscle-specific microRNA, was markedly downregulated by nicotine. Consistently, caspase-9, a target gene for miR-133, was significantly upregulated, leading to an increase in caspase-3, in nicotine-treated cardiomyocytes compared to non-treated cells. Furthermore, ERK1/2 protein levels were considerably downregulated, along with reduction of serum response factor (SRF), which is a downstream target protein of ERK1/2 and an upstream transactivator of miR-133 as well. Our findings therefore revealed that inhibition of the ERK1/2-SRF-miR-133 signaling pathway to increase caspases-9 and −3 is a novel mechanism for nicotine to induce cardiomyocyte apoptosis and these tobacco smokers. [ABSTRACT FROM AUTHOR]

Abstract: Future particle accelerators will require continuous wave operation of SRF cavities capable of supporting high beam currents. An example of this is the Energy Recovery Linac (ERL) at Cornell University, a next generation light source designed to run high currents (100mA) with a high bunch repetition rate (1.3GHz). Obtaining the beam emittance necessary to meet design specification requires strong damping of higher-order modes that can lead to beam breakup. We discuss the optimization and verification of the accelerating cavity. Next we show that an ERL constructed from the optimized cavity geometry – including realistic shape errors – can support beam currents in excess of 300mA while still maintaining beam stability. A niobium prototype 7-cell cavity was fabricated and tested in a horizontal cryomodule. We show that the prototype cavity exceeds quality factor and gradient specifications of at 16.2MV/m at 1.8K by 50%, reaching . The prototype cavity also satisfies all design constraints and has a higher order mode spectrum consistent with the optimized shape geometry. At 1.6K, the cavity set a record for quality factor of a multicell cavity installed in a horizontal cryomodule reaching . [Copyright &y& Elsevier]

Highlights: [•] Appropriate solution for MSW management in new and future EU countries. [•] Decrease of landfill disposal applying an Integrated MSW approach. [•] Technological impediments and environmental assessment. [ABSTRACT FROM AUTHOR]

Aims: In 2017, a subset of cellular variants of myofibroma and myopericytoma with a smooth muscle-like immunophenotype and harbouring recurrent SRF::RELA gene fusions was reported. Although the anatomical distribution was found to be quite broad, no tumours with these gene fusions in the female reproductive system have been illustrated to date., Methods and Results: Herein, we report the histological and immunophenotypical features of three uterine tumours with SRF::RELA gene fusions. Microscopically, all three tumours were composed of cellular oval to spindle cells arranged in intersecting fascicles with variable amounts of collagen and a rich capillary network. Mitotic figures were scant. Regarding immunohistochemistry, diffuse staining for desmin, oestrogen receptor and progesterone receptor was observed in all three cases. The first case exhibited focal staining for h-caldesmon, whereas the latter two cases had diffuse staining. Furthermore, SRF::RELA rearrangement was observed in all three cases by using next-generation sequencing (NGS). Follow-up, ranging from 11 to 15 months, was available for these three patients, all of whom were well without evidence of disease., Conclusions: In conclusion, we reported a special group of uterine neoplasms with myogenic differentiation harbouring SRF::RELA rearrangement. Although the follow-up time was limited, morphological characteristics and other studies with follow-up data supported that this type of uterine neoplasm appeared to behave in a benign manner. Further studies with longer follow-up are needed to clarify the biological nature of this particular type of uterine tumour., (© 2022 John Wiley & Sons Ltd.)

Serum response factor (SRF) is a representative transcription factor that plays crucial roles in various biological phenomena by regulating immediate early genes (IEGs) and genes related to cell morphology and motility, among others. Over the years, the signal transduction pathways activating SRF have been clarified and SRF-target genes have been identified. In this overview, we initially briefly summarize the basic biology of SRF and its cofactors, ternary complex factor (TCF) and megakaryoblastic leukemia (MKL)/myocardin-related transcription factor (MRTF). Progress in the generation of nervous system-specific knockout (KO) or genetically modified mice as well as genetic analyses over the last few decades has not only identified novel SRF-target genes but also highlighted the neurochemical importance of SRF and its cofactors. Therefore, here we next present the phenotypes of mice with nervous system-specific KO of SRF or its cofactors by depicting recent findings associated with brain development, plasticity, epilepsy, stress response, and drug addiction, all of which result from function or dysfunction of the SRF axis. Last, we develop a hypothesis regarding the possible involvement of SRF and its cofactors in human neurological disorders including neurodegenerative, psychiatric, and neurodevelopmental diseases. This overview should deepen our understanding, highlight promising future directions for developing novel therapeutic strategies, and lead to illumination of the mechanisms underlying higher brain functions based on neuronal structure and function., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Acute pancreatitis (AP) is an inflammatory process of the pancreas resulting from biliary obstruction or alcohol consumption. Approximately, 10-20% of AP can evolve into severe AP (SAP). In this study, we sought to explore the physiological roles of the transcription factor serum response factor (SRF), annexin A2 (ANXA2), and nuclear factor-kappaB (NF-κB) in SAP., Methods: C57BL/6 mice and rat pancreatic acinar cells (AR42J) were used to establish an AP model in vivo and in vitro by cerulein with or without lipopolysaccharide (LPS). Production of pro-inflammatory cytokines (IL-1β and TNF-α) were examined by ELISA and immunoblotting analysis. Hematoxylin and eosin (HE) staining and TUNEL staining were performed to evaluate pathological changes in the course of AP. Apoptosis was examined by flow cytometric and immunoblotting analysis. Molecular interactions were tested by dual luciferase reporter, ChIP, and Co-IP assays., Results: ANXA2 was overexpressed in AP and correlated to the severity of AP. ANXA2 knockdown rescued pancreatic acinar cells against inflammation and apoptosis induced by cerulein with or without LPS. Mechanistic investigations revealed that SRF bound with the ANXA2 promoter region and repressed its expression. ANXA2 could activate the NF-κB signaling pathway by inducing the nuclear translocation of p50. SRF-mediated transcriptional repression of ANXA2-protected pancreatic acinar cells against AP-like injury through repressing the NF-κB signaling pathway., Conclusion: Our study highlighted a regulatory network consisting of SRF, ANXA2, and NF-κB that was involved in AP progression, possibly providing some novel targets for treating SAP., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

High-resolution data are increasingly used for various applications, yet the revisit time is still low for some applications, particularly in frequently cloud-covered areas. Therefore, sensors are often combined, which raises issues on data consistency. In this study, we start from L1 to L3 data, and investigate the impact of harmonization measures, correcting for difference in radiometric gain and spectral response function (SRF), and the use of a common processing chain with the same atmospheric correction for Sentinel-2A/B, Landsat-8, DEIMOS-1, and Proba-V center cameras. These harmonization measures are evaluated step-wise in two applications: (1) agricultural monitoring, and (2) hydrological modelling in an urban context, using biophysical parameters and NDVI. The evaluation includes validation with in situ data, relative consistency analysis between different sensors, and the evaluation of the time series noise. A higher accuracy was not obtained when validating against in situ data. Yet, the relative analysis and the time series noise analysis clearly demonstrated that the largest improvement in consistency between sensors was obtained when applying the same atmospheric correction to all sensors. The gain correction obtained and its impact on the results was small, indicating that the sensors were already well calibrated. We could not demonstrate an improved consistency after SRF correction. It is likely that other factors, such as anisotropy effects, play a larger role, requiring further research. [ABSTRACT FROM AUTHOR]

Abstract: Background: A large body of evidence showed that arsenic trioxide (As2O3), a front-line drug for the treatment of acute promyelocytic leukemia, induced abnormal cardiac QT prolongation, which hampers its clinical use. The molecular mechanisms for this cardiotoxicity remained unclear. This study aimed to elucidate whether microRNAs (miRs) participate in As2O3-induced QT prolongation. Methods: A guinea pig model of As2O3-induced QT prolongation was established by intravenous injection with As2O3. Real-time PCR and Western blot were employed to determine the expression alterations of miRs and mRNAs, and their corresponding proteins. Results: The QT interval and QRS complex were significantly prolonged in a dose-dependent fashion after 7-day administration of As2O3. As2O3 induced a significant upregulation of the muscle-specific miR-1 and miR-133, as well as their transactivator serum response factor. As2O3 depressed the protein levels of ether-a-go-go related gene (ERG) and Kir2.1, the K+ channel subunits responsible for delayed rectifier K+ current I Kr and inward rectifier K+ current I K1, respectively. In vivo transfer of miR-133 by direct intramuscular injection prolonged QTc interval and increased mortality rate, along with depression of ERG protein and I Kr in guinea pig hearts. Similarly, forced expression of miR-1 widened QTc interval and QRS complex and increased mortality rate, accompanied by downregulation of Kir2.1 protein and I K1. Application of antisense inhibitors to knockdown miR-1 and miR-133 abolished the cardiac electrical disorders caused by As2O3. Conclusions: Deregulation of miR-133 and miR-1 underlies As2O3-induced cardiac electrical disorders and these miRs may serve as potential therapeutic targets for the handling of As2O3 cardiotoxicity. [Copyright &y& Elsevier]

Highlights: [•] The updated definition and explanation of Oldenburg's SRF are proposed and elucidated. [•] The methodology is firstly applied on China's Shenhua CCS project. [•] The evaluated site with six reservoir-seal combinations is in low risk. [ABSTRACT FROM AUTHOR]

Abstract: CCG-1423 (1) is a novel inhibitor of Rho/MKL1/SRF-mediated gene transcription that inhibits invasion of PC-3 prostate cancer cells in a Matrigel model of metastasis. We recently reported the design and synthesis of conformationally restricted analogs (e.g., 2) with improved selectivity for inhibiting invasion versus acute cytotoxicity. In this study we conducted a survey of aromatic substitution with the goal of improving physicochemical parameters (e.g., C log P, MW) for future efficacy studies in vivo. Two new compounds were identified that attenuated cytotoxicity even further, and were fourfold more potent than 2 at inhibiting PC-3 cell migration in a scratch wound assay. One of these (8a, CCG-203971, IC50 =4.2μM) was well tolerated in mice for 5days at 100mg/kg/day i.p., and was able to achieve plasma levels exceeding the migration IC50 for up to 3h. [Copyright &y& Elsevier]

Aims The expression of the sodium/calcium exchanger NCX1 increases during cardiac hypertrophy and heart failure, playing an important role in Ca2+ extrusion. This increase is presumed to result from stress signalling induced changes in the interplay between transcriptional and post-transcriptional regulations. We aimed to determine the impact of the SRF transcription factor known to regulate the NCX1 promoter and microRNA genes, on the expression of NCX1 mRNA and protein and Annexin A5 (AnxA5), a Ca2+-binding protein interacting with NCX1 and increased during HF. Methods and results NCX1 mRNA was decreased while the protein was increased in the failing heart of the cardiomyocyte-restricted SRF knock-out mice (SRFHKO). The induction of NCX1 mRNA by the pro-hypertrophic drug phenylephrine observed in control mice was abolished in the SRFHKO though the protein was strongly increased. AnxA5 protein expression profile paralleled the expression of NCX1 protein in the SRFHKO. MiR-1, a microRNA regulated by SRF, was decreased in the SRFHKO and repressed by phenylephrine. In vitro and in vivo manipulation of miR-1 levels and site-directed mutagenesis showed that NCX1 and AnxA5 mRNAs are targets of miR-1. AnxA5 overexpression slowed down Ca2+ extrusion during caffeine application in adult rat cardiomyocytes. Conclusion Our study reveals the existence of a complex regulatory loop where SRF regulates the transcription of NCX1 and miR-1, which in turn functions as a rheostat limiting the translation of NCX1 and AnxA5 proteins. The decrease of miR-1 and increase of AnxA5 appear as important modulators of NCX1 expression and activity during heart failure. [ABSTRACT FROM AUTHOR]

Efficient angiogenic sprouting is essential for embryonic, postnatal and tumor development. Serum response factor (SRF) is known to be important for embryonic vascular development. Here, we studied the effect of inducible endothelial-specific deletion of Srf in postnatal and adult mice. We find that endothelial SRF activity is vital for postnatal growth and survival, and is equally required for developmental and pathological angiogenesis, including during tumor growth. Our results demonstrate that SRF is selectively required for endothelial filopodia formation and cell contractility during sprouting angiogenesis, but seems dispensable for vascular remodeling. At the molecular level, we observe that vascular endothelial growth factor A induces nuclear accumulation of myocardinrelated transcription factors (MRTFs) and regulates MRTF/SRF-dependent target genes including Myl9, which is important for endothelial cell migration in vitro. We conclude that SRF has a unique function in regulating migratory tip cell behavior during sprouting angiogenesis. We hypothesize that targeting the SRF pathway could provide an opportunity to selectively target tip cell filopodia-driven angiogenesis to restrict tumor growth. [ABSTRACT FROM AUTHOR]

OBJECTIVES Serum response factor (SRF), E2F1 and survivin are well-known factors involved in a multitude of cancer-related regulation processes. However, to date, no suitable means has been found to apply their potential in the therapy of non-small cell lung cancer (NSCLC). This study deals with questions of small interfering ribonucleic acid (siRNA) transfection efficiency by a non-viral transfection of NSCLC cell-lines and the power of siRNA to transiently influence cell division by specific silencing. METHODS Different NSCLC cell lines were cultured under standard conditions and transfected, with specific siRNA targeting SRF, E2F1 and survivin in a non-viral manner. Cells treated with non-specific siRNA (SCR-siRNA) served as controls. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed for messenger RNA (mRNA) expression levels. Additionally, transfection efficiency was evaluated by flow cytometry. The analysis of cell proliferation was determined with a CASY cell counter 3 days after transfection with SRF or SCR-siRNA. RESULTS Transfection of the NSCLC cell lines with specific siRNAs against SRF, E2F1 and survivin resulted in a very considerable reduction of the intracellular mRNA concentration. CASY confirmation of cell viability demonstrated an excellent survival of the cell lines treated with non-specific siRNA, in contrast to with application of specific siRNA. CONCLUSIONS This study reports a reliable transfectability of NSCLC-cell lines by siRNA, initially in a non-viral manner, and a reproducible knockdown of the focussed targets, consequently leading to the death of the tumour cells. This constitutes a strong candidate for a new assessment strategy in the therapy of non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

Background and aims: The response of soil respiration (SR) to elevated CO is driven by a number of processes and feedbacks. This work aims to i) detect the effect of elevated CO on soil respiration during the second rotation of a short rotation forest, at two levels of N availability; and ii) identify the main drivers behind any changes in soil respiration. Methods: A poplar plantation (POP-EUROFACE) was grown for two rotations of 3 years under elevated CO maintained by a FACE (Free Air CO Enrichment) technique. Root biomass, litter production and soil respiration were followed for two consecutive years after coppice. Results: In the plantation, the stimulation of fine root and litter production under elevated CO observed at the beginning of the rotation declined over time. Soil respiration (SR) was continuously stimulated by elevated CO, with a much larger enhancement during the growing (up to 111 %) than in the dormant season (40 %). The SR increase at first appeared to be due to the increase in fine root biomass, but at the end of the 2nd rotation was supported by litter decomposition and the availability of labile C. Soil respiration increase under elevated CO was not affected by N availability. Conclusions: The stimulation of SR by elevated CO was sustained by the decomposition of above and belowground litter and by the greater availability of easily decomposable substrates into the soil. In the final year as elevated CO did not increase C allocation to roots, the higher SR suggests greater C losses from the soil, thus reducing the potential for C accumulation. [ABSTRACT FROM AUTHOR]

Abstract: The main fine particle (dp <1μm) forming elements found in combustion gases of anthropogenic waste or biomass fired boilers are typically K, Na and Cl, possibly complemented with S. When these are excluded, in solid recovered fuel (SRF) combustion the main elements were found to be: Ba, Br, Cr, Cu, Fe, Pb, Sb, Sn and Zn. Fine particle composition is presented for 6 different furnace heights of a bubbling fluidized bed (BFB) boiler. As the fine particles are formed of vaporized ash species the experimental results are discussed with the support of thermodynamic equilibrium modeling for estimating the forms of the gaseous elements in the furnace. The occurrence of bromine was found to be similar to chlorine as the main forms of bromine in the furnace were estimated to be KBr(g) and NaBr(g) complemented with CuBr3(g). It is proposed that the trace elements mentioned originate mainly from plastics and rubber where they are used as production additives, stabilisers, dyes, colorants and flame retardants. Cr, Cu and Zn may originate to a large extent from alloys and other metallic impurities. SEM-EDS analyses carried out for the SRF supports the postulated origin of the elements. [Copyright &y& Elsevier]