Ground Reaction Forces of the Lead and Trail Limbs when Stepping Over an Obstacle

PubMed Central

Bovonsunthonchai, Sunee; Khobkhun, Fuengfa; Vachalathiti, Roongtiwa

2015-01-01

Background Precise force generation and absorption during stepping over different obstacles need to be quantified for task accomplishment. This study aimed to quantify how the lead limb (LL) and trail limb (TL) generate and absorb forces while stepping over obstacle of various heights. Material/Methods Thirteen healthy young women participated in the study. Force data were collected from 2 force plates when participants stepped over obstacles. Two limbs (right LL and left TL) and 4 conditions of stepping (no obstacle, stepping over 5 cm, 20 cm, and 30 cm obstacle heights) were tested for main effect and interaction effect by 2-way ANOVA. Paired t-test and 1-way repeated-measure ANOVA were used to compare differences of variables between limbs and among stepping conditions, respectively. The main effects on the limb were found in first peak vertical force, minimum vertical force, propulsive peak force, and propulsive impulse. Results Significant main effects of condition were found in time to minimum force, time to the second peak force, time to propulsive peak force, first peak vertical force, braking peak force, propulsive peak force, vertical impulse, braking impulse, and propulsive impulse. Interaction effects of limb and condition were found in first peak vertical force, propulsive peak force, braking impulse, and propulsive impulse. Conclusions Adaptations of force generation in the LL and TL were found to involve adaptability to altered external environment during stepping in healthy young adults. PMID:26169293

MiR-126 and miR-126* regulate shear-resistant firm leukocyte adhesion to human brain endothelium

PubMed Central

Cerutti, Camilla; Edwards, Laura J.; de Vries, Helga E.; Sharrack, Basil; Male, David K.; Romero, Ignacio A.

2017-01-01

Leukocyte adhesion to brain endothelial cells, the blood-brain barrier main component, is a critical step in the pathogenesis of neuroinflammatory diseases such as multiple sclerosis (MS). Leukocyte adhesion is mediated mainly by selectins, cell adhesion molecules and chemokines induced by pro-inflammatory cytokines such as TNFα and IFNγ, but the regulation of this process is not fully clear. This study investigated the regulation of firm leukocyte adhesion to human brain endothelium by two different brain endothelial microRNAs (miRs), miR-126 and miR-126*, that are downregulated by TNFα and IFNγ in a human brain endothelial cell line, hCMEC/D3. Using a leukocyte adhesion in vitro assay under shear forces mimicking blood flow, we observed that reduction of endothelial miR-126 and miR-126* enhanced firm monocyte and T cell adhesion to hCMEC/D3 cells, whereas their increased expression partially prevented THP1, Jurkat and primary MS patient-derived PBMC firm adhesion. Furthermore, we observed that miR-126* and miR-126 downregulation increased E-selectin and VCAM1, respectively, while miR-126 overexpression reduced VCAM1 and CCL2 expression by hCMEC/D3 cells, suggesting that these miRs regulate leukocyte adhesion by modulating the expression of adhesion-associated endothelial mRNA targets. Hence, human brain endothelial miR-126 and miR-126* could be used as a therapeutic tool to reduce leukocyte adhesion and thus reduce neuroinflammation. PMID:28358058

Impulse noise generator--design and operation.

PubMed

Brinkmann, H

1991-01-01

In the seventies PFANDER (Pfander, 1975) proposed a screening test with an impulse noise simulator to check the particular responsivity of soldiers on vulnerability of the inner ear concerning the impulse noise-induced hearing loss. According to a system developed at the University of Oldenburg (Germany) (Klug & Radek, 1987), we have constructed an impulse noise generator designed for our specific requirements that will be presented. The simulator consists of an electrical ignited impulse noise spark gap which is supplied by a 3.5 kV high voltage source. At a distance of 1.10 m from the center of the impulse noise spark gap a peak pressure level of 155 dB with a C-Duration (Pfander, 1975) of .2 msec and with the main energy in the frequency range from 1 kHz to 2 kHz was good reproducible. It would be preferable to shift the impulse noise spectrum to lower frequencies but experimental effort has failed so far.

MicroRNA analysis in mouse neuro-2a cells after pseudorabies virus infection.

PubMed

Li, Yongtao; Zheng, Guanmin; Zhang, Yujuan; Yang, Xia; Liu, Hongying; Chang, Hongtao; Wang, Xinwei; Zhao, Jun; Wang, Chuanqing; Chen, Lu

2017-06-01

Pseudorabies virus (PRV), an alpha herpesvirus can enter the mammalian nervous system, causing Aujezsky's disease. Previous studies have reported an alteration of microRNA (miRNA) expression levels during PRV infections. However, knowledge regarding miRNA response in nervous cells to PRV infection is still unknown. To address this issue, small RNA libraries from infected and uninfected mouse neuroblastoma cells were assessed after Illumina deep sequencing. A total of eight viral miRNA were identified, and ten host miRNAs showed significantly different expression upon PRV infection. Among these, five were analyzed by stem-loop RT-qPCR, which confirmed the above data. Interestingly, these viral miRNAs were mainly found in the large latency transcript region of PRV, and predicted to target a variety of genes, forming a complicated regulatory network. Moreover, ten cellular miRNAs were expressed differently upon PRV infection, including nine upregulated and one downregulated miRNAs. Host targets of these miRNAs obtained by bioinformatics analysis belonged to large signaling networks, mainly encompassing calcium signaling pathway, cAMP signaling pathway, MAPK signaling pathway, and other nervous-associated pathways. These findings further highlighted miRNA features in nervous cells after PRV infection and contributed to unveil the underlying mechanisms of neurotropism as well as the neuropathogenesis of PRV.

Suicidality in temporal lobe epilepsy: measuring the weight of impulsivity and depression.

PubMed

de Oliveira, Guilherme Nogueira M; Kummer, Arthur; Salgado, João Vinícius; Filho, Gerardo Maria de Araújo; David, Anthony S; Teixeira, Antônio Lúcio

2011-12-01

The aim of the work described here was to measure the role of psychopathological features, specifically impulsivity and depression, in suicidality in patients with temporal lobe epilepsy (TLE). Neuropsychiatric evaluation of 66 outpatients with TLE was performed with the following instruments: a structured clinical interview (Mini International Neuropsychiatric Interview Plus), the Barratt Impulsiveness Scale, the Hamilton Anxiety Scale, the Beck Depression Inventory, and the Brief Psychiatric Rating Scale. A current Axis I psychiatric diagnosis, mainly mood and anxiety disorders, was assigned to 37 subjects (56.1%) Presence of suicide risk was identified in 19 patients (28.8%), and 14 (21.2%) had attempted suicide. Frequency of seizures (P=0.012), current major depression (P=0.001), and motor impulsivity (P=0.005) were associated with suicide risk on univariate analysis. Logistic regression stressed the main relevance of major depression (OR=12.82, 95% CI=2.58-63.76, P=0.002) and motor impulsivity (OR=1.21, 95% CI=1.06-1.38, P=0.005) to suicide risk. Depression has a major influence on suicidality in epilepsy. Motor impulsivity is also relevant and may be an important component of depression in TLE associated with suicide risk. Copyright © 2011 Elsevier Inc. All rights reserved.

Spin Tracking of Polarized Protons in the Main Injector at Fermilab

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiao, M.; Lorenzon, W.; Aldred, C.

2016-07-01

The Main Injector (MI) at Fermilab currently produces high-intensity beams of protons at energies of 120 GeV for a variety of physics experiments. Acceleration of polarized protons in the MI would provide opportunities for a rich spin physics program at Fermilab. To achieve polarized proton beams in the Fermilab accelerator complex, shown in Fig.1.1, detailed spin tracking simulations with realistic parameters based on the existing facility are required. This report presents studies at the MI using a single 4-twist Si-berian snake to determine the depolarizing spin resonances for the relevant synchrotrons. Results will be presented first for a perfect MImore » lattice, followed by a lattice that includes the real MI imperfections, such as the measured magnet field errors and quadrupole misalignments. The tolerances of each of these factors in maintaining polariza-tion in the Main Injector will be discussed.« less

Differential Expression of MicroRNAs in Breast Cancers from Four Different Ethnicities.

PubMed

Pollard, Jennifer; Burns, Phil A; Hughes, Tom A; Ho-Yen, Colan; Jones, J Louise; Mukherjee, Geetashree; Omoniyi-Esan, Ganiat O; Titloye, Nicholas Akinwale; Speirs, Valerie; Shaaban, Abeer M

2018-05-23

Breast cancer outcomes vary across different ethnic groups. MicroRNAs (miRs) are small non-coding RNA molecules that regulate gene expression across a range of pathologies, including breast cancer. The aim of this study was to evaluate the presence and expression of miRs in breast cancer samples from different ethnic groups. Breast cancer tissue from 4 ethnic groups, i.e., British Caucasian, British Black, Nigerian, and Indian, were identified and matched for patients' age, tumour grade/type, and 10 × 10 µm sections taken. Tumour areas were macrodissected, total RNA was extracted, and cDNA was synthesised. cDNA was applied to human miScript PCR arrays allowing the quantification of 84 of the most abundantly expressed/best-characterised miRs. Differential expression of 9 miRs was seen across the 4 groups. Significantly higher levels of miR-140-5p, miR-194 and miR-423-5p (the last of which harbours the single-nucleotide polymorphism rs6505162) were seen in the breast tumours of Nigerian patients when compared with other ethnic groups (all p < 0.0001). miR-101 was overexpressed in breast cancers in the Indian patients. An in silico analysis of miR-423-5p showed that the AC genotype is mainly associated with Europeans (57%), while Asians display mostly CC (approx. 60%), and Africans mainly AA (approx. 60%). This study shows divergence in miR expression in breast cancers from different ethnic groups, and suggests that specific genetic variants in miR genes may affect breast cancer risk in these groups. Predicted targets of these miRs may uncover useful biomarkers that could have clinical value in breast cancers in different ethnic groups. © 2018 S. Karger AG, Basel.

Polypyrrole-chitosan conductive biomaterial synchronizes cardiomyocyte contraction and improves myocardial electrical impulse propagation.

PubMed

Cui, Zhi; Ni, Nathan C; Wu, Jun; Du, Guo-Qing; He, Sheng; Yau, Terrence M; Weisel, Richard D; Sung, Hsing-Wen; Li, Ren-Ke

2018-01-01

Background: The post-myocardial infarction (MI) scar interrupts electrical impulse propagation and delays regional contraction, which contributes to ventricular dysfunction. We investigated the potential of an injectable conductive biomaterial to restore scar tissue conductivity and re-establish synchronous ventricular contraction. Methods: A conductive biomaterial was generated by conjugating conductive polypyrrole (PPY) onto chitosan (CHI) backbones. Trypan blue staining of neonatal rat cardiomyocytes (CMs) cultured on biomaterials was used to evaluate the biocompatibility of the conductive biomaterials. Ca 2+ imaging was used to visualize beating CMs. A cryoablation injury rat model was used to investigate the ability of PPY:CHI to improve cardiac electrical propagation in the injured heart in vivo . Electromyography was used to evaluate conductivity of scar tissue ex vivo . Results: Cell survival and morphology were similar between cells cultured on biomaterials-coated and uncoated-control dishes. PPY:CHI established synchronous contraction of two distinct clusters of spontaneously-beating CMs. Intramyocardial PPY:CHI injection into the cryoablation-induced injured region improved electrical impulse propagation across the scarred tissue and decreased the QRS interval, whereas saline- or CHI-injected hearts continued to have delayed propagation patterns and significantly reduced conduction velocity compared to healthy controls. Ex vivo evaluation found that scar tissue from PPY:CHI-treated rat hearts had higher signal amplitude compared to those from saline- or CHI-treated rat heart tissue. Conclusions: The PPY:CHI biomaterial is electrically conductive, biocompatible and injectable. It improved synchronous contraction between physically separated beating CM clusters in vitro . Intra-myocardial injection of PPY:CHI following cardiac injury improved electrical impulse propagation of scar tissue in vivo .

On the interpretation of kernels - Computer simulation of responses to impulse pairs

NASA Technical Reports Server (NTRS)

Hung, G.; Stark, L.; Eykhoff, P.

1983-01-01

A method is presented for the use of a unit impulse response and responses to impulse pairs of variable separation in the calculation of the second-degree kernels of a quadratic system. A quadratic system may be built from simple linear terms of known dynamics and a multiplier. Computer simulation results on quadratic systems with building elements of various time constants indicate reasonably that the larger time constant term before multiplication dominates in the envelope of the off-diagonal kernel curves as these move perpendicular to and away from the main diagonal. The smaller time constant term before multiplication combines with the effect of the time constant after multiplication to dominate in the kernel curves in the direction of the second-degree impulse response, i.e., parallel to the main diagonal. Such types of insight may be helpful in recognizing essential aspects of (second-degree) kernels; they may be used in simplifying the model structure and, perhaps, add to the physical/physiological understanding of the underlying processes.

The role of neuroimmune signaling in alcoholism.

PubMed

Crews, Fulton T; Lawrimore, Colleen J; Walter, T Jordan; Coleman, Leon G

2017-08-01

Alcohol consumption and stress increase brain levels of known innate immune signaling molecules. Microglia, the innate immune cells of the brain, and neurons respond to alcohol, signaling through Toll-like receptors (TLRs), high-mobility group box 1 (HMGB1), miRNAs, pro-inflammatory cytokines and their associated receptors involved in signaling between microglia, other glia and neurons. Repeated cycles of alcohol and stress cause a progressive, persistent induction of HMGB1, miRNA and TLR receptors in brain that appear to underlie the progressive and persistent loss of behavioral control, increased impulsivity and anxiety, as well as craving, coupled with increasing ventral striatal responses that promote reward seeking behavior and increase risk of developing alcohol use disorders. Studies employing anti-oxidant, anti-inflammatory, anti-depressant, and innate immune antagonists further link innate immune gene expression to addiction-like behaviors. Innate immune molecules are novel targets for addiction and affective disorders therapies. This article is part of the Special Issue entitled "Alcoholism". Copyright © 2017 Elsevier Ltd. All rights reserved.

[Assessment of functional and dysfunctional impulsivity in substance-addicted patients by means of Dickman's Inventory].

PubMed

Pedrero Pérez, Eduardo J

2009-11-01

Impulsivity is a dispositional trait consistently linked to addiction. Nevertheless, Dickman proposed two different types of impulsivity, a functional variant and another, dysfunctional one. Almost all studies in addiction have exclusively explored the dysfunctional facet of impulsivity. The main purpose of this study was to check the applicability of the Dickman Impulsivity Inventory to explore both types of impulsivity in addicted individuals. We applied a Spanish version of the inventory and studied its psychometric properties. We found adequate internal consistency, construct validity and convergence of measures with related instruments, both in non-clinical (N = 398) and in treated substance-addicted (diacetylmorphine, cocaine, alcohol and cannabis; N = 140) samples. Addicted individuals did not differ from the non-clinical population in their functional impulsivity, but we found a great effect size (eta2p = 0.35) in the differences when exploring the dysfunctional type, with higher scores in addicts. Dysfunctional impulsivity was related to dysexecutive symptoms (r2 = 0.39), and personality traits such as Novelty Seeking (r2 = 0.57), but not with the Exploratory Excitability subdimension (r2 = 0.01), this latter being more closely related to functional impulsivity (r2 = 0.16). Data support the usefulness of this inventory to estimate types of impulsivity related to the prevention and treatment of addictive behaviors.

Characterization of Transporters in the Hepatic Uptake of TAK-475 M-I, a Squalene Synthase Inhibitor, in Rats and Humans.

PubMed

Ebihara, T; Takeuchi, T; Moriya, Y; Tagawa, Y; Kondo, T; Moriwaki, T; Asahi, S

2016-06-01

TAK-475 (lapaquistat acetate) is a squalene synthase inhibitor and M-I is a pharmacologically active metabolite of TAK-475. Preclinical pharmacokinetic studies have demonstrated that most of the dosed TAK-475 was hydrolyzed to M-I during the absorption process and the concentrations of M-I in the liver, the main organ of cholesterol biosynthesis, were much higher than those in the plasma after oral administration to rats. In the present study, the mechanism of the hepatic uptake of M-I was investigated.The uptake studies of (14)C-labeled M-I into rat and human hepatocytes indicated that the uptakes of M-I were concentrative, temperature-dependent and saturable in both species with Km values of 4.7 and 2.8 μmol/L, respectively. M-I uptake was also inhibited by cyclosporin A, an inhibitor for hepatic uptake transporters including organic anion transporting polypeptide (OATP). In the human hepatocytes, M-I uptake was hardly inhibited by estrone 3-sulfate as an inhibitor for OATP1B1, and most of the M-I uptake was Na(+)-independent. Uptake studies using human transporter-expressing cells revealed the saturable uptake of M-I for OATP1B3 with a Km of 2.13 μmol/L. No obvious uptake of M-I was observed in the OATP1B1-expressing cells.These results indicated that M-I was taken up into hepatocytes via transporters in both rats and humans. OATP1B3 would be mainly involved in the hepatic uptake of M-I in humans. These findings suggested that hepatic uptake transporters might contribute to the liver-selective inhibition of cholesterol synthesis by TAK-475. This is the first to clarify a carrier-mediated hepatic uptake mechanism for squalene synthase inhibitors. © Georg Thieme Verlag KG Stuttgart · New York.

Effects of myo-inositol plus alpha-lactalbumin in myo-inositol-resistant PCOS women.

PubMed

Montanino Oliva, Mario; Buonomo, Giovanna; Calcagno, Marco; Unfer, Vittorio

2018-05-10

Myo-inositol (MI), successfully used in polycystic ovary syndrome (PCOS), was administered with α-LA to exploit its action of favouring the passage of other molecules through biological barriers, and also considering its anti-inflammatory effect. PCOS patients, according to the Rotterdam ESHRE-ASRM criteria, with anovulation and infertility > 1 year, were included in this open and prospective study. The preliminary phase was aimed at determining a set of MI-resistant PCOS patients. This treatment involved 2 g MI, taken twice per day by oral route, for three months. The Homeostasis Model Assessment (HOMA) index and MI plasma levels were measured. In the main phase, previously selected MI-resistant patients received the same daily amount of MI plus 50 mg α-LA twice a day, for a further three months. Ovulation was assessed using ultrasound examination on days 12, 14 and 20 of the cycle. The HOMA index, lipid, hormone and MI plasma levels were detected at baseline and at the end of this phase. Thirty-seven anovulatory PCOS subjects were included in the study. Following MI treatment, 23 of the 37 women (62%) ovulated, while 14 (38%) were resistant and did not ovulate. In the latter group, MI plasma levels did not increase. These MI-resistant patients underwent treatment in the main phase of the study, receiving MI and α-LA. After this combined treatment, 12 (86%) of them ovulated. Their MI plasma levels were found to be significantly higher than at baseline; also, a hormone and lipid profile improvement was recorded. The combination of MI with α-LA allowed us to obtain significant progress in the treatment of PCOS MI-resistant patients. Therefore, this new formulation was able to re-establish ovulation, greatly increasing the chances of desired pregnancy. Clinical trial registration number: NCT03422289 ( ClinicalTrials.gov registry).

Frontal dysfunctions of impulse control - a systematic review in borderline personality disorder and attention-deficit/hyperactivity disorder.

PubMed

Sebastian, Alexandra; Jung, Patrick; Krause-Utz, Annegret; Lieb, Klaus; Schmahl, Christian; Tüscher, Oliver

2014-01-01

Disorders such as borderline personality disorder (BPD) or attention-deficit/hyperactivity disorder (ADHD) are characterized by impulsive behaviors. Impulsivity as used in clinical terms is very broadly defined and entails different categories including personality traits as well as different cognitive functions such as emotion regulation or interference resolution and impulse control. Impulse control as an executive function, however, is neither cognitively nor neurobehaviorally a unitary function. Recent findings from behavioral and cognitive neuroscience studies suggest related but dissociable components of impulse control along functional domains like selective attention, response selection, motivational control, and behavioral inhibition. In addition, behavioral and neural dissociations are seen for proactive vs. reactive inhibitory motor control. The prefrontal cortex with its sub-regions is the central structure in executing these impulse control functions. Based on these concepts of impulse control, neurobehavioral findings of studies in BPD and ADHD were reviewed and systematically compared. Overall, patients with BPD exhibited prefrontal dysfunctions across impulse control components rather in orbitofrontal, dorsomedial, and dorsolateral prefrontal regions, whereas patients with ADHD displayed disturbed activity mainly in ventrolateral and medial prefrontal regions. Prefrontal dysfunctions, however, varied depending on the impulse control component and from disorder to disorder. This suggests a dissociation of impulse control related frontal dysfunctions in BPD and ADHD, although only few studies are hitherto available to assess frontal dysfunctions along different impulse control components in direct comparison of these disorders. Yet, these findings might serve as a hypothesis for the future systematic assessment of impulse control components to understand differences and commonalities of prefrontal cortex dysfunction in impulsive disorders.

MicroRNAs as diagnostic and prognostic biomarkers in colorectal cancer

PubMed Central

Yi, Rui; Li, Yao; Wang, Fei-Liang; Miao, Gang; Qi, Ruo-Mei; Zhao, Yan-Yang

2016-01-01

MicroRNAs (miRNAs) are key regulators involved in various tumors. They regulate cell cycle, apoptosis and cancer stemness, metastasis and chemoresistance by controlling their target gene expressions. Here, we mainly discuss the potential uses of miRNAs in colorectal cancer (CRC) diagnosis. We also shed light on the important corresponding miRNA targets and on the major regulators of miRNAs. Furthermore, we discuss miRNA activity in assessing the prognosis and recurrence of CRC as well as in modulating responsiveness to chemotherapy. Based on the various pro-oncogenic/anti-oncogenic roles of miRNAs, the advantages of a therapeutic strategy based on the delivery of miRNA mimics are also mentioned. Together, miRNA seems to be an excellent tool for effectively monitoring and targeting CRC. PMID:27096028

The microRNAs involved in human myeloid differentiation and myelogenous/myeloblastic leukemia

PubMed Central

Wang, Xiao-Shuang; Zhang, Jun-Wu

2008-01-01

Abstract MicroRNAs (miRNAs) are endogenously expressed, functional RNAs that interact with native coding mRNAs to cleave mRNA or repress translation. Several miRNAs contribute to normal haematopoietic processes and some miRNAs act both as tumour suppressors and oncogenes in the pathology of haematological malignancies. While most effort is engaged in identifying and investigating the target genes of miRNAs, miRNA gene promoter methylation or transcriptional regulation is another important field of investigation, since these two main mechanisms can form a regulatory circuit. This review focuses on recent researches on miRNAs with important roles in myeloid cells. PMID:18554315

Effects of simulated microgravity on microRNA and mRNA expression profile of rat soleus

NASA Astrophysics Data System (ADS)

Dai, Zhongquan; Wu, Feng; Qu, Lina

Abstract Spaceflight induces muscle atrophy but mechanism is not well understood. Here, we quantified microRNAs (miRNAs) and mRNA shifts of rat soleus after 7, 14 and 28 days tail suspension (TS). Microarray data revealed that TS altered 23 miRNAs and 1313 mRNAs at least 2-fold change. QRT-PCR confirmed changes of miRNAs and mRNAs related to muscle atrophy. MiR-214, miR-486-5p and miR-320 family decreased, but Let-7e increased. Actn3 and myh4 displayed abundant upregulation and a3galt2 downregulated. Predicted targeted genes (whyz, ywhaz and SFRP2) of altered miRNAs decreased. Further analysis of gene functional annotation confirmed consistency of alteration profile between miRNAs and mRNA and enrichment of main clusters in regulation of muscle metabolism. Our results highlight the importance of miR-214, miR-486-5p, miR-320 and Let-7e in muscle atrophy process induced by microgravity.

High-throughput characterization of Echinococcus spp. metacestode miRNomes.

PubMed

Cucher, Marcela; Macchiaroli, Natalia; Kamenetzky, Laura; Maldonado, Lucas; Brehm, Klaus; Rosenzvit, Mara Cecilia

2015-03-01

Echinococcosis is a worldwide zoonosis of great public health concern, considered a neglected disease by the World Health Organisation. The cestode parasites Echinococcus granulosus sensu lato (s. l.) and Echinococcus multilocularis are the main aetiological agents. In the intermediate host, these parasites display particular developmental traits that lead to different patterns of disease progression. In an attempt to understand the causes of these differences, we focused on the analysis of microRNAs (miRNAs), small non-coding regulatory RNAs with major roles in development of animals and plants. In this work, we analysed the small RNA expression pattern of the metacestode, the stage of sanitary relevance, and provide a detailed description of Echinococcus miRNAs. Using high-throughput small RNA sequencing, we believe that we have carried out the first experimental identification of miRNAs in E. multilocularis and have expanded the Echinococcus miRNA catalogue to 38 miRNA genes, including one miRNA only present in E. granulosus s. l. Our findings show that although both species share the top five highest expressed miRNAs, 13 are differentially expressed, which could be related to developmental differences. We also provide evidence that uridylation is the main miRNA processing mechanism in Echinococcus spp. These results provide detailed information on Echinococcus miRNAs, which is the first step in understanding their role in parasite biology and disease establishment and/or progression, and their future potential use as drug or diagnostic targets. Copyright © 2015 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Intracellular and extracellular microRNA: An update on localization and biological role.

PubMed

Makarova, Julia A; Shkurnikov, Maxim U; Wicklein, Daniel; Lange, Tobias; Samatov, Timur R; Turchinovich, Andrey A; Tonevitsky, Alexander G

2016-11-01

MicroRNA (miRNA) is a class of small non-coding RNAs which mediate post-transcriptional gene silencing (PTGS) by sequence-specific inhibition of target mRNAs translation and/or lowering their half-lives in the cytoplasm. Together with their binding partners, Argonaute (AGO) proteins, miRNAs form cores of RNA-induced silencing complexes (RISC). Despite a substantial progress in understanding RISC structure, until recently little was known about its localization in the cell. This review is aimed to provide an overview of the emerging picture of miRNA and RISC localization and function both in the intracellular space and outside of the cell. In contrast to the common assumption that PTGS occurs in the cytoplasm, it was found to operate mainly on the membranes of the endoplasmic reticulum (ER). Besides ER membranes miRNAs were found in all main cellular compartments including nucleus, nucleolus and mitochondria where they regulate various processes including transcription, translation, alternative splicing and DNA repair. Moreover, a certain pool of miRNAs may not be associated with RISC and carry completely different functions. Finally, the discovery of cell-free miRNAs in all biological fluids suggests that miRNAs might also act as signaling molecules outside the cell, and may be utilized as biomarkers for a variety of diseases. In this review we discuss miRNA secretion mechanisms and possible pathways of cell-cell communication via miRNA-containing exosomes in vivo. Copyright © 2016 Elsevier GmbH. All rights reserved.

75 FR 45011 - MainStreet Savings Bank, FSB, Hastings, MI; Notice of Appointment of Receiver

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-30

... DEPARTMENT OF THE TREASURY Office of Thrift Supervision MainStreet Savings Bank, FSB, Hastings, MI... section 5(d)(2) of the Home Owners' Loan Act, the Office of Thrift Supervision has duly appointed the..., (OTS No. 00966) on July 16, 2010. Dated: July 23, 2010. By the Office of Thrift Supervision. Sandra E...

1. Photocopy of undated wash drawing. The largest building is ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. Photocopy of undated wash drawing. The largest building is the Hotel Williams. Next to it is the Williams House (Williams Hotel Annex), HABS No. MI-258 A. Below them are the log cabins built by the American Fur Company (from left to right): Log Building No. 1 (MI-258 C), Log Building No. 2 (MI-258 D), Log Building No. 3 (not documented), Log Building No. 4 (MI-258 E), and Log Building No. 5 (MI-258 F). (Williams Log House, MI-258 B, and Log Building No. 8, MI-258 G, are not shown). The drawing is in the collection of the Michigan Historical Commission. Although it does not have a date, it was painted in the early 20th century after the main building was constructed. - Hotel Williams, Murray Bay, Munising, Alger County, MI

Frontal Dysfunctions of Impulse Control – A Systematic Review in Borderline Personality Disorder and Attention-Deficit/Hyperactivity Disorder

PubMed Central

Sebastian, Alexandra; Jung, Patrick; Krause-Utz, Annegret; Lieb, Klaus; Schmahl, Christian; Tüscher, Oliver

2014-01-01

Disorders such as borderline personality disorder (BPD) or attention-deficit/hyperactivity disorder (ADHD) are characterized by impulsive behaviors. Impulsivity as used in clinical terms is very broadly defined and entails different categories including personality traits as well as different cognitive functions such as emotion regulation or interference resolution and impulse control. Impulse control as an executive function, however, is neither cognitively nor neurobehaviorally a unitary function. Recent findings from behavioral and cognitive neuroscience studies suggest related but dissociable components of impulse control along functional domains like selective attention, response selection, motivational control, and behavioral inhibition. In addition, behavioral and neural dissociations are seen for proactive vs. reactive inhibitory motor control. The prefrontal cortex with its sub-regions is the central structure in executing these impulse control functions. Based on these concepts of impulse control, neurobehavioral findings of studies in BPD and ADHD were reviewed and systematically compared. Overall, patients with BPD exhibited prefrontal dysfunctions across impulse control components rather in orbitofrontal, dorsomedial, and dorsolateral prefrontal regions, whereas patients with ADHD displayed disturbed activity mainly in ventrolateral and medial prefrontal regions. Prefrontal dysfunctions, however, varied depending on the impulse control component and from disorder to disorder. This suggests a dissociation of impulse control related frontal dysfunctions in BPD and ADHD, although only few studies are hitherto available to assess frontal dysfunctions along different impulse control components in direct comparison of these disorders. Yet, these findings might serve as a hypothesis for the future systematic assessment of impulse control components to understand differences and commonalities of prefrontal cortex dysfunction in impulsive disorders. PMID:25232313

Testing the Relations Between Impulsivity-Related Traits, Suicidality, and Nonsuicidal Self-Injury: A Test of the Incremental Validity of the UPPS Model

PubMed Central

Lynam, Donald R.; Miller, Joshua D.; Miller, Drew J.; Bornovalova, Marina A.; Lejuez, C. W.

2011-01-01

Borderline personality disorder (BPD) has received significant attention as a predictor of suicidal behavior (SB) and nonsuicidal self-injury (NSSI). Despite significant promise, trait impulsivity has received less attention. Understanding the relations between impulsivity and SB and NSSI is confounded, unfortunately, by the heterogeneous nature of impulsivity. This study examined the relations among 4 personality pathways to impulsive behavior studied via the UPPS model of impulsivity and SB and NSSI in a residential sample of drug abusers (N = 76). In this study, we tested whether these 4 impulsivity-related traits (i.e., Negative Urgency, Sensation Seeking, Lack of Premeditation, and Lack of Perseverance) provide incremental validity in the statistical prediction of SB and NSSI above and beyond BPD; they do. We also tested whether BPD symptoms provide incremental validity in the prediction of SB and NSSI above and beyond these impulsivity-related traits; they do not. In addition to the main effects of Lack of Premeditation and Negative Urgency, we found evidence of a robust interaction between these 2 personality traits. The current results argue strongly for the consideration of these 2 impulsivity-related domains—alone and in interaction—when attempting to understand and predict SB and NSSI. PMID:21833346

Testing the relations between impulsivity-related traits, suicidality, and nonsuicidal self-injury: a test of the incremental validity of the UPPS model.

PubMed

Lynam, Donald R; Miller, Joshua D; Miller, Drew J; Bornovalova, Marina A; Lejuez, C W

2011-04-01

Borderline personality disorder (BPD) has received significant attention as a predictor of suicidal behavior (SB) and nonsuicidal self-injury (NSSI). Despite significant promise, trait impulsivity has received less attention. Understanding the relations between impulsivity and SB and NSSI is confounded, unfortunately, by the heterogeneous nature of impulsivity. This study examined the relations among 4 personality pathways to impulsive behavior studied via the UPPS model of impulsivity and SB and NSSI in a residential sample of drug abusers (N = 76). In this study, we tested whether these 4 impulsivity-related traits (i.e., Negative Urgency, Sensation Seeking, Lack of Premeditation, and Lack of Perseverance) provide incremental validity in the statistical prediction of SB and NSSI above and beyond BPD; they do. We also tested whether BPD symptoms provide incremental validity in the prediction of SB and NSSI above and beyond these impulsivity-related traits; they do not. In addition to the main effects of Lack of Premeditation and Negative Urgency, we found evidence of a robust interaction between these 2 personality traits. The current results argue strongly for the consideration of these 2 impulsivity-related domains--alone and in interaction--when attempting to understand and predict SB and NSSI.

Microprocessor activity controls differential miRNA biogenesis In Vivo.

PubMed

Conrad, Thomas; Marsico, Annalisa; Gehre, Maja; Orom, Ulf Andersson

2014-10-23

In miRNA biogenesis, pri-miRNA transcripts are converted into pre-miRNA hairpins. The in vivo properties of this process remain enigmatic. Here, we determine in vivo transcriptome-wide pri-miRNA processing using next-generation sequencing of chromatin-associated pri-miRNAs. We identify a distinctive Microprocessor signature in the transcriptome profile from which efficiency of the endogenous processing event can be accurately quantified. This analysis reveals differential susceptibility to Microprocessor cleavage as a key regulatory step in miRNA biogenesis. Processing is highly variable among pri-miRNAs and a better predictor of miRNA abundance than primary transcription itself. Processing is also largely stable across three cell lines, suggesting a major contribution of sequence determinants. On the basis of differential processing efficiencies, we define functionality for short sequence features adjacent to the pre-miRNA hairpin. In conclusion, we identify Microprocessor as the main hub for diversified miRNA output and suggest a role for uncoupling miRNA biogenesis from host gene expression. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

The role of depression and anxiety in impulsive and obsessive-compulsive behaviors among anorexic and bulimic patients.

PubMed

Finzi-Dottan, Ricky; Zubery, Eynat

2009-01-01

Eating disorders are believed to range across a spectrum of varying degrees of obsessive-compulsive and impulsive behavior. Sixty anorexic (mean age = 19.8; sd = 5.9) and 109 bulimic (mean age = 26.9; sd = 11.3) female patients completed self-report questionnaires assessing obsessive-compulsiveness, impulsivity, depression and anxiety, as well as two eating disorder scales. Results yielded significantly higher levels of impulsivity and negative body image in the bulimic compared to the anorexic group. Regression analysis predicting impulsivity showed that bulimia and negative body image were the main contributors. Regression analysis for predicting obsessive-compulsive behavior suggested that depression and anxiety obscure the link between anorexia and obsessive-compulsive behavior, and a high BMI intensifies the association between anxiety and obsessive-compulsive behavior. The high rates of both impulsivity and obsessive-compulsiveness found in both groups, and their association with the severity of the eating disorder, may suggest that impulsivity and obsessive-compulsiveness are not mutually exclusive and can both be found among anorexic and bulimic patients.

Role of impulsivity and other personality dimensions in attempted suicide with self-poisoning among children and adolescents.

PubMed

Ghanem, Mohamed; Gamaluddin, Hany; Mansour, Mona; Samiee', Afaf Abdel; Shaker, Nermin Mahmoud; El Rafei, Heba

2013-01-01

The objective of this study was to clarify the role of impulsivity and personality dimensions in attempted suicide among youth. The study included 120 youths who attempted suicide and 100 matched controls. Attempters of suicide had higher total scores and subscales of impulsivity than controls. They had higher novelty seeking, harm avoidance, and reward dependence scores, lower scores on persistence, self-directedness, and cooperativeness. A total of 77.5% of suicide attempters had psychiatric disorders compared to 2% of controls. Main factors predicting the occurrence of suicidal attempts were the presence of psychiatric disorder, impulsivity, stressful life events, and high reward dependence of suicide attempters. The study supports that impulsivity and personality traits play an important role in youth suicide independently or as a part of other interacting factors.

MicroRNA-mediated responses to long-term magnesium-deficiency in Citrus sinensis roots revealed by Illumina sequencing.

PubMed

Liang, Wei-Wei; Huang, Jing-Hao; Li, Chun-Ping; Yang, Lin-Tong; Ye, Xin; Lin, Dan; Chen, Li-Song

2017-08-24

Magnesium (Mg)-deficiency occurs most frequently in strongly acidic, sandy soils. Citrus are grown mainly on acidic and strong acidic soils. Mg-deficiency causes poor fruit quality and low fruit yield in some Citrus orchards. For the first time, we investigated Mg-deficiency-responsive miRNAs in 'Xuegan' (Citrus sinensis) roots using Illumina sequencing in order to obtain some miRNAs presumably responsible for Citrus Mg-deficiency tolerance. We obtained 101 (69) miRNAs with increased (decreased) expression from Mg-starved roots. Our results suggested that the adaptation of Citrus roots to Mg-deficiency was related to the several aspects: (a) inhibiting root respiration and related gene expression via inducing miR158 and miR2919; (b) enhancing antioxidant system by down-regulating related miRNAs (miR780, miR6190, miR1044, miR5261 and miR1151) and the adaptation to low-phosphorus (miR6190); (c) activating transport-related genes by altering the expression of miR6190, miR6485, miR1044, miR5029 and miR3437; (d) elevating protein ubiquitination due to decreased expression levels of miR1044, miR5261, miR1151 and miR5029; (e) maintaining root growth by regulating miR5261, miR6485 and miR158 expression; and (f) triggering DNA repair (transcription regulation) by regulating miR5176 and miR6485 (miR6028, miR6190, miR6485, miR5621, miR160 and miR7708) expression. Mg-deficiency-responsive miRNAs involved in root signal transduction also had functions in Citrus Mg-deficiency tolerance. We obtained several novel Mg-deficiency-responsive miRNAs (i.e., miR5261, miR158, miR6190, miR6485, miR1151 and miR1044) possibly contributing to Mg-deficiency tolerance. These results revealed some novel clues on the miRNA-mediated adaptation to nutrient deficiencies in higher plants.

Progesterone attenuates impulsive action in a Go/No-Go task for sucrose pellets in female and male rats

PubMed Central

Swalve, Natashia; Smethells, John R.; Carroll, Marilyn E.

2016-01-01

Impulsivity, or a tendency to act without anticipation of future consequences, is associated with drug abuse. Impulsivity is typically separated into two main measures, impulsive action and impulsive choice. Given the association of impulsivity and drug abuse, treatments that reduce impulsivity have been proposed as an effective method for countering drug addiction. Progesterone has emerged as a promising treatment, as it is associated with decreased addiction-related behaviors and impulsive action. The goal of the present study was to determine the effects of progesterone (PRO) on impulsive action for food: a Go/No-Go task. Female and male rats responded for sucrose pellets during a Go component when lever pressing was reinforced on a variable-interval 30-s schedule. During the alternate No-Go component, withholding a lever press was reinforced on a differential reinforcement of other (DRO) behavior 30-s schedule, where a lever press reset the DRO timer. Impulsive action was operationally defined as the inability to withhold a response during the No-Go component (i.e. the number of DRO resets). Once Go/No-Go behavior was stable, responding between rats treated with PRO (0.5 mg/kg) or vehicle was examined. Progesterone significantly decreased the total number of DRO resets in both males and females, but it did not affect VI responding for sucrose pellets. This suggests that PRO decreases motor impulsivity for sucrose pellets without affecting motivation for food. Thus, PRO may reduce motor impulsivity, a behavior underlying drug addiction. PMID:27497836

Screening of Critical Genes and MicroRNAs in Blood Samples of Patients with Ruptured Intracranial Aneurysms by Bioinformatic Analysis of Gene Expression Data.

PubMed

Bo, Lijuan; Wei, Bo; Wang, Zhanfeng; Kong, Daliang; Gao, Zheng; Miao, Zhuang

2017-09-20

BACKGROUND This study aimed to identify more potential genes and miRNAs associated with the pathogenesis of intracranial aneurysms (IAs). MATERIAL AND METHODS The dataset of GSE36791 (accession number) was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened for in the blood samples from patients with ruptured IAs and controls, followed by functional and pathway enrichment analyses. In addition, gene co-expression network was constructed and significant modules were extracted from the network by WGCNA R package. Screening for miRNAs that could regulate DEGs in the modules was performed and an analysis of regulatory relationships was conducted. RESULTS A total of 304 DEGs (167 up-regulated and 137 down-regulated genes) were screened for in blood samples from patients with ruptured IAs compared with those from controls. Functional enrichment analysis showed that the up-regulated genes were mainly associated with immune response and the down-regulated DEGs were mainly concerned with the structure of ribosome and translation. Besides, six functional modules were significantly identified, including four modules enriched by up-regulated genes and two modules enriched by down-regulated genes. Thereinto, the blue, yellow, and turquoise modules of up-regulated genes were all linked with immune response. Additionally, 16 miRNAs were predicted to regulate DEGs in the three modules associated with immune response, such as hsa-miR-1304, hsa-miR-33b, hsa-miR-125b, and hsa-miR-125a-5p. CONCLUSIONS Several genes and miRNAs (such as miR-1304, miR-33b, IRS2 and KCNJ2) may take part in the pathogenesis of IAs.

Alteration of the microRNA network during the progression of Alzheimer's disease

PubMed Central

Lau, Pierre; Bossers, Koen; Janky, Rekin's; Salta, Evgenia; Frigerio, Carlo Sala; Barbash, Shahar; Rothman, Roy; Sierksma, Annerieke S R; Thathiah, Amantha; Greenberg, David; Papadopoulou, Aikaterini S; Achsel, Tilmann; Ayoubi, Torik; Soreq, Hermona; Verhaagen, Joost; Swaab, Dick F; Aerts, Stein; De Strooper, Bart

2013-01-01

An overview of miRNAs altered in Alzheimer's disease (AD) was established by profiling the hippocampus of a cohort of 41 late-onset AD (LOAD) patients and 23 controls, showing deregulation of 35 miRNAs. Profiling of miRNAs in the prefrontal cortex of a second independent cohort of 49 patients grouped by Braak stages revealed 41 deregulated miRNAs. We focused on miR-132-3p which is strongly altered in both brain areas. Downregulation of this miRNA occurs already at Braak stages III and IV, before loss of neuron-specific miRNAs. Next-generation sequencing confirmed a strong decrease of miR-132-3p and of three family-related miRNAs encoded by the same miRNA cluster on chromosome 17. Deregulation of miR-132-3p in AD brain appears to occur mainly in neurons displaying Tau hyper-phosphorylation. We provide evidence that miR-132-3p may contribute to disease progression through aberrant regulation of mRNA targets in the Tau network. The transcription factor (TF) FOXO1a appears to be a key target of miR-132-3p in this pathway. PMID:24014289

Tocopherol levels in different mango varieties correlate with MiHPPD expression and its over-expression elevates tocopherols in transgenic Arabidopsis and tomato.

PubMed

Singh, Rajesh K; Chaurasia, Akhilesh K; Bari, Rupesh; Sane, Vidhu A

2017-10-01

Mango fruit tocopherol levels vary in different varieties during ripening. This study shows that tocopherol accumulation is highly correlated with its p-hydroxyphenyl pyruvate dioxygenase ( MiHPPD ) gene expression during ripening. MiHPPD transcript is ethylene induced and differentially expressed in four mango varieties used in this study. Higher/lower accumulation of tocopherol (mainly α-tocopherol) was achieved by heterologous expression of MiHPPD in Arabidopsis and tomato. The results suggest that tocopherol accumulation in mango fruit is correlated to MiHPPD gene expression. Over-expression of MiHPPD gene channelizes the flux towards tocophreol biosynthesis and could be used as a potential tool for metabolic engineering.

Human miRNome profiling in colorectal cancer and liver metastasis development

PubMed Central

Perilli, Lisa; Pizzini, Silvia; Bisognin, Andrea; Mandruzzato, Susanna; Biasiolo, Marta; Facciolli, Arianna; Rossi, Elisabetta; Esposito, Giovanni; Rugge, Massimo; Pilati, Pierluigi; Mocellin, Simone; Nitti, Donato; Bortoluzzi, Stefania; Zanovello, Paola

2014-01-01

Qualitative alterations or abnormal expression of microRNAs (miRNAs) in colorectal cancer has mainly been demonstrated in primary tumors. The miRNA expression profiles in 78 samples from 46 patients were analyzed to identify changes in miRNA expression level among normal colon mucosa, primary tumor and liver metastasis samples. Using this dataset, we describe the interplay of miRNA groups in regulating pathways that are important for tumor development. Here we describe in details the contents and quality controls for the miRNA expression and clinical data associated with the study published by Pizzini and colleagues in the BMC Genomics in 2013 (Pizzini et al., 2013). Data are deposited in GEO database as GSE35834 series. PMID:26484092

MiR-200c Inhibits the Tumor Progression of Glioma via Targeting Moesin

PubMed Central

Qin, Yuanyuan; Chen, Weilong; Liu, Bingjie; Zhou, Lei; Deng, Lu; Niu, Wanxiang; Bao, Dejun; Cheng, Chuandong; Li, Dongxue; Liu, Suling; Niu, Chaoshi

2017-01-01

We attempt to demonstrate the regulatory role of miR-200c in glioma progression and its mechanisms behind. Here, we show that miR-200c expression was significantly reduced in the glioma tissues compared to paratumor tissues, especially in malignant glioma. Exogenous overexpression of miR-200c inhibited the proliferation and invasion of glioma cells. In addition, the in vivo mouse xenograft model showed that miR-200c inhibited glioma growth and liver metastasis, which is mainly regulated by targeting moesin (MSN). We demonstrated that the expression of MSN in glioma specimens were negatively correlated with miR-200c expression, and MSN overexpression rescued the phenotype about cell proliferation and invasion induced by miR-200c. Moreover, knockdown of MSN was able to mimic the effects induced by miR-200c in glioma cells. These results indicate that miR-200c plays an important role in the regulation of glioma through targeting MSN. PMID:28529643

The NuMI neutrino beam

NASA Astrophysics Data System (ADS)

Adamson, P.; Anderson, K.; Andrews, M.; Andrews, R.; Anghel, I.; Augustine, D.; Aurisano, A.; Avvakumov, S.; Ayres, D. S.; Baller, B.; Barish, B.; Barr, G.; Barrett, W. L.; Bernstein, R. H.; Biggs, J.; Bishai, M.; Blake, A.; Bocean, V.; Bock, G. J.; Boehnlein, D. J.; Bogert, D.; Bourkland, K.; Cao, S. V.; Castromonte, C. M.; Childress, S.; Choudhary, B. C.; Coelho, J. A. B.; Cobb, J. H.; Corwin, L.; Crane, D.; Cravens, J. P.; Cronin-Hennessy, D.; Ducar, R. J.; De Jong, J. K.; Devan, A. V.; Devenish, N. E.; Diwan, M. V.; Erwin, A. R.; Escobar, C. O.; Evans, J. J.; Falk, E.; Feldman, G. J.; Fields, T. H.; Ford, R.; Frohne, M. V.; Gallagher, H. R.; Garkusha, V.; Gomes, R. A.; Goodman, M. C.; Gouffon, P.; Graf, N.; Gran, R.; Grossman, N.; Grzelak, K.; Habig, A.; Hahn, S. R.; Harding, D.; Harris, D.; Harris, P. G.; Hartnell, J.; Hatcher, R.; Hays, S.; Heller, K.; Holin, A.; Huang, J.; Hylen, J.; Ibrahim, A.; Indurthy, D.; Irwin, G. M.; Isvan, Z.; Jaffe, D. E.; James, C.; Jensen, D.; Johnstone, J.; Kafka, T.; Kasahara, S. M. S.; Koizumi, G.; Kopp, S.; Kordosky, M.; Kreymer, A.; Lang, K.; Laughton, C.; Lefeuvre, G.; Ling, J.; Litchfield, P. J.; Loiacono, L.; Lucas, P.; Mann, W. A.; Marchionni, A.; Marshak, M. L.; Mayer, N.; McGivern, C.; Medeiros, M. M.; Mehdiyev, R.; Meier, J. R.; Messier, M. D.; Michael, D. G.; Milburn, R. H.; Miller, J. L.; Miller, W. H.; Mishra, S. R.; Moed Sher, S.; Moore, C. D.; Morfín, J.; Mualem, L.; Mufson, S.; Murgia, S.; Murtagh, M.; Musser, J.; Naples, D.; Nelson, J. K.; Newman, H. B.; Nichol, R. J.; Nowak, J. A.; O`Connor, J.; Oliver, W. P.; Olsen, M.; Orchanian, M.; Osprey, S.; Pahlka, R. B.; Paley, J.; Para, A.; Patterson, R. B.; Patzak, T.; Pavlović, Ž.; Pawloski, G.; Perch, A.; Peterson, E. A.; Petyt, D. A.; Pfützner, M. M.; Phan-Budd, S.; Plunkett, R. K.; Poonthottathil, N.; Prieto, P.; Pushka, D.; Qiu, X.; Radovic, A.; Rameika, R. A.; Ratchford, J.; Rebel, B.; Reilly, R.; Rosenfeld, C.; Rubin, H. A.; Ruddick, K.; Sanchez, M. C.; Saoulidou, N.; Sauer, L.; Schneps, J.; Schoo, D.; Schreckenberger, A.; Schreiner, P.; Shanahan, P.; Sharma, R.; Smart, W.; Smith, C.; Sousa, A.; Stefanik, A.; Tagg, N.; Talaga, R. L.; Tassotto, G.; Thomas, J.; Thompson, J.; Thomson, M. A.; Tian, X.; Timmons, A.; Tinsley, D.; Tognini, S. C.; Toner, R.; Torretta, D.; Trostin, I.; Tzanakos, G.; Urheim, J.; Vahle, P.; Vaziri, K.; Villegas, E.; Viren, B.; Vogel, G.; Webber, R. C.; Weber, A.; Webb, R. C.; Wehmann, A.; White, C.; Whitehead, L.; Whitehead, L. H.; Wojcicki, S. G.; Wong-Squires, M. L.; Yang, T.; Yumiceva, F. X.; Zarucheisky, V.; Zwaska, R.

2016-01-01

This paper describes the hardware and operations of the Neutrinos at the Main Injector (NuMI) beam at Fermilab. It elaborates on the design considerations for the beam as a whole and for individual elements. The most important design details of individual components are described. Beam monitoring systems and procedures, including the tuning and alignment of the beam and NuMI long-term performance, are also discussed.

Impulse-induced localized control of chaos in starlike networks.

PubMed

Chacón, Ricardo; Palmero, Faustino; Cuevas-Maraver, Jesús

2016-06-01

Locally decreasing the impulse transmitted by periodic pulses is shown to be a reliable method of taming chaos in starlike networks of dissipative nonlinear oscillators, leading to both synchronous periodic states and equilibria (oscillation death). Specifically, the paradigmatic model of damped kicked rotators is studied in which it is assumed that when the rotators are driven synchronously, i.e., all driving pulses transmit the same impulse, the networks display chaotic dynamics. It is found that the taming effect of decreasing the impulse transmitted by the pulses acting on particular nodes strongly depends on their number and degree of connectivity. A theoretical analysis is given explaining the basic physical mechanism as well as the main features of the chaos-control scenario.

Characteristics of individuals who make impulsive suicide attempts.

PubMed

Spokas, Megan; Wenzel, Amy; Brown, Gregory K; Beck, Aaron T

2012-02-01

Previous research has identified only a few variables that have been associated with making an impulsive suicide attempt. The aim of the current study was to compare individuals who made an impulsive suicide attempt with those who made a premeditated attempt on both previously examined and novel characteristics. Participants were classified as making an impulsive or premeditated attempt based on the Suicide Intent Scale (Beck et al., 1974a) and were compared on a number of characteristics relevant to suicidality, psychiatric history, and demographics. Individuals who made an impulsive attempt expected that their attempts would be less lethal; yet the actual lethality of both groups' attempts was similar. Those who made an impulsive attempt were less depressed and hopeless than those who made a premeditated attempt. Participants who made an impulsive attempt were less likely to report a history of childhood sexual abuse and more likely to be diagnosed with an alcohol use disorder than those who made a premeditated attempt. Although the sample size was adequate for bivariate statistics, future studies using larger sample sizes will allow for multivariate analyses of characteristics that differentiate individuals who make impulsive and premeditated attempts. Clinicians should not minimize the significance of impulsive attempts, as they are associated with a similar level of lethality as premeditated attempts. Focusing mainly on depression and hopelessness as indicators of suicide risk has the potential to under-identify those who are at risk for making impulsive attempts. Copyright © 2011 Elsevier B.V. All rights reserved.

Differential Sensitivity of Target Genes to Translational Repression by miR-17~92

PubMed Central

Jin, Hyun Yong; Oda, Hiroyo; Chen, Pengda; Kang, Seung Goo; Valentine, Elizabeth; Liao, Lujian; Zhang, Yaoyang; Gonzalez-Martin, Alicia; Shepherd, Jovan; Head, Steven R.; Kim, Pyeung-Hyeun; Fu, Guo; Liu, Wen-Hsien; Han, Jiahuai

2017-01-01

MicroRNAs (miRNAs) are thought to exert their functions by modulating the expression of hundreds of target genes and each to a small degree, but it remains unclear how small changes in hundreds of target genes are translated into the specific function of a miRNA. Here, we conducted an integrated analysis of transcriptome and translatome of primary B cells from mutant mice expressing miR-17~92 at three different levels to address this issue. We found that target genes exhibit differential sensitivity to miRNA suppression and that only a small fraction of target genes are actually suppressed by a given concentration of miRNA under physiological conditions. Transgenic expression and deletion of the same miRNA gene regulate largely distinct sets of target genes. miR-17~92 controls target gene expression mainly through translational repression and 5’UTR plays an important role in regulating target gene sensitivity to miRNA suppression. These findings provide molecular insights into a model in which miRNAs exert their specific functions through a small number of key target genes. PMID:28241004

Higher Impulsivity As a Distinctive Trait of Severe Cocaine Addiction among Individuals Treated for Cocaine or Alcohol Use Disorders.

PubMed

García-Marchena, Nuria; Ladrón de Guevara-Miranda, David; Pedraz, María; Araos, Pedro Fernando; Rubio, Gabriel; Ruiz, Juan Jesús; Pavón, Francisco Javier; Serrano, Antonia; Castilla-Ortega, Estela; Santín, Luis J; Rodríguez de Fonseca, Fernando

2018-01-01

Despite alcohol being the most often used addictive substance among addicted patients, use of other substances such as cocaine has increased over recent years, and the combination of both drugs aggravates health impairment and complicates clinical assessment. The aim of this study is to identify and characterize heterogeneous subgroups of cocaine- and alcohol-addicted patients with common characteristics based on substance use disorders, psychiatric comorbidity and impulsivity. A total of 214 subjects with cocaine and/or alcohol use disorders were recruited from outpatient treatment programs and clinically assessed. A latent class analysis was used to establish phenotypic categories according to diagnosis of cocaine and alcohol use disorders, mental disorders, and impulsivity scores. Relevant variables were examined in the latent classes (LCs) using correlation and analyses of variance and covariance. Four LCs of addicted patients were identified: Class 1 (45.3%) formed by alcohol-dependent patients exhibiting lifetime mood disorder diagnosis and mild impulsivity; Class 2 (14%) formed mainly by lifetime cocaine use disorder patients with low probability of comorbid mental disorders and mild impulsivity; Class 3 (10.7%) formed by cocaine use disorder patients with elevated probability to course with lifetime anxiety, early and personality disorders, and greater impulsivity scores; and Class 4 (29.9%) formed mainly by patients with alcohol and cocaine use disorders, with elevated probability in early and personality disorders and elevated impulsivity. Furthermore, there were significant differences among classes in terms of Diagnostic and Statistical Manual of Mental Disorders-4th Edition-Text Revision criteria for abuse and dependence: Class 3 showed more criteria for cocaine use disorders than other classes, while Class 1 and Class 4 showed more criteria for alcohol use disorders. Cocaine- and alcohol-addicted patients who were grouped according to diagnosis of substance use disorders, psychiatric comorbidity, and impulsivity show different clinical and sociodemographic variables. Whereas mood and anxiety disorders are more prevalent in alcohol-addicted patients, personality disorders are associated with cocaine use disorders and diagnosis of comorbid substance use disorders. Notably, increased impulsivity is a distinctive characteristic of patients with severe cocaine use disorder and comorbid personality disorders. Psychiatric disorders and impulsivity should be considered for improving the stratification of addicted patients with shared clinical and sociodemographic characteristics to select more appropriate treatments.

75 FR 5967 - Procurement List; Additions and Deletions

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-05

...., Fresno, CA 3971 RESEARCH PARK DRIVE, ANN ARBOR, MI 22600 HALL ROAD, CLINTON TOWNSHIP, MI 477 MICHIGAN AVE... COUNTRY CLUB RD, EUGENE, OR GUS J. SOLOMON CTHSE: 620 SW MAIN ST, PORTLAND, OR E.GREEN--W.WYATT FB: 1220...

Alteration of the microRNA network during the progression of Alzheimer's disease.

PubMed

Lau, Pierre; Bossers, Koen; Janky, Rekin's; Salta, Evgenia; Frigerio, Carlo Sala; Barbash, Shahar; Rothman, Roy; Sierksma, Annerieke S R; Thathiah, Amantha; Greenberg, David; Papadopoulou, Aikaterini S; Achsel, Tilmann; Ayoubi, Torik; Soreq, Hermona; Verhaagen, Joost; Swaab, Dick F; Aerts, Stein; De Strooper, Bart

2013-10-01

An overview of miRNAs altered in Alzheimer's disease (AD) was established by profiling the hippocampus of a cohort of 41 late-onset AD (LOAD) patients and 23 controls, showing deregulation of 35 miRNAs. Profiling of miRNAs in the prefrontal cortex of a second independent cohort of 49 patients grouped by Braak stages revealed 41 deregulated miRNAs. We focused on miR-132-3p which is strongly altered in both brain areas. Downregulation of this miRNA occurs already at Braak stages III and IV, before loss of neuron-specific miRNAs. Next-generation sequencing confirmed a strong decrease of miR-132-3p and of three family-related miRNAs encoded by the same miRNA cluster on chromosome 17. Deregulation of miR-132-3p in AD brain appears to occur mainly in neurons displaying Tau hyper-phosphorylation. We provide evidence that miR-132-3p may contribute to disease progression through aberrant regulation of mRNA targets in the Tau network. The transcription factor (TF) FOXO1a appears to be a key target of miR-132-3p in this pathway. © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

The evolution of microRNAs in plants

PubMed Central

Cui, Jie; You, Chenjiang; Chen, Xuemei

2016-01-01

MicroRNAs (miRNAs) are a central player in post-transcriptional regulation of gene expression and are involved in numerous biological processes in eukaryotes. Knowledge of the origins and divergence of miRNAs paves the way for a better understanding of the complexity of the regulatory networks that they participate in. The biogenesis, degradation, and regulatory activities of miRNAs are relatively better understood, but the evolutionary history of miRNAs still needs more exploration. Inverted duplication of target genes, random hairpin sequences and small transposable elements constitute three main models that explain the origination of miRNA genes (MIR). Both inter- and intra-species divergence of miRNAs exhibits functional adaptation and adaptation to changing environments in evolution. Here we summarize recent progress in studies on the evolution of MIR and related genes. PMID:27886593

MiRNAs in bone diseases.

PubMed

Moore, Benjamin T; Xiao, Peng

2013-01-01

MicroRNAs (miRNAs), which mainly inhibit protein expression by targeting the 3'UTR (untranslated region) of mRNAs, are known to play various roles in the pathogenesis of many different types of diseases. Specifically, in bone diseases, recent emphasis has been placed on the involvement of miRNAs in the differentiation and proliferation of bone and cartilage cells, particularly with regards to how these mechanisms contribute to bone homeostasis. In this review, we summarize miRNAs that are important in the differentiation and proliferation of bone cells, and specific miRNAs associated with bone diseases, such as osteoporosis, osteoarthritis and rheumatoid arthritis. This review also provides the perspective that miRNA studies will identify not only new mechanisms in basic bone research, but also potential novel diagnostic biomarkers and drug targets for bone diseases.

The NuMI neutrino beam

DOE PAGES

Adamson, P.; Anderson, K.; Andrews, M.; ...

2015-10-20

Our paper describes the hardware and operations of the Neutrinos at the Main Injector (NuMI) beam at Fermilab. It elaborates on the design considerations for the beam as a whole and for individual elements. The most important part of our design details pertaining to individual components is described. Beam monitoring systems and procedures, including the tuning and alignment of the beam and NuMI long-term performance, are also discussed.

Modulation instability in high power laser amplifiers.

PubMed

Rubenchik, Alexander M; Turitsyn, Sergey K; Fedoruk, Michail P

2010-01-18

The modulation instability (MI) is one of the main factors responsible for the degradation of beam quality in high-power laser systems. The so-called B-integral restriction is commonly used as the criteria for MI control in passive optics devices. For amplifiers the adiabatic model, assuming locally the Bespalov-Talanov expression for MI growth, is commonly used to estimate the destructive impact of the instability. We present here the exact solution of MI development in amplifiers. We determine the parameters which control the effect of MI in amplifiers and calculate the MI growth rate as a function of those parameters. The safety range of operational parameters is presented. The results of the exact calculations are compared with the adiabatic model, and the range of validity of the latest is determined. We demonstrate that for practical situations the adiabatic approximation noticeably overestimates MI. The additional margin of laser system design is quantified.

The pro-differentiating role of miR-124: indicating the road to become a neuron.

PubMed

Maiorano, Nicola Antonio; Mallamaci, Antonello

2010-01-01

miRNAs are essential post-transcriptional modulators affecting cell identity and fate, with a central role in cellular and developmental processes. The brain-enriched neuronal specific miRNAs-124 has been identified as a promoter of neuronogenesis in various conditions, in vitro and in vivo, with a potential role in regulating also activities of post-mitotic neurons, such as synaptic plasticity and memory formation. In this point of view, we recapitulate the main experimental findings substantiating the positive correlation between miR-124 expression and neuronogenesis progression. Then, we describe the impact of miR-124 on the molecular network driving the profound changes which take place in differentiating neuronal cells. Finally, we consider the possibility of a post-transcriptional modulation of miR-124 biogenesis, which may finely regulate--in turn--the activities of miR-124 in neural precursor cells.

High-throughput identification of miRNAs of Taenia ovis, a cestode threatening sheep industry.

PubMed

Zheng, Yadong

2017-07-01

Taenia ovis is a tapeworm that is mainly transmitted between dogs and sheep or goats and has an adverse effect on sheep industry. miRNAs are short regulatory non-coding RNAs, involved in parasite development and growth as well as parasite infection. The miRNA profile of T. ovis remains to be established. Herein, 33 known miRNAs belonging to 23 different families were identified in T. ovis metacestodes using deep sequencing approach. Of them, expression of some miRNAs such as tov-miR-10 and -let-7 was absolutely predominant. Moreover, comparative analysis revealed the presence of a miR-71/2b/2c cluster in T. ovis, which was also completely conserved in other 6 cestodes. The study provides rich data for further understandings of T. ovis biology. Copyright © 2017 Elsevier B.V. All rights reserved.

RNA sequencing reveals significant miRNAs in Atypical endometrial hyperplasia.

PubMed

Tang, Shiqian; Dai, Yinmei

2018-06-01

In this paper, we aimed to investigate the miRNAs that played a regulatory role in the development of atypical endometrial hyperplasia (AEH). RNA sequencing was performed for endometrial tissues from 3 AEH patients and 3 endometrial normal hyperplasia patients. RNA sequencing data were processed and differentially expressed (DE) miRNAs were identified between AEH and controls. The target genes for DE miRNAs were identified and mapped to the protein-protein interaction (PPI) network. The miRNA related functions were predicted and miRNA-disease gene network was constructed. Total 18 DE miRNAs were overlapped in three sample groups, among which hsa-miR-577, hsa-miR-182-5p and hsa-miR-183-5p were top three miRNAs that targeting largest number of genes. Function analysis showed that the 18 overlapped miRNAs mainly related with cancer and signaling transduction related pathways. PPI network showed that total 12 genes were among top 20 genes based on three network topological features including BCL2, UMPS, MAPK13, PRKCB, CREB1, IGF1, SP1, SMAD3, IGF1R, NOTCH2, WNT5A, TK2. Top 10 miRNAs in miRNA-disease gene network were identified such as hsa-miR-577 (degree = 17), hsa-miR-182-5p (degree = 16) and hsa-miR-3609 (degree = 13). hsa-miR-577 and hsa-miR-182-5p may play regulatory role in AEH through AMPK signal pathway and Wnt signaling pathway. Copyright © 2018 Elsevier B.V. All rights reserved.

Suicide Risk Associated with Experience of Violence and Impulsivity in Alcohol Dependent Patients.

PubMed

Khemiri, Lotfi; Jokinen, Jussi; Runeson, Bo; Jayaram-Lindström, Nitya

2016-01-19

Alcohol dependence (AD) and aggression-impulsivity are both associated with increased suicide risk. There is a need to evaluate clinical tools in order to improve suicide risk assessment of AD patients. The present study consisted of 95 individuals with a diagnosis of AD, consecutively admitted for addiction treatment, compared with 95 healthy controls. Suicidal risk was assessed together with exposure of violence and impulsivity. AD patients reported significantly higher rates of exposure to violence in childhood, as measured by the Karolinska Interpersonal Violence Scale (KIVS), compared to HC. Within the AD group, individuals with history of suicidal ideation and suicidal behavior reported higher levels of violence experience compared to AD individuals without such history. AD patients with previous suicidal ideation scored higher on self-reported impulsivity as assessed by the Barratt Impulsivity Scale (BIS). Our main finding was that experience of trauma and expression of violent behavior, coupled with increased impulsivity are associated with an elevated suicide risk in AD patients. Future longitudinal studies assessing these traits are needed to evaluate their potential role in identifying AD patients at risk of future suicide.

Suicide Risk Associated with Experience of Violence and Impulsivity in Alcohol Dependent Patients

PubMed Central

Khemiri, Lotfi; Jokinen, Jussi; Runeson, Bo; Jayaram-Lindström, Nitya

2016-01-01

Alcohol dependence (AD) and aggression-impulsivity are both associated with increased suicide risk. There is a need to evaluate clinical tools in order to improve suicide risk assessment of AD patients. The present study consisted of 95 individuals with a diagnosis of AD, consecutively admitted for addiction treatment, compared with 95 healthy controls. Suicidal risk was assessed together with exposure of violence and impulsivity. AD patients reported significantly higher rates of exposure to violence in childhood, as measured by the Karolinska Interpersonal Violence Scale (KIVS), compared to HC. Within the AD group, individuals with history of suicidal ideation and suicidal behavior reported higher levels of violence experience compared to AD individuals without such history. AD patients with previous suicidal ideation scored higher on self-reported impulsivity as assessed by the Barratt Impulsivity Scale (BIS). Our main finding was that experience of trauma and expression of violent behavior, coupled with increased impulsivity are associated with an elevated suicide risk in AD patients. Future longitudinal studies assessing these traits are needed to evaluate their potential role in identifying AD patients at risk of future suicide. PMID:26784730

A prospective cohort study on sustained effects of low-dose ecstasy use on the brain in new ecstasy users.

PubMed

de Win, Maartje M L; Reneman, Liesbeth; Jager, Gerry; Vlieger, Erik-Jan P; Olabarriaga, Sílvia D; Lavini, Cristina; Bisschops, Ivo; Majoie, Charles B L M; Booij, Jan; den Heeten, Gerard J; van den Brink, Wim

2007-02-01

It is debated whether ecstasy use has neurotoxic effects on the human brain and what the effects are of a low dose of ecstasy use. We prospectively studied sustained effects (>2 weeks abstinence) of a low dose of ecstasy on the brain in ecstasy-naive volunteers using a combination of advanced MR techniques and self-report questionnaires on psychopathology as part of the NeXT (Netherlands XTC Toxicity) study. Outcomes of proton magnetic resonance spectroscopy (1H-MRS), diffusion tensor imaging (DTI), perfusion-weighted imaging (PWI), and questionnaires on depression, impulsivity, and sensation seeking were compared in 30 subjects (12M, 21.8+/-3.1 years) in two sessions before and after first ecstasy use (1.8+/-1.3 tablets). Interval between baseline and follow-up was on average 8.1+/-6.5 months and time between last ecstasy use and follow-up was 7.7+/-4.4 weeks. Using 1H-MRS, no significant changes were observed in metabolite concentrations of N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), and creatine (Cr), nor in ratios of NAA, Cho, and mI relative to Cr. However, ecstasy use was followed by a sustained 0.9% increase in fractional anisotropy (FA) in frontoparietal white matter, a 3.4% decrease in apparent diffusion (ADC) in the thalamus and a sustained decrease in relative regional cerebral blood volume (rrCBV) in the thalamus (-6.2%), dorsolateral frontal cortex (-4.0%), and superior parietal cortex (-3.0%) (all significant at p<0.05, paired t-tests). After correction for multiple comparisons, only the rrCBV decrease in the dorsolateral frontal cortex remained significant. We also observed increased impulsivity (+3.7% on the Barratt Impulsiveness Scale) and decreased depression (-28.0% on the Beck Depression Inventory) in novel ecstasy users, although effect sizes were limited and clinical relevance questionable. As no indications were found for structural neuronal damage with the currently used techniques, our data do not support the concern that incidental ecstasy use leads to extensive axonal damage. However, sustained decreases in rrCBV and ADC values may indicate that even low ecstasy doses can induce prolonged vasoconstriction in some brain areas, although it is not known whether this effect is permanent. Additional studies are needed to replicate these findings.

MINOS Experiment and NuMI Beam Home Page

Science.gov Websites

Injector The NuMI Beamline is a facility at Fermilab, near Chicago, which uses protons from the Main . MINOS uses two detectors, one located at Fermilab, at the source of the neutrinos, and the other located

Validating the EXCEL hypothesis: a propensity score matched 3-year comparison of percutaneous coronary intervention versus coronary artery bypass graft in left main patients with SYNTAX score ≤32.

PubMed

Capodanno, Davide; Caggegi, Anna; Capranzano, Piera; Cincotta, Glauco; Miano, Marco; Barrano, Gionbattista; Monaco, Sergio; Calvo, Francesco; Tamburino, Corrado

2011-06-01

The aim of this study is to verify the study hypothesis of the EXCEL trial by comparing percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) in an EXCEL-like population of patients. The upcoming EXCEL trial will test the hypothesis that left main patients with SYNTAX score ≤ 32 experience similar rates of 3-year death, myocardial infarction (MI), or cerebrovascular accidents (CVA) following revascularization by PCI or CABG. We compared the 3-year rates of death/MI/CVA and death/MI/CVA/target vessel revascularization (MACCE) in 556 patients with left main disease and SYNTAX score ≤ 32 undergoing PCI (n = 285) or CABG (n = 271). To account for confounders, outcome parameters underwent extensive statistical adjustment. The unadjusted incidence of death/MI/CVA was similar between PCI and CABG (12.7% vs. 8.4%, P = 0.892), while MACCE were higher in the PCI group compared to the CABG group (27.0% vs. 11.8%, P < 0.001). After propensity score matching, PCI was not associated with a significant increase in the rate of death/MI/CVA (11.8% vs. 10.7%, P = 0.948), while MACCE were more frequently noted among patients treated with PCI (28.8% vs. 14.1%, P = 0.002). Adjustment by means of SYNTAX score and EUROSCORE, covariates with and without propensity score, and propensity score alone did not change significantly these findings. In an EXCEL-like cohort of patients with left main disease, there seems to be a clinical equipoise between PCI and CABG in terms of death/MI/CVA. However, even in patients with SYNTAX score ≤ 32, CABG is superior to PCI when target vessel revascularization is included in the combined endpoint. Copyright © 2011 Wiley-Liss, Inc.

Reliability of the Kinetic Measures under Different Heel Conditions during Normal Walking

ERIC Educational Resources Information Center

Liu, Yuanlong; Wang, Yong Tai

2004-01-01

The purpose of this study was to determine and compare the reliability of 3 dimension reaction forces and impulses in walking with 3 different heel shoe conditions. These results suggest that changing the height of the heels affects mainly the reliability of the ground reaction force and impulse measures on the medial and lateral dimension and not…

MicroRNAome of Spodoptera frugiperda cells (Sf9) and its alteration following baculovirus infection.

PubMed

Mehrabadi, Mohammad; Hussain, Mazhar; Asgari, Sassan

2013-06-01

MicroRNAs (miRNAs) as small non-coding RNAs play important roles in many biological processes such as development, cell signalling and immune response. Studies also suggest that miRNAs are important in host-virus interactions where the host limits virus infection by differentially expressing miRNAs that target essential viral genes. Here, we identified conserved and new miRNAs from Spodoptera frugiperda cells (Sf9) using a combination of deep sequencing and bioinformatics as well as experimental approaches. S. frugiperda miRNAs share common features of miRNAs in other organisms, such as uracil (U) at the 5' end of miRNA. The 5' ends of the miRNAs were more conserved than the 3' ends, revealing evolutionary protection of the seed region in miRNAs. The predominant miRNAs were found to be conserved among arthropods. The majority of homologous miRNAs were found in Bombyx mori, with 76 of the 90 identified miRNAs. We found that seed shifting and arm switching have happened in this insect's miRNAs. Expression levels of the majority of miRNAs changed following baculovirus infection. Results revealed that baculovirus infection mainly led to an overall suppression of cellular miRNAs. We found four different genes being regulated by sfr-miR-184 at the post-transcriptional level. The data presented here further support conservation of miRNAs in insects and other organisms. In addition, the results reveal a differential expression of host miRNAs upon baculovirus infection, suggesting their potential roles in host-virus interactions. Seed shifting and arm switching happened during evolution of miRNAs in different insects and caused miRNA diversification, which led to changes in the target repository of miRNAs.

miR-340 alleviates chemoresistance of osteosarcoma cells by targeting ZEB1.

PubMed

Yan, Haibin; Zhang, Bingyun; Fang, Chongbin; Chen, Liqiu

2018-06-01

Chemoresistance during treatment of osteosarcoma (OS) is attracting more and more attention as the main clinical obstacle. The purpose of this study was to elucidate the role of miR-340 in chemoresistance of OS. Plasmid construction and transfection, miRNA arrays, PCR analyses, and western blot analysis, as well as MTT, apoptosis, and luciferase assays were carried out in MG-63 cells and MG-63/cisplatin (DDP)-resistant cells. The results showed that miR-340 was downregulated in OS tissues and drug-resistant OS cells. Moreover, a negative correlation was observed between miR-340 and ZEB1 expression in OS tissues. Forced expression of miR-340 in drug-resistant OS cells significantly reduced multidrug resistance-1 and P-gp expression. Overexpression of miR-340 enhanced sensitivity to DDP by inhibiting viability and promoting apoptosis. The luciferase assay and western blot analysis identified ZEB1 as a direct target of miR-340, and miR-340 negatively regulated ZEB1 expression. Ectopic expression of ZEB1 reversed the effects of miR-340 on P-gp expression, cell viability, and apoptosis. miR-340 alleviated chemoresistance of OS cells by targeting ZEB1. Our results indicate that targeting miR-340 may be a potential therapeutic approach to treat drug-resistant OS.

MicroRNAs in the development and neoplasia of the mammary gland.

PubMed

Jena, Manoj Kumar

2017-01-01

Study on the role of microRNAs (miRs) as regulators of gene expression through posttranscriptional gene silencing is currently gaining much interest,due to their wide involvement in different physiological processes. Understanding mammary gland development, lactation, and neoplasia in relation to miRs is essential. miR expression profiling of the mammary gland from different species in various developmental stages shows their role as critical regulators of development. miRs such as miR-126, miR-150, and miR-145 have been shown to be involved in lipid metabolism during lactation. In addition, lactogenic hormones influence miR expression as evidenced by overexpression of miR-148a in cow mammary epithelial cells, leading to enhanced lactation. Similarly, the miR-29 family modulates lactation-related gene expression by regulating DNA methylation of their promoters. Besides their role in development, lactation and involution, miRs are responsible for breast cancer development. Perturbed estrogen (E2) signaling is one of the major causes of breast cancer. Increased E2 levels cause altered expression of ERα, and ERα-miR cross-talk promotes tumour progression. miRs, such as miR-206, miR-34a, miR-17-5p, and miR-125 a/b are found to be tumour suppressors; whereas miR-21, miR-10B, and miR-155 are oncogenes. Oncogenic miRs like miR-21, miR-221, and miR-210 are overexpressed in triple negative breast cancer cases which can be diagnostic biomarker for this subtype of cancer.  This review focuses on the recent findings concerning the role of miRs in developmental stages of the mammary gland (mainly lactation and involution stages) and their involvement in breast cancer progression. Further studies in this area will help us to understand the molecular details of mammary gland biology, as well as miRs that could be therapeutic targets of breast cancer.

Identification of new stress-induced microRNA and their targets in wheat using computational approach.

PubMed

Pandey, Bharati; Gupta, Om Prakash; Pandey, Dev Mani; Sharma, Indu; Sharma, Pradeep

2013-05-01

MicroRNAs (miRNAs) are a class of short endogenous non-coding small RNA molecules of about 18-22 nucleotides in length. Their main function is to downregulate gene expression in different manners like translational repression, mRNA cleavage and epigenetic modification. Computational predictions have raised the number of miRNAs in wheat significantly using an EST based approach. Hence, a combinatorial approach which is amalgamation of bioinformatics software and perl script was used to identify new miRNA to add to the growing database of wheat miRNA. Identification of miRNAs was initiated by mining the EST (Expressed Sequence Tags) database available at National Center for Biotechnology Information. In this investigation, 4677 mature microRNA sequences belonging to 50 miRNA families from different plant species were used to predict miRNA in wheat. A total of five abiotic stress-responsive new miRNAs were predicted and named Ta-miR5653, Ta-miR855, Ta-miR819k, Ta-miR3708 and Ta-miR5156. In addition, four previously identified miRNA, i.e., Ta-miR1122, miR1117, Ta-miR1134 and Ta-miR1133 were predicted in newly identified EST sequence and 14 potential target genes were subsequently predicted, most of which seems to encode ubiquitin carrier protein, serine/threonine protein kinase, 40S ribosomal protein, F-box/kelch-repeat protein, BTB/POZ domain-containing protein, transcription factors which are involved in growth, development, metabolism and stress response. Our result has increased the number of miRNAs in wheat, which should be useful for further investigation into the biological functions and evolution of miRNAs in wheat and other plant species.

miRNAmeConverter: an R/bioconductor package for translating mature miRNA names to different miRBase versions.

PubMed

Haunsberger, Stefan J; Connolly, Niamh M C; Prehn, Jochen H M

2017-02-15

The miRBase database is the central and official repository for miRNAs and the current release is miRBase version 21.0. Name changes in different miRBase releases cause inconsistencies in miRNA names from version to version. When working with only a small number of miRNAs the translation can be done manually. However, with large sets of miRNAs, the necessary correction of such inconsistencies becomes burdensome and error-prone. We developed miRNAmeConverter , available as a Bioconductor R package and web interface that addresses the challenges associated with mature miRNA name inconsistencies. The main algorithm implemented enables high-throughput automatic translation of species-independent mature miRNA names to user selected miRBase versions. The web interface enables users less familiar with R to translate miRNA names given in form of a list or embedded in text and download of the results. The miRNAmeConverter R package is open source under the Artistic-2.0 license. It is freely available from Bioconductor ( http://bioconductor.org/packages/miRNAmeConverter ). The web interface is based on R Shiny and can be accessed under the URL http://www.systemsmedicineireland.ie/tools/mirna-name-converter/ . The database that miRNAmeConverter depends on is provided by the annotation package miRBaseVersions.db and can be downloaded from Bioconductor ( http://bioconductor.org/packages/miRBaseVersions.db ). Minimum R version 3.3.0 is required. stefanhaunsberger@rcsi.ie. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

MicroRNAs in the pineal gland: miR-483 regulates melatonin synthesis by targeting arylalkylamine N-acetyltransferase.

PubMed

Clokie, Samuel J H; Lau, Pierre; Kim, Hyun Hee; Coon, Steven L; Klein, David C

2012-07-20

MicroRNAs (miRNAs) play a broad range of roles in biological regulation. In this study, rat pineal miRNAs were profiled for the first time, and their importance was evaluated by focusing on the main function of the pineal gland, melatonin synthesis. Massively parallel sequencing and related methods revealed the miRNA population is dominated by a small group of miRNAs as follows: ~75% is accounted for by 15 miRNAs; miR-182 represents 28%. In addition to miR-182, miR-183 and miR-96 are also highly enriched in the pineal gland, a distinctive pattern also found in the retina. This effort also identified previously unrecognized miRNAs and other small noncoding RNAs. Pineal miRNAs do not exhibit a marked night/day difference in abundance with few exceptions (e.g. 2-fold night/day differences in the abundance of miR-96 and miR-182); this contrasts sharply with the dynamic 24-h pattern that characterizes the pineal transcriptome. During development, the abundance of most pineal gland-enriched miRNAs increases; however, there is a marked decrease in at least one, miR-483. miR-483 is a likely regulator of melatonin synthesis, based on the following. It inhibits melatonin synthesis by pinealocytes in culture; it acts via predicted binding sites in the 3"-UTR of arylalkylamine N-acetyltransferase (Aanat) mRNA, the penultimate enzyme in melatonin synthesis, and it exhibits a developmental profile opposite to that of Aanat transcripts. Additionally, a miR-483 targeted antagonist increased melatonin synthesis in neonatal pinealocytes. These observations support the hypothesis that miR-483 suppresses Aanat mRNA levels during development and that the developmental decrease in miR-483 abundance promotes melatonin synthesis.

Great Lakes and St. Lawrence Seaway Navigation Season Extension. Volume 1. Main Report and Final Environmental Impact Statement

DTIC Science & Technology

1979-08-01

MN - Taconite, MN - Silver Bay, MN - Presque Isle , MI - Marquette, MI 30 iC V.)Lake Michigan - Burns Harbor, IN - Gary, IN - Indiana, IN - Milwaukee...14,263 3.7 Presque Isle , MI 1,703 516 3.3 Marquette, MI 159 192 0.8 Taconite, MN 5,640 1,723 3.3 Silver Bay, MN 5,623 1,744 3.2 Ash-and, WI 250 668 0.4...required -for Taconite, Two Harbors, and Presque Isle and that only a single line of bubblers would be required in Ashland, MaLquette, and Silver Bay

Resting-state functional connectivity of neurotransmitter producing sites in female patients with borderline personality disorder.

PubMed

Wagner, Gerd; Krause-Utz, Annegret; de la Cruz, Feliberto; Schumann, Andy; Schmahl, Christian; Bär, Karl-Jürgen

2018-04-20

Impulsive behavior, difficulties in controlling anger and suicidal behavior are typical patterns of affective/behavioral dysregulation in patients with borderline personality disorder (BPD). Previous functional MRI studies in the resting state condition demonstrated altered functional connectivity (FC) between the anterior cingulate cortex (ACC) and the frontoparietal executive control network (ECN), which was significantly associated with impulsivity in BPD. Impulsivity is often defined as a function of inhibitory control, strongly relying on the proper functioning of the fronto-cingulo-striatal network. Noradrenergic, dopaminergic and serotonergic neurotransmitter systems are assumed to be involved in different forms of impulsive behavior and inhibitory control. In our previous study, we investigated the FC of the main monoamine-producing nuclei within the midbrain and brainstem, which were functionally integrated in specific resting-state networks. In the present study we investigated the resting-state FC of midbrain/brainstem nuclei in 33 unmedicated female patients with BPD and 33 matched healthy controls. We further related altered functional connectivity of these nuclei to the patient's degree of impulsivity. The main finding was that BPD patients showed stronger FC from the noradrenergic locus coeruleus (LC) to the ACC. Functional connectivity between the LC and ACC was positively associated with the degree of motor impulsivity in the total group. Controlling for aggression, a stronger FC was also found between serotonergic nucleus centralis superior (NCS) and the frontopolar cortex (FPC) in patients compared to controls. Furthermore, patients showed a weaker "anti-correlation" from the substantia nigra (SNc) to the left dorsolateral prefrontal cortex (DLPFC). The observed enhanced LC-ACC FC in BPD and its association with the motor impulsivity might be indicative of a noradrenergic dysfunction in the neural inhibitory control network, whereas the significant relationship between NCS-FPC FC and aggression points toward serotonergic contribution to prefrontal control of aggressive reactions. Copyright © 2018 Elsevier Inc. All rights reserved.

miR-874 regulates myocardial necrosis by targeting caspase-8

PubMed Central

Wang, K; Liu, F; Zhou, L-Y; Ding, S-L; Long, B; Liu, C-Y; Sun, T; Fan, Y-Y; Sun, L; Li, P-F

2013-01-01

Cardiomyocyte death is an important reason for the cardiac syndromes, such as heart failure (HF) and myocardial infarction (MI). In the heart diseases, necrosis is one of the main forms of cell death. MicroRNAs (miRNAs) are a class of small non-coding RNAs that mediate post-transcriptional gene silencing. Hitherto, it is not yet clear whether miRNA can regulate necrosis in cardiomyocyte. In this work, we performed a microarray to detect miRNAs in response to H2O2 treatment, and the results showed that miR-874 was substantially increased. We further studied the function of miR-874, and observed that knockdown of miR-874 attenuated necrosis in the cellular model and also MI in the animal model. We searched for the downstream mediator of miR-874 and identified that caspase-8 was a target of miR-874. Caspase-8 was able to antagonize necrosis. When suppressed by miR-874, caspase-8 lost the ability to repress necrotic program. In exploring the molecular mechanism by which miR-874 expression is regulated, we identified that Foxo3a could transcriptionally repress miR-874 expression. Foxo3a transgenic or knockout mice exhibited a low or high expression level of miR-874, and a reduced or enhanced necrosis and MI. Our present study reveals a novel myocardial necrotic regulating model, which is composed of Foxo3a, miR-874 and caspase-8. Modulation of their levels may provide a new approach for tackling myocardial necrosis. PMID:23828572

miRNA-15a, miRNA-15b, and miRNA-499 are Reduced in Erythrocytes of Pre-Diabetic African-American Adults

PubMed Central

Fluitt, Maurice B.; Kumari, Namita; Nunlee-Bland, Gail; Nekhai, Sergei; Gambhir, Kanwal K.

2017-01-01

Aims The use of circulatory miRNAs as biomarkers and therapeutic targets for T2DM is an explosive area of study. However, no study has investigated circulatory miRNA expression exclusively in African-American adults. The aim of this study was to identify the expression of nine selected miRNAs in erythrocytes of pre-diabetic and type 2 diabetic African-American adults. Main Methods Patients were recruited from the Howard University Hospital Diabetes Treatment Center following an 8 to 10 hour overnight fast. Expression of the nine selected miRNAs (miRNA-499, miRNA-146, miRNA-126, miRNA-223, miRNA-15a, miRNA-15b, miRNA-224, miRNA-326, and miRNA-375) was evaluated using quantitative real time PCR. Key Findings miRNA-15a, miRNA-15b, and miRNA-499 were significantly reduced in erythrocytes of pre-diabetic African-American adults. In the T2DM group, we found significant correlations between miRNA-15a and BMI (r=0.59, p=0.04), miRNA-15a and weight (r=0.52, p=0.01), and miRNA-15b and diastolic blood pressure (r=−0.52, p=0.02). In the pre-diabetic group, we found significant correlations between miRNA-15b and weight (r=0.90, p=0.02) and miRNA-499 and HbA1c (r=−0.89, p=0.01). Significance To our knowledge, this is the first study investigating miRNA expression in erythrocytes of non-diabetic high-risk obese--pre-diabetic and type 2 diabetic African-American adults. The findings of this study are consistent with previous reports of reduced expression of miRNA-15a, miRNA-15b, and miRNA-499 in human plasma or serum and in animal models. The current findings support the use of circulating miRNA-15a, miRNA-15b, and miRNA-499 as potential biomarkers for T2DM in African-American adults. PMID:29399662

The universal 2012 definition of myocardial infarction compared to the 2007 definition.

PubMed

Langørgen, Jørund; Ebbing, Marta; Igland, Jannicke; Nordrehaug, Jan Erik; Vollset, Stein Emil; Kask, Anne; Tell, Grethe S; Nygård, Ottar

2016-08-01

The third Universal 2012 definition of myocardial infarction (MI) has not been compared to the Universal 2007 definition with regard to the number of cases identified, classification and mortality. We examined potential MI events according to the two universal definitions in 1494 patients admitted to the University hospital during the 12 months. Patients were included either because of an MI discharge diagnosis (815 patients) or due to elevated troponin I levels without an MI discharge diagnosis (679 patients). Applying the Universal 2012 definition resulted in 760 of the 1494 patients suffering from MI, as compared to 769 according to the Universal 2007 definition. The lower number of MI events applying the 2012 definition was mainly explained by the stricter definition of Type 4a MI. The 760 MI events were classified as Type 1 (685), 2 (27), 3 (28), 4a (13), 4b (3) and 5 (4). The application of the third Universal 2012 definition of MI instead of the Universal 2007 definition resulted in a 1% reduction of the total number of MIs. For a practical clinical purpose, the reduction was confined to patients with Type 4a MI. The change of definition had no impact on all-cause mortality.

Development of a low-cost detection method for miRNA microarray.

PubMed

Li, Wei; Zhao, Botao; Jin, Youxin; Ruan, Kangcheng

2010-04-01

MicroRNA (miRNA) microarray is a powerful tool to explore the expression profiling of miRNA. The current detection method used in miRNA microarray is mainly fluorescence based, which usually requires costly detection system such as laser confocal scanner of tens of thousands of dollars. Recently, we developed a low-cost yet sensitive detection method for miRNA microarray based on enzyme-linked assay. In this approach, the biotinylated miRNAs were captured by the corresponding oligonucleotide probes immobilized on microarray slide; and then the biotinylated miRNAs would capture streptavidin-conjugated alkaline phosphatase. A purple-black precipitation on each biotinylated miRNA spot was produced by the enzyme catalytic reaction. It could be easily detected by a charge-coupled device digital camera mounted on a microscope, which lowers the detection cost more than 100 fold compared with that of fluorescence method. Our data showed that signal intensity of the spot correlates well with the biotinylated miRNA concentration and the detection limit for miRNAs is at least 0.4 fmol and the detection dynamic range spans about 2.5 orders of magnitude, which is comparable to that of fluorescence method.

Substantial Loss of Conserved and Gain of Novel MicroRNA Families in Flatworms

PubMed Central

Fromm, Bastian; Worren, Merete Molton; Hahn, Christoph; Hovig, Eivind; Bachmann, Lutz

2013-01-01

Recent studies on microRNA (miRNA) evolution focused mainly on the comparison of miRNA complements between animal clades. However, evolution of miRNAs within such groups is poorly explored despite the availability of comparable data that in some cases lack only a few key taxa. For flatworms (Platyhelminthes), miRNA complements are available for some free-living flatworms and all major parasitic lineages, except for the Monogenea. We present the miRNA complement of the monogenean flatworm Gyrodactylus salaris that facilitates a comprehensive analysis of miRNA evolution in Platyhelminthes. Using the newly designed bioinformatics pipeline miRCandRef, the miRNA complement was disentangled from next-generation sequencing of small RNAs and genomic DNA without a priori genome assembly. It consists of 39 miRNA hairpin loci of conserved miRNA families, and 22 novel miRNAs. A comparison with the miRNA complements of Schmidtea mediterranea (Turbellaria), Schistosoma japonicum (Trematoda), and Echinococcus granulosus (Cestoda) reveals a substantial loss of conserved bilaterian, protostomian, and lophotrochozoan miRNAs. Eight of the 46 expected conserved miRNAs were lost in all flatworms, 16 in Neodermata and 24 conserved miRNAs could not be detected in the cestode and the trematode. Such a gradual loss of miRNAs has not been reported before for other animal phyla. Currently, little is known about miRNAs in Platyhelminthes, and for the majority of the lost miRNAs there is no prediction of function. As suggested earlier they might be related to morphological simplifications. The presence and absence of 153 conserved miRNAs was compared for platyhelminths and 32 other metazoan taxa. Phylogenetic analyses support the monophyly of Platyhelminthes (Turbellaria + Neodermata [Monogenea {Trematoda + Cestoda}]). PMID:24025793

miRNA expression in control and FSHD fetal human muscle biopsies.

PubMed

Portilho, Débora Morueco; Alves, Marcelo Ribeiro; Kratassiouk, Gueorgui; Roche, Stéphane; Magdinier, Frédérique; de Santana, Eliane Corrêa; Polesskaya, Anna; Harel-Bellan, Annick; Mouly, Vincent; Savino, Wilson; Butler-Browne, Gillian; Dumonceaux, Julie

2015-01-01

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disorder and is one of the most common forms of muscular dystrophy. We have recently shown that some hallmarks of FSHD are already expressed in fetal FSHD biopsies, thus opening a new field of investigation for mechanisms leading to FSHD. As microRNAs (miRNAs) play an important role in myogenesis and muscle disorders, in this study we compared miRNAs expression levels during normal and FSHD muscle development. Muscle biopsies were obtained from quadriceps of both healthy control and FSHD1 fetuses with ages ranging from 14 to 33 weeks of development. miRNA expression profiles were analyzed using TaqMan Human MicroRNA Arrays. During human skeletal muscle development, in control muscle biopsies we observed changes for 4 miRNAs potentially involved in secondary muscle fiber formation and 5 miRNAs potentially involved in fiber maturation. When we compared the miRNA profiles obtained from control and FSHD biopsies, we did not observe any differences in the muscle specific miRNAs. However, we identified 8 miRNAs exclusively expressed in FSHD1 samples (miR-330, miR-331-5p, miR-34a, miR-380-3p, miR-516b, miR-582-5p, miR-517* and miR-625) which could represent new biomarkers for this disease. Their putative targets are mainly involved in muscle development and morphogenesis. Interestingly, these FSHD1 specific miRNAs do not target the genes previously described to be involved in FSHD. This work provides new candidate mechanisms potentially involved in the onset of FSHD pathology. Whether these FSHD specific miRNAs cause deregulations during fetal development, or protect against the appearance of the FSHD phenotype until the second decade of life still needs to be investigated.

MicroRNAs in the Pineal Gland

PubMed Central

Clokie, Samuel J. H.; Lau, Pierre; Kim, Hyun Hee; Coon, Steven L.; Klein, David C.

2012-01-01

MicroRNAs (miRNAs) play a broad range of roles in biological regulation. In this study, rat pineal miRNAs were profiled for the first time, and their importance was evaluated by focusing on the main function of the pineal gland, melatonin synthesis. Massively parallel sequencing and related methods revealed the miRNA population is dominated by a small group of miRNAs as follows: ∼75% is accounted for by 15 miRNAs; miR-182 represents 28%. In addition to miR-182, miR-183 and miR-96 are also highly enriched in the pineal gland, a distinctive pattern also found in the retina. This effort also identified previously unrecognized miRNAs and other small noncoding RNAs. Pineal miRNAs do not exhibit a marked night/day difference in abundance with few exceptions (e.g. 2-fold night/day differences in the abundance of miR-96 and miR-182); this contrasts sharply with the dynamic 24-h pattern that characterizes the pineal transcriptome. During development, the abundance of most pineal gland-enriched miRNAs increases; however, there is a marked decrease in at least one, miR-483. miR-483 is a likely regulator of melatonin synthesis, based on the following. It inhibits melatonin synthesis by pinealocytes in culture; it acts via predicted binding sites in the 3′-UTR of arylalkylamine N-acetyltransferase (Aanat) mRNA, the penultimate enzyme in melatonin synthesis, and it exhibits a developmental profile opposite to that of Aanat transcripts. Additionally, a miR-483 targeted antagonist increased melatonin synthesis in neonatal pinealocytes. These observations support the hypothesis that miR-483 suppresses Aanat mRNA levels during development and that the developmental decrease in miR-483 abundance promotes melatonin synthesis. PMID:22908386

Characterization of miRNAs responsive to exogenous ethylene in grapevine berries at whole genome level.

PubMed

Zhao, Fanggui; Wang, Chen; Han, Jian; Zhu, Xudong; Li, Xiaopeng; Wang, Xicheng; Fang, Jinggui

2017-05-01

MicroRNAs (miRNAs) are critical regulators of various biological and metabolic processes of plants. Numerous miRNAs and their functions have been identified and analyzed in many plants. However, till now, the involvement of miRNAs in the response of grapevine berries to ethylene has not been reported yet. Here, Solexa technology was employed to deeply sequence small RNA libraries constructed from grapevine berries treated with and without ethylene. A total of 124 known and 78 novel miRNAs were identified. Among these miRNAs, 162 miRNAs were clearly responsive to ethylene, with 55 downregulated, 59 upregulated, and 14 unchanged miRNAs detected only in the control. The other 35 miRNAs responsive to ethylene were induced by ethylene and detected only in the ethylene-treated grapevine materials. Expression analysis of 27 conserved and 26 novel miRNAs revealed that 13 conserved and 18 novel ones were regulated by ethylene during the whole development of grapevine berries. High-throughput sequencing and qRT-PCR assays revealed consistent results on the expression results of ethylene-responsive miRNAs. Moreover, 90 target genes for 34 novel miRNAs were predicted, most of which were involved in responses to various stresses, especially like exogenous ethylene treatment. The identified miRNAs may be mainly involved in grapevine berry development and response to various environmental conditions.

Procrastination as a Self-Regulation Failure: The Role of Impulsivity and Intrusive Thoughts.

PubMed

Rebetez, Marie My Lien; Rochat, Lucien; Barsics, Catherine; Van der Linden, Martial

2018-02-01

Procrastination has been described as the quintessence of self-regulatory failure. This study examines the relationships between this self-regulatory failure and other manifestations of self-regulation problems, namely impulsivity and intrusive thoughts. One hundred and forty-one participants completed questionnaires assessing procrastination, impulsivity (in particular, the urgency and lack of perseverance dimensions), and intrusive thoughts (i.e., rumination and daydreaming). Main results show that urgency mediated the association between rumination and procrastination, whereas rumination did not mediate the relation between urgency and procrastination. Lack of perseverance mediated the association between daydreaming and procrastination, and daydreaming mediated the relation between lack of perseverance and procrastination. This study highlights the role of impulsivity and intrusive thoughts in procrastination, specifies the links between these self-regulation problems, and provides insights into their (potential) underlying mechanisms. It also opens interesting prospects for management strategies for implementing targeted psychological interventions to reduce impulsive manifestations and/or thought control difficulties accompanying procrastination.

Inter-individual differences in the impulsive/compulsive dimension: deciphering related dopaminergic and serotonergic metabolisms at rest.

PubMed

Dellu-Hagedorn, Françoise; Rivalan, Marion; Fitoussi, Aurélie; De Deurwaerdère, Philippe

2018-04-19

Several impulse control disorders such as ADHD, mania, personality disorders or substance abuse share common behavioural traits, like impulsiveness, risk-taking or inflexible behaviour. These disorders are treated with drugs targeting dopamine (DA) and/or serotonin (5-HT). However, the patient's monoamine imbalance that these neurotransmitters compensate is unclear. This study aims to investigate the patterns of DA and 5-HT metabolisms at rest within selected brain regions related to inter-individual variability in six main components of impulsivity/compulsivity (anticipatory hyperactivity, premature responses, delay discounting, risk-taking, perseveration, flexibility). Rats with adaptive and highly inadaptive behaviours were identified in each task and a sensitive biochemical approach allowed mapping of post-mortem endogenous monoamine tissue content in 20 brain areas. Distinct patterns of 5-HT and DA metabolisms were revealed according to the behavioural traits. Except for hyperactive responses, lower control of actions was mainly associated with a lower DA or 5-HT metabolism in prefrontal and/or subcortical areas (i.e. in orbitofrontal cortex (DA), amygdala and anterior cingulate cortex (5-HT) for inflexible and risk-prone rats). Our results reveal the complex nature of behavioural traits related to impulse control disorders through their associated monoaminergic networks at rest, paving the way for understanding the link between mental disorders and drug therapeutic actions.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'. © 2018 The Author(s).

A pilot genetic study of the continuum between compulsivity and impulsivity in females: the serotonin transporter promoter polymorphism.

PubMed

Baca-García, Enrique; Salgado, Beatríz Rodríguez; Segal, Helen Dolengevich; Lorenzo, Concepción Vaquero; Acosta, Mercedes Navio; Romero, Manuel Arrojo; Hernández, Montserrat Díaz; Saiz-Ruiz, Jeronimo; Fernandez Piqueras, Jose; de Leon, Jose

2005-06-01

According to some authors the obsessive-compulsive (OC) spectrum includes on one extreme, the Obsessive-Compulsive Disorder (OCD) and on the other extreme the most impulsive behaviors. This is a controversial idea and other authors define the OC spectrum in different ways. The serotonin transporter (5-HTT) gene is one of the main genes that control serotonergic function. A polymorphism in the promoter area of this gene classifies subjects with low expression as S individuals (s/s or s/l) and subjects with high expression as L individuals (l/l). This polymorphism was studied in female OCD patients (n = 24), non-impulsive controls (n = 112) and impulsive suicidal patients (n = 118) to support the OC spectrum hypothesis from a genetic perspective. A linear association exists among the serotonin transporter promoter functional genotypes (S versus L individuals) (chi2 linear by linear association = 8.9; df = 1; p = 0.003). The frequency of S individuals (s/l or s/s) was lowest in OCD (54%, 13/24); intermediate in non-impulsive controls (71%, 80/112) and highest in impulsive suicide attempters (82%, 96/117). More importantly, future studies need to consider that genetics may be related to behavioral dimensions (compulsivity to impulsivity) instead of to specific psychiatric disorders defined in clinical terms.

miR-138 protects cardiomyocytes from hypoxia-induced apoptosis via MLK3/JNK/c-jun pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

He, Siyi; Liu, Peng; Jian, Zhao

2013-11-29

Highlights: •First time to find miR-138 is up-regulated in hypoxic cardiomyocytes. •First time to find miR-138 targets MLK3 and regulates JNK/c-jun pathway. •Rare myocardial biopsy of patients with CHD were collected. •Both silence and overexpression of miR-138 were implemented. •Various methods were used to detect cell function. -- Abstract: Cardiomyocytes experience a series of complex endogenous regulatory mechanisms against apoptosis induced by chronic hypoxia. MicroRNAs are a class of endogenous small non-coding RNAs that regulate cellular pathophysiological processes. Recently, microRNA-138 (miR-138) has been found related to hypoxia, and beneficial for cell proliferation. Therefore, we intend to study the role ofmore » miR-138 in hypoxic cardiomyocytes and the main mechanism. Myocardial samples of patients with congenital heart disease (CHD) were collected to test miR-138 expression. Agomir or antagomir of miR-138 was transfected into H9C2 cells to investigate its effect on cell apoptosis. Higher miR-138 expression was observed in patients with cyanotic CHD, and its expression gradually increased with prolonged hypoxia time in H9C2 cells. Using MTT and LDH assays, cell growth was significantly greater in the agomir group than in the negative control (NC) group, while antagomir decreased cell survival. Dual luciferase reporter gene and Western-blot results confirmed MLK3 was a direct target of miR-138. It was found that miR-138 attenuated hypoxia-induced apoptosis using TUNEL, Hoechst staining and Annexin V-PE/7-AAD flow cytometry analysis. We further detected expression of apoptosis-related proteins. In the agomir group, the level of pro-apoptotic proteins such as cleaved-caspase-3, cleaved-PARP and Bad significantly reduced, while Bcl-2 and Bcl-2/Bax ratio increased. Opposite changes were observed in the antagomir group. Downstream targets of MLK3, JNK and c-jun, were also suppressed by miR-138. Our study demonstrates that up-regulation of miR-138 plays a protective role in myocardial adaptation to chronic hypoxia, which is mediated mainly by MLK3/JNK/c-jun signaling pathway.« less

About miRNAs, miRNA seeds, target genes and target pathways.

PubMed

Kehl, Tim; Backes, Christina; Kern, Fabian; Fehlmann, Tobias; Ludwig, Nicole; Meese, Eckart; Lenhof, Hans-Peter; Keller, Andreas

2017-12-05

miRNAs are typically repressing gene expression by binding to the 3' UTR, leading to degradation of the mRNA. This process is dominated by the eight-base seed region of the miRNA. Further, miRNAs are known not only to target genes but also to target significant parts of pathways. A logical line of thoughts is: miRNAs with similar (seed) sequence target similar sets of genes and thus similar sets of pathways. By calculating similarity scores for all 3.25 million pairs of 2,550 human miRNAs, we found that this pattern frequently holds, while we also observed exceptions. Respective results were obtained for both, predicted target genes as well as experimentally validated targets. We note that miRNAs target gene set similarity follows a bimodal distribution, pointing at a set of 282 miRNAs that seems to target genes with very high specificity. Further, we discuss miRNAs with different (seed) sequences that nonetheless regulate similar gene sets or pathways. Most intriguingly, we found miRNA pairs that regulate different gene sets but similar pathways such as miR-6886-5p and miR-3529-5p. These are jointly targeting different parts of the MAPK signaling cascade. The main goal of this study is to provide a general overview on the results, to highlight a selection of relevant results on miRNAs, miRNA seeds, target genes and target pathways and to raise awareness for artifacts in respective comparisons. The full set of information that allows to infer detailed results on each miRNA has been included in miRPathDB, the miRNA target pathway database (https://mpd.bioinf.uni-sb.de).

miR-22 and miR-29a Are Members of the Androgen Receptor Cistrome Modulating LAMC1 and Mcl-1 in Prostate Cancer.

PubMed

Pasqualini, Lorenza; Bu, Huajie; Puhr, Martin; Narisu, Narisu; Rainer, Johannes; Schlick, Bettina; Schäfer, Georg; Angelova, Mihaela; Trajanoski, Zlatko; Börno, Stefan T; Schweiger, Michal R; Fuchsberger, Christian; Klocker, Helmut

2015-07-01

The normal prostate as well as early stages and advanced prostate cancer (PCa) require a functional androgen receptor (AR) for growth and survival. The recent discovery of microRNAs (miRNAs) as novel effector molecules of AR disclosed the existence of an intricate network between AR, miRNAs and downstream target genes. In this study DUCaP cells, characterized by high content of wild-type AR and robust AR transcriptional activity, were chosen as the main experimental model. By integrative analysis of chromatin immunoprecipitation-sequencing (ChIP-seq) and microarray expression profiling data, miRNAs putatively bound and significantly regulated by AR were identified. A direct AR regulation of miR-22, miR-29a, and miR-17-92 cluster along with their host genes was confirmed. Interestingly, endogenous levels of miR-22 and miR-29a were found to be reduced in PCa cells expressing AR. In primary tumor samples, miR-22 and miR-29a were less abundant in the cancerous tissue compared with the benign counterpart. This specific expression pattern was associated with a differential DNA methylation of the genomic AR binding sites. The identification of laminin gamma 1 (LAMC1) and myeloid cell leukemia 1 (MCL1) as direct targets of miR-22 and miR-29a, respectively, suggested a tumor-suppressive role of these miRNAs. Indeed, transfection of miRNA mimics in PCa cells induced apoptosis and diminished cell migration and viability. Collectively, these data provide additional information regarding the complex regulatory machinery that guides miRNAs activity in PCa, highlighting an important contribution of miRNAs in the AR signaling.

Cryopreservation of boar sperm induces differential microRNAs expression.

PubMed

Zhang, Yan; Dai, Dinghui; Chang, Yu; Li, Yuan; Zhang, Ming; Zhou, Guangbin; Peng, Zhanghua; Zeng, Changjun

2017-06-01

Lower conception rates and litter sizes limit the wide use of artificial insemination with frozen-thawed boar sperm, due to a lack of understanding of the mechanisms that cause cryodamage and cryoinjury to sperm during cryopreservation. CryoMiRs, a family of freeze-related microRNAs (miRNAs), are associated with freeze tolerance, and regulate metabolism in mammalian hibernators and insects. Thus, we speculate that miRNAs maybe involved in the regulation of the freeze-thaw process and may affect boar sperm function. In this study, we studied the differential expression of 46 miRNAs that have roles in spermatogenesis, sperm maturation, and sperm quality in response to cryopreservation (with or without 3% glycerol). The results indicated that, in response to cryopreservation with 3% glycerol, 14 miRNAs were significantly up-regulated, but only two miRNAs (miR-22 and miR-450b-5p) were significantly down-regulated, relative to fresh sperm. Preservation with 3% glycerol caused up-regulation of 17 miRNAs, but only caused down-regulation of one miRNA (miR-24), relative to sperm cryopreserved without glycerol. Functional annotations of these differentially expressed miRNAs indicated that these miRNAs and their targets are mainly associated with metabolic and cellular processes. Therefore, our findings show that cryopreservation results in changes in miRNA expression, and suggest that the anti-freeze mechanisms of boar sperm need to be studied further. Copyright © 2017 Elsevier Inc. All rights reserved.

Response of ionospheric electric fields at mid-low latitudes during geomagnetic sudden commencements

NASA Astrophysics Data System (ADS)

Takahashi, N.; Kasaba, Y.; Shinbori, A.; Nishimura, Y.; Kikuchi, T.; Ebihara, Y.; Nagatsuma, T.

2014-12-01

Geomagnetic sudden commencements (SCs) are known as one of the distinct magnetospheric disturbance phenomena triggered by solar wind disturbances. Many previous studies have focused on the generation mechanism of SCs by using in-situ observations and simulations. However, the global evolution of ionospheric electric fields has primarily been estimated from the ionospheric current. Although a few studies utilized electric field data from radar observations, the coverage is limited in time, and limited component of the electric field is obtained. In this study, we investigated the response and local time dependence of the ionospheric electric field at mid-low latitudes associated with 203 SCs occurred from 1999 to 2004 by the in-situ observation of the ROCSAT-1 spacecraft. We found that the ionospheric electric field associated with SCs instantaneously responds to geomagnetic fields regardless of spacecraft local time. Our statistical analysis also showed the instantaneous response of the electric field, which indicates the global instant transmission of the electric field from polar region. In contrast, peak times in the preliminary impulse (PI) and main impulse (MI) phases were different between the ionospheric electric field and equatorial geomagnetic field (20 sec in the PI phase). Based on a comparison to the ground-ionosphere waveguide model by Kikuchi [2014], this time lag is suggested to be due to the latitudinal difference of the ionospheric conductivity. After constructing the local time distribution of the SC amplitude, we found that the dayside feature was seen at 18-22 h even the ionospheric conductivity is lower than that at dayside. We performed a magnetohydrodynamic (MHD) simulation for an ideal SC. The result of the simulation showed that the electric potential distribution is asymmetric with respect to the noon-midnight meridian, which is similar to our observational result. It appears to result from the divergence of the Hall current under the non-uniform ionospheric conductivity near the terminator as well as the auroral region.

Brain functional connectivity changes in children that differ in impulsivity temperamental trait

PubMed Central

Inuggi, Alberto; Sanz-Arigita, Ernesto; González-Salinas, Carmen; Valero-García, Ana V.; García-Santos, Jose M.; Fuentes, Luis J.

2014-01-01

Impulsivity is a core personality trait forming part of normal behavior and contributing to adaptive functioning. However, in typically developing children, altered patterns of impulsivity constitute a risk factor for the development of behavioral problems. Since both pathological and non-pathological states are commonly characterized by continuous transitions, we used a correlative approach to investigate the potential link between personality and brain dynamics. We related brain functional connectivity of typically developing children, measured with magnetic resonance imaging at rest, with their impulsivity scores obtained from a questionnaire completed by their parents. We first looked for areas within the default mode network (DMN) whose functional connectivity might be modulated by trait impulsivity. Then, we calculated the functional connectivity among these regions and the rest of the brain in order to assess if impulsivity trait altered their relationships. We found two DMN clusters located at the posterior cingulate cortex and the right angular gyrus which were negatively correlated with impulsivity scores. The whole-brain correlation analysis revealed the classic network of correlating and anti-correlating areas with respect to the DMN. The impulsivity trait modulated such pattern showing that the canonical anti-phasic relation between DMN and action-related network was reduced in high impulsive children. These results represent the first evidence that the impulsivity, measured as personality trait assessed through parents' report, exerts a modulatory influence over the functional connectivity of resting state brain networks in typically developing children. The present study goes further to connect developmental approaches, mainly based on data collected through the use of questionnaires, and behavioral neuroscience, interested in how differences in brain structure and functions reflect in differences in behavior. PMID:24834038

Brain functional connectivity changes in children that differ in impulsivity temperamental trait.

PubMed

Inuggi, Alberto; Sanz-Arigita, Ernesto; González-Salinas, Carmen; Valero-García, Ana V; García-Santos, Jose M; Fuentes, Luis J

2014-01-01

Impulsivity is a core personality trait forming part of normal behavior and contributing to adaptive functioning. However, in typically developing children, altered patterns of impulsivity constitute a risk factor for the development of behavioral problems. Since both pathological and non-pathological states are commonly characterized by continuous transitions, we used a correlative approach to investigate the potential link between personality and brain dynamics. We related brain functional connectivity of typically developing children, measured with magnetic resonance imaging at rest, with their impulsivity scores obtained from a questionnaire completed by their parents. We first looked for areas within the default mode network (DMN) whose functional connectivity might be modulated by trait impulsivity. Then, we calculated the functional connectivity among these regions and the rest of the brain in order to assess if impulsivity trait altered their relationships. We found two DMN clusters located at the posterior cingulate cortex and the right angular gyrus which were negatively correlated with impulsivity scores. The whole-brain correlation analysis revealed the classic network of correlating and anti-correlating areas with respect to the DMN. The impulsivity trait modulated such pattern showing that the canonical anti-phasic relation between DMN and action-related network was reduced in high impulsive children. These results represent the first evidence that the impulsivity, measured as personality trait assessed through parents' report, exerts a modulatory influence over the functional connectivity of resting state brain networks in typically developing children. The present study goes further to connect developmental approaches, mainly based on data collected through the use of questionnaires, and behavioral neuroscience, interested in how differences in brain structure and functions reflect in differences in behavior.

Contingency management improves smoking cessation treatment outcomes among highly impulsive adolescent smokers relative to cognitive behavioral therapy.

PubMed

Morean, Meghan E; Kong, Grace; Camenga, Deepa R; Cavallo, Dana A; Carroll, Kathleen M; Pittman, Brian; Krishnan-Sarin, Suchitra

2015-03-01

Impulsive adolescents have difficulty quitting smoking. We examined if treatments that provide behavioral incentives for abstinence improve treatment outcomes among impulsive adolescent smokers, who have been shown to be highly sensitive to reward. We ran secondary data analyses on 64 teen smokers (mean age=16.36 [1.44]; cigarettes/day=13.97 [6.61]; 53.1% female; 90.6% Caucasian) who completed a four-week smoking cessation trial to determine whether impulsive adolescents differentially benefit from receiving cognitive behavioral therapy (CBT), contingency management (CM), or the combination of the two (CM/CBT). Indices of treatment efficacy included self-report percent days abstinent and end of treatment biochemically-confirmed 7-day point prevalence abstinence (EOT abstinence). We assessed self-reported impulsivity using the Brief Barratt Impulsiveness Scale. We used univariate Generalized Linear Modeling to examine main effects and interactions of impulsivity and treatment condition as predictors of self-reported abstinence, and exact logistic regression to examine EOT abstinence. CM/CBT and CM were comparably effective in promoting abstinence, so analyses were conducted comparing the efficacy of CBT to treatments with a CM component (i.e., CM and CM/CBT). CBT and deficient self-regulation predicted lower self-reported abstinence rates within the total analytic sample. Treatments containing CM were more effective than CBT in predicting 1) self-reported abstinence among behaviorally impulsive adolescents (% days abstinent: CM 77%; CM/CBT 81%; CBT 30%) and 2) EOT point prevalence abstinence among behaviorally impulsive adolescents and adolescents with significant deficits in self-regulation. CM-based interventions may improve the low smoking cessation rates previously observed among impulsive adolescent smokers. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Impulsivity: What are the consequences on compliance to rehabilitation?].

PubMed

Cancel, A; Naudet, F; Rousseau, P F; Millet, B; Drapier, D

2016-08-01

Impulsivity is a transnosographical dimension with major consequences on medical care with which psychiatrists are frequently confronted. Furthermore, compliance is a major variable that can affect the efficiency of therapeutics and hospitalizations in psychiatry. A study was carried out in three drug and alcohol rehabilitation hospitalization units to find out if impulsivity can have consequences on compliance. The studied population was composed of 85 patients aged from 18 to 70, hospitalized for one or more addiction disorders in a psychometric hospital in Vannes (France). Impulsivity was measured for all patients with the BIS-11 at the beginning of the rehabilitation program. Because no tool to evaluate a total rehab program compliance existed, a scale, used at the end of the hospitalization, was created to measure patient compliance. This score was composed of two simple numeric scales (one used by the nurses and one used by the patient's psychiatrist) and a coefficient of hospitalization duration that was the ratio of completed to planned days of hospitalization. Correlations were made between the different dimensions: impulsivity and compliance, impulsivity and hospitalization conditions, compliance and hospitalization conditions (voluntary or involuntary, planned by a psychiatrist or not, etc.). The main statistically significant result of the study was a negative correlation existing between the motor dimension of impulsivity and compliance (r=-0.37 and P=0.001). The other dimensions of impulsivity showed no significant correlation with compliance score. The study revealed that the different hospitalization conditions showed no link with compliance or impulsivity. These original results show that motor impulsive patients need an adaptation of the rehabilitation programs. Shorter programs might be more efficient. Copyright © 2015 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

miR-192 suppresses leptomeningeal dissemination of medulloblastoma by modulating cell proliferation and anchoring through the regulation of DHFR, integrins, and CD47.

PubMed

Yang, Seung Yeob; Choi, Seung Ah; Lee, Ji Yeoun; Park, Ae-Kyung; Wang, Kyu-Chang; Phi, Ji Hoon; Koh, Eun Jung; Park, Woong-Yang; Park, Sung-Hye; Hwang, Do Won; Jung, Hee Won; Kim, Seung-Ki

2015-12-22

The main cause of death in medulloblastoma is recurrence associated with leptomeningeal dissemination. During this process, the role of microRNAs (miRs) in the acquisition of metastatic phenotype remains poorly understood. This study aimed to identify the miR involved in leptomeningeal dissemination and to elucidate its biological functional mechanisms. We analyzed the miR expression profiles of 29 medulloblastomas according to the presence of cerebrospinal fluid (CSF) seeding. Differentially expressed miRs (DEmiRs) were validated in 29 medulloblastoma tissues and three medulloblastoma cell lines. The biological functions of the selected miRs were evaluated using in vitro and in vivo studies. A total of 12 DEmiRs were identified in medulloblastoma with seeding, including miR-192. The reduced expression of miR-192 was confirmed in the tumor seeding group and in the medulloblastoma cells. Overexpression of miR-192 inhibited cellular proliferation by binding DHFR. miR-192 decreased cellular anchoring via the repression of ITGAV, ITGB1, ITGB3, and CD47. Animals in the miR-192-treated group demonstrated a reduction of spinal seeding (P < 0.05) and a significant survival benefit (P < 0.05). Medulloblastoma with seeding showed specific DEmiRs compared with those without. miR-192 suppresses leptomeningeal dissemination of medulloblastoma by modulating cell proliferation and anchoring ability.

miRNA-based therapies: Strategies and delivery platforms for oligonucleotide and non-oligonucleotide agents

PubMed Central

Baumann, V; Winkler, J

2015-01-01

The discovery of microRNAs as important regulatory agents for gene expression has expanded the therapeutic opportunities for oligonucleotides. In contrast to siRNA, miRNA-targeted therapy is able to influence not only a single gene, but entire cellular pathways or processes. It is possible to supplement down regulated or non-functional miRNAs by synthetic oligonucleotides, as well as alleviating effects caused by overexpression of malignant miRNAs through artificial antagonists, either oligonucleotides or small molecules. Chemical oligonucleotide modifications together with an efficient delivery system seem to be mandatory for successful therapeutic application. While miRNA-based therapy benefits from the decades of research spent on other therapeutic oligonucleotides, there are some specific challenges associated with miRNA therapy, mainly caused by the short target sequence. The current status and recent progress of miRNA-targeted therapeutics is described and future challenges and potential applications in treatment of cancer and viral infections are discussed. PMID:25495987

The predictive value of selected serum microRNAs for acute GVHD by TaqMan MicroRNA arrays.

PubMed

Zhang, Chunyan; Bai, Nan; Huang, Wenrong; Zhang, Pengjun; Luo, Yuan; Men, Shasha; Wen, Ting; Tong, Hongli; Wang, Shuhong; Tian, Ya-Ping

2016-10-01

Currently, the diagnosis of acute graft-versus-host disease (aGVHD) is mainly based on clinical symptoms and biopsy results. This study was designed to further explore new no noninvasive biomarkers for aGVHD prediction/diagnosis. We profiled miRNAs in serum pools from patients with aGVHD (grades II-IV) (n = 9) and non-aGVHD controls (n = 9) by real-time qPCR-based TaqMan MicroRNA arrays. Then, predictive models were established using related miRNAs (n = 38) and verified by a double-blind trial (n = 54). We found that miR-411 was significantly down regulated when aGVHD developed and recovered when aGVHD was controlled, which demonstrated that miR-411 has potential as an indicator for aGVHD monitoring. We developed and validated a predictive model and a diagnostic model for aGVHD. The predictive model included two miRNAs (miR-26b and miR-374a), which could predict an increased risk for aGVHD 1 or 2 weeks in advance, with an AUC, Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of 0.722, 76.19 %, and 69.70 %, respectively. The diagnostic model included three miRNAs (miR-28-5p, miR-489, and miR-671-3p) with an AUC, PPV, and NPV of 0.841, 85.71 % and 83.33 %, respectively. Our results show that circulating miRNAs (miR-26b and miR-374a, miR-28-5p, miR-489 and miR-671-3p) may serve as biomarkers for the prediction and diagnosis of grades II-IV aGVHD.

Profiling microRNA expression during multi-staged date palm (Phoenix dactylifera L.) fruit development.

PubMed

Xin, Chengqi; Liu, Wanfei; Lin, Qiang; Zhang, Xiaowei; Cui, Peng; Li, Fusen; Zhang, Guangyu; Pan, Linlin; Al-Amer, Ali; Mei, Hailiang; Al-Mssallem, Ibrahim S; Hu, Songnian; Al-Johi, Hasan Awad; Yu, Jun

2015-04-01

MicroRNAs (miRNAs) play crucial roles in multiple stages of plant development and regulate gene expression at posttranscriptional and translational levels. In this study, we first identified 238 conserved miRNAs in date palm (Phoenix dactylifera) based on a high-quality genome assembly and defined 78 fruit-development-associated (FDA) miRNAs, whose expression profiles are variable at different fruit development stages. Using experimental data, we subsequently detected 276 novel P. dactylifera-specific FDA miRNAs and predicted their targets. We also revealed that FDA miRNAs function mainly in regulating genes involved in starch/sucrose metabolisms and other carbon metabolic pathways; among them, 221 FDA miRNAs exhibit negative correlation with their corresponding targets, which suggests their direct regulatory roles on mRNA targets. Our data define a comprehensive set of conserved and novel FDA miRNAs along with their expression profiles, which provide a basis for further experimentation in assigning discrete functions of these miRNAs in P. dactylifera fruit development. Copyright © 2015. Published by Elsevier Inc.

Inhibition of breast cancer metastasis with microRNA-302a by downregulation of CXCR4 expression.

PubMed

Liang, Zhongxing; Bian, Xuehai; Shim, Hyunsuk

2014-08-01

Metastasis remains a main cause of mortality from breast cancer and an unresolved issue. The purpose of this study is to investigate the role of miR-302a in the development of breast cancer metastasis mediated by CXCR4, a critical regulator of metastasis, and to identify miR-302a as an effective therapeutic agent for therapy and prevention of breast cancer metastasis. Our studies show that miR-302a expression levels were downregulated in metastatic breast cancer cells and tumor tissues. Additionally, the expression levels of miR-302a were inversely correlated with CXCR4 levels. More promisingly, miR-302a inhibited the invasion and metastasis of breast cancer cells in vitro and in vivo and reduced the expression of CXCR4. Our findings demonstrated that the repression of miR-302a levels contributes to breast cancer metastasis and restoration of miR-302a baseline expression inhibits the invasion and metastasis of breast cancer cells. These data suggest that miR-302a mimics are potential therapeutic agents for breast cancer metastasis.

Identification and comparative analysis of the microRNA transcriptome in roots of two contrasting tobacco genotypes in response to cadmium stress

NASA Astrophysics Data System (ADS)

He, Xiaoyan; Zheng, Weite; Cao, Fangbin; Wu, Feibo

2016-09-01

Tobacco (Nicotiana tabacum L.) is more acclimated to cadmium (Cd) uptake and preferentially enriches Cd in leaves than other crops. MicroRNAs (miRNAs) play crucial roles in regulating expression of various stress response genes in plants. However, genome-wide expression of miRNAs and their target genes in response to Cd stress in tobacco are still unknown. Here, miRNA high-throughput sequencing technology was performed using two contrasting tobacco genotypes Guiyan 1 and Yunyan 2 of Cd-sensitive and tolerance. Comprehensive analysis of miRNA expression profiles in control and Cd treated plants identified 72 known (27 families) and 14 novel differentially expressed miRNAs in the two genotypes. Among them, 28 known (14 families) and 5 novel miRNAs were considered as Cd tolerance associated miRNAs, which mainly involved in cell growth, ion homeostasis, stress defense, antioxidant and hormone signaling. Finally, a hypothetical model of Cd tolerance mechanism in Yunyan 2 was presented. Our findings suggest that some miRNAs and their target genes and pathways may play critical roles in Cd tolerance.

Dynamics of cholera epidemics with impulsive vaccination and disinfection.

PubMed

Sisodiya, Omprakash Singh; Misra, O P; Dhar, Joydip

2018-04-01

Waterborne diseases have a tremendous influence on human life. The contaminated drinking water causes water-borne disease like cholera. Pulse vaccination is an important and effective strategy for the elimination of infectious diseases. A waterborne disease like cholera can also be controlled by using impulse technique. In this paper, we have proposed a delayed SEIRB epidemic model with impulsive vaccination and disinfection. We have studied the pulse vaccination strategy and sanitation to control the cholera disease. The existence and stability of the disease-free and endemic periodic solution are investigated both analytically and numerically. It is shown that there exists an infection-free periodic solution, using the impulsive dynamical system defined by the stroboscopic map. It is observed that the infection-free periodic solution is globally attractive when the impulse period is less than some critical value. From the analysis of the model, we have obtained a sufficient condition for the permanence of the epidemic with pulse vaccination. The main highlight of this paper is to introduce impulse technique along with latent period into the SEIRB epidemic model to investigate the role of pulse vaccination and disinfection on the dynamics of the cholera epidemics. Copyright © 2018 Elsevier Inc. All rights reserved.

miRNAs Expressions and Interaction with Biological Systems in Patients with Alzheimer`s Disease. Using miRNAs as a Diagnosis and Prognosis Biomarker.

PubMed

Negoita, Silvius I; Sandesc, Dorel; Rogobete, Alexandru F; Dutu, Madalina; Bedreag, Ovidiu H; Papurica, Marius; Ercisli, Muhammed F; Popovici, Sonia E; Dumache, Raluca; Sandesc, Mihai; Dinu, Anca; Sas, Adriana M; Serban, Denis; Corneci, Dan

2017-09-01

A high percentage of patients develop Alzheimer`s disease (AD). The main signs are loss of memory and cognitive functions which have a significant impact on lifestyle. Numerous studies have been conducted to identify new biomarkers for early diagnosis of patients with AD. An ideal biomarker is represented by the expression of miRNAs. In this paper, we want to summarize expressions miRNAs in AD. We also want to present the pathophysiological and genetic interactions of miRNAs with protein systems in these patients. For the study, we examined available studies in scientific databases, such as PubMed and Scopus. The studies were searched using the keywords "miRNAs expression", "Alzheimer`s disease", "genetic polymorphisms", and "genetic biomarkers". For the assessment and monitoring of patients with AD, the expression of miRNAs can be used successfully due to increased specificity and selectivity. Moreover, the expression of miRNAs can provide important answers regarding possible genetic interactions and genetic therapeutic regimens. For the evaluation and non-invasive monitoring of patients with Alzheimer`s disease the expression of miRNAs can be successfully used.

MiR-103 Controls Milk Fat Accumulation in Goat (Capra hircus) Mammary Gland during Lactation

PubMed Central

Lin, Xianzi; Luo, Jun; Zhang, Liping; Wang, Wei; Gou, Deming

2013-01-01

Milk is the primary source of nutrition for young mammals including humans. The nutritional value of milk is mainly attributable to fats and proteins fractions. In comparison to cow milk, goat milk contains greater amounts of total fat, including much higher levels of the beneficial unsaturated fatty acids. MicroRNAs (miRNAs), a well-defined group of small RNAs containing about 22 nucleotides (nt), participate in various metabolic processes across species. However, little is known regarding the role of miRNAs in regulating goat milk composition. In the present study, we performed high-throughput sequencing to identify mammary gland-enriched miRNAs in lactating goats. We identified 30 highly expressed miRNAs in the mammary gland, including miR-103. Further studies revealed that miR-103 expression correlates with the lactation. Further functional analysis showed that over-expression of miR-103 in mammary gland epithelial cells increases transcription of genes associated with milk fat synthesis, resulting in an up-regulation of fat droplet formation, triglyceride accumulation, and the proportion of unsaturated fatty acids. This study provides new insight into the functions of miR-103, as well as the molecular mechanisms that regulate milk fat synthesis. PMID:24244462

MicroRNA-targeted therapeutics for lung cancer treatment.

PubMed

Xue, Jing; Yang, Jiali; Luo, Meihui; Cho, William C; Liu, Xiaoming

2017-02-01

Lung cancer is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs) are endogenous non-coding small RNAs that repress the expression of a broad array of target genes. Many efforts have been made to therapeutically target miRNAs in cancer treatments using miRNA mimics and miRNA antagonists. Areas covered: This article summarizes the recent findings with the role of miRNAs in lung cancer, and discusses the potential and challenges of developing miRNA-targeted therapeutics in this dreadful disease. Expert opinion: The development of miRNA-targeted therapeutics has become an important anti-cancer strategy. Results from both preclinical and clinical trials of microRNA replacement therapy have shown some promise in cancer treatment. However, some obstacles, including drug delivery, specificity, off-target effect, toxicity mediation, immunological activation and dosage determination should be addressed. Several delivery strategies have been employed, including naked oligonucleotides, liposomes, aptamer-conjugates, nanoparticles and viral vectors. However, delivery remains a main challenge in miRNA-targeting therapeutics. Furthermore, immune-related serious adverse events are also a concern, which indicates the complexity of miRNA-based therapy in clinical settings.

Drug-eluting versus bare-metal stents in unprotected left main coronary artery stenosis a meta-analysis.

PubMed

Pandya, Sanjay B; Kim, Young-Hak; Meyers, Sheridan N; Davidson, Charles J; Flaherty, James D; Park, Duk-Woo; Mediratta, Anuj; Pieper, Karen; Reyes, Eric; Bonow, Robert O; Park, Seung-Jung; Beohar, Nirat

2010-06-01

We undertook a meta-analysis to assess outcomes for drug-eluting stents (DES) and bare-metal stents (BMS) in percutaneous coronary intervention for unprotected left main coronary artery (ULMCA) stenosis. Uncertainty exists regarding the relative performance of DES versus BMS in percutaneous coronary intervention for unprotected left main coronary stenosis. Of a total of 838 studies, 44 met inclusion criteria (n = 10,342). The co-primary end points were mortality, myocardial infarction (MI), target vessel/lesion revascularization (TVR/TLR), and major adverse cardiac events (MACE: mortality, MI, TVR/TLR). Event rates for DES and BMS were calculated at 6 to 12 months, at 2 years, and at 3 years. Crude event rates at 3 years were mortality (8.8% and 12.7%), MI (4.0% and 3.4%), TVR/TLR (8.0% and 16.4%), and MACE (21.4% and 31.6%). Nine studies were included in a comparative analysis (n = 5,081). At 6 to 12 months the adjusted odds ratio (OR) for DES versus BMS were: mortality 0.94 (95% confidence interval [CI]: 0.06 to 15.48; p = 0.97), MI 0.64 (95% CI: 0.19 to 2.17; p = 0.47), TVR/TLR 0.10 (95% CI: 0.01 to 0.84; p = 0.01), and MACE 0.34 (95% CI: 0.15 to 0.78; p = 0.01). At 2 years, the OR for DES versus BMS were: mortality 0.42 (95% CI: 0.28 to 0.62; p < 0.01), MI 0.16 (95% CI: 0.01 to 3.53; p = 0.13), and MACE 0.31 (95% CI: 0.15 to 0.66; p < 0.01). At 3 years, the OR for DES versus BMS were: mortality 0.70 (95% CI: 0.53 to 0.92; p = 0.01), MI 0.49 (95% CI: 0.26 to 0.92; p = 0.03), TVR/TLR 0.46 (95% CI: 0.30 to 0.69; p < 0.01), and MACE 0.78 (95% CI: 0.57 to 1.07; p = 0.12). Our meta-analysis suggests that DES is associated with favorable outcomes for mortality, MI, TVR/TLR, and MACE as compared to BMS in percutaneous coronary intervention for unprotected left main coronary artery stenosis. Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

The MetOp second generation 3MI mission

NASA Astrophysics Data System (ADS)

Manolis, Ilias; Caron, Jérôme; Grabarnik, Semen; Bézy, Jean-Loup; Betto, Maurizio; Barré, Hubert; Mason, Graeme; Meynart, Roland

2017-11-01

ESA is currently running two parallel, competitive phase A/B1 studies for MetOp Second Generation (MetOp-SG). MetOp-SG is the space segment of EUMETSAT Polar System (EPS-SG) consisting of the satellites and instruments. The Phase A/B1 studies will be completed in the first quarter of 2013. The final implementation phases (B2/C/D) are planned to start 2013. ESA is responsible for instrument design of five missions, namely Microwave Sounding Mission (MWS), Scatterometer mission (SCA), Radio Occultation mission (RO), Microwave Imaging mission (MWI), Ice Cloud Imaging (ICI) mission, and Multiviewing, Multi-channel, Multi-polarization imaging mission (3MI). This paper will present the instrument main design elements of the 3MI mission, primarily aimed at providing aerosol characterization for climate monitoring, Numerical Weather Prediction (NWP), atmospheric chemistry and air quality. The 3MI instrument is a passive radiometer measuring the polarized radiances reflected by the Earth under different viewing geometries and across several spectral bands spanning the visible and short-wave infrared spectrum. The paper will present the main performances of the instrument and will concentrate mainly on the performance improvements with respect to its heritage derived by the POLDER instrument. The engineering of some key performance requirements (multiviewing, polarization sensitivity, etc.) will also be discussed.

A comparative study of the characterization of miR-155 in knockout mice

PubMed Central

Zhang, Dong; Cui, Yongchun; Li, Bin; Luo, Xiaokang; Li, Bo; Tang, Yue

2017-01-01

miR-155 is one of the most important miRNAs and plays a very important role in numerous biological processes. However, few studies have characterized this miRNA in mice under normal physiological conditions. We aimed to characterize miR-155 in vivo by using a comparative analysis. In our study, we compared miR-155 knockout (KO) mice with C57BL/6 wild type (WT) mice in order to characterize miR-155 in mice under normal physiological conditions using many evaluation methods, including a reproductive performance analysis, growth curve, ultrasonic estimation, haematological examination, and histopathological analysis. These analyses showed no significant differences between groups in the main evaluation indices. The growth and development were nearly normal for all mice and did not differ between the control and model groups. Using a comparative analysis and a summary of related studies published in recent years, we found that miR-155 was not essential for normal physiological processes in 8-week-old mice. miR-155 deficiency did not affect the development and growth of naturally ageing mice during the 42 days after birth. Thus, studying the complex biological functions of miR-155 requires the further use of KO mouse models. PMID:28278287

Outbreak of contact sensitization to methylisothiazolinone: an analysis of French data from the REVIDAL-GERDA network.

PubMed

Hosteing, Stéphanie; Meyer, Nicolas; Waton, Julie; Barbaud, Annick; Bourrain, Jean-Luc; Raison-Peyron, Nadia; Felix, Brigitte; Milpied-Homsi, Brigitte; Ferrier Le Bouedec, Marie-Christine; Castelain, Michel; Vital-Durand, Dominique; Debons, Michèle; Collet, Evelyne; Avenel-Audran, Martine; Mathelier-Fusade, Pascale; Vermeulen, Christophe; Assier, Haudrey; Gener, Gwendoline; Lartigau-Sezary, Isabelle; Catelain-Lamy, Amandine; Giordano-Labadie, Françoise

2014-05-01

The preservative methylisothiazolinone (MI) is used in combination with methylchloroisothiazolinone (MCI), but the MCI/MI mixture has been identified as highly allergenic. MI is considered to be less allergenic, and since the mid-2000s has been widely used alone, but is now clearly identified as a contact allergen. The French Vigilance Network for Dermatology and Allergy of the Study and Research Group on Contact Dermatitis (REVIDAL-GERDA) added MI to its baseline patch testing series in 2010. To evaluate the change in the proportion of MI-positive tests in France between 2010 and 2012. We conducted a nationwide, multicentre, retrospective study of all MI-tested patients between 2010 and 2012. Sixteen centres participated in the study (7874 patients were tested). Patch tests were performed mainly at a concentration of MI 200 ppm aq. We observed a significant increase in the proportion of MI-positive tests in 2012 and 2011 as compared with 2010 (5.6%, 3.3%, and 1.5%, respectively; p < 0.001). We report a significant increase in the number of MI-positive tests. MI is confirmed to be a rapidly emerging allergen, as also observed in other European countries. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Role of Cleaning Products in Epidemic Allergic Contact Dermatitis to Methylchloroisothiazolinone/Methylisothiazolinone.

PubMed

Marrero-Alemán, Gabriel; Saavedra Santana, Pedro; Liuti, Federica; Hernández, Noelia; López-Jiménez, Esmeralda; Borrego, Leopoldo

Sensitivity to methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI) has increased rapidly over recent years. This increase is mainly related to the extensive use of high concentrations of MI in cosmetic products, although a growing number of cases of occupational allergic contact dermatitis are caused by MCI/MI. The aim of this study was to examine the association between the increase in MCI/MI sensitization and the work performed by the patients in our area. A retrospective study was undertaken of the records of a total of 1179 patients who had undergone contact skin patch tests for MCI/MI from January 2005 to December 2015. A multivariate logistic regression analysis was performed to identify the factors independently associated with sensitivity to MCI/MI. A constant increase in MCI/MI sensitization was observed over the observation period. The only work associated with a significant increase in the prevalence of MCI/MI sensitization was cleaning, with 38.5% of the cleaning professionals with MCI/MI sensitization consulting for cosmetics-related dermatitis. Occupational sensitization to MCI/MI in cleaning professionals is worryingly increasing. This, in turn, could possibly account for many cases of cosmetics-associated contact dermatitis. Our findings suggest that a review of the regulations with regard to isothiazolinone concentrations in industrial and household detergents is necessary.

Biological implications and clinical value of mir-210 in gastrointestinal cancer.

PubMed

Yang, Wanli; Ma, Jiaojiao; Zhou, Wei; Zhou, Xin; Cao, Bo; Fan, Daiming; Hong, Liu

2017-06-01

Hypoxia, a common feature of tumor microenvironment, is known to accelerate tumor development and growth by promoting the formation of a neoplastic environment. Recent studies have provided a wealth of evidence that miRNAs are significant members of the adaptive response to low oxygen in tumors. miR-210 is one of the hypoxia-induced miRNAs, which has been reported extensively in cancer researches. However, there is no systematic discussion about the role of miR-210 in gastrointestinal cancer. We conducted a literature research in database including PubMed, Elsevier Science Direct and Medline before 16 September 2016, in order to collect articles of miR-210 in gastrointestinal cancer. Areas covered: In the present review, we mainly discuss the following aspects: hypoxia-induced dysregulation of miR-210, the expression of miR-210 and tumorigenesis, the resultant changes of miR-210 targets and its roles in different types of gastrointestinal cancer progression, the diagnostic, therapeutic and prognostic value of miR-210 in gastrointestinal cancer. Expert commentary: Numerous researches have demonstrated the values of miR-210 in cancer diagnosis, prognosis and targeted therapies, especially in gastrointestinal cancers. However, there are also some existing problems and challenges in translating the new research findings into clinical utility. Further investigations and studies are still urgently required.

Correlated miR-mRNA expression signatures of mouse hematopoietic stem and progenitor cell subsets predict "Stemness" and "Myeloid" interaction networks.

PubMed

Heiser, Diane; Tan, Yee Sun; Kaplan, Ian; Godsey, Brian; Morisot, Sebastien; Cheng, Wen-Chih; Small, Donald; Civin, Curt I

2014-01-01

Several individual miRNAs (miRs) have been implicated as potent regulators of important processes during normal and malignant hematopoiesis. In addition, many miRs have been shown to fine-tune intricate molecular networks, in concert with other regulatory elements. In order to study hematopoietic networks as a whole, we first created a map of global miR expression during early murine hematopoiesis. Next, we determined the copy number per cell for each miR in each of the examined stem and progenitor cell types. As data is emerging indicating that miRs function robustly mainly when they are expressed above a certain threshold (∼100 copies per cell), our database provides a resource for determining which miRs are expressed at a potentially functional level in each cell type. Finally, we combine our miR expression map with matched mRNA expression data and external prediction algorithms, using a Bayesian modeling approach to create a global landscape of predicted miR-mRNA interactions within each of these hematopoietic stem and progenitor cell subsets. This approach implicates several interaction networks comprising a "stemness" signature in the most primitive hematopoietic stem cell (HSC) populations, as well as "myeloid" patterns associated with two branches of myeloid development.

Detection of motor imagery of swallow EEG signals based on the dual-tree complex wavelet transform and adaptive model selection

NASA Astrophysics Data System (ADS)

Yang, Huijuan; Guan, Cuntai; Sui Geok Chua, Karen; San Chok, See; Wang, Chuan Chu; Kok Soon, Phua; Tang, Christina Ka Yin; Keng Ang, Kai

2014-06-01

Objective. Detection of motor imagery of hand/arm has been extensively studied for stroke rehabilitation. This paper firstly investigates the detection of motor imagery of swallow (MI-SW) and motor imagery of tongue protrusion (MI-Ton) in an attempt to find a novel solution for post-stroke dysphagia rehabilitation. Detection of MI-SW from a simple yet relevant modality such as MI-Ton is then investigated, motivated by the similarity in activation patterns between tongue movements and swallowing and there being fewer movement artifacts in performing tongue movements compared to swallowing. Approach. Novel features were extracted based on the coefficients of the dual-tree complex wavelet transform to build multiple training models for detecting MI-SW. The session-to-session classification accuracy was boosted by adaptively selecting the training model to maximize the ratio of between-classes distances versus within-class distances, using features of training and evaluation data. Main results. Our proposed method yielded averaged cross-validation (CV) classification accuracies of 70.89% and 73.79% for MI-SW and MI-Ton for ten healthy subjects, which are significantly better than the results from existing methods. In addition, averaged CV accuracies of 66.40% and 70.24% for MI-SW and MI-Ton were obtained for one stroke patient, demonstrating the detectability of MI-SW and MI-Ton from the idle state. Furthermore, averaged session-to-session classification accuracies of 72.08% and 70% were achieved for ten healthy subjects and one stroke patient using the MI-Ton model. Significance. These results and the subjectwise strong correlations in classification accuracies between MI-SW and MI-Ton demonstrated the feasibility of detecting MI-SW from MI-Ton models.

The Pathway Analysis of Micrornas Regulated Drug-Resistant Responses in HeLa Cells.

PubMed

Yang, Yubo; Dai, Cuihong; Cai, Zhipeng; Hou, Aiju; Cheng, Dayou; Wu, Guanying; Li, Jing; Cui, Jie; Xu, Dechang

2016-03-01

Chemotherapy is the main strategy in the treatment of cancer; however, the development of drug-resistance is the obstacle in long-term treatment of cervical cancer. Cisplatin is one of the most common drugs used in cancer therapy. Recently, accumulating evidence suggests that miRNAs are involved in various bioactivities in oncogenesis. It is not unexpected that miRNAs play a key role in acquiring of drug-resistance in the progression of tumor. In this study, we induced and maintained four levels of cisplatin-resistant HeLa cell lines (HeLa/CR1, HeLa/CR2, HeLa/CR3, and HeLa/CR4). According to the previous studies and existing evidence, we selected five miRNAs (miR-183, miR-182, miR-30a, miR-15b, and miR-16) and their potential target mRNAs as our research targets. The real-time RT-PCR was adopted to detect the relative expression of miRNAs and their mRNAs. The results show that miR-182 and miR-15b were up-regulated in resistant cell lines, while miR-30a was significantly down-regulated. At the same time, their targets are related to drug resistance. Compared to their parent HeLa cell line, the expression of selected miRNAs in resistant cell lines altered. The alteration suggests that HeLa cell drug resistance is associated with distinct miRNAs, which indicates that miRNAs may be one of the therapy targets in the treatment of cervical cancer by sensitizing cell to chemotherapy. We suggested a possible network diagram based on the existing theory and the preliminary results of candidate miRNAs and their targets in HeLa cells during development of drug resistance.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wedeken, U.; Voelker, H.; Knott, K.

The SSC occurring on March 22, 1979, at 0826 UT had an unusually sharp onset in Scandinavia, in Middle Europe and in experiments on the geostationary satellite GEOS 2, which was near noon, local magnetic time. The ground magnetometer stations showed a small preimpuse which started approx.5 s before the main impulse. Both impulses needed approx.2 s to ''propagate'' from ground stations at L = 6.3-4.6. Search coil magnetometers indicate a very small precursor in northern Finland (Lapprox.4.4-6.0) which started approx.15-20 s before the main impulse. This small precursor also occurred close to the time of the SSC onset atmore » GEOS 2. We interpret this precursor as an effect of precipitating electrons changing the ionospheric conductivity in a localized region. The main impulse triggered damped magnetic pulsations (Psc) with periods near 160 s and 50 s visible in northern Scandinavia and the electric field detector on GEOS 2. Furthermore, the magnetic field and the energetic ions at GEOS observed pulsations with periods near 80 s, but these could only be observed at the northernmost ground stations. There are several indications that the first three harmonics of standing hydromagnetic waves are detected. They may correspond to periodic oscillations of the subsolar point or eigenperiods of the SSC-excited fast mode (compressional cavity resonance). The tentatively identified second harmonic wave (period approx.80 s) is indicative of a bounce resonance of ring current protons. Inside the plasmasphere the dominant period of a superimposed Psc 4 event increased with latitude for the H component indicating several toroidal eigenoscillations.« less

miR-155 promotes cutaneous wound healing through enhanced keratinocytes migration by MMP-2.

PubMed

Yang, Longlong; Zheng, Zhao; Zhou, Qin; Bai, Xiaozhi; Fan, Lei; Yang, Chen; Su, Linlin; Hu, Dahai

2017-04-01

Inflammation, re-epithelization and tissue remodeling are three essential steps during wound healing. The re-epithelization process plays the most important role which mainly involves keratinocyte proliferation and migration. miR-155 has been reported to participate in cell migration and transformation, however, its function in skin wound healing is largely unknown. Here we hypothesize that overexpression of miR-155 at wound edges could accelerate wound healing mediated by enhanced keratinocyte migration. To test this hypothesis, direct local injection of miR-155 expression plasmid to wound edges was conducted to overexpress miR-155 in vivo. Results shown that miR-155 significantly promoted wound healing and re-epithelization compared to control, while did not affect wound contraction. Also, miR-155 overexpression accelerated primarily cultured keratinocyte migration in vitro, but had no effect on cell proliferation. Importantly, western blot analysis shown that MMP-2 was significantly upregulated whiles its inhibitor TIMP-1 downregulated after miR-155 treatment. Moreover, the use of ARP-101, an MMP-2 inhibitor, effectively attenuated the accelerative effects on cell migration induced by miR-155. Taken together, our results suggest that miR-155 has the promote effect on wound healing that is probably mediated by accelerating keratinocyte migration via upregulated MMP-2 level. This study provides a rationale for the therapeutic effect of miR-155 on wound healing.

The microRNAs as potential biomarkers for predicting the onset of aflatoxin exposure in human beings: a review.

PubMed

Valencia-Quintana, Rafael; Sánchez-Alarcón, Juana; Tenorio-Arvide, María G; Deng, Youjun; Montiel-González, José M R; Gómez-Arroyo, Sandra; Villalobos-Pietrini, Rafael; Cortés-Eslava, Josefina; Flores-Márquez, Ana R; Arenas-Huertero, Francisco

2014-01-01

The identification of aflatoxins as human carcinogens has stimulated extensive research efforts, which continue to the present, to assess potential health hazards resulting from contamination of the human food supply and to minimize exposure. The use of biomarkers that are mechanistically supported by toxicological studies will be important tools for identifying stages in the progression of development of the health effects of environmental agents. miRNAs are small non-coding mRNAs that regulate post-transcriptional gene expression. Also, they are molecular markers of cellular responses to various chemical agents. Growing evidence has demonstrated that environmental chemicals can induce changes in miRNA expression. miRNAs are good biomarkers because they are well defined, chemically uniform, restricted to a manageable number of species, and stable in cells and in the circulation. miRNAs have been used as serological markers of HCC and other tumors. The expression patterns of different miRNAs can distinguish among HCC-hepatitis viruses related, HCC cirrhosis-derivate, and HCC unrelated to either of them. The main objective of this review is to find unreported miRNAs in HCC related to other causes, so that they can be used as specific molecular biomarkers in populations exposed to aflatoxins and as early markers of exposure, damage/presence of HCC. Until today specific miRNAs as markers for aflatoxins-exposure and their reliability are currently lacking. Based on their elucidated mechanisms of action, potential miRNAs that could serve as possible markers of HCC by exposure to aflatoxins are miR-27a, miR-27b, miR-122, miR-148, miR-155, miR-192, miR-214, miR-221, miR-429, and miR-500. Future validation for all of these miRNAs will be needed to assess their prognostic significance and confirm their relationship with the induction of HCC due to aflatoxin exposure.

Changes in metal properties after thermal and electric impulse processing

NASA Astrophysics Data System (ADS)

Shaburova, N. A.

2015-04-01

The results of the experiments on processing metal melts by powerful electromagnetic impulses are given. The generator used in the experiments has the following characteristics: pulse height - 10KV, duration - 1ns, leading edge - 0.1ns, repetition rate - 1KHz, the output - 100KWt. The duration of the processing is 10-15min. The comparative analysis of the processed and unprocessed samples results in the changes of structure, increase of density, solidity, plasticity and resilience of cast metal. The result analysis of different external physical processing methods on alloys shows full agreement with the results of the ultrasonic processing of metals. The hypothesis of ultrasonic shock wave formation at the pulse front was adopted as the main mechanism of the electromagnetic impulse impact on alloys. The theoretical part of the research describes the transformation process of electromagnetic impulses into acoustic ones.

Role of microRNAs and Exosomes in Helicobacter pylori and Epstein-Barr Virus Associated Gastric Cancers

PubMed Central

Polakovicova, Iva; Jerez, Sofia; Wichmann, Ignacio A.; Sandoval-Bórquez, Alejandra; Carrasco-Véliz, Nicolás; Corvalán, Alejandro H.

2018-01-01

Emerging evidence suggests that chronic inflammation caused by pathogen infection is connected to the development of various types of cancer. It is estimated that up to 20% of all cancer deaths is linked to infections and inflammation. In gastric cancer, such triggers can be infection of the gastric epithelium by either Helicobacter pylori (H. pylori), a bacterium present in half of the world population; or by Epstein-Barr virus (EBV), a double-stranded DNA virus which has recently been associated with gastric cancer. Both agents can establish lifelong inflammation by evolving to escape immune surveillance and, under certain conditions, contribute to the development of gastric cancer. Non-coding RNAs, mainly microRNAs (miRNAs), influence the host innate and adaptive immune responses, though long non-coding RNAs and viral miRNAs also alter these processes. Reports suggest that chronic infection results in altered expression of host miRNAs. In turn, dysregulated miRNAs modulate the host inflammatory immune response, favoring bacterial survival and persistence within the gastric mucosa. Given the established roles of miRNAs in tumorigenesis and innate immunity, they may serve as an important link between H. pylori- and EBV-associated inflammation and carcinogenesis. Example of this is up-regulation of miR-155 in H. pylori and EBV infection. The tumor environment contains a variety of cells that need to communicate with each other. Extracellular vesicles, especially exosomes, allow these cells to deliver certain type of information to other cells promoting cancer growth and metastasis. Exosomes have been shown to deliver not only various types of genetic information, mainly miRNAs, but also cytotoxin-associated gene A (CagA), a major H. pylori virulence factor. In addition, a growing body of evidence demonstrates that exosomes contain genetic material of viruses and viral miRNAs and proteins such as EBV latent membrane protein 1 (LMP1) which are delivered into recipient cells. In this review, we focus on the dysregulated H. pylori- and EBV-associated miRNAs while trying to unveil possible causal mechanisms. Moreover, we discuss the role of exosomes as vehicles for miRNA delivery in H. pylori- and EBV-related carcinogenesis. PMID:29675003

MicroRNA-143 Regulates Human Osteosarcoma Metastasis by Regulating Matrix Metalloprotease-13 Expression

PubMed Central

Osaki, Mitsuhiko; Takeshita, Fumitaka; Sugimoto, Yui; Kosaka, Nobuyoshi; Yamamoto, Yusuke; Yoshioka, Yusuke; Kobayashi, Eisuke; Yamada, Tesshi; Kawai, Akira; Inoue, Toshiaki; Ito, Hisao; Oshimura, Mitsuo; Ochiya, Takahiro

2011-01-01

Pulmonary metastases are the main cause of death in patients with osteosarcoma, however, the molecular mechanisms of metastasis are not well understood. To detect lung metastasis-related microRNA (miRNA) in human osteosarcoma, we compared parental (HOS) and its subclone (143B) human osteosarcoma cell lines showing lung metastasis in a mouse model. miR-143 was the most downregulated miRNA (P < 0.01), and transfection of miR-143 into 143B significantly decreased its invasiveness, but not cell proliferation. Noninvasive optical imaging technologies revealed that intravenous injection of miR-143, but not negative control miRNA, significantly suppressed lung metastasis of 143B (P < 0.01). To search for miR-143 target mRNA in 143B, microarray analyses were performed using an independent RNA pool extracted by two different comprehensive miR-143-target mRNA collecting systems. Western blot analyses revealed that MMP-13 was mostly protein downregulated by miR-143. Immunohistochemistry using clinical samples clearly revealed MMP-13-positive cells in lung metastasis-positive cases, but not in at least three cases showing higher miR-143 expression in the no metastasis group. Taken together, these data indicated that the downregulation of miR-143 correlates with the lung metastasis of human osteosarcoma cells by promoting cellular invasion, probably via MMP-13 upregulation, suggesting that miRNA could be used to develop new molecular targets for osteosarcoma metastasis. PMID:21427707

Shift of microRNA profile upon orthotopic xenografting of glioblastoma spheroid cultures.

PubMed

Halle, Bo; Thomassen, Mads; Venkatesan, Ranga; Kaimal, Vivek; Marcusson, Eric G; Munthe, Sune; Sørensen, Mia D; Aaberg-Jessen, Charlotte; Jensen, Stine S; Meyer, Morten; Kruse, Torben A; Christiansen, Helle; Schmidt, Steffen; Mollenhauer, Jan; Schulz, Mette K; Andersen, Claus; Kristensen, Bjarne W

2016-07-01

Glioblastomas always recur despite surgery, radiotherapy and chemotherapy. A key player in the therapeutic resistance may be immature tumor cells with stem-like properties (TSCs) escaping conventional treatment. A group of promising molecular targets are microRNAs (miRs). miRs are small non-coding RNAs exerting post-transcriptional regulation of gene expression. In this study we aimed to identify over-expressed TSC-related miRs potentially amenable for therapeutic targeting. We used non-differentiated glioblastoma spheroid cultures (GSCs) containing TSCs and compared these to xenografts using a NanoString nCounter platform. This revealed 19 over-expressed miRs in the non-differentiated GSCs. Additionally, non-differentiated GSCs were compared to neural stem cells (NSCs) using a microarray platform. This revealed four significantly over-expressed miRs in the non-differentiated GSCs in comparison to the NSCs. The three most over-expressed miRs in the non-differentiated GSCs compared to xenografts were miR-126, -137 and -128. KEGG pathway analysis suggested the main biological function of these over-expressed miRs to be cell-cycle arrest and diminished proliferation. To functionally validate the profiling results suggesting association of these miRs with stem-like properties, experimental over-expression of miR-128 was performed. A consecutive limiting dilution assay confirmed a significantly elevated spheroid formation in the miR-128 over-expressing cells. This may provide potential therapeutic targets for anti-miRs to identify novel treatment options for GBM patients.

Analysis of plasma microRNA expression profiles revealed different cancer susceptibility in healthy young adult smokers and middle-aged smokers

PubMed Central

Shi, Bing; Gao, Hongmin; Zhang, Tianyang; Cui, Qinghua

2016-01-01

Cigarette smoking is a world-wide habit and an important risk factor for cancer. It was known that cigarette smoking can change the expression of circulating microRNAs (miRNAs) in healthy middle-aged adults. However, it remains unclear whether cigarette smoking can change the levels of circulating miRNAs in young healthy smokers and whether there are differences in cancer susceptibility for the two cases. In this study, the miRNA expression profiles of 28 smokers and 12 non-smokers were determined by Agilent human MicroRNA array. We further performed bioinformatics analysis for the differentially expressed miRNAs. The result showed that 35 miRNAs were differentially expressed. Among them, 24 miRNAs were up-regulated and 11 miRNAs were down-regulated in smokers. Functional enrichment analysis showed that the deregulated miRNAs are related to immune system and hormones regulation. Strikingly, the up-regulated miRNAs are mostly associated with hematologic cancers, such as lymphoma, leukemia. As a comparison, the up-regulated plasma miRNAs in middle-aged smokers are mostly associated with solid cancers, such as hepatocellular carcinoma and lung cancer, suggesting that smoking could have different influences on young adults and middle-aged adults. In a conclusion, we identified the circulating miRNAs deregulated by cigarette smoking and revealed that the age-dependent deregulated miRNAs tend to be mainly involved in different types of human cancers. PMID:26943588

Analysis of plasma microRNA expression profiles revealed different cancer susceptibility in healthy young adult smokers and middle-aged smokers.

PubMed

Shi, Bing; Gao, Hongmin; Zhang, Tianyang; Cui, Qinghua

2016-04-19

Cigarette smoking is a world-wide habit and an important risk factor for cancer. It was known that cigarette smoking can change the expression of circulating microRNAs (miRNAs) in healthy middle-aged adults. However, it remains unclear whether cigarette smoking can change the levels of circulating miRNAs in young healthy smokers and whether there are differences in cancer susceptibility for the two cases. In this study, the miRNA expression profiles of 28 smokers and 12 non-smokers were determined by Agilent human MicroRNA array. We further performed bioinformatics analysis for the differentially expressed miRNAs. The result showed that 35 miRNAs were differentially expressed. Among them, 24 miRNAs were up-regulated and 11 miRNAs were down-regulated in smokers. Functional enrichment analysis showed that the deregulated miRNAs are related to immune system and hormones regulation. Strikingly, the up-regulated miRNAs are mostly associated with hematologic cancers, such as lymphoma, leukemia. As a comparison, the up-regulated plasma miRNAs in middle-aged smokers are mostly associated with solid cancers, such as hepatocellular carcinoma and lung cancer, suggesting that smoking could have different influences on young adults and middle-aged adults. In a conclusion, we identified the circulating miRNAs deregulated by cigarette smoking and revealed that the age-dependent deregulated miRNAs tend to be mainly involved in different types of human cancers.

miR-192 suppresses leptomeningeal dissemination of medulloblastoma by modulating cell proliferation and anchoring through the regulation of DHFR, integrins, and CD47

PubMed Central

Lee, Ji Yeoun; Park, Ae-Kyung; Wang, Kyu-Chang; Phi, Ji Hoon; Koh, Eun Jung; Park, Woong-Yang; Park, Sung-Hye; Hwang, Do Won; Jung, Hee Won; Kim, Seung-Ki

2015-01-01

Background The main cause of death in medulloblastoma is recurrence associated with leptomeningeal dissemination. During this process, the role of microRNAs (miRs) in the acquisition of metastatic phenotype remains poorly understood. This study aimed to identify the miR involved in leptomeningeal dissemination and to elucidate its biological functional mechanisms. Materials and methods We analyzed the miR expression profiles of 29 medulloblastomas according to the presence of cerebrospinal fluid (CSF) seeding. Differentially expressed miRs (DEmiRs) were validated in 29 medulloblastoma tissues and three medulloblastoma cell lines. The biological functions of the selected miRs were evaluated using in vitro and in vivo studies. Results A total of 12 DEmiRs were identified in medulloblastoma with seeding, including miR-192. The reduced expression of miR-192 was confirmed in the tumor seeding group and in the medulloblastoma cells. Overexpression of miR-192 inhibited cellular proliferation by binding DHFR. miR-192 decreased cellular anchoring via the repression of ITGAV, ITGB1, ITGB3, and CD47. Animals in the miR-192-treated group demonstrated a reduction of spinal seeding (P < 0.05) and a significant survival benefit (P < 0.05). Conclusions Medulloblastoma with seeding showed specific DEmiRs compared with those without. miR-192 suppresses leptomeningeal dissemination of medulloblastoma by modulating cell proliferation and anchoring ability. PMID:26506238

Identification of several circulating microRNAs from a genome-wide circulating microRNA expression profile as potential biomarkers for impaired glucose metabolism in polycystic ovarian syndrome.

PubMed

Jiang, Linlin; Huang, Jia; Chen, Yaxiao; Yang, Yabo; Li, Ruiqi; Li, Yu; Chen, Xiaoli; Yang, Dongzi

2016-07-01

This study aimed to detect serum microRNAs (miRNAs) differentially expressed between polycystic ovary syndrome (PCOS) patients with impaired glucose metabolism (IGM), PCOS patients with normal glucose tolerance (NGT), and healthy controls. A TaqMan miRNA array explored serum miRNA profiles as a pilot study, then selected miRNAs were analyzed in a validation cohort consisting of 65 PCOS women with IGM, 65 PCOS women with NGT, and 45 healthy women The relative expression of miR-122, miR-193b, and miR-194 was up-regulated in PCOS patients compared with controls, whereas that of miR-199b-5p was down-regulated. Furthermore, miR-122, miR-193b, and miR-194 were increased in the PCOS-IGM group compared with the PCOS-NGT group. Multiple linear regression analyses revealed that miR-193b and body mass index contributed independently to explain 43.7 % (P < 0.0001) of homeostasis model assessment-insulin resistance after adjustment for age. Investigation of diagnostic values confirmed the optimal combination of BMI and miR-193b to explore the possibility of IGM in PCOS women with area under the curve of 0.752 (95 % CI 0.667-0.837, P < 0.001). Bioinformatics analysis indicated that the predicted target functions of these miRNAs mainly involved glycometabolism and ovarian follicle development pathways, including the insulin signaling pathway, the neurotrophin signaling pathway, the PI3K-AKT signaling pathway, and regulation of actin cytoskeleton. This study expands our knowledge of the serum miRNA expression profiles of PCOS patients with IGM and the predicted target signal pathways involved in disease pathophysiology.

Increased serum miR-300 level serves as a potential biomarker of lipopolysaccharide-induced lung injury by targeting IκBα.

PubMed

Cao, Wei; Dai, Hong; Yang, Shengqing; Liu, Zhijun; Yi Chen, Qian

2017-01-10

MicroRNAs (miRs) are reported to play key roles in various disease models. In this study, the functional role of miR-300 in the regulation of lung injury was explored to assess the feasibility of serum miR-300 as a potential biomarker for lung injury. Firstly, the expression of miR-300 was studied in the serum of 50 lung injury patients and 50 healthy controls. And the expression of miR-300 was also explored in the serum and lung tissues of mouse models. To further explore the possible mechanism in which miR-300 may contribute to lung injury, the target genes of miR-300 were predicted by TargetScan and validated using dual luciferase reporter assay. Moreover, the expression of inflammation factors was studied after transfection of miR-300 mimics and inhibitors into A549 cells. Here, we first identified that the level of miR-300 was significantly upregulated in the blood samples of acute lung injury patients compared with healthy control. Meanwhile, miR-300 was also found to be enhanced in the blood samples and lung tissues of LPS-induced mouse models. Further study showed that miR-300 significantly suppressed the expression of IκBα and luciferase reporter assay showed that IκBα was a target gene of miR-300. More importantly, the levels of inflammatory factors, such as TNFα, COX-2, iNOS, IL-6 and IL8, were significantly upregulated accompanied by overexpression of miR-300 in A549 cells. In summary, enhanced miR-300 expression in the peripheral blood contributed to the lung injury mainly by inhibiting the expression of IκBα.

MicroRNA-127-3p inhibits proliferation and invasion by targeting SETD8 in human osteosarcoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Jun; Hou, Wengen; Chai, Mingxiang

2016-01-22

MicroRNAs (miRNAs) play an essential role in cancer development. Several studies have indicated that miRNAs mediate tumorigenesis processes, such as, inflammation, proliferation, apoptosis and invasion. In the present study, we focused on the influence of the miR-127-3p on the proliferation, migration and invasion of osteosarcoma (OS). MiR-127-3p was found at reduced levels in OS tissues and cell lines. Overexpression of miR-127-3p in the OS cell lines significantly inhibited the cell proliferation, migration and invasion; however, inhibition of miR-127-3p increased the proliferation, migration and invasion of OS in vitro. SETD8 was identified as a direct target of miR-127-3p, and SETD8 expression decreasedmore » post miR-127-3p overexpression, while SETD8 overexpression could reverse the potential influence of miR-127-3p on the migration and invasion of OS cells. MiR-127-3p is suggested to act mainly via the suppression of SETD8 expression. Overall, the results revealed that miR-127-3p acts as a tumor suppressor and that its down-regulation in cancer may contribute to OS progression and metastasis, suggesting that miR-127-3p could be a potential therapeutic target in the treatment of OS. - Highlights: • MiR-127-3p is decreased in osteosarcoma tissues and cell lines. • MiR-127-3p overexpression suppresses cell migration and invasion in MG63 and U2OS. • SETD8 overexpression abolishes the roles of miR-127-3p in osteosarcoma.« less

Tuning of major signaling networks (TGF-β, Wnt, Notch and Hedgehog) by miRNAs in human stem cells commitment to different lineages: Possible clinical application.

PubMed

Aval, Sedigheh Fekri; Lotfi, Hajie; Sheervalilou, Roghayeh; Zarghami, Nosratollah

2017-07-01

Two distinguishing characteristics of stem cells, their continuous division in the undifferentiated state and growth into any cell types, are orchestrated by a number of cell signaling pathways. These pathways act as a niche factor in controlling variety of stem cells. The core stem cell signaling pathways include Wingless-type (Wnt), Hedgehog (HH), and Notch. Additionally, they critically regulate the self-renewal and survival of cancer stem cells. Conversely, stem cells' main properties, lineage commitment and stemness, are tightly controlled by epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNA-mediated regulatory events. MicroRNAs (miRNAs) are cellular switches that modulate stem cells outcomes in response to diverse extracellular signals. Numerous scientific evidences implicating miRNAs in major signal transduction pathways highlight new crosstalks of cellular processes. Aberrant signaling pathways and miRNAs levels result in developmental defects and diverse human pathologies. This review discusses the crosstalk between the components of main signaling networks and the miRNA machinery, which plays a role in the context of stem cells development and provides a set of examples to illustrate the extensive relevance of potential novel therapeutic targets. Copyright © 2017. Published by Elsevier Masson SAS.

Overview of large animal myocardial infarction models (review).

PubMed

Lukács, E; Magyari, B; Tóth, L; Petrási, Zs; Repa, I; Koller, A; Horváth, Iván

2012-12-01

There are several experimental models for the in vivo investigation of myocardial infarction (MI) in small (mouse, rat) and large animals (dog, pig, sheep and baboons). The application of large animal models raises ethical concerns, the design of experiments needs longer follow-up times, requiring proper breeding and housing conditions, therefore resulting in higher cost, than in vitro or small animal studies. On the other hand, the relevance of large animal models is very important, since they mostly resemble to human physiological and pathophysiological processes. The first main difference among MI models is the method of induction (open or closed chest, e.g. surgical or catheter based); the second main difference is the presence or absence of reperfusion. The former (i.e. reperfused MI) allows the investigation of reperfusion injury and new catheter based techniques during percutaneous coronary interventions, while the latter (i.e. nonreperfused MI) serves as a traditional coronary occlusion model, to test the effects of new pharmacological agents and biological therapies, as cell therapy. The reperfused and nonreperfused myocardial infarction has different outcomes, regarding left ventricular function, remodelling, subsequent heart failure, aneurysm formation and mortality. Our aim was to review the literature and report our findings regarding experimental MI models, regarding the differences among species, methods, reproducibility and interpretation.

Infinite horizon optimal impulsive control with applications to Internet congestion control

NASA Astrophysics Data System (ADS)

Avrachenkov, Konstantin; Habachi, Oussama; Piunovskiy, Alexey; Zhang, Yi

2015-04-01

We investigate infinite-horizon deterministic optimal control problems with both gradual and impulsive controls, where any finitely many impulses are allowed simultaneously. Both discounted and long-run time-average criteria are considered. We establish very general and at the same time natural conditions, under which the dynamic programming approach results in an optimal feedback policy. The established theoretical results are applied to the Internet congestion control, and by solving analytically and nontrivially the underlying optimal control problems, we obtain a simple threshold-based active queue management scheme, which takes into account the main parameters of the transmission control protocols, and improves the fairness among the connections in a given network.

Tip-path-plane angle effects on rotor blade-vortex interaction noise levels and directivity

NASA Technical Reports Server (NTRS)

Burley, Casey L.; Martin, Ruth M.

1988-01-01

Acoustic data of a scale model BO-105 main rotor acquired in a large aeroacoustic wind tunnel are presented to investigate the parametric effects of rotor operating conditions on blade-vortex interaction (BVI) impulsive noise. Contours of a BVI noise metric are employed to quantify the effects of rotor advance ratio and tip-path-plane angle on BVI noise directivity and amplitude. Acoustic time history data are presented to illustrate the variations in impulsive characteristics. The directionality, noise levels and impulsive content of both advancing and retreating side BVI are shown to vary significantly with tip-path-plane angle and advance ratio over the range of low and moderate flight speeds considered.

Impulsivity and Stress Response in Pathological Gamblers During the Trier Social Stress Test.

PubMed

Maniaci, G; Goudriaan, A E; Cannizzaro, C; van Holst, R J

2018-03-01

Gambling has been associated with increased sympathetic nervous system output and stimulation of the hypothalamic-pituitary-adrenal axis. However it is unclear how these systems are affected in pathological gambling. This study aimed to investigate the effect of the Trier Social Stress Test (TSST) on cortisol and on cardiac interbeat intervals in relation to impulsivity, in a sample of male pathological gamblers compared to healthy controls. In addition, we investigated the correlation between the TSST, duration of the disorder and impulsivity. A total of 35 pathological gamblers and 30 healthy controls, ranging from 19 to 58 years old and all male, participated in this study. Stress response was measured during and after the TSST by salivary cortisol and cardiac interbeat intervals; impulsivity was assessed with the Barratt Impulsiveness Scale (BIS-11). Exposure to the TSST produced a significant increase in salivary cortisol and interbeat intervals in both groups, without differences between groups. We found a negative correlation between baseline cortisol and duration of pathological gambling indicating that the longer the duration of the disorder the lower the baseline cortisol levels. Additionally, we found a main effect of impulsivity across groups on interbeat interval during the TSST, indicating an association between impulsivity and the intensity of the neurovegetative stress response during the TSST. Involvement of the hypothalamic-pituitary-adrenal axis in pathological gambling was confirmed together with evidence of a correlation between length of the disorder and diminished baseline cortisol levels. Impulsivity emerged as a personality trait expressed by pathological gamblers; however the neurovegetative response to the TSST, although associated with impulsivity, appeared to be independent of the presence of pathological gambling.

Selective Cytotoxicity of 1,3,4-Thiadiazolium Mesoionic Derivatives on Hepatocarcinoma Cells (HepG2)

PubMed Central

Valdameri, Glaucio; Rocha, Maria Eliane Merlin; Martinez, Glaucia Regina; Noleto, Guilhermina Rodrigues; Acco, Alexandra; Alves de Souza, Carlos Eduardo; Echevarria, Aurea; Moretto dos Reis, Camilla; Di Pietro, Attilio; Suter Correia Cadena, Sílvia Maria

2015-01-01

In this work, we evaluated the cytotoxicity of mesoionic 4-phenyl-5-(2-Y, 4-X or 4-X-cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chloride derivatives (MI-J: X=OH, Y=H; MI-D: X=NO2, Y=H; MI-4F: X=F, Y=H; MI-2,4diF: X=Y=F) on human hepatocellular carcinoma (HepG2), and non-tumor cells (rat hepatocytes) for comparison. MI-J, M-4F and MI-2,4diF reduced HepG2 viability by ~ 50% at 25 μM after 24-h treatment, whereas MI-D required a 50 μM concentration, as shown by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. The cytotoxicity was confirmed with lactate dehydrogenase assay, of which activity was increased by 55, 24 and 16% for MI-J, MI-4F and MI-2,4diF respectively (at 25 μM after 24 h). To identify the death pathway related to cytotoxicity, the HepG2 cells treated by mesoionic compounds were labeled with both annexin V and PI, and analyzed by flow cytometry. All compounds increased the number of doubly-stained cells at 25 μM after 24 h: by 76% for MI-J, 25% for MI-4F and MI-2,4diF, and 11% for MI-D. It was also verified that increased DNA fragmentation occurred upon MI-J, MI-4F and MI-2,4diF treatments (by 12%, 9% and 8%, respectively, at 25 μM after 24 h). These compounds were only weakly, or not at all, transported by the main multidrug transporters, P-glycoprotein, ABCG2 and MRP1, and were able to slightly inhibit their drug-transport activity. It may be concluded that 1,3,4-thiadiazolium compounds, especially the hydroxy derivative MI-J, constitute promising candidates for future investigations on in-vivo treatment of hepatocellular carcinoma. PMID:26083249

microRNA analysis of Taenia crassiceps cysticerci under praziquantel treatment and genome-wide identification of Taenia solium miRNAs.

PubMed

Pérez, Matías Gastón; Macchiaroli, Natalia; Lichtenstein, Gabriel; Conti, Gabriela; Asurmendi, Sebastián; Milone, Diego Humberto; Stegmayer, Georgina; Kamenetzky, Laura; Cucher, Marcela; Rosenzvit, Mara Cecilia

2017-09-01

MicroRNAs (miRNAs) are small non-coding RNAs that have emerged as important regulators of gene expression and perform critical functions in development and disease. In spite of the increased interest in miRNAs from helminth parasites, no information is available on miRNAs from Taenia solium, the causative agent of cysticercosis, a neglected disease affecting millions of people worldwide. Here we performed a comprehensive analysis of miRNAs from Taenia crassiceps, a laboratory model for T. solium studies, and identified miRNAs in the T. solium genome. Moreover, we analysed the effect of praziquantel, one of the two main drugs used for cysticercosis treatment, on the miRNA expression profile of T. crassiceps cysticerci. Using small RNA-seq and two independent algorithms for miRNA prediction, as well as northern blot validation, we found transcriptional evidence of 39 miRNA loci in T. crassiceps. Since miRNAs were mapped to the T. solium genome, these miRNAs are considered common to both parasites. The miRNA expression profile of T. crassiceps was biased to the same set of highly expressed miRNAs reported in other cestodes. We found a significant altered expression of miR-7b under praziquantel treatment. In addition, we searched for miRNAs predicted to target genes related to drug response. We performed a detailed target prediction for miR-7b and found genes related to drug action. We report an initial approach to study the effect of sub-lethal drug treatment on miRNA expression in a cestode parasite, which provides a platform for further studies of miRNA involvement in drug effects. The results of our work could be applied to drug development and provide basic knowledge of cysticercosis and other neglected helminth infections. Copyright © 2017 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

Transactivation of micrornA-320 by microRNA-383 regulates granulosa cell functions by targeting E2F1 and SF-1 proteins.

PubMed

Yin, Mianmian; Wang, Xiaorong; Yao, Guidong; Lü, Mingrong; Liang, Meng; Sun, Yingpu; Sun, Fei

2014-06-27

Our previous studies have shown that microRNA-320 (miR-320) is one of the most down-regulated microRNAs (miRNA) in mouse ovarian granulosa cells (GCs) after TGF-β1 treatment. However, the underlying mechanisms of miR-320 involved in GC function during follicular development remain unknown. In this study, we found that pregnant mare serum gonadotropin treatment resulted in the suppression of miR-320 expression in a time-dependent manner. miR-320 was mainly expressed in GCs and oocytes of mouse ovarian follicles in follicular development. Overexpression of miR-320 inhibited estradiol synthesis and proliferation of GCs through targeting E2F1 and SF-1. E2F1/SF-1 mediated miR-320-induced suppression of GC proliferation and of GC steroidogenesis. FSH down-regulated the expression of miR-320 and regulated the function of miR-320 in mouse GCs. miR-383 promoted the expression of miR-320 and enhanced miR-320-mediated suppression of GC proliferation. Injection of miR-320 into the ovaries of mice partially promoted the production of testosterone and progesterone but inhibited estradiol release in vivo. Moreover, the expression of miR-320 and miR-383 was up-regulated in the follicular fluid of polycystic ovarian syndrome patients, although the expression of E2F1 and SF-1 was down-regulated in GCs. These data demonstrated that miR-320 regulates the proliferation and steroid production by targeting E2F1 and SF-1 in the follicular development. Understanding the regulation of miRNA biogenesis and function in the follicular development will potentiate the usefulness of miRNA in the treatment of reproduction and some steroid-related disorders. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

MicroRNA Expression in Alpha and Beta Cells of Human Pancreatic Islets

PubMed Central

Vargas, Nancy; Rosero, Samuel; Piroso, Julieta; Ichii, Hirohito; Umland, Oliver; Zhijie, Jiang; Tsinoremas, Nicholas; Ricordi, Camillo; Inverardi, Luca; Domínguez-Bendala, Juan; Pastori, Ricardo L.

2013-01-01

microRNAs (miRNAs) play an important role in pancreatic development and adult β-cell physiology. Our hypothesis is based on the assumption that each islet cell type has a specific pattern of miRNA expression. We sought to determine the profile of miRNA expression in α-and β-cells, the main components of pancreatic islets, because this analysis may lead to a better understanding of islet gene regulatory pathways. Highly enriched (>98%) subsets of human α-and β-cells were obtained by flow cytometric sorting after intracellular staining with c-peptide and glucagon antibody. The method of sorting based on intracellular staining is possible because miRNAs are stable after fixation. MiRNA expression levels were determined by quantitative high throughput PCR-based miRNA array platform screening. Most of the miRNAs were preferentially expressed in β-cells. From the total of 667 miRNAs screened, the Significant Analysis of Microarray identified 141 miRNAs, of which only 7 were expressed more in α-cells (α-miRNAs) and 134 were expressed more in β-cells (β-miRNAs). Bioinformatic analysis identified potential targets of β-miRNAs analyzing the Beta Cell Gene Atlas, described in the T1Dbase, the web platform, supporting the type 1 diabetes (T1D) community. cMaf, a transcription factor regulating glucagon expression expressed selectively in α-cells (TFα) is targeted by β-miRNAs; miR-200c, miR-125b and miR-182. Min6 cells treated with inhibitors of these miRNAs show an increased expression of cMaf RNA. Conversely, over expression of miR-200c, miR-125b or miR-182 in the mouse alpha cell line αTC6 decreases the level of cMAF mRNA and protein. MiR-200c also inhibits the expression of Zfpm2, a TFα that inhibits the PI3K signaling pathway, at both RNA and protein levels. In conclusion, we identified miRNAs differentially expressed in pancreatic α- and β-cells and their potential transcription factor targets that could add new insights into different aspects of islet biology and pathophysiology. PMID:23383059

MicroRNA expression in alpha and beta cells of human pancreatic islets.

PubMed

Klein, Dagmar; Misawa, Ryosuke; Bravo-Egana, Valia; Vargas, Nancy; Rosero, Samuel; Piroso, Julieta; Ichii, Hirohito; Umland, Oliver; Zhijie, Jiang; Tsinoremas, Nicholas; Ricordi, Camillo; Inverardi, Luca; Domínguez-Bendala, Juan; Pastori, Ricardo L

2013-01-01

microRNAs (miRNAs) play an important role in pancreatic development and adult β-cell physiology. Our hypothesis is based on the assumption that each islet cell type has a specific pattern of miRNA expression. We sought to determine the profile of miRNA expression in α-and β-cells, the main components of pancreatic islets, because this analysis may lead to a better understanding of islet gene regulatory pathways. Highly enriched (>98%) subsets of human α-and β-cells were obtained by flow cytometric sorting after intracellular staining with c-peptide and glucagon antibody. The method of sorting based on intracellular staining is possible because miRNAs are stable after fixation. MiRNA expression levels were determined by quantitative high throughput PCR-based miRNA array platform screening. Most of the miRNAs were preferentially expressed in β-cells. From the total of 667 miRNAs screened, the Significant Analysis of Microarray identified 141 miRNAs, of which only 7 were expressed more in α-cells (α-miRNAs) and 134 were expressed more in β-cells (β-miRNAs). Bioinformatic analysis identified potential targets of β-miRNAs analyzing the Beta Cell Gene Atlas, described in the T1Dbase, the web platform, supporting the type 1 diabetes (T1D) community. cMaf, a transcription factor regulating glucagon expression expressed selectively in α-cells (TFα) is targeted by β-miRNAs; miR-200c, miR-125b and miR-182. Min6 cells treated with inhibitors of these miRNAs show an increased expression of cMaf RNA. Conversely, over expression of miR-200c, miR-125b or miR-182 in the mouse alpha cell line αTC6 decreases the level of cMAF mRNA and protein. MiR-200c also inhibits the expression of Zfpm2, a TFα that inhibits the PI3K signaling pathway, at both RNA and protein levels.In conclusion, we identified miRNAs differentially expressed in pancreatic α- and β-cells and their potential transcription factor targets that could add new insights into different aspects of islet biology and pathophysiology.

MINERvA’s flux prediction

DOE PAGES

Golan, Tomasz; Aliaga, Leonidas; Kordosky, Mike

2016-12-12

Here, the MINERvA (Main INjector ExpeRiment: νA) experiment is focused on the measurement of neutrino cross sections on various nuclear targets. For this kind of study it is crucial to know precisely neutrino flux. MINERvA uses the NuMI (Neutrinos at the Main Injector) beam produced at Fermilab. The recent study on the evaluation of the beam and its uncertainty is presented. The NuMI beam is also used by other neutrino experiment, like MINOS, ArgoNeuT, PEANUT, and NOvA, therefore, the results can be used by other collaborations.

Generalizability of EXCEL and NOBLE results to a large registry population with unprotected left main coronary artery disease.

PubMed

Lee, Pil Hyung; Kang, Se Hun; Han, Seungbong; Ahn, Jung-Min; Bae, Jae Seok; Lee, Cheol Hyun; Kang, Soo-Jin; Lee, Seung-Whan; Kim, Young-Hak; Lee, Cheol Whan; Park, Seong-Wook; Park, Duk-Woo; Park, Seung-Jung

2017-12-01

The aim of this study was to determine how trial-based findings of EXCEL and NOBLE might be interpreted and generalizable in 'real-world' settings with comparison of data from the large-scaled, all-comer Interventional Research Incorporation Society-Left MAIN Revascularization (IRIS-MAIN) registry. We compared baseline clinical and procedural characteristics and also determined how the relative treatment effect of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) was different in EXCEL and NOBLE, compared with those of the multicenter, IRIS-MAIN registry (n=2481). The primary outcome for between-study comparison was a composite of death, myocardial infarction (MI), or stroke. There were between-study differences in patient risk profiles (age, BMI, diabetes, and clinical presentation), lesion complexities, and procedural characteristics (stent type, the use of off-pump surgery, and radial artery); the proportion of diabetes and acute coronary syndrome was particularly lower in NOBLE than in other studies. Although there was interstudy heterogeneity for the protocol definition of MI, the risks for serious composite outcome of death, MI, or stroke were similar between PCI and CABG in EXCEL [hazard ratio (HR): 1.00; 95% confidence interval (CI): 0.79-1.26; P=0.98] and in the matched cohort of IRIS-MAIN (HR: 1.08; 95%CI: 0.85-1.38; P=0.53), whereas it was significantly higher after PCI than after CABG in NOBLE (HR: 1.47; 95%CI: 1.06-2.05; P=0.02), which was driven by more common MI and stroke after PCI. In the comparison of a large-sized, all-comer registry, the EXCEL trial might represent better generalizability with respect to baseline characteristics and observed clinical outcomes compared with the NOBLE trial.

Performance of Dower's inverse transform and Frank lead system for Identification of Myocardial Infarction.

PubMed

Aranda, A; Bonizzi, P; Karel, J; Peeters, R

2015-08-01

This study performs a comparison between Dower's inverse transform and Frank lead system for Myocardial Infarction (MI) identification. We have selected a set of relevant features for MI detection from the vectorcardiogram and used the lasso method after that to build a model for the Dower's inverse transform and one for the Frank leads system. Then we analyzed the performance between both models on MI detection. The proposed methods have been tested using PhysioNet PTB database that contains 550 records from which 368 are MIs. Two main conclusions are coming from this study. The first one is that Dower's inverse transform performs equally well than Frank leads in identification of MI patients. The second one is that lead positions have a large influence on the accuracy of MI patient identification.

Circulating microRNA Signatures in Patients With Idiopathic and Postmenopausal Osteoporosis and Fragility Fractures.

PubMed

Kocijan, Roland; Muschitz, Christian; Geiger, Elisabeth; Skalicky, Susanna; Baierl, Andreas; Dormann, Rainer; Plachel, Fabian; Feichtinger, Xaver; Heimel, Patrick; Fahrleitner-Pammer, Astrid; Grillari, Johannes; Redl, Heinz; Resch, Heinrich; Hackl, Matthias

2016-11-01

Established bone turnover markers do not reflect fracture risk in idiopathic male and premenopausal osteoporosis and the role of microRNAs (miRNAs) in these patients is currently unclear. miRNAs are a class of small non-coding RNAs that regulate gene expression and bone tissue homeostasis. They are considered a new class of endocrine regulators with promising potential as biomarkers. Evaluation of circulating miRNA signatures in male and female subjects with idiopathic and postmenopausal osteoporotic low-traumatic fractures. This was a case-control study of cross-sectional design of 36 patients with prevalent low-traumatic fractures and 39 control subjects Main Outcome Measures: One hundred eighty-seven miRNAs were quantified in serum by qPCR, compared between groups and correlated with established bone turnover markers. Significant differences in serum levels of circulating miRNAs were identified in all three subgroups (46 in premenopausal, 52 in postmenopausal, 55 in male). A set of 19 miRNAs was consistently regulated in all three subgroups. Eight miRNAs [miR-152-3p, miR-30e-5p, miR-140-5p, miR-324-3p, miR-19b-3p, miR-335-5p, miR-19a-3p, miR-550a-3p] were excellent discriminators of patients with low-traumatic fractures, regardless of age and sex, with area under the curve values > 0.9. The 11 remaining miRNAs showed area under the curve values between 0.81 and 0.89. Correlation analysis identified significant correlations between miR-29b-3p and P1NP, and miR-365-5p and iPTH, TRAP5b, P1NP and Osteocalcin, as well as BMD L1-L4 and miR-19b-3p, miR-324-3p, miR-532-5p, and miR-93-5p. Specific serum miRNA profiles are strongly related to bone pathologies. Therefore miRNAs might be directly linked to bone tissue homeostasis. In particular, miR-29b-3p has previously been reported as regulator of osteogenic differentiation and could serve as a novel marker of bone turnover in osteoporotic patients as a member of a miRNA signature.

Coronary microvascular dysfunction after myocardial infarction: increased coronary zero flow pressure both in the infarcted and in the remote myocardium is mainly related to left ventricular filling pressure

PubMed Central

Van Herck, P L; Carlier, S G; Claeys, M J; Haine, S E; Gorissen, P; Miljoen, H; Bosmans, J M; Vrints, C J

2007-01-01

Objective To investigate the underlying mechanisms of a decreased coronary flow reserve after myocardial infarction (MI) by analysing the characteristics of the diastolic hyperaemic coronary pressure–flow relationship. Design Prospective study. Setting Tertiary care hospital. Patients 68 patients with a recent MI and 27 patients with stable angina pectoris (AP; control group). Main outcome measures The intercept with the pressure axis (the zero flow pressure or Pzf) and slope index of the pressure–flow relationship (SIPF) were calculated from the simultaneously recorded hyperaemic intracoronary blood flow velocity and aortic pressure after successful coronary stenting. Results A stepwise increase in Pzf from AP (14.6 (8.0) mm Hg), over non‐Q‐wave MI (22.5 (9.1) mm Hg), to Q‐wave MI (37.1 (12.9) mm Hg; p<0.001) was observed. Similar changes in Pzf were found in a reference artery perfusing the non‐infarcted myocardium. Multivariate analysis showed that in both regions the left ventricular end‐diastolic pressure (LVEDP) was the most important determinant of the Pzf. The SIPF was not statistically different in the treated vessel between patients with MI and AP, but was increased in MI patients with a markedly increased LVEDP. Conclusions After an MI, the coronary pressure–flow relationship is shifted to the right both in the infarcted and in the non‐infarcted remote myocardium, as shown by the increased Pzf. The correlation with Pzf suggests that elevated left ventricular filling pressures contribute to the impediment of myocardial perfusion in patients with infarction. PMID:17395671

A glance at subgenomic flavivirus RNAs and microRNAs in flavivirus infections.

PubMed

Bavia, Lorena; Mosimann, Ana Luiza Pamplona; Aoki, Mateus Nóbrega; Duarte Dos Santos, Claudia Nunes

2016-05-28

The family Flaviviridae comprises a wide variety of viruses that are distributed worldwide, some of which are associated with high rates of morbidity and mortality. There are neither vaccines nor antivirals for most flavivirus infections, reinforcing the importance of research on different aspects of the viral life cycle. During infection, cytoplasmic accumulation of RNA fragments mainly originating from the 3' UTRs, which have been designated subgenomic flavivirus RNAs (sfRNAs), has been detected. It has been shown that eukaryotic exoribonucleases are involved in viral sfRNA production. Additionally, viral and human small RNAs (sRNAs) have also been found in flavivirus-infected cells, especially microRNAs (miRNAs). miRNAs were first described in eukaryotic cells and in a mature and functional state present as single-stranded 18-24 nt RNA fragments. Their main function is the repression of translation through base pairing with cellular mRNAs, besides other functions, such as mRNA degradation. Canonical miRNA biogenesis involves Drosha and Dicer, however miRNA can also be generated by alternative pathways. In the case of flaviviruses, alternative pathways have been suggested. Both sfRNAs and miRNAs are involved in viral infection and host cell response modulation, representing interesting targets of antiviral strategies. In this review, we focus on the generation and function of viral sfRNAs, sRNAs and miRNAs in West Nile, dengue, Japanese encephalitis, Murray Valley encephalitis and yellow fever infections, as well as their roles in viral replication, translation and cell immune response evasion. We also give an overview regarding other flaviviruses and the generation of cellular miRNAs during infection.

miRNA-23 regulates high glucose induced epithelial to mesenchymal transition in human mesotheial peritoneal cells by targeting VDR.

PubMed

Yang, Lina; Fan, Yi; Zhang, Xiuli; Ma, Jianfei

2017-11-15

Epithelial-mesenchymal transition(EMT) is the main reason for peritoneal fibrosis and the mechanism underlying peritoneal EMT were extensively studied in recent years. Recent researches showed that miRNAs were so important in the development of organ EMT and fibrosis, the role of microRNAs on peritoneal dialysis have also been studied. In the current study, we investigated microRNA-23(miR-23) expression in high glucose(HG) induced EMT in human mesotheial peritoneal cells(HPMCs). We found that HG promoted EMT, which was characterized by the upregulation of mesenchymal markers α-SMA and FN and downregulation of epithelial marker E-cadherin. The expression miR-23 showed a significant upregulation when treated with HG. Enhanced expression of miR-23 could aggravate HG induced EMT by targeting VDR, inhibition of miR-23 in HPMCs could reverse HG induced EMT by targeting VDR. Furthermore, VDRshRNA exacerbated the EMT process and reversed miR-23 inhibitor-attenuated EMT process in HPMCs. These data manifested that miR-23 played a key role in HG-induced EMT of HPMCs by targeting VDR. Copyright © 2017 Elsevier Inc. All rights reserved.

Mapping interictal epileptic discharges using mutual information between concurrent EEG and fMRI.

PubMed

Caballero-Gaudes, César; Van de Ville, Dimitri; Grouiller, Frédéric; Thornton, Rachel; Lemieux, Louis; Seeck, Margitta; Lazeyras, François; Vulliemoz, Serge

2013-03-01

The mapping of haemodynamic changes related to interictal epileptic discharges (IED) in simultaneous electroencephalography (EEG) and functional MRI (fMRI) studies is usually carried out by means of EEG-correlated fMRI analyses where the EEG information specifies the model to test on the fMRI signal. The sensitivity and specificity critically depend on the accuracy of EEG detection and the validity of the haemodynamic model. In this study we investigated whether an information theoretic analysis based on the mutual information (MI) between the presence of epileptic activity on EEG and the fMRI data can provide further insights into the haemodynamic changes related to interictal epileptic activity. The important features of MI are that: 1) both recording modalities are treated symmetrically; 2) no requirement for a-priori models for the haemodynamic response function, or assumption of a linear relationship between the spiking activity and BOLD responses, and 3) no parametric model for the type of noise or its probability distribution is necessary for the computation of MI. Fourteen patients with pharmaco-resistant focal epilepsy underwent EEG-fMRI and intracranial EEG and/or surgical resection with positive postoperative outcome (seizure freedom or considerable reduction in seizure frequency) was available in 7/14 patients. We used nonparametric statistical assessment of the MI maps based on a four-dimensional wavelet packet resampling method. The results of MI were compared to the statistical parametric maps obtained with two conventional General Linear Model (GLM) analyses based on the informed basis set (canonical HRF and its temporal and dispersion derivatives) and the Finite Impulse Response (FIR) models. The MI results were concordant with the electro-clinically or surgically defined epileptogenic area in 8/14 patients and showed the same degree of concordance as the results obtained with the GLM-based methods in 12 patients (7 concordant and 5 discordant). In one patient, the information theoretic analysis improved the delineation of the irritative zone compared with the GLM-based methods. Our findings suggest that an information theoretic analysis can provide clinically relevant information about the BOLD signal changes associated with the generation and propagation of interictal epileptic discharges. The concordance between the MI, GLM and FIR maps support the validity of the assumptions adopted in GLM-based analyses of interictal epileptic activity with EEG-fMRI in such a manner that they do not significantly constrain the localization of the epileptogenic zone. Copyright © 2012 Elsevier Inc. All rights reserved.

MicroRNAs in osteosarcoma: diagnostic and therapeutic aspects.

PubMed

Miao, Jinglei; Wu, Song; Peng, Zhi; Tania, Mousumi; Zhang, Chaoyue

2013-08-01

MicroRNAs (miRNAs) are small RNA molecules, which can interfere with the expression of several genes and act as gene regulator. miRNAs have been proved as a successful diagnostic and therapeutic tool in several cancers. In this review, the differential expression of miRNAs in osteosarcoma and their possibility to be used as diagnostic and therapeutic tools have been discussed. Osteosarcoma is the most common primary bone tumor that mainly affects children and adolescents. The current treatment of osteosarcoma remains difficult, and osteosarcoma causes many deaths because of its complex pathogenesis and resistance to conventional treatments. Several studies demonstrated that the differential expression patterns of miRNAs are a promising tool for the diagnosis and treatment of osteosarcoma. Although some aspect of the mechanism of action of miRNAs in controlling osteosarcoma has been identified (e.g., targeting the Notch signaling pathway), it is far beyond to the clear understanding of miRNA targets in osteosarcoma. Identification of the specific target of miRNAs may aid molecular targets for drug development and future relief of osteosarcoma.

Characterization of serum microRNAs profile of PCOS and identification of novel non-invasive biomarkers.

PubMed

Long, Wei; Zhao, Chun; Ji, Chenbo; Ding, Hongjuan; Cui, Yugui; Guo, Xirong; Shen, Rong; Liu, Jiayin

2014-01-01

Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women of reproductive age, is characterized by polycystic ovaries, chronic anovulation, hyperandrogenism and insulin resistance. Despite the high prevalence of hyperandrogenemia, a definitive endocrine marker for PCOS has so far not been identified. Circulating miRNAs have recently been shown to serve as diagnostic/prognostic biomarkers in patients with cancers. Our current study focused on the altered expression of serum miRNAs and their correlation with PCOS. We systematically used the TaqMan Low Density Array followed by individual quantitative reverse transcription polymerase chain reaction assays to identify and validate the expression of serum miRNAs of PCOS patients. The expression levels of three miRNAs (miR-222, miR-146a and miR-30c) were significantly increased in PCOS patients with respect to the controls in our discovery evaluation and followed validation. The area under the receiver operating characteristic (ROC) curve (AUC) is 0.799, 0.706, and 0.688, respectively. The combination of the three miRNAs using multiple logistic regression analysis showed a larger AUC (0.852) that was more efficient for the diagnosis of PCOS. In addition, logistic binary regression analyses show miR-222 is positively associated with serum insulin, while miR-146a is negatively associated with serum testosterone. Furthermore, bioinformatics analysis indicated that the predicted targets function of the three miRNAs mainly involved in the metastasis, cell cycle, apoptosis and endocrine. Serum miRNAs are differentially expressed between PCOS patients and controls. We identified and validated a class of three serum miRNAs that could act as novel non-invasive biomarkers for diagnosis of PCOS. These miRNAs may be involved in the pathogenesis of PCOS. © 2014 S. Karger AG, Basel.

Profiling of expression of human papillomavirus-related cancer miRNAs in penile squamous cell carcinomas.

PubMed

Barzon, Luisa; Cappellesso, Rocco; Peta, Elektra; Militello, Valentina; Sinigaglia, Alessandro; Fassan, Matteo; Simonato, Francesca; Guzzardo, Vincenza; Ventura, Laura; Blandamura, Stella; Gardiman, Marina; Palù, Giorgio; Fassina, Ambrogio

2014-12-01

Penile squamous cell carcinoma (PSCC) is a rare tumor associated with high-risk human papillomavirus (HR-HPV) infection in 30% to 60% of cases. Altered expression of miRNAs has been reported in HPV-related cervical and head and neck cancers, but such data have not been available for PSCC. We analyzed a series of 59 PSCCs and 8 condylomata for presence of HPV infection, for p16(INK4a), Ki-67, and p53 immunohistochemical expression, and for expression of a panel of cellular miRNAs (let-7c, miR-23b, miR-34a, miR-145, miR-146a, miR-196a, and miR-218) involved in HPV-related cancer. HR-HPV DNA (HPV16 in most cases) was detected in 17/59 (29%) PSCCs; all penile condylomata (8/8) were positive for low-risk HPV6 or HPV11. HR-HPV(+) PSCCs overexpressed p16(INK4a) in 88% cases and p53 in 35% of cases, whereas HR-HPV(-) PSCCs were positive for p16(INK4a) and p53 immunostaining in 9% and 44% of cases, respectively. Among the miRNAs investigated, expression of miR-218 was lower in PSCCs with HR-HPV infection and in p53(-) cancers. Hypermethylation of the promoter of the SLIT2 gene, which contains miR-218-1 in its intronic region, was frequently observed in PSCCs, mainly in those with low miR-218 expression. Epigenetic silencing of miR-218 is a common feature in HR-HPV(+) PSCCs and in HR-HPV(-) PSCCs without immunohistochemical detection of p53. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Characterisation of microRNAs from apple (Malus domestica 'Royal Gala') vascular tissue and phloem sap.

PubMed

Varkonyi-Gasic, Erika; Gould, Nick; Sandanayaka, Manoharie; Sutherland, Paul; MacDiarmid, Robin M

2010-08-04

Plant microRNAs (miRNAs) are a class of small, non-coding RNAs that play an important role in development and environmental responses. Hundreds of plant miRNAs have been identified to date, mainly from the model species for which there are available genome sequences. The current challenge is to characterise miRNAs from plant species with agricultural and horticultural importance, to aid our understanding of important regulatory mechanisms in crop species and enable improvement of crops and rootstocks. Based on the knowledge that many miRNAs occur in large gene families and are highly conserved among distantly related species, we analysed expression of twenty-one miRNA sequences in different tissues of apple (Malus x domestica 'Royal Gala'). We identified eighteen sequences that are expressed in at least one of the tissues tested. Some, but not all, miRNAs expressed in apple tissues including the phloem tissue were also detected in the phloem sap sample derived from the stylets of woolly apple aphids. Most of the miRNAs detected in apple phloem sap were also abundant in the phloem sap of herbaceous species. Potential targets for apple miRNAs were identified that encode putative proteins shown to be targets of corresponding miRNAs in a number of plant species. Expression patterns of potential targets were analysed and correlated with expression of corresponding miRNAs. This study validated tissue-specific expression of apple miRNAs that target genes responsible for plant growth, development, and stress response. A subset of characterised miRNAs was also present in the apple phloem translocation stream. A comparative analysis of phloem miRNAs in herbaceous species and woody perennials will aid our understanding of non-cell autonomous roles of miRNAs in plants.

Characterisation of microRNAs from apple (Malus domestica 'Royal Gala') vascular tissue and phloem sap

PubMed Central

2010-01-01

Background Plant microRNAs (miRNAs) are a class of small, non-coding RNAs that play an important role in development and environmental responses. Hundreds of plant miRNAs have been identified to date, mainly from the model species for which there are available genome sequences. The current challenge is to characterise miRNAs from plant species with agricultural and horticultural importance, to aid our understanding of important regulatory mechanisms in crop species and enable improvement of crops and rootstocks. Results Based on the knowledge that many miRNAs occur in large gene families and are highly conserved among distantly related species, we analysed expression of twenty-one miRNA sequences in different tissues of apple (Malus x domestica 'Royal Gala'). We identified eighteen sequences that are expressed in at least one of the tissues tested. Some, but not all, miRNAs expressed in apple tissues including the phloem tissue were also detected in the phloem sap sample derived from the stylets of woolly apple aphids. Most of the miRNAs detected in apple phloem sap were also abundant in the phloem sap of herbaceous species. Potential targets for apple miRNAs were identified that encode putative proteins shown to be targets of corresponding miRNAs in a number of plant species. Expression patterns of potential targets were analysed and correlated with expression of corresponding miRNAs. Conclusions This study validated tissue-specific expression of apple miRNAs that target genes responsible for plant growth, development, and stress response. A subset of characterised miRNAs was also present in the apple phloem translocation stream. A comparative analysis of phloem miRNAs in herbaceous species and woody perennials will aid our understanding of non-cell autonomous roles of miRNAs in plants. PMID:20682080

Unraveling the microRNA of Caragana korshinskii along a precipitation gradient on the Loess Plateau, China, using high-throughput sequencing.

PubMed

Ning, Pengbo; Zhou, Yulu; Gao, Lifang; Sun, Yingying; Zhou, Wenfei; Liu, Furong; Yao, Zhenye; Xie, Lifang; Wang, Junhui; Gong, Chunmei

2017-01-01

Drought remains one of the main factors that negatively affect plant growth and development. Caragana korshinskii is widely distributed on the Loess Plateau, China, where it mediates soil and water loss and helps prevent desertification. However, little is known about the stress response mechanisms of C. korshinskii in water-starved environments. MicroRNAs (miRNAs) have been implicated in the regulation of plant responses to several types of biotic and abiotic stress. Here, we describe the miRNAs of wild C. korshinskii from Huangling, Yulin, and Dalad Banner, which occur along a precipitation gradient. Using next-generation sequencing technology, we obtained a total of 13 710 681, 15 048 945, and 15 198 442 reads for each location, respectively; after filtering and BLAST analysis, 490 conserved miRNAs and 96 novel miRNAs were characterized from the sRNAome data, with key functions determined using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. We also designed stem-loop qRT-PCR to validate the expression patterns of 5 conserved miRNAs (miR390, miR398, miR530, miR2119, and miR5559) that obviously responded to water stress in plants grown both under natural and experimental water stress conditions and found that the expression levels of miR2119 and miR5559 were negatively correlated with their predicted target genes. This study is the first to identify miRNAs from wild C. korshinskii and provides a basis for future studies of miRNA-mediated gene regulation of stress responses in C. korshinskii.

Differentially expressed microRNAs in the corpus cavernosum from a murine model with type 2 diabetes mellitus-associated erectile dysfunction.

PubMed

Pan, Feng; You, Jinwei; Liu, Yuan; Qiu, Xuefeng; Yu, Wen; Ma, Jiehua; Pan, Lianjun; Zhang, Aixia; Zhang, Qipeng

2016-12-01

To better understand the molecular aetiology of type 2 diabetes mellitus-associated erectile dysfunction (T2DMED) and to provide candidates for further study of its diagnosis and treatment, this study was designed to investigate differentially expressed microRNAs (miRNAs) in the corpus cavernosum (CC) of mice with T2DMED using GeneChip array techniques (Affymetrix miRNA 4.0 Array) and to predict target genes and signalling pathways regulated by these miRNAs based on bioinformatic analysis using TargetScan, the DAIAN web platform and DAVID. In the initial screening, 21 miRNAs appeared distinctly expressed in the T2DMED group (fold change ≥3, p ≤ 0.01). Among them, the differential expression of miR-18a, miR-206, miR-122, and miR-133 were confirmed by qRT-PCR (p < 0.05 and FDR <5 %). According to bioinformatic analysis, the four miRNAs were speculated to play potential roles in the mechanisms of T2DMED via regulating 28 different genes and several pathways, including apoptosis, fibrosis, eNOS/cGMP/PKG, and vascular smooth muscle contraction processes, which mainly focused on influencing the functions of the endothelium and smooth muscle in the CC. IGF-1, as one of the target genes, was verified to decrease in the CCs of T2DMED animals via ELISA and was confirmed as the target of miR-18a or miR-206 via luciferase assay. Finally, these four miRNAs deserve further confirmation as biomarkers of T2DMED in larger studies. Additionally, miR-18a and/or miR-206 may provide new preventive/therapeutic targets for ED management by targeting IGF-1.

Identification of potential therapeutic target genes, key miRNAs and mechanisms in oral lichen planus by bioinformatics analysis.

PubMed

Gong, Cuihua; Sun, Shangtong; Liu, Bing; Wang, Jing; Chen, Xiaodong

2017-06-01

The study aimed to identify the potential target genes and key miRNAs as well as to explore the underlying mechanisms in the pathogenesis of oral lichen planus (OLP) by bioinformatics analysis. The microarray data of GSE38617 were downloaded from Gene Expression Omnibus (GEO) database. A total of 7 OLP and 7 normal samples were used to identify the differentially expressed genes (DEGs) and miRNAs. The DEGs were then performed functional enrichment analyses. Furthermore, DEG-miRNA network and miRNA-function network were constructed by Cytoscape software. Total 1758 DEGs (598 up- and 1160 down-regulated genes) and 40 miRNAs (17 up- and 23 down-regulated miRNAs) were selected. The up-regulated genes were related to nuclear factor-Kappa B (NF-κB) signaling pathway, while down-regulated genes were mainly enriched in the function of ribosome. Tumor necrosis factor (TNF), caspase recruitment domain family, member 11 (CARD11) and mitochondrial ribosomal protein (MRP) genes were identified in these functions. In addition, miR-302 was a hub node in DEG-miRNA network and regulated cyclin D1 (CCND1). MiR-548a-2 was the key miRNA in miRNA-function network by regulating multiple functions including ribosomal function. The NF-κB signaling pathway and ribosome function may be the pathogenic mechanisms of OLP. The genes such as TNF, CARD11, MRP genes and CCND1 may be potential therapeutic target genes in OLP. MiR-548a-2 and miR-302 may play important roles in OLP development. Copyright © 2017 Elsevier Ltd. All rights reserved.

MiR-495 and miR-218 regulate the expression of the Onecut transcription factors HNF-6 and OC-2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Simion, Alexandru; Laudadio, Ilaria; Prevot, Pierre-Paul

2010-01-01

MicroRNAs are small, non-coding RNAs that posttranscriptionally regulate gene expression mainly by binding to the 3'UTR of their target mRNAs. Recent data revealed that microRNAs have an important role in pancreas and liver development and physiology. Using cloning and microarray profiling approaches, we show that a unique repertoire of microRNAs is expressed at the onset of liver and pancreas organogenesis, and in pancreas and liver at key stages of cell fate determination. Among the microRNAs that are expressed at these stages, miR-495 and miR-218 were predicted to, respectively, target the Onecut (OC) transcription factors Hepatocyte Nuclear Factor-6 (HNF-6/OC-1) and OC-2,more » two important regulators of liver and pancreas development. MiR-495 and miR-218 are dynamically expressed in developing liver and pancreas, and by transient transfection, we show that they target HNF-6 and OC-2 3'UTRs. Moreover, when overexpressed in cultured cells, miR-495 and miR-218 decrease the endogenous levels of HNF-6 and OC-2 mRNA. These results indicate that the expression of regulators of liver and pancreas development is modulated by microRNAs. They also suggest a developmental role for miR-495 and miR-218.« less

An OFDM Receiver with Frequency Domain Diversity Combined Impulsive Noise Canceller for Underwater Network.

PubMed

Saotome, Rie; Hai, Tran Minh; Matsuda, Yasuto; Suzuki, Taisaku; Wada, Tomohisa

2015-01-01

In order to explore marine natural resources using remote robotic sensor or to enable rapid information exchange between ROV (remotely operated vehicles), AUV (autonomous underwater vehicle), divers, and ships, ultrasonic underwater communication systems are used. However, if the communication system is applied to rich living creature marine environment such as shallow sea, it suffers from generated Impulsive Noise so-called Shrimp Noise, which is randomly generated in time domain and seriously degrades communication performance in underwater acoustic network. With the purpose of supporting high performance underwater communication, a robust digital communication method for Impulsive Noise environments is necessary. In this paper, we propose OFDM ultrasonic communication system with diversity receiver. The main feature of the receiver is a newly proposed Frequency Domain Diversity Combined Impulsive Noise Canceller. The OFDM receiver utilizes 20-28 KHz ultrasonic channel and subcarrier spacing of 46.875 Hz (MODE3) and 93.750 Hz (MODE2) OFDM modulations. In addition, the paper shows Impulsive Noise distribution data measured at a fishing port in Okinawa and at a barge in Shizuoka prefectures and then proposed diversity OFDM transceivers architecture and experimental results are described. By the proposed Impulsive Noise Canceller, frame bit error rate has been decreased by 20-30%.

Translation, Adaptation, and Validation of the Brazilian Version of the Dickman Impulsivity Inventory (Br-DII).

PubMed

Gomes, Áurea K V; Diniz, Leandro F M; Lage, Guilherme M; de Miranda, Débora M; de Paula, Jonas J; Costa, Danielle; Albuquerque, Maicon R

2017-01-01

Impulsivity has mainly been described as a negative or dysfunctional characteristic associated with several disorders. However, impulsivity is not only related to dysfunctional outcomes and may explain individual differences in optimal human functioning as well. The Dickman Impulsivity Inventory (DII) is a self-report instrument measuring both the dysfunctional and the functional aspects of impulsivity. In this study, we performed the translation and cultural adaptation of the DII to the Brazilian context and analyzed its psychometric properties. Translation and cultural adaptation followed a rigorous process, which relied on an expert panel in the cross-cultural adaptation of psychological instruments. Data from 405 undergraduate students were obtained for the Brazilian version of the DII (Br-DII). The 23 items of the Br-DII was considered unsuitable according to model fit indices of the Confirmatory Factor Analysis (both for Oblique and Orthogonal models). Exploratory Factor Analysis showed an 18 items version of the Br-DII to be suitable (CFI = 0.92; TLI = 0.90, and RMSEA = 0.057). The DII's 18 items version also showed adequate Cronbach's alpha, intraclass correlation coefficient, and convergent and discriminant validity with the BIS-11. Therefore, the Br-DII demonstrated reliability and validity in the measurement of functional and dysfunctional impulsivity.

Hazardous drinking and dimensions of impulsivity, behavioral approach, and inhibition in adult men and women.

PubMed

Hamilton, Kristen R; Sinha, Rajita; Potenza, Marc N

2012-06-01

Hazardous drinking is characterized by decisions to engage in excessive or risky patterns of alcohol consumption. Levels of impulsivity and behavioral approach and inhibition may differ in hazardous drinkers and nonhazardous drinkers. A comparison of the relative levels of dimensions of impulsivity and behavioral inhibition and approach in adult men and women hazardous and nonhazardous drinkers may inform treatment and prevention efforts. In the present research, 466 men and women from a community sample were administered the Alcohol Use Disorders Identification Test (AUDIT), the Behavioral Inhibition System/Behavioral Approach System (BIS/BAS) scale, and the Barratt Impulsiveness Scale, version 11 (BIS-11). Relations among the dimensions of these constructs were examined using multivariate analysis of covariance (MANCOVA), with age and race as covariates. There were main effects of hazardous drinking on all 3 dimensions of impulsivity, the behavioral inhibition system, and the behavioral activation system Reward Responsiveness, and Fun-Seeking components, with hazardous drinkers scoring higher than nonhazardous drinkers. This research provides a better understanding of the manner in which impulsivity and behavioral inhibition and approach tendencies relate to hazardous alcohol use in men and women. The present results have implications for alcohol-related prevention and treatment strategies for adult men and women. Copyright © 2012 by the Research Society on Alcoholism.

Impulsivity-focused group intervention to reduce binge eating episodes in patients with binge eating disorder: study protocol of the randomised controlled IMPULS trial.

PubMed

Schag, Kathrin; Leehr, Elisabeth J; Martus, Peter; Bethge, Wolfgang; Becker, Sandra; Zipfel, Stephan; Giel, Katrin E

2015-12-18

The core symptom of binge eating disorder (BED) is recurrent binge eating that is accompanied by a sense of loss of control. BED is frequently associated with obesity, one of the main public health challenges today. Experimental studies deliver evidence that general trait impulsivity and disorder-specific food-related impulsivity constitute risk factors for BED. Cognitive-behavioural treatment (CBT) is deemed to be the most effective intervention concerning BED. We developed a group intervention based on CBT and especially focusing on impulsivity. We hypothesise that such an impulsivity-focused group intervention is able to increase control over impulsive eating behaviour, that is, reduce binge eating episodes, further eating pathology and impulsivity. Body weight might also be influenced in the long term. The present randomised controlled trial investigates the feasibility, acceptance and efficacy of this impulsivity-focused group intervention in patients with BED. We compare 39 patients with BED in the experimental group to 39 patients with BED in the control group at three appointments: before and after the group intervention and in a 3-month follow-up. Patients with BED in the experimental group receive 8 weekly sessions of the impulsivity-focused group intervention with 5-6 patients per group. Patients with BED in the control group receive no group intervention. The primary outcome is the binge eating frequency over the past 4 weeks. Secondary outcomes comprise further eating pathology, general impulsivity and food-related impulsivity assessed by eye tracking methodology, and body weight. Additionally, we assess binge eating and other impulsive behaviour weekly in process analyses during the time period of the group intervention. This study has been approved by the ethics committee of the medical faculty of Eberhard Karls University Tübingen and the University Hospital Tübingen. Data are monitored by the Centre of Clinical Studies, University Hospital Tübingen. German Clinical Trials Register, DRKS00007689, 14/01/2015, version from 11/06/2015, pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Characterization of circulating microRNA expression in patients with a ventricular septal defect.

PubMed

Li, Dong; Ji, Long; Liu, Lianbo; Liu, Yizhi; Hou, Haifeng; Yu, Kunkun; Sun, Qiang; Zhao, Zhongtang

2014-01-01

Ventricular septal defect (VSD), one of the most common types of congenital heart disease (CHD), results from a combination of environmental and genetic factors. Recent studies demonstrated that microRNAs (miRNAs) are involved in development of CHD. This study was to characterize the expression of miRNAs that might be involved in the development or reflect the consequences of VSD. MiRNA microarray analysis and reverse transcription-polymerase chain reaction (RT-PCR) were employed to determine the miRNA expression profile from 3 patients with VSD and 3 VSD-free controls. 3 target gene databases were employed to predict the target genes of differentially expressed miRNAs. miRNAs that were generally consensus across the three databases were selected and then independently validated using real time PCR in plasma samples from 20 VSD patients and 15 VSD-free controls. Target genes of validated 8 miRNAs were predicted using bioinformatic methods. 36 differentially expressed miRNAs were found in the patients with VSD and the VSD-free controls. Compared with VSD-free controls, expression of 15 miRNAs were up-regulated and 21 miRNAs were downregulated in the VSD group. 15 miRNAs were selected based on database analysis results and expression levels of 8 miRNAs were validated. The results of the real time PCR were consistent with those of the microarray analysis. Gene ontology analysis indicated that the top target genes were mainly related to cardiac right ventricle morphogenesis. NOTCH1, HAND1, ZFPM2, and GATA3 were predicted as targets of hsa-let-7e-5p, hsa-miR-222-3p and hsa-miR-433. We report for the first time the circulating miRNA profile for patients with VSD and showed that 7 miRNAs were downregulated and 1 upregulated when matched to VSD-free controls. Analysis revealed target genes involved in cardiac development were probably regulated by these miRNAs.

Expressed microRNA associated with high rate of egg production in chicken ovarian follicles.

PubMed

Wu, N; Gaur, U; Zhu, Q; Chen, B; Xu, Z; Zhao, X; Yang, M; Li, D

2017-04-01

MicroRNA (miRNA) is a highly conserved class of small noncoding RNA about 19-24 nucleotides in length that function in a specific manner to post-transcriptionally regulate gene expression in organisms. Tissue miRNA expression studies have discovered a myriad of functions for miRNAs in various aspects, but a role for miRNAs in chicken ovarian tissue at 300 days of age has not hitherto been reported. In this study, we performed the first miRNA analysis of ovarian tissues in chickens with low and high rates of egg production using high-throughput sequencing. By comparing low rate of egg production chickens with high rate of egg production chickens, 17 significantly differentially expressed miRNAs were found (P < 0.05), including 11 known and six novel miRNAs. We found that all 11 known miRNAs were involved mainly in pathways of reproduction regulation, such as steroid hormone biosynthesis and dopaminergic synapse. Additionally, expression profiling of six randomly selected differentially regulated miRNAs were validated by quantitative real-time polymerase chain reaction (RT-qPCR). Some miRNAs, such as gga-miR-34b, gga-miR-34c and gga-miR-216b, were reported to regulate processes such as proliferation, cell cycle, apoptosis and metastasis and were expressed differentially in ovaries of chickens with high rates of egg production, suggesting that these miRNAs have an important role in ovary development and reproductive management of chicken. Furthermore, we uncovered that a significantly up-regulated miRNA-gga-miR-200a-3p-is ubiquitous in reproduction-regulation-related pathways. This miRNA may play a special central role in the reproductive management of chicken, and needs to be further studied for confirmation. © 2016 Stichting International Foundation for Animal Genetics.

Insilico profiling of microRNAs in Korean ginseng (Panax ginseng Meyer)

PubMed Central

Mathiyalagan, Ramya; Subramaniyam, Sathiyamoorthy; Natarajan, Sathishkumar; Kim, Yeon Ju; Sun, Myung Suk; Kim, Se Young; Kim, Yu-Jin; Yang, Deok Chun

2013-01-01

MicroRNAs (miRNAs) are a class of recently discovered non-coding small RNA molecules, on average approximately 21 nucleotides in length, which underlie numerous important biological roles in gene regulation in various organisms. The miRNA database (release 18) has 18,226 miRNAs, which have been deposited from different species. Although miRNAs have been identified and validated in many plant species, no studies have been reported on discovering miRNAs in Panax ginseng Meyer, which is a traditionally known medicinal plant in oriental medicine, also known as Korean ginseng. It has triterpene ginseng saponins called ginsenosides, which are responsible for its various pharmacological activities. Predicting conserved miRNAs by homology-based analysis with available expressed sequence tag (EST) sequences can be powerful, if the species lacks whole genome sequence information. In this study by using the EST based computational approach, 69 conserved miRNAs belonging to 44 miRNA families were identified in Korean ginseng. The digital gene expression patterns of predicted conserved miRNAs were analyzed by deep sequencing using small RNA sequences of flower buds, leaves, and lateral roots. We have found that many of the identified miRNAs showed tissue specific expressions. Using the insilico method, 346 potential targets were identified for the predicted 69 conserved miRNAs by searching the ginseng EST database, and the predicted targets were mainly involved in secondary metabolic processes, responses to biotic and abiotic stress, and transcription regulator activities, as well as a variety of other metabolic processes. PMID:23717176

A validation of the Danish microbiology database (MiBa) and incidence rate of Actinotignum schaalii (Actinobaculum schaalii) bacteraemia in Denmark.

PubMed

Bank, S; Søby, K M; Kristensen, L H; Voldstedlund, M; Prag, J

2015-12-01

Actinotignum schaalii (former named Actinobaculum schaalii) can cause urinary tract infections (UTIs) and bacteraemia, mainly in the elderly. A. schaalii is difficult to identify with conventional biochemical tests, and it is often overlooked if the urine is only cultured in ambient air. The aim of this study was to validate data from the nationwide Danish microbiology database (MiBa) with data from the laboratory information system (LIS) at the local department of microbiology in Viborg-Herning, and to evaluate the incidence rate of bacteraemia caused by A. schaalii in Denmark by using data from the MiBa. All departments of microbiology in Denmark report data to the MiBa. All microbiological samples with A. schaalii in Denmark were extracted for a period of 5 years from the MiBa and from the local LISs. All data obtained from our local LIS were also found in the MiBa, except for data on real-time PCR, which were not registered, owing to missing ID codes in the MiBa. From 2010 to 2014, there was a significant increase in the incidence rate of blood cultures with A. schaalii, from 1.8 to 6.8 cases per million, which was probably due to coincident implementation of matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) in routine diagnostics. We found that A. schaalii caused bacteraemia and UTIs mainly in the elderly. In conclusion, the MiBa can be a useful source of nationwide microbiological data in Denmark. Our results suggest that the incidence rate of A. schaalii as a cause of bacteraemia has been underestimated, and that culture of urine in CO2 can improve the detection of A. schaalii. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Longer-term oral antiplatelet use in stable post-myocardial infarction patients: Insights from the long Term rIsk, clinical manaGement and healthcare Resource utilization of stable coronary artery dISease (TIGRIS) observational study.

PubMed

Goodman, Shaun G; Nicolau, Jose C; Requena, Gema; Maguire, Andrew; Blankenberg, Stefan; Chen, Ji Yan; Granger, Christopher B; Grieve, Richard; Pocock, Stuart J; Simon, Tabassome; Yasuda, Satoshi; Vega, Ana Maria; Brieger, David

2017-06-01

To describe contemporary patient characteristics and treatment patterns, including antithrombotic management, of post-myocardial infarction (MI) stable coronary artery disease (CAD) patients at high atherothrombotic risk from different geographical regions. Patients ≥50years with prior MI 1-3years ago and ≥1 risk factor (age ≥65years, diabetes, 2nd prior MI >1yr ago, multivessel CAD, creatinine clearance 15-<60ml/min) were enrolled by 369 physicians (96% cardiologists) in 25 countries (2013-14) in the prospective TIGRIS study (NCT01866904). 9225 patients were enrolled (median 1.8years) post-MI: 52% with prior ST-elevation MI, median age 67years, 24% women, 67% Caucasian, 55% had ≥2 additional qualifying risk factors, 14% current smokers, 67% overweight/obese, 34% with blood pressure ≥140/90mmHg. 81% underwent percutaneous coronary intervention (PCI; 66% with drug-eluting stents) for the index MI. 75% of patients had been discharged on dual antiplatelet therapy (DAPT; acetylsalicylic acid [ASA]+ADP receptor inhibitor [ADPri]), mainly clopidogrel (75%). 63% had discontinued antiplatelet treatment (60% ADPri) around 1year, most commonly by physician recommendation (90%). At enrolment, 97% were taking an antithrombotic drug, most commonly ASA (88%), with 27% on DAPT (median duration 1.6years); continued DAPT >1year was highest (39%) in Asia-Pacific and lowest (12%) in Europe. Despite guideline recommendations, 1 in 4 post-MI patients did not receive DAPT for ~1year. In contrast to guideline recommendations supporting newer ADPris, clopidogrel was mainly prescribed. Prior to recent RCT data supporting DAPT >1year post-MI/PCI, >1 in 4 patients have continued on DAPT, though with substantial international variability. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

MicroRNA-34a expression is predictive of recurrence after radiofrequency ablation in early hepatocellular carcinoma.

PubMed

Cui, Xianping; Wu, Yaguang; Wang, Zhiyi; Liu, Xin; Wang, Shikang; Qin, Chengkun

2015-05-01

The prognosis of hepatocellular carcinoma (HCC) treated by radiofrequency ablation (RFA) is mainly associated with tumor recurrence. So far, no tissue biomarker of recurrence has been confirmed in biopsy specimens. Previous studies have reported that aberrant expression of microRNA-34a (miR-34a) is involved in oncogenesis and progression of HCC. The aim of this study was to investigate the prognostic value of tissue miR-34a expression in patients with HCC treated with RFA. Patients with early-stage single-nodule HCC treated with RFA were included, and tissue expression of miR-34a were assessed by quantitative reverse-transcription polymerase chain reaction. Main clinical endpoints were overall and early recurrence. The Kaplan-Meier method was used to plot recurrence curves and univariable and multivariable Cox regression analyses were performed to assess independent predictive factors for recurrence. Of 120 patients, recurrence occurred in 67 patients (55.8 %) with a median follow-up of 31 months. Forty-one patients (34.2 %) recurred within 2 years after RFA. The median miR-34a level was 0.87 (range 0.06-21.54). Low miR-34a level was associated with larger tumor size (P = 0.033) and higher serum alpha-fetoprotein (AFP) level (P = 0.004). When analyzed with a Cox regression model, the two independent predictive factors for overall recurrence were high serum AFP level (hazard ratio [HR] = 1.21; 95 % confidence interval [CI] = 1.04-1.36; P = 0.039) and low miR-34a level (HR = 1.44; 95 % CI = 1.13-1.72; P = 0.011). The expression of miR-34a was also an independent predictive factor for early recurrence (HR = 1.49; 95 % CI = 1.15-1.79; P = 0.008). Taken together, this study suggests that the expression of miR-34a in HCC biopsy specimens has an independent predictive value of early recurrence after RFA.

Explaining suicide attempt with personality traits of aggression and impulsivity in a high risk tribal population of India

PubMed Central

2018-01-01

Introduction Suicide is a spectrum of behavior including suicide ideation and suicidal attempt and is undoubtedly the outcome of the interaction of several factors. The role of two main constructs of human nature, aggression and impulsivity, has been discussed broadly in relation to suicide, as endophenotypes or traits of personality, in research and in clinical practice across diagnoses. The objective of our study was to assess impulsive and aggressive behaviors among primitive people of the Idu Mishmi tribe, who are known for high suicide completer and attempter rates. Methods The study group was comprised of 177 unrelated Idu Mishmi participants divided into two sets: 39 suicide attempters and 138 non-attempters. Data on demographic factors and details of suicide attempts were collected. Participants completed a set of instruments for assessment of aggression and impulsivity traits. Results In the Idu Mishimi population we screened (n = 177), 22.03% of the individuals had attempted suicide, a high percentage. The suicide attempters also showed a significant sex difference: 35.9% were male and 64.10% were female (p = .002*). The suicide attempters (A) scored significantly higher than non-attempters (NA) on aggression (A = 23.93,NA = 18.46) and impulsivity (A = 75.53,NA = 71.59, with p value = 0.05). The trait impulsiveness showed a significantly higher difference (F (1, 117) = 7.274) in comparison to aggression (F (1, 117) = 2.647), suggesting a profound role of impulsiveness in suicide attempts in the Idu Mishmi population. Analysis of sub-traits of aggression and impulsivity revealed significant correlations between them. Using different models, multivariate logistic regression implied roles of gender (OR = 1.079 (0.05)) and impulsiveness (OR = 3.355 (0.013)) in suicide attempts. Conclusion Results demonstrate that gender and impulsivity are strong risk factors for suicide attempts in the Idu Mishmi population. PMID:29447300

Explaining suicide attempt with personality traits of aggression and impulsivity in a high risk tribal population of India.

PubMed

Singh, Piyoosh Kumar; Rao, V R

2018-01-01

Suicide is a spectrum of behavior including suicide ideation and suicidal attempt and is undoubtedly the outcome of the interaction of several factors. The role of two main constructs of human nature, aggression and impulsivity, has been discussed broadly in relation to suicide, as endophenotypes or traits of personality, in research and in clinical practice across diagnoses. The objective of our study was to assess impulsive and aggressive behaviors among primitive people of the Idu Mishmi tribe, who are known for high suicide completer and attempter rates. The study group was comprised of 177 unrelated Idu Mishmi participants divided into two sets: 39 suicide attempters and 138 non-attempters. Data on demographic factors and details of suicide attempts were collected. Participants completed a set of instruments for assessment of aggression and impulsivity traits. In the Idu Mishimi population we screened (n = 177), 22.03% of the individuals had attempted suicide, a high percentage. The suicide attempters also showed a significant sex difference: 35.9% were male and 64.10% were female (p = .002*). The suicide attempters (A) scored significantly higher than non-attempters (NA) on aggression (A = 23.93,NA = 18.46) and impulsivity (A = 75.53,NA = 71.59, with p value = 0.05). The trait impulsiveness showed a significantly higher difference (F (1, 117) = 7.274) in comparison to aggression (F (1, 117) = 2.647), suggesting a profound role of impulsiveness in suicide attempts in the Idu Mishmi population. Analysis of sub-traits of aggression and impulsivity revealed significant correlations between them. Using different models, multivariate logistic regression implied roles of gender (OR = 1.079 (0.05)) and impulsiveness (OR = 3.355 (0.013)) in suicide attempts. Results demonstrate that gender and impulsivity are strong risk factors for suicide attempts in the Idu Mishmi population.

Cancer-associated fibroblasts promote cancer cell growth through a miR-7-RASSF2-PAR-4 axis in the tumor microenvironment

PubMed Central

Yan, Ming; Li, Rongrong; Chen, Gang; Zhang, Jianjun; Chen, Wantao

2017-01-01

Cancer-associated fibroblasts (CAFs), a major component of cancer stroma, play an important role in cancer progression but little is known about how CAFs affect tumorigenesis and development. MicroRNAs (miRNAs) are small non-coding RNAs that can negatively regulate target mRNA expression at post-transcriptional levels. In head and neck cancer (HNC), our analysis of miRNA arrays showed that miR-7, miR-196 and miR-335 were significantly up-regulated in CAFs when compared with their paired normal fibroblasts (NFs). FAP, α-SMA and FSP, specific markers of CAFs, were significantly expressed in CAFs. Functionally, exogenous expression of miR-7 in NFs induced a functional conversion of NFs into CAFs. In contrast, inhibition of miR-7 expression in CAFs could induce a functional conversion of CAFs into NFs. Our study demonstrated that overexpression of miR-7 in NFs significantly increased the migration activity and growth rates of cancer cells in co-culture experiments. Mechanistically, we confirmed that the RASSF2-PAR-4 axis was mainly responsible for miR-7 functions in CAFs using bioinformatics methods. Overexpression of miR-7 in CAFs led to down-regulation of RASSF2, which dramatically decreased the secretion of PAR-4 from CAFs and then enhanced the proliferation and migration of the co-cultured cancer cells. Thus, these results reveal that the inactivation of the RASSF2-PAR-4 axis controlled by miR-7 may be a novel strategy for gene therapy in HNCs. PMID:27901488

Common features of microRNA target prediction tools

PubMed Central

Peterson, Sarah M.; Thompson, Jeffrey A.; Ufkin, Melanie L.; Sathyanarayana, Pradeep; Liaw, Lucy; Congdon, Clare Bates

2014-01-01

The human genome encodes for over 1800 microRNAs (miRNAs), which are short non-coding RNA molecules that function to regulate gene expression post-transcriptionally. Due to the potential for one miRNA to target multiple gene transcripts, miRNAs are recognized as a major mechanism to regulate gene expression and mRNA translation. Computational prediction of miRNA targets is a critical initial step in identifying miRNA:mRNA target interactions for experimental validation. The available tools for miRNA target prediction encompass a range of different computational approaches, from the modeling of physical interactions to the incorporation of machine learning. This review provides an overview of the major computational approaches to miRNA target prediction. Our discussion highlights three tools for their ease of use, reliance on relatively updated versions of miRBase, and range of capabilities, and these are DIANA-microT-CDS, miRanda-mirSVR, and TargetScan. In comparison across all miRNA target prediction tools, four main aspects of the miRNA:mRNA target interaction emerge as common features on which most target prediction is based: seed match, conservation, free energy, and site accessibility. This review explains these features and identifies how they are incorporated into currently available target prediction tools. MiRNA target prediction is a dynamic field with increasing attention on development of new analysis tools. This review attempts to provide a comprehensive assessment of these tools in a manner that is accessible across disciplines. Understanding the basis of these prediction methodologies will aid in user selection of the appropriate tools and interpretation of the tool output. PMID:24600468

Common features of microRNA target prediction tools.

PubMed

Peterson, Sarah M; Thompson, Jeffrey A; Ufkin, Melanie L; Sathyanarayana, Pradeep; Liaw, Lucy; Congdon, Clare Bates

2014-01-01

The human genome encodes for over 1800 microRNAs (miRNAs), which are short non-coding RNA molecules that function to regulate gene expression post-transcriptionally. Due to the potential for one miRNA to target multiple gene transcripts, miRNAs are recognized as a major mechanism to regulate gene expression and mRNA translation. Computational prediction of miRNA targets is a critical initial step in identifying miRNA:mRNA target interactions for experimental validation. The available tools for miRNA target prediction encompass a range of different computational approaches, from the modeling of physical interactions to the incorporation of machine learning. This review provides an overview of the major computational approaches to miRNA target prediction. Our discussion highlights three tools for their ease of use, reliance on relatively updated versions of miRBase, and range of capabilities, and these are DIANA-microT-CDS, miRanda-mirSVR, and TargetScan. In comparison across all miRNA target prediction tools, four main aspects of the miRNA:mRNA target interaction emerge as common features on which most target prediction is based: seed match, conservation, free energy, and site accessibility. This review explains these features and identifies how they are incorporated into currently available target prediction tools. MiRNA target prediction is a dynamic field with increasing attention on development of new analysis tools. This review attempts to provide a comprehensive assessment of these tools in a manner that is accessible across disciplines. Understanding the basis of these prediction methodologies will aid in user selection of the appropriate tools and interpretation of the tool output.

Effects of unweighting and speed on in-shoe regional loading during running on a lower body positive pressure treadmill.

PubMed

Smoliga, James M; Wirfel, Leah Anne; Paul, Danielle; Doarnberger, Mary; Ford, Kevin R

2015-07-16

The purpose of this study was to determine how unweighted running on a lower body positive pressure treadmill (LBPPT) modifies in-shoe regional loading. Ten experienced runners were fit with pressure distribution measurement insoles and ran at 100%, 120%, and 140% of self-reported easy training pace on a LBPPT at 20%, 40%, 60%, 80%, and 100% body weight percentage settings (BWSet). Speeds and BWSet were in random order. A linear mixed effect model (p<0.05 significance level) was used to compare differences in whole foot and regional maximum in-shoe plantar force (FMAX), impulse, and relative load distribution across speeds and BWSet. There were significant main effects (p<0.001) for running speed and BWSet for whole foot Fmax and impulse. The model revealed 1.4% and 0.24% increases in whole foot FMAX (times body weight) and impulse, respectively, for every unit increase in body weight percentage. There was a significant main effect for BWSet on Fmax and relative load (p<0.05) for each of the nine foot regions examined, though four regions were not different between 80% and 100% BWSet. There was a significant (p<0.001) main effect for BWSet on forefoot to rear foot relative load. Linear relationships were found between increases in BWSet and increases in-shoe Fmax and impulse, resulting from regional changes in foot pressure which represent a shift towards forefoot loading, most evident <80% BWSet. Estimating in-shoe regional loading parameters may be useful during rehabilitation and training to appropriately prescribe specific speed and body weight levels, without exceeding certain critical peak force levels while running. Copyright © 2015 Elsevier Ltd. All rights reserved.

Useful Citizens, Useful Citizenship: Cultural Contexts of Sámi Education in Early Twentieth-Century Norway, Sweden, and Finland

ERIC Educational Resources Information Center

Kortekangas, Otso

2017-01-01

This article investigates Sámi elementary education in early twentieth-century Finland, Norway, and Sweden. The main focus lies on cultural contexts that frame and limit language use. The key analytical concepts are "useful citizen" and "useful citizenship". Through these concepts the article probes the ways in which…

A microRNA expression signature of the postprandial state in response to a high-saturated-fat challenge.

PubMed

Lopez, Sergio; Bermudez, Beatriz; Montserrat-de la Paz, Sergio; Abia, Rocio; Muriana, Francisco J G

2018-07-01

The postprandial hypertriglyceridemia is an important and largely silent disturbance involved in the genesis of numerous pathological conditions. Exaggerated and prolonged states of postprandial hypertriglyceridemia are frequently related to the ingestion of meals enriched in saturated fatty acids (SFAs). MicroRNAs are noncoding RNAs that function as gene regulators and play significant roles in both health and disease. However, differential miRNA expression between fasting and postprandial states has never been elucidated. Here, we studied the impact of a high-saturated-fat meal, mainly rich in palmitic acid, on the miRNA signature in peripheral blood mononuclear cells (PBMCs) of nine male healthy individuals in the postprandial period by using a two-step analysis: miRNA array and validation through quantitative real-time polymerase chain reaction. Compared with miRNA expression signature in PBMCs at fasting, 36 miRNAs were down-regulated and 43 miRNAs were up-regulated in PBMCs at postprandial hypertriglyceridemic peak. Six chromosomes (3, 7, 8, 12, 14 and 19) had nearly half (48.1%) of dysregulated miRNA-gene-containing regions. Down-regulated miR-300 and miR-369-3p and up-regulated miR-495-3p, miR-129-5p and miR-7-2-3p had the highest number of target genes. The differentially expressed miRNAs and their predicted target genes involved pathways in cancer, MAPK signaling pathway, endocytosis and axon guidance. Only down-regulated miRNAs notably targeted PI3K-Akt signaling pathways, whereas only up-regulated miRNAs targeted focal adhesion, Wnt signaling pathway, transcriptional misregulation in cancer and ubiquitin-mediated proteolysis. This is the first study of miRNA expression analysis of human PBMCs during postprandial hypertriglyceridemia and offers insight into new potential mechanisms by which dietary SFAs influence health or disease. Copyright © 2018 Elsevier Inc. All rights reserved.

PDAC-derived exosomes enrich the microenvironment in MDSCs in a SMAD4-dependent manner through a new calcium related axis.

PubMed

Basso, Daniela; Gnatta, Elisa; Padoan, Andrea; Fogar, Paola; Furlanello, Sara; Aita, Ada; Bozzato, Dania; Zambon, Carlo-Federico; Arrigoni, Giorgio; Frasson, Chiara; Franchin, Cinzia; Moz, Stefania; Brefort, Thomas; Laufer, Thomas; Navaglia, Filippo; Pedrazzoli, Sergio; Basso, Giuseppe; Plebani, Mario

2017-10-17

Tumor genetics and escape from immune surveillance concur in the poor prognosis of PDAC. In this study an experimental model was set up to verify whether SMAD4 , deleted in about 55% PDAC and associated with poor prognosis, is involved in determining immunosuppression through Exosomes (Exo). Potential mechanisms and mediators underlying SMAD4 -dependent immunosuppression were evaluated by studying intracellular calcium (Fluo-4), Exo-miRNAs (microarray) and Exo-proteins (SILAC). Two PDAC cell lines expressing (BxPC3- SMAD4 +) or not-expressing (BxPC3) SMAD4 were used to prepare Exo-enriched conditioned media, employed in experiments with blood donors PBMCs. Exo expanded myeloid derived suppressor cells (gMDSC and mMDSC, flow cytometry) and altered intracellular calcium fluxes in an SMAD4 dependent manner. BxPC3- SMAD4 +, but mainly BxPC3 Exo, increased calcium fluxes of PBMCs ( p = 0.007) and this increased intracellular calcium trafficking characterized mMDSCs. The analysis of de-regulated Exo-miRNAs and transfection experiments revealed hsa-miR-494-3p and has-miR-1260a as potential mediators of SMAD4- associated de-regulated calcium fluxes. Eleven main biological processes were identified by the analysis of SMAD4 -associated de-regulated Exo-proteins, including translation, cell adhesion, cell signaling and glycolysis. A reverse Warburg effect was observed by treating PBMCs with PDAC-derived Exo: BxPC3 Exo induced a higher glucose consumption and lactate production than BxPC3- SMAD4 + Exo. PDAC-derived Exo from cells with , but mainly from those without SMAD4 expression, create an immunosuppressive myeloid cell background by increasing calcium fluxes and glycolysis through the transfer of SMAD4 -related differentially expressed miRNAs and proteins.

PDAC-derived exosomes enrich the microenvironment in MDSCs in a SMAD4-dependent manner through a new calcium related axis

PubMed Central

Basso, Daniela; Gnatta, Elisa; Padoan, Andrea; Fogar, Paola; Furlanello, Sara; Aita, Ada; Bozzato, Dania; Zambon, Carlo-Federico; Arrigoni, Giorgio; Frasson, Chiara; Franchin, Cinzia; Moz, Stefania; Brefort, Thomas; Laufer, Thomas; Navaglia, Filippo; Pedrazzoli, Sergio; Basso, Giuseppe; Plebani, Mario

2017-01-01

Tumor genetics and escape from immune surveillance concur in the poor prognosis of PDAC. In this study an experimental model was set up to verify whether SMAD4, deleted in about 55% PDAC and associated with poor prognosis, is involved in determining immunosuppression through Exosomes (Exo). Potential mechanisms and mediators underlying SMAD4-dependent immunosuppression were evaluated by studying intracellular calcium (Fluo-4), Exo-miRNAs (microarray) and Exo-proteins (SILAC). Two PDAC cell lines expressing (BxPC3-SMAD4+) or not-expressing (BxPC3) SMAD4 were used to prepare Exo-enriched conditioned media, employed in experiments with blood donors PBMCs. Exo expanded myeloid derived suppressor cells (gMDSC and mMDSC, flow cytometry) and altered intracellular calcium fluxes in an SMAD4 dependent manner. BxPC3-SMAD4+, but mainly BxPC3 Exo, increased calcium fluxes of PBMCs (p = 0.007) and this increased intracellular calcium trafficking characterized mMDSCs. The analysis of de-regulated Exo-miRNAs and transfection experiments revealed hsa-miR-494-3p and has-miR-1260a as potential mediators of SMAD4-associated de-regulated calcium fluxes. Eleven main biological processes were identified by the analysis of SMAD4-associated de-regulated Exo-proteins, including translation, cell adhesion, cell signaling and glycolysis. A reverse Warburg effect was observed by treating PBMCs with PDAC-derived Exo: BxPC3 Exo induced a higher glucose consumption and lactate production than BxPC3-SMAD4+ Exo. Conclusion: PDAC-derived Exo from cells with, but mainly from those without SMAD4 expression, create an immunosuppressive myeloid cell background by increasing calcium fluxes and glycolysis through the transfer of SMAD4-related differentially expressed miRNAs and proteins. PMID:29156694

BMI predicts emotion-driven impulsivity and cognitive inflexibility in adolescents with excess weight.

PubMed

Delgado-Rico, Elena; Río-Valle, Jacqueline S; González-Jiménez, Emilio; Campoy, Cristina; Verdejo-García, Antonio

2012-08-01

Adolescent obesity is increasingly viewed as a brain-related dysfunction, whereby reward-driven urges for pleasurable foods "hijack" response selection systems, such that behavioral control progressively shifts from impulsivity to compulsivity. In this study, we aimed to examine the link between personality factors (sensitivity to reward (SR) and punishment (SP), BMI, and outcome measures of impulsivity vs. flexibility in--otherwise healthy--excessive weight adolescents. Sixty-three adolescents (aged 12-17) classified as obese (n = 26), overweight (n = 16), or normal weight (n = 21) participated in the study. We used psychometric assessments of the SR and SP motivational systems, impulsivity (using the UPPS-P scale), and neurocognitive measures with discriminant validity to dissociate inhibition vs. flexibility deficits (using the process-approach version of the Stroop test). We tested the relative contribution of age, SR/SP, and BMI on estimates of impulsivity and inhibition vs. switching performance using multistep hierarchical regression models. BMI significantly predicted elevations in emotion-driven impulsivity (positive and negative urgency) and inferior flexibility performance in adolescents with excess weight--exceeding the predictive capacity of SR and SP. SR was the main predictor of elevations in sensation seeking and lack of premeditation. These findings demonstrate that increases in BMI are specifically associated with elevations in emotion-driven impulsivity and cognitive inflexibility, supporting a dimensional path in which adolescents with excess weight increase their proneness to overindulge when under strong affective states, and their difficulties to switch or reverse habitual behavioral patterns.

Identification of an Enhancer That Increases miR-200b~200a~429 Gene Expression in Breast Cancer Cells

PubMed Central

Attema, Joanne L.; Bert, Andrew G.; Lim, Yat-Yuen; Kolesnikoff, Natasha; Lawrence, David M.; Pillman, Katherine A.; Smith, Eric; Drew, Paul A.; Khew-Goodall, Yeesim; Shannon, Frances; Goodall, Gregory J.

2013-01-01

The miR-200b~200a~429 gene cluster is a key regulator of EMT and cancer metastasis, however the transcription-based mechanisms controlling its expression during this process are not well understood. We have analyzed the miR-200b~200a~429 locus for epigenetic modifications in breast epithelial and mesenchymal cell lines using chromatin immunoprecipitation assays and DNA methylation analysis. We discovered a novel enhancer located approximately 5.1kb upstream of the miR-200b~200a~429 transcriptional start site. This region was associated with the active enhancer chromatin signature comprising H3K4me1, H3K27ac, RNA polymerase II and CpG dinucleotide hypomethylation. Luciferase reporter assays revealed the upstream enhancer stimulated the transcription of the miR-200b~200a~429 minimal promoter region approximately 27-fold in breast epithelial cells. Furthermore, we found that a region of the enhancer was transcribed, producing a short, GC-rich, mainly nuclear, non-polyadenylated RNA transcript designated miR-200b eRNA. Over-expression of miR-200b eRNA had little effect on miR-200b~200a~429 promoter activity and its production did not correlate with miR-200b~200a~429 gene expression. While additional investigations of miR-200b eRNA function will be necessary, it is possible that miR-200b eRNA may be involved in the regulation of miR-200b~200a~429 gene expression and silencing. Taken together, these findings reveal the presence of a novel enhancer, which contributes to miR-200b~200a~429 transcriptional regulation in epithelial cells. PMID:24086551

microRNA-340 induces apoptosis by downregulation of BAG3 in ovarian cancer SKOV3 cells.

PubMed

Qu, Fei; Wang, Xiufen

2017-08-01

Aberrant expression of miR-340 has been found in several kinds of cancers including ovarian cancer. Pro-apoptotic and anti-metastasis roles of miR-340 in ovarian cancer have also been reported; however, the underling molecular mechanisms by which miR-340 suppresses ovarian cancer are still unclear. This study focused on the role and molecular mechanism of miR-340 in ovarian cancer. Human ovarian carcinoma SKOV3 cells were used and transfected with miR-340 mimic, miR-340 inhibitor and their correspondingly negative controls (mimic control and inhibitor control). Thereafter, cell viability, apoptosis, and the expressions of apoptosis-associated factors and BAG3 were respectively assessed by MTT assay, flow cytometry, qRT-PCR and Western blotting. SKOV3 cells were then co-transfected with miR-340 inhibitor and BAG3 targeted siRNA, then cell viability, apoptosis and the expression of apoptosis-associated factors were retested. Besides, the expressions of main factors in PI3K/AKT pathway were detected. Overexpression of miR-340 suppressed BAG3 cells viability (P < 0.05), but improved apoptosis (P < 0.001). BAG3 was negatively regulated by miR-340 (P < 0.05 or P < 0.01). BAG3 silence significantly induced cell apoptosis (P < 0.001), and abolished miR-340 suppression-induced increase in cell viability (P < 0.001). Besides, BAG3 silence abolished miR-340 suppression-induced activation of PI3K and AKT. This study revealed the tumor suppressive role of miR-340 in SKOV3 cells by negative regulation of BAG3. PI3K/AKT pathway might be involved in the regulation of miR-340 and BAG3.

Why standard brain-computer interface (BCI) training protocols should be changed: an experimental study

NASA Astrophysics Data System (ADS)

Jeunet, Camille; Jahanpour, Emilie; Lotte, Fabien

2016-06-01

Objective. While promising, electroencephaloraphy based brain-computer interfaces (BCIs) are barely used due to their lack of reliability: 15% to 30% of users are unable to control a BCI. Standard training protocols may be partly responsible as they do not satisfy recommendations from psychology. Our main objective was to determine in practice to what extent standard training protocols impact users’ motor imagery based BCI (MI-BCI) control performance. Approach. We performed two experiments. The first consisted in evaluating the efficiency of a standard BCI training protocol for the acquisition of non-BCI related skills in a BCI-free context, which enabled us to rule out the possible impact of BCIs on the training outcome. Thus, participants (N = 54) were asked to perform simple motor tasks. The second experiment was aimed at measuring the correlations between motor tasks and MI-BCI performance. The ten best and ten worst performers of the first study were recruited for an MI-BCI experiment during which they had to learn to perform two MI tasks. We also assessed users’ spatial ability and pre-training μ rhythm amplitude, as both have been related to MI-BCI performance in the literature. Main results. Around 17% of the participants were unable to learn to perform the motor tasks, which is close to the BCI illiteracy rate. This suggests that standard training protocols are suboptimal for skill teaching. No correlation was found between motor tasks and MI-BCI performance. However, spatial ability played an important role in MI-BCI performance. In addition, once the spatial ability covariable had been controlled for, using an ANCOVA, it appeared that participants who faced difficulty during the first experiment improved during the second while the others did not. Significance. These studies suggest that (1) standard MI-BCI training protocols are suboptimal for skill teaching, (2) spatial ability is confirmed as impacting on MI-BCI performance, and (3) when faced with difficult pre-training, subjects seemed to explore more strategies and therefore learn better.

Impulsive Control for Continuous-Time Markov Decision Processes: A Linear Programming Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dufour, F., E-mail: dufour@math.u-bordeaux1.fr; Piunovskiy, A. B., E-mail: piunov@liv.ac.uk

2016-08-15

In this paper, we investigate an optimization problem for continuous-time Markov decision processes with both impulsive and continuous controls. We consider the so-called constrained problem where the objective of the controller is to minimize a total expected discounted optimality criterion associated with a cost rate function while keeping other performance criteria of the same form, but associated with different cost rate functions, below some given bounds. Our model allows multiple impulses at the same time moment. The main objective of this work is to study the associated linear program defined on a space of measures including the occupation measures ofmore » the controlled process and to provide sufficient conditions to ensure the existence of an optimal control.« less

Uncovering MicroRNA and Transcription Factor Mediated Regulatory Networks in Glioblastoma

PubMed Central

Sun, Jingchun; Gong, Xue; Purow, Benjamin; Zhao, Zhongming

2012-01-01

Glioblastoma multiforme (GBM) is the most common and lethal brain tumor in humans. Recent studies revealed that patterns of microRNA (miRNA) expression in GBM tissue samples are different from those in normal brain tissues, suggesting that a number of miRNAs play critical roles in the pathogenesis of GBM. However, little is yet known about which miRNAs play central roles in the pathology of GBM and their regulatory mechanisms of action. To address this issue, in this study, we systematically explored the main regulation format (feed-forward loops, FFLs) consisting of miRNAs, transcription factors (TFs) and their impacting GBM-related genes, and developed a computational approach to construct a miRNA-TF regulatory network. First, we compiled GBM-related miRNAs, GBM-related genes, and known human TFs. We then identified 1,128 3-node FFLs and 805 4-node FFLs with statistical significance. By merging these FFLs together, we constructed a comprehensive GBM-specific miRNA-TF mediated regulatory network. Then, from the network, we extracted a composite GBM-specific regulatory network. To illustrate the GBM-specific regulatory network is promising for identification of critical miRNA components, we specifically examined a Notch signaling pathway subnetwork. Our follow up topological and functional analyses of the subnetwork revealed that six miRNAs (miR-124, miR-137, miR-219-5p, miR-34a, miR-9, and miR-92b) might play important roles in GBM, including some results that are supported by previous studies. In this study, we have developed a computational framework to construct a miRNA-TF regulatory network and generated the first miRNA-TF regulatory network for GBM, providing a valuable resource for further understanding the complex regulatory mechanisms in GBM. The observation of critical miRNAs in the Notch signaling pathway, with partial verification from previous studies, demonstrates that our network-based approach is promising for the identification of new and important miRNAs in GBM and, potentially, other cancers. PMID:22829753

Apigenin sensitizes BEL-7402/ADM cells to doxorubicin through inhibiting miR-101/Nrf2 pathway

PubMed Central

Gao, Ai-Mei; Zhang, Xiao-Yu; Ke, Zun-Ping

2017-01-01

Chemo-resistance is one of the main obstacle in hepatocellular carcinoma therapy. Apigenin as a natural bioflavonoid has been exhibited anti-cancer properties in various malignant cancers. The aim of this study is to evaluate the potential chemo-sensitization effect of apigenin in doxorubicin-resistant hepatocellular carcinoma cell line BEL-7402/ADM and to investigate its possible mechanism. We found that apigenin significantly reversed doxorubicin sensitivity and induced caspase-dependent apoptosis in BEL-7402/ADM cells. Furthermore, apigenin induced miR-101 expression, and overexpression of miR-101 mimicked the doxorubicin-sensitizing effect of apigenin. Importantly, we showed that miR-101 was able to target the 3′-UTR of Nrf2. The results suggested that apigenin sensitizes BEL-7402/ADM cells to doxorubicin through miR-101/Nrf2 pathway, which furtherly supports apigenin as a potential chemo-sensitizer for hepatocellular carcinoma. PMID:29137246

MicroRNAs and toxicology: A love marriage.

PubMed

Schraml, Elisabeth; Hackl, Matthias; Grillari, Johannes

2017-01-01

With the dawn of personalized medicine, secreted microRNAs (miRNAs) have come into the very focus of biomarker development for various diseases. MiRNAs fulfil key requirements of diagnostic tools such as i) non or minimally invasive accessibility, ii) robust, standardized and non-expensive quantitative analysis, iii) rapid turnaround of the test result and iv) most importantly because they provide a comprehensive snapshot of the ongoing physiologic processes in cells and tissues that package and release miRNAs into cell-free space. These characteristics have also established circulating miRNAs as promising biomarker candidates for toxicological studies, where they are used as biomarkers of drug-, or chemical-induced tissue injury for safety assessment. The tissue-specificity and early release of circulating miRNAs upon tissue injury, when damage is still reversible, are main factors for their clinical utility in toxicology. Here we summarize in brief, current knowledge of this field.

[The health status of Yanomámi Indians: diagnosis from the Casa do Indio, Boa Vista, Roraima, 1987 - 1989].

PubMed

Pithan, O A; Confalonieri, U E; Morgado, A F

1991-01-01

The change in the morbidity profile of the Yanomámi Indians admitted to the Casa do Indio, at Boa Vista, Roraima, from January 1987 to August 1989, is reported. The most frequent diseases observed in 495 patients were malaria, acute respiratory infections, tuberculosis, severe under nutrition, and sexually transmitted diseases. Malaria was the main cause of death of 114 Indians throughout the period. A striking increase in hospital admissions was noted in the population from the villages which were in closer contact with gold miners. The global impact of the invasion of the Yanomámi territory by miners on the quality of life and health levels of the Yanomámi is discussed.

Development and evaluation of form three mathematics i-Think module (Mi-T3) on algebraic formulae topic

NASA Astrophysics Data System (ADS)

Sam, Sazilah; Abdullah, Mohd Faizal Nizam Lee

2017-05-01

This article introduces the Form Three Mathematics i-Think Module (Mi-T3). The main objective of this Mi-T3 is to assist form three students develop their higher order thinking skills (HOTS). The Sidek Module Development Model (SMDM) and eight innovative thinking maps (i-Think) were applied as a guideline in developing Mi-T3. A validation stage was carried out by eight experts, and content validation achievement more than 90% obtained. A group of form three students and teachers was piloted to check the module's reliability through one to one and small group evaluation and Cronbach Alpha more than 0.90 was obtained. Implications of the study are discussed in this article.

Cleaning of Root Canal System by Different Irrigation Methods.

PubMed

Tanomaru-Filho, Mário; Miano, Lucas Martinati; Chávez-Andrade, Gisselle Moraima; Torres, Fernanda Ferrari Esteves; Leonardo, Renato de Toledo; Guerreiro-Tanomaru, Juliane Maria

2015-11-01

The aim of this study was to compare the cleaning of main and lateral canals using the irrigation methods: negative pressure irrigation (EndoVac system), passive ultrasonic irrigation (PUI) and manual irrigation (MI). Resin teeth were used. After root canal preparation, four lateral canals were made at 2 and 7 mm from the apex. Root canals were filled with contrast solution and radiographed pre- and post-irrigation using digital radiographic system [radiovisiography (RVG)]. The irrigation protocols were: MI1-manual irrigation [22 G needle at 5 mm short of working length-WL]; MI2-manual irrigation (30G needle at 2 mm short of WL); PUI; EV1-EndoVac (microcannula at 1 mm short of WL); EV2-Endovac (microcannula at 3 mm short of WL). The obtained images, initial (filled with contrast solution) and final (after irrigation) were analyzed by using image tool 3.0 software. Statistical analysis was performed by analysis of variance (ANOVA) and Tukey tests (5% significance level). EV1 and EV2, followed by PUI showed better cleaning capacity than manual irrigation (MI1 and MI2) (p < 0.05). Negative pressure irrigation and PUI promoted better cleaning of main and simulated lateral canals. Conventional manual irrigation technique may promote less root canal cleaning in the apical third. For this reason, the search for other irrigation protocols is important, and EndoVac and PUI are alternatives to contribute to irrigation effectiveness.

Achieving a hybrid brain-computer interface with tactile selective attention and motor imagery

NASA Astrophysics Data System (ADS)

Ahn, Sangtae; Ahn, Minkyu; Cho, Hohyun; Jun, Sung Chan

2014-12-01

Objective. We propose a new hybrid brain-computer interface (BCI) system that integrates two different EEG tasks: tactile selective attention (TSA) using a vibro-tactile stimulator on the left/right finger and motor imagery (MI) of left/right hand movement. Event-related desynchronization (ERD) from the MI task and steady-state somatosensory evoked potential (SSSEP) from the TSA task are retrieved and combined into two hybrid senses. Approach. One hybrid approach is to measure two tasks simultaneously; the features of each task are combined for testing. Another hybrid approach is to measure two tasks consecutively (TSA first and MI next) using only MI features. For comparison with the hybrid approaches, the TSA and MI tasks are measured independently. Main results. Using a total of 16 subject datasets, we analyzed the BCI classification performance for MI, TSA and two hybrid approaches in a comparative manner; we found that the consecutive hybrid approach outperformed the others, yielding about a 10% improvement in classification accuracy relative to MI alone. It is understood that TSA may play a crucial role as a prestimulus in that it helps to generate earlier ERD prior to MI and thus sustains ERD longer and to a stronger degree; this ERD may give more discriminative information than ERD in MI alone. Significance. Overall, our proposed consecutive hybrid approach is very promising for the development of advanced BCI systems.

A Meloidogyne incognita effector MiISE5 suppresses programmed cell death to promote parasitism in host plant.

PubMed

Shi, Qianqian; Mao, Zhenchuan; Zhang, Xi; Zhang, Xiaoping; Wang, Yunsheng; Ling, Jian; Lin, Runmao; Li, Denghui; Kang, Xincong; Sun, Wenxian; Xie, Bingyan

2018-05-08

Root-knot nematodes (RKNs) are highly specialized parasites that interact with their host plants using a range of strategies. The esophageal glands are the main places where nematodes synthesize effector proteins, which play central roles in successful invasion. The Meloidogyne incognita effector MiISE5 is exclusively expressed within the subventral esophageal cells and is upregulated during early parasitic stages. In this study, we show that MiISE5 can be secreted to barley cells through infectious hyphae of Magnaporthe oryzae. Transgenic Arabidopsis plants expressing MiISE5 became significantly more susceptible to M. incognita. Inversely, the tobacco rattle virus (TRV)-mediated silence of MiISE5 decreased nematode parasitism. Moreover, transient expression of MiISE5 suppressed cell death caused by Burkholderia glumae in Nicotiana benthamiana. Based on transcriptome analysis of MiISE5 transgenic sample and the wild-type (WT) sample, we obtained 261 DEGs, and the results of GO and KEGG enrichment analysis indicate that MiISE5 can interfere with various metabolic and signaling pathways, especially the JA signaling pathway, to facilitate nematode parasitism. Results from the present study suggest that MiISE5 plays an important role during the early stages of parasitism and provides evidence to decipher the molecular mechanisms underlying the manipulation of host immune defense responses by M. incognita.

Altered regulation of miR-34a and miR-483-3p in alcoholic hepatitis and DDC fed mice.

PubMed

Liu, Hui; French, Barbara A; Li, Jun; Tillman, Brittany; French, Samuel W

2015-12-01

MicroRNAs are small noncoding RNAs that negatively regulate gene expression by binding to the untranslated regions of their target mRNAs. Deregulation of miRNAs is shown to play pivotal roles in tumorigenesis and progression. Mallory-Denk Bodies (MDBs) are prevalent in various liver diseases including alcoholic hepatitis (AH) and are formed in mice livers by feeding DDC. By comparing AH livers where MDBs had formed with normal livers, there were significant changes of miR-34a and miR-483-3p by RNA sequencing (RNA-Seq) analyses. Real-time PCR further shows a 3- and 6-fold upregulation (respectively) of miR-34a in the AH livers and in the livers of DDC re-fed mice, while miR-483-3p was significantly downregulated in AH and DDC re-fed mice livers. This indicates that miR-34a and miR-483-3p may be crucial for liver MDB formation. P53 mRNA was found to be significantly downregulated both in the AH livers and in the livers of DDC re-fed mice, indicating that the upregulation of miR-34a is permitted by the decrease of p53 in AH since miR-34a is a main target of p53. Overexpression of miR-34a leads to an increase of p53 targets such as p27, which inhibits the cell cycle leading to cell cycle arrest. Importantly, BRCA1 is a target gene of miR-483-3p by RNA-Seq analyses and the downregulation of miR-483-3p may be the mechanism for liver MDB formation since the BRCA1 signal was markedly upregulated in AH livers. These results constitute a demonstration of the altered regulation of miR-34a and miR-483-3p in the livers of AH and mice fed DDC where MDBs formed, providing further insight into the mechanism of MDB formation mediated by miR-34a and miR-483-3p in AH. Copyright © 2015 Elsevier Inc. All rights reserved.

Selection of Reference Genes for Normalization of MicroRNA Expression by RT-qPCR in Sugarcane Buds under Cold Stress

PubMed Central

Yang, Yuting; Zhang, Xu; Chen, Yun; Guo, Jinlong; Ling, Hui; Gao, Shiwu; Su, Yachun; Que, Youxiong; Xu, Liping

2016-01-01

Sugarcane, accounting for 80% of world's sugar, originates in the tropics but is cultivated mainly in the subtropics. Therefore, chilling injury frequently occurs and results in serious losses. Recent studies in various plant species have established microRNAs as key elements in the post-transcriptional regulation of response to biotic and abiotic stresses including cold stress. Though, its accuracy is largely influenced by the use of reference gene for normalization, quantitative PCR is undoubtedly a popular method used for identification of microRNAs. For identifying the most suitable reference genes for normalizing miRNAs expression in sugarcane under cold stress, 13 candidates among 17 were investigated using four algorithms: geNorm, NormFinder, deltaCt, and Bestkeeper, and four candidates were excluded because of unsatisfactory efficiency and specificity. Verification was carried out using cold-related genes miR319 and miR393 in cold-tolerant and sensitive cultivars. The results suggested that miR171/18S rRNA and miR171/miR5059 were the best reference gene sets for normalization for miRNA RT-qPCR, followed by the single miR171 and 18S rRNA. These results can aid research on miRNA responses during sugarcane stress, and the development of sugarcane tolerant to cold stress. This study is the first report concerning the reference gene selection of miRNA RT-qPCR in sugarcane. PMID:26904058

MicroRNA-122 Influences the Development of Sperm Abnormalities from Human Induced Pluripotent Stem Cells by Regulating TNP2 Expression

PubMed Central

Huang, Yongyi; Liu, Jianjun; Zhao, Yanhui; Jiang, Lizhen; Huang, Qin

2013-01-01

Sperm abnormalities are one of the main factors responsible for male infertility; however, their pathogenesis remains unclear. The role of microRNAs in the development of sperm abnormalities in infertile men has not yet been investigated. Here, we used human induced pluripotent stem cells to investigate the influence of miR-122 expression on the differentiation of these cells into spermatozoa-like cells in vitro. After induction, mutant miR-122-transfected cells formed spermatozoa-like cells. Flow cytometry of DNA content revealed a significant increase in the haploid cell population in spermatozoa-like cells derived from mutant miR-122-transfected cells as compared to those derived from miR-122-transfected cells. During induction, TNP2 and protamine mRNA and protein levels were significantly higher in mutant miR-122-transfected cells than in miR-122-transfected cells. High-throughput isobaric tags for relative and absolute quantification were used to identify and quantify the different protein expression levels in miR-122- and mutant miR-122-transfected cells. Among all the proteins analyzed, the expression of lipoproteins, for example, APOB and APOA1, showed the most significant difference between the two groups. This study illustrates that miR-122 expression is associated with abnormal sperm development. MiR-122 may influence spermatozoa-like cells by suppressing TNP2 expression and inhibiting the expression of proteins associated with sperm development. PMID:23327642

miR-133b, a particular member of myomiRs, coming into playing its unique pathological role in human cancer.

PubMed

Li, Daojiang; Xia, Lu; Chen, Miao; Lin, Changwei; Wu, Hao; Zhang, Yi; Pan, Songqing; Li, Xiaorong

2017-07-25

MicroRNAs, a family of single-stranded and non-coding RNAs, play a crucial role in regulating gene expression at posttranscriptional level, by which it can mediate various types of physiological and pathological process in normal developmental progress and human disease, including cancer. The microRNA-133b originally defined as canonical muscle-specific microRNAs considering their function to the development and health of mammalian skeletal and cardiac muscles, but new findings coming from our group and others revealed that miR-133b have frequently abnormal expression in various kinds of human cancer and its complex complicated regulatory networks affects the tumorigenicity and development of malignant tumors. Very few existing reviews on miR-133b, until now, are principally about its role in homologous cluster (miR-1, -133 and -206s), however, most of constantly emerging new researches now are focused mainly on one of them, so In this article, to highlight the unique pathological role of miR-133b playing in tumor, we conduct a review to summarize the current understanding about one of the muscle-specific microRNAs, namely miR-133b, acting in human cancer. The review focused on the following four aspects: the overview of miR-133b, the target genes of miR-133b involved in human cancer, the expression of miR-133b and regulatory mechanisms leading to abnormal expression of miR-133b.

Profile of microRNA in Giant Panda Blood: A Resource for Immune-Related and Novel microRNAs

PubMed Central

Yang, Mingyu; Du, Lianming; Li, Wujiao; Shen, Fujun; Fan, Zhenxin; Jian, Zuoyi; Hou, Rong; Shen, Yongmei; Yue, Bisong; Zhang, Xiuyue

2015-01-01

The giant panda (Ailuropoda melanoleuca) is one of the world’s most beloved endangered mammals. Although the draft genome of this species had been assembled, little was known about the composition of its microRNAs (miRNAs) or their functional profiles. Recent studies demonstrated that changes in the expression of miRNAs are associated with immunity. In this study, miRNAs were extracted from the blood of four healthy giant pandas and sequenced by Illumina next generation sequencing technology. As determined by miRNA screening, a total of 276 conserved miRNAs and 51 novel putative miRNAs candidates were detected. After differential expression analysis, we noticed that the expressions of 7 miRNAs were significantly up-regulated in young giant pandas compared with that of adults. Moreover, 2 miRNAs were up-regulated in female giant pandas and 1 in the male individuals. Target gene prediction suggested that the miRNAs of giant panda might be relevant to the expressions of 4,602 downstream genes. Subseuqently, the predicted target genes were conducted to KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and we found that these genes were mainly involved in host immunity, including the Ras signaling pathway, the PI3K-Akt signaling pathway, and the MAPK signaling pathway. In conclusion, our results provide the first miRNA profiles of giant panda blood, and the predicted functional analyses may open an avenue for further study of giant panda immunity. PMID:26599861

Functional study of miR-27a in human hepatic stellate cells by proteomic analysis: comprehensive view and a role in myogenic tans-differentiation.

PubMed

Ji, Yuhua; Zhang, Jinsheng; Wang, Wenwen; Ji, Juling

2014-01-01

We previous reported that miR-27a regulates lipid metabolism and cell proliferation during hepatic stellate cells (HSCs) activation. To further explore the biological function and underlying mechanisms of miR-27a in HSCs, global protein expression affected by overexpression of miR-27a in HSCs was analyzed by a cleavable isotope-coded affinity tags (cICAT) based comparative proteomic approach. In the present study, 1267 non-redundant proteins were identified with unique accession numbers (score ≥1.3, i.e. confidence ≥95%), among which 1171 were quantified and 149 proteins (12.72%) were differentially expressed with a differential expression ratio of 1.5. We found that up-regulated proteins by miR-27a mainly participate in cell proliferation and myogenesis, while down-regulated proteins were the key enzymes involved in de novo lipid synthesis. The expression of a group of six miR-27a regulated proteins was validated and the function of one miR-27a regulated protein was further validated. The results not only delineated the underlying mechanism of miR-27a in modulating fat metabolism and cell proliferation, but also revealed a novel role of miR-27a in promoting myogenic tans-differentiation during HSCs activation. This study also exemplified proteomics strategy as a powerful tool for the functional study of miRNA.

MicroRNAs As Potential Targets for Abiotic Stress Tolerance in Plants

PubMed Central

Shriram, Varsha; Kumar, Vinay; Devarumath, Rachayya M.; Khare, Tushar S.; Wani, Shabir H.

2016-01-01

The microRNAs (miRNAs) are small (20–24 nt) sized, non-coding, single stranded riboregulator RNAs abundant in higher organisms. Recent findings have established that plants assign miRNAs as critical post-transcriptional regulators of gene expression in sequence-specific manner to respond to numerous abiotic stresses they face during their growth cycle. These small RNAs regulate gene expression via translational inhibition. Usually, stress induced miRNAs downregulate their target mRNAs, whereas, their downregulation leads to accumulation and function of positive regulators. In the past decade, investigations were mainly aimed to identify plant miRNAs, responsive to individual or multiple environmental factors, profiling their expression patterns and recognizing their roles in stress responses and tolerance. Altered expressions of miRNAs implicated in plant growth and development have been reported in several plant species subjected to abiotic stress conditions such as drought, salinity, extreme temperatures, nutrient deprivation, and heavy metals. These findings indicate that miRNAs may hold the key as potential targets for genetic manipulations to engineer abiotic stress tolerance in crop plants. This review is aimed to provide recent updates on plant miRNAs, their biogenesis and functions, target prediction and identification, computational tools and databases available for plant miRNAs, and their roles in abiotic stress-responses and adaptive mechanisms in major crop plants. Besides, the recent case studies for overexpressing the selected miRNAs for miRNA-mediated enhanced abiotic stress tolerance of transgenic plants have been discussed. PMID:27379117

Enhancing performance of a motor imagery based brain-computer interface by incorporating electrical stimulation-induced SSSEP

NASA Astrophysics Data System (ADS)

Yi, Weibo; Qiu, Shuang; Wang, Kun; Qi, Hongzhi; Zhao, Xin; He, Feng; Zhou, Peng; Yang, Jiajia; Ming, Dong

2017-04-01

Objective. We proposed a novel simultaneous hybrid brain-computer interface (BCI) by incorporating electrical stimulation into a motor imagery (MI) based BCI system. The goal of this study was to enhance the overall performance of an MI-based BCI. In addition, the brain oscillatory pattern in the hybrid task was also investigated. Approach. 64-channel electroencephalographic (EEG) data were recorded during MI, selective attention (SA) and hybrid tasks in fourteen healthy subjects. In the hybrid task, subjects performed MI with electrical stimulation which was applied to bilateral median nerve on wrists simultaneously. Main results. The hybrid task clearly presented additional steady-state somatosensory evoked potential (SSSEP) induced by electrical stimulation with MI-induced event-related desynchronization (ERD). By combining ERD and SSSEP features, the performance in the hybrid task was significantly better than in both MI and SA tasks, achieving a ~14% improvement in total relative to the MI task alone and reaching ~89% in mean classification accuracy. On the contrary, there was no significant enhancement obtained in performance while separate ERD feature was utilized in the hybrid task. In terms of the hybrid task, the performance using combined feature was significantly better than using separate ERD or SSSEP feature. Significance. The results in this work validate the feasibility of our proposed approach to form a novel MI-SSSEP hybrid BCI outperforming a conventional MI-based BCI through combing MI with electrical stimulation.

Profile of microRNA in Giant Panda Blood: A Resource for Immune-Related and Novel microRNAs.

PubMed

Yang, Mingyu; Du, Lianming; Li, Wujiao; Shen, Fujun; Fan, Zhenxin; Jian, Zuoyi; Hou, Rong; Shen, Yongmei; Yue, Bisong; Zhang, Xiuyue

2015-01-01

The giant panda (Ailuropoda melanoleuca) is one of the world's most beloved endangered mammals. Although the draft genome of this species had been assembled, little was known about the composition of its microRNAs (miRNAs) or their functional profiles. Recent studies demonstrated that changes in the expression of miRNAs are associated with immunity. In this study, miRNAs were extracted from the blood of four healthy giant pandas and sequenced by Illumina next generation sequencing technology. As determined by miRNA screening, a total of 276 conserved miRNAs and 51 novel putative miRNAs candidates were detected. After differential expression analysis, we noticed that the expressions of 7 miRNAs were significantly up-regulated in young giant pandas compared with that of adults. Moreover, 2 miRNAs were up-regulated in female giant pandas and 1 in the male individuals. Target gene prediction suggested that the miRNAs of giant panda might be relevant to the expressions of 4,602 downstream genes. Subseuqently, the predicted target genes were conducted to KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and we found that these genes were mainly involved in host immunity, including the Ras signaling pathway, the PI3K-Akt signaling pathway, and the MAPK signaling pathway. In conclusion, our results provide the first miRNA profiles of giant panda blood, and the predicted functional analyses may open an avenue for further study of giant panda immunity.

miR-520 promotes DNA-damage-induced trophoblast cell apoptosis by targeting PARP1 in recurrent spontaneous abortion (RSA).

PubMed

Dong, Xiujuan; Yang, Long; Wang, Hui

2017-04-01

The establishment and maintenance of successful pregnancy mainly depends on trophoblast cells. Their dysfunction has been implicated in recurrent spontaneous abortion (RSA), a major complication of pregnancy. However, the underlying mechanisms of trophoblasts dysfunction remain unclear. DNA-damage-induced cell apoptosis has been reported to play a vital role in cell death. In this study, we identified a novel microRNA (miR-520) in RSA progression via regulating trophoblast cell apoptosis. Microarray analysis showed that miR-520 was highly expressed in villus of RSA patients. By using flow cytometry analysis, we observed miR-520 expression was correlated with human trophoblast cell apoptosis in vitro, along with decreased poly (ADP-ribose) polymerase-1 (PARP1) expression. With the analysis of clinic samples, we observed that miR-520 level was negatively correlated with PARP1 level in RSA villus. In addition, overexpression of PARP1 restored the miR-520-induced trophoblast cell apoptosis in vitro. The status of chromosome in trophoblast implied that miR-520-promoted DNA-damage-induced cell apoptosis to regulate RSA progression. These results indicated that the level of miR-520 might associate with RSA by prompting trophoblast cell apoptosis via PARP1 dependent DNA-damage pathway.

[Immigrant women care in a health intercultural mediation program].

PubMed

Alcaraz Quevedo, Manuela; Paredes-Carbonell, Joan J; Sancho Mestre, Carla; López-Sánchez, Pilar; García Moreno, J Luis; Vivas Consuelo, David

2014-01-01

Intercultural Mediation is a strategy for quality health care aimed at reducing inequalities in immigrant population. The aim is to analyse main reasons consultation with the mediation service, women care profile and characteristics of intervention. Cross-sectional study of 339 episodes of care by two intercultural mediators (MI) from February 2008 to October 2011 in Valencia. Variables were analysed individual records of the consultations of the MI: reasons for referral to MI and professionals who refer, motives and problems identified by MI, kind of intervention, kind of derivation of MI and socio-economic variables. To evaluate the differences between countries, X2 test was used for qualitative variables and one-way ANOVA test for quantitative variables. 123 women (36,3%), were referred to the MI by the Sexual and Reproductive Health Centre and 98 (28,9%) by the midwife. 272 women (80,24%) were referred for information and demand for contraception. The MI conducted health education and detected social problems in 67 women (19,7%) and gender violence in 38 (11,21%). The women attending were Latin American immigrants (those of Bolivia showed more vulnerability) and were referred for contraception. The MI provided information, education and facilitated access to reproductive health services. Bolivian women showed more vulnerability factors: irregular situation, precarious work and low residence time.

Regulation of NK92-MI cell cytotoxicity by substance P.

PubMed

Fu, W X; Qin, B; Zhou, A P; Yu, Q Y; Huang, Q J; Liang, Z F

2011-08-01

The neuropeptide substance P (SP) can regulate a number of immunological functions in vitro and in vivo and may regulate natural killer (NK) cell activity. Here, we investigated whether SP has a role in regulating NK92-MI cell function in vitro, and how it influences NK cell activity. We found that SP dose dependently increased the cytotoxicity of NK92-MI cells and had a maximal effect at a concentration of 10(-12) and 10(-10) m. Furthermore, the expression of cytotoxic-associated molecules (perforin, granzyme) and activating receptor NKp46 [a member of natural cytotoxicity receptors (NCRs)] was observed to be upregulated by SP at optimal concentration, at which SP enhanced the cytotoxicity of NK92-MI cells. Neurokinin-1 receptor (NK-1R), a functional receptor of SP, was found on NK92-MI cells, and the observed effects of SP on NK92-MI cells could be more partially blocked by an NK-1R antagonist. Our data suggest that SP induces NK92-MI cell cytotoxicity by directly increasing the expression of cytotoxic granules and upregulates NK92-MI cell receptor-mediated functions indirectly. Thus, SP may regulate NK cell function mainly through NK-1R. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.

MicroRNA-198 inhibited tumorous behaviors of human osteosarcoma through directly targeting ROCK1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Shilian, E-mail: shilian_zhang@126.com; Zhao, Yuehua; Wang, Lijie

2016-04-08

Osteosarcoma is an aggressive primary sarcoma of bone and occurs mainly in adolescents and young adults. The prognosis of OS remains poor, and most of them will die due to local relapse or metastases. The discovery of microRNAs provides a new possibility for the early diagnosis and treatment of OS. Thus, the aim of this study was to explore the expression and functions of microRNA-198 (miR-198) in osteosarcoma. The expression levels of miR-198 were determined by qRT-PCR in osteosarcoma tissues and cell lines. Cell proliferation assays, migration and invasion assays were adopted to investigate the effects of miR-198 on tumorousmore » behaviors of osteosarcoma cells. The results showed that miR-198 expression levels were lower in osteosarcoma tissues and cell lines. In addition, low miR-198 expression levels were correlated with TNM stage and distant metastasis. After miR-198 mimics transfection, cell proliferation, migration and invasion were significantly suppressed in the osteosarcoma cells. Furthermore, ROCK1 was identified as a novel direct target of miR-198 in osteosarcoma. These findings suggested that miR-198 may act not only as a novel prognostic marker, but also as a potential target for molecular therapy of osteosarcoma.« less

Androgen receptor (AR) suppresses miRNA-145 to promote renal cell carcinoma (RCC) progression independent of VHL status

PubMed Central

Chen, Yuan; Sun, Yin; Rao, Qun; Xu, Hua; Li, Lei; Chang, Chawnshang

2015-01-01

Mutational inactivation of the VHL tumor suppressor plays key roles in the development of renal cell carcinoma (RCC), and mutated VHL-mediated VEGF induction has become the main target for the current RCC therapy. Here we identified a signal pathway of VEGF induction by androgen receptor (AR)/miRNA-145 as a new target to suppress RCC progression. Mechanism dissection revealed that AR might function through binding to the androgen receptor element (ARE) located on the promoter region of miRNA-145 to suppress p53's ability to induce expression of miRNA-145 that normally suppresses expression of HIF2α/VEGF/MMP9/CCND1. Suppressing AR with AR-shRNA or introducing exogenous miRNA-145 mimic can attenuate RCC progression independent of VHL status. MiR-145 mimic in preclinical RCC orthotopic xenograft mouse model revealed its efficacy in suppression of RCC progression. These results together identified signals by AR-suppressed miRNA-145 as a key player in the RCC progression via regulating HIF2α/VEGF/MMP9/CCND1 expression levels. Blockade of the newly identified signal by AR inhibition or miRNA-145 mimics has promising therapeutic benefit to suppress RCC progression. PMID:26304926

Global exponential stability of positive periodic solution of the n-species impulsive Gilpin-Ayala competition model with discrete and distributed time delays.

PubMed

Zhao, Kaihong

2018-12-01

In this paper, we study the n-species impulsive Gilpin-Ayala competition model with discrete and distributed time delays. The existence of positive periodic solution is proved by employing the fixed point theorem on cones. By constructing appropriate Lyapunov functional, we also obtain the global exponential stability of the positive periodic solution of this system. As an application, an interesting example is provided to illustrate the validity of our main results.

Discharge current modes of high power impulse magnetron sputtering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Zhongzhen, E-mail: wuzz@pkusz.edu.cn; Xiao, Shu; Ma, Zhengyong

2015-09-15

Based on the production and disappearance of ions and electrons in the high power impulse magnetron sputtering plasma near the target, the expression of the discharge current is derived. Depending on the slope, six possible modes are deduced for the discharge current and the feasibility of each mode is discussed. The discharge parameters and target properties are simplified into the discharge voltage, sputtering yield, and ionization energy which mainly affect the discharge plasma. The relationship between these factors and the discharge current modes is also investigated.

133. Photocopy of photograph, 1915 (Chrysler) MAIN BUILDING #1, SECOND ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

133. Photocopy of photograph, 1915 (Chrysler) MAIN BUILDING #1, SECOND FLOOR CHASSIS ASSEMBLY LINE, VIEW SOUTH, 1980 - Dodge Brothers Motor Car Company Plant, Between Joseph Campau & Conant Avenues, Hamtramck, MI

Atmospheric Mining in the Outer Solar System: Outer Planet Orbital Transfer and Lander Analyses

NASA Technical Reports Server (NTRS)

Palaszewski, Bryan

2016-01-01

High energy propellants for human lunar missions are analyzed, focusing on very advanced ozone and atomic hydrogen. One of the most advanced launch vehicle propulsion systems, such as the Space Shuttle Main Engine (SSME), used hydrogen and oxygen and had a delivered specific impulse of 453 seconds. In the early days of the space program, other propellants (or so called metapropellants) were suggested, including atomic hydrogen and liquid ozone. Theoretical and experimental studies of atomic hydrogen and ozone were conducted beginning in the late 1940s. This propellant research may have provided screenwriters with the idea of an atomic hydrogen-ozone rocket engine in the 1950 movie, Rocketship X-M. This paper presents analyses showing that an atomic hydrogen-ozone rocket engine could produce a specific impulse over a wide range of specific impulse values reaching as high as 1,600 seconds. A series of single stage and multistage rocket vehicle analyses were conducted to find the minimum specific impulse needed to conduct high energy round trip lunar missions.

Dielectric breakdown strength of magnetic nanofluid based on insulation oil after impulse test

NASA Astrophysics Data System (ADS)

Nazari, M.; Rasoulifard, M. H.; Hosseini, H.

2016-02-01

In this study, the dielectric breakdown strength of magnetic nanofluids based on transformer mineral oil for use in power systems is reviewed. Nano oil samples are obtained from dispersion of the magnetic nanofluid within uninhibited transformer mineral oil NYTRO LIBRA as the base fluid. AC dielectric breakdown voltage measurement was carried out according to IEC 60156 standard and the lightning impulse breakdown voltage was obtained by using the sphere-sphere electrodes in an experimental setup for nano oil in volume concentration of 0.1-0.6%. Results indicate improved AC and lightning impulse breakdown voltage of nano oil compared to the base oil. AC test was performed again after applying impulse current and result showed that nano oil unlike the base oil retains its dielectric properties. Increase the dielectric strength of the nano oil is mainly due to dielectric and magnetic properties of Fe3O4 nanoparticles that act as free electrons snapper, and reduce the rate of free electrons in the ionization process.

Impulsivity makes more susceptible to overeating after contextual appetitive conditioning.

PubMed

van den Akker, Karolien; Jansen, Anita; Frentz, Florentine; Havermans, Remco C

2013-11-01

Animals can learn that specific contexts are associated with important biological events such as food intake through classical conditioning. Very few studies suggest this is also possible in humans and contextual appetitive conditioning might even be a main determinant of habitual overeating in vulnerable humans. A Virtual Reality laboratory was used to test whether humans show conditioned responding (increased food desires and expectations, increased salivation and increased food intake) to a specific context after repeated pairings of this context with intake. It was also examined whether the personality trait impulsivity strengthens this contextual appetitive conditioning. Conditioned context-induced reactivity was indeed demonstrated and impulsivity predicted increased intake in only the intake-associated context. It is concluded that humans easily learn desires to eat in intake-related environments. The data also suggest that in particular more impulsive people are vulnerable for conditioned context-induced overeating. This relatively easy learning of associations between specific contexts and intake might stimulate habitual overeating and contribute to increased obesity prevalence. Copyright © 2013 Elsevier Ltd. All rights reserved.

Propulsion Estimates for High Energy Lunar Missions Using Future Propellants

NASA Technical Reports Server (NTRS)

Palaszewski, Bryan A.; Bennett, Gary L.

2016-01-01

High energy propellants for human lunar missions are analyzed, focusing on very advanced ozone and atomic hydrogen. One of the most advanced launch vehicle propulsion systems, such as the Space Shuttle Main Engine (SSME), used hydrogen and oxygen and had a delivered specific impulse of 453 seconds. In the early days of the space program, other propellants (or so called metapropellants) were suggested, including atomic hydrogen and liquid ozone. Theoretical and experimental studies of atomic hydrogen and ozone were conducted beginning in the late 1940s. This propellant research may have provided screenwriters with the idea of an atomic hydrogen-ozone rocket engine in the 1950 movie, Rocketship X-M. This paper presents analyses showing that an atomic hydrogen-ozone rocket engine could produce a specific impulse over a wide range of specific impulse values reaching as high as 1,600 s. A series of single stage and multistage rocket vehicle analyses were conducted to find the minimum specific impulse needed to conduct high energy round trip lunar missions.

Short interspersed DNA elements and miRNAs: a novel hidden gene regulation layer in zebrafish?

PubMed

Scarpato, Margherita; Angelini, Claudia; Cocca, Ennio; Pallotta, Maria M; Morescalchi, Maria A; Capriglione, Teresa

2015-09-01

In this study, we investigated by in silico analysis the possible correlation between microRNAs (miRNAs) and Anamnia V-SINEs (a superfamily of short interspersed nuclear elements), which belong to those retroposon families that have been preserved in vertebrate genomes for millions of years and are actively transcribed because they are embedded in the 3' untranslated region (UTR) of several genes. We report the results of the analysis of the genomic distribution of these mobile elements in zebrafish (Danio rerio) and discuss their involvement in generating miRNA gene loci. The computational study showed that the genes predicted to bear V-SINEs can be targeted by miRNAs with a very high hybridization E-value. Gene ontology analysis indicates that these genes are mainly involved in metabolic, membrane, and cytoplasmic signaling pathways. Nearly all the miRNAs that were predicted to target the V-SINEs of these genes, i.e., miR-338, miR-9, miR-181, miR-724, miR-735, and miR-204, have been validated in similar regulatory roles in mammals. The large number of genes bearing a V-SINE involved in metabolic and cellular processes suggests that V-SINEs may play a role in modulating cell responses to different stimuli and in preserving the metabolic balance during cell proliferation and differentiation. Although they need experimental validation, these preliminary results suggest that in the genome of D. rerio, as in other TE families in vertebrates, the preservation of V-SINE retroposons may also have been favored by their putative role in gene network modulation.

Illumina microRNA profiles reveal the involvement of miR397a in Citrus adaptation to long-term boron toxicity via modulating secondary cell-wall biosynthesis.

PubMed

Huang, Jing-Hao; Qi, Yi-Ping; Wen, Shou-Xing; Guo, Peng; Chen, Xiao-Min; Chen, Li-Song

2016-03-10

The mechanisms underlying tolerance to B-toxicity in plants are still controversial. Our previous studies indicated that B-toxicity is mainly limited to leaves in Citrus and that alternations of cell-wall structure in vascular bundles are involved in tolerance to B-toxicity. Here, miRNAs and their expression patterns were first identified in B-treated Citrus sinensis (tolerant) and C. grandis (intolerant) leaves via high-throughput sequencing. Candidate miRNAs were then verified with molecular and anatomical approaches. The results showed that 51 miRNAs in C. grandis and 20 miRNAs in C. sinensis were differentially expressed after B-toxic treatment. MiR395a and miR397a were the most significantly up-regulated miRNAs in B-toxic C. grandis leaves, but both were down-regulated in B-toxic C. sinensis leaves. Four auxin response factor genes and two laccase (LAC) genes were confirmed through 5'-RACE to be real targets of miR160a and miR397a, respectively. Up-regulation of LAC4 resulted in secondary deposition of cell-wall polysaccharides in vessel elements of C. sinensis, whereas down-regulation of both LAC17 and LAC4, led to poorly developed vessel elements in C. grandis. Our findings demonstrated that miR397a plays a pivotal role in woody Citrus tolerance to B-toxicity by targeting LAC17 and LAC4, both of which are responsible for secondary cell-wall synthesis.

MiR-29b affects the secretion of PROG and promotes the proliferation of bovine corpus luteum cells

PubMed Central

Zhang, Li-Qun; Sun, Xu-Lei; Luo, Dan; Fu, Yao; Gao, Yan; Zhang, Jia-Bao

2018-01-01

The regulatory role of miRNAs has been explored in ovarian cells, and their effects on gonadal development, apoptosis, ovulation, steroid production and corpus luteum (CL) development have been revealed. In this study, we analyzed the expression of miR-29b at different stages of bovine CL development and predicted the target genes of miR-29b. We confirmed that miR-29b reduces the expression of the oxytocin receptor (OXTR), affects progesterone (PROG) secretion and regulates the function of the CL. RT-PCR showed that the expression of miR-29b was significantly higher in functional CL phases than in the regressed CL phase. Immunohistochemistry showed that OXTR was expressed in both large and small CL cells and was mainly located in the cell membrane and cytoplasm of these cells. We analyzed the expression levels of OXTR and found that transfection with a miR-29b mimic decreased OXTR expression, but transfection with the inhibitor had a limited effect on the expression of the OXTR protein. At the same time, the secretion of PROG was significantly increased in the miR-29b mimic-transfected group. We also analyzed the effect of miR-29b on the apoptosis of CL cells. Finally, we found that miR-29b could promote the proliferation of bovine CL cells. In conclusion, we found that miR-29b reduces the expression of OXTR and can promote PROG secretion and the proliferation of CL cells via OXTR. PMID:29617446

Illumina microRNA profiles reveal the involvement of miR397a in Citrus adaptation to long-term boron toxicity via modulating secondary cell-wall biosynthesis

PubMed Central

Huang, Jing-Hao; Qi, Yi-Ping; Wen, Shou-Xing; Guo, Peng; Chen, Xiao-Min; Chen, Li-Song

2016-01-01

The mechanisms underlying tolerance to B-toxicity in plants are still controversial. Our previous studies indicated that B-toxicity is mainly limited to leaves in Citrus and that alternations of cell-wall structure in vascular bundles are involved in tolerance to B-toxicity. Here, miRNAs and their expression patterns were first identified in B-treated Citrus sinensis (tolerant) and C. grandis (intolerant) leaves via high-throughput sequencing. Candidate miRNAs were then verified with molecular and anatomical approaches. The results showed that 51 miRNAs in C. grandis and 20 miRNAs in C. sinensis were differentially expressed after B-toxic treatment. MiR395a and miR397a were the most significantly up-regulated miRNAs in B-toxic C. grandis leaves, but both were down-regulated in B-toxic C. sinensis leaves. Four auxin response factor genes and two laccase (LAC) genes were confirmed through 5′-RACE to be real targets of miR160a and miR397a, respectively. Up-regulation of LAC4 resulted in secondary deposition of cell-wall polysaccharides in vessel elements of C. sinensis, whereas down-regulation of both LAC17 and LAC4, led to poorly developed vessel elements in C. grandis. Our findings demonstrated that miR397a plays a pivotal role in woody Citrus tolerance to B-toxicity by targeting LAC17 and LAC4, both of which are responsible for secondary cell-wall synthesis. PMID:26962011

Circulating microRNAs as Potential Biomarkers of Infectious Disease

PubMed Central

Correia, Carolina N.; Nalpas, Nicolas C.; McLoughlin, Kirsten E.; Browne, John A.; Gordon, Stephen V.; MacHugh, David E.; Shaughnessy, Ronan G.

2017-01-01

microRNAs (miRNAs) are a class of small non-coding endogenous RNA molecules that regulate a wide range of biological processes by post-transcriptionally regulating gene expression. Thousands of these molecules have been discovered to date, and multiple miRNAs have been shown to coordinately fine-tune cellular processes key to organismal development, homeostasis, neurobiology, immunobiology, and control of infection. The fundamental regulatory role of miRNAs in a variety of biological processes suggests that differential expression of these transcripts may be exploited as a novel source of molecular biomarkers for many different disease pathologies or abnormalities. This has been emphasized by the recent discovery of remarkably stable miRNAs in mammalian biofluids, which may originate from intracellular processes elsewhere in the body. The potential of circulating miRNAs as biomarkers of disease has mainly been demonstrated for various types of cancer. More recently, however, attention has focused on the use of circulating miRNAs as diagnostic/prognostic biomarkers of infectious disease; for example, human tuberculosis caused by infection with Mycobacterium tuberculosis, sepsis caused by multiple infectious agents, and viral hepatitis. Here, we review these developments and discuss prospects and challenges for translating circulating miRNA into novel diagnostics for infectious disease. PMID:28261201

Induction of specific micro RNA (miRNA) species by ROS-generating metal sulfates in primary human brain cells

PubMed Central

Lukiw, Walter J.; Pogue, Aileen I.

2007-01-01

Iron- and aluminum-sulfate together, at nanomolar concentrations, trigger the production of reactive oxygen species (ROS) in cultures of human brain cells. Previous studies have shown that following ROS induction, a family of pathogenic brain genes that promote inflammatory signalling, cellular apoptosis and brain cell death is significantly over-expressed. Notably, iron- and aluminum-sulfate induce genes in cultured human brain cells that exhibit expression patterns similar to those observed to be up-regulated in moderate- to late-stage Alzheimer's disease (AD). In this study we have extended our investigations to analyze the expression of micro RNA (miRNA) populations in iron- and aluminum-sulfate treated human neural cells in primary culture. The main finding was that these ROS-generating neurotoxic metal sulfates also up-regulate a specific set of miRNAs that includes miR-9, miR-125b and miR-128. Notably, these same miRNAs are up-regulated in AD brain. These findings further support the idea that iron- and aluminum-sulfates induce genotoxicity via a ROS-mediated up-regulation of specific regulatory elements and pathogenic genes that redirect brain cell fate towards progressive dysfunction and apoptotic cell death. PMID:17629564

Presentational Focus in Heritage and Monolingual Spanish

ERIC Educational Resources Information Center

Hoot, Bradley

2012-01-01

In Spanish, it is most commonly claimed that constituents in narrow presentational focus appear rightmost, where they also get main stress (1a), while stress in situ (1b) is infelicitous. (1) [Context: Who bought a car?]. a. Compró un carro mi [mamá][subscript F]. bought a car my mom. b. Mi [mamá ][subscript F] compró un carro. However, some…

Sources of Popular Literature Online: New York Times Information Bank and the Magazine Index.

ERIC Educational Resources Information Center

Kelly, Alex M.; Slade, Rod

1979-01-01

A comparison of the Magazine Index (MI) and the New York Times Information Bank (IB) showed the two data bases have little in common, mainly due to differences in focus, indexing, vocabulary, use online, and output. For business and government users, IB is the best choice; for more general and academic purposes, MI provides access to more…

MicroRNA-29b regulates TGF-β1-mediated epithelial–mesenchymal transition of retinal pigment epithelial cells by targeting AKT2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Min; Li, Hui; Liu, Xiaoqiang

2016-07-15

The role of microRNA (miRNA) in proliferative vitreoretinopathy (PVR) progression has not been studied extensively, especially in retinal pigment epithelial–mesenchymal transition (EMT) which is the main reason for formation of PVR. In this study, we first investigated the miRNA expression profile in transforming growth factor beta 1 (TGF-β1) mediated EMT of ARPE-19 cells. Among the five changed miRNAs, miR-29b showed the most significant downregulation. Enhanced expression of miR-29b could reverse TGF-β1 induced EMT through targeting Akt2. Akt2 downregulation could inhibit TGF-β1-induced EMT. Furthermore, inhibition of miR-29b in ARPE-19 cells directly triggered EMT process, which characterized by the phenotypic transition andmore » the upregulation of α-smooth muscle actin (α-SMA) and downregulation of E-cadherin and zona occludin-1 (ZO-1) with increased cell migration. Akt2-shRNA also inhibited miR-29 inhibitor-induced EMT process. These data indicate that miR-29b plays an important role in TGF-β1-mediated EMT in ARPE-19 cells by targeting Akt2. - Highlights: • MiR-29b expression is decreased in TGF-β1-induced EMT of ARPE-19 cells. • MiR-29b inhibits TGF-β1-induced EMT in ARPE-19 cells. • MiR-29b inhibitor induces EMT in ARPE-19 cells. • Akt2 is the target for miR-29b. • Downregulation of Akt2 prevents TGF-β1-induced EMT of ARPE-19 cells.« less

Identification and characterization of microRNAs in the pancreatic fluke Eurytrema pancreaticum.

PubMed

Xu, Min-Jun; Wang, Chun-Ren; Huang, Si-Yang; Fu, Jing-Hua; Zhou, Dong-Hui; Chang, Qiao-Cheng; Zheng, Xu; Zhu, Xing-Quan

2013-01-25

Eurytrema pancreaticum is one of the most common flukes, which mainly infects ruminants globally and infects human beings accidentally; causing eurytremiasis that has high veterinary and economic importance. MicroRNAs (miRNAs) are small non-coding RNAs and are now considered as a key mechanism of gene regulation at the post-transcription level. We investigated the global miRNA expression profile of E. pancreaticum adults using next-generation sequencing technology combined with real-time quantitative PCR. By using the genome of the closely-related species Schistosoma japonicum as reference, we obtained 27 miRNA candidates out of 16.45 million raw sequencing reads, with 13 of them found as known miRNAs in S. japonicum and/or S. mansoni, and the remaining 14 miRNAs were considered as novel. Five out of the 13 known miRNAs coming from one family named as sja-miR-2, including family members from miR-2a to miR-2e. Targets of 19 miRNAs were successfully predicated out of the 17401 mRNA and EST non-redundant sequences of S. japonicum. It was found that a significant high number of targets were related to "chch domain-containing protein mitochondrial precursor" (n = 29), "small subunit ribosomal protein s30e" (n = 21), and "insulin-induced gene 1 protein" (n = 9). Besides, "egg protein cp3842" (n = 2), "fumarate hydratase" (n = 2), "ubiquitin-conjugating enzyme" (n = 2), and "sperm-associated antigen 6" (n = 1) were also found as targets of the miRNAs of E. pancreaticum. The present study represents the first global characterization of E. pancreaticum miRNAs, which provides novel resources for a better understanding of the parasite, which, in turn, has implications for the effective control of the disease it causes.

Is impulsivity a link between childhood abuse and suicide?

PubMed

Braquehais, M Dolores; Oquendo, Maria A; Baca-García, Enrique; Sher, Leo

2010-01-01

Childhood abuse and neglect are known to affect psychological states through behavioral, emotional, and cognitive pathways. They increase the risk of having psychiatric diseases in adulthood and have been considered risk factors for suicidal behavior in all diagnostic categories. Early, prolonged, and severe trauma is also known to increase impulsivity, diminishing the capacity of the brain to inhibit negative actions and to control and modulate emotions. Many neurobiological studies hold that childhood maltreatment may lead to a persistent failure of the inhibitory processes ruled mainly by the frontal cortex over a fear-motivated hyperresponsive limbic system. Multiple neurotransmitters and hormones are involved in the stress response, but, to our knowledge, the two major biological consequences of the chronic exposure to trauma are the hypofunction of the serotonergic system and changes in the hypothalamic-pituitary-adrenal axis function. Some of these findings overlap with the neurobiological features of impulsivity and of suicidal behavior. Impulsivity has also been said to be both a consequence of trauma and a risk factor for the development of a pathological response to trauma. Thus, we suggest that impulsivity could be one of the links between childhood trauma and suicidal behavior. Prevention of childhood abuse could significantly reduce suicidal behavior in adolescents and adults, in part, through a decrease in the frequency of impulsive behaviors in the future. Copyright 2010 Elsevier Inc. All rights reserved.

Decision-making deficits in pathological gambling: the role of executive functions, explicit knowledge and impulsivity in relation to decisions made under ambiguity and risk.

PubMed

Ochoa, Cristian; Alvarez-Moya, Eva M; Penelo, Eva; Aymami, M Neus; Gómez-Peña, Mónica; Fernández-Aranda, Fernando; Granero, Roser; Vallejo-Ruiloba, Julio; Menchón, José Manuel; Lawrence, Natalia S; Jiménez-Murcia, Susana

2013-01-01

A variety of cognitive and emotional processes influence the decision-making deficits observed in pathological gambling (PG). This study investigated the role of immediate/delayed sensitivity to reward and punishment, executive functions, impulsivity and explicit knowledge in relation to decision-making performance on the original Iowa Gambling Task (IGT-ABCD) and a variant (IGT-EFGH). We assessed 131 consecutive patients with a diagnosis of PG by using executive functioning and decision-making tasks, self-report measures of impulsivity and explicit knowledge. The majority of pathological gamblers (PGs) showed deficits in decision-making, characterized mainly by myopia for the future. Decisions made under risk showed different predictors. Performance on the IGT-ABCD for decisions made under risk was predicted by medium and high levels of explicit knowledge of the task, as well as by scores on the Disorderliness subscale and the degree of Stroop interference. By contrast, IGT-EFGH results were only associated with self-report impulsivity measures. Decision making in PG involves distinct patterns of deficits, and the predictors differ depending on the reinforcement schedule. Decisions made under risk on the IGT-ABCD are associated with explicit knowledge, executive functions and impulsivity traits related to conscious awareness and control processes. On the IGT-EFGH, however, only impulsivity traits predict decision making. Copyright © American Academy of Addiction Psychiatry.

Impact of microRNAs on regulatory networks and pathways in human colorectal carcinogenesis and development of metastasis

PubMed Central

2013-01-01

Background Qualitative alterations or abnormal expression of microRNAs (miRNAs) in colon cancer have mainly been demonstrated in primary tumors. Poorly overlapping sets of oncomiRs, tumor suppressor miRNAs and metastamiRs have been linked with distinct stages in the progression of colorectal cancer. To identify changes in both miRNA and gene expression levels among normal colon mucosa, primary tumor and liver metastasis samples, and to classify miRNAs into functional networks, in this work miRNA and gene expression profiles in 158 samples from 46 patients were analysed. Results Most changes in miRNA and gene expression levels had already manifested in the primary tumors while these levels were almost stably maintained in the subsequent primary tumor-to-metastasis transition. In addition, comparing normal tissue, tumor and metastasis, we did not observe general impairment or any rise in miRNA biogenesis. While only few mRNAs were found to be differentially expressed between primary colorectal carcinoma and liver metastases, miRNA expression profiles can classify primary tumors and metastases well, including differential expression of miR-10b, miR-210 and miR-708. Of 82 miRNAs that were modulated during tumor progression, 22 were involved in EMT. qRT-PCR confirmed the down-regulation of miR-150 and miR-10b in both primary tumor and metastasis compared to normal mucosa and of miR-146a in metastases compared to primary tumor. The upregulation of miR-201 in metastasis compared both with normal and primary tumour was also confirmed. A preliminary survival analysis considering differentially expressed miRNAs suggested a possible link between miR-10b expression in metastasis and patient survival. By integrating miRNA and target gene expression data, we identified a combination of interconnected miRNAs, which are organized into sub-networks, including several regulatory relationships with differentially expressed genes. Key regulatory interactions were validated experimentally. Specific mixed circuits involving miRNAs and transcription factors were identified and deserve further investigation. The suppressor activity of miR-182 on ENTPD5 gene was identified for the first time and confirmed in an independent set of samples. Conclusions Using a large dataset of CRC miRNA and gene expression profiles, we describe the interplay of miRNA groups in regulating gene expression, which in turn affects modulated pathways that are important for tumor development. PMID:23987127

Evolutionary conserved microRNAs are ubiquitously expressed compared to tick-specific miRNAs in the cattle tick Rhipicephalus (Boophilus) microplus

PubMed Central

2011-01-01

Background MicroRNAs (miRNAs) are small non-coding RNAs that act as regulators of gene expression in eukaryotes modulating a large diversity of biological processes. The discovery of miRNAs has provided new opportunities to understand the biology of a number of species. The cattle tick, Rhipicephalus (Boophilus) microplus, causes significant economic losses in cattle production worldwide and this drives us to further understand their biology so that effective control measures can be developed. To be able to provide new insights into the biology of cattle ticks and to expand the repertoire of tick miRNAs we utilized Illumina technology to sequence the small RNA transcriptomes derived from various life stages and selected organs of R. microplus. Results To discover and profile cattle tick miRNAs we employed two complementary approaches, one aiming to find evolutionary conserved miRNAs and another focused on the discovery of novel cattle-tick specific miRNAs. We found 51 evolutionary conserved R. microplus miRNA loci, with 36 of these previously found in the tick Ixodes scapularis. The majority of the R. microplus miRNAs are perfectly conserved throughout evolution with 11, 5 and 15 of these conserved since the Nephrozoan (640 MYA), Protostomian (620MYA) and Arthropoda (540 MYA) ancestor, respectively. We then employed a de novo computational screening for novel tick miRNAs using the draft genome of I. scapularis and genomic contigs of R. microplus as templates. This identified 36 novel R. microplus miRNA loci of which 12 were conserved in I. scapularis. Overall we found 87 R. microplus miRNA loci, of these 15 showed the expression of both miRNA and miRNA* sequences. R. microplus miRNAs showed a variety of expression profiles, with the evolutionary-conserved miRNAs mainly expressed in all life stages at various levels, while the expression of novel tick-specific miRNAs was mostly limited to particular life stages and/or tick organs. Conclusions Anciently acquired miRNAs in the R. microplus lineage not only tend to accumulate the least amount of nucleotide substitutions as compared to those recently acquired miRNAs, but also show ubiquitous expression profiles through out tick life stages and organs contrasting with the restricted expression profiles of novel tick-specific miRNAs. PMID:21699734

Genome-wide identification of microRNAs in pomegranate (Punica granatum L.) by high-throughput sequencing.

PubMed

Saminathan, Thangasamy; Bodunrin, Abiodun; Singh, Nripendra V; Devarajan, Ramajayam; Nimmakayala, Padma; Jeff, Moersfelder; Aradhya, Mallikarjuna; Reddy, Umesh K

2016-05-26

MicroRNAs (miRNAs), a class of small non-coding endogenous RNAs that regulate gene expression post-transcriptionally, play multiple key roles in plant growth and development and in biotic and abiotic stress response. Knowledge and roles of miRNAs in pomegranate fruit development have not been explored. Pomegranate, which accumulates a large amount of anthocyanins in skin and arils, is valuable to human health, mainly because of its antioxidant properties. In this study, we developed a small RNA library from pooled RNA samples from young seedlings to mature fruits and identified both conserved and pomegranate-specific miRNA from 29,948,480 high-quality reads. For the pool of 15- to 30-nt small RNAs, ~50 % were 24 nt. The miR157 family was the most abundant, followed by miR156, miR166, and miR168, with variants within each family. The base bias at the first position from the 5' end had a strong preference for U for most 18- to 26-nt sRNAs but a preference for A for 18-nt sRNAs. In addition, for all 24-nt sRNAs, the nucleotide U was preferred (97 %) in the first position. Stem-loop RT-qPCR was used to validate the expression of the predominant miRNAs and novel miRNAs in leaves, male and female flowers, and multiple fruit developmental stages; miR156, miR156a, miR159a, miR159b, and miR319b were upregulated during the later stages of fruit development. Higher expression of miR156 in later fruit developmental may positively regulate anthocyanin biosynthesis by reducing SPL transcription factor. Novel miRNAs showed variation in expression among different tissues. These novel miRNAs targeted different transcription factors and hormone related regulators. Gene ontology and KEGG pathway analyses revealed predominant metabolic processes and catalytic activities, important for fruit development. In addition, KEGG pathway analyses revealed the involvement of miRNAs in ascorbate and linolenic acid, starch and sucrose metabolism; RNA transport; plant hormone signaling pathways; and circadian clock. Our first and preliminary report of miRNAs will provide information on the synthesis of biochemical compounds of pomegranate for future research. The functions of the targets of the novel miRNAs need further investigation.

miR-16-5p Is a Stably-Expressed Housekeeping MicroRNA in Breast Cancer Tissues from Primary Tumors and from Metastatic Sites

PubMed Central

Rinnerthaler, Gabriel; Hackl, Hubert; Gampenrieder, Simon Peter; Hamacher, Frank; Hufnagl, Clemens; Hauser-Kronberger, Cornelia; Zehentmayr, Franz; Fastner, Gerd; Sedlmayer, Felix; Mlineritsch, Brigitte; Greil, Richard

2016-01-01

For quantitative microRNA analyses in formalin-fixed paraffin-embedded (FFPE) tissue, expression levels have to be normalized to endogenous controls. To investigate the most stably-expressed microRNAs in breast cancer and its surrounding tissue, we used tumor samples from primary tumors and from metastatic sites. MiRNA profiling using TaqMan® Array Human MicroRNA Cards, enabling quantification of 754 unique human miRNAs, was performed in FFPE specimens from 58 patients with metastatic breast cancer. Forty-two (72%) samples were collected from primary tumors and 16 (28%) from metastases. In a cross-platform analysis of a validation cohort of 32 FFPE samples from patients with early breast cancer genome-wide microRNA expression analysis using SurePrintG3 miRNA (8 × 60 K)® microarrays from Agilent® was performed. Eleven microRNAs could be detected in all samples analyzed. Based on NormFinder and geNorm stability values and the high correlation (rho ≥ 0.8) with the median of all measured microRNAs, miR-16-5p, miR-29a-3p, miR-126-3p, and miR-222-3p are suitable single gene housekeeper candidates. In the cross-platform validation, 29 human microRNAs were strongly expressed (mean log2-intensity > 10) and 21 of these microRNAs including miR-16-5p and miR-29a-3p were also stably expressed (CV < 5%). Thus, miR-16-5p and miR-29a-3p are both strong housekeeper candidates. Their Normfinder stability values calculated across the primary tumor and metastases subgroup indicate that miR-29a-3p can be considered as the strongest housekeeper in a cohort with mainly samples from primary tumors, whereas miR-16-5p might perform better in a metastatic sample enriched cohort. PMID:26821018

miR-16-5p Is a Stably-Expressed Housekeeping MicroRNA in Breast Cancer Tissues from Primary Tumors and from Metastatic Sites.

PubMed

Rinnerthaler, Gabriel; Hackl, Hubert; Gampenrieder, Simon Peter; Hamacher, Frank; Hufnagl, Clemens; Hauser-Kronberger, Cornelia; Zehentmayr, Franz; Fastner, Gerd; Sedlmayer, Felix; Mlineritsch, Brigitte; Greil, Richard

2016-01-26

For quantitative microRNA analyses in formalin-fixed paraffin-embedded (FFPE) tissue, expression levels have to be normalized to endogenous controls. To investigate the most stably-expressed microRNAs in breast cancer and its surrounding tissue, we used tumor samples from primary tumors and from metastatic sites. MiRNA profiling using TaqMan(®) Array Human MicroRNA Cards, enabling quantification of 754 unique human miRNAs, was performed in FFPE specimens from 58 patients with metastatic breast cancer. Forty-two (72%) samples were collected from primary tumors and 16 (28%) from metastases. In a cross-platform analysis of a validation cohort of 32 FFPE samples from patients with early breast cancer genome-wide microRNA expression analysis using SurePrintG3 miRNA (8 × 60 K)(®) microarrays from Agilent(®) was performed. Eleven microRNAs could be detected in all samples analyzed. Based on NormFinder and geNorm stability values and the high correlation (rho ≥ 0.8) with the median of all measured microRNAs, miR-16-5p, miR-29a-3p, miR-126-3p, and miR-222-3p are suitable single gene housekeeper candidates. In the cross-platform validation, 29 human microRNAs were strongly expressed (mean log2-intensity > 10) and 21 of these microRNAs including miR-16-5p and miR-29a-3p were also stably expressed (CV < 5%). Thus, miR-16-5p and miR-29a-3p are both strong housekeeper candidates. Their Normfinder stability values calculated across the primary tumor and metastases subgroup indicate that miR-29a-3p can be considered as the strongest housekeeper in a cohort with mainly samples from primary tumors, whereas miR-16-5p might perform better in a metastatic sample enriched cohort.

Molecular Mechanisms Underlying the Role of MicroRNAs in the Chemoresistance of Pancreatic Cancer

PubMed Central

Garajová, Ingrid; Le Large, Tessa Y.; Frampton, Adam E.; Voortman, Johannes

2014-01-01

Pancreatic ductal adenocarcinoma (PDAC) is an extremely severe disease where the mortality and incidence rates are almost identical. This is mainly due to late diagnosis and limited response to current treatments. The tumor macroenvironment/microenvironment have been frequently reported as the major contributors to chemoresistance in PDAC, preventing the drugs from reaching their intended site of action (i.e., the malignant duct cells). However, the recent discovery of microRNAs (miRNAs) has provided new directions for research on mechanisms underlying response to chemotherapy. Due to their tissue-/disease-specific expression and high stability in tissues and biofluids, miRNAs represent new promising diagnostic and prognostic/predictive biomarkers and therapeutic targets. Furthermore, several studies have documented that selected miRNAs, such as miR-21 and miR-34a, may influence response to chemotherapy in several tumor types, including PDAC. In this review, we summarize the current knowledge on the role of miRNAs in PDAC and recent advances in understanding their role in chemoresistance through multiple molecular mechanisms. PMID:25250326

Molecular mechanisms underlying the role of microRNAs in the chemoresistance of pancreatic cancer.

PubMed

Garajová, Ingrid; Le Large, Tessa Y; Frampton, Adam E; Rolfo, Christian; Voortman, Johannes; Giovannetti, Elisa

2014-01-01

Pancreatic ductal adenocarcinoma (PDAC) is an extremely severe disease where the mortality and incidence rates are almost identical. This is mainly due to late diagnosis and limited response to current treatments. The tumor macroenvironment/microenvironment have been frequently reported as the major contributors to chemoresistance in PDAC, preventing the drugs from reaching their intended site of action (i.e., the malignant duct cells). However, the recent discovery of microRNAs (miRNAs) has provided new directions for research on mechanisms underlying response to chemotherapy. Due to their tissue-/disease-specific expression and high stability in tissues and biofluids, miRNAs represent new promising diagnostic and prognostic/predictive biomarkers and therapeutic targets. Furthermore, several studies have documented that selected miRNAs, such as miR-21 and miR-34a, may influence response to chemotherapy in several tumor types, including PDAC. In this review, we summarize the current knowledge on the role of miRNAs in PDAC and recent advances in understanding their role in chemoresistance through multiple molecular mechanisms.

Detection of circulatory microRNAs in prostate cancer.

PubMed

Srivastava, Anvesha; Goldberger, Helle; Afzal, Zainab; Suy, Simeng; Collins, Sean P; Kumar, Deepak

2015-01-01

Prostate cancer (PCa) is one of the most common cancer worldwide and accounts for 14.4 % of all new cancer cases. The clinical outcome and management of PCa can be significantly improved by use of biomarker assays for early detection, prognosis and also for prediction and monitoring of treatment response. MiRNAs are short, endogenous, single-stranded RNA molecules that play important role in regulation of gene expression and can modulate a number of cellular processes. Discovery of miRNAs in circulation has not only facilitated understanding their role in various diseases but also paved new avenues for biomarker discovery due to their ease of access and stability. The fact that a minimally invasive test based on miRNAs profiles can distinguish the presence or absence of disease illustrates immense potential of these molecules as predictive biomarkers.In this chapter, we have summarized the presumed mechanisms of miRNA release into the circulation and systematically summarized the studies of circulatory miRNAs in PCa. Also, we have mainly focused on the methodology of identification of circulatory miRNAs from biofluids.

[Dectection and analysis of miRNA expression in breast cancer-associated fibroblasts].

PubMed

Zeng, Zongyue; Hu, Ping; Tang, Xi; Zhang, Hailong; Du, Yane; Wen, Siyang; Liu, Manran

2014-10-01

To investigate the difference of miRNA expression levels of cancer-associated fibroblasts (CAFs) and normal fibroblasts (NFs) in human breast cancer microenvironment and its effect on the biological features of CAFs. Collagenase-1 was used to digest the cancer and adjacent tissues to isolate CAFs and NFs. The isolated cells were cultured and characterized in purity and biological features. The expression of fibroblast secretory protein (FSP) in CAFs and NFs was detected by immunofluorescence staining and Western blotting. Transwell(TM) assay was adopted to compare the invasion ability of CAFs and NFs. The different expressions of miRNAs in CAFs versus NFs were detected by miRNA microarray and analyzed by Significance Analysis of Microarrays (SAM). The differences in miR-205 and miR-221 expressions were verified by real-time quantitative PCR (qRT-PCR). The common target genes of the miRNAs were predicted using multi-bioinformatics tools. The pathway analysis was conducted through the Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.7. The secreting products of TGF-β or IL-6 signaling pathway, matrix metalloproteinase (MMP)-1, MMP-2 and MMP-9 were analyzed by ELISA. The primary CAFs and NFs were isolated from breast cancer patients with a purity of over 95%. Compared with NFs, the expression of FSP was obviously elevated in CAFs, and the invasion ability of CAFs was enhanced. The miRNA microarray results showed that there were 10 miRNA genes dysregulated in CAFs, including 3 up-regulated (miR-221-5p, miR-31-3p, miR-221-3p) and 7 down-regulated genes (miR-205, miR-200b , miR-200c, miR-141, miR-101, miR-342-3p, let-7g). The common targets genes of the dysregulated miRNAs were mainly focused on HGF, chemokine signaling, insulin signaling, MAPK signaling, tight junction signaling, adherence junction signaling, EGF1 signaling, androgen-receptor signaling, Wnt and IL-7 signaling. In addition, dysregulated miR-200b/c and miR-141 et al. affect TGF-β and IL-6 signaling through inhibiting their target genes in CAFs, thus promoting invasion and migration of CAFs. The miRNA expression profile was markedly dysregulated in CAFs. Those dysregulated miRNAs may take part in the transformation from NFs to CAFs, and also have a close relationship with adhesion, migration, proliferation, secretion and cell-cell interaction of CAFs.

Impulsiveness, overactivity, and poorer sustained attention improve by chronic treatment with low doses of l-amphetamine in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD).

PubMed

Sagvolden, Terje

2011-03-30

ADHD is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. Overactivity, impulsiveness, and inattentiveness are presently regarded as the main clinical symptoms. There is no biological marker, but there is considerable evidence to suggest that ADHD behavior is associated with poor dopaminergic and noradrenergic modulation of neuronal circuits that involve the frontal lobes. The best validated animal model of ADHD, the Spontaneously Hypertensive Rat (SHR), shows pronounced overactivity, impulsiveness, and deficient sustained attention. The primary objective of the present research was to investigate behavioral effects of a range of doses of chronic l-amphetamine on ADHD-like symptoms in the SHR. The present study tested the behavioral effects of 0.75 and 2.2 mg l-amphetamine base/kg i.p. in male SHRs and their controls, the Wistar Kyoto rat (WKY). ADHD-like behavior was tested with a visual discrimination task measuring overactivity, impulsiveness and inattentiveness. The striking impulsiveness, overactivity, and poorer sustained attention seen during baseline conditions in the SHR were improved by chronic treatment with l-amphetamine. The dose-response curves were, however, different for the different behaviors. Most significantly, the 0.75 mg/kg dose of l-amphetamine improved sustained attention without reducing overactivity and impulsiveness. The 2.2 mg/kg dose improved sustained attention as well as reduced SHR overactivity and impulsiveness. The effects of l-amphetamine to reduce the behavioral symptoms of ADHD in the SHR were maintained over the 14 days of daily dosing with no evidence of tolerance developing.

Studying the energy variation in the powered Swing-By in the Sun-Mercury system

NASA Astrophysics Data System (ADS)

Ferreira, A. F. S.; Prado, A. F. B. A.; Winter, O. C.; Santos, D. P. S.

2017-10-01

A maneuver where a spacecraft passes close to Mercury and uses the gravity of this body combined with an impulse applied at the periapsis, with different magnitudes and directions, is presented. The main objective of this maneuver is the fuel economy in space missions. Using this maneuver, it is possible to insert the spacecraft into an orbit captured around the Sun or Mercury. Trajectories escaping the Solar System are also obtained and mapped. Maps of the spacecraft energy variation relative to the Sun and the types of orbits resulting from the maneuver are presented, based in numerical integrations. The results show that applying the impulse out of the direction of motion can optimize the maneuver due to the effect of the combination of the impulse and the gravity.

MiRNA-362-3p induces cell cycle arrest through targeting of E2F1, USF2 and PTPN1 and is associated with recurrence of colorectal cancer.

PubMed

Christensen, Lise Lotte; Tobiasen, Heidi; Holm, Anja; Schepeler, Troels; Ostenfeld, Marie S; Thorsen, Kasper; Rasmussen, Mads H; Birkenkamp-Demtroeder, Karin; Sieber, Oliver M; Gibbs, Peter; Lubinski, Jan; Lamy, Philippe; Laurberg, Søren; Oster, Bodil; Hansen, Kristian Q; Hagemann-Madsen, Rikke; Byskov, Kristina; Ørntoft, Torben F; Andersen, Claus L

2013-07-01

Colorectal cancer (CRC) is one of the leading causes of cancer deaths in Western countries. A significant number of CRC patients undergoing curatively intended surgery subsequently develop recurrence and die from the disease. MicroRNAs (miRNAs) are aberrantly expressed in cancers and appear to have both diagnostic and prognostic significance. In this study, we identified novel miRNAs associated with recurrence of CRC, and their possible mechanism of action. TaqMan(®) Human MicroRNA Array Set v2.0 was used to profile the expression of 667 miRNAs in 14 normal colon mucosas and 46 microsatellite stable CRC tumors. Four miRNAs (miR-362-3p, miR-570, miR-148 a* and miR-944) were expressed at a higher level in tumors from patients with no recurrence (p<0.015), compared with tumors from patients with recurrence. A significant association with increased disease free survival was confirmed for miR-362-3p in a second independent cohort of 43 CRC patients, using single TaqMan(®) microRNA assays. In vitro functional analysis showed that over-expression of miR-362-3p in colon cancer cell lines reduced cell viability, and proliferation mainly due to cell cycle arrest. E2F1, USF2 and PTPN1 were identified as potential miR-362-3p targets by mRNA profiling of HCT116 cells over-expressing miR-362-3p. Subsequently, these genes were confirmed as direct targets by Luciferase reporter assays and their knockdown in vitro phenocopied the effects of miR-362-3p over-expression. We conclude that miR-362-3p may be a novel prognostic marker in CRC, and hypothesize that the positive effects of augmented miR-362-3p expression may in part be mediated through the targets E2F1, USF2 and PTPN1. Copyright © 2012 UICC.

MicroRNA-Target Network Inference and Local Network Enrichment Analysis Identify Two microRNA Clusters with Distinct Functions in Head and Neck Squamous Cell Carcinoma

PubMed Central

Sass, Steffen; Pitea, Adriana; Unger, Kristian; Hess, Julia; Mueller, Nikola S.; Theis, Fabian J.

2015-01-01

MicroRNAs represent ~22 nt long endogenous small RNA molecules that have been experimentally shown to regulate gene expression post-transcriptionally. One main interest in miRNA research is the investigation of their functional roles, which can typically be accomplished by identification of mi-/mRNA interactions and functional annotation of target gene sets. We here present a novel method “miRlastic”, which infers miRNA-target interactions using transcriptomic data as well as prior knowledge and performs functional annotation of target genes by exploiting the local structure of the inferred network. For the network inference, we applied linear regression modeling with elastic net regularization on matched microRNA and messenger RNA expression profiling data to perform feature selection on prior knowledge from sequence-based target prediction resources. The novelty of miRlastic inference originates in predicting data-driven intra-transcriptome regulatory relationships through feature selection. With synthetic data, we showed that miRlastic outperformed commonly used methods and was suitable even for low sample sizes. To gain insight into the functional role of miRNAs and to determine joint functional properties of miRNA clusters, we introduced a local enrichment analysis procedure. The principle of this procedure lies in identifying regions of high functional similarity by evaluating the shortest paths between genes in the network. We can finally assign functional roles to the miRNAs by taking their regulatory relationships into account. We thoroughly evaluated miRlastic on a cohort of head and neck cancer (HNSCC) patients provided by The Cancer Genome Atlas. We inferred an mi-/mRNA regulatory network for human papilloma virus (HPV)-associated miRNAs in HNSCC. The resulting network best enriched for experimentally validated miRNA-target interaction, when compared to common methods. Finally, the local enrichment step identified two functional clusters of miRNAs that were predicted to mediate HPV-associated dysregulation in HNSCC. Our novel approach was able to characterize distinct pathway regulations from matched miRNA and mRNA data. An R package of miRlastic was made available through: http://icb.helmholtz-muenchen.de/mirlastic. PMID:26694379

MicroRNA-Target Network Inference and Local Network Enrichment Analysis Identify Two microRNA Clusters with Distinct Functions in Head and Neck Squamous Cell Carcinoma.

PubMed

Sass, Steffen; Pitea, Adriana; Unger, Kristian; Hess, Julia; Mueller, Nikola S; Theis, Fabian J

2015-12-18

MicroRNAs represent ~22 nt long endogenous small RNA molecules that have been experimentally shown to regulate gene expression post-transcriptionally. One main interest in miRNA research is the investigation of their functional roles, which can typically be accomplished by identification of mi-/mRNA interactions and functional annotation of target gene sets. We here present a novel method "miRlastic", which infers miRNA-target interactions using transcriptomic data as well as prior knowledge and performs functional annotation of target genes by exploiting the local structure of the inferred network. For the network inference, we applied linear regression modeling with elastic net regularization on matched microRNA and messenger RNA expression profiling data to perform feature selection on prior knowledge from sequence-based target prediction resources. The novelty of miRlastic inference originates in predicting data-driven intra-transcriptome regulatory relationships through feature selection. With synthetic data, we showed that miRlastic outperformed commonly used methods and was suitable even for low sample sizes. To gain insight into the functional role of miRNAs and to determine joint functional properties of miRNA clusters, we introduced a local enrichment analysis procedure. The principle of this procedure lies in identifying regions of high functional similarity by evaluating the shortest paths between genes in the network. We can finally assign functional roles to the miRNAs by taking their regulatory relationships into account. We thoroughly evaluated miRlastic on a cohort of head and neck cancer (HNSCC) patients provided by The Cancer Genome Atlas. We inferred an mi-/mRNA regulatory network for human papilloma virus (HPV)-associated miRNAs in HNSCC. The resulting network best enriched for experimentally validated miRNA-target interaction, when compared to common methods. Finally, the local enrichment step identified two functional clusters of miRNAs that were predicted to mediate HPV-associated dysregulation in HNSCC. Our novel approach was able to characterize distinct pathway regulations from matched miRNA and mRNA data. An R package of miRlastic was made available through: http://icb.helmholtz-muenchen.de/mirlastic.

Conservation and divergence of microRNAs in Populus

PubMed Central

Barakat, Abdelali; Wall, Phillip K; DiLoreto, Scott; dePamphilis, Claude W; Carlson, John E

2007-01-01

Background MicroRNAs (miRNAs) are small RNAs (sRNA) ~21 nucleotides in length that negatively control gene expression by cleaving or inhibiting the translation of target gene transcripts. miRNAs have been extensively analyzed in Arabidopsis and rice and partially investigated in other non-model plant species. To date, 109 and 62 miRNA families have been identified in Arabidopsis and rice respectively. However, only 33 miRNAs have been identified from the genome of the model tree species (Populus trichocarpa), of which 11 are Populus specific. The low number of miRNA families previously identified in Populus, compared with the number of families identified in Arabidopsis and rice, suggests that many miRNAs still remain to be discovered in Populus. In this study, we analyzed expressed small RNAs from leaves and vegetative buds of Populus using high throughput pyrosequencing. Results Analysis of almost eighty thousand small RNA reads allowed us to identify 123 new sequences belonging to previously identified miRNA families as well as 48 new miRNA families that could be Populus-specific. Comparison of the organization of miRNA families in Populus, Arabidopsis and rice showed that miRNA family sizes were generally expanded in Populus. The putative targets of non-conserved miRNA include both previously identified targets as well as several new putative target genes involved in development, resistance to stress, and other cellular processes. Moreover, almost half of the genes predicted to be targeted by non-conserved miRNAs appear to be Populus-specific. Comparative analyses showed that genes targeted by conserved and non-conserved miRNAs are biased mainly towards development, electron transport and signal transduction processes. Similar results were found for non-conserved miRNAs from Arabidopsis. Conclusion Our results suggest that while there is a conserved set of miRNAs among plant species, a large fraction of miRNAs vary among species. The non-conserved miRNAs may regulate cellular, physiological or developmental processes specific to the taxa that produce them, as appears likely to be the case for those miRNAs that have only been observed in Populus. Non-conserved and conserved miRNAs seem to target genes with similar biological functions indicating that similar selection pressures are acting on both types of miRNAs. The expansion in the number of most conserved miRNAs in Populus relative to Arabidopsis, may be linked to the recent genome duplication in Populus, the slow evolution of the Populus genome, or to differences in the selection pressure on duplicated miRNAs in these species. PMID:18166134

MiR-3613-3p affects cell proliferation and cell cycle in hepatocellular carcinoma

PubMed Central

Zhang, Donghui; Liu, Enqin; Kang, Jian; Yang, Xin; Liu, Hong

2017-01-01

Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumors with poor sensitivity to chemotherapy drugs and poor prognosis among patients. In the present study, we downloaded the original data from the Gene Expression Omnibus and compared gene expression profiles of liver cancer cells in patients with HCC with those of colon epithelial cells of healthy controls to identify differentially expressed genes (DEGs). After filtering target microRNAs (miRNA) from core DEGs, we cultured HepG2 cells in vitro, knocked down the miRNA and core mRNAs, and analyzed the effects. We found 228 differentially expressed genes between liver cancer tissue and healthy control tissue. We also integrated the protein-proteininteraction network and module analysis to screen 13 core genes, consisting of 12 up-regulated genes and 1 down-regulated gene. Five core genes were regulated hsa-miR-3613-3p, therefor we hypothesized that hsa-miR-3613-3p was a critical miRNA. After the transfection procedure, we found that changes in hsa-miR-3613-3p were the most obvious. Therefore, we speculated that hsa-miR-3613-3p was a main target miRNA. In addition, we transfected with si (BIRC5, CDK1, NUF2, ZWINT and SPC24), to target genes that can be targeted by miR-3613-3p. Our data shows that BIRC5, NUF2, and SPC24 may be promising liver cancer biomarkers that may not only predict disease occurrence but also potential personalized treatment options. PMID:29190974

CG200745, an HDAC inhibitor, induces anti-tumour effects in cholangiocarcinoma cell lines via miRNAs targeting the Hippo pathway.

PubMed

Jung, Dawoon E; Park, Soo Been; Kim, Kahee; Kim, Chanyang; Song, Si Young

2017-09-07

Cholangiocarcinoma is a devastating malignancy with fatal complications that exhibits low response and resistance to chemotherapy. Here, we evaluated the anticancer effects of CG200745, a novel histone deacetylase inhibitor, either alone or in combination with standard chemotherapy drugs in cholangiocarcinoma cells. CG200745 dose-dependently reduced the viability of cholangiocarcinoma cells in vitro and decreased tumour volume and weight in a xenograft model. Administering CG200745 along with other chemotherapeutic agents including gemcitabine, 5-fluorouracil (5-FU), cisplatin, oxaliplatin, or gemcitabine plus cisplatin further decreased cholangiocarcinoma cell viability, with a combination index < 1 that indicated synergistic action. CG200745 also enhanced the sensitivity of gemcitabine-resistant cells to gemcitabine and 5-FU, thereby decreasing cell viability and inducing apoptosis. This was accompanied by downregulation of YAP, TEAD4, TGF-β2, SMAD3, NOTCH3, HES5, Axl, and Gas6 and upregulation of the miRNAs miR-22-3p, miR-22-5p, miR-194-5p, miR-194-3p, miR-194-5p, miR-210-3p, and miR-509-3p. The Ingenuity Pathway Analysis revealed that CG200745 mainly targets the Hippo signalling pathway by inducing miR-509-3p expression. Thus, CG200745 inhibits cholangiocarcinoma growth in vitro and in vivo, and acts synergistically when administered in combination with standard chemotherapeutic agents, enabling dose reduction. CG200745 is therefore expected to improve the outcome of cholangiocarcinoma patients who exhibit resistance to conventional therapies.

Exosome-mediated delivery of miR-9 induces cancer-associated fibroblast-like properties in human breast fibroblasts

PubMed Central

Baroni, S; Romero-Cordoba, S; Plantamura, I; Dugo, M; D'Ippolito, E; Cataldo, A; Cosentino, G; Angeloni, V; Rossini, A; Daidone, M G; Iorio, M V

2016-01-01

It is established that the interaction between microenvironment and cancer cells has a critical role in tumor development, given the dependence of neoplastic cells on stromal support. However, how this communication promotes the activation of normal (NFs) into cancer-associated fibroblasts (CAFs) is still not well understood. Most microRNA (miRNA) studies focused on tumor cell, but there is increasing evidence of their involvement in reprogramming NFs into CAFs. Here we show that miR-9, upregulated in various breast cancer cell lines and identified as pro-metastatic miRNA, affects the properties of human breast fibroblasts, enhancing the switch to CAF phenotype, thus contributing to tumor growth. Expressed at higher levels in primary triple-negative breast CAFs versus NFs isolated from patients, miR-9 improves indeed migration and invasion capabilities when transfected in immortalized NFs; viceversa, these properties are strongly impaired in CAFs upon miR-9 inhibition. We also demonstrate that tumor-secreted miR-9 can be transferred via exosomes to recipient NFs and this uptake results in enhanced cell motility. Moreover, we observed that this miRNA is also secreted by fibroblasts and in turn able to alter tumor cell behavior, by modulating its direct target E-cadherin, and NFs themselves. Consistently with the biological effects observed, gene expression profiles of NFs upon transient transfection with miR-9 show the modulation of genes mainly involved in cell motility and extracellular matrix remodeling pathways. Finally, we were able to confirm the capability of NFs transiently transfected with miR-9 to promote in vivo tumor growth. Taken together, these data provide new insights into the role of miR-9 as an important player in the cross-talk between cancer cells and stroma. PMID:27468688

Exosome-mediated delivery of miR-9 induces cancer-associated fibroblast-like properties in human breast fibroblasts.

PubMed

Baroni, S; Romero-Cordoba, S; Plantamura, I; Dugo, M; D'Ippolito, E; Cataldo, A; Cosentino, G; Angeloni, V; Rossini, A; Daidone, M G; Iorio, M V

2016-07-28

It is established that the interaction between microenvironment and cancer cells has a critical role in tumor development, given the dependence of neoplastic cells on stromal support. However, how this communication promotes the activation of normal (NFs) into cancer-associated fibroblasts (CAFs) is still not well understood. Most microRNA (miRNA) studies focused on tumor cell, but there is increasing evidence of their involvement in reprogramming NFs into CAFs. Here we show that miR-9, upregulated in various breast cancer cell lines and identified as pro-metastatic miRNA, affects the properties of human breast fibroblasts, enhancing the switch to CAF phenotype, thus contributing to tumor growth. Expressed at higher levels in primary triple-negative breast CAFs versus NFs isolated from patients, miR-9 improves indeed migration and invasion capabilities when transfected in immortalized NFs; viceversa, these properties are strongly impaired in CAFs upon miR-9 inhibition. We also demonstrate that tumor-secreted miR-9 can be transferred via exosomes to recipient NFs and this uptake results in enhanced cell motility. Moreover, we observed that this miRNA is also secreted by fibroblasts and in turn able to alter tumor cell behavior, by modulating its direct target E-cadherin, and NFs themselves. Consistently with the biological effects observed, gene expression profiles of NFs upon transient transfection with miR-9 show the modulation of genes mainly involved in cell motility and extracellular matrix remodeling pathways. Finally, we were able to confirm the capability of NFs transiently transfected with miR-9 to promote in vivo tumor growth. Taken together, these data provide new insights into the role of miR-9 as an important player in the cross-talk between cancer cells and stroma.

Unravelling site-specific breast cancer metastasis: a microRNA expression profiling study

PubMed Central

Schrijver, Willemijne A.M.E.; van Diest, Paul J.; Moelans, Cathy B

2017-01-01

Distant metastasis is still the main cause of death from breast cancer. MicroRNAs (miRs) are important regulators of many physiological and pathological processes, including metastasis. Molecular breast cancer subtypes are known to show a site-specific pattern of metastases formation. In this study, we set out to determine the underlying molecular mechanisms of site-specific breast cancer metastasis by microRNA expression profiling. To identify a miR signature for metastatic breast carcinoma that could predict metastatic localization, we compared global miR expression in 23 primary breast cancer specimens with their corresponding multiple distant metastases to ovary (n=9), skin (n=12), lung (n=10), brain (n=4) and gastrointestinal tract (n=10) by miRCURY microRNA expression arrays. For validation, we performed quantitative real-time (qRT) PCR on the discovery cohort and on an independent validation cohort of 29 primary breast cancer specimens and their matched metastases. miR expression was highly patient specific and miR signatures in the primary tumor were largely retained in the metastases, with the exception of several differentially expressed, location specific miRs. Validation with qPCR demonstrated that hsa-miR-106b-5p was predictive for the development of lung metastases. In time, the second metastasis often showed a miR upregulation compared to the first metastasis. This study discovered a metastatic site-specific miR and found miR expression to be highly patient specific. This may lead to novel biomarkers predicting site of distant metastases, and to adjuvant, personalized targeted therapy strategies that could prevent such metastases from becoming clinically manifest. PMID:27902972

Unravelling site-specific breast cancer metastasis: a microRNA expression profiling study.

PubMed

Schrijver, Willemijne A M E; van Diest, Paul J; Moelans, Cathy B

2017-01-10

Distant metastasis is still the main cause of death from breast cancer. MicroRNAs (miRs) are important regulators of many physiological and pathological processes, including metastasis. Molecular breast cancer subtypes are known to show a site-specific pattern of metastases formation. In this study, we set out to determine the underlying molecular mechanisms of site-specific breast cancer metastasis by microRNA expression profiling.To identify a miR signature for metastatic breast carcinoma that could predict metastatic localization, we compared global miR expression in 23 primary breast cancer specimens with their corresponding multiple distant metastases to ovary (n=9), skin (n=12), lung (n=10), brain (n=4) and gastrointestinal tract (n=10) by miRCURY microRNA expression arrays. For validation, we performed quantitative real-time (qRT) PCR on the discovery cohort and on an independent validation cohort of 29 primary breast cancer specimens and their matched metastases.miR expression was highly patient specific and miR signatures in the primary tumor were largely retained in the metastases, with the exception of several differentially expressed, location specific miRs. Validation with qPCR demonstrated that hsa-miR-106b-5p was predictive for the development of lung metastases. In time, the second metastasis often showed a miR upregulation compared to the first metastasis.This study discovered a metastatic site-specific miR and found miR expression to be highly patient specific. This may lead to novel biomarkers predicting site of distant metastases, and to adjuvant, personalized targeted therapy strategies that could prevent such metastases from becoming clinically manifest.

Comparative analysis of miRNA expression during the development of insects of different metamorphosis modes and germ-band types.

PubMed

Ylla, Guillem; Piulachs, Maria-Dolors; Belles, Xavier

2017-10-11

Do miRNAs contribute to specify the germ-band type and the body structure in the insect embryo? Our goal was to address that issue by studying the changes in miRNA expression along the ontogeny of the German cockroach Blattella germanica, which is a short germ-band and hemimetabolan species. We sequenced small RNA libraries representing 11 developmental stages of B. germanica ontogeny (with especial emphasis on embryogenesis) and the changes in miRNA expression were examined. Data were compared with equivalent data for two long germ-band holometabolan species Drosophila melanogaster and Drosophila virilis, and the short germ-band holometabolan species Tribolium castaneum. The identification of B. germanica embryo small RNA sequences unveiled miRNAs not detected in previous studies, such as those of the MIR-309 family and 54 novel miRNAs. Four main waves of miRNA expression were recognized (with most miRNA changes occurring during the embryonic stages): the first from day 0 to day 1 of embryogenesis, the second during mid-embryogenesis (days 0-6), the third (with an acute expression peak) on day 2 of embryonic development, and the fourth during post-embryonic development. The second wave defined the boundaries of maternal-to-zygotic transition, with maternal mRNAs being cleared, presumably by Mir-309 and associated scavenger miRNAs. miRNAs follow well-defined patterns of expression over hemimetabolan ontogeny, patterns that are more diverse during embryonic development than during the nymphal stages. The results suggest that miRNAs play important roles in the developmental transitions between the embryonic stages of development (starting with maternal loading), during which they might influence the germ-band type and metamorphosis mode.

Identifying content-based and relational techniques to change behaviour in motivational interviewing.

PubMed

Hardcastle, Sarah J; Fortier, Michelle; Blake, Nicola; Hagger, Martin S

2017-03-01

Motivational interviewing (MI) is a complex intervention comprising multiple techniques aimed at changing health-related motivation and behaviour. However, MI techniques have not been systematically isolated and classified. This study aimed to identify the techniques unique to MI, classify them as content-related or relational, and evaluate the extent to which they overlap with techniques from the behaviour change technique taxonomy version 1 [BCTTv1; Michie, S., Richardson, M., Johnston, M., Abraham, C., Francis, J., Hardeman, W., … Wood, C. E. (2013). The behavior change technique taxonomy (v1) of 93 hierarchically clustered techniques: Building an international consensus for the reporting of behavior change interventions. Annals of Behavioral Medicine, 46, 81-95]. Behaviour change experts (n = 3) content-analysed MI techniques based on Miller and Rollnick's [(2013). Motivational interviewing: Preparing people for change (3rd ed.). New York: Guildford Press] conceptualisation. Each technique was then coded for independence and uniqueness by independent experts (n = 10). The experts also compared each MI technique to those from the BCTTv1. Experts identified 38 distinct MI techniques with high agreement on clarity, uniqueness, preciseness, and distinctiveness ratings. Of the identified techniques, 16 were classified as relational techniques. The remaining 22 techniques were classified as content based. Sixteen of the MI techniques were identified as having substantial overlap with techniques from the BCTTv1. The isolation and classification of MI techniques will provide researchers with the necessary tools to clearly specify MI interventions and test the main and interactive effects of the techniques on health behaviour. The distinction between relational and content-based techniques within MI is also an important advance, recognising that changes in motivation and behaviour in MI is a function of both intervention content and the interpersonal style in which the content is delivered.

Evolutionary conservation and expression of miR-10a-3p in olive flounder and rock bream.

PubMed

Jo, Ara; Im, Jennifer; Lee, Hee-Eun; Jang, Dongmin; Nam, Gyu-Hwi; Mishra, Anshuman; Kim, Woo-Jin; Kim, Won; Cha, Hee-Jae; Kim, Heui-Soo

2017-09-10

MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) that mainly bind to the seed sequences located within the 3' untranslated region (3' UTR) of target genes. They perform an important biological function as regulators of gene expression. Different genes can be regulated by the same miRNA, whilst different miRNAs can be regulated by the same genes. Here, the evolutionary conservation and expression pattern of miR-10a-3p in olive flounder and rock bream was examined. Binding sites (AAAUUC) to seed region of the 3' UTR of target genes were highly conserved in various species. The expression pattern of miR-10a-3p was ubiquitous in the examined tissues, whilst its expression level was decreased in gill tissues infected by viral hemorrhagic septicemia virus (VHSV) compared to the normal control. In the case of rock bream, the spleen, kidney, and liver tissues showed dominant expression levels of miR-10a-3p. Only the liver tissues in the rock bream samples infected by the iridovirus indicated a dominant miR-10a-3p expression. The gene ontology (GO) analysis of predicted target genes for miR-10a-3p revealed that multiple genes are related to binding activity, catalytic activity, cell components as well as cellular and metabolic process. Overall the results imply that the miR-10a-3p could be used as a biomarker to detect VHSV infection in olive flounder and iridovirus infection in rock bream. In addition, the data provides fundamental information for further study of the complex interaction between miR-10a-3p and gene expression. Copyright © 2017 Elsevier B.V. All rights reserved.

Context-dependent miR-204 and miR-211 affect the biological properties of amelanotic and melanotic melanoma cells

PubMed Central

Vitiello, Marianna; Tuccoli, Andrea; D’Aurizio, Romina; Sarti, Samanta; Giannecchini, Laura; Lubrano, Simone; Marranci, Andrea; Evangelista, Monica; Peppicelli, Silvia; Ippolito, Chiara; Barravecchia, Ivana; Guzzolino, Elena; Montagnani, Valentina; Gowen, Michael; Mercoledi, Elisa; Mercatanti, Alberto; Comelli, Laura; Gurrieri, Salvatore; Wu, Lawrence W.; Ope, Omotayo; Flaherty, Keith; Boland, Genevieve M.; Hammond, Marc R.; Kwong, Lawrence; Chiariello, Mario; Stecca, Barbara; Zhang, Gao; Salvetti, Alessandra; Angeloni, Debora; Pitto, Letizia; Calorini, Lido; Chiorino, Giovanna; Pellegrini, Marco; Herlyn, Meenhard; Osman, Iman; Poliseno, Laura

2017-01-01

Despite increasing amounts of experimental evidence depicting the involvement of non-coding RNAs in cancer, the study of BRAFV600E-regulated genes has thus far focused mainly on protein-coding ones. Here, we identify and study the microRNAs that BRAFV600E regulates through the ERK pathway. By performing small RNA sequencing on A375 melanoma cells and a vemurafenib-resistant clone that was taken as negative control, we discover miR-204 and miR-211 as the miRNAs most induced by vemurafenib. We also demonstrate that, although belonging to the same family, these two miRNAs have distinctive features. miR-204 is under the control of STAT3 and its expression is induced in amelanotic melanoma cells, where it acts as an effector of vemurafenib's anti-motility activity by targeting AP1S2. Conversely, miR-211, a known transcriptional target of MITF, is induced in melanotic melanoma cells, where it targets EDEM1 and consequently impairs the degradation of TYROSINASE (TYR) through the ER-associated degradation (ERAD) pathway. In doing so, miR-211 serves as an effector of vemurafenib's pro-pigmentation activity. We also show that such an increase in pigmentation in turn represents an adaptive response that needs to be overcome using appropriate inhibitors in order to increase the efficacy of vemurafenib. In summary, we unveil the distinct and context-dependent activities exerted by miR-204 family members in melanoma cells. Our work challenges the widely accepted “same miRNA family = same function” rule and provides a rationale for a novel treatment strategy for melanotic melanomas that is based on the combination of ERK pathway inhibitors with pigmentation inhibitors. PMID:28445987

High-resolution identification and abundance profiling of cassava (Manihot esculenta Crantz) microRNAs.

PubMed

Khatabi, Behnam; Arikit, Siwaret; Xia, Rui; Winter, Stephan; Oumar, Doungous; Mongomake, Kone; Meyers, Blake C; Fondong, Vincent N

2016-01-28

Small RNAs (sRNAs) are endogenous sRNAs that play regulatory roles in plant growth, development, and biotic and abiotic stress responses. In plants, one subset of sRNAs, microRNAs (miRNAs) exhibit tissue-differential expression and regulate gene expression mainly through direct cleavage of mRNA or indirectly via production of secondary phased siRNAs (phasiRNAs) that silence cognate target transcripts in trans. Here, we have identified cassava (Manihot esculenta Crantz) miRNAs using high resolution sequencing of sRNA libraries from leaf, stem, callus, male and female flower tissues. To analyze the data, we built a cassava genome database and, via sequence analysis and secondary structure prediction, 38 miRNAs not previously reported in cassava were identified. These new cassava miRNAs included two miRNAs not previously been reported in any plant species. The miRNAs exhibited tissue-differential accumulation as confirmed by quantitative RT-PCR and Northern blot analysis, largely reflecting levels observed in sequencing data. Some of the miRNAs identified were predicted to trigger production of secondary phased siRNAs (phasiRNAs) from 80 PHAS loci. Cassava is a woody perennial shrub, grown principally for its starch-rich storage roots, which are rich in calories. In this study, new miRNAs were identified and their expression was validated using qRT-PCR of RNA from five different tissues. The data obtained expand the list of annotated miRNAs and provide additional new resources for cassava improvement research.

MiR-17/20/93/106 promote hematopoietic cell expansion by targeting sequestosome 1–regulated pathways in mice

PubMed Central

Meenhuis, Annemarie; van Veelen, Peter A.; de Looper, Hans; van Boxtel, Nicole; van den Berge, Iris J.; Sun, Su M.; Taskesen, Erdogan; Stern, Patrick; de Ru, Arnoud H.; van Adrichem, Arjan J.; Demmers, Jeroen; Jongen-Lavrencic, Mojca; Löwenberg, Bob; Touw, Ivo P.; Sharp, Phillip A.

2011-01-01

MicroRNAs (miRNAs) are pivotal for regulation of hematopoiesis but their critical targets remain largely unknown. Here, we show that ectopic expression of miR-17, -20,-93 and -106, all AAAGUGC seed-containing miRNAs, increases proliferation, colony outgrowth and replating capacity of myeloid progenitors and results in enhanced P-ERK levels. We found that these miRNAs are endogenously and abundantly expressed in myeloid progenitors and down-regulated in mature neutrophils. Quantitative proteomics identified sequestosome 1 (SQSTM1), an ubiquitin-binding protein and regulator of autophagy-mediated protein degradation, as a major target for these miRNAs in myeloid progenitors. In addition, we found increased expression of Sqstm1 transcripts during CSF3-induced neutrophil differentiation of 32D-CSF3R cells and an inverse correlation of SQSTM1 protein levels and miR-106 expression in AML samples. ShRNA-mediated silencing of Sqstm1 phenocopied the effects of ectopic miR-17/20/93/106 expression in hematopoietic progenitors in vitro and in mice. Further, SQSTM1 binds to the ligand-activated colony-stimulating factor 3 receptor (CSF3R) mainly in the late endosomal compartment, but not in LC3 positive autophagosomes. SQSTM1 regulates CSF3R stability and ligand-induced mitogen-activated protein kinase signaling. We demonstrate that AAAGUGC seed-containing miRNAs promote cell expansion, replating capacity and signaling in hematopoietic cells by interference with SQSTM1-regulated pathways. PMID:21628417

The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia

PubMed Central

Díaz-Beyá, M; Brunet, S; Nomdedéu, J; Cordeiro, A; Tormo, M; Escoda, L; Ribera, J M; Arnan, M; Heras, I; Gallardo, D; Bargay, J; Queipo de Llano, M P; Salamero, O; Martí, J M; Sampol, A; Pedro, C; Hoyos, M; Pratcorona, M; Castellano, J J; Nomdedeu, M; Risueño, R M; Sierra, J; Monzó, M; Navarro, A; Esteve, J

2015-01-01

Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML. PMID:26430723

NF-kB and c-Jun induce the expression of the oncogenic miR-221 and miR-222 in prostate carcinoma and glioblastoma cells

PubMed Central

Galardi, Silvia; Mercatelli, Neri; Farace, Maria G.; Ciafrè, Silvia A.

2011-01-01

MicroRNAs (miRNAs) are potent negative regulators of gene expression involved in all aspects of cell biology. They finely modulate virtually all physiological pathways in metazoans, and are deeply implicated in all main pathologies, among which cancer. Mir-221 and miR-222, two closely related miRNAs encoded in cluster from a genomic region on chromosome X, are strongly upregulated in several forms of human tumours. In this work, we report that the ectopic modulation of NF-kB modifies miR-221/222 expression in prostate carcinoma and glioblastoma cell lines, where we had previously shown their oncogenic activity. We identify two separate distal regions upstream of miR-221/222 promoter which are bound by the NF-kB subunit p65 and drive efficient transcription in luciferase reporter assays; consistently, the site-directed mutagenesis disrupting p65 binding sites or the ectopical inhibition of NF-kB activity significantly reduce luciferase activity. In the most distal enhancer region, we also define a binding site for c-Jun, and we show that the binding of this factor cooperates with that of p65, fully accounting for the observed upregulation of miR-221/222. Thus our work uncovers an additional mechanism through which NF-kB and c-Jun, two transcription factors deeply involved in cancer onset and progression, contribute to oncogenesis, by inducing miR-221/222 transcription. PMID:21245048

Diagnostic value of selected markers and apoptotic pathways for pancreatic cancer

PubMed Central

Słotwińska, Sylwia Małgorzata

2017-01-01

Pancreatic cancer occupies the fourth place as a cause of death from cancer, and the mortality rate is similar to the number of newly detected cases. Due to the late diagnosis, only 5-6% of patients with pancreatic cancer survive for five years. Given that early diagnosis is critical for improving patients’ survival rates, there is an urgent need for the discovery and validation of new biomarkers with sufficient sensitivity and specificity to help diagnose pancreatic cancer early. Detection of serum tumor markers (CA19-9, CEA, CA125 and CA242) is conducive to the early diagnosis of pancreatic cancer. The combination of miR-16, miR-196a and CA19-9 plasma level was more effective, especially in early tumor screening. Furthermore, recent studies reported that mainly miR-21, miR-155 and miR-196 were dysregulated in IPMN (intraductal papillary mucinous neoplasms) and PanIN (pancreatic intraepithelial neoplasia) lesions, suggesting their usefulness as early biomarkers of these diseases. The reduced rate of apoptosis plays a crucial role in carcinogenesis, and it is one of the most important characteristics acquired by pancreatic cancer cells, which protects them from attack by the immune system and reduces the effectiveness of pharmacological treatment. This review summarizes the data concerning the clinical utility of selected biomarkers in pancreatic cancer patients. The review mainly focuses on the genetic aspects of signaling pathway disorders associated with apoptosis in the pathogenesis and diagnosis of pancreatic cancer. PMID:28450803

Interrupted E2F1-miR-34c-SCF negative feedback loop by hyper-methylation promotes colorectal cancer cell proliferation

PubMed Central

Yang, Shu; Wu, Bo; Sun, Haimei; Ji, Fengqing; Sun, Tingyi; Zhao, Yan; Zhou, Deshan

2015-01-01

Tumour suppressor miR-34c deficiency resulted from hyper-methylation in its promoter is believed to be one of the main causes of colorectal cancer (CRC). Till date, miR-34c has been validated as a direct target of p53; but previous evidence suggested other transcription factor(s) must be involved in miR-34c transcription. In the present study, we in the first place identified a core promoter region (−1118 to −883 bp) of pre-miR-34c which was embedded within a hyper-methylated CpG island. Secondly, E2F1 promoted miR-34c transcription by physical interaction with the miR-34c promoter at site −897 to −889 bp. The transcriptional activating effect of E2F1 on miR-34c was in a p53 independent manner but profoundly promoted in the presence of p53 with exposure to 5-aza-2′-deoxycytidine (DAC). Thirdly, stem cell factor (SCF), a miR-34c target, was specifically reduced upon an introduction of E2F1 which lead to suppression of CRC cell proliferation. The E2F1-suppressed cell proliferation was partially abrogated by additional miR-34c inhibitor, indicating that the anti-proliferation effect of E2F1 was probably through activating miR-34c-SCF axis. Finally, SCF/KIT signalling increased E2F1 production by reducing its proteosomal degradation dependent on PI3K/Akt-GSK3β pathway. In conclusion, our results suggested the existence of E2F1-miR-34c-SCF negative feedback loop which was interrupted by the hyper-methylation of miR-34c promoter in CRC cells and increased cell proliferation. PMID:26704889

MicroRNA-196b Inhibits Cell Growth and Metastasis of Lung Cancer Cells by Targeting Runx2.

PubMed

Bai, Xiaoxue; Meng, Lin; Sun, Huijie; Li, Zhuo; Zhang, Xiufang; Hua, Shucheng

2017-01-01

Lung cancer is one of the most common causes of cancer related deaths worldwide. The role of several microRNAs (miRNAs) including miR-196b in different cancers has already been established. The study was aimed to explore the role of miR-196b in lung cancer and its possible underlying mechanism. Human lung cancer cell line A549 was transfected with miR-196b mimic, miR-196b inhibitor and corresponding controls. Then cell viability, migration, invasion, and apoptosis of A549 lung cancer cells either with overexpression or with suppression of miR-196b were estimated sequentially. Next, dual luciferase activity assay was performed to clarify whether Runx2 was a direct target of miR-196b. Finally, the expressions of main factors associated with epithelial mesenchymal transition (EMT), PI3K/AKT/GSK3β, Smad, and JNK pathways were detected by western blot. MiR-196b expression was significantly decreased in A549, H1650 and H1299 cell lines compared with in WI-38 and HEL-1 cell lines. Overexpression of miR-196b suppressed cell viability, migration, invasion, and induced apoptosis as well as inhibited TGF-β induced EMT process in A549 cells. In addition, Runx2 was a putative target of miR-196b, and Runx2 silence remarkably increased cell apoptosis and abolished the promotive effects of miR-196b suppression on cell viability, migration and invasion. Finally, miR-196b also mediated its action by inactivation of PI3K/AKT/GSK3β, Smad, and JNK pathways by down-regulation of Runx2. MiR-196b functions as a tumor suppressor that inhibited cell growth and metastasis of lung cancer cells by targeting Runx2. These findings provided further evidences for treatment of lung cancer. The Author(s). Published by S. Karger AG, Basel.

smRNAome profiling to identify conserved and novel microRNAs in Stevia rebaudiana Bertoni

PubMed Central

2012-01-01

Background MicroRNAs (miRNAs) constitute a family of small RNA (sRNA) population that regulates the gene expression and plays an important role in plant development, metabolism, signal transduction and stress response. Extensive studies on miRNAs have been performed in different plants such as Arabidopsis thaliana, Oryza sativa etc. and volume of the miRNA database, mirBASE, has been increasing on day to day basis. Stevia rebaudiana Bertoni is an important perennial herb which accumulates high concentrations of diterpene steviol glycosides which contributes to its high indexed sweetening property with no calorific value. Several studies have been carried out for understanding molecular mechanism involved in biosynthesis of these glycosides, however, information about miRNAs has been lacking in S. rebaudiana. Deep sequencing of small RNAs combined with transcriptomic data is a powerful tool for identifying conserved and novel miRNAs irrespective of availability of genome sequence data. Results To identify miRNAs in S. rebaudiana, sRNA library was constructed and sequenced using Illumina genome analyzer II. A total of 30,472,534 reads representing 2,509,190 distinct sequences were obtained from sRNA library. Based on sequence similarity, we identified 100 miRNAs belonging to 34 highly conserved families. Also, we identified 12 novel miRNAs whose precursors were potentially generated from stevia EST and nucleotide sequences. All novel sequences have not been earlier described in other plant species. Putative target genes were predicted for most conserved and novel miRNAs. The predicted targets are mainly mRNA encoding enzymes regulating essential plant metabolic and signaling pathways. Conclusions This study led to the identification of 34 highly conserved miRNA families and 12 novel potential miRNAs indicating that specific miRNAs exist in stevia species. Our results provided information on stevia miRNAs and their targets building a foundation for future studies to understand their roles in key stevia traits. PMID:23116282

Genome-wide identification of alternate bearing-associated microRNAs (miRNAs) in olive (Olea europaea L.)

PubMed Central

2013-01-01

Background Alternate bearing is a widespread phenomenon among crop plants, defined as the tendency of certain fruit trees to produce a high-yield crop one year ("on-year"), followed by a low-yield or even no crop the following year ("off-year"). Several factors may affect the balance between such developmental phase-transition processes. Among them are the microRNA (miRNA), being gene-expression regulators that have been found to be involved as key determinants in several physiological processes. Results Six olive (Olea europaea L. cv. Ayvalik variety) small RNA libraries were constructed from fruits (ripe and unripe) and leaves (”on year” and ”off year” leaves in July and in November, respectively) and sequenced by high-throughput Illumina sequencing. The RNA was retrotranscribed and sequenced using the high-throughput Illumina platform. Bioinformatics analyses of 93,526,915 reads identified 135 conserved miRNA, belonging to 22 miRNA families in the olive. In addition, 38 putative novel miRNAs were discovered in the datasets. Expression of olive tree miRNAs varied greatly among the six libraries, indicating the contribution of diverse miRNA in balancing between reproductive and vegetative phases. Predicted targets of miRNA were categorized into 108 process ontology groups with significance abundance. Among those, potential alternate bearing-associated processes were found, such as development, hormone-mediated signaling and organ morphogenesis. The KEGG analyses revealed that the miRNA-targeted genes are involved in seven main pathways, belonging to carbohydrate metabolism and hormone signal-transduction pathways. Conclusion A comprehensive study on olive miRNA related to alternate bearing was performed. Regulation of miRNA under different developmental phases and tissues indicated that control of nutrition and hormone, together with flowering processes had a noteworthy impact on the olive tree alternate bearing. Our results also provide significant data on the miRNA-fruit development interaction and advance perspectives in the miRNA profile of the olive tree. PMID:23320600

miR-203 inhibits cell proliferation and promotes cisplatin induced cell death in tongue squamous cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Jiong; Lin, Yao; Fan, Li

Oral squamous cell carcinoma (OSCC) is one of the most common types of the head and neck cancer. Chemo resistance of OSCC has been identified as a substantial therapeutic hurdle. In this study, we analyzed the role of miR-203 in the OSCC and its effects on cisplatin-induced cell death in an OSCC cell line, Tca8113. There was a significant decrease of miR-203 expression in OSCC samples, compared with the adjacent normal, non-cancerous tissue. After 3 days cisplatin treatment, the survived Tca8113 cells had a lower expression of miR-203 than that in the untreated control group. In contrast, PIK3CA showed an inversemore » expression in cancer and cisplatin survived Tca8113 cells. Transfection of Tca8113 cells with miR-203 mimics greatly reduced PIK3CA expression and Akt activation. Furthermore, miR-203 repressed PIK3CA expression through targeting the 3′UTR. Restoration of miR-203 not only suppressed cell proliferation, but also sensitized cells to cisplatin induced cell apoptosis. This effect was absent in cells that were simultaneously treated with PIK3CA RNAi. In summary, these findings suggest miR-203 plays an important role in cisplatin resistance in OSCC, and furthermore delivery of miR-203 analogs may serve as an adjuvant therapy for OSCC. - Highlights: • Much lower miR-203 expression in cisplatin resistant Tca8113 cells is discovered. • Delivery of miR-203 can sensitize the Tca8113 cells to cisplatin induced cell death. • MiR-203 can downregulate PIK3CA through the 3′UTR. • The effects of miR-203 on cisplatin sensitivity is mainly through PIK3CA pathway.« less

miR-338 modulates proliferation and autophagy by PI3K/AKT/mTOR signaling pathway in cervical cancer.

PubMed

Lu, Rong; Yang, Zhanhua; Xu, Guoying; Yu, Shengsheng

2018-06-10

Cervical cancer (CC) is a malignant solid tumor, which is one of the main causes of morbidity and mortality in women. Given that autophagy is an important factor promoting tumor progression, we aim to investigate the functional role of miR-338 in autophagy and proliferation of cervical cancer. In our study, expression of miR-338 was validated by quantitative RT-PCR in 30 paired cervical cancer tissues and normal tissues. We performed MTT, colony formation and cell cycle assay to explore the effect of miR-338 on cell proliferation. The level of autophagy was evaluated by observing the expression of LC3 formation under fluorescence microscope and detected the LC3 expression by western blot. We used luciferase reporter assays to identify the target gene about miR-338. We not only found that the level of miR-338 is decreased in cervical cancer tissues and cells, but also negatively correlated with the protein level of ATF2. In turn, restoring the expression of miR-338 inhibited proliferation in Hela and SiHa cells. Further mechanistic study identified that ATF2 as a direct target of miR-338. Forced lowexpression of miR-338 directly led to increased the level of autophagy in cervical cancer cells, which was similar to the mTOR signaling inhibitor rapamycin. The western blot analysis show that inhibited miR-338 expression could decrease the p-mTOR and p-p70S6 expression. Thus, we infer that miR-338 decreases autophagy level in cervical cancer cells by activating mTOR signaling pathway. In summary, our study demonstrate that miR-338 could inhibites proliferation and autophagy by targeting ATF2 via mTOR signaling pathway on cervical cancer cells. These results suggest a potential application of miR-338 in cervical cancer as a novel mechanism of tumor therapeutic. Copyright © 2018. Published by Elsevier Masson SAS.

smRNAome profiling to identify conserved and novel microRNAs in Stevia rebaudiana Bertoni.

PubMed

Mandhan, Vibha; Kaur, Jagdeep; Singh, Kashmir

2012-11-01

MicroRNAs (miRNAs) constitute a family of small RNA (sRNA) population that regulates the gene expression and plays an important role in plant development, metabolism, signal transduction and stress response. Extensive studies on miRNAs have been performed in different plants such as Arabidopsis thaliana, Oryza sativa etc. and volume of the miRNA database, mirBASE, has been increasing on day to day basis. Stevia rebaudiana Bertoni is an important perennial herb which accumulates high concentrations of diterpene steviol glycosides which contributes to its high indexed sweetening property with no calorific value. Several studies have been carried out for understanding molecular mechanism involved in biosynthesis of these glycosides, however, information about miRNAs has been lacking in S. rebaudiana. Deep sequencing of small RNAs combined with transcriptomic data is a powerful tool for identifying conserved and novel miRNAs irrespective of availability of genome sequence data. To identify miRNAs in S. rebaudiana, sRNA library was constructed and sequenced using Illumina genome analyzer II. A total of 30,472,534 reads representing 2,509,190 distinct sequences were obtained from sRNA library. Based on sequence similarity, we identified 100 miRNAs belonging to 34 highly conserved families. Also, we identified 12 novel miRNAs whose precursors were potentially generated from stevia EST and nucleotide sequences. All novel sequences have not been earlier described in other plant species. Putative target genes were predicted for most conserved and novel miRNAs. The predicted targets are mainly mRNA encoding enzymes regulating essential plant metabolic and signaling pathways. This study led to the identification of 34 highly conserved miRNA families and 12 novel potential miRNAs indicating that specific miRNAs exist in stevia species. Our results provided information on stevia miRNAs and their targets building a foundation for future studies to understand their roles in key stevia traits.

High Throughput Sequencing Identifies MicroRNAs Mediating α-Synuclein Toxicity by Targeting Neuroactive-Ligand Receptor Interaction Pathway in Early Stage of Drosophila Parkinson's Disease Model

PubMed Central

Kong, Yan; Liang, Xijun; Liu, Lin; Zhang, Dongdong; Wan, Chao; Gan, Zhenji; Yuan, Liudi

2015-01-01

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder with pathological features including death of dopaminergic neurons in the substantia nigra and intraneuronal accumulations of Lewy bodies. As the main component of Lewy bodies, α-synuclein is implicated in PD pathogenesis by aggregation into insoluble filaments. However, the detailed mechanisms underlying α-synuclein induced neurotoxicity in PD are still elusive. MicroRNAs are ~20nt small RNA molecules that fine-tune gene expression at posttranscriptional level. A plethora of miRNAs have been found to be dysregulated in the brain and blood cells of PD patients. Nevertheless, the detailed mechanisms and their in vivo functions in PD still need further investigation. By using Drosophila PD model expressing α-synuclein A30P, we examined brain miRNA expression with high-throughput small RNA sequencing technology. We found that five miRNAs (dme-miR-133-3p, dme-miR-137-3p, dme-miR-13b-3p, dme-miR-932-5p, dme-miR-1008-5p) were upregulated in PD flies. Among them, miR-13b, miR-133, miR-137 are brain enriched and highly conserved from Drosophila to humans. KEGG pathway analysis using DIANA miR-Path demonstrated that neuroactive-ligand receptor interaction pathway was most likely affected by these miRNAs. Interestingly, miR-137 was predicted to regulate most of the identified targets in this pathway, including dopamine receptor (DopR, D2R), γ-aminobutyric acid (GABA) receptor (GABA-B-R1, GABA-B-R3) and N-methyl-D-aspartate (NMDA) receptor (Nmdar2). The validation experiments showed that the expression of miR-137 and its targets was negatively correlated in PD flies. Further experiments using luciferase reporter assay confirmed that miR-137 could act on specific sites in 3’ UTR region of D2R, Nmdar2 and GABA-B-R3, which downregulated significantly in PD flies. Collectively, our findings indicate that α-synuclein could induce the dysregulation of miRNAs, which target neuroactive ligand-receptor interaction pathway in vivo. We believe it will help us further understand the contribution of miRNAs to α-synuclein neurotoxicity and provide new insights into the pathogenesis driving PD. PMID:26361355

High Throughput Sequencing Identifies MicroRNAs Mediating α-Synuclein Toxicity by Targeting Neuroactive-Ligand Receptor Interaction Pathway in Early Stage of Drosophila Parkinson's Disease Model.

PubMed

Kong, Yan; Liang, Xijun; Liu, Lin; Zhang, Dongdong; Wan, Chao; Gan, Zhenji; Yuan, Liudi

2015-01-01

Parkinson's disease (PD) is a prevalent neurodegenerative disorder with pathological features including death of dopaminergic neurons in the substantia nigra and intraneuronal accumulations of Lewy bodies. As the main component of Lewy bodies, α-synuclein is implicated in PD pathogenesis by aggregation into insoluble filaments. However, the detailed mechanisms underlying α-synuclein induced neurotoxicity in PD are still elusive. MicroRNAs are ~20nt small RNA molecules that fine-tune gene expression at posttranscriptional level. A plethora of miRNAs have been found to be dysregulated in the brain and blood cells of PD patients. Nevertheless, the detailed mechanisms and their in vivo functions in PD still need further investigation. By using Drosophila PD model expressing α-synuclein A30P, we examined brain miRNA expression with high-throughput small RNA sequencing technology. We found that five miRNAs (dme-miR-133-3p, dme-miR-137-3p, dme-miR-13b-3p, dme-miR-932-5p, dme-miR-1008-5p) were upregulated in PD flies. Among them, miR-13b, miR-133, miR-137 are brain enriched and highly conserved from Drosophila to humans. KEGG pathway analysis using DIANA miR-Path demonstrated that neuroactive-ligand receptor interaction pathway was most likely affected by these miRNAs. Interestingly, miR-137 was predicted to regulate most of the identified targets in this pathway, including dopamine receptor (DopR, D2R), γ-aminobutyric acid (GABA) receptor (GABA-B-R1, GABA-B-R3) and N-methyl-D-aspartate (NMDA) receptor (Nmdar2). The validation experiments showed that the expression of miR-137 and its targets was negatively correlated in PD flies. Further experiments using luciferase reporter assay confirmed that miR-137 could act on specific sites in 3' UTR region of D2R, Nmdar2 and GABA-B-R3, which downregulated significantly in PD flies. Collectively, our findings indicate that α-synuclein could induce the dysregulation of miRNAs, which target neuroactive ligand-receptor interaction pathway in vivo. We believe it will help us further understand the contribution of miRNAs to α-synuclein neurotoxicity and provide new insights into the pathogenesis driving PD.

Combined microRNA and mRNA expression analysis in pediatric multiple sclerosis: an integrated approach to uncover novel pathogenic mechanisms of the disease.

PubMed

Liguori, Maria; Nuzziello, Nicoletta; Licciulli, Flavio; Consiglio, Arianna; Simone, Marta; Viterbo, Rosa Gemma; Creanza, Teresa Maria; Ancona, Nicola; Tortorella, Carla; Margari, Lucia; Grillo, Giorgio; Giordano, Paola; Liuni, Sabino; Trojano, Maria

2018-01-01

Multiple sclerosis (MS) is a complex disease of the CNS that usually affects young adults, although 3-5% of cases are diagnosed in childhood and adolescence (hence called pediatric MS, PedMS). Genetic predisposition, among other factors, seems to contribute to the risk of the onset, in pediatric as in adult ages, but few studies have investigated the genetic 'environmentally naïve' load of PedMS. The main goal of this study was to identify circulating markers (miRNAs), target genes (mRNAs) and functional pathways associated with PedMS; we also verified the impact of miRNAs on clinical features, i.e. disability and cognitive performances. The investigation was performed in 19 PedMS and 20 pediatric controls (PCs) using a High-Throughput Next-generation Sequencing (HT-NGS) approach followed by an integrated bioinformatics/biostatistics analysis. Twelve miRNAs were significantly upregulated (let-7a-5p, let-7b-5p, miR-25-3p, miR-125a-5p, miR-942-5p, miR-221-3p, miR-652-3p, miR-182-5p, miR-185-5p, miR-181a-5p, miR-320a, miR-99b-5p) and 1 miRNA was downregulated (miR-148b-3p) in PedMS compared with PCs. The interactions between the significant miRNAs and their targets uncovered predicted genes (i.e. TNFSF13B, TLR2, BACH2, KLF4) related to immunological functions, as well as genes involved in autophagy-related processes (i.e. ATG16L1, SORT1, LAMP2) and ATPase activity (i.e. ABCA1, GPX3). No significant molecular profiles were associated with any PedMS demographic/clinical features. Both miRNAs and mRNA expressions predicted the phenotypes (PedMS-PC) with an accuracy of 92% and 91%, respectively. In our view, this original strategy of contemporary miRNA/mRNA analysis may help to shed light in the genetic background of the disease, suggesting further molecular investigations in novel pathogenic mechanisms. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Measuring the costs of outreach motivational interviewing for smoking cessation and relapse prevention among low-income pregnant women

PubMed Central

Ruger, Jennifer Prah; Emmons, Karen M; Kearney, Margaret H; Weinstein, Milton C

2009-01-01

Background Economic theory provides the philosophical foundation for valuing costs in judging medical and public health interventions. When evaluating smoking cessation interventions, accurate data on costs are essential for understanding resource consumption. Smoking cessation interventions, for which prior data on resource costs are typically not available, present special challenges. We develop a micro-costing methodology for estimating the real resource costs of outreach motivational interviewing (MI) for smoking cessation and relapse prevention among low-income pregnant women and report results from a randomized controlled trial (RCT) employing the methodology. Methodological standards in cost analysis are necessary for comparison and uniformity in analysis across interventions. Estimating the costs of outreach programs is critical for understanding the economics of reaching underserved and hard-to-reach populations. Methods Randomized controlled trial (1997-2000) collecting primary cost data for intervention. A sample of 302 low-income pregnant women was recruited from multiple obstetrical sites in the Boston metropolitan area. MI delivered by outreach health nurses vs. usual care (UC), with economic costs as the main outcome measures. Results The total cost of the MI intervention for 156 participants was $48,672 or $312 per participant. The total cost of $311.8 per participant for the MI intervention compared with a cost of $4.82 per participant for usual care, a difference of $307 ([CI], $289.2 to $322.8). The total fixed costs of the MI were $3,930 and the total variable costs of the MI were $44,710. The total expected program costs for delivering MI to 500 participants would be 147,430, assuming no economies of scale in program delivery. The main cost components of outreach MI were intervention delivery, travel time, scheduling, and training. Conclusion Grounded in economic theory, this methodology systematically identifies and measures resource utilization, using a process tracking system and calculates both component-specific and total costs of outreach MI. The methodology could help improve collection of accurate data on costs and estimates of the real resource costs of interventions alongside clinical trials and improve the validity and reliability of estimates of resource costs for interventions targeted at underserved and hard-to-reach populations. PMID:19775455

Experimental uncertainty survey and assessment. [Space Shuttle Main Engine testing

NASA Technical Reports Server (NTRS)

Coleman, Hugh W.

1992-01-01

An uncertainty analysis and assessment of the specific impulse determination during Space Shuttle Main Engine testing is reported. It is concluded that in planning and designing tests and in interpreting the results of tests, the bias and precision components of experimental uncertainty should be considered separately. Recommendations for future research efforts are presented.

Positive radionuclide imaging of miRNA expression using RILES and the human sodium iodide symporter as reporter gene is feasible and supports a protective role of miRNA-23a in response to muscular atrophy

PubMed Central

Simion, Viorel; Sobilo, Julien; Clemoncon, Rudy; Natkunarajah, Sharuja; Ezzine, Safia; Abdallah, Florence; Lerondel, Stephanie; Pichon, Chantal

2017-01-01

MicroRNAs (miRNAs) are key players in many biological processes and are considered as an emerging class of pharmacology drugs for diagnosis and therapy. However to fully exploit the therapeutic potential of miRNAs, it is becoming crucial to monitor their expression pattern using medical imaging modalities. Recently, we developed a method called RILES, for RNAi-Inducible Luciferase Expression System that relies on an engineered regulatable expression system to switch-ON the expression of the luciferase gene when a miRNA of interest is expressed in cells. Here we investigated whether replacing the luciferase reporter gene with the human sodium iodide symporter (hNIS) reporter gene will be also suited to monitor the expression of miRNAs in a clinical setting context. We provide evidence that radionuclide imaging of miRNA expression using hNIS is feasible although it is not as robust as when the luciferase reporter gene is used. However, under appropriate conditions, we monitored the expression of several miRNAs in cells, in the liver and in the tibialis anterior muscle of mice undergoing muscular atrophy. We demonstrated that radiotracer accumulation in transfected cells correlated with the induction of hNIS and with the expression of miRNAs detected by real time PCR. We established the kinetic of miRNA-23a expression in mice and demonstrated that this miRNA follows a biphasic expression pattern characterized by a loss of expression at a late time point of muscular atrophy. At autopsy, we found an opposite expression pattern between miRNA-23a and one of the main transcriptional target of this miRNA, APAF-1, and as downstream target, Caspase 9. Our results report the first positive monitoring of endogenously expressed miRNAs in a nuclear medicine imaging context and support the development of additional work to establish the potential therapeutic value of miRNA-23 to prevent the damaging effects of muscular atrophy. PMID:28493972

Positive radionuclide imaging of miRNA expression using RILES and the human sodium iodide symporter as reporter gene is feasible and supports a protective role of miRNA-23a in response to muscular atrophy.

PubMed

Simion, Viorel; Sobilo, Julien; Clemoncon, Rudy; Natkunarajah, Sharuja; Ezzine, Safia; Abdallah, Florence; Lerondel, Stephanie; Pichon, Chantal; Baril, Patrick

2017-01-01

MicroRNAs (miRNAs) are key players in many biological processes and are considered as an emerging class of pharmacology drugs for diagnosis and therapy. However to fully exploit the therapeutic potential of miRNAs, it is becoming crucial to monitor their expression pattern using medical imaging modalities. Recently, we developed a method called RILES, for RNAi-Inducible Luciferase Expression System that relies on an engineered regulatable expression system to switch-ON the expression of the luciferase gene when a miRNA of interest is expressed in cells. Here we investigated whether replacing the luciferase reporter gene with the human sodium iodide symporter (hNIS) reporter gene will be also suited to monitor the expression of miRNAs in a clinical setting context. We provide evidence that radionuclide imaging of miRNA expression using hNIS is feasible although it is not as robust as when the luciferase reporter gene is used. However, under appropriate conditions, we monitored the expression of several miRNAs in cells, in the liver and in the tibialis anterior muscle of mice undergoing muscular atrophy. We demonstrated that radiotracer accumulation in transfected cells correlated with the induction of hNIS and with the expression of miRNAs detected by real time PCR. We established the kinetic of miRNA-23a expression in mice and demonstrated that this miRNA follows a biphasic expression pattern characterized by a loss of expression at a late time point of muscular atrophy. At autopsy, we found an opposite expression pattern between miRNA-23a and one of the main transcriptional target of this miRNA, APAF-1, and as downstream target, Caspase 9. Our results report the first positive monitoring of endogenously expressed miRNAs in a nuclear medicine imaging context and support the development of additional work to establish the potential therapeutic value of miRNA-23 to prevent the damaging effects of muscular atrophy.

Role of bioinformatics in establishing microRNAs as modulators of abiotic stress responses: the new revolution

PubMed Central

Tripathi, Anita; Goswami, Kavita; Sanan-Mishra, Neeti

2015-01-01

microRNAs (miRs) are a class of 21–24 nucleotide long non-coding RNAs responsible for regulating the expression of associated genes mainly by cleavage or translational inhibition of the target transcripts. With this characteristic of silencing, miRs act as an important component in regulation of plant responses in various stress conditions. In recent years, with drastic change in environmental and soil conditions different type of stresses have emerged as a major challenge for plants growth and productivity. The identification and profiling of miRs has itself been a challenge for research workers given their small size and large number of many probable sequences in the genome. Application of computational approaches has expedited the process of identification of miRs and their expression profiling in different conditions. The development of High-Throughput Sequencing (HTS) techniques has facilitated to gain access to the global profiles of the miRs for understanding their mode of action in plants. Introduction of various bioinformatics databases and tools have revolutionized the study of miRs and other small RNAs. This review focuses the role of bioinformatics approaches in the identification and study of the regulatory roles of plant miRs in the adaptive response to stresses. PMID:26578966

DOE Office of Scientific and Technical Information (OSTI.GOV)

Syuhada, O. Nurfarahana; Kalaivani, N.

Sheath blight disease, caused by Rhizoctonia solani 1802/KB was screened on two rice varieties, Oryza sativaindica cultivar MR219 and Oryza sativa indica cultivar UKMRC9. The disease symptom was severe in MR219 compared to UKMRC9. Total RNA from R. solani 1802/KB, infected rice leaves of MR219 and infected rice leaves of UKMRC9 were extracted using TRIzol reagent, purified and sent for small RNA sequencing. Three miRNA libraries were generated and analyzed. The libraries generated 65 805, 78 512 and 81 325 known miRNAs respectively. The structure of miRNA of these samples was predicted. The up-regulated and down-regulated of miRNAs target genemore » prediction and its target functions were discovered and were mainly related to the growth and development of metabolism, protein transport, transcriptional regulation, stress response, and hormone signaling and electron transfer. Sheath blight-induced differential expression of known miRNAs tends to targetMYB transcription factor, F-box proteins, NBS-LRR, leucine-rich repeat receptor protein kinases and zinc finger proteins. Detecting new miRNAs and measuring the expression profiles of known miRNAs is an important tasks required for a better understanding of various biological conditions. Therefore, further analysis using Gene Ontology Slim will be conducted to deduce some biological information from the datasets obtained.« less

Addendum to NuMI shielding assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vaziri, Kamran; /Fermilab

2007-10-01

The original safety assessment and the Safety Envelope for the NuMI beam line corresponds to 400 kW of beam power. The Main Injector is currently capable of and approved for producing 500 kW of beam power2. However, operation of the NuMI beam line at 400 kW of power brings up the possibility of an occasional excursion above 400 kW due to better than usual tuning in one of the machines upstream of the NuMI beam line. An excursion above the DOE approved Safety Envelope will constitute a safety violation. The purpose of this addendum is to evaluate the radiological issuesmore » and modifications required to operate the NuMI beam line at 500 kW. This upgrade will allow 400 kW operations with a reasonable safety margin. Configuration of the NuMI beam line, boundaries, safety system and the methodologies used for the calculations are as described in the original NuMI SAD. While most of the calculations presented in the original shielding assessment were based on Monte Carlo simulations, which were based on the design geometries, most of the results presented in this addendum are based on the measurements conducted by the AD ES&H radiation safety group.« less

Existence and stability of periodic solution of a Lotka-Volterra predator-prey model with state dependent impulsive effects

NASA Astrophysics Data System (ADS)

Nie, Linfei; Peng, Jigen; Teng, Zhidong; Hu, Lin

2009-02-01

According to biological and chemical control strategy for pest, we investigate the dynamic behavior of a Lotka-Volterra predator-prey state-dependent impulsive system by releasing natural enemies and spraying pesticide at different thresholds. By using Poincaré map and the properties of the Lambert W function, we prove that the sufficient conditions for the existence and stability of semi-trivial solution and positive periodic solution. Numerical simulations are carried out to illustrate the feasibility of our main results.

Cognitive insensitivity and cognitive impulsivity as mediators of bullying continuity: Extending the psychological inertia construct to bullying behavior.

PubMed

Walters, Glenn D; Espelage, Dorothy L

2018-06-21

Psychological inertia, the process by which social-cognitive variables help maintain behavioral patterns over time, has been found to explain crime continuity. The present study sought to determine whether psychological inertia can also be used to explain continuity in bullying behavior. A group of 1,161 youth (567 male) from the Illinois Study of Bullying and Sexual Violence were surveyed 3 times over a period of 1 year in an effort to determine which of two dimensions of precriminal cognition-cognitive insensitivity (callous, self-serving) or cognitive impulsivity (reckless, emotional)-mediated the past bullying-future bullying relationship. Consistent with research on crime continuity, cognitive impulsivity mediated bullying continuity, but cognitive insensitivity did not. Congruent with research on psychological inertia and crime continuity, the main reason why cognitive insensitivity did not mediate bullying continuity was that prior bullying behavior failed to predict subsequent cognitive insensitivity. In addition to providing support for a 2-dimensional (insensitivity, impulsivity) model of bullying development, these results suggest that 1 way bullying behavior can be managed is by challenging and reducing cognitive impulsivity, which in the current study was found to be a major contributor to bullying continuity. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Influence of process conditions during impulsed electrostatic droplet formation on size distribution of hydrogel beads.

PubMed

Lewińska, Dorota; Rosiński, Stefan; Weryński, Andrzej

2004-02-01

In the medical applications of microencapsulation of living cells there are strict requirements concerning the high size uniformity and the optimal diameter, the latter dependent on the kind of therapeutic application, of manufactured gel beads. The possibility of manufacturing small size gel bead samples (diameter 300 microm and below) with a low size dispersion (less than 10%), using an impulsed voltage droplet generator, was examined in this work. The main topic was the investigation of the influence of values of electric parameters (voltage U, impulse time tau and impulse frequency f) on the quality of obtained droplets. It was concluded that, owing to the implementation of the impulse mode and regulation of tau and f values, it is possible to work in a controlled manner in the jet flow regime (U> critical voltage UC). It is also possible to obtain uniform bead samples with the average diameter, deff, significantly lower than the nozzle inner diameter dI (bead diameters 0.12-0.25 mm by dI equal to 0.3 mm, size dispersion 5-7%). Alterations of the physical parameters of the process (polymer solution physico-chemical properties, flow rate, distance between nozzle and gellifying bath) enable one to manufacture uniform gel beads in the wide range of diameters using a single nozzle.

Correlations between the disintegration of melt and the measured impulses in steam explosions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Froehlich, G.; Linca, A.; Schindler, M.

To find our correlations in steam explosions (melt water interactions) between the measured impulses and the disintegration of the melt, experiments were performed in three configurations i.e. stratified, entrapment and jet experiments. Linear correlations were detected between the impulse and the total surface of the fragments. Theoretical considerations point out that a linear correlation assumes superheating of a water layer around the fragments of a constant thickness during the fragmentation process to a constant temperature (here the homogeneous nucleation temperature of water was assumed) and a constant expansion velocity of the steam in the main expansion time. The correlation constantmore » does not depend on melt temperature and trigger pressure, but it depends on the configuration of the experiment or of a scenario of an accident. Further research is required concerning the correlation constant. For analysing steam explosion accidents the explosivity is introduced. The explosivity is a mass specific impulse. The explosivity is linear correlated with the degree of fragmentation. Knowing the degree of fragmentation with proper correlation constant the explosivity can be calculated and from the explosivity combined with the total mass of fragments the impulse is obtained which can be used to an estimation of the maximum force.« less

Ubiquinone Function in Neurospora crassa

PubMed Central

Drabikowska, Alicja K.; Kruszewska, Anna

1972-01-01

Mitochondria of cytoplasmic respiratory mutants [mi-1] (poky) and [mi-4] contain about a fourfold molar excess of ubiquinone as compared to the wild-type strain of Neurospora crassa. In the wild type and [mi-1] cultures the concentration of ubiquinone remains constant during the exponential and stationary phase of growth. In [mi-4] cultures it markedly decreases in the stationary phase. The reduction of ubiquinone by substrates is approximately the same in the three strains tested and amounts 60 to 70% of total ubiquinone present in mitochondria, independent of its absolute amount. The reduction of ubiquinone on addition of substrates is accompanied by the similar reduction of cytochrome c. These indicate that mitochondrial ubiquinone and cytochrome c are involved in processes of oxidation in Neurospora and that ubiquinone belongs mainly if not entirely to the cytochrome system of electron transport in these strains. PMID:4344917

Downregulation of miR-221-3p contributes to IL-1β-induced cartilage degradation by directly targeting the SDF1/CXCR4 signaling pathway.

PubMed

Zheng, Xin; Zhao, Feng-Chao; Pang, Yong; Li, Dong-Ya; Yao, Sheng-Cheng; Sun, Shao-Song; Guo, Kai-Jin

2017-06-01

Osteoarthritis (OA) is characterized by degradation of chondrocyte extracellular matrix (ECM). Accumulating evidence suggests that microRNAs (miRNAs) are associated with OA, but little is known of their function in chondrocyte ECM degradation. The objective of this study was to investigate the expression and function of miRNAs in OA. miRNA expression profile was determined in OA cartilage tissues and controls, employing Solexa sequencing and reverse transcription quantitative PCR (RT-qPCR). According to a modified Mankin scale, cartilage degradation was evaluated. Functional analysis of the miRNAs on chondrocyte ECM degradation was performed after miRNA transfection and IL-1β treatment. Luciferase reporter assays and western blotting were employed to determine miRNA targets. Expression of miR-221-3p was downregulated in OA cartilage tissues, which was significantly correlated with a modified Mankin scale. Through gain-of-function and loss-of-function studies, miR-221-3p was shown to significantly affect matrix synthesis gene expression and chondrocyte proliferation and apoptosis. Using SW1353 and C28I2 cells, SDF1 was identified as a target of miR-221-3p. SDF1 overexpression resulted in increased expression of catabolic genes such as MMP-13 and ADAMTS-5 in response to IL-1β, but these effects were moderated by miR-221-3p. SDF1 treatment antagonized this effect, while knockdown of SDF1 by shSDF1 induced inhibitory effects on the expression of CXCR4 and its main target genes, similar to miR-221-3p. The results indicate that upregulation of miR-221-3p could prevent IL-1β-induced ECM degradation in chondrocytes. Targeting the SDF1/CXCR4 signaling pathway may be used as a therapeutic approach for OA. miR-221-3p is downregulated in human cartilage tissues. miR-221-3p levels are associated with cartilage degeneration grade. miR-221-3p upregulation prevents IL-1β-induced ECM degradation in chondrocytes. Protection of ECM degradation by miR-223-3p occurs via SDF1/CXCR4 signaling. miR-221-3p is identified as a novel potential therapeutic target for osteoarthritis. KEY MESSAGES: miR-221-3p is downregulated in human cartilage tissues. miR-221-3p levels are associated with cartilage degeneration grade. miR-221-3p upregulation prevents IL-1β-induced ECM degradation in chondrocytes. Protection of ECM degradation by miR-223-3p occurs via SDF1/CXCR4 signaling. miR-221-3p is identified as a novel potential therapeutic target for osteoarthritis.

Direct test of static stress versus dynamic stress triggering of aftershocks

USGS Publications Warehouse

Pollitz, F.F.; Johnston, M.J.S.

2006-01-01

Aftershocks observed over time scales of minutes to months following a main shock are plausibly triggered by the static stress change imparted by the main shock, dynamic shaking effects associated with passage of seismic waves from the main shock, or a combination of the two. We design a direct test of static versus dynamic triggering of aftershocks by comparing the near-field temporal aftershock patterns generated by aseismic and impulsive events occurring in the same source area. The San Juan Bautista, California, area is ideally suited for this purpose because several events of both types of M???5 have occurred since 1974. We find that aftershock rates observed after impulsive events are much higher than those observed after aseismic events, and this pattern persists for several weeks after the event. This suggests that, at least in the near field, dynamic triggering is the dominant cause of aftershocks, and that it generates both immediate and delayed aftershock activity.

Radiosensitizing effects of miR-18a-5p on lung cancer stem-like cells via downregulating both ATM and HIF-1α.

PubMed

Chen, Xu; Wu, Lei; Li, Dezhi; Xu, Yanmei; Zhang, Luping; Niu, Kai; Kong, Rui; Gu, Jiaoyang; Xu, Zihan; Chen, Zhengtang; Sun, Jianguo

2018-06-02

Lung cancer is one of the main causes of cancer mortality globally. Most patients received radiotherapy during the course of disease. However, radioresistance generally occurs in the majority of these patients, leading to poor curative effect, and the underlying mechanism remains unclear. In the present study, miR-18a-5p expression was downregulated in irradiated lung cancer cells. Overexpression of miR-18a-5p increased the radiosensitivity of lung cancer cells and inhibited the growth of A549 xenografts after radiation exposure. Dual luciferase report system and miR-18a-5p overexpression identified ataxia telangiectasia mutated (ATM) and hypoxia inducible factor 1 alpha (HIF-1α) as the targets of miR-18a-5p. The mRNA and protein expressions of ATM and HIF-1α were dramatically downregulated by miR-18a-5p in vitro and in vivo. Clinically, plasma miR-18a-5p expression was significantly higher in radiosensitive than in radioresistant group (P < .001). The cutoff value of miR-18a-5p >2.28 was obtained from receiver operating characteristic (ROC) curve. The objective response rate (ORR) was significantly higher in miR-18a-5p-high group than in miR-18a-5p-low group (P < .001). A tendency demonstrated that the median local progression-free survival (PFS) from radiotherapy was longer in miR-18a-5p-high than in miR-18a-5p-low group (P = .082). The median overall survival (OS) from radiotherapy was numerically longer in miR-18a-5p-high than in miR-18a-5p-low group (P = .281). The sensitivity and specificity of plasma miR-18a-5p to predict radiosensitivity was 87% and 95%, respectively. Collectively, these results indicate that miR-18a-5p increases the radiosensitivity in lung cancer cells and CD133 + stem-like cells via downregulating ATM and HIF-1α expressions. Plasma miR-18a-5p would be an available indicator of radiosensitivity in lung cancer patients. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Xenosensor CAR mediates down-regulation of miR-122 and up-regulation of miR-122 targets in the liver

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kazantseva, Yuliya A.; Yarushkin, Andrei A.; Mostovich, Lyudmila A.

MiR-122 is a major hepatic microRNA, accounting for more than 70% of the total liver miRNA population. It has been shown that miR-122 is associated with liver diseases, including hepatocellular carcinoma. Mir-122 is an intergenic miRNA with its own promoter. Pri-miR-122 expression is regulated by liver-enriched transcription factors, mainly by HNF4α, which mediates the expression via the interaction with a specific DR1 site. It has been shown that phenobarbital-mediated activation of constitutive androstane receptor (CAR), xenobiotic nuclear receptor, is associated with a decrease in miR-122 in the liver. In the present study, we investigated HNF4α–CAR cross-talk in the regulation ofmore » miR-122 levels and promitogenic signalling in mouse livers. The level of miR-122 was significantly repressed by treatment with 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), which is an agonist of mouse CAR. ChIP assays demonstrated that TCPOBOP-activated CAR inhibited HNF4α transactivation by competing with HNF4α for binding to the DR1 site in the pri-miR-122 promoter. Such transcription factor replacement was strongly correlated with miR-122 down-regulation. Additionally, the decrease in miR-122 levels produced by CAR activation is accompanied by an increase in mRNA and cellular protein levels of E2f1 and its accumulation on the target cMyc gene promoter. The increase in accumulation of E2f1 on the target cMyc gene promoter is accompanied by an increase in cMyc levels and transcriptional activity. Thus, our results provide evidence to support the conclusion that CAR activation decreases miR-122 levels through suppression of HNF4α transcriptional activity and indirectly regulates the promitogenic protein cMyc. HNF4α–CAR cross-talk may provide new opportunities for understanding liver diseases and developing more effective therapeutic approaches to better drug treatments. - Highlights: • CAR activation decreased the level of miR-122 in mouse livers. • CAR decreases the miR-122 level through the suppression of HNF4α transcriptional activity. • CAR activation increases the cMyc level through the repression of miR-122.« less

Child Maltreatment, Impulsivity, and Antisocial Behavior in African-American Children: Moderation Effects from a Cumulative Dopaminergic Gene Index

PubMed Central

Thibodeau, Eric L.; Cicchetti, Dante; Rogosch, Fred A.

2015-01-01

A model examining the effects of an increasing number of maltreatment subtypes experienced on antisocial behavior, as mediated by impulsivity and moderated by a polygenic index of dopaminergic genotypes, was investigated. An African American sample of children (N = 1012, M age = 10.07) with and without maltreatment histories participated. Indicators of aggression, delinquency, and disruptive peer behavior were obtained from peer and counselor rated measures to form a latent variable of antisocial behavior; impulsivity was assessed by counselor report. Five genotypes in four dopaminergic genes (DRD4, DRD2, DAT1, and COMT) conferring heightened environmental sensitivity were combined into one polygenic index. Using SEM, a first-stage, moderated-mediation model was evaluated. Age and sex were entered as covariates, both as main effects and in interaction with maltreatment and the gene index. The model had excellent fit: χ2(32, N =1012) = 86..51, p<0.001; CFI = 0.982; TLI = 0.977; RMSEA = 0.041; SRMR = 0.022. The effect of maltreatment subtypes on antisocial behavior was partially mediated by impulsivity (β= 0.173, p<0.001), and these relations were moderated by the number of differentiating dopaminergic genotypes. Specifically, a significant GxE interaction (b = 0.016, p = 0.013) indicated that the relation between maltreatment and impulsivity was stronger as children evinced more differentiating genotypes, thereby strengthening the mediational effect of impulsivity on antisocial behavior. These findings elucidate the manner by which maltreated children develop early signs of antisocial behavior, and the genetic mechanisms involved in greater vulnerability for maladaptation in impulse-control within context of child maltreatment. PMID:26535948

The Contribution of Maternal ADHD Symptomatology, Maternal DAT1, and Home Atmosphere to Child ADHD Symptomatology at 7 Years of Age.

PubMed

Auerbach, Judith G; Zilberman-Hayun, Yael; Atzaba-Poria, Naama; Berger, Andrea

2017-04-01

Children of mothers with attention-deficit/hyperactivity disorder (ADHD) have an increased genetic and environmental risk for ADHD. The unique and interactive contributions of a maternal dopamine receptor gene (DAT1), maternal ADHD symptoms (hyperactive- impulsive, inattentive), and home atmosphere to the prediction of ADHD symptoms (hyperactive- impulsive, inattentive) in 7- year-old boys (N = 96) were examined using data from a longitudinal study of familial risk for ADHD. During the first 6 months of the study, mothers and their spouses completed a questionnaire about the mother's ADHD symptoms. Home atmosphere questionnaire data were collected 4 years later. At the 7-year assessment, mothers reported on their child's ADHD symptoms. Negative home atmosphere was significantly associated with child hyperactive-impulsive and inattentive symptoms. Maternal inattentive symptoms were significantly correlated with both child symptom dimensions. Regression models, with child genotype and maternal education controlled, showed main effects for maternal inattentive symptoms, maternal DAT1 10/10 genotype, and home atmosphere in the prediction of child inattentive symptoms. Only home atmosphere predicted child hyperactive-impulsive symptoms. There was a significant home atmosphere x maternal hyperactive-impulsive symptoms interaction in the prediction of child hyperactive-impulsive symptoms. Boys with higher levels of symptoms came from homes characterized by higher levels of negative atmosphere and had mothers with higher levels of hyperactive-impulsive symptoms. There was also a trend (p = 0.075) for a maternal DAT1 x home atmosphere interaction. Boys with higher levels of inattentive symptoms came from homes with higher levels of negative atmosphere and had mothers with the homozygous 10/10 genotype. The maternal heterozygous 9/10 genotype did not predict child symptoms.

Oscillatory Activity in the Medial Prefrontal Cortex and Nucleus Accumbens Correlates with Impulsivity and Reward Outcome

PubMed Central

Rich, P. Dylan; Nevado-Holgado, Alejo J.; Fernando, Anushka B. P.; Van Dijck, Gert; Holzhammer, Tobias; Paul, Oliver; Ruther, Patrick; Paulsen, Ole; Robbins, Trevor W.; Dalley, Jeffrey W.

2014-01-01

Actions expressed prematurely without regard for their consequences are considered impulsive. Such behaviour is governed by a network of brain regions including the prefrontal cortex (PFC) and nucleus accumbens (NAcb) and is prevalent in disorders including attention deficit hyperactivity disorder (ADHD) and drug addiction. However, little is known of the relationship between neural activity in these regions and specific forms of impulsive behaviour. In the present study we investigated local field potential (LFP) oscillations in distinct sub-regions of the PFC and NAcb on a 5-choice serial reaction time task (5-CSRTT), which measures sustained, spatially-divided visual attention and action restraint. The main findings show that power in gamma frequency (50–60 Hz) LFP oscillations transiently increases in the PFC and NAcb during both the anticipation of a cue signalling the spatial location of a nose-poke response and again following correct responses. Gamma oscillations were coupled to low-frequency delta oscillations in both regions; this coupling strengthened specifically when an error response was made. Theta (7–9 Hz) LFP power in the PFC and NAcb increased during the waiting period and was also related to response outcome. Additionally, both gamma and theta power were significantly affected by upcoming premature responses as rats waited for the visual cue to respond. In a subgroup of rats showing persistently high levels of impulsivity we found that impulsivity was associated with increased error signals following a nose-poke response, as well as reduced signals of previous trial outcome during the waiting period. Collectively, these in-vivo neurophysiological findings further implicate the PFC and NAcb in anticipatory impulsive responses and provide evidence that abnormalities in the encoding of rewarding outcomes may underlie trait-like impulsive behaviour. PMID:25333512

Impulsiveness, overactivity, and poorer sustained attention improve by chronic treatment with low doses of l-amphetamine in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD)

PubMed Central

2011-01-01

Background ADHD is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. Overactivity, impulsiveness, and inattentiveness are presently regarded as the main clinical symptoms. There is no biological marker, but there is considerable evidence to suggest that ADHD behavior is associated with poor dopaminergic and noradrenergic modulation of neuronal circuits that involve the frontal lobes. The best validated animal model of ADHD, the Spontaneously Hypertensive Rat (SHR), shows pronounced overactivity, impulsiveness, and deficient sustained attention. The primary objective of the present research was to investigate behavioral effects of a range of doses of chronic l-amphetamine on ADHD-like symptoms in the SHR. Methods The present study tested the behavioral effects of 0.75 and 2.2 mg l-amphetamine base/kg i.p. in male SHRs and their controls, the Wistar Kyoto rat (WKY). ADHD-like behavior was tested with a visual discrimination task measuring overactivity, impulsiveness and inattentiveness. Results The striking impulsiveness, overactivity, and poorer sustained attention seen during baseline conditions in the SHR were improved by chronic treatment with l-amphetamine. The dose-response curves were, however, different for the different behaviors. Most significantly, the 0.75 mg/kg dose of l-amphetamine improved sustained attention without reducing overactivity and impulsiveness. The 2.2 mg/kg dose improved sustained attention as well as reduced SHR overactivity and impulsiveness. Discussion The effects of l-amphetamine to reduce the behavioral symptoms of ADHD in the SHR were maintained over the 14 days of daily dosing with no evidence of tolerance developing. PMID:21450079

Design feasibility via ascent optimality for next-generation spacecraft

NASA Astrophysics Data System (ADS)

Miele, A.; Mancuso, S.

This paper deals with the optimization of the ascent trajectories for single-stage-sub-orbit (SSSO), single-stage-to-orbit (SSTO), and two-stage-to-orbit (TSTO) rocket-powered spacecraft. The maximum payload weight problem is studied for different values of the engine specific impulse and spacecraft structural factor. The main conclusions are that: feasibility of SSSO spacecraft is guaranteed for all the parameter combinations considered; feasibility of SSTO spacecraft depends strongly on the parameter combination chosen; not only feasibility of TSTO spacecraft is guaranteed for all the parameter combinations considered, but the TSTO payload is several times the SSTO payload. Improvements in engine specific impulse and spacecraft structural factor are desirable and crucial for SSTO feasibility; indeed, aerodynamic improvements do not yield significant improvements in payload. For SSSO, SSTO, and TSTO spacecraft, simple engineering approximations are developed connecting the maximum payload weight to the engine specific impulse and spacecraft structural factor. With reference to the specific impulse/structural factor domain, these engineering approximations lead to the construction of zero-payload lines separating the feasibility region (positive payload) from the unfeasibility region (negative payload).

Effects of Alcohol and Initial Gambling Outcomes on Within-Session Gambling Behavior

PubMed Central

Cronce, Jessica M.; Corbin, William R.

2011-01-01

Concurrent drinking and gambling is prevalent among young adults and may increase negative consequences associated with each behavior. The effects of alcohol, initial gambling outcomes, gambling-related cognitions, and impulsivity on gambling behavior were evaluated. Initial gambling outcomes, gambling-related cognitions, and impulsivity were also assessed as potential moderators of the relation between alcohol and gambling behavior. Participants (N = 130) were randomly assigned to receive active placebo or alcohol (0.84 g/kg and 0.76 g/kg for men and women, respectively) and were invited to wager on a simulated slot machine programmed to produce 1 of 3 initial outcomes (win, breakeven, or loss) before beginning a progressive loss schedule. Alcohol consumption was associated with larger average bets and more rapid loss of all available funds, though no evidence was found for predicted main effects and interactions for gambling persistence. The effect of impulsivity was moderated by beverage condition, such that higher levels of impulsivity were associated with larger average bets for participants in the placebo but not the alcohol group. Results have direct implications for individual-focused and public-health interventions. PMID:20384426

Psychopathic Personality Traits and Environmental Contexts: Differential Correlates, Gender Differences, and Genetic Mediation

PubMed Central

Hicks, Brian M.; Carlson, Marie D.; Blonigen, Daniel M.; Patrick, Christopher J.; Iacono, William G.; MGue, Matt

2011-01-01

Theorists have speculated that primary psychopathy (or Factor 1 affective-interpersonal features) is prominently heritable whereas secondary psychopathy (or Factor 2 social deviance) is more environmentally determined. We tested this differential heritability hypothesis using a large adolescent twin sample. Trait-based proxies of primary and secondary psychopathic tendencies were assessed using Multidimensional Personality Questionnaire (MPQ; Tellegen & Waller, 2008) estimates of Fearless Dominance and Impulsive Antisociality, respectively (Benning et al., 2005). The environmental contexts of family, school, peers, and stressful life events were assessed using multiple raters and methods. Consistent with prior research, MPQ Impulsive Antisociality was robustly associated with each environmental risk factor, and these associations were significantly greater than those for MPQ Fearless Dominance. However, MPQ Fearless Dominance and Impulsive Antisociality exhibited similar heritability, and genetic effects mediated the associations between MPQ Impulsive Antisociality and the environmental measures. Results were largely consistent across male and female twins. We conclude that gene-environment correlations rather than main effects of genes and environments account for the differential environmental correlates of primary and secondary psychopathy. PMID:22452762

Potential biomarkers for paclitaxel sensitivity in hypopharynx cancer cell.

PubMed

Xu, Cheng-Zhi; Shi, Run-Jie; Chen, Dong; Sun, Yi-Yuan; Wu, Qing-Wei; Wang, Tao; Wang, Pei-Hua

2013-01-01

Paclitaxel has been proved to be active in treatment and larynx preservation of HNSCC, however, the fact that about 20-40% patients do not respond to paclitaxel makes it urgent to figure out the biomarkers for paclitaxel-based treatment in Hypopharynx cancer (HPC) patients to improve the therapy effect. In this work, Fadu cells, treated or untreated with low dose of paclitaxel for 24 h, were applied to DNA microarray chips. The differential expression in mRNAs and miRs was analyzed and the network between expression-altered mRNAs and miRs was constructed. Differentially expressed genes were mainly enriched in superpathway of cholesterol biosynthesis (ACAT2, MSMO1, LSS, FDFT1 and FDPS etc.), complement system (C3, C1R, C1S, CFR and CFB etc.), interferon signaling (IFIT1, IFIT3, IFITM1 and MX1 etc.), mTOR signaling (MRAS, PRKAA2, PLD1, RND3 and EIF4A1 etc.) and IGF1 signaling (MRAS, IGFBP7, JUN and FOS etc.), most of these pathways are implicated in tumorigenesis or chemotherapy resistance. The first three pathways were predicted to be suppressed, while the last two pathways were predicted to be induced by paclitaxel, suggesting the combination therapy with mTOR inhibition and paclitaxel might be better than single one. The dramatically expression-altered miRs were miR-112, miR-7, miR-1304, miR-222*, miR-29b-1* (these five miRs were upregulated) and miR-210 (downregulated). The 26 putative target genes mediated by the 6 miRs were figured out and the miR-gene network was constructed. Furthermore, immunoblotting assay showed that ERK signaling in Fadu cells was active by low dose of paclitaxel but repressed by high dose of paclitaxel. Collectively, our data would provide potential biomarkers and therapeutic targets for paclitaxel-based therapy in HPC patients.

Potential biomarkers for paclitaxel sensitivity in hypopharynx cancer cell

PubMed Central

Xu, Cheng-Zhi; Shi, Run-Jie; Chen, Dong; Sun, Yi-Yuan; Wu, Qing-Wei; Wang, Tao; Wang, Pei-Hua

2013-01-01

Paclitaxel has been proved to be active in treatment and larynx preservation of HNSCC, however, the fact that about 20-40% patients do not respond to paclitaxel makes it urgent to figure out the biomarkers for paclitaxel-based treatment in Hypopharynx cancer (HPC) patients to improve the therapy effect. In this work, Fadu cells, treated or untreated with low dose of paclitaxel for 24 h, were applied to DNA microarray chips. The differential expression in mRNAs and miRs was analyzed and the network between expression-altered mRNAs and miRs was constructed. Differentially expressed genes were mainly enriched in superpathway of cholesterol biosynthesis (ACAT2, MSMO1, LSS, FDFT1 and FDPS etc.), complement system (C3, C1R, C1S, CFR and CFB etc.), interferon signaling (IFIT1, IFIT3, IFITM1 and MX1 etc.), mTOR signaling (MRAS, PRKAA2, PLD1, RND3 and EIF4A1 etc.) and IGF1 signaling (MRAS, IGFBP7, JUN and FOS etc.), most of these pathways are implicated in tumorigenesis or chemotherapy resistance. The first three pathways were predicted to be suppressed, while the last two pathways were predicted to be induced by paclitaxel, suggesting the combination therapy with mTOR inhibition and paclitaxel might be better than single one. The dramatically expression-altered miRs were miR-112, miR-7, miR-1304, miR-222*, miR-29b-1* (these five miRs were upregulated) and miR-210 (downregulated). The 26 putative target genes mediated by the 6 miRs were figured out and the miR-gene network was constructed. Furthermore, immunoblotting assay showed that ERK signaling in Fadu cells was active by low dose of paclitaxel but repressed by high dose of paclitaxel. Collectively, our data would provide potential biomarkers and therapeutic targets for paclitaxel-based therapy in HPC patients. PMID:24294361

miRNAs mediate SnRK1-dependent energy signaling in Arabidopsis

PubMed Central

Confraria, Ana; Martinho, Cláudia; Elias, Alexandre; Rubio-Somoza, Ignacio; Baena-González, Elena

2013-01-01

The SnRK1 protein kinase, the plant ortholog of mammalian AMPK and yeast Snf1, is activated by the energy depletion caused by adverse environmental conditions. Upon activation, SnRK1 triggers extensive transcriptional changes to restore homeostasis and promote stress tolerance and survival partly through the inhibition of anabolism and the activation of catabolism. Despite the identification of a few bZIP transcription factors as downstream effectors, the mechanisms underlying gene regulation, and in particular gene repression by SnRK1, remain mostly unknown. microRNAs (miRNAs) are 20–24 nt RNAs that regulate gene expression post-transcriptionally by driving the cleavage and/or translation attenuation of complementary mRNA targets. In addition to their role in plant development, mounting evidence implicates miRNAs in the response to environmental stress. Given the involvement of miRNAs in stress responses and the fact that some of the SnRK1-regulated genes are miRNA targets, we postulated that miRNAs drive part of the transcriptional reprogramming triggered by SnRK1. By comparing the transcriptional response to energy deprivation between WT and dcl1-9, a mutant deficient in miRNA biogenesis, we identified 831 starvation genes misregulated in the dcl1-9 mutant, out of which 155 are validated or predicted miRNA targets. Functional clustering analysis revealed that the main cellular processes potentially co-regulated by SnRK1 and miRNAs are translation and organelle function and uncover TCP transcription factors as one of the most highly enriched functional clusters. TCP repression during energy deprivation was impaired in miR319 knockdown (MIM319) plants, demonstrating the involvement of miR319 in the stress-dependent regulation of TCPs. Altogether, our data indicates that miRNAs are components of the SnRK1 signaling cascade contributing to the regulation of specific mRNA targets and possibly tuning down particular cellular processes during the stress response. PMID:23802004

Aerobic training and l-arginine supplementation promotes rat heart and hindleg muscles arteriogenesis after myocardial infarction.

PubMed

Ranjbar, Kamal; Rahmani-Nia, Farhad; Shahabpour, Elham

2016-09-01

Arteriogenesis is a main defense mechanism to prevent heart and local tissues dysfunction in occlusive artery disease. TGF-β and angiostatin have a pivotal role in arteriogenesis. We tested the hypothesis that aerobic training and l-arginine supplementation promotes cardiac and skeletal muscles arteriogenesis after myocardial infarction (MI) parallel to upregulation of TGF-β and downregulation of angiostatin. For this purpose, 4 weeks after LAD occlusion, 50 male Wistar rats were randomly distributed into five groups: (1) sham surgery without MI (sham, n = 10), (2) control-MI (Con-MI, n = 10), (3) l-arginine-MI (La-MI, n = 10), (4) exercise training-MI (Ex-MI, n = 10), and (5) exercise and l-arginine-MI (Ex + La-MI). Exercise training groups running on a treadmill for 10 weeks with moderate intensity. Rats in the l-arginine-treated groups drank water containing 4 % l-arginine. Arteriolar density with different diameters (11-25, 26-50, 51-75, and 76-150 μm), TGF-β, and angiostatin gene expression were measured in cardiac (area at risk) and skeletal (soleus and gastrocnemius) muscles. Smaller arterioles decreased in cardiac after MI. Aerobic training and l-arginine increased the number of cardiac arterioles with 11-25 and 26-50 μm diameters parallel to TGF-β overexpression. In gastrocnemius muscle, the number of arterioles/mm(2) was only increased in the 11 to 25 μm in response to training with and without l-arginine parallel to angiostatin downregulation. Soleus arteriolar density with different size was not different between experimental groups. Results showed that 10 weeks aerobic exercise training and l-arginine supplementation promotes arteriogenesis of heart and gastrocnemius muscles parallel to overexpression of TGF-β and downregulation of angiostatin in MI rats.

Dysregulated expression of microRNAs and mRNAs in pulmonary artery remodeling in ascites syndrome in broiler chickens

PubMed Central

Zhuang, Yu; Xiao, Qingyang; Cao, Huabin; Zhang, Caiying; Wang, Tiancheng; Lin, Huayuan; Guo, Xiaoquan; Hu, Guoliang

2017-01-01

Ascites syndrome (AS), also known as pulmonary artery hypertension, remains a challenging disease that severely affects both humans and broiler chickens. Pulmonary artery remodeling presents a key step in the development of AS. In this study, we obtained pulmonary artery tissues from broilers with and without AS to perform miRNA sequencing analysis, miRNA-mRNA association analysis and pathological examinations. 29 significantly differentially expressed miRNAs were found both in known and novel miRNAs with 18 up-regulated and 11 down-regulated miRNAs. Their predicted potential targets were involved in a wide range of functional clusters as indicated via GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses. The upregulation of miR-155, miR-23b-3p, miR-146b-5p and miR-146b-3p were found closely associated with the pathogenesis of pulmonary artery remodeling in AS progression. The association analysis for the miRNAs-mRNAs showed that these 29 significantly differentially expressed miRNAs regulate 162 differentially expressed target genes. Among them, 20 miRNAs correlated with 18 predicted target genes that appear to be involved in pulmonary artery remodeling, mainly in three broad physiological processes: the hypoxia sensing response (HIF1a, NHE1, STAT5 and STAT3), endothelial permeability dysfunction (CD44, TRAF2, CDK2AP1, LZTFL1, JAZF1, PEBP1, LRP1B, RPS14 and THBS2) and inflammation (MEOX2, STAT5, STAT3, IRF8, MAP3K8, IL-1BETA and TNFRSF1B). Pathological pulmonary artery remodeling in the AS broilers was consistently observed in the present study. Taken together, the current analysis further illuminates the molecular mechanism of pulmonary artery remodeling underlying AS progression. PMID:27791988

Angiotensin II receptor blocker valsartan ameliorates cardiac fibrosis partly by inhibiting miR-21 expression in diabetic nephropathy mice.

PubMed

Wang, Jinyang; Duan, Lijun; Gao, Yanbin; Zhou, Shuhong; Liu, Yongming; Wei, Suhong; An, Siqin; Liu, Jing; Tian, Liming; Wang, Shaocheng

2017-12-09

Cardiac fibrosis with diabetic nephropathy (DN) is one of major diabetic complications. miR-21 and MMP-9 were closely associated with fibrosis diseases. Angiotensin II receptor blockers (ARB) have cardioprotective effects. However, it remains unclear whether miR-21 was involved in the mechanism of cardiac fibrosis with DN by target MMP-9 and ARB ameliorates cardiac fibrosis partly by inhibiting miR-21 expression. In this study, In Situ Hybridization(ISH), RT-PCR, cell transfection, western blotting and laser confocal telescope were used, respectively. ISH showed that miR-21, concentrated in cytoplasmic foci in the proximity of the nucleus, was mainly localized in cardiac fibroblasts and at relatively low levels in cardiomyocytes within cardiac tissue with DN. RT-PCR showed that miR-21 expression was significantly enhanced in cardiac tissue with DN, accompanied by the increase of col-IV, FN, CVF, PVCA, LVMI, HWI and NT-pro-BNP (p < 0.05). Bioinformatics analysis and Luciferase reporter gene assays showed that MMP-9 was a validated target of miR-21. Furthermore, cell transfection experiments showed that miR-21 overexpression directly decreased MMP-9 expression. Interestingly, miR-21 levels in cardiac tissue was positively correlated with ACR (r = -0.870, P = 0.003), whereas, uncorrelated with SBP, HbA1C and T-Cho (p > 0.05). More importantly, ARB can significantly decrease miR-21 expression in cardiac tissue, cardiac fibroblasts and serum. Overall, our results suggested that miR-21 may contribute to the pathogenesis of cardiac fibrosis with DN by target MMP-9, and that miR-21 may be a new possible therapeutic target for ARB in cardiac fibrosis with DN. Copyright © 2017. Published by Elsevier B.V.

Identification of microRNAs regulating Escherichia coli F18 infection in Meishan weaned piglets.

PubMed

Wu, Zhengchang; Qin, Weiyun; Wu, Seng; Zhu, Guoqiang; Bao, Wenbin; Wu, Shenglong

2016-11-03

Escherichia coli F18 is mainly responsible for post-weaning diarrhea (PWD) in piglets. The molecular regulation of E. coli F18 resistance in Chinese domestic weaned piglets is still obscure. We used Meishan piglets as model animals to test their susceptibility to E. coli F18. Small RNA duodenal libraries were constructed for E. coli F18-sensitive and -resistant weaned piglets challenged with E. coli F18 and sequenced using Illumina Solexa high-throughput sequencing technology. Sequencing results showed that 3,475,231 and 37,198,259 clean reads were obtained, with 311 known miRNAs differently expressed in resistant and sensitive groups, respectively. Twenty-four miRNAs, including 15 up-regulated and 9 down-regulated, demonstrated more than a 2-fold differential expression between the F18-resistant and -sensitive piglets. Stem-loop RT-qPCR showed that miR-136, miR-196b, miR-499-5p and miR-218-3p significantly expressed in intestinal tissue (p < 0.05). KEGG pathway analysis for target genes revealed that differently expressed miRNAs were involved in infectious diseases, signal transduction and immune system pathways. Interestingly, the expression of miR-218-3p in intestinal tissue had a very significant negative correlation with target DLG5 (P < 0.01). Based on the expression correlation between miRNA and target genes analysis, we speculate that miR-218-3p targeting to DLG5, appears to be very promising candidate for miRNAs involved in response to E. coli F18 infection. The present study provides improved database information on pig miRNAs, better understanding of the genetic basis of E. coli F18 resistance in local Chinese pig breeds and lays a new foundation for identifying novel markers of E. coli F18 resistance. This article was reviewed by Neil R Smalheiser and Weixiong Zhang.

Metabolism of isorhynchophylline in rats detected by LC-MS.

PubMed

Wang, Wei; Ma, Chao-Mei; Hattori, Masao

2010-01-01

This paper investigates the metabolic fate of isorhynchophylline (ISOR) as a main bioactive oxindole alkaloid in the traditional Chinese medicine. After oral administration of ISOR to rats, plasma, bile, urine and feces were analyzed by LC-MS. Hydroxylation of ISOR and successive glucuronidation proceeded in vitro by incubation with rat liver microsomes. ISOR was identified in plasma, 11-hydroxyisorhynchophylline 11-O--D-glucuronide (MI1) and 10-hydroxyisorhynchophylline 10-O--D-glucuronide (MI2) in bile, and free 11-hydroxyisorhynchophylline (MI3) and 10-hydroxyisorhynchophylline (MI4) in urine and feces. Within 24 h, 71.6% of ISOR was excreted into the feces (in 20.0 g) and 13.8% into the urine (in 20.0 ml) of rats after oral administration of 37.5 mg/kg. Monitoring by LC-MS showed that 8.5% of ISOR was metabolized to MI3 and MI4 in a ratio of ca. 1:1. Specific inhibition of CYP isozymes indicated that CYP2D, CYP1A1/2 and CYP2C participate in ISOR hydroxylation. ISOR was involved in the circulatory system after oral administration. Cytochrome P450 (CYP) in rat liver microsomes played a key role in ISOR hydroxylation.

Fishing Into the MicroRNA Transcriptome

PubMed Central

Herkenhoff, Marcos E.; Oliveira, Arthur C.; Nachtigall, Pedro G.; Costa, Juliana M.; Campos, Vinicius F.; Hilsdorf, Alexandre W. S.; Pinhal, Danillo

2018-01-01

In the last decade, several studies have been focused on revealing the microRNA (miRNA) repertoire and determining their functions in farm animals such as poultry, pigs, cattle, and fish. These small non-protein coding RNA molecules (18–25 nucleotides) are capable of controlling gene expression by binding to messenger RNA (mRNA) targets, thus interfering in the final protein output. MiRNAs have been recognized as the main regulators of biological features of economic interest, including body growth, muscle development, fat deposition, and immunology, among other highly valuable traits, in aquatic livestock. Currently, the miRNA repertoire of some farmed fish species has been identified and characterized, bringing insights about miRNA functions, and novel perspectives for improving health and productivity. In this review, we summarize the current advances in miRNA research by examining available data on Neotropical and other key species exploited by fisheries and in aquaculture worldwide and discuss how future studies on Neotropical fish could benefit from this knowledge. We also make a horizontal comparison of major results and discuss forefront strategies for miRNA manipulation in aquaculture focusing on forward-looking ideas for forthcoming research. PMID:29616080

Canonical and non-canonical barriers facing antimiR cancer therapeutics.

PubMed

Cheng, Christopher J; Saltzman, W Mark; Slack, Frank J

2013-01-01

Once considered genetic "oddities", microRNAs (miRNAs) are now recognized as key epigenetic regulators of numerous biological processes, including some with a causal link to the pathogenesis, maintenance, and treatment of cancer. The crux of small RNA-based therapeutics lies in the antagonism of potent cellular targets; the main shortcoming of the field in general, lies in ineffective delivery. Inhibition of oncogenic miRNAs is a relatively nascent therapeutic concept, but as with predecessor RNA-based therapies, success hinges on delivery efficacy. This review will describes the canonical (e.g. pharmacokinetics and clearance, cellular uptake, endosome escape, etc.) and non-canonical (e.g. spatial localization and accessibility of miRNA, technical limitations of miRNA inhibition, off-target impacts, etc.) challenges to the delivery of antisense-based anti-miRNA therapeutics (i.e. antimiRs) for the treatment of cancer. Emphasis will be placed on how the current leading antimiR platforms-ranging from naked chemically modified oligonucleotides to nanoscale delivery vehicles-are affected by and overcome these barriers. The perplexity of antimiR delivery presents both engineering and biological hurdles that must be overcome in order to capitalize on the extensive pharmacological benefits of antagonizing tumor-associated miRNAs.

Increased risk of polycystic ovary syndrome (PCOS) associated with CC genotype of miR-146a gene variation.

PubMed

Ebrahimi, Seyed Omar; Reiisi, Somayeh; Parchami Barjui, Shahrbanou

2018-04-11

Polycystic ovary syndrome (PCOS) is an endocrinopathy in reproductive-age women believed to be affected by several genetics and environmental factors or both. Different miRNAs are one of such genetic factors that their associations with PCOS have been implicated. For instance, miR-146a that is well known for strongly regulating the immune response and inflammation was upregulated in serum plasma, follicular fluid and granulosa cells of PCOS patients. Different studies have shown that genetic changes in pre-miRNA can cause change in the expression or biological function of mature miRNA. Therefore, the main aim of this study was to investigate the association of miR-146a gene variation (rs2910164) with the susceptibility to PCOS. This study consists of 180 patients with PCOS and 192 healthy women matched by age and geographical region. Genotyping were determined by using PCR-RFLP in all subjects. The genotype frequency and allele distributions of all subjects were evaluated using Fisher's exact test directed by SPSS v.20. The genotype and allele frequencies of the miR-146a polymorphism (rs2910164) significantly differ between PCOS and healthy controls. The frequencies of CC genotype (p = .054) and 'C' allele (p = .0001) of the miR-146a variant indicated a significant incidence in cases compared to controls. Such association was obtained in co-dominant (OR = 3.16) and dominant (OR = 2.29) models. Result of this study can be proposed that women with miR-146a variation are at a higher risk for developing PCOS, which can be due to up-regulation of miR-146a.

Up-regulation of miR-95-3p in hepatocellular carcinoma promotes tumorigenesis by targeting p21 expression

PubMed Central

Ye, Jian; Yao, Yufeng; Song, Qixue; Li, Sisi; Hu, Zhenkun; Yu, Yubing; Hu, Changqing; Da, Xingwen; Li, Hui; Chen, Qiuyun; Wang, Qing K.

2016-01-01

Hepatocellular carcinoma (HCC) is one of the most common malignant cancers. To elucidate new regulatory mechanisms for heptocarcinogenesis, we investigated the regulation of p21, a cyclin-dependent kinase (CDK) inhibitor encoded by CDKN1A, in HCC. The expression level of p21 is decreased with the progression of HCC. Luciferase assays with a luciferase-p21-3′ UTR reporter and its serial deletions identified a 15-bp repressor element at the 3′-UTR of CDKN1A, which contains a binding site for miR-95-3p. Mutation of the binding site eliminated the regulatory effect of miR-95-3p on p21 expression. Posttranscriptional regulation of p21 expression by miR-95-3p is mainly on the protein level (suppression of translation). Overexpression of miR-95-3p in two different HCC cell lines, HepG2 and SMMC7721, significantly promoted cell proliferation, cell cycle progression and cell migration, whereas a miR-95-3p specific inhibitor decreased cell proliferation, cell cycle progression and cell migration. The effects of miR-95-3p on cellular functions were rescued by overexpression of p21. Overexpression of miR-95-3p promoted cell proliferation and tumor growth in HCC xenograft mouse models. Expression of miR-95-3p was significantly higher in HCC samples than in adjacent non-cancerous samples. These results demonstrate that miR-95-3p is a potential new marker for HCC and regulates hepatocarcinogenesis by directly targeting CDKN1A/p21 expression. PMID:27698442

Prediction of target genes for miR-140-5p in pulmonary arterial hypertension using bioinformatics methods.

PubMed

Li, Fangwei; Shi, Wenhua; Wan, Yixin; Wang, Qingting; Feng, Wei; Yan, Xin; Wang, Jian; Chai, Limin; Zhang, Qianqian; Li, Manxiang

2017-12-01

The expression of microRNA (miR)-140-5p is known to be reduced in both pulmonary arterial hypertension (PAH) patients and monocrotaline-induced PAH models in rat. Identification of target genes for miR-140-5p with bioinformatics analysis may reveal new pathways and connections in PAH. This study aimed to explore downstream target genes and relevant signaling pathways regulated by miR-140-5p to provide theoretical evidences for further researches on role of miR-140-5p in PAH. Multiple downstream target genes and upstream transcription factors (TFs) of miR-140-5p were predicted in the analysis. Gene ontology (GO) enrichment analysis indicated that downstream target genes of miR-140-5p were enriched in many biological processes, such as biological regulation, signal transduction, response to chemical stimulus, stem cell proliferation, cell surface receptor signaling pathways. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis found that downstream target genes were mainly located in Notch, TGF-beta, PI3K/Akt, and Hippo signaling pathway. According to TF-miRNA-mRNA network, the important downstream target genes of miR-140-5p were PPI, TGF-betaR1, smad4, JAG1, ADAM10, FGF9, PDGFRA, VEGFA, LAMC1, TLR4, and CREB. After thoroughly reviewing published literature, we found that 23 target genes and seven signaling pathways were truly inhibited by miR-140-5p in various tissues or cells; most of these verified targets were in accordance with our present prediction. Other predicted targets still need further verification in vivo and in vitro .

Computational Prediction of Alzheimer’s and Parkinson’s Disease MicroRNAs in Domestic Animals

PubMed Central

Wang, Hai Yang; Lin, Zi Li; Yu, Xian Feng; Bao, Yuan; Cui, Xiang-Shun; Kim, Nam-Hyung

2016-01-01

As the most common neurodegenerative diseases, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are two of the main health concerns for the elderly population. Recently, microRNAs (miRNAs) have been used as biomarkers of infectious, genetic, and metabolic diseases in humans but they have not been well studied in domestic animals. Here we describe a computational biology study in which human AD- and PD-associated miRNAs (ADM and PDM) were utilized to predict orthologous miRNAs in the following domestic animal species: dog, cow, pig, horse, and chicken. In this study, a total of 121 and 70 published human ADM and PDM were identified, respectively. Thirty-seven miRNAs were co-regulated in AD and PD. We identified a total of 105 unrepeated human ADM and PDM that had at least one 100% identical animal homolog, among which 81 and 54 showed 100% sequence identity with 241 and 161 domestic animal miRNAs, respectively. Over 20% of the total mature horse miRNAs (92) showed perfect matches to AD/PD-associated miRNAs. Pigs, dogs, and cows have similar numbers of AD/PD-associated miRNAs (63, 62, and 59). Chickens had the least number of perfect matches (34). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses suggested that humans and dogs are relatively similar in the functional pathways of the five selected highly conserved miRNAs. Taken together, our study provides the first evidence for better understanding the miRNA-AD/PD associations in domestic animals, and provides guidance to generate domestic animal models of AD/PD to replace the current rodent models. PMID:26954182

Pluripotent and Multipotent Stem Cells Display Distinct Hypoxic miRNA Expression Profiles

PubMed Central

Agrawal, Rahul; Dale, Tina P.; Al-Zubaidi, Mohammed A.; Benny Malgulwar, Prit; Forsyth, Nicholas R.; Kulshreshtha, Ritu

2016-01-01

MicroRNAs are reported to have a crucial role in the regulation of self-renewal and differentiation of stem cells. Hypoxia has been identified as a key biophysical element of the stem cell culture milieu however, the link between hypoxia and miRNA expression in stem cells remains poorly understood. We therefore explored miRNA expression in hypoxic human embryonic and mesenchymal stem cells (hESCs and hMSCs). A total of 50 and 76 miRNAs were differentially regulated by hypoxia (2% O2) in hESCs and hMSCs, respectively, with a negligible overlap of only three miRNAs. We found coordinate regulation of precursor and mature miRNAs under hypoxia suggesting their regulation mainly at transcriptional level. Hypoxia response elements were located upstream of 97% of upregulated hypoxia regulated miRNAs (HRMs) suggesting hypoxia-inducible-factor (HIF) driven transcription. HIF binding to the candidate cis-elements of specific miRNAs under hypoxia was confirmed by Chromatin immunoprecipitation coupled with qPCR. Role analysis of a subset of upregulated HRMs identified linkage to reported inhibition of differentiation while a downregulated subset of HRMs had a putative role in the promotion of differentiation. MiRNA-target prediction correlation with published hypoxic hESC and hMSC gene expression profiles revealed HRM target genes enriched in the cytokine:cytokine receptor, HIF signalling and pathways in cancer. Overall, our study reveals, novel and distinct hypoxia-driven miRNA signatures in hESCs and hMSCs with the potential for application in optimised culture and differentiation models for both therapeutic application and improved understanding of stem cell biology. PMID:27783707

Methylation of microRNA genes regulates gene expression in bisexual flower development in andromonoecious poplar.

PubMed

Song, Yuepeng; Tian, Min; Ci, Dong; Zhang, Deqiang

2015-04-01

Previous studies showed sex-specific DNA methylation and expression of candidate genes in bisexual flowers of andromonoecious poplar, but the regulatory relationship between methylation and microRNAs (miRNAs) remains unclear. To investigate whether the methylation of miRNA genes regulates gene expression in bisexual flower development, the methylome, microRNA, and transcriptome were examined in female and male flowers of andromonoecious poplar. 27 636 methylated coding genes and 113 methylated miRNA genes were identified. In the coding genes, 64.5% of the methylated reads mapped to the gene body region; by contrast, 60.7% of methylated reads in miRNA genes mainly mapped in the 5' and 3' flanking regions. CHH methylation showed the highest methylation levels and CHG showed the lowest methylation levels. Correlation analysis showed a significant, negative, strand-specific correlation of methylation and miRNA gene expression (r=0.79, P <0.05). The methylated miRNA genes included eight long miRNAs (lmiRNAs) of 24 nucleotides and 11 miRNAs related to flower development. miRNA172b might play an important role in the regulation of bisexual flower development-related gene expression in andromonoecious poplar, via modification of methylation. Gynomonoecious, female, and male poplars were used to validate the methylation patterns of the miRNA172b gene, implying that hyper-methylation in andromonoecious and gynomonoecious poplar might function as an important regulator in bisexual flower development. Our data provide a useful resource for the study of flower development in poplar and improve our understanding of the effect of epigenetic regulation on genes other than protein-coding genes. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

MicroRNA-19b/221/222 induces endothelial cell dysfunction via suppression of PGC-1α in the progression of atherosclerosis.

PubMed

Xue, Yunxing; Wei, Zhe; Ding, Hanying; Wang, Qiang; Zhou, Zhen; Zheng, Shasha; Zhang, Yujing; Hou, Dongxia; Liu, Yuchen; Zen, Ke; Zhang, Chen-Yu; Li, Jing; Wang, Dongjin; Jiang, Xiaohong

2015-08-01

Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a master regulator of cellular energy metabolism that is associated with many cardiovascular diseases, including atherosclerosis. However, the role and underling regulatory mechanisms of PGC-1α in the pathogenesis of atherosclerosis are not completely understood. Here, we identified the microRNAs that post-transcriptionally regulate PGC-1α production and their roles in the pathogenesis of atherosclerosis. A significant down-regulation of PGC-1α protein was observed in human atherosclerotic vessel samples. Using microarray and bioinformatics analyses, PGC-1α was identified as a common target gene of miR-19b-3p, miR-221-3p and miR-222-3p, which are mainly located in the intima of atherosclerotic vessels. In vitro induction of miR-19b-3p, miR-221-3p and miR-222-3p by the inflammatory cytokines TNFα and IFNγ may affect PGC-1α protein production and consequently result in mitochondrial dysfunction in Human Aortic Endothelial Cells (HAECs). The overexpression of miR-19b-3p, miR-221-3p and miR-222-3p in HAECs caused intracellular ROS accumulation, which led to cellular apoptosis. Taken together, these results demonstrate that PGC-1α plays a protective role against the vascular complications of atherosclerosis. Moreover, the posttranscriptional regulation of PGC-1α by miR-19b/221/222 was unveiled, which provides a novel mechanism in which a panel of microRNAs can modulate endothelial cell apoptosis via the regulation mitochondrial function. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Plasma levels of miRNA-155 as a powerful diagnostic marker for dedifferentiated liposarcoma

PubMed Central

Boro, Aleksandar; Bauer, David; Born, Walter; Fuchs, Bruno

2016-01-01

Atypic lipomatous tumors (ALT) and dedifferentiated liposarcomas (DDLS) are closely related liposarcoma subtypes, often difficult to distinguish but they exhibit an entirely different clinical outcome. Recently discovered regulatory functions of miRNAs in liposarcoma progression prompted us to investigate miRNAs as potential diagnostic biomarkers in liposarcoma with a main focus on circulating miRNAs for fast and reliable differential diagnosis. Tumor and blood samples of 35 patients with lipomatous lesions collected between June 2011 and September 2014 were analyzed by qRT-PCR. They included 10 lipomas, 7 ALT, 5 DDLS and 13 myxoid liposarcomas (MLS). Ten samples of normal fat tissue and blood from 20 healthy volunteers were used as controls. A meta-analysis of public data on miRNA expression in liposarcoma revealed 9 miRNAs with potential diagnostic power. Out of these, miRNA-155 was found significantly elevated in the circulation of DDLS patients as compared to the plasma levels detected in all other liposarcoma subtypes and in healthy subjects. miRNA-155 levels in the plasma samples correlated significantly (r=0.41, p=0.02) with those in corresponding tumor extracts. This correlation was even more pronounced in an analysis of plasma and tumor extracts of malignant liposarcoma subtypes alone (r=0.51, p=0.02). Receiver operating characteristic analysis indicated that plasma miRNA-155 levels have a high diagnostic accuracy for distinguishing DDLS from healthy subjects (AUC=0.91, p=0.005) and from lipomas (AUC=0.86, p=0.02), MLS (AUC=0.92, p=0.006) and most importantly ALT (AUC=0.91, p=0.01) patients. In conclusion, this study identified miRNA-155 as a first blood biomarker for the differential diagnosis of DDLS. PMID:27186423

Methylation of microRNA genes regulates gene expression in bisexual flower development in andromonoecious poplar

PubMed Central

Song, Yuepeng; Tian, Min; Ci, Dong; Zhang, Deqiang

2015-01-01

Previous studies showed sex-specific DNA methylation and expression of candidate genes in bisexual flowers of andromonoecious poplar, but the regulatory relationship between methylation and microRNAs (miRNAs) remains unclear. To investigate whether the methylation of miRNA genes regulates gene expression in bisexual flower development, the methylome, microRNA, and transcriptome were examined in female and male flowers of andromonoecious poplar. 27 636 methylated coding genes and 113 methylated miRNA genes were identified. In the coding genes, 64.5% of the methylated reads mapped to the gene body region; by contrast, 60.7% of methylated reads in miRNA genes mainly mapped in the 5′ and 3′ flanking regions. CHH methylation showed the highest methylation levels and CHG showed the lowest methylation levels. Correlation analysis showed a significant, negative, strand-specific correlation of methylation and miRNA gene expression (r=0.79, P <0.05). The methylated miRNA genes included eight long miRNAs (lmiRNAs) of 24 nucleotides and 11 miRNAs related to flower development. miRNA172b might play an important role in the regulation of bisexual flower development-related gene expression in andromonoecious poplar, via modification of methylation. Gynomonoecious, female, and male poplars were used to validate the methylation patterns of the miRNA172b gene, implying that hyper-methylation in andromonoecious and gynomonoecious poplar might function as an important regulator in bisexual flower development. Our data provide a useful resource for the study of flower development in poplar and improve our understanding of the effect of epigenetic regulation on genes other than protein-coding genes. PMID:25617468

DETAIL OF EAST (CANADIAN) CANTILEVER AND ANCHOR ARMS OF MAIN ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

DETAIL OF EAST (CANADIAN) CANTILEVER AND ANCHOR ARMS OF MAIN SPAN, SHOWING PIER C. VIEW TO NORTH. - Blue Water Bridge, Spanning St. Clair River at I-69, I-94, & Canadian Route 402, Port Huron, St. Clair County, MI

EAST (CANADIAN) PORTAL OF MAIN SECTION OF BRIDGE, SHOWING PANEL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

EAST (CANADIAN) PORTAL OF MAIN SECTION OF BRIDGE, SHOWING PANEL OVER PIER C IN CENTER. VIEW TO WEST. - Blue Water Bridge, Spanning St. Clair River at I-69, I-94, & Canadian Route 402, Port Huron, St. Clair County, MI

miR-221 stimulates breast cancer cells and cancer-associated fibroblasts (CAFs) through selective interference with the A20/c-Rel/CTGF signaling.

PubMed

Santolla, Maria Francesca; Lappano, Rosamaria; Cirillo, Francesca; Rigiracciolo, Damiano Cosimo; Sebastiani, Anna; Abonante, Sergio; Tassone, Pierfrancesco; Tagliaferri, Pierosandro; Di Martino, Maria Teresa; Maggiolini, Marcello; Vivacqua, Adele

2018-05-02

MicroRNA (miRNAs) are non-coding small RNA molecules that regulate gene expression by inhibiting the translation of target mRNAs. Among several dysregulated miRNAs in human cancer, the up-regulation of miR-221 has been associated with development of a variety of hematologic and solid malignancies. In this study, we investigated the involvement of miR-221 in breast cancer. TaqMan microRNA assay was used to detect the miR-221 levels in normal cells and in MDA-MB 231 and SkBr3 breast cancer cells as well as in main players of the tumor microenvironment, namely cancer-associated fibroblasts (CAFs). miR-221 mimic sequence and locked nucleic acid (LNA)-i-miR-221 construct were used to induce or inhibit, respectively, the miR-221 expression in cells used. Quantitative PCR and western blotting analysis were performed to evaluate the levels of the miR-221 target gene A20 (TNFAIP3), as well as the member of the NF-kB complex namely c-Rel and the connective tissue growth factor (CTGF). Chromatin immunoprecipitation (ChIP) assay was performed to ascertain the recruitment of c-Rel to the CTFG promoter. Finally, the cell growth and migration in the presence of LNA-i-miR-221 or silencing c-Rel and CTGF by specific short hairpin were assessed by cell count, colony formation and boyden chambers assays. Statistical analysis was performed by ANOVA. We first demonstrated that LNA-i-miR-221 inhibits both endogenous and ectopic expression of miR-221 in our experimental models. Next, we found that the A20 down-regulation, as well as the up-regulation of c-Rel induced by miR-221 were no longer evident using LNA-i-miR-221. Moreover, we established that the miR-221 dependent recruitment of c-Rel to the NF-kB binding site located within the CTGF promoter region is prevented by using LNA-i-miR-221. Furthermore, we determined that the up-regulation of CTGF mRNA and protein levels by miR-221 is no longer evident using LNA-i-miR221 and silencing c-Rel. Finally, we assessed that cell growth and migration induced by miR-221 in MDA-MB 231 and SkBr3 breast cancer cells as well as in CAFs are abolished by LNAi-miR-221 and silencing c-Rel or CTGF. Overall, these data provide novel insights into the stimulatory action of miR-221 in breast cancer cells and CAFs, suggesting that its inhibition may be considered toward targeted therapeutic approaches in breast cancer patients.

Effects of exposure to Streptococcus iniae on microRNA expression in the head kidney of genetically improved farmed tilapia (Oreochromis niloticus).

PubMed

Qiang, Jun; Tao, Fanyi; He, Jie; Sun, Lanyi; Xu, Pao; Bao, Wenjin

2017-02-20

Genetically improved farmed tilapia (GIFT, Oreochromis niloticus) are susceptible to infection by Streptococcus iniae when maintained in modern intensive culture systems. GIFT are commercially important fishes that are cultured widely in southern China. The role of microRNAs (miRNAs) in the regulatory response of GIFT to S. iniae infection has been underestimated and has not yet been well studied. Head kidney has an important immune function in teleost fishes. The main aim of this study was to determine the possible function of miRNAs in head kidney of S. iniae-infected GIFT. MiRNAs are small, non-coding RNAs that regulate gene expression by binding to the 3'-untranslated regions of their target mRNAs. MiRNAs are known to regulate immune-regulated signaling and inflammatory response pathways. High-throughput deep sequencing of two libraries (control group [CO] and infected group [IN]) of RNA extracted from GIFT head kidney tissues generated 12,089,630 (CO) and 12,624,975 (IN) clean reads. Bioinformatics analysis identified 1736 and 1729 conserved miRNAs and 164 and 165 novel miRNAs in the CO and IN libraries, respectively. Three miRNAs (miR-310-3p, miR-92, and miR-127) were found to be up-regulated and four miRNAs (miR-92d-3p, miR-375-5p, miR-146-3p, and miR-694) were found to be down-regulated in the S. iniae-infected GIFT. The expressions of these miRNAs were verified by quantitative real-time PCR. RNAhybrid and TargetScan were used to identify complementary miRNA and mRNA target sites, and the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were used to annotate and predict potential downstream regulation of biological pathways. Seven target genes, which encode immune-related proteins (complement C3, cytidine deaminase, regulator of G-protein Rgs22, mitogen-activated protein kinase Mapk1, metabotropic glutamate receptorm GluR8, calcium-sensing receptor CaSR, and microtubule-associated protein Map1S) were predicted to play crucial roles in the GIFT response to S. iniae infection. S. iniae outbreaks have hindered the development of the tilapia industry in China. Understanding the miRNA transcriptome of S. iniae-infected GIFT is important for exploring the immune responses regulated by miRNAs as well as for studying novel regulated networks to prevent and treat S. iniae infections in the future.

Genome-wide identification of conserved and novel microRNAs in one bud and two tender leaves of tea plant (Camellia sinensis) by small RNA sequencing, microarray-based hybridization and genome survey scaffold sequences.

PubMed

Jeyaraj, Anburaj; Zhang, Xiao; Hou, Yan; Shangguan, Mingzhu; Gajjeraman, Prabu; Li, Yeyun; Wei, Chaoling

2017-11-21

MicroRNAs (miRNAs) are important for plant growth and responses to environmental stresses via post-transcriptional regulation of gene expression. Tea, which is primarily produced from one bud and two tender leaves of the tea plant (Camellia sinensis), is one of the most popular non-alcoholic beverages worldwide owing to its abundance of secondary metabolites. A large number of miRNAs have been identified in various plants, including non-model species. However, due to the lack of reference genome sequences and/or information of tea plant genome survey scaffold sequences, discovery of miRNAs has been limited in C. sinensis. Using small RNA sequencing, combined with our recently obtained genome survey data, we have identified and analyzed 175 conserved and 83 novel miRNAs mainly in one bud and two tender leaves of the tea plant. Among these, 93 conserved and 18 novel miRNAs were validated using miRNA microarray hybridization. In addition, the expression pattern of 11 conserved and 8 novel miRNAs were validated by stem-loop-qRT-PCR. A total of 716 potential target genes of identified miRNAs were predicted. Further, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that most of the target genes were primarily involved in stress response and enzymes related to phenylpropanoid biosynthesis. The predicted targets of 4 conserved miRNAs were further validated by 5'RLM-RACE. A negative correlation between expression profiles of 3 out of 4 conserved miRNAs (csn-miR160a-5p, csn-miR164a, csn-miR828 and csn-miR858a) and their targets (ARF17, NAC100, WER and MYB12 transcription factor) were observed. In summary, the present study is one of few such studies on miRNA detection and identification in the tea plant. The predicted target genes of majority of miRNAs encoded enzymes, transcription factors, and functional proteins. The miRNA-target transcription factor gene interactions may provide important clues about the regulatory mechanism of these miRNAs in the tea plant. The data reported in this study will make a huge contribution to knowledge on the potential miRNA regulators of the secondary metabolism pathway and other important biological processes in C. sinensis.

Smoke-induced microRNA and related proteome alterations. Modulation by chemopreventive agents.

PubMed

De Flora, Silvio; Balansky, Roumen; D'Agostini, Francesco; Cartiglia, Cristina; Longobardi, Mariagrazia; Steele, Vernon E; Izzotti, Alberto

2012-12-15

Dysregulation of microRNAs (miRNAs) has important consequences on gene and protein expression since a single miRNA targets a number of genes simultaneously. This article provides a review of published data and ongoing studies regarding the effects of cigarette smoke (CS), either mainstream (MCS) or environmental (ECS), on the expression of miRNAs and related proteins. The results generated in mice, rats, and humans provided evidence that exposure to CS results in an intense dysregulation of miRNA expression in the respiratory tract, which is mainly oriented in the sense of downregulation. In parallel, there was an upregulation of proteins targeted by the downregulated miRNAs. These trends reflect an attempt to defend the respiratory tract by means of antioxidant mechanisms, detoxification of carcinogens, DNA repair, anti-inflammatory pathways, apoptosis, etc. However, a long-lasting exposure to CS causes irreversible miRNA alterations that activate carcinogenic mechanisms, such as modulation of oncogenes and oncosuppressor genes, cell proliferation, recruitment of undifferentiated stem cells, inflammation, inhibition of intercellular communications, angiogenesis, invasion, and metastasis. The miRNA alterations induced by CS in the lung of mice and rats are similar to those observed in the human respiratory tract. Since a number of miRNAs that are modulated by CS and/or chemopreventive agents are subjected to single nucleotide polymorphisms in humans, they can be evaluated according to toxicogenomic/pharmacogenomics approaches. A variety of cancer chemopreventive agents tested in our laboratory modulated both baseline and CS-related miRNA and proteome alterations, thus contributing to evaluate both safety and efficacy of dietary and pharmacological agents. Copyright © 2012 UICC.

In Silico Identification of OncomiRs in Different Cancer Types

NASA Astrophysics Data System (ADS)

Bhattacharyya, Malay; Bandyopadhyay, Sanghamitra

2012-03-01

The diagnosis, prognosis and therapeutics of various kinds of cancers are challenging domains of research. Current landmark of cancer research at the molecular level mainly focuses on the regulation of genes for studying cancer pathways. Recent investigations highlight that there is a significant association of a class of short RNAs in the progression of different types of cancer. In this paper, the involvement of microRNAs (miRNAs), a type of small endogenous RNAs, is explored in two categories of cancers in human, one tumor-based and another non-tumorous. A new approach of in silico identification of the miRNAs that might be associated with these cancer types is proposed. The oncomiRs, miRNAs associated with cancer, are identified by analyzing the differentially co-expressed miRNAs and further exploring how they cooperate with each other. Extensive computational analysis on miRNA expression profiles for the discovery of novel oncomiRs is pursued. The results are found to be promising by going deep into the regulatory information available on oncogenes from the up-to-date literature. Some of the miRNAs as oncogenic are identified by the approach like hsa-miR-186 and hsa-miR-154 for leukemia and prostate cancer, respectively, which are not included in standard databases. However, some of the emerging studies give evidences to these findings. Statistical and biological studies, on the other hand, strengthen the effectiveness of the proposed method in futuristic investigations for the exploration of undiscovered oncomiRs. On the whole, these analyses provide insight into the discovery of miRNA markers.

MicroRNA-17-5p contributes to osteoarthritis progression by binding p62/SQSTM1.

PubMed

Li, Huihui; Miao, Daoyi; Zhu, Qi; Huang, Jianghua; Lu, Guangxian; Xu, Weiguo

2018-02-01

Autophagy has been reported to be widely involved in the pathogenesis of osteoarthritis (OA). Increasing evidence suggested the important role of microRNAs (miRs) in the progression of OA. However, the functional role of miR-17-5p in OA development has remained to be fully elucidated. First, a mouse model of OA was established and the relative level of miR-17-5p was determined using PCR. Safranin O-fast green staining was applied to determine cartilage degeneration. TargetScan software and a dual luciferase reporter assay were applied to determine potential target genes of miR-17-5P. Autophagy measurement was performed using green fluorescent protein-microtubule-associated protein 1 light chain 3 (LC3) dot analysis. The results demonstrated that the relative expression of miR-17-5p was significantly decreased in OA model mice. In addition, the level of miR-17-5p was decreased in SW1353 human chondrosarcoma cells treated with interleukin-1β. Furthermore, autophagy was found to be suppressed in the knee joints of experimental OA model mice. The dual luciferase reporter assay confirmed that p62/sequestosome 1 was a target gene of miR-17-5p. Of note, miR-17-5p inhibitor-induced reduction of LC3 dots was markedly reversed by knockdown of p62 in SW1353 cells. In conclusion, decreased miR-17-5p expression in chondrocytes induced autophagy mainly through suppressing the expression of p62, thereby contributing to OA progression.

Effects of MicroRNA-23a on Differentiation and Gene Expression Profiles in 3T3-L1 Adipocytes

PubMed Central

Huang, Yong; Huang, Jinxiu; Qi, Renli; Wang, Qi; Wu, Yongjiang; Wang, Jing

2016-01-01

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate growth, development, and programmed death of cells. A newly-published study has shown that miRNA-23a could regulate 3T3-L1 adipocyte differentiation. Here, we identified miRNA-23a as a negative regulator of 3T3-L1 adipocyte differentiation again. Over-expression of miRNA-23a inhibited differentiation and decreased lipogenesis as well as down-regulated mRNA and protein expression of both peroxisome proliferator-activated receptor (PPAR) γ and fatty acid binding protein (FABP) 4, whereas knock down of miRNA-23a showed the opposite effects on differentiation as well as increasing the number of apoptotic cells. Additionally, digital gene expression profiling sequencing (DGE-Seq) was used to assay changes in gene expression profiles following alterations in the level of miR-23a. In total, over-expression or knock down of miRNA-23a significantly changed the expression of 313 and 425 genes, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that these genes were mainly involved in the stress response, immune system, metabolism, cell cycle, among other pathways. Additionally, the signal transducer and activator of transcription 1 (Stat1) was shown to be a target of miRNA-23a by computational and dual-luciferase reporter assays that indicated Janus Kinase (Jak)-Stat signal pathway was implicated in regulating adipogenesis mediated by miRNA-23a in adipocytes. PMID:27783036

Dopamine risk and paternal ADHD symptomatology associated with ADHD symptoms in four and a half-year-old boys.

PubMed

Auerbach, Judith G; Atzaba-Poria, Naama; Berger, Andrea; Landau, Rivka; Arbelle, Shoshana; Raz, Yael; Ebstein, Richard

2010-08-01

This study examined the influence of allelic variation in two dopamine genes, the dopamine receptor D4 (DRD4) gene and the dopamine transporter D1 (DAT1) gene, and paternal attention-deficit hyperactivity disorder (ADHD) symptomatology on the level of ADHD symptoms in 96 four and a half-year-old boys. DNA was collected by means of a buccal swab and genotyped for DRD4 and DAT1. Mothers completed the Dupaul ADHD checklist on their sons. ADHD symptomatology ratings for fathers were based on a summed father self-reported and spouse-reported symptoms (Conners Adult ADHD Rating Scale). There were main effects for DAT1 and father symptomatology for the child Total ADHD and Hyperactivity-Impulsivity scores. The main effects for DRD4 were limited to the child Hyperactivity-Impulsivity scores. Child Inattentive scores were influenced only by father symptomatology. Interaction effects between DAT1 and DRD4 and between DAT1 and the father ADHD risk group were found for child Hyperactivity-Impulsivity scores. Boys with the highest level of symptomatology were those with the 10/10 DAT1 genotype and the DRD4-7 genotype or fathers with high symptomatology. The findings of this study indicate that the risk for ADHD, particularly hyperactivity-impulsivity, is exacerbated in the presence of dopamine risk genes and paternal ADHD symptomatology. This study adds to the growing literature on the efficacy of including multiple genetic and environmental risk factors in studies related to the development of psychopathology.

Characterization of miR-122-independent propagation of HCV

PubMed Central

Motooka, Daisuke; Nakamura, Shota; Yamamoto, Satomi; Mori, Hiroyuki; Sato, Asuka; Uemura, Kentaro; Fauzyah, Yuzy; Suda, Takahiro; Nishio, Akira; Hmwe, Su Su; Okamoto, Toru; Tatsumi, Tomohide; Takehara, Tetsuo; Chayama, Kazuaki; Wakita, Takaji; Koike, Kazuhiko

2017-01-01

miR-122, a liver-specific microRNA, is one of the determinants for liver tropism of hepatitis C virus (HCV) infection. Although miR-122 is required for efficient propagation of HCV, we have previously shown that HCV replicates at a low rate in miR-122-deficient cells, suggesting that HCV-RNA is capable of propagating in an miR-122-independent manner. We herein investigated the roles of miR-122 in both the replication of HCV-RNA and the production of infectious particles by using miR-122-knockout Huh7 (Huh7-122KO) cells. A slight increase of intracellular HCV-RNA levels and infectious titers in the culture supernatants was observed in Huh7-122KO cells upon infection with HCV. Moreover, after serial passages of HCV in miR-122-knockout Huh7.5.1 cells, we obtained an adaptive mutant, HCV122KO, possessing G28A substitution in the 5’UTR of the HCV genotype 2a JFH1 genome, and this mutant may help to enhance replication complex formation, a possibility supported by polysome analysis. We also found the introduction of adaptive mutation around miR-122 binding site in the genotype 1b/2a chimeric virus, which originally had an adenine at the nucleotide position 29. HCV122KO exhibited efficient RNA replication in miR-122-knockout cells and non-hepatic cells without exogenous expression of miR-122. Competition assay revealed that the G28A mutant was dominant in the absence of miR-122, but its effects were equivalent to those of the wild type in the presence of miR-122, suggesting that the G28A mutation does not confer an advantage for propagation in miR-122-rich hepatocytes. These observations may explain the clinical finding that the positive rate of G28A mutation was higher in miR-122-deficient PBMCs than in the patient serum, which mainly included the hepatocyte-derived virus from HCV-genotype-2a patients. These results suggest that the emergence of HCV mutants that can propagate in non-hepatic cells in an miR-122-independent manner may participate in the induction of extrahepatic manifestations in chronic hepatitis C patients. PMID:28494029

microRNAs and Their Targets in Apple (Malus domestica cv. "Fuji") Involved in Response to Infection of Pathogen Valsa mali.

PubMed

Feng, Hao; Xu, Ming; Zheng, Xiang; Zhu, Tongyi; Gao, Xiaoning; Huang, Lili

2017-01-01

miRNAs are important regulators involving in plant-pathogen interactions. However, their roles in apple tree response to Valsa canker pathogen ( Valsa mali, Vm ) infection were poorly understood. In this study, we constructed two miRNA libraries using the twig bark tissues of apple tree ( Malus domestica Borkh. cv. "Fuji") inoculated with Vm (IVm) and PDA medium (control, BMd). Among all detected miRNAs, 23 miRNAs were specifically isolated from BMd and 39 miRNAs were specifically isolated from IVm. Meanwhile, the expression of 294 miRNAs decreased; and another 172 miRNAs showed an increased expression trend in IVm compared with that in BMd. Furthermore, two degradome sequencing libraries were also constructed to identify the target genes of these miRNAs. In total, 353 differentially expressed miRNAs between IVm and BMd were detected to be able to target 1,077 unigenes with 2,251 cleavage sites. Based on GO and KEGG analysis, these genes were found to be mainly related to transcription regulation and signal transduction. In addition, we selected 17 miRNAs and 22 corresponding target genes to screen the expression profiles when apple twigs were infected by Vm . The expression trends of most miRNAs/target genes were consist with the results of deep sequencing. Many of them may involve in the apple twig- Vm interaction by inducing/reducing their expression. What's more, miRNAs and their target genes regulate the apple twig- Vm interaction by forming many complicated regulation networks rather than one to one model. It is worth that a conserved miRNAs mdm-miR482b, which was down regulated in IVm compared with BMd, has 14 potential target genes, most of which are disease resistance related genes. This indicates that mdm-miR482b may play important roles in apple twig response to Vm . More important, the feedback regulation of sRNA pathway in apple twig is also very complex, and play critical role in the interaction between apple twig and Vm based on the results of expression analysis. In all, the results will provide insights into the crucial functions of miRNAs in the woody plant, apple tree- Vm interaction.

microRNAs and Their Targets in Apple (Malus domestica cv. “Fuji”) Involved in Response to Infection of Pathogen Valsa mali

PubMed Central

Feng, Hao; Xu, Ming; Zheng, Xiang; Zhu, Tongyi; Gao, Xiaoning; Huang, Lili

2017-01-01

miRNAs are important regulators involving in plant-pathogen interactions. However, their roles in apple tree response to Valsa canker pathogen (Valsa mali, Vm) infection were poorly understood. In this study, we constructed two miRNA libraries using the twig bark tissues of apple tree (Malus domestica Borkh. cv. “Fuji”) inoculated with Vm (IVm) and PDA medium (control, BMd). Among all detected miRNAs, 23 miRNAs were specifically isolated from BMd and 39 miRNAs were specifically isolated from IVm. Meanwhile, the expression of 294 miRNAs decreased; and another 172 miRNAs showed an increased expression trend in IVm compared with that in BMd. Furthermore, two degradome sequencing libraries were also constructed to identify the target genes of these miRNAs. In total, 353 differentially expressed miRNAs between IVm and BMd were detected to be able to target 1,077 unigenes with 2,251 cleavage sites. Based on GO and KEGG analysis, these genes were found to be mainly related to transcription regulation and signal transduction. In addition, we selected 17 miRNAs and 22 corresponding target genes to screen the expression profiles when apple twigs were infected by Vm. The expression trends of most miRNAs/target genes were consist with the results of deep sequencing. Many of them may involve in the apple twig-Vm interaction by inducing/reducing their expression. What's more, miRNAs and their target genes regulate the apple twig-Vm interaction by forming many complicated regulation networks rather than one to one model. It is worth that a conserved miRNAs mdm-miR482b, which was down regulated in IVm compared with BMd, has 14 potential target genes, most of which are disease resistance related genes. This indicates that mdm-miR482b may play important roles in apple twig response to Vm. More important, the feedback regulation of sRNA pathway in apple twig is also very complex, and play critical role in the interaction between apple twig and Vm based on the results of expression analysis. In all, the results will provide insights into the crucial functions of miRNAs in the woody plant, apple tree-Vm interaction. PMID:29270184

MiRroring the Multiple Potentials of MicroRNAs in Acute Myocardial Infarction

PubMed Central

Paiva, Solenne; Agbulut, Onnik

2017-01-01

At present, cardiovascular diseases are depicted to be the leading cause of death worldwide according to the World Health Organization. In the future, projections predict that ischemic heart disease will persist in the top main causes of illness. Within this alarming context, some tiny master regulators of gene expression programs, namely, microRNAs (miRNAs) carry three promising potentials. In fact, miRNAs can prove to be useful not only in terms of biomarkers allowing heart injury detection but also in terms of therapeutics to overcome limitations of past strategies and treat the lesions. In a more creative approach, they can even be used in the area of human engineered cardiac tissues as maturation tools for cardiomyocytes (CMs) derived from pluripotent stem cell. Very promising not only for patient-specific cell-based therapies but also to develop biomimetic microsystems for disease modeling and drug screening, these cells greatly contribute to personalized medicine. To get into the heart of the matter, the focus of this review lies primarily on miRNAs as acute myocardial infarction (AMI) biomarkers. Only large cohort studies comprising over 100 individuals to reach a potent statistical value were considered. Certain miRNAs appeared to possibly complement protein-based biomarkers and classical risk factors. Some were even described to bear potential in the discrimination of similar symptomatic pathologies. However, differences between pre-analytical and analytical approaches substantially influenced miRNA data. Further supported by meta-analysis studies, this problem had to be addressed. A detailed critical analysis of each step to define miRNAs biomarker potential is provided to inspire a future improved universal strategy. Interestingly, a recurrent set of cardiomyocyte-enriched miRNAs was found, namely, miR-1; miR-133; miR-208a/b; and miR-499a. Each member of this myomiRs group displayed promising roles either individually or in combination as AMI diagnostic or prognostic biomarkers. Furthermore, a precise combo was shown to be powerful enough to transdifferentiate human fibroblasts into CMs opening doors in the therapeutics. Following these discoveries, they also emerged as optional tools to transfect in order to mature CMs derived from pluripotent stem cells. Ultimately, the multiple potentials carried by the myomiRs miR-1; miR-133; miR-208a/b; and miR-499a still remain to be fully unveiled. PMID:29209617

Occupations at risk of developing contact allergy to isothiazolinones in Danish contact dermatitis patients: results from a Danish multicentre study (2009-2012).

PubMed

Schwensen, Jakob F; Menné, Torkil; Andersen, Klaus E; Sommerlund, Mette; Johansen, Jeanne D

2014-11-01

In recent years, the prevalence of contact allergy to isothiazolinones has reached epidemic levels. Few studies have presented data on occupations at risk of developing contact allergy to isothiazolinones. To present demographics and examine risk factors for sensitization to methylisothiazolinone (MI), methylchloroisothiazolinone (MCI) in combination with MI and benzisothiazolinone (BIT) in Danish dermatitis patients. A retrospective epidemiological analysis of data from three Danish hospitals departments was conducted. All patients consecutively patch tested with MI, MCI/MI and BIT between 2009 and 2013 were included. MI contact allergy showed a significantly increased trend in prevalence from 1.8% in 2009 to 4.2% in 2012 (p < 0.001). Females with facial dermatitis mainly drove the increase in 2012. Adjusted logistic regression analysis showed that MI sensitization was significantly associated with occupational exposures, hand and facial dermatitis, age > 40 years, and the occupational groups of tile setters/terrazzo workers, machine operators, and painters. MCI/MI contact allergy was significantly associated with the following high-risk occupations: painting, welding (blacksmiths), machine operating, and cosmetology. The occupational group of painting was frequent in the group of patients with BIT contact allergy. Several high-risk occupations for sensitization to isothiazolinones exist. Regulation on the allowed concentration of isothiazolinones, and especially MI, in both consumer products and industrial products is needed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Suppression of SIK1 by miR-141 in human ovarian cancer cell lines and tissues.

PubMed

Chen, Jin-Long; Chen, Fang; Zhang, Ting-Ting; Liu, Nai-Fu

2016-06-01

Epithelial ovarian cancer (EOC), the sixth most common cancer in women worldwide, is the most commonly fatal gynecologic malignancy in developed countries. One of the main reasons for this is that relatively little was known about the molecular events responsible for the development of this highly aggressive disease. In the present study, we demonstrated that salt‑inducible kinase 1 (SIK1; which is also known as MSK/SIK/SNF1LK) was downregulated in ovarian cancer tissue samples. Using HEY ovarian cancer cells, we noted that SIK1 overexpression inhibited proliferation as well as cancer stem cell-associated traits. Silencing SIK1 promoted the proliferation of the EG ovarian cancer cell line. We performed an analysis of potential microRNAs (miRNAs or miRs) target sites using three commonly used prediction algorithms: miRanda, TargetScan and PicTar. All three algorithms predicted that miR-141 targets the 3'UTR of SIK1. Subsequent experiments not only confirmed this prediction, but also showed that miR-141 was associated with the progression of this disease. Finally, we found that miR-141 promoted proliferation of EG cells, whereas silencing miR-141 restored SIK1 expression and inhibited the proliferation of the HEY cells. Elucidating the molecular mechanism of ovarian cancer not only enables us to further understand the pathogenesis and progression of the disease, but also provides new targets for effective therapies.

Transition Crossing in the Main Injector for PIP-II

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ainsworth, R.; Chaurize, S.; Kourbanis, I.

2017-05-01

Proton Improvement Plan-II (PIP-II) [1] is Fermilab’s plan for providing powerful, high-intensity proton beams to the laboratory’s experiments. PIP II will include upgrades to the Booster, Recycler and Main Injector which will be required to accelerate 50% more beam as well as increasing the Booster repetition rate from 15 to 20 Hz. To accommodate the faster rate, the momentum separation of the slip stacking beams in the Recycler must increase which will result in in larger longitudinal emittance bunches in MI. In order to cross transition without losses, it is expected a gamma-t jump will be needed. Gamma-t jump schemesmore » for the MI are investigated.« less

Transition Crossing in the Main Injector for PIP-II

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ainsworth, R.; Chaurize, S.; Kourbanis, I.

2017-01-01

Proton Improvement Plan-II (PIP-II) is Fermilab’s plan for providing powerful, high-intensity proton beams to the laboratory’s experiments. PIP II will include upgrades to the Booster, Recycler and Main Injector which will be required to accelerate 50% more beam as well as increasing the Booster repetition rate from 15 to 20 Hz. To accommodate the faster rate, the momentum separation of the slip stacking beams in the Recycler must increase which will result in in larger longitudinal emittance bunches in MI. In order to cross transition without losses, it is expected a gammat jump will be needed. Gamma-t jump schemes formore » the MI are investigated« less

Autonomic nervous system correlates in movement observation and motor imagery

PubMed Central

Collet, C.; Di Rienzo, F.; El Hoyek, N.; Guillot, A.

2013-01-01

The purpose of the current article is to provide a comprehensive overview of the literature offering a better understanding of the autonomic nervous system (ANS) correlates in motor imagery (MI) and movement observation. These are two high brain functions involving sensori-motor coupling, mediated by memory systems. How observing or mentally rehearsing a movement affect ANS activity has not been extensively investigated. The links between cognitive functions and ANS responses are not so obvious. We will first describe the organization of the ANS whose main purposes are controlling vital functions by maintaining the homeostasis of the organism and providing adaptive responses when changes occur either in the external or internal milieu. We will then review how scientific knowledge evolved, thus integrating recent findings related to ANS functioning, and show how these are linked to mental functions. In turn, we will describe how movement observation or MI may elicit physiological responses at the peripheral level of the autonomic effectors, thus eliciting autonomic correlates to cognitive activity. Key features of this paper are to draw a step-by step progression from the understanding of ANS physiology to its relationships with high mental processes such as movement observation or MI. We will further provide evidence that mental processes are co-programmed both at the somatic and autonomic levels of the central nervous system (CNS). We will thus detail how peripheral physiological responses may be analyzed to provide objective evidence that MI is actually performed. The main perspective is thus to consider that, during movement observation and MI, ANS activity is an objective witness of mental processes. PMID:23908623

Paeonol Suppresses Chondrosarcoma Metastasis through Up-Regulation of miR-141 by Modulating PKCδ and c-Src Signaling Pathway

PubMed Central

Horng, Chi-Ting; Shieh, Po-Chuen; Tan, Tzu-Wei; Yang, Wei-Hung; Tang, Chih-Hsin

2014-01-01

Chondrosarcoma, a primary malignant bone cancer, has potential for local invasion and distant metastasis, especially to the lungs. Patients diagnosed with it show poor prognosis. Paeonol (2'-hydroxy-4'-methoxyacetophenone), the main active compound of traditional Chinese remedy Paeonia lactiflora Pallas, exhibits anti-inflammatory and anti-tumor activity; whether paeonol regulates metastatic chondrosarcoma is largely unknown. Here, we find paeonol do not increase apoptosis. By contrast, at non-cytotoxic concentrations, paeonol suppresses migration and invasion of chondrosarcoma cells. We also demonstrate paeonol enhancing miR-141 expression and miR-141 inhibitor reversing paeonol-inhibited cell motility; paeonol also reduces protein kinase C (PKC)δ and c-Src kinase activity. Since paeonol inhibits migration and invasion of human chondrosarcoma via up-regulation of miR-141 via PKCδ and c-Src pathways, it thus might be a novel anti-metastasis agent for treatment of metastatic chondrosarcoma. PMID:24992595

Micro-RNA-126 Reduces the Blood Thrombogenicity in Diabetes Mellitus via Targeting of Tissue Factor.

PubMed

Witkowski, Marco; Weithauser, Alice; Tabaraie, Termeh; Steffens, Daniel; Kränkel, Nicolle; Witkowski, Mario; Stratmann, Bernd; Tschoepe, Diethelm; Landmesser, Ulf; Rauch-Kroehnert, Ursula

2016-06-01

Diabetes mellitus involves vascular inflammatory processes and is a main contributor to cardiovascular mortality. Notably, heightened levels of circulating tissue factor (TF) account for the increased thrombogenicity and put those patients at risk for thromboembolic events. Here, we sought to investigate the role of micro-RNA (miR)-driven TF expression and thrombogenicity in diabetes mellitus. Plasma samples of patients with diabetes mellitus were analyzed for TF protein and activity as well as miR-126 expression before and after optimization of the antidiabetic treatment. We found low miR-126 levels to be associated with markedly increased TF protein and TF-mediated thrombogenicity. Reduced miR-126 expression was accompanied by increased vascular inflammation as evident from the levels of vascular adhesion molecule-1 and fibrinogen, as well as leukocyte counts. With optimization of the antidiabetic treatment miR-126 levels increased and thrombogenicity was reduced. Using a luciferase reporter system, we demonstrated miR-126 to directly bind to the F3-3'-untranslated region, thereby reducing TF expression both on mRNA and on protein levels in human microvascular endothelial cells as well as TF mRNA and activity in monocytes. Circulating miR-126 exhibits antithrombotic properties via regulating post-transcriptional TF expression, thereby impacting the hemostatic balance of the vasculature in diabetes mellitus. © 2016 The Authors.

miR-133b down-regulates ABCC1 and enhances the sensitivity of CRC to anti-tumor drugs.

PubMed

Chen, Miao; Li, Daojiang; Gong, Ni; Wu, Hao; Su, Chen; Xie, Canbin; Xiang, Hong; Lin, Changwei; Li, Xiaorong

2017-08-08

Multidrug resistance (MDR) is the main cause of failed chemotherapy treatments. Therefore, preventing MDR is pivotal in treating colorectal cancer (CRC). In a previous study miR-133b was shown to be a tumor suppressor. Additionally, in CRC cells transfected with miR-133b, ATP-binding cassette (ABC) subfamily C member 1(ABCC1) was shown to be significantly down regulated. Whether miR-133b also enhances the chemosensitivity of drugs used to treat CRC by targeting ABCC1 is still unclear. Here, we utilized flow cytometry and high-performance liquid chromatography (HPLC) analysis to identify the ability of miR-133b to reserve MDR in CRC. We then used a dual-luciferase reporter assay to validate that miR-133b targets ABCC1. Further in vivo experiments were designed to validate the method in which miR-133b reversed MDR in CRC cells. The results demonstrated that the level of miR-133b was down-regulated and the expression of ABCC1 was up-regulated in drug-resistant CRC cells compared to non-drug-resistant CRC cells. The restoration of miR-133b expression in CRC drug-resistant cells in vitro resulted in reduced IC50s to chemotherapeutic drugs, significantly induced G1 accumulation, inhibited growth and promoted necrosis in combination with either 5-fluorouracil (5-FU) or vincristine (VCR), and decreased the expression of ABCC1. The dual-luciferase assay demonstrated that miR-133b directly targets ABCC1. The combination of agomiRNA-133b with chemotherapeutic drugs in vivo inhibited tumor growth induced by CRC drug-resistant cells. A xenograft from the in vivo model resulted in up-regulated levels of miR-133b and down-regulated levels of ABCC1. Therefore, miR-133b enhances the chemosensitivity of CRC cells to anti-tumor drugs by directly down-regulating ABCC1. This discovery provides a therapeutic strategy in which miR-133b is used as a potential sensitizer for drug-resistant CRC.

Plasma profile of microRNA after supplementation with high doses of vitamin D3 for 12 months

PubMed Central

2012-01-01

Background Recently a large number of short non-coding-RNAs (microRNAs, (miRNA)) have been identified. These miRNAs act as post-transcriptional regulators where they generally have an inhibitory function. miRNAs are present in all human cells, and they are also detected in serum or plasma. The miRNAs have a broad range of actions, and their biogenesis must therefore be under tight control. One putative regulator of miRNA biogenesis or miRNA level could be vitamin D, an ancient hormone with effects on cell growth and differentiation, apoptosis and the immune system. In our study miRNA were reversed transcribed in total RNA isolated from plasma and analyzed by quantitative real-time PCR (qPCR) using the miRCURY LNA Universal RT microRNA PCR system (Exiqon). In 10 pilot subjects 136 miRNAs were detected in one or more plasma samples drawn at baseline and after 12 months of vitamin D supplementation. The twelve miRNAs that showed the greatest change in expression in these pilots were further analyzed by RT-qPCR of RNA from baseline and 12 months plasma samples in 40 subjects given high dose vitamin D3 (20.000 – 40.000 IU per week) and 37 subjects given placebo. Results At baseline there was a significant and positive correlation between serum 25-hydroxyvitamin D and miR-532-3p expression (r = 0.24, P = 0.04). The change in expression of miR-221 from baseline to 12 months (ddCp value) was also significantly different between the vitamin D and placebo group (P =0.04), mainly due to a change in the placebo group. Conclusions We have not been able to demonstrate a consistent effect of vitamin D supplementation on the expression profile of miRNA in plasma. However, further studies are needed as this approach might potentially throw light on unknown aspects of vitamin D physiology. PMID:22594500

Altered miR-193a-5p expression in children with cow's milk allergy.

PubMed

D'Argenio, V; Del Monaco, V; Paparo, L; De Palma, F D E; Nocerino, R; D'Alessio, F; Visconte, F; Discepolo, V; Del Vecchio, L; Salvatore, F; Berni Canani, R

2018-02-01

Cow's milk allergy (CMA) is one of the most common food allergies in children. Epigenetic mechanisms have been suggested to play a role in CMA pathogenesis. We have shown that DNA methylation of Th1/Th2 cytokine genes and FoxP3 affects CMA disease course. Preliminary evidence suggests that also the miRNome could be implicated in the pathogenesis of allergy. Main study outcome was to comparatively evaluate miRNome in children with CMA and in healthy controls. Peripheral blood mononuclear cells were obtained from children aged 4-18 months: 10 CMA patients, 9 CMA patients who outgrew CMA, and 11 healthy controls. Small RNA libraries were sequenced using a next-generation sequencing-based approach. Functional assessment of IL-4 expression was also performed. Among the miRNAs differently expressed, 2 were upregulated and 14 were downregulated in children with active CMA compared to healthy controls. miR-193a-5p resulted the most downregulated miRNA in children with active CMA compared to healthy controls. The predicted targets of miR-193a-5p resulted upregulated in CMA patients compared to healthy controls. Peripheral blood CD4 + T cells transfected with a miR193a-5 inhibitor showed a significant upregulation of IL-4 mRNA and its protein expression. Children who outgrew CMA showed miRNA-193a-5p level, and its related targets expression, similar to that observed in healthy controls. Our results suggest that miR-193a-5p is a post-transcriptional regulator of IL-4 expression and could have a role in IgE-mediated CMA. This miRNA could be a novel diagnostic and therapeutic target for this common form of food allergy in childhood. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

MicroRNA-17-92 cluster promotes the proliferation and the chemokine production of keratinocytes: implication for the pathogenesis of psoriasis.

PubMed

Zhang, Weigang; Yi, Xiuli; An, Yawen; Guo, Sen; Li, Shuli; Song, Pu; Chang, Yuqian; Zhang, Shaolong; Gao, Tianwen; Wang, Gang; Li, Chunying

2018-05-11

Keratinocytes are the main epidermal cell type that constitutes the skin barrier against environmental damages, which emphasizes the balance between the growth and the death of keratinocytes in maintaining skin homeostasis. Aberrant proliferation of keratinocytes and the secretion of inflammatory factors from keratinocytes are related to the formation of chronic inflammatory skin diseases like psoriasis. MicroRNA-17-92 (miRNA-17-92 or miR-17-92) is a miRNA cluster that regulates cell growth and immunity, but the role of miR-17-92 cluster in keratinocytes and its relation to skin diseases have not been well investigated. In the present study, we initially found that miR-17-92 cluster promoted the proliferation and the cell-cycle progression of keratinocytes via suppressing cyclin-dependent kinase inhibitor 2B (CDKN2B). Furthermore, miR-17-92 cluster facilitated the secretion of C-X-C motif chemokine ligand 9 (CXCL9) and C-X-C motif chemokine ligand 10 (CXCL10) from keratinocytes by inhibiting suppressor of cytokine signaling 1 (SOCS1), which enhanced the chemotaxis for T lymphocytes formed by keratinocytes. In addition, we detected increased expression of miR-17-92 cluster in psoriatic lesions and the level of lesional miR-17-92 cluster was positively correlated with the disease severity in psoriasis patients. At last, miR-17-92 cluster was increased in keratinocytes by cytokines through the activation of signal transducers and activators of transcription 1 (STAT1) signaling pathway. Our findings demonstrate that cytokine-induced overexpression of miR-17-92 cluster can promote the proliferation and the immune function of keratinocytes, and thus may contribute to the development of inflammatory skin diseases like psoriasis, which implicates miR-17-92 cluster as a potential therapeutic target for psoriasis and other skin diseases with similar inflammatory pathogenesis.

Up-Regulation of MicroRNA-190b Plays a Role for Decreased IGF-1 That Induces Insulin Resistance in Human Hepatocellular Carcinoma

PubMed Central

Hung, Tzu-Min; Ho, Cheng-Maw; Liu, Yen-Chun; Lee, Jia-Ling; Liao, Yow-Rong; Wu, Yao-Ming; Ho, Ming-Chih; Chen, Chien-Hung; Lai, Hong-Shiee; Lee, Po-Huang

2014-01-01

Background & Aims Insulin-like growth factor, (IGF)-1, is produced mainly by the liver and plays important roles in promoting growth and regulating metabolism. Previous study reported that development of hepatocellular carcinoma (HCC) was accompanied by a significant reduction in serum IGF-1 levels. Here, we hypothesized that dysregulation of microRNAs (miRNA) in HCC can modulate IGF-1 expression post-transcriptionally. Methods The miRNAs expression profiles in a dataset of 29 HCC patients were examined using illumina BeadArray. Specific miRNA (miR)-190b, which was significantly up-regulated in HCC tumor tissues when compared with paired non-tumor tissues, was among those predicted to interact with 3′-untranslated region (UTR) of IGF-1. In order to explore the regulatory effects of miR-190b on IGF-1 expression, luciferase reporter assay, quantitative real-time PCR, western blotting and immunofluorecence analysis were performed in HCC cells. Results Overexpression of miR-190b in Huh7 cells attenuated the expression of IGF-1, whereas inhibition of miR-190b resulted in up-regulation of IGF-1. Restoration of IGF-1 expression reversed miR-190b-mediated impaired insulin signaling in Huh7 cells, supporting that IGF-1 was a direct and functional target of miR-190b. Additionally, low serum IGF-1 level was associated with insulin resistance and poor overall survival in HCC patients. Conclusions Increased expression of miR-190 may cause decreased IGF-1 in HCC development. Insulin resistance appears to be a part of the physiopathologic significance of decreased IGF-1 levels in HCC progression. This study provides a novel miRNA-mediated regulatory mechanism for controlling IGF-1 expression in HCC and elucidates the biological relevance of this interaction in HCC. PMID:24586785

miR-15a/16 Enhances Radiation Sensitivity of Non-Small Cell Lung Cancer Cells by Targeting the TLR1/NF-κB Signaling Pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lan, Fengming; Radiation Oncology Department, Tianjin Hospital, Tianjin; Yue, Xiao

2015-01-01

Purpose: Many miRNAs have been identified as essential issues and core determining factors in tumor radiation. Recent reports have demonstrated that miRNAs and Toll-like receptors could exert reciprocal effects to control cancer development in various ways. However, a novel role of miR-15a/16 in enhancing radiation sensitivity by directly targeting TLR1 has not been reported, to our knowledge. Methods and Materials: Bioinformatic analyses, luciferase reporter assay, biochemical assays, and subcutaneous tumor establishment were used to characterize the signaling pathways of miRNA-15a/16 in response to radiation treatment. Results: First, an inverse correlation between the expression of miR-15a/16 and TLR1 protein was revealedmore » in non-small cell lung cancer (NSCLC) and normal lung tissues. Next, we corroborated that miR-15a/16 specifically bound to TLR1 3′UTR and inhibited the expression of TLR1 in H358 and A549 cells. Furthermore, miR-15a/16 downregulated the activity of the NF-κB signaling pathway through TLR1. In addition, overexpression of miR-15a/16 inhibited survival capability and increased radiation-induced apoptosis, resulting in enhancement of radiosensitivity in H358 and A549 cells. Finally, subcutaneous tumor bearing NSCLC cells in a nude mice model was established, and the results showed that combined groups (miR-15a/16 + radiation) inhibited tumor growth more significantly than did radiation alone. Conclusions: We mainly elucidate that miRNA-15a/16 can enhance radiation sensitivity by regulating the TLR1/NF-κB signaling pathway and act as a potential therapeutic approach to overcome radioresistance for lung cancer treatment.« less

Identification of MicroRNAs and their Targets Associated with Embryo Abortion during Chrysanthemum Cross Breeding via High-Throughput Sequencing.

PubMed

Zhang, Fengjiao; Dong, Wen; Huang, Lulu; Song, Aiping; Wang, Haibin; Fang, Weimin; Chen, Fadi; Teng, Nianjun

2015-01-01

MicroRNAs (miRNAs) are important regulators in plant development. They post-transcriptionally regulate gene expression during various biological and metabolic processes by binding to the 3'-untranslated region of target mRNAs to facilitate mRNA degradation or inhibit translation. Chrysanthemum (Chrysanthemum morifolium) is one of the most important ornamental flowers with increasing demand each year. However, embryo abortion is the main reason for chrysanthemum cross breeding failure. To date, there have been no experiments examining the expression of miRNAs associated with chrysanthemum embryo development. Therefore, we sequenced three small RNA libraries to identify miRNAs and their functions. Our results will provide molecular insights into chrysanthemum embryo abortion. Three small RNA libraries were built from normal chrysanthemum ovules at 12 days after pollination (DAP), and normal and abnormal chrysanthemum ovules at 18 DAP. We validated 228 miRNAs with significant changes in expression frequency during embryonic development. Comparative profiling revealed that 69 miRNAs exhibited significant differential expression between normal and abnormal embryos at 18 DAP. In addition, a total of 1037 miRNA target genes were predicted, and their annotations were defined by transcriptome data. Target genes associated with metabolic pathways were most highly represented according to the annotation. Moreover, 52 predicted target genes were identified to be associated with embryonic development, including 31 transcription factors and 21 additional genes. Gene ontology (GO) annotation also revealed that high-ranking miRNA target genes related to cellular processes and metabolic processes were involved in transcription regulation and the embryo developmental process. The present study generated three miRNA libraries and gained information on miRNAs and their targets in the chrysanthemum embryo. These results enrich the growing database of new miRNAs and lay the foundation for the further understanding of miRNA biological function in the regulation of chrysanthemum embryo abortion.

Human cardiomyocyte calcium handling and transverse tubules in mid-stage of post-myocardial-infarction heart failure.

PubMed

Høydal, Morten Andre; Kirkeby-Garstad, Idar; Karevold, Asbjørn; Wiseth, Rune; Haaverstad, Rune; Wahba, Alexander; Stølen, Tomas L; Contu, Riccardo; Condorelli, Gianluigi; Ellingsen, Øyvind; Smith, Godfrey L; Kemi, Ole J; Wisløff, Ulrik

2018-06-01

Cellular processes in the heart rely mainly on studies from experimental animal models or explanted hearts from patients with terminal end-stage heart failure (HF). To address this limitation, we provide data on excitation contraction coupling, cardiomyocyte contraction and relaxation, and Ca 2+ handling in post-myocardial-infarction (MI) patients at mid-stage of HF. Nine MI patients and eight control patients without MI (non-MI) were included. Biopsies were taken from the left ventricular myocardium and processed for further measurements with epifluorescence and confocal microscopy. Cardiomyocyte function was progressively impaired in MI cardiomyocytes compared with non-MI cardiomyocytes when increasing electrical stimulation towards frequencies that simulate heart rates during physical activity (2 Hz); at 3 Hz, we observed almost total breakdown of function in MI. Concurrently, we observed impaired Ca 2+ handling with more spontaneous Ca 2+ release events, increased diastolic Ca 2+ , lower Ca 2+ amplitude, and prolonged time to diastolic Ca 2+ removal in MI (P < 0.01). Significantly reduced transverse-tubule density (-35%, P < 0.01) and sarcoplasmic reticulum Ca 2+ adenosine triphosphatase 2a (SERCA2a) function (-26%, P < 0.01) in MI cardiomyocytes may explain the findings. Reduced protein phosphorylation of phospholamban (PLB) serine-16 and threonine-17 in MI provides further mechanisms to the reduced function. Depressed cardiomyocyte contraction and relaxation were associated with impaired intracellular Ca 2+ handling due to impaired SERCA2a activity caused by a combination of alteration in the PLB/SERCA2a ratio and chronic dephosphorylation of PLB as well as loss of transverse tubules, which disrupts normal intracellular Ca 2+ homeostasis and handling. This is the first study that presents these mechanisms from viable and intact cardiomyocytes isolated from the left ventricle of human hearts at mid-stage of post-MI HF. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Circular RNA participates in the carcinogenesis and the malignant behavior of cancer.

PubMed

Zhao, Zhen-Jun; Shen, Jun

2017-05-04

Circular RNAs (circRNAs) are long, non-coding RNAs that result from the non-canonical splicing of linear pre-mRNAs. However, the characteristics and the critical role of circRNA in co-/post-transcriptional regulation were not well recognized until the "microRNA sponge" function of circRNA is discovered. Recent studies have mainly been devoted to the function of the circular RNA sponge for miR-7 (ciRS-7) and sex-determining region Y (SRY) by targeting microRNA-7 (miR-7) and microRNA-138 (miR-138), respectively. In this review, we illustrate the specific role of circRNAs in a wide variety of cancers and in regulating the biological behavior of cancers via miR-7 or miR-138 regulation. Furthermore, circRNA, together with its gene silencing ability, also shows its potential in RNA interference (RNAi) therapy by binding to target RNAs, which provides a novel perspective in cancer treatment. Thus, this review concerns the biogenesis, biological function, oncogenesis, progression and possible therapies for cancer involving circRNAs.

Circular RNA participates in the carcinogenesis and the malignant behavior of cancer

PubMed Central

Zhao, Zhen-Jun; Shen, Jun

2017-01-01

Abstract Circular RNAs (circRNAs) are long, non-coding RNAs that result from the non-canonical splicing of linear pre-mRNAs. However, the characteristics and the critical role of circRNA in co-/post-transcriptional regulation were not well recognized until the “microRNA sponge” function of circRNA is discovered. Recent studies have mainly been devoted to the function of the circular RNA sponge for miR-7 (ciRS-7) and sex-determining region Y (SRY) by targeting microRNA-7 (miR-7) and microRNA-138 (miR-138), respectively. In this review, we illustrate the specific role of circRNAs in a wide variety of cancers and in regulating the biological behavior of cancers via miR-7 or miR-138 regulation. Furthermore, circRNA, together with its gene silencing ability, also shows its potential in RNA interference (RNAi) therapy by binding to target RNAs, which provides a novel perspective in cancer treatment. Thus, this review concerns the biogenesis, biological function, oncogenesis, progression and possible therapies for cancer involving circRNAs. PMID:26649774

Initiation of geyser during the resettlement of cryogenic liquid under impulsive reverse gravity acceleration in microgravity environment

NASA Technical Reports Server (NTRS)

Hung, R. J.; Shyu, K. L.

1991-01-01

The requirement to settle or to position liquid fluid over the outlet end of spacecraft propellant tank prior to main engine restart poses a microgravity fluid behavior problem. Resettlement or reorientation of liquid propellant can be accomplished by providing optimal acceleration to the spacecraft such that the propellant is reoriented over the tank outlet without any vapor entrainment, any excessive geysering, or any other undesirable fluid motion for the space fluid management under microgravity environment. The purpose of present study is to investigate most efficient technique for propellant resettling through the minimization of propellant usage and weight penalties. Comparison between the constant reverse gravity acceleration and impulsive reverse gravity acceleration to be used for the activation of propellant resettlement, it shows that impulsive reverse gravity thrust is superior to constant reverse gravity thrust for liquid reorientation in a reduced gravity environment.

Walking dynamics of the passive compass-gait model under OGY-based control: Emergence of bifurcations and chaos

NASA Astrophysics Data System (ADS)

Gritli, Hassène; Belghith, Safya

2017-06-01

An analysis of the passive dynamic walking of a compass-gait biped model under the OGY-based control approach using the impulsive hybrid nonlinear dynamics is presented in this paper. We describe our strategy for the development of a simplified analytical expression of a controlled hybrid Poincaré map and then for the design of a state-feedback control. Our control methodology is based mainly on the linearization of the impulsive hybrid nonlinear dynamics around a desired nominal one-periodic hybrid limit cycle. Our analysis of the controlled walking dynamics is achieved by means of bifurcation diagrams. Some interesting nonlinear phenomena are displayed, such as the period-doubling bifurcation, the cyclic-fold bifurcation, the period remerging, the period bubbling and chaos. A comparison between the raised phenomena in the impulsive hybrid nonlinear dynamics and the hybrid Poincaré map under control was also presented.

Molecular imaging and neural networks in impulse control disorders in Parkinson's disease.

PubMed

Aracil-Bolaños, I; Strafella, A P

2016-01-01

Impulse control disorders (ICDs) may arise in Parkinson's disease (PD) in relation to the use of dopamine agonists (DA). A dysfunction of reward circuits is considered the main underlying mechanism. Neuroimaging has been largely used in this setting to understand the structure of the reward system and its abnormalities brought by exogenous stimulation in PD. Dopaminergic changes, such as increased dopamine release, reduced dopamine transporter activity and other changes, have been shown to be a consistent feature of ICDs in PD. Beyond the striatum, alterations of prefrontal cortical function may also impact an individuals' propensity for impulsivity. Neuroimaging is advancing our knowledge of the mechanisms involved in the development of these behavioral addictions. An increased understanding of these disorders may lead to the discovery of new therapeutic targets, or the identification of risk factors for the development of these disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

78 FR 11185 - Notice to All Interested Parties of the Termination of the Receiverships of 10016 Main Street...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-15

... Receiverships of 10016 Main Street Bank, Northville, MI Notice is hereby given that the Federal Deposit Insurance Corporation (``FDIC'') as Receiver for Main Street Bank, Northville, Michigan (``the Receiver... Bank on October 10, 2008. The liquidation of the receivership assets has been completed. To the extent...

Laboratory studies of near-grazing impulsive sound propagating over rough water.

PubMed

Qin, Qin; Lukaschuk, Sergei; Attenborough, Keith

2008-08-01

Acoustic impulses due to an electrical spark source (main acoustic energy near 15 kHz) have been measured after propagating near to the water surface in a shallow container resting on a vibrating platform. Control of the platform vibration enabled control of water wave amplitudes. Analysis of the results reveals systematic variations in the received acoustic waveforms as the mean trough-to-crest water wave amplitude is increased up to 7 mm. The amplitudes of the peaks corresponding to specular reflections are reduced and the variability in the tails of the waveforms is increased.

Microwave and hard X-ray emissions during the impulsive phase of solar flares: Nonthermal electron spectrum and time delay

NASA Technical Reports Server (NTRS)

Gu, Ye-Ming; Li, Chung-Sheng

1986-01-01

On the basis of the summing-up and analysis of the observations and theories about the impulsive microwave and hard X-ray bursts, the correlations between these two kinds of emissions were investigated. It is shown that it is only possible to explain the optically-thin microwave spectrum and its relations with the hard X-ray spectrum by means of the nonthermal source model. A simple nonthermal trap model in the mildly-relativistic case can consistently explain the main characteristics of the spectrum and the relative time delays.

Hostile Attributional Bias, Negative Emotional Responding, and Aggression in Adults: Moderating Effects of Gender and Impulsivity

PubMed Central

Chen, Pan; Coccaro, Emil F.; Jacobson, Kristen C.

2012-01-01

The current study examined the main effects of hostile attributional bias (HAB) and negative emotional responding on a variety of aggressive behaviors in adults, including general aggression, physical aggression, relational aggression, and verbal aggression. Effects of both externalizing (anger) and internalizing (embarrassment/upset) negative emotions were considered. In addition, the moderating roles of gender and impulsivity on the effects of HAB and negative emotional responding were explored. Multilevel models were fitted to data from 2,749 adult twins aged 20–55 from the PennTwins cohort. HAB was positively associated with all four forms of aggression. There was also a significant interaction between impulsivity and HAB for general aggression. Specifically, the relationship between HAB and general aggression was only significant for individuals with average or above-average levels of impulsivity. Negative emotional responding was also found to predict all measures of aggression, although in different ways. Anger was positively associated with all forms of aggression, whereas embarrassment/upset predicted decreased levels of general, physical, and verbal aggression but increased levels of relational aggression. The associations between negative emotional responding and aggression were generally stronger for males than females. The current study provides evidence for the utility of HAB and negative emotional responding as predictors of adult aggression and further suggests that gender and impulsivity may moderate their links with aggression. PMID:24833604

Hostile attributional bias, negative emotional responding, and aggression in adults: moderating effects of gender and impulsivity.

PubMed

Chen, Pan; Coccaro, Emil F; Jacobson, Kristen C

2012-01-01

The current study examined the main effects of hostile attributional bias (HAB) and negative emotional responding on a variety of aggressive behaviors in adults, including general aggression, physical aggression, relational aggression, and verbal aggression. Effects of both externalizing (anger) and internalizing (embarrassment/upset) negative emotions were considered. In addition, the moderating roles of gender and impulsivity on the effects of HAB and negative emotional responding were explored. Multilevel models were fitted to data from 2,749 adult twins aged 20-55 from the PennTwins cohort. HAB was positively associated with all four forms of aggression. There was also a significant interaction between impulsivity and HAB for general aggression. Specifically, the relationship between HAB and general aggression was only significant for individuals with average or above-average levels of impulsivity. Negative emotional responding was also found to predict all measures of aggression, although in different ways. Anger was positively associated with all forms of aggression, whereas embarrassment/upset predicted decreased levels of general, physical, and verbal aggression but increased levels of relational aggression. The associations between negative emotional responding and aggression were generally stronger for males than females. The current study provides evidence for the utility of HAB and negative emotional responding as predictors of adult aggression and further suggests that gender and impulsivity may moderate their links with aggression. © 2011 Wiley Periodicals, Inc.

Overexpression of microRNA-95-3p suppresses brain metastasis of lung adenocarcinoma through downregulation of cyclin D1.

PubMed

Hwang, Su Jin; Lee, Hye Won; Kim, Hye Ree; Song, Hye Jin; Lee, Dong Heon; Lee, Hong; Shin, Chang Hoon; Joung, Je-Gun; Kim, Duk-Hwan; Joo, Kyeung Min; Kim, Hyeon Ho

2015-08-21

Despite great efforts to improve survival rates, the prognosis of lung cancer patients is still very poor, mainly due to high invasiveness. We developed brain metastatic PC14PE6/LvBr4 cells through intracardiac injection of lung adenocarcinoma PC14PE6 cells. Western blot and RT-qPCR analyses revealed that PC14PE6/LvBr4 cells had mesenchymal characteristics and higher invasiveness than PC14PE6 cells. We found that cyclin D1 was upregulated, miR-95-3p was inversely downregulated, and pri-miR-95 and its host gene, ABLIM2, were consistently decreased in PC14PE6/LvBr4 cells. MiR-95-3p suppressed cyclin D1 expression through direct binding to the 3' UTR of cyclin D1 mRNA and suppressed invasiveness, proliferation, and clonogenicity of PC14PE6/LvBr4 cells. Ectopic cyclin D1 reversed miR-95-3p-mediated inhibition of invasiveness and clonogenicity, demonstrating cyclin D1 downregulation is involved in function of miR-95-3p. Using bioluminescence imaging, we found that miR-95-3p suppressed orthotopic tumorigenicity and brain metastasis in vivo and increased overall survival and brain metastasis-free survival. Consistent with in vitro metastatic cells, the levels of miR-95-3p, pri-miR-95, and ABLIM2 mRNA were decreased in brain metastatic tissues compared with lung cancer tissues and higher cyclin D1 expression was involved in poor prognosis. Taken together, our results demonstrate that miR-95-3p is a potential therapeutic target for brain metastasis of lung adenocarcinoma cells.

Anodal transcranial direct current stimulation enhances the effects of motor imagery training in a finger tapping task.

PubMed

Saimpont, Arnaud; Mercier, Catherine; Malouin, Francine; Guillot, Aymeric; Collet, Christian; Doyon, Julien; Jackson, Philip L

2016-01-01

Motor imagery (MI) training and anodal transcranial direct current stimulation (tDCS) applied over the primary motor cortex can independently improve hand motor function. The main objective of this double-blind, sham-controlled study was to examine whether anodal tDCS over the primary motor cortex could enhance the effects of MI training on the learning of a finger tapping sequence. Thirty-six right-handed young human adults were assigned to one of three groups: (i) who performed MI training combined with anodal tDCS applied over the primary motor cortex; (ii) who performed MI training combined with sham tDCS; and (iii) who received tDCS while reading a book. The MI training consisted of mentally rehearsing an eight-item complex finger sequence for 13 min. Before (Pre-test), immediately after (Post-test 1), and at 90 min after (Post-test 2) MI training, the participants physically repeated the sequence as fast and as accurately as possible. An anova showed that the number of sequences correctly performed significantly increased between Pre-test and Post-test 1 and remained stable at Post-test 2 in the three groups (P < 0.001). Furthermore, the percentage increase in performance between Pre-test and Post-test 1 and Post-test 2 was significantly greater in the group that performed MI training combined with anodal tDCS compared with the other two groups (P < 0.05). As a potential physiological explanation, the synaptic strength within the primary motor cortex could have been reinforced by the association of MI training and tDCS compared with MI training alone and tDCS alone. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Post-transcriptional regulation of α-1-antichymotrypsin by microRNA-137 in chronic heart failure and mechanical support.

PubMed

Lok, Sjoukje I; van Mil, Alain; Bovenschen, Niels; van der Weide, Petra; van Kuik, Joyce; van Wichen, Dick; Peeters, Ton; Siera, Erica; Winkens, Bjorn; Sluijter, Joost P G; Doevendans, Pieter A; da Costa Martins, Paula A; de Jonge, Nicolaas; de Weger, Roel A

2013-07-01

Better understanding of the molecular mechanisms of remodeling has become a major objective of heart failure (HF) research to stop or reverse its progression. Left ventricular assist devices (LVADs) are being used in patients with HF, leading to partial reverse remodeling. In the present study, proteomics identified significant changes in α-1-antichymotrypsin (ACT) levels during LVAD support. Moreover, the potential role of ACT in reverse remodeling was studied in detail. Expression of ACT mRNA (quantitative-polymerase chain reaction) decreased significantly in post-LVAD myocardial tissue compared with pre-LVAD tissue (n=15; P<0.01). Immunohistochemistry revealed that ACT expression and localization changed during LVAD support. Circulating ACT levels were elevated in HF patients (n=18) as compared with healthy controls (n=6; P=0.001) and normalized by 6 months of LVAD support. Because increasing evidence implicates that microRNAs (miRs) are involved in myocardial disease processes, we also investigated whether ACT is post-transcriptionally regulated by miRs. Bioinformatics analysis pointed miR-137 as a potential regulator of ACT. The miR-137 expression is inversely correlated with ACT mRNA in myocardial tissue. Luciferase activity assays confirmed ACT as a direct target for miR-137, and in situ hybridization indicated that ACT and miR-137 were mainly localized in cardiomyocytes and stromal cells. High ACT plasma levels in HF normalized during LVAD support, which coincides with decreased ACT mRNA in heart tissue, whereas miR-137 levels increased. MiR-137 directly targeted ACT, thereby indicating that ACT and miR-137 play a role in the pathophysiology of HF and reverse remodeling during mechanical support.

Effect of Green and Brown Propolis Extracts on the Expression Levels of microRNAs, mRNAs and Proteins, Related to Oxidative Stress and Inflammation.

PubMed

Zaccaria, Vincenzo; Curti, Valeria; Di Lorenzo, Arianna; Baldi, Alessandra; Maccario, Cristina; Sommatis, Sabrina; Mocchi, Roberto; Daglia, Maria

2017-10-01

A large body of evidence highlights that propolis exerts many biological functions that can be ascribed to its antioxidant and anti-inflammatory components, including different polyphenol classes. Nevertheless, the molecular mechanisms are yet unknown. The aim of this study is to investigate the mechanisms at the basis of propolis anti-inflammatory and antioxidant activities. The effects of two brown and green propolis extracts-chemically characterized by RP-HPLC-PDA-ESI-MSn-on the expression levels of miRNAs associated with inflammatory responses (miR-19a-3p and miR-203a-3p) and oxidative stress (miR-27a-3p and miR-17-3p), were determined in human keratinocyte HaCat cell lines, treated with non-cytotoxic concentrations. The results showed that brown propolis, whose major polyphenolic components are flavonoids, induced changes in the expression levels of all miRNAs, and was more active than green propolis (whose main polyphenolic components are hydroxycinnamic acid derivatives) which caused changes only in the expression levels of miR-19a-3p and miR-27a-3p. In addition, only brown propolis was able to modify (1) the expression levels of mRNAs, the target of the reported miRNAs, which code for Tumor Necrosis Factor-α (TNF-α), Nuclear Factor, Erythroid 2 Like 2 (NFE2L2) and Glutathione Peroxidase 2 (GPX2), and (2) the protein levels of TNF-α and NFE2L2. In conclusion, brown and green propolis, which showed different metabolite profiles, exert their biological functions through different mechanisms of action.

Bipolar Disorder Associated microRNA, miR-1908-5p, Regulates the Expression of Genes Functioning in Neuronal Glutamatergic Synapses

PubMed Central

Kim, Yoonhee; Zhang, Yinhua; Pang, Kaifang; Kang, Hyojin; Park, Heejoo; Lee, Yeunkum; Lee, Bokyoung; Lee, Heon-Jeong; Kim, Won-Ki; Geum, Dongho

2016-01-01

Bipolar disorder (BD), characterized by recurrent mood swings between depression and mania, is a highly heritable and devastating mental illness with poorly defined pathophysiology. Recent genome-wide molecular genetic studies have identified several protein-coding genes and microRNAs (miRNAs) significantly associated with BD. Notably, some of the proteins expressed from BD-associated genes function in neuronal synapses, suggesting that abnormalities in synaptic function could be one of the key pathogenic mechanisms of BD. In contrast, however, the role of BD-associated miRNAs in disease pathogenesis remains largely unknown, mainly because of a lack of understanding about their target mRNAs and pathways in neurons. To address this problem, in this study, we focused on a recently identified BD-associated but uncharacterized miRNA, miR-1908-5p. We identified and validated its novel target genes including DLGAP4, GRIN1, STX1A, CLSTN1 and GRM4, which all function in neuronal glutamatergic synapses. Moreover, bioinformatic analyses of human brain expression profiles revealed that the expression levels of miR-1908-5p and its synaptic target genes show an inverse-correlation in many brain regions. In our preliminary experiments, the expression of miR-1908-5p was increased after chronic treatment with valproate but not lithium in control human neural progenitor cells. In contrast, it was decreased by valproate in neural progenitor cells derived from dermal fibroblasts of a BD subject. Together, our results provide new insights into the potential role of miR-1908-5p in the pathogenesis of BD and also propose a hypothesis that neuronal synapses could be a key converging pathway of some BD-associated protein-coding genes and miRNAs. PMID:28035180

Micro-RNA-181a suppresses progestin-promoted breast cancer cell growth.

PubMed

Gu, Muqing; Wang, Lijuan; Yang, Chun; Li, Xue; Jia, Chanwei; Croteau, Stephane; Ruan, Xiangyan; Hardy, Pierre

2018-08-01

Recent investigations have indicated that hormone therapy may increase the risk of breast cancer (BC), and the addition of synthetic progestins may play a critical role in this. Several studies have pointed out the important role of progesterone receptor membrane component 1 (PGRMC1) in the development of BC, especially with hormone therapy using progestins. Although the deregulation of microRNA-181a (miR-181a) is often associated with human BC, the effect of miR-181a on PGRMC1 expression during hormone therapy has not been investigated. Cell viability assay and apoptosis assay were performed to investigate the pro-BC effect of progestin (norethisterone, NET) and anti-BC effect of miR-181a on MCF-7 cells. Quantitative RT-PCR and Western blot analysis were used to evaluate gene expressions in the NET-treated MCF-7 cells. NET dose-dependently increased BC cell viability and this effect was accompanied by increased expression of PGRMC1. Overexpression of miR-181a strongly reduced the cell viability of MCF-7 cells, mainly through increased apoptosis, which was evidenced by substantially increased gene expression of pro-apoptosis factors such as BAX and CASPASE 9 in miR-181a overexpressed cells. Importantly, miR-181a abrogated NET-stimulated cell viability and PGRMC1 expression. We provide evidence that miR-181a promotes MCF-7 cell apoptosis. Moreover, miR-181a suppressed NET-provoked cell viability and PGRMC1 expression in MCF-7 cells. These data may suggest a therapeutic strategy of using miR-181a to reduce BC risk in progestin hormone replacement therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

The role of anthropometric, growth and maturity index (AGaMI) influencing youth soccer relative performance

NASA Astrophysics Data System (ADS)

Bisyri Husin Musawi Maliki, Ahmad; Razali Abdullah, Mohamad; Juahir, Hafizan; Muhamad, Wan Siti Amalina Wan; Afiqah Mohamad Nasir, Nur; Muazu Musa, Rabiu; Musliha Mat-Rasid, Siti; Adnan, Aleesha; Azura Kosni, Norlaila; Abdullah, Farhana; Ain Shahirah Abdullah, Nurul

2018-04-01

The main purpose of this study was to develop Anthropometric, Growth and Maturity Index (AGaMI) in soccer and explore its differences to soccer player physical attributes, fitness, motivation and skills. A total 223 adolescent soccer athletes aged 12 to 18 years old were selected as respondent. AGaMI was develop based on anthropometric components (bicep, tricep, subscapular, suprailiac, calf circumference and muac) with growth and maturity component using tanner scale. Meanwhile, relative performance namely physical, fitness, motivation and skills attributes of soccer were measured as dependent variables. The Principal Component Analysis (PCA) and Analysis of Variance (ANOVA) are used to achieve the objective in this study. AGaMI had categorized players into three different groups namely; high (5 players), moderate (88 players) and low (91 players). PCA revealed a moderate to very strong dominant range of 0.69 to 0.90 of factor loading on AGaMI. Further analysis assigned AGaMI groups as treated as independent variables (IV) and physical, fitness, motivation and skills attributes were treated as dependent variables (DV). Finally, ANOVA showed that flexibility, leg power, age, weight, height, sitting height, short and long pass are the most significant parameters statistically differentiate by the groups of AGaMI (p<0.05). As a summary, body fat mass, growth and maturity are an essential component differentiating the output of the soccer players relative performance. In future, information of the AGaMI model are useful to the coach and players for identifying the suitable biological and physiological demand reflects more comprehensive means of youth soccer relative performance. This study further highlights the importance of assessing AGaMI when identifying soccer relative performance.

Evaluation of a joint Bioinformatics and Medical Informatics international course in Peru

PubMed Central

Curioso, Walter H; Hansen, Jacquelyn R; Centurion-Lara, Arturo; Garcia, Patricia J; Wolf, Fredric M; Fuller, Sherrilynne; Holmes, King K; Kimball, Ann Marie

2008-01-01

Background New technologies that emerge at the interface of computational and biomedical science could drive new advances in global health, therefore more training in technology is needed among health care workers. To assess the potential for informatics training using an approach designed to foster interaction at this interface, the University of Washington and the Universidad Peruana Cayetano Heredia developed and assessed a one-week course that included a new Bioinformatics (BIO) track along with an established Medical/Public Health Informatics track (MI) for participants in Peru. Methods We assessed the background of the participants, and measured the knowledge gained by track-specific (MI or BIO) 30-minute pre- and post-tests. Participants' attitudes were evaluated both by daily evaluations and by an end-course evaluation. Results Forty-three participants enrolled in the course – 20 in the MI track and 23 in the BIO track. Of 20 questions, the mean % score for the MI track increased from 49.7 pre-test (standard deviation or SD = 17.0) to 59.7 (SD = 15.2) for the post-test (P = 0.002, n = 18). The BIO track mean score increased from 33.6 pre-test to 51.2 post-test (P < 0.001, n = 21). Most comments (76%) about any aspect of the course were positive. The main perceived strength of the course was the quality of the speakers, and the main perceived weakness was the short duration of the course. Overall, the course acceptability was very good to excellent with a rating of 4.1 (scale 1–5), and the usefulness of the course was rated as very good. Most participants (62.9%) expressed a positive opinion about having had the BIO and MI tracks come together for some of the lectures. Conclusion Pre- and post-test results and the positive evaluations by the participants indicate that this first joint Bioinformatics and Medical/Public Health Informatics (MI and BIO) course was a success. PMID:18194533

Evaluation of a joint Bioinformatics and Medical Informatics international course in Peru.

PubMed

Curioso, Walter H; Hansen, Jacquelyn R; Centurion-Lara, Arturo; Garcia, Patricia J; Wolf, Fredric M; Fuller, Sherrilynne; Holmes, King K; Kimball, Ann Marie

2008-01-14

New technologies that emerge at the interface of computational and biomedical science could drive new advances in global health, therefore more training in technology is needed among health care workers. To assess the potential for informatics training using an approach designed to foster interaction at this interface, the University of Washington and the Universidad Peruana Cayetano Heredia developed and assessed a one-week course that included a new Bioinformatics (BIO) track along with an established Medical/Public Health Informatics track (MI) for participants in Peru. We assessed the background of the participants, and measured the knowledge gained by track-specific (MI or BIO) 30-minute pre- and post-tests. Participants' attitudes were evaluated both by daily evaluations and by an end-course evaluation. Forty-three participants enrolled in the course - 20 in the MI track and 23 in the BIO track. Of 20 questions, the mean % score for the MI track increased from 49.7 pre-test (standard deviation or SD = 17.0) to 59.7 (SD = 15.2) for the post-test (P = 0.002, n = 18). The BIO track mean score increased from 33.6 pre-test to 51.2 post-test (P < 0.001, n = 21). Most comments (76%) about any aspect of the course were positive. The main perceived strength of the course was the quality of the speakers, and the main perceived weakness was the short duration of the course. Overall, the course acceptability was very good to excellent with a rating of 4.1 (scale 1-5), and the usefulness of the course was rated as very good. Most participants (62.9%) expressed a positive opinion about having had the BIO and MI tracks come together for some of the lectures. Pre- and post-test results and the positive evaluations by the participants indicate that this first joint Bioinformatics and Medical/Public Health Informatics (MI and BIO) course was a success.

Traffic-related air pollution and the onset of myocardial infarction: disclosing benzene as a trigger? A small-area case-crossover study.

PubMed

Bard, Denis; Kihal, Wahida; Schillinger, Charles; Fermanian, Christophe; Ségala, Claire; Glorion, Sophie; Arveiler, Dominique; Weber, Christiane

2014-01-01

Exposure to traffic is an established risk factor for the triggering of myocardial infarction (MI). Particulate matter, mainly emitted by diesel vehicles, appears to be the most important stressor. However, the possible influence of benzene from gasoline-fueled cars has not been explored so far. We conducted a case-crossover study from 2,134 MI cases recorded by the local Coronary Heart Disease Registry (2000-2007) in the Strasbourg Metropolitan Area (France). Available individual data were age, gender, previous history of ischemic heart disease and address of residence at the time of the event. Nitrogen dioxide, particles of median aerodynamic diameter <10 µm (PM10), ozone, carbon monoxide and benzene air concentrations were modeled on an hourly basis at the census block level over the study period using the deterministic ADMS-Urban air dispersion model. Model input data were emissions inventories, background pollution measurements, and meteorological data. We have found a positive, statistically significant association between concentrations of benzene and the onset of MI: per cent increase in risk for a 1 µg/m3 increase in benzene concentration in the previous 0, 0-1 and 1 day was 10.4 (95% confidence interval 3-18.2), 10.7 (2.7-19.2) and 7.2 (0.3-14.5), respectively. The associations between the other pollutants and outcome were much lower and in accordance with the literature. We have observed that benzene in ambient air is strongly associated with the triggering of MI. This novel finding needs confirmation. If so, this would mean that not only diesel vehicles, the main particulate matter emitters, but also gasoline-fueled cars--main benzene emitters-, should be taken into account for public health action.

Epigenetics of bone diseases.

PubMed

Michou, Laetitia

2017-12-12

Histone deacetylation, DNA methylation, and micro-RNAs (miRNAs) are the three main epigenetic mechanisms that regulate gene expression. All the physiological processes involved in bone remodeling are tightly regulated by epigenetic factors. This review discusses the main epigenetic modifications seen in tumoral and non-tumoral bone diseases, with emphasis on miRNAs. The role for epigenetic modifications of gene expression in the most common bone diseases is illustrated by drawing on the latest publications in the field. In multifactorial bone diseases such as osteoporosis, many epigenetic biomarkers, either alone or in combination, have been associated with bone mineral density or suggested to predict osteoporotic fractures. In addition, treatments designed to modulate bone remodeling by selectively targeting the function of specific miRNAs are being evaluated. Advances in the understanding of epigenetic regulation shed new light on the pathophysiology of other non-tumoral bone diseases, including genetic conditions inherited on a Mendelian basis. Finally, in the area of primary and metastatic bone tumors, the last few years have witnessed considerable progress in elucidating the epigenetic regulation of oncogenesis and its local interactions with bone tissue. These new data may allow the development of epigenetic outcome predictors, which are in very high demand, and of innovative therapeutic agents acting via miRNA modulation. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

miRNA as a New Regulatory Mechanism of Estrogen Vascular Action.

PubMed

Pérez-Cremades, Daniel; Mompeón, Ana; Vidal-Gómez, Xavier; Hermenegildo, Carlos; Novella, Susana

2018-02-06

The beneficial effects of estrogen on the cardiovascular system have been reported extensively. In fact, the incidence of cardiovascular diseases in women is lower than in age-matched men during their fertile stage of life, a benefit that disappears after menopause. These sex-related differences point to sexual hormones, mainly estrogen, as possible cardiovascular protective factors. The regulation of vascular function by estrogen is mainly related to the maintenance of normal endothelial function and is mediated by both direct and indirect gene transcription through the activity of specific estrogen receptors. Some of these mechanisms are known, but many remain to be elucidated. In recent years, microRNAs have been established as non-coding RNAs that regulate the expression of a high percentage of protein-coding genes in mammals and are related to the correct function of human physiology. Moreover, within the cardiovascular system, miRNAs have been related to physiological and pathological conditions. In this review, we address what is known about the role of estrogen-regulated miRNAs and their emerging involvement in vascular biology.

Analysis of the impact of digital watermarking on computer-aided diagnosis in medical imaging.

PubMed

Garcia-Hernandez, Jose Juan; Gomez-Flores, Wilfrido; Rubio-Loyola, Javier

2016-01-01

Medical images (MI) are relevant sources of information for detecting and diagnosing a large number of illnesses and abnormalities. Due to their importance, this study is focused on breast ultrasound (BUS), which is the main adjunct for mammography to detect common breast lesions among women worldwide. On the other hand, aiming to enhance data security, image fidelity, authenticity, and content verification in e-health environments, MI watermarking has been widely used, whose main goal is to embed patient meta-data into MI so that the resulting image keeps its original quality. In this sense, this paper deals with the comparison of two watermarking approaches, namely spread spectrum based on the discrete cosine transform (SS-DCT) and the high-capacity data-hiding (HCDH) algorithm, so that the watermarked BUS images are guaranteed to be adequate for a computer-aided diagnosis (CADx) system, whose two principal outcomes are lesion segmentation and classification. Experimental results show that HCDH algorithm is highly recommended for watermarking medical images, maintaining the image quality and without introducing distortion into the output of CADx. Copyright © 2015 Elsevier Ltd. All rights reserved.

Feature Selection Has a Large Impact on One-Class Classification Accuracy for MicroRNAs in Plants.

PubMed

Yousef, Malik; Saçar Demirci, Müşerref Duygu; Khalifa, Waleed; Allmer, Jens

2016-01-01

MicroRNAs (miRNAs) are short RNA sequences involved in posttranscriptional gene regulation. Their experimental analysis is complicated and, therefore, needs to be supplemented with computational miRNA detection. Currently computational miRNA detection is mainly performed using machine learning and in particular two-class classification. For machine learning, the miRNAs need to be parametrized and more than 700 features have been described. Positive training examples for machine learning are readily available, but negative data is hard to come by. Therefore, it seems prerogative to use one-class classification instead of two-class classification. Previously, we were able to almost reach two-class classification accuracy using one-class classifiers. In this work, we employ feature selection procedures in conjunction with one-class classification and show that there is up to 36% difference in accuracy among these feature selection methods. The best feature set allowed the training of a one-class classifier which achieved an average accuracy of ~95.6% thereby outperforming previous two-class-based plant miRNA detection approaches by about 0.5%. We believe that this can be improved upon in the future by rigorous filtering of the positive training examples and by improving current feature clustering algorithms to better target pre-miRNA feature selection.

The miRNA Transcriptome Directly Reflects the Physiological and Biochemical Differences between Red, White, and Intermediate Muscle Fiber Types.

PubMed

Ma, Jideng; Wang, Hongmei; Liu, Rui; Jin, Long; Tang, Qianzi; Wang, Xun; Jiang, Anan; Hu, Yaodong; Li, Zongwen; Zhu, Li; Li, Ruiqiang; Li, Mingzhou; Li, Xuewei

2015-04-29

MicroRNAs (miRNAs) are small non-coding RNAs that can regulate their target genes at the post-transcriptional level. Skeletal muscle comprises different fiber types that can be broadly classified as red, intermediate, and white. Recently, a set of miRNAs was found expressed in a fiber type-specific manner in red and white fiber types. However, an in-depth analysis of the miRNA transcriptome differences between all three fiber types has not been undertaken. Herein, we collected 15 porcine skeletal muscles from different anatomical locations, which were then clearly divided into red, white, and intermediate fiber type based on the ratios of myosin heavy chain isoforms. We further illustrated that three muscles, which typically represented each muscle fiber type (i.e., red: peroneal longus (PL), intermediate: psoas major muscle (PMM), white: longissimus dorsi muscle (LDM)), have distinct metabolic patterns of mitochondrial and glycolytic enzyme levels. Furthermore, we constructed small RNA libraries for PL, PMM, and LDM using a deep sequencing approach. Results showed that the differentially expressed miRNAs were mainly enriched in PL and played a vital role in myogenesis and energy metabolism. Overall, this comprehensive analysis will contribute to a better understanding of the miRNA regulatory mechanism that achieves the phenotypic diversity of skeletal muscles.

Circulating MicroRNAs as Potential Biomarkers of Exercise Response

PubMed Central

Polakovičová, Mája; Musil, Peter; Laczo, Eugen; Hamar, Dušan; Kyselovič, Ján

2016-01-01

Systematic physical activity increases physical fitness and exercise capacity that lead to the improvement of health status and athletic performance. Considerable effort is devoted to identifying new biomarkers capable of evaluating exercise performance capacity and progress in training, early detection of overtraining, and monitoring health-related adaptation changes. Recent advances in OMICS technologies have opened new opportunities in the detection of genetic, epigenetic and transcriptomic biomarkers. Very promising are mainly small non-coding microRNAs (miRNAs). miRNAs post-transcriptionally regulate gene expression by binding to mRNA and causing its degradation or inhibiting translation. A growing body of evidence suggests that miRNAs affect many processes and play a crucial role not only in cell differentiation, proliferation and apoptosis, but also affect extracellular matrix composition and maintaining processes of homeostasis. A number of studies have shown changes in distribution profiles of circulating miRNAs (c-miRNAs) associated with various diseases and disorders as well as in samples taken under physiological conditions such as pregnancy or physical exercise. This overview aims to summarize the current knowledge related to the response of blood c-miRNAs profiles to different modes of exercise and to highlight their potential application as a novel class of biomarkers of physical performance capacity and training adaptation. PMID:27782053

Involvement of microRNAs-MMPs-E-cadherin in the migration and invasion of gastric cancer cells infected with Helicobacter pylori.

PubMed

Yang, Yongmei; Li, Xiaohui; Du, Jie; Yin, Youcong; Li, Yuanjian

2018-06-15

It has been found that Helicobacter pylori （H. pylori）is not only the main cause of gastric cancer, but also closely related to its metastasis. E-cadherin cleavage induced by matrix metalloproteinases (MMPs) plays an important role in the tumor metastasis. In the present study, we investigated the role of microRNAs-MMPs-E-cadherin in migration and invasion of gastric cancer cells treated with H. pylori. The results showed that H. pylori induced migration and invasion of SGC-7901 cells with a down-regulation of E-cadherin expression, which were abolished by MMPs knock down, E-cadherin overexpression, mimics of miR128 and miR148a. MiR128/miR148a inhibitors restored MMP-3/MMP-7 expression, down-regulated E-cadherin level, and accelerated cellular migration and invasion. This study suggests that H. pylori induces migration and invasion of gastric cancer cells through reduction of E-cadherin function by activation of MMP-3, - 7. The present results also suggest that the activated MMPs/E-cadherin pathway is related with down-regulation of miR128/miR148a in the human gastric cancer cells infected with H. pylori. Copyright © 2018. Published by Elsevier Inc.

Novel method to detect microRNAs using chip-based QuantStudio 3D digital PCR.

PubMed

Conte, Davide; Verri, Carla; Borzi, Cristina; Suatoni, Paola; Pastorino, Ugo; Sozzi, Gabriella; Fortunato, Orazio

2015-10-23

Research efforts for the management of cancer, in particular for lung cancer, are directed to identify new strategies for its early detection. MicroRNAs (miRNAs) are a new promising class of circulating biomarkers for cancer detection, but lack of consensus on data normalization methods has affected the diagnostic potential of circulating miRNAs. There is a growing interest in techniques that allow an absolute quantification of miRNAs which could be useful for early diagnosis. Recently, digital PCR, mainly based on droplets generation, emerged as an affordable technology for precise and absolute quantification of nucleic acids. In this work, we described a new interesting approach for profiling circulating miRNAs in plasma samples using a chip-based platform, the QuantStudio 3D digital PCR. The proposed method was validated using synthethic oligonucleotide at serial dilutions in plasma samples of lung cancer patients and in lung tissues and cell lines. Given its reproducibility and reliability, our approach could be potentially applied for the identification and quantification of miRNAs in other biological samples such as circulating exosomes or protein complexes. As chip-digital PCR becomes more established, it would be a robust tool for quantitative assessment of miRNA copy number for diagnosis of lung cancer and other diseases.

MicroRNA-188-5p regulates contribution of bone marrow-derived cells to choroidal neovascularization development by targeting MMP-2/13.

PubMed

Hou, Huiyuan; Gao, Fan; Liang, Hongliang; Lv, Yang; Li, Manhong; Yao, Libo; Zhang, Jian; Dou, Guorui; Wang, Yusheng

2018-06-14

Our previous investigations have shown that bone marrow-derived cells (BMCs), including mesenchymal stem cells (MSCs), contribute to the development of choroidal neovascularization (CNV) as sources of cells and angiogenic factors. Two main steps for circulating BMCs to integrate into CNV lesions are extracellular matrix remodeling and consequential cell migration. MicroRNAs (miRNAs) were found to be involved in CNV development; however, little is known about whether miRNAs regulate the contribution of BMCs to CNV. In the present study, we found that the expression of miR-188-5p was decreased in cultured hypoxic MSCs and BMCs within laser-induced CNV in mice. Matrix metalloproteinase 2 (MMP-2) and MMP-13 were both discovered as targets of miR-188-5p by bioinformatics predictions and dual-luciferase reporter system. Accordingly, increased expression of MMP-2/13 was found in hypoxic MSCs and BMCs in CNV lesions. Furthermore, miR-188-5p mimic transfection caused downregulation of MMP-2/13 in hypoxic MSCs and decreased tube formation of co-cultured vascular endothelial cells. Intravitreal injections of a miR-188-5p agomir attenuated the severity of CNV and inhibited the migration of BMCs into CNV lesions in mice. Our study suggests that miR-188-5p regulates the contribution of BMCs to CNV development by targeting MMP-2/13-mediated extracellular matrix degeneration, and miR-188-5p serves as a therapeutic target to treat CNV-related diseases. Copyright © 2018. Published by Elsevier Ltd.

MiR-300 Serves as Potential Biomarker to Screen Knee Osteoarthritis Patients by Targeting TNFα.

PubMed

Zhou, Zihao; Tian, Fengde; An, Ning; Zhang, Yao; Wang, Changcheng; Guo, Lin

2018-04-01

This study mainly explored the serum level of miR-300 with the risk of knee OA, thereby evaluating their diagnostic ability for treatment of knee osteoarthritis (KOA) patients. In the current study, we evaluated the level of TNFα in KOA patients and HCs. The serum was used to quantify the level of TNF-α by way of a sandwich enzyme-linked immunosorbent assay. Dual luciferase reporter assay was carried out to identify the possible target gene of miR-300. In line with previous studies, our data showed that serum TNFα level was increased along with K/L grades and WOMAC scoring, suggesting TNFα induced inflammatory responses correlating with the severity of KOA. We also showed that serum miR-300 level was increased with the severity of KOA according to X ray examination and K/L grades. Furthermore, we showed that serum miR-300 level positively correlated with K/L grades, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scoring and WOMAC function scoring. Bioinformatic predictions showed a conserved binding site of miR-300 in the 3'UTR of IκBα. We then carried out a dual luciferase reporter assay and found miR-300 significantly suppressed pmirGLO-IκBα-3'UTR luciferase activity. Serum miR-300 is increased with the severity of KOA according to X-ray examination and K/L grades, thereby reflecting the severity of KOA and the degree of cartilage damage. Therefore, it could be used as a potential biomarker to screen KOA patients from healthy controls.

BDNF–ERK–CREB signalling mediates the role of miR-132 in the regulation of the effects of oleanolic acid in male mice

PubMed Central

Yi, Li-Tao; Li, Jing; Liu, Bin-Bin; Luo, Liu; Liu, Qing; Geng, Di

2014-01-01

Background Although previous study has demonstrated that brain-derived neurotrophic factor (BDNF) is involved in the antidepressant-like effect of oleanolic acid, there is little information regarding the details of the molecular mechanism involved in this effect. Methods We used a chronic unpredictable mild stress (CUMS) model to test the antidepressant-like effect of oleanolic acid on depressant-like behaviour, miR-132 expression and synaptic protein expression in the male mouse hippocampus. Furthermore, we explored the possible signalling pathways associated with miR-132 expression that mediate the effect of oleanolic acid on neuronal proliferation. Results The results demonstrated that a 3-week treatment with oleanolic acid ameliorated CUMS-induced anhedonic and anxiogenic behaviours. Furthermore, we found that oleanolic acid led to the BDNF-related phosphorylation and activation of extracellular signal-regulated kinases (ERK) and cyclic adenosine monophosphate response element binding protein (CREB), which was associated with the upregulation of miR-132 and hippocampal neuronal proliferation. Moreover, experiments with an miR-132 antagomir revealed that targeting miR-132 led to inhibition of neuronal proliferation and the postsynaptic density protein 95, but did not affect presynaptic protein synapsin I. Limitations Several other stimuli can also induce CREB phosphorylation in the hippocampus. Thus, regulation of miR-132 may not be restricted to neurotrophic signalling. Conclusion Our results show that oleanolic acid induces the upregulation of miR-132, which serves as an important regulator of neurotrophic actions, mainly through the activation of the hippocampal BDNF–ERK–CREB signalling pathways. PMID:25079084

EEG Spectral Generators Involved in Motor Imagery: A swLORETA Study

PubMed Central

Cebolla, Ana-Maria; Palmero-Soler, Ernesto; Leroy, Axelle; Cheron, Guy

2017-01-01

In order to characterize the neural generators of the brain oscillations related to motor imagery (MI), we investigated the cortical, subcortical, and cerebellar localizations of their respective electroencephalogram (EEG) spectral power and phase locking modulations. The MI task consisted in throwing a ball with the dominant upper limb while in a standing posture, within an ecological virtual reality (VR) environment (tennis court). The MI was triggered by the visual cues common to the control condition, during which the participant remained mentally passive. As previously developed, our paradigm considers the confounding problem that the reference condition allows two complementary analyses: one which uses the baseline before the occurrence of the visual cues in the MI and control resting conditions respectively; and the other which compares the analog periods between the MI and the control resting-state conditions. We demonstrate that MI activates specific, complex brain networks for the power and phase modulations of the EEG oscillations. An early (225 ms) delta phase-locking related to MI was generated in the thalamus and cerebellum and was followed (480 ms) by phase-locking in theta and alpha oscillations, generated in specific cortical areas and the cerebellum. Phase-locking preceded the power modulations (mainly alpha–beta ERD), whose cortical generators were situated in the frontal BA45, BA11, BA10, central BA6, lateral BA13, and posterior cortex BA2. Cerebellar-thalamic involvement through phase-locking is discussed as an underlying mechanism for recruiting at later stages the cortical areas involved in a cognitive role during MI. PMID:29312028

Blood miRNomes and transcriptomes reveal novel longevity mechanisms in the long-lived bat, Myotis myotis.

PubMed

Huang, Zixia; Jebb, David; Teeling, Emma C

2016-11-10

Chiroptera, the bats, are the only order of mammals capable of true self-powered flight. Bats exhibit a number of other exceptional traits such as echolocation, viral tolerance and, perhaps most puzzlingly, extreme longevity given their body size. Little is known about the molecular mechanisms driving their extended longevity particularly at the levels of gene expression and post-transcriptional regulation. To elucidate the molecular mechanisms that may underlie their unusual longevity, we have deep sequenced 246.5 million small RNA reads from whole blood of the long-lived greater mouse-eared bats, Myotis myotis, and conducted a series of genome-wide comparative analyses between bat and non-bat mammals (human, pig and cow) in both blood miRNomes and transcriptomes, for the first time. We identified 539 miRNA gene candidates from bats, of which 468 unique mature miRNA were obtained. More than half of these miRNA (65.1 %) were regarded as bat-specific, regulating genes involved in the immune, ageing and tumorigenesis pathways. We have also developed a stringent pipeline for genome-wide miRNome comparisons across species, and identified 37 orthologous miRNA groups shared with bat, human, pig and cow, 6 of which were differentially expressed. For bats, 3 out of 4 up-regulated miRNA (miR-101-3p, miR-16-5p, miR-143-3p) likely function as tumor suppressors against various kinds of cancers, while one down-regulated miRNA (miR-221-5p) acts as a tumorigenesis promoter in human breast and pancreatic cancers. Additionally, a genome-wide comparison of mRNA transcriptomes across species also revealed specific gene expression patterns in bats. 127 up-regulated genes were enriched mainly in mitotic cell cycle and DNA repair mechanisms, while 364 down-regulated genes were involved primarily in mitochondrial activity. Our comprehensive and integrative analyses revealed bat-specific and differentially expressed miRNA and mRNA that function in key longevity pathways, producing a distinct bat gene expression pattern. For the first time, we show that bats may possess unique regulatory mechanisms for resisting tumorigenesis, repairing cellular damage and preventing oxidative stresses, all of which likely contribute to the extraordinary lifespan of Myotis myotis.

Assessing and Refining Myocardial Infarction Risk Estimation among Patients with Human Immunodeficiency Virus

PubMed Central

Feinstein, Matthew J.; Nance, Robin M.; Drozd, Daniel R.; Ning, Hongyan; Delaney, Joseph A.; Heckbert, Susan R.; Budoff, Matthew J.; Mathews, William C.; Kitahata, Mari M.; Saag, Michael S.; Eron, Joseph J.; Moore, Richard D.; Achenbach, Chad J.; Lloyd-Jones, Donald M.; Crane, Heidi M.

2017-01-01

Importance Persons with human immunodeficiency virus (HIV) treated with antiretroviral therapy (ART) have improved longevity but are at elevated risk for myocardial infarction (MI) due to common MI risk factors and HIV-specific factors. Despite these elevated MI rates, optimal methods to predict MI risks for HIV-infected persons remain unclear. Objective To determine the extent to which existing and de novo estimation tools predict MI in a multi-center HIV cohort with rigorous MI adjudication. Design We evaluated the performance of standard-of-care and two new data-derived MI risk estimation models in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) multi-center prospective clinical cohort. The new risk estimation models were validated in a cohort separate from the derivation cohort. Setting Clinical sites across the U.S. where HIV-infected adults receive medical care in inpatient and outpatient settings. Participants HIV-infected adults receiving care anytime since 1995 at 5 CNICS sites where MIs were adjudicated (N=19829). Exposures Common cardiovascular risk factors, HIV viral load, CD4 count, and medication use were used to calculate predicted event rates. Main Outcome and Measures Observed MI rates over the course of follow-up, scaled to 10 years using an observed prime approach to account for dropout and loss to follow-up prior to 10 years. Results MI rates were higher among blacks, older participants, and participants who were not virally suppressed. The 2013 Pooled Cohort Equations (PCEs), which predict composite rates of MI and stroke, adequately discriminated MI risk (Harrell’s C Statistic = 0.75). Two data-derived models incorporating HIV-specific covariates exhibited weak calibration in a validation sample and did not discriminate risk any better (Harrell’s C Statistic = 0.72 and 0.73) than the PCEs. The PCEs were moderately calibrated in CNICS but predicted consistently lower than observed prime rates of MI. The PCEs Conclusions and relevance The PCEs discriminated MI risk and were moderately calibrated in this multi-center HIV cohort. Adding HIV-specific factors did not improve model performance. As HIV-infected cohorts capture and assess outcomes of MI and stroke, the performance of risk estimation tools should be revisited. PMID:28002550

HITCal: a software tool for analysis of video head impulse test responses.

PubMed

Rey-Martinez, Jorge; Batuecas-Caletrio, Angel; Matiño, Eusebi; Perez Fernandez, Nicolás

2015-09-01

The developed software (HITCal) may be a useful tool in the analysis and measurement of the saccadic video head impulse test (vHIT) responses and with the experience obtained during its use the authors suggest that HITCal is an excellent method for enhanced exploration of vHIT outputs. To develop a (software) method to analyze and explore the vHIT responses, mainly saccades. HITCal was written using a computational development program; the function to access a vHIT file was programmed; extended head impulse exploration and measurement tools were created and an automated saccade analysis was developed using an experimental algorithm. For pre-release HITCal laboratory tests, a database of head impulse tests (HITs) was created with the data collected retrospectively in three reference centers. This HITs database was evaluated by humans and was also computed with HITCal. The authors have successfully built HITCal and it has been released as open source software; the developed software was fully operative and all the proposed characteristics were incorporated in the released version. The automated saccades algorithm implemented in HITCal has good concordance with the assessment by human observers (Cohen's kappa coefficient = 0.7).

A Novel Sensor Selection and Power Allocation Algorithm for Multiple-Target Tracking in an LPI Radar Network

PubMed Central

She, Ji; Wang, Fei; Zhou, Jianjiang

2016-01-01

Radar networks are proven to have numerous advantages over traditional monostatic and bistatic radar. With recent developments, radar networks have become an attractive platform due to their low probability of intercept (LPI) performance for target tracking. In this paper, a joint sensor selection and power allocation algorithm for multiple-target tracking in a radar network based on LPI is proposed. It is found that this algorithm can minimize the total transmitted power of a radar network on the basis of a predetermined mutual information (MI) threshold between the target impulse response and the reflected signal. The MI is required by the radar network system to estimate target parameters, and it can be calculated predictively with the estimation of target state. The optimization problem of sensor selection and power allocation, which contains two variables, is non-convex and it can be solved by separating power allocation problem from sensor selection problem. To be specific, the optimization problem of power allocation can be solved by using the bisection method for each sensor selection scheme. Also, the optimization problem of sensor selection can be solved by a lower complexity algorithm based on the allocated powers. According to the simulation results, it can be found that the proposed algorithm can effectively reduce the total transmitted power of a radar network, which can be conducive to improving LPI performance. PMID:28009819

Relevance of miR-21 in regulation of tumor suppressor gene PTEN in human cervical cancer cells.

PubMed

Peralta-Zaragoza, Oscar; Deas, Jessica; Meneses-Acosta, Angélica; De la O-Gómez, Faustino; Fernández-Tilapa, Gloria; Gómez-Cerón, Claudia; Benítez-Boijseauneau, Odelia; Burguete-García, Ana; Torres-Poveda, Kirvis; Bermúdez-Morales, Victor Hugo; Madrid-Marina, Vicente; Rodríguez-Dorantes, Mauricio; Hidalgo-Miranda, Alfredo; Pérez-Plasencia, Carlos

2016-03-14

Expression of the microRNA miR-21 has been found to be altered in almost all types of cancers and it has been classified as an oncogenic microRNA or oncomir. Due to the critical functions of its target proteins in various signaling pathways, miR-21 is an attractive target for genetic and pharmacological modulation in various cancers. Cervical cancer is the second most common cause of death from cancer in women worldwide and persistent HPV infection is the main etiologic agent. This malignancy merits special attention for the development of new treatment strategies. In the present study we analyze the role of miR-21 in cervical cancer cells. To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression in a cervical intraepithelial neoplasia-derived cell lines using siRNAs. The effect of miR-21 on gene expression was assessed in cervical cancer cells transfected with the siRNA expression plasmid pSIMIR21. We identified the tumor suppressor gene PTEN as a target of miR-21 and determined the mechanism of its regulation throughout reporter construct plasmids. Using this model, we analyzed the expression of miR-21 and PTEN as well as functional effects such as autophagy and apoptosis induction. In SiHa cells, there was an inverse correlation between miR-21 expression and PTEN mRNA level as well as PTEN protein expression in cervical cancer cells. Transfection with the pSIMIR21 plasmid increased luciferase reporter activity in construct plasmids containing the PTEN-3'-UTR microRNA response elements MRE21-1 and MRE21-2. The role of miR-21 in cell proliferation was also analyzed in SiHa and HeLa cells transfected with the pSIMIR21 plasmid, and tumor cells exhibited markedly reduced cell proliferation along with autophagy and apoptosis induction. We conclude that miR-21 post-transcriptionally down-regulates the expression of PTEN to promote cell proliferation and cervical cancer cell survival. Therefore, it may be a potential therapeutic target in gene therapy for cervical cancer.

Responses of symbiotic nitrogen-fixing common bean to aluminum toxicity and delineation of nodule responsive microRNAs.

PubMed

Mendoza-Soto, Ana B; Naya, Loreto; Leija, Alfonso; Hernández, Georgina

2015-01-01

Aluminum (Al) toxicity is widespread in acidic soils where the common bean (Phaseolus vulgaris), the most important legume for human consumption, is produced and it is a limiting factor for crop production and symbiotic nitrogen fixation. We characterized the nodule responses of common bean plants inoculated with Rhizobioum tropici CIAT899 and the root responses of nitrate-fertilized plants exposed to excess Al in low pH, for long or short periods. A 43-50% reduction in nitrogenase activity indicates that Al toxicity (Alt) highly affected nitrogen fixation in common bean. Bean roots and nodules showed characteristic symptoms for Alt. In mature nodules Al accumulation and lipoperoxidation were observed in the infected zone, while callose deposition and cell death occurred mainly in the nodule cortex. Regulatory mechanisms of plant responses to metal toxicity involve microRNAs (miRNAs) along other regulators. Using a miRNA-macroarray hybridization approach we identified 28 (14 up-regulated) Alt nodule-responsive miRNAs. We validated (quantitative reverse transcriptase-PCR) the expression of eight nodule responsive miRNAs in roots and in nodules exposed to high Al for long or short periods. The inverse correlation between the target and miRNA expression ratio (stress:control) was observed in every case. Generally, miRNAs showed a higher earlier response in roots than in nodules. Some of the common bean Alt-responsive miRNAs identified has also been reported as differentially expressed in other plant species subjected to similar stress condition. miRNA/target nodes analyzed in this work are known to be involved in relevant signaling pathways, thus we propose that the participation of miR164/NAC1 (NAM/ATAF/CUC transcription factor) and miR393/TIR1 (TRANSPORT INHIBITOR RESPONSE 1-like protein) in auxin and of miR170/SCL (SCARECROW-like protein transcription factor) in gibberellin signaling is relevant for common bean response/adaptation to Al stress. Our data provide a foundation for evaluating the individual roles of miRNAs in the response of common bean nodules to Alt.

Responses of symbiotic nitrogen-fixing common bean to aluminum toxicity and delineation of nodule responsive microRNAs

PubMed Central

Mendoza-Soto, Ana B.; Naya, Loreto; Leija, Alfonso; Hernández, Georgina

2015-01-01

Aluminum (Al) toxicity is widespread in acidic soils where the common bean (Phaseolus vulgaris), the most important legume for human consumption, is produced and it is a limiting factor for crop production and symbiotic nitrogen fixation. We characterized the nodule responses of common bean plants inoculated with Rhizobioum tropici CIAT899 and the root responses of nitrate-fertilized plants exposed to excess Al in low pH, for long or short periods. A 43–50% reduction in nitrogenase activity indicates that Al toxicity (Alt) highly affected nitrogen fixation in common bean. Bean roots and nodules showed characteristic symptoms for Alt. In mature nodules Al accumulation and lipoperoxidation were observed in the infected zone, while callose deposition and cell death occurred mainly in the nodule cortex. Regulatory mechanisms of plant responses to metal toxicity involve microRNAs (miRNAs) along other regulators. Using a miRNA-macroarray hybridization approach we identified 28 (14 up-regulated) Alt nodule-responsive miRNAs. We validated (quantitative reverse transcriptase-PCR) the expression of eight nodule responsive miRNAs in roots and in nodules exposed to high Al for long or short periods. The inverse correlation between the target and miRNA expression ratio (stress:control) was observed in every case. Generally, miRNAs showed a higher earlier response in roots than in nodules. Some of the common bean Alt-responsive miRNAs identified has also been reported as differentially expressed in other plant species subjected to similar stress condition. miRNA/target nodes analyzed in this work are known to be involved in relevant signaling pathways, thus we propose that the participation of miR164/NAC1 (NAM/ATAF/CUC transcription factor) and miR393/TIR1 (TRANSPORT INHIBITOR RESPONSE 1-like protein) in auxin and of miR170/SCL (SCARECROW-like protein transcription factor) in gibberellin signaling is relevant for common bean response/adaptation to Al stress. Our data provide a foundation for evaluating the individual roles of miRNAs in the response of common bean nodules to Alt. PMID:26284103

Modeling Study of the Geospace System Response to the Solar Wind Dynamic Pressure Enhancement on 17 March 2015

NASA Astrophysics Data System (ADS)

Ozturk, D. S.; Zou, S.; Ridley, A. J.; Slavin, J. A.

2018-04-01

The global magnetosphere-ionosphere-thermosphere system is intrinsically coupled and susceptible to external drivers such as solar wind dynamic pressure enhancements. In order to understand the large-scale dynamic processes in the magnetosphere-ionosphere-thermosphere system due to the compression from the solar wind, the 17 March 2015 sudden commencement was studied in detail using global numerical models. This storm was one of the most geoeffective events of the solar cycle 24 with a minimum Dst of -222 nT. The Wind spacecraft recorded a 10-nPa increment in the solar wind dynamic pressure, while the interplanetary magnetic field BZ became further northward. The University of Michigan Block-Adaptive-Tree Solar wind Roe-type Upwind Scheme global magnetohydrodynamic code was utilized to study the generation and propagation of perturbations associated with the compression of the magnetosphere system. In addition, the high-resolution electric potential and auroral power output from the magnetohydrodynamic model was used to drive the global ionosphere-thermosphere model to investigate the ionosphere-thermosphere system response to pressure enhancement. During the compression, the electric potentials and convection patterns in the polar ionosphere were significantly altered when the preliminary impulse and main impulse field-aligned currents moved from dayside to nightside. As a result of enhanced frictional heating, plasma and neutral temperatures increased at the locations where the flow speeds were enhanced, whereas the electron density dropped at these locations. In particular, the region between the preliminary impulse and main impulse field-aligned currents experienced the most significant heating with 1000-K ion temperature increase and 20-K neutral temperature increase within 2 min. Comparison of the simulation results with the Poker Flat Incoherent Scatter Radar observations showed reasonable agreements despite underestimated magnitudes.

Association of low-activity MAOA allelic variants with violent crime in incarcerated offenders

PubMed Central

Stetler, Dean A.; Davis, Chad; Leavitt, Kathryn; Schriger, Ilana; Benson, Katie; Bhakta, Samir; Wang, Lam Chee; Oben, Cynthia; Watters, Matthew; Haghnegahdar, Tara; Bortolato, Marco

2015-01-01

The main enzyme for serotonin degradation, monoamine oxidase (MAO) A, has recently emerged as a key biological factor in the predisposition to impulsive aggression. Male carriers of low-activity variants of the main functional polymorphism of the MAOA gene (MAOA-uVNTR) have been shown to exhibit a greater proclivity to engage in violent acts. Thus, we hypothesized that low-activity MAOA-uVNTR alleles may be associated with a higher risk for criminal violence among male offenders. To test this possibility, we analyzed the MAOA-uVNTR variants of violent (n=49) and non-violent (n=40) male Caucasian and African-American convicts in a correctional facility. All participants were also tested with the Childhood Trauma Questionnaire (CTQ), Barratt Impulsivity Scale (BIS-11) and Buss-Perry Aggression Questionnaire (BPAQ) to assess their levels of childhood trauma exposure, impulsivity and aggression, respectively. Our results revealed a robust (P<0.0001) association between low-activity MAOA-uVNTR alleles and violent crime. This association was replicated in the group of Caucasian violent offenders (P<0.01), but reached only a marginal trend (P=0.08) in their African American counterparts. While violent crime charges were not associated with CTQ, BIS-11 and BPAQ scores, carriers of low-activity alleles exhibited a mild, yet significant (P<0.05) increase in BIS-11 total and attentional-impulsiveness scores. In summary, these findings support the role of MAOA gene as a prominent genetic determinant for criminal violence. Further studies are required to confirm these results in larger samples of inmates and evaluate potential interactions between MAOA alleles and environmental vulnerability factors. PMID:25082653

Association of low-activity MAOA allelic variants with violent crime in incarcerated offenders.

PubMed

Stetler, Dean A; Davis, Chad; Leavitt, Kathryn; Schriger, Ilana; Benson, Katie; Bhakta, Samir; Wang, Lam Chee; Oben, Cynthia; Watters, Matthew; Haghnegahdar, Tara; Bortolato, Marco

2014-11-01

The main enzyme for serotonin degradation, monoamine oxidase (MAO) A, has recently emerged as a key biological factor in the predisposition to impulsive aggression. Male carriers of low-activity variants of the main functional polymorphism of the MAOA gene (MAOA-uVNTR) have been shown to exhibit a greater proclivity to engage in violent acts. Thus, we hypothesized that low-activity MAOA-uVNTR alleles may be associated with a higher risk for criminal violence among male offenders. To test this possibility, we analyzed the MAOA-uVNTR variants of violent (n = 49) and non-violent (n = 40) male Caucasian and African-American convicts in a correctional facility. All participants were also tested with the Childhood Trauma Questionnaire (CTQ), Barratt Impulsivity Scale (BIS-11) and Buss-Perry Aggression Questionnaire (BPAQ) to assess their levels of childhood trauma exposure, impulsivity and aggression, respectively. Our results revealed a robust (P < 0.0001) association between low-activity MAOA-uVNTR alleles and violent crime. This association was replicated in the group of Caucasian violent offenders (P < 0.01), but reached only a marginal trend (P = 0.08) in their African American counterparts. While violent crime charges were not associated with CTQ, BIS-11 and BPAQ scores, carriers of low-activity alleles exhibited a mild, yet significant (P < 0.05) increase in BIS-11 total and attentional-impulsiveness scores. In summary, these findings support the role of MAOA gene as a prominent genetic determinant for criminal violence. Further studies are required to confirm these results in larger samples of inmates and evaluate potential interactions between MAOA alleles and environmental vulnerability factors. Copyright © 2014 Elsevier Ltd. All rights reserved.

Assessment of Myocardial Remodeling Using an Elastin/Tropoelastin Specific Agent with High Field Magnetic Resonance Imaging (MRI).

PubMed

Protti, Andrea; Lavin, Begoña; Dong, Xuebin; Lorrio, Silvia; Robinson, Simon; Onthank, David; Shah, Ajay M; Botnar, Rene M

2015-08-13

Well-defined inflammation, proliferation, and maturation phases orchestrate the remodeling of the injured myocardium after myocardial infarction (MI) by controlling the formation of new extracellular matrix. The extracellular matrix consists mainly of collagen but also fractions of elastin. It is thought that elastin is responsible for maintaining elastic properties of the myocardium, thus reducing the risk of premature rupture. An elastin/tropoelastin-specific contrast agent (Gd-ESMA) was used to image tropoelastin and mature elastin fibers for in vivo assessment of extracellular matrix remodeling post-MI. Gd-ESMA enhancement was studied in a mouse model of myocardial infarction using a 7 T MRI scanner and results were compared to those achieved after injection of a nonspecific control contrast agent, gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). In the infarcted tissue, Gd-ESMA uptake (measured as R1 relaxation rate) steadily increased from day 3 to day 21 as a result of the synthesis of elastin/tropoelastin. R1 values were in good agreement with histological findings. A similar R1 behavior was observed in the remote myocardium. No mature cross-linked elastin was found at any time point. In contrast, Gd-DTPA uptake was only observed in the infarct with no changes in R1 values between 3 and 21 days post-MI. We demonstrate the feasibility of in vivo imaging of extracellular matrix remodeling post-MI using a tropoelastin/elastin binding MR contrast agent, Gd-ESMA. We found that tropoelastin is the main contributor to the increased MRI signal at late stages of MI where its augmentation in areas of infarction was in good agreement with the R1 increase. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

microRNA regulatory mechanism by which PLLA aligned nanofibers influence PC12 cell differentiation

NASA Astrophysics Data System (ADS)

Yu, Yadong; Lü, Xiaoying; Ding, Fei

2015-08-01

Objective. Aligned nanofibers (AFs) are regarded as promising biomaterials in nerve tissue engineering. However, a full understanding of the biocompatibility of AFs at the molecular level is still challenging. Therefore, the present study focused on identifying the microRNA (miRNA)-mediated regulatory mechanism by which poly-L-lactic acid (PLLA) AFs influence PC12 cell differentiation. Approach. Firstly, the effects of PLLA random nanofibers (RFs)/AFs and PLLA films (control) on the biological responses of PC12 cells that are associated with neuronal differentiation were examined. Then, SOLiD sequencing and cDNA microarray were employed to profile the expressions of miRNAs and mRNAs. The target genes of the misregulated miRNAs were predicted and compared with the mRNA profile data. Functions of the matched target genes (the intersection between the predicted target genes and the experimentally-determined, misregulated genes) were analyzed. Main results. The results revealed that neurites spread in various directions in control and RF groups. In the AF group, most neurites extended in parallel with each other. The glucose consumption and lactic acid production in the RF and AF groups were higher than those in the control group. Compared with the control group, 42 and 94 miRNAs were significantly dysregulated in the RF and AF groups, respectively. By comparing the predicted target genes with the mRNA profile data, five and 87 matched target genes were found in the RF and AF groups, respectively. Three of the matched target genes in the AF group were found to be associated with neuronal differentiation, whereas none had this association in the RF group. The PLLA AFs induced the dysregulation of miRNAs that regulate many biological functions, including axonal guidance, lipid metabolism and long-term potentiation. In particular, two miRNA-matched target gene-biological function modules associated with neuronal differentiation were identified as follows: (1) miR-23b, miR-18a, miR-107 and miR-103 regulate the Rras2 and Nf1 gene and thereby, affect cytoskeleton regulation and MAPK pathway; (2) miR-92a, miR-339-5p, miR-25, miR-125a-5p, miR-351 and miR-19b co-regulate the Pafah1b1 gene, affecting PC12 cell migration and differentiation. Significance. This work demonstrates a bioinformatic approach to accomplish miRNA-mRNA profile integrative analysis and provides more insights for understanding the regulatory mechanism of miRNA in AFs affecting neuronal differentiation. These findings will be greatly beneficial for the application and design of AFs in nerve tissue engineering.

Association of US Centers for Medicare and Medicaid Services Hospital 30-Day Risk-Standardized Readmission Metric With Care Quality and Outcomes After Acute Myocardial Infarction

PubMed Central

Pandey, Ambarish; Golwala, Harsh; Hall, Hurst M.; Wang, Tracy Y.; Lu, Di; Xian, Ying; Chiswell, Karen; Joynt, Karen E.; Goyal, Abhinav; Das, Sandeep R.; Kumbhani, Dharam; Julien, Howard; Fonarow, Gregg C.

2017-01-01

Importance The US Centers for Medicare and Medicaid Services Hospital Readmissions Reduction Program penalizes hospitals with higher-than-expected risk-adjusted 30-day readmission rates (excess readmission ratio [ERR] > 1) after acute myocardial infarction (MI). However, the association of ERR with MI care processes and outcomes are not well established. Objective To evaluate the association between ERR for MI with in-hospital process of care measures and 1-year clinical outcomes. Design, Setting, and Participants Observational analysis of hospitalized patients with MI from National Cardiovascular Data Registry/Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With the Guidelines centers subject to the first cycle of the Hospital Readmissions Reduction Program between July 1, 2008, and June 30, 2011. Exposures The ERR for MI (MI-ERR) in 2011. Main Outcomes and Measures Adherence to process of care measures during index hospitalization in the overall study population and risk of the composite outcome of mortality or all-cause readmission within 1 year of discharge and its individual components among participants with available Centers for Medicare and Medicaid Services–linked data. Results The median ages of patients in the MI-ERR greater than 1 and tertiles 1, 2, and 3 of the MI-ERR greater than 1 groups were 64, 63, 64, and 63 years, respectively. Among 380 hospitals that treated a total of 176 644 patients with MI during the study period, 43% had MI-ERR greater than 1. The proportions of patients of black race, those with heart failure signs at admission, and bleeding complications increased with higher MI-ERR. There was no significant association between adherence to MI performance measures and MI-ERR (adjusted odds ratio, 0.94; 95% CI, 0.81-1.08, per 0.1-unit increase in MI-ERR for overall defect-free care). Among the 51 453 patients with 1-year outcomes data available, higher MI-ERR was associated with higher adjusted risk of the composite outcome and all-cause readmission within 1 year of discharge. This association was largely driven by readmissions early after discharge and was not significant in landmark analyses beginning 30 days after discharge. The MI-ERR was not associated with risk for mortality within 1 year of discharge in the overall and 30-day landmark analyses. Conclusions and Relevance During the first cycle of the Hospital Readmissions Reduction Program, participating hospitals’ risk-adjusted 30-day readmission rates following MI were not associated with in-hospital quality of MI care or clinical outcomes occurring after the first 30 days after discharge. PMID:28445559

MitomiRs in human inflamm-aging: a hypothesis involving miR-181a, miR-34a and miR-146a.

PubMed

Rippo, Maria Rita; Olivieri, Fabiola; Monsurrò, Vladia; Prattichizzo, Francesco; Albertini, Maria Cristina; Procopio, Antonio Domenico

2014-08-01

Mitochondria are intimately involved in the aging process. The decline of autophagic clearance during aging affects the equilibrium between mitochondrial fusion and fission, leading to a build-up of dysfunctional mitochondria, oxidative stress, chronic low-grade inflammation, and increased apoptosis rates, the main hallmarks of aging. Current research suggests that a large number of microRNAs (miRs or miRNAs) are differentially expressed during cell aging. Other lines of evidence indicate that several miRs likely share in "inflamm-aging", an aging-related state characterized by systemic chronic inflammation that in turn provides a biological background favoring susceptibility to age-related diseases and disabilities. Interestingly, miRs can modulate mitochondrial activity, and a discrete miR set has recently been identified in mitochondria of different species and cell types (mitomiRs). Here we show that some mitomiRs (let7b, mir-146a, -133b, -106a, -19b, -20a, -34a, -181a and -221) are also among the miRs primarily involved in cell aging and in inflamm-aging. Of note, Ingenuity Pathway Analysis (IPA) of aging-related mitomiR targets has disclosed a number of resident mitochondrial proteins playing large roles in energy metabolism, mitochondrial transport and apoptosis. Among these, Bcl-2 family members--which are critically involved in maintaining mitochondrial integrity--may play a role in controlling mitochondrial function and dysfunction during cellular aging, also considering that Bcl-2, the master member of the family, is an anti-oxidant and anti-apoptotic factor and regulates mitochondrial fission/fusion and autophagy. This intriguing hypothesis is supported by several observations: i) in endothelial cells undergoing replicative senescence (HUVECs), a well-established model of cell senescence, miR-146a, miR-34a, and miR-181a are over-expressed whereas their target Bcl-2 is down-regulated; ii) IPA of the miR-146a, miR-34a and miR-181a network shows that they are closely linked to each other, to Bcl-2 and to mitochondria; and iii) miR-146a, miR-34a, and miR-181a are involved in important cell functions (growth, proliferation, death, survival, maintenance) and age-related diseases (cancer, skeletal and muscle disorders, neurological, cardiovascular and metabolic diseases). In conclusion several aging-related mitomiRs may play a direct role in controlling mitochondrial function by regulating mitochondrial protein expression. Their modulation could thus mediate the loss of mitochondrial integrity and function in aging cells, inducing or contributing to the inflammatory response and to age-related diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

Efficient FIR Filter Implementations for Multichannel BCIs Using Xilinx System Generator.

PubMed

Ghani, Usman; Wasim, Muhammad; Khan, Umar Shahbaz; Mubasher Saleem, Muhammad; Hassan, Ali; Rashid, Nasir; Islam Tiwana, Mohsin; Hamza, Amir; Kashif, Amir

2018-01-01

Background . Brain computer interface (BCI) is a combination of software and hardware communication protocols that allow brain to control external devices. Main purpose of BCI controlled external devices is to provide communication medium for disabled persons. Now these devices are considered as a new way to rehabilitate patients with impunities. There are certain potentials present in electroencephalogram (EEG) that correspond to specific event. Main issue is to detect such event related potentials online in such a low signal to noise ratio (SNR). In this paper we propose a method that will facilitate the concept of online processing by providing an efficient filtering implementation in a hardware friendly environment by switching to finite impulse response (FIR). Main focus of this research is to minimize latency and computational delay of preprocessing related to any BCI application. Four different finite impulse response (FIR) implementations along with large Laplacian filter are implemented in Xilinx System Generator. Efficiency of 25% is achieved in terms of reduced number of coefficients and multiplications which in turn reduce computational delays accordingly.

Identification of age- and disease-related alterations in circulating miRNAs in a mouse model of Alzheimer's disease

PubMed Central

Garza-Manero, Sylvia; Arias, Clorinda; Bermúdez-Rattoni, Federico; Vaca, Luis; Zepeda, Angélica

2015-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder characterized clinically by the progressive decline of memory and cognition. Histopathologically, two main hallmarks have been identified in AD: amyloid-β peptide extracellular neuritic plaques and neurofibrillary tangles formed by posttranslational modified tau protein. A definitive diagnosis can only be achieved after the post mortem verification of the histological mentioned alterations. Therefore, the development of biomarkers that allow an early diagnosis and/or predict disease progression is imperative. The prospect of a blood-based biomarker is possible with the finding of circulating microRNAs (miRNAs), a class of small non-coding RNAs of 22–25 nucleotides length that regulate mRNA translation rate. miRNAs travel through blood and recent studies performed in potential AD cases suggest the possibility of finding pathology-associated differences in circulating miRNA levels that may serve to assist in early diagnosis of the disease. However, these studies analyzed samples at a single time-point, limiting the use of miRNAs as biomarkers in AD progression. In this study we evaluated miRNA levels in plasma samples at different time-points of the evolution of an AD-like pathology in a transgenic mouse model of the disease (3xTg-AD). We performed multiplex qRT-PCR and compared the plasmatic levels of 84 miRNAs previously associated to central nervous system development and disease. No significant differences were detected between WT and transgenic young mice. However, age-related significant changes in miRNA abundance were observed for both WT and transgenic mice, and some of these were specific for the 3xTg-AD. In agreement, variations in the levels of particular miRNAs were identified between WT and transgenic old mice thus suggesting that the age-dependent evolution of the AD-like pathology, rather than the presence and expression of the transgenes, modifies the circulating miRNA levels in the 3xTg-AD mice. PMID:25745387

Identification of age- and disease-related alterations in circulating miRNAs in a mouse model of Alzheimer's disease.

PubMed

Garza-Manero, Sylvia; Arias, Clorinda; Bermúdez-Rattoni, Federico; Vaca, Luis; Zepeda, Angélica

2015-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder characterized clinically by the progressive decline of memory and cognition. Histopathologically, two main hallmarks have been identified in AD: amyloid-β peptide extracellular neuritic plaques and neurofibrillary tangles formed by posttranslational modified tau protein. A definitive diagnosis can only be achieved after the post mortem verification of the histological mentioned alterations. Therefore, the development of biomarkers that allow an early diagnosis and/or predict disease progression is imperative. The prospect of a blood-based biomarker is possible with the finding of circulating microRNAs (miRNAs), a class of small non-coding RNAs of 22-25 nucleotides length that regulate mRNA translation rate. miRNAs travel through blood and recent studies performed in potential AD cases suggest the possibility of finding pathology-associated differences in circulating miRNA levels that may serve to assist in early diagnosis of the disease. However, these studies analyzed samples at a single time-point, limiting the use of miRNAs as biomarkers in AD progression. In this study we evaluated miRNA levels in plasma samples at different time-points of the evolution of an AD-like pathology in a transgenic mouse model of the disease (3xTg-AD). We performed multiplex qRT-PCR and compared the plasmatic levels of 84 miRNAs previously associated to central nervous system development and disease. No significant differences were detected between WT and transgenic young mice. However, age-related significant changes in miRNA abundance were observed for both WT and transgenic mice, and some of these were specific for the 3xTg-AD. In agreement, variations in the levels of particular miRNAs were identified between WT and transgenic old mice thus suggesting that the age-dependent evolution of the AD-like pathology, rather than the presence and expression of the transgenes, modifies the circulating miRNA levels in the 3xTg-AD mice.

miR-1338-5p Modulates Growth Hormone Secretion and Glucose Utilization by Regulating ghitm in Genetically Improved Farmed Tilapia (GIFT, Oreochromis niloticus)

PubMed Central

Qiang, Jun; Bao, Jing Wen; Li, Hong Xia; Chen, De Ju; He, Jie; Tao, Yi Fan; Xu, Pao

2017-01-01

MicroRNAs (miRNAs) are endogenous, non-coding small RNA molecules about 22 nt in length, which could regulate the expressions of target genes and participate in growth and development of organisms. Genetically improved farmed tilapia (GIFT, Oreochromis niloticus) is an important economic freshwater species in China and the growth performance is one of the main breeding indicators. Growth hormone inducible transmembrane protein (ghitm) plays an important role in growth and development of both mammals and invertebrates; however, little studies have been reported on fish. Our previous experiments indicated that miR-1338-5p expression may be negatively correlated with ghitm expression. In this study, we firstly used qRT-PCR and northern blot to verify the expression of miR-1338-5p and ghitm, and determined the binding site of miR-1338-5p in the ghitm 3′-untranslated region (UTR) by luciferase reporter assay. Secondly, juveniles GIFT injected with miR-1338-5p antagomir were used to analyze the regulatory function of the miR-1338-5p-ghitm pair in vivo. The results showed that the ghitm 3′-UTR was complementary to the 5′ 2–8-nt site of miR-1338-5p. Inhibition of miR-1338-5p promoted ghitm expression in the pituitary and liver of GIFT. ghitm could interfere in the growth hormone (Gh)–growth hormone receptor (Ghr)–insulin-like growth factor (Igf) signaling pathway by competing with the ghr1 for combination with Gh, and then reduce the growth of GIFT. Moreover, the reduction of Gh in serum may regulate insulin secretion and result in the increasing sugar and fat storage in serum and liver. Our results suggest that miR-1338-5p participates in the growth and development of GIFT through the regulation of ghitm, which provides theoretical support for the study of the fish growth mechanism. PMID:29270127

miR-1338-5p Modulates Growth Hormone Secretion and Glucose Utilization by Regulating ghitm in Genetically Improved Farmed Tilapia (GIFT, Oreochromis niloticus).

PubMed

Qiang, Jun; Bao, Jing Wen; Li, Hong Xia; Chen, De Ju; He, Jie; Tao, Yi Fan; Xu, Pao

2017-01-01

MicroRNAs (miRNAs) are endogenous, non-coding small RNA molecules about 22 nt in length, which could regulate the expressions of target genes and participate in growth and development of organisms. Genetically improved farmed tilapia (GIFT, Oreochromis niloticus ) is an important economic freshwater species in China and the growth performance is one of the main breeding indicators. Growth hormone inducible transmembrane protein ( ghitm ) plays an important role in growth and development of both mammals and invertebrates; however, little studies have been reported on fish. Our previous experiments indicated that miR-1338-5p expression may be negatively correlated with ghitm expression. In this study, we firstly used qRT-PCR and northern blot to verify the expression of miR-1338-5p and ghitm , and determined the binding site of miR-1338-5p in the ghitm 3'-untranslated region (UTR) by luciferase reporter assay. Secondly, juveniles GIFT injected with miR-1338-5p antagomir were used to analyze the regulatory function of the miR-1338-5p- ghitm pair in vivo . The results showed that the ghitm 3'-UTR was complementary to the 5' 2-8-nt site of miR-1338-5p. Inhibition of miR-1338-5p promoted ghitm expression in the pituitary and liver of GIFT. ghitm could interfere in the growth hormone (Gh)-growth hormone receptor (Ghr)-insulin-like growth factor (Igf) signaling pathway by competing with the ghr1 for combination with Gh, and then reduce the growth of GIFT. Moreover, the reduction of Gh in serum may regulate insulin secretion and result in the increasing sugar and fat storage in serum and liver. Our results suggest that miR-1338-5p participates in the growth and development of GIFT through the regulation of ghitm , which provides theoretical support for the study of the fish growth mechanism.

Salivary Matrix Metalloproteinase-8 and -9 and Myeloperoxidase in Relation to Coronary Heart and Periodontal Diseases: A Subgroup Report from the PAROKRANK Study (Periodontitis and Its Relation to Coronary Artery Disease).

PubMed

Rathnayake, Nilminie; Gustafsson, Anders; Norhammar, Anna; Kjellström, Barbro; Klinge, Björn; Rydén, Lars; Tervahartiala, Taina; Sorsa, Timo

2015-01-01

Matrix metalloproteinase (MMP) -8, -9 and myeloperoxidase (MPO) are inflammatory mediators. The potential associations between MMP-8, -9, MPO and their abilities to reflect cardiovascular risk remains to be evaluated in saliva. The objective of this study was to investigate the levels and associations of salivary MMP-8, -9, MPO and tissue inhibitors of metalloproteinase (TIMP)-1 in myocardial infarction (MI) patients and controls with or without periodontitis. 200 patients with a first MI admitted to coronary care units in Sweden from May 2010 to December 2011 and 200 controls matched for age, gender, residential area and without previous MI were included. Dental examination and saliva sample collection was performed 6-10 weeks after the MI in patients and at baseline in controls. The biomarkers MMP -8, -9, MPO and TIMP-1 were analyzed by time-resolved immunofluorescence assay (IFMA), Western blot and Enzyme-Linked ImmunoSorbent Assay (ELISA). After compensation for gingivitis, gingival pockets and smoking, the mean salivary levels of MMP-8 (543 vs 440 ng/mL, p = 0.003) and MPO (1899 vs 1637 ng/mL, p = 0.02) were higher in non-MI subjects compared to MI patients. MMP-8, -9 and MPO correlated positively with clinical signs of gingival/periodontal inflammation while TIMP-1 correlated mainly negatively with these signs. The levels of latent and active forms of MMP-8 did not differ between the MI and non-MI groups. Additionally, MMP-8, MPO levels and MMP-8/TIMP-1 ratio were significantly higher in men compared to women with MI. This study shows that salivary levels of the analyzed biomarkers are associated with periodontal status. However, these biomarkers could not differentiate between patients with or without a MI. These findings illustrate the importance to consider the influence of oral conditions when analyzing levels of inflammatory salivary biomarkers.

Expression of miR-34c in response to overexpression of Boule and Stra8 in dairy goat male germ line stem cells (mGSCs).

PubMed

Li, Mingzhao; Yu, Meng; Liu, Chao; Zhu, Haijing; Hua, Jinlian

2013-06-01

Reproduction is required for the survival of all mammalian animals. Spermatogenesis is an essential and complex developmental process that ultimately results in production of haploid spermatozoa. Recent studies demonstrated that Boule and stimulated by retinoic acid 8 (Stra8) played important roles in initiation meiosis in male germ cells. miR-34c is indispensable in the late steps of spermatogenesis; remarkably, the main function of miR-34c is to reduce cell proliferation potentiality and promote cellular apoptosis. The objectives of this study were to investigate the expression patterns of Boule, Stra8, P53 and miR-34c in dairy goat testis and their relationship in male germ line stem cells (mGSCs). The results first revealed the expression patterns of Boule, Stra8, P53 and miR-34c in 30 dpp, 90 dpp and adult testes of dairy goats. The expression levels of Boule, Stra8, P53 and miR-34c in adult dairy goat testes were significantly higher than that of 30 dpp. Overexpression of Boule and Stra8 promoted the expression of miR-34c in dairy goat mGSCs. In our previous study, we showed that miR-34c was P53 dependent in mGSCs. These results have shown that the up-regulation of miR-34c was not due to P53 protein activation but which might be caused by the up-regulation of Boule and Stra8 promoting the advance of meiosis. In addition, we found retinoic acid would decrease the expression of P53 and miR-34c, however, did not change the expression of c-Myc greatly. It suggested that the function of driving differentiation of dairy goat mGSCs by retinoic acid might not be caused by P53. Copyright © 2013 John Wiley & Sons, Ltd.

The Potential of MicroRNAs as Prostate Cancer Biomarkers.

PubMed

Fabris, Linda; Ceder, Yvonne; Chinnaiyan, Arul M; Jenster, Guido W; Sorensen, Karina D; Tomlins, Scott; Visakorpi, Tapio; Calin, George A

2016-08-01

Short noncoding RNAs known as microRNAs (miRNAs) control protein expression through the degradation of RNA or the inhibition of protein translation. The miRNAs influence a wide range of biologic processes and are often deregulated in cancer. This family of small RNAs constitutes potentially valuable markers for the diagnosis, prognosis, and therapeutic choices in prostate cancer (PCa) patients, as well as potential drugs (miRNA mimics) or drug targets (anti-miRNAs) in PCa management. To review the currently available data on miRNAs as biomarkers in PCa and as possible tools for early detection and prognosis. A systematic review was performed searching the PubMed database for articles in English using a combination of the following terms: microRNA, miRNA, cancer, prostate cancer, miRNA profiling, diagnosis, prognosis, therapy response, and predictive marker. We summarize the existing literature regarding the profiling of miRNA in PCa detection, prognosis, and response to therapy. The articles were reviewed with the main goal of finding a common recommendation that could be translated from bench to bedside in future clinical practice. The miRNAs are important regulators of biologic processes in PCa progression. A common expression profile characterizing each tumor subtype and stage has still not been identified for PCa, probably due to molecular heterogeneity as well as differences in study design and patient selection. Large-scale studies that should provide additional important information are still missing. Further studies, based on common clinical parameters and guidelines, are necessary to validate the translational potential of miRNAs in PCa clinical management. Such common signatures are promising in the field and emerge as potential biomarkers. The literature shows that microRNAs hold potential as novel biomarkers that could aid prostate cancer management, but additional studies with larger patient cohorts and common guidelines are necessary before clinical implementation. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

MEN1 mutations and potentially MEN1-targeting miRNAs are responsible for menin deficiency in sporadic and MEN1 syndrome-associated primary hyperparathyroidism.

PubMed

Grolmusz, Vince Kornél; Borka, Katalin; Kövesdi, Annamária; Németh, Kinga; Balogh, Katalin; Dékány, Csaba; Kiss, András; Szentpéteri, Anna; Sármán, Beatrix; Somogyi, Anikó; Csajbók, Éva; Valkusz, Zsuzsanna; Tóth, Miklós; Igaz, Péter; Rácz, Károly; Patócs, Attila

2017-09-01

Inherited, germline mutations of menin-coding MEN1 gene cause multiple endocrine neoplasia type 1 (MEN1), while somatic MEN1 mutations are the sole main driver mutations in sporadic primary hyperparathyroidism (PHPT), suggesting that menin deficiency has a central role in the pathogenesis of PHPT. MiRNAs are small, noncoding RNAs posttranscriptionally regulating gene expression. Our aim was to investigate both the role of MEN1 mutations and potentially MEN1-targeting miRNAs as the underlying cause of menin deficiency in MEN1-associated and sporadic PHPT tissues. Fifty six PHPT tissues, including 16 MEN1-associated tissues, were evaluated. Diagnosis of MEN1 syndrome was based on identification of germline MEN1 mutations. In silico target prediction was used to identify miRNAs potentially targeting MEN1. Menin expression was determined by immunohistochemistry while expression of miRNAs was analyzed by quantitative real-time PCR. Sporadic PHPT tissues were subjected to somatic MEN1 mutation analysis as well. Lack of nuclear menin was identified in all MEN1-associated and in 28% of sporadic PHPT tissues. Somatic MEN1 mutations were found in 25% of sporadic PHPTs. The sensitivity and specificity of menin immunohistochemistry to detect a MEN1 mutation were 86 and 87%, respectively. Expression levels of hsa-miR-24 and hsa-miR-28 were higher in sporadic compared to MEN1-associated PHPT tissues; however, no difference in miRNA levels occurred between menin-positive and menin-negative PHPT tissues. Menin deficiency is the consequence of a MEN1 mutation in most menin-negative PHPT tissues. Elevated expression of hsa-miR-24 and hsa-miR-28 mark the first epigenetic changes observed between sporadic and MEN1-associated PHPT.

[Heart rupture in acute myocardial infarction: multicenter observational study of the coronary unit of Piedmont].

PubMed

Pron, Paolo Giay; Angelino, Paolo; Varbella, Ferdinando; Bongioanni, Sergio; Masi, Andrea Sibona; Iazzolino, Ernesto; Bonfiglio, Giovanna; Brusin, Maria Cristina Rosa; Mainardi, Loredana; Nicastro, Cristina; Bouslenko, Zoe; Conte, Maria Rosa

2002-02-01

The aim of this study was to prospectively evaluate the incidence of cardiac rupture during myocardial infarction (MI) as well as the predictive value of the main cardiac rupture risk factors. The study was carried out in 17 coronary care units (CCU) between January and December 1999 in the Piedmont region (Italy). The incidence of cardiac rupture was 1.4% of the total number of MI (n = 3041). Data from 13 out of 17 CCU showed the following causes of death during MI: 66% heart failure, 16% cardiac rupture, 7% arrhythmias, 11% others. Twenty-seven percent out of 44 cardiac ruptures had prior angina, 9% prior MI; 24% of patients were diabetic; 38% had anterior wall MI; 62% infero-postero-lateral MI; 86% showed ST-segment elevation, and 79.5% developed Q waves. Thrombolysis was administered in 39% of cases. Forty-three percent cardiac ruptures occurred within 24 hours. Electromechanical dissociation was present in 73% of cases, syncope and hypotension in 43%, bradycardia in 30%. An echocardiogram was performed in 89% of cases in the suspicion of cardiac rupture but only 45% showed severe pericardial effusion. One patient was referred to surgery but he died in the postoperative period. Autoptical diagnosis was made in 32% of cases. All patients died. The analysis of some qualitative variables (gender, thrombolysis, MI localization, ST-segment/non-ST-segment elevation) in 8 out of 17 CCU, between the cardiac rupture group (n = 22) and the MI group (n = 1330) showed a significant result only for the female gender. Cardiac rupture is the second cause of death during MI after heart failure; there is a higher incidence of cardiac rupture in infero-postero-lateral MI, after the first 24 hours particularly in the female gender; there is a low global incidence (1.4%).

MicroRNA-138 and MicroRNA-25 Down-regulate Mitochondrial Calcium Uniporter, Causing the Pulmonary Arterial Hypertension Cancer Phenotype

PubMed Central

Hong, Zhigang; Chen, Kuang-Hueih; DasGupta, Asish; Potus, Francois; Dunham-Snary, Kimberly; Bonnet, Sebastien; Tian, Lian; Fu, Jennifer; Breuils-Bonnet, Sandra; Provencher, Steeve; Wu, Danchen; Mewburn, Jeffrey; Ormiston, Mark L.

2017-01-01

Rationale: Pulmonary arterial hypertension (PAH) is an obstructive vasculopathy characterized by excessive pulmonary artery smooth muscle cell (PASMC) proliferation, migration, and apoptosis resistance. This cancer-like phenotype is promoted by increased cytosolic calcium ([Ca2+]cyto), aerobic glycolysis, and mitochondrial fission. Objectives: To determine how changes in mitochondrial calcium uniporter (MCU) complex (MCUC) function influence mitochondrial dynamics and contribute to PAH’s cancer-like phenotype. Methods: PASMCs were isolated from patients with PAH and healthy control subjects and assessed for expression of MCUC subunits. Manipulation of the pore-forming subunit, MCU, in PASMCs was achieved through small interfering RNA knockdown or MCU plasmid-mediated up-regulation, as well as through modulation of the upstream microRNAs (miRs) miR-138 and miR-25. In vivo, nebulized anti-miRs were administered to rats with monocrotaline-induced PAH. Measurements and Main Results: Impaired MCUC function, resulting from down-regulation of MCU and up-regulation of an inhibitory subunit, mitochondrial calcium uptake protein 1, is central to PAH’s pathogenesis. MCUC dysfunction decreases intramitochondrial calcium ([Ca2+]mito), inhibiting pyruvate dehydrogenase activity and glucose oxidation, while increasing [Ca2+]cyto, promoting proliferation, migration, and fission. In PAH PASMCs, increasing MCU decreases cell migration, proliferation, and apoptosis resistance by lowering [Ca2+]cyto, raising [Ca2+]mito, and inhibiting fission. In normal PASMCs, MCUC inhibition recapitulates the PAH phenotype. In PAH, elevated miRs (notably miR-138) down-regulate MCU directly and also by decreasing MCU’s transcriptional regulator cAMP response element–binding protein 1. Nebulized anti-miRs against miR-25 and miR-138 restore MCU expression, reduce cell proliferation, and regress established PAH in the monocrotaline model. Conclusions: These results highlight miR-mediated MCUC dysfunction as a unifying mechanism in PAH that can be therapeutically targeted. PMID:27648837

Culturally and economically important nontimber forest products of northern Maine

Treesearch

Michelle J. Baumflek; Marla R. Emery; Clare Ginger

2010-01-01

Nontimber forest products (NTFPs) gathered for food, medicine, craft, spiritual, aesthetic, and utilitarian purposes make substantial contributions to the economic viability and cultural vitality of communities. In the St. John River watershed of northern Maine, people identifying with cultural groups including Acadian, Maliseet, Mi'kmaq, Scotch-Irish, and Swedish...

A novel RNA-sequencing-based miRNA signature predicts with recurrence and outcome of hepatocellular carcinoma.

PubMed

Fumao, Bai; Zhou, Huaibin; Ma, Mengni; Guan, Chen; Lyu, Jianxin; Meng, Qing H

2018-05-02

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer and the second leading cause of cancer-related deaths worldwide. Given that the rate of HCC recurrence 5 years after liver resection is as high as 70%, patient with HCC typically have a poor outcome. A biomarker or set of biomarkers that could predict disease recurrence would have a substantial clinical impact, allowing earlier detection of recurrence and more effective treatment. With the aim of identifying a new microRNA (miRNA) signature associated with HCC recurrence, we analyzed data on 306 HCC patients for whom both miRNA expression profiles and complete clinical information were available from The Cancer Genome Atlas (TCGA) database. Through this analysis, we identified a six-miRNA signature that could effectively predict patients' recurrence risk; the high-risk and low-risk groups had significantly different recurrence-free survival rates. Time-dependent receiver operating characteristic analysis indicated that this signature had a good predictive performance. Multivariable Cox regression and stratified analyses demonstrated that the six-miRNA signature was independent of other clinical features. Functional enrichment analysis of the gene targets of the six prognostic miRNAs indicated enrichment mainly in cancer-related pathways and important cell biological processes. Our results support use of this six-miRNA signature as an independent factor for predicting recurrence and outcome of patients with HCC. Molecular Oncology (2018) © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Role of Forkhead Box Class O proteins in cancer progression and metastasis.

PubMed

Kim, Chang Geun; Lee, Hyemin; Gupta, Nehal; Ramachandran, Sharavan; Kaushik, Itishree; Srivastava, Sangeeta; Kim, Sung-Hoon; Srivastava, Sanjay K

2018-06-01

It is now widely accepted that several gene alterations including transcription factors are critically involved in cancer progression and metastasis. Forkhead Box Class O proteins (FoxOs) including FoxO1/FKHR, FoxO3/FKHRL1, FoxO4/AFX and FoxO6 transcription factors are known to play key roles in proliferation, apoptosis, metastasis, cell metabolism, aging and cancer biology through their phosphorylation, ubiquitination, acetylation and methylation. Though FoxOs are proved to be mainly regulated by upstream phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3 K)/Akt signaling pathway, the role of FoxOs in cancer progression and metastasis still remains unclear so far. Thus, with previous experimental evidences, the present review discussed the role of FoxOs in association with metastasis related molecules including cannabinoid receptor 1 (CNR1), Cdc25A/Cdk2, Src, serum and glucocorticoid inducible kinases (SGKs), CXCR4, E-cadherin, annexin A8 (ANXA8), Zinc finger E-box-binding homeobox 2 (ZEB2), human epidermal growth factor receptor 2 (HER2) and mRNAs such as miR-182, miR-135b, miR-499-5p, miR-1274a, miR-150, miR-34b/c and miR-622, subsequently analyzed the molecular mechanism of some natural compounds targeting FoxOs and finally suggested future research directions in cancer progression and metastasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

MicroRNAs for osteosarcoma in the mouse: a meta-analysis

PubMed Central

Chang, Junli; Yao, Min; Li, Yimian; Zhao, Dongfeng; Hu, Shaopu; Cui, Xuejun; Liu, Gang; Shi, Qi; Wang, Yongjun; Yang, Yanping

2016-01-01

Osteosarcoma (OS) is the most common primary malignant bone carcinoma with high morbidity that happens mainly in children and young adults. As the key components of gene-regulatory networks, microRNAs (miRNAs) control many critical pathophysiological processes, including initiation and progression of cancers. The objective of this study is to summarize and evaluate the potential of miRNAs as targets for prevention and treatment of OS in mouse models, and to explore the methodological quality of current studies. We searched PubMed, Web of Science, Embase, Wan Fang Database, VIP Database, China Knowledge Resource Integrated Database, and Chinese BioMedical since their beginning date to 10 May 2016. Two reviewers separately screened the controlled studies, which estimate the effects of miRNAs on osteosarcoma in mice. A pair-wise analysis was performed. Thirty six studies with enough randomization were selected and included in the meta-analysis. We found that blocking oncogenic or restoring decreased miRNAs in cancer cells could significantly suppress the progression of OS in vivo, as assessed by tumor volume and tumor weight. This meta-analysis suggests that miRNAs are potential therapeutic targets for OS and correction of the altered expression of miRNAs significantly suppresses the progression of OS in mouse models, however, the overall methodological quality of studies included here was low, and more animal studies with the rigourous design must be carried out before a miRNA-based treatment could be translated from animal studies to clinical trials. PMID:27852052

Estrogenic gper signaling regulates mir144 expression in cancer cells and cancer-associated fibroblasts (cafs).

PubMed

Vivacqua, Adele; De Marco, Paola; Santolla, Maria Francesca; Cirillo, Francesca; Pellegrino, Michele; Panno, Maria Luisa; Abonante, Sergio; Maggiolini, Marcello

2015-06-30

MicroRNAs (miRNAs) are small non coding RNA molecules that play a crucial role in several pathophysiological conditions, including cancer. The stimulation of hormone-sensitive tumors by estrogens are mediated by estrogen receptor (ER)α and G protein estrogen receptor (GPER). Previous studies have reported that ERα regulates miRNA expression, while this ability of GPER remains to be elucidated. Here, we demonstrate that in SkBr3 breast cancer and HepG2 hepatocarcinoma cells, 17β-estradiol (E2) and the selective GPER ligand G-1 induce miR144 expression through GPER and the involvement of the PI3K/ERK1/2/Elk1 transduction pathway. Moreover, we show that E2 and G-1 down-regulate through miR144 the onco-suppressor Runx1 and increase cell cycle progression. The capability of E2 and G-1 in triggering the induction of miR144 and the down-regulation of Runx1 was also confirmed in cancer-associated fibroblasts (CAFs) that are main components of the tumor microenvironment driving cancer progression. Further confirming these results, Runx1 protein levels were found decreased in tumor xenografts upon G-1 treatment. On the basis of our findings miR144 and Runx1 may be included among the oncotargets of GPER action. Moreover, the present data provide new insights regarding the ability of estrogens to trigger the GPER/miR144/Runx1 transduction pathway toward the stimulation of cancer progression.

Neutrino-Nucleon Deep Inelastic Scattering in MINERvA

NASA Astrophysics Data System (ADS)

Norrick, Anne; Minerva Collaboration

2015-04-01

Neutrino-Nucleon Deep Inelastic Scattering (DIS) events provide a probe into the structure of the nucleus that cannot be accessed via charged lepton-nucleon interactions. The MINERvA experiment is stationed in the Neutrinos from the Main Injector (NuMI) beam line at Fermi National Accelerator Laboratory. The projected sensitivity of nuclear structure function analyses using MINERvA's suite of nuclear targets (C, CH, Fe and Pb) in the upgraded 6 GeV neutrino energy NuMI beam will be explored, and their impact discussed.

Characterization of long-range functional connectivity in epileptic networks by neuronal spike-triggered local field potentials

NASA Astrophysics Data System (ADS)

Lopour, Beth A.; Staba, Richard J.; Stern, John M.; Fried, Itzhak; Ringach, Dario L.

2016-04-01

Objective. Quantifying the relationship between microelectrode-recorded multi-unit activity (MUA) and local field potentials (LFPs) in distinct brain regions can provide detailed information on the extent of functional connectivity in spatially widespread networks. These methods are common in studies of cognition using non-human animal models, but are rare in humans. Here we applied a neuronal spike-triggered impulse response to electrophysiological recordings from the human epileptic brain for the first time, and we evaluate functional connectivity in relation to brain areas supporting the generation of seizures. Approach. Broadband interictal electrophysiological data were recorded from microwires adapted to clinical depth electrodes that were implanted bilaterally using stereotactic techniques in six presurgical patients with medically refractory epilepsy. MUA and LFPs were isolated in each microwire, and we calculated the impulse response between the MUA on one microwire and the LFPs on a second microwire for all possible MUA/LFP pairs. Results were compared to clinical seizure localization, including sites of seizure onset and interictal epileptiform discharges. Main results. We detected significant interictal long-range functional connections in each subject, in some cases across hemispheres. Results were consistent between two independent datasets, and the timing and location of significant impulse responses reflected anatomical connectivity. However, within individual subjects, the spatial distribution of impulse responses was unique. In two subjects with clear seizure localization and successful surgery, the epileptogenic zone was associated with significant impulse responses. Significance. The results suggest that the spike-triggered impulse response can provide valuable information about the neuronal networks that contribute to seizures using only interictal data. This technique will enable testing of specific hypotheses regarding functional connectivity in epilepsy and the relationship between functional properties and imaging findings. Beyond epilepsy, we expect that the impulse response could be more broadly applied as a measure of long-range functional connectivity in studies of cognition.

Telomere length in alcohol dependence: A role for impulsive choice and childhood maltreatment.

PubMed

Kang, Jee In; Hwang, Syung Shick; Choi, Jong Rak; Lee, Seung-Tae; Kim, Jieun; Hwang, In Sik; Kim, Hae Won; Kim, Chan-Hyung; Kim, Se Joo

2017-09-01

Telomere shortening, a marker of cellular aging, has been considered to be linked with psychosocial stress as well as with chronic alcohol consumption, possibly mediated by oxidative stress and inflammatory response. Recent findings suggested that early life adversity on telomere dynamics may be related to impulsive choice. To further our understanding of the association of impulsive choice and childhood trauma on telomere length, we examined whether delayed discounting and childhood trauma or their interaction is related to leukocyte telomere length, while controlling for multiple potential confounding variables, in patients with alcohol dependence who are considered to have higher impulsive choice and shorter telomere length. We recruited 253 male patients with chronic alcohol dependence. All participants performed the delay discounting task, and the area under curve was used as a measure of delay discounting. Steeper delay discounting represents more impulsive choices. The modified Parent-Child Conflict Tactics Scale was used to measure childhood maltreatment. In addition, confounding factors, including socio-demographic characteristics, the Alcohol Use Disorders Identification Test, the Buss-Perry Aggression Questionnaire, the Resilience Quotient, the Beck Depression Inventory, and the Beck Anxiety Inventory, were also assessed. Hierarchical regression analyses showed a significant main effect of delay discounting (β=0.161, t=2.640, p=0.009), and an interaction effect between delay discounting and childhood maltreatment on leukocyte telomere length (β=0.173, t=2.138, p=0.034). In subsequent analyses stratified by childhood maltreatment, patients with alcohol dependence and high childhood trauma showed a significant relationship between delay discounting and leukocyte telomere length (β=0.279, t=3.183, p=0.002), while those with low trauma showed no association between them. Our findings suggest that higher impulsive choice is associated with shorter telomere length, and childhood trauma may exert a moderating effect in the relationship between impulsive choice and telomere length. Copyright © 2017. Published by Elsevier Ltd.

A new approach to impulsive rendezvous near circular orbit

NASA Astrophysics Data System (ADS)

Carter, Thomas; Humi, Mayer

2012-04-01

A new approach is presented for the problem of planar optimal impulsive rendezvous of a spacecraft in an inertial frame near a circular orbit in a Newtonian gravitational field. The total characteristic velocity to be minimized is replaced by a related characteristic-value function and this related optimization problem can be solved in closed form. The solution of this problem is shown to approach the solution of the original problem in the limit as the boundary conditions approach those of a circular orbit. Using a form of primer-vector theory the problem is formulated in a way that leads to relatively easy calculation of the optimal velocity increments. A certain vector that can easily be calculated from the boundary conditions determines the number of impulses required for solution of the optimization problem and also is useful in the computation of these velocity increments. Necessary and sufficient conditions for boundary conditions to require exactly three nonsingular non-degenerate impulses for solution of the related optimal rendezvous problem, and a means of calculating these velocity increments are presented. A simple example of a three-impulse rendezvous problem is solved and the resulting trajectory is depicted. Optimal non-degenerate nonsingular two-impulse rendezvous for the related problem is found to consist of four categories of solutions depending on the four ways the primer vector locus intersects the unit circle. Necessary and sufficient conditions for each category of solutions are presented. The region of the boundary values that admit each category of solutions of the related problem are found, and in each case a closed-form solution of the optimal velocity increments is presented. Similar results are presented for the simpler optimal rendezvous that require only one-impulse. For brevity degenerate and singular solutions are not discussed in detail, but should be presented in a following study. Although this approach is thought to provide simpler computations than existing methods, its main contribution may be in establishing a new approach to the more general problem.

Characterization of long-range functional connectivity in epileptic networks by neuronal spike-triggered local field potentials

PubMed Central

Lopour, Beth A; Staba, Richard J; Stern, John M; Fried, Itzhak; Ringach, Dario L

2017-01-01

Objective Quantifying the relationship between microelectrode-recorded multi-unit activity (MUA) and local field potentials (LFPs) in distinct brain regions can provide detailed information on the extent of functional connectivity in spatially widespread networks. These methods are common in studies of cognition using non-human animal models, but are rare in humans. Here we applied a neuronal spike-triggered impulse response to electrophysiological recordings from the human epileptic brain for the first time, and we evaluate functional connectivity in relation to brain areas supporting the generation of seizures. Approach Broadband interictal electrophysiological data were recorded from microwires adapted to clinical depth electrodes that were implanted bilaterally using stereotactic techniques in six presurgical patients with medically refractory epilepsy. MUA and LFPs were isolated in each microwire, and we calculated the impulse response between the MUA on one microwire and the LFPs on a second microwire for all possible MUA/LFP pairs. Results were compared to clinical seizure localization, including sites of seizure onset and interictal epileptiform discharges. Main results We detected significant interictal long-range functional connections in each subject, in some cases across hemispheres. Results were consistent between two independent datasets, and the timing and location of significant impulse responses reflected anatomical connectivity. However, within individual subjects, the spatial distribution of impulse responses was unique. In two subjects with clear seizure localization and successful surgery, the epileptogenic zone was associated with significant impulse responses. Significance The results suggest that the spike-triggered impulse response can provide valuable information about the neuronal networks that contribute to seizures using only interictal data. This technique will enable testing of specific hypotheses regarding functional connectivity in epilepsy and the relationship between functional properties and imaging findings. Beyond epilepsy, we expect that the impulse response could be more broadly applied as a measure of long-range functional connectivity in studies of cognition. PMID:26975603

[Impulsivity - aggression - depression: study of adolescents' problem behavior in light of their personality traits].

PubMed

Pikó, Bettina; Pinczés, Tamás

2014-01-01

Impulsivity is a personality trait that may determine our everyday living, quality of life, decisions. Impulsivity in particular has a great significance during adolescence as a part of the adolescent neuroanatomical and neuropsychiatric developmental processes. The main goal of the present study was to examine correlations among depressive symptomatology, types of aggressive behaviors (verbal, physical, psychic), impulsivity and other personality traits (risk-taking, empathy and self-efficacy) in adolescents. Data collection was going on in Debrecen during the first semester of the year 2012 using classes from three high schools (N = 413), 237 (57,4%) boys and 176 (42,6%) girls. The self-administered questionnaire contained items on mental health and personality traits beyond sociodemographics. After descriptive statistics, correlation and multiple linear regression analyses were applied to detect correlations. Girls reported more depressive symptoms and their level of empathy was also higher. In terms of aggression, significant gender difference was detected only in case of physical aggression with a surplus of boys. Based on multiple regression analyses, we may conclude that impulsivity acted as a risk factor both for mean levels of depressive symptomatology and aggression scales. Besides, lack of empathy proved to be related to physical aggression. In both sexes, self-efficacy was positively associated with verbal and physical aggression. Among girls, self-efficacy was a negative predictor of psychic aggression, that is, it seems to act as a protective factor. In summary, we may conclude that there are strong correlations among depressive symptomatology, aggressive behaviors and impulsivity, and this association may be colored by further personality traits, such as risk-taking, empathy, and self-efficacy. There is a need for learning some basic effective techniques for aggression management and self control as early as adolescence.

Sex modulates approach systems and impulsivity in substance dependence.

PubMed

Perry, Robert I; Krmpotich, Theodore; Thompson, Laetitia L; Mikulich-Gilbertson, Susan K; Banich, Marie T; Tanabe, Jody

2013-11-01

Personality traits such as pathological engagement in approach behaviors, high levels of impulsivity and heightened negative affect are consistently observed in substance dependent individuals (SDI). The clinical course of addiction has been shown to differ between sexes. For example, women increase their rates of consumption of some drugs of abuse more quickly than men. Despite the potential influence of personality and sex on features of addiction, few studies have investigated the interaction of these factors in substance dependence. Fifty-one SDI (26 males, 25 females) and 66 controls (41 males, 25 females) completed the Behavioral Inhibition/Behavioral Activation System (BIS/BAS) Scales, the Barratt Impulsiveness Scale, and the Positive and Negative Affect Schedule (PANAS-X). Data were analyzed with 2×2 ANCOVAs testing for main effects of group, sex and group by sex interactions, adjusting for education level. Significant group by sex interactions were observed for BAS scores [F(1,116)=7.03, p<.01] and Barratt Motor Impulsiveness [F(1,116)=6.11, p<.02] with female SDI showing the highest approach tendencies and impulsivity followed by male SDI, male controls, and finally female controls. SDI scored higher on negative affect [F(1,116)=25.23, p<.001] than controls. Behavioral Inhibition System scores were higher in women than men [F(1,116)=14.03, p<.001]. Higher BAS and motor impulsivity in SDI women relative to SDI men and control women suggest that personality traits that have been previously associated with drug use may be modulated by sex. These factors may contribute to differences in the disease course observed in male compared to female drug users. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

MicroRNA-142-3p Induces Atherosclerosis-Associated Endothelial Cell Apoptosis by Directly Targeting Rictor.

PubMed

Qin, Bing; Shu, Yaqing; Long, Ling; Li, Haiyan; Men, Xuejiao; Feng, Li; Yang, Huan; Lu, Zhengqi

2018-06-27

Atherosclerosis, a multifactorial chronic disease, is the main cause of death and impairment in the world. Endothelial cells (ECs) apoptosis plays a crucial role in the onset and development of atherosclerosis, whereas the underlying molecular mechanisms are unclear. MicroRNA-142-3p (miR-142-3p) is a well-defined tumor suppressor in several types of cancer, while the role of miR-142-3p in ECs apoptosis and the development of atherosclerosis has yet to be elucidated. Therefore, the present study aimed to investigate the role of miR-142-3p in ECs apoptosis during atherosclerosis and the underlying mechanism. Human aortic endothelial cells (HAECs) were treated with oxidized low-density lipoprotein (ox-LDL). The expression level of miR-142-3p was detected using qRT-PCR. Apoptosis was determined via flow cytometry and Caspase-3 activity assay. Prediction of the binding between miR-142-3p and 3'-UTR of Rictor mRNA was performed by bioinformatics analyses and confirmed by a dual luciferase reporter assay. The effects of miR-142-3p on endothelial apoptosis and atherosclerosis were further analyzed in an in vivo model using ApoE-/- mice fed with high-fat diet (HFD). MiR-142-3p expression was substantially up-regulated during the ox-LDL-elicited apoptosis in HAECs. Forced expression of miR-142-3p exacerbated apoptosis in ECs whereas inhibition of miR-142-3p could partly alleviate apoptotic cell death mediated by ox-LDL. Further analysis identified Rictor as a direct target of miR-142-3p, and Rictor knockdown abolished the anti-apoptotic effect of miR-142-3p inhibitor. Moreover, the Akt/endothelial nitric oxide synthase (eNOS) signaling pathway was found to mediate the beneficial effect of miR-142-3p inhibitor on endothelial apoptosis. Finally, systemic treatment with miR-142-3p antagomir attenuated endothelial apoptosis and retarded the progression of atherosclerosis in the aorta of ApoE-/- mice. Down-regulation of miR-142-3p inhibited ECs apoptosis and atherosclerotic development by up-regulating the expression of Rictor and activating the Akt/eNOS signaling pathway. This indicates that miR-142-3p may be a potential target for the prevention and treatment of atherosclerosis. © 2018 The Author(s). Published by S. Karger AG, Basel.

MiR-133 modulates TGF-β1-induced bladder smooth muscle cell hypertrophic and fibrotic response: implication for a role of microRNA in bladder wall remodeling caused by bladder outlet obstruction.

PubMed

Duan, Liu Jian; Qi, Jun; Kong, Xiang Jie; Huang, Tao; Qian, Xiao Qiang; Xu, Ding; Liang, Jun Hao; Kang, Jian

2015-02-01

Bladder outlet obstruction (BOO) evokes urinary bladder wall remodeling significantly, including the phenotype shift of bladder smooth muscle cells (BSMCs) where transforming growth factor-beta1 (TGF-β1) plays a pivotal role given the emerging function of modulating cellular phenotype. miR-133 plays a role in cardiac and muscle remodeling, however, little is known about its roles in TGF-β1-induced BSMC hypertrophic and fibrotic response. Here, we verified BOO induced bladder wall remodeling and TGF-β1 expression mainly located in bladder endothelium. Furthermore, we uncovered miR-133a/b expression profile in BOO rats, and then explored its regulated effects on BSMCs' phenotypic shift. Our study found that miR-133 became down-regulated during rat bladder remodeling. Next, we sought to examine whether the expression of miR-133 was down-regulated in primary BSMCs in response to TGF-β1 stimulation and whether forced overexpression of miR-133 could regulate profibrotic TGF-β signaling. We found that stimulation of BSMCs with exogenous TGF-β1 of increasing concentrations resulted in a dose-dependent decrease of miR-133a/b levels and transfection with miR-133 mimics attenuated TGF-β1-induced α-smooth muscle actin, extracellular matrix subtypes and fibrotic growth factor expression, whereas it upregulated high molecular weight caldesmon expression compared with the negative control. Also, downregulation of p-Smad3, not p-Smad2 by miR-133 was detected. Additionally, miR-133 overexpression suppressed TGF-β1-induced BSMC hypertrophy and proliferation through influencing cell cycle distribution. Bioinformatics analyses predicted that connective tissue growth factor (CTGF) was the potential target of miR-133, and then binding to the 3'-untranslated region of CTGF was validated by luciferase reporter assay. These results reveal a novel regulator for miR-133 to modulate TGF-β1-induced BSMC phenotypic changes by targeting CTGF through the TGF-β-Smad3 signaling pathway. A novel antifibrotic functional role for miR-133 is presented which may represent a potential target for diagnostic and therapeutic strategies in bladder fibrosis. Copyright © 2014 Elsevier Inc. All rights reserved.

Role of the long non-coding RNA PVT1 in the dysregulation of the ceRNA-ceRNA network in human breast cancer

PubMed Central

Conte, Federica; Fiscon, Giulia; Chiara, Matteo; Colombo, Teresa; Farina, Lorenzo

2017-01-01

Recent findings have identified competing endogenous RNAs (ceRNAs) as the drivers in many disease conditions, including cancers. The ceRNAs indirectly regulate each other by reducing the amount of microRNAs (miRNAs) available to target messenger RNAs (mRNAs). The ceRNA interactions mediated by miRNAs are modulated by a titration mechanism, i.e. large changes in the ceRNA expression levels either overcome, or relieve, the miRNA repression on competing RNAs; similarly, a very large miRNA overexpression may abolish competition. The ceRNAs are also called miRNA “decoys” or miRNA “sponges” and encompass different RNAs competing with each other to attract miRNAs for interactions: mRNA, long non-coding RNAs (lncRNAs), pseudogenes, or circular RNAs. Recently, we developed a computational method for identifying ceRNA-ceRNA interactions in breast invasive carcinoma. We were interested in unveiling which lncRNAs could exert the ceRNA activity. We found a drastic rewiring in the cross-talks between ceRNAs from the physiological to the pathological condition. The main actor of this dysregulated lncRNA-associated ceRNA network was the lncRNA PVT1, which revealed a net biding preference towards the miR-200 family members in normal breast tissues. Despite its up-regulation in breast cancer tissues, mimicked by the miR-200 family members, PVT1 stops working as ceRNA in the cancerous state. The specific conditions required for a ceRNA landscape to occur are still far from being determined. Here, we emphasized the importance of the relative concentration of the ceRNAs, and their related miRNAs. In particular, we focused on the withdrawal in breast cancer tissues of the PVT1 ceRNA activity and performed a gene expression and sequence analysis of its multiple isoforms. We found that the PVT1 isoform harbouring the binding site for a representative miRNA of the miR-200 family shows a drastic decrease in its relative concentration with respect to the miRNA abundance in breast cancer tissues, providing a plausibility argument to the breakdown of the sponge program orchestrated by the oncogene PVT1. PMID:28187158

Plasma reactivity in high-power impulse magnetron sputtering through oxygen kinetics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vitelaru, Catalin; National Institute for Optoelectronics, Magurele-Bucharest, RO 077125; Lundin, Daniel

2013-09-02

The atomic oxygen metastable dynamics in a Reactive High-Power Impulse Magnetron Sputtering (R-HiPIMS) discharge has been characterized using time-resolved diode laser absorption in an Ar/O{sub 2} gas mixture with a Ti target. Two plasma regions are identified: the ionization region (IR) close to the target and further out the diffusion region (DR), separated by a transition region. The μs temporal resolution allows identifying the main atomic oxygen production and destruction routes, which are found to be very different during the pulse as compared to the afterglow as deduced from their evolution in space and time.

[The use of synthetic mesh implants in surgical treatment of pelvic organ prolapse].

PubMed

Pastorčáková, M; Huser, M; Belkov, A I; Ventruba, P

2014-04-01

Pelvic organ prolapse (POP) surgical treatment went through major changes thanks to availability and wider expansion of mesh implants (MI). This work is focused on critical analysis of outcomes of these surgical procedures and recommendation prescription for their uses in application pelvic surgery. There was made analysis of published outcomes and experience with MI use in POP surgical treatment. OUTCOMES were analysed separately for each pelvic bottom section. Main criteria were surgical complications and treatment effectivity based on objective measurable parameters and subjective patients evaluation. There are formalized suitable indications and conditions for individual pelvic bottom sections for safe MI use in reconstructive POP surgery. On the basis of objective data authors also define specific situations when MI use doesn't bring any benefit and it is not recommended. Mesh implants have their definite place in POP surgical treatment. Implants with right indication and right surgical technique in comparison with classic surgical procedures have significantly lower recurrence risk with comparable or higher surgical complication rate.

The miRNA Mirage: How Close Are We to Finding a Non-Invasive Diagnostic Biomarker in Endometriosis? A Systematic Review

PubMed Central

Agrawal, Swati; Tapmeier, Thomas T.; Rahmioglu, Nilufer; Kirtley, Shona; Zondervan, Krina T.; Becker, Christian M.

2018-01-01

Background: Endometriosis is a common disorder of the reproductive age group, characterised by the presence of ectopic endometrial tissue. The disease not only causes enormous suffering to the affected women, but also brings a tremendous medical and economic burden to bear on society. There is a long lag phase between the onset and diagnosis of the disease, mainly due to its non-specific symptoms and the lack of a non-invasive test. Endometriosis can only be diagnosed invasively by laparoscopy. A specific, non-invasive test to diagnose endometriosis is an unmet clinical need. The recent discovery of microRNAs (miRNAs) as modulators of gene expression, and their stability and specificity, make them an attractive candidate biomarker. Various studies on miRNAs in endometriosis have identified their cardinal role in the pathogenesis of the disease, and have proposed them as potential biomarkers in endometriosis. Rationale/Objectives: The aims of this review were to study the role of circulatory miRNAs in endometriosis, and bring to light whether circulatory miRNAs could be potential non-invasive biomarkers to diagnose the disease. Search methods: Three databases, PubMed, EMBASE, and BIOSIS were searched, using a combination of Mesh or Emtree headings and free-text terms, to identify literature relating to circulating miRNAs in endometriosis published from 1996 to 31 December 2017. Only peer-reviewed, full-text original research articles in English were included in the current review. The studies meeting the inclusion criteria were critically assessed and checked using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool. The dysregulated miRNAs were assessed regarding the concordance between the various studies and their role in the disease. Outcomes: Nine studies were critically analysed, and 42 different miRNAs were found to be dysregulated in them, with only one common miRNA (miR-20a) differentially expressed in more than one study. miR-17-5p/20a, miR-200, miR-199a, miR-143, and miR-145 were explored for their pivotal role in the aetiopathogenesis of endometriosis. Wider implications: It is emerging that miRNAs play a central role in the pathogenesis of endometriosis and have the potential of being promising biomarkers. Circulating miRNAs as a non-invasive diagnostic tool may shorten the delay in the diagnosis of the disease, thus alleviating the suffering of women and reducing the burden on health care systems. However, despite numerous studies on circulating miRNAs in endometriosis, no single miRNA or any panel of them seems to meet the criteria of a diagnostic biomarker. The disagreement between the various studies upholds the demand of larger, well-controlled systematic validation studies with uniformity in the research approaches and involving diverse populations. PMID:29463003

Simulations of High Current NuMI Magnetic Horn Striplines at FNAL

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sipahi, Taylan; Biedron, Sandra; Hylen, James

2016-06-01

Both the NuMI (Neutrinos and the Main Injector) beam line, that has been providing intense neutrino beams for several Fermilab experiments (MINOS, MINERVA, NOVA), and the newly proposed LBNF (Long Baseline Neutrino Facility) beam line which plans to produce the highest power neutrino beam in the world for DUNE (the Deep Underground Neutrino Experiment) need pulsed magnetic horns to focus the mesons which decay to produce the neutrinos. The high-current horn and stripline design has been evolving as NuMI reconfigures for higher beam power and to meet the needs of the LBNF design. The CSU particle accelerator group has aidedmore » the neutrino physics experiments at Fermilab by producing EM simulations of magnetic horns and the required high-current striplines. In this paper, we present calculations, using the Poisson and ANSYS Maxwell 3D codes, of the EM interaction of the stripline plates of the NuMI horns at critical stress points. In addition, we give the electrical simulation results using the ANSYS Electric code. These results are being used to support the development of evolving horn stripline designs to handle increased electrical current and higher beam power for NuMI upgrades and for LBNF« less

MicroRNAs as biomarkers for graft-versus-host disease following allogeneic stem cell transplantation.

PubMed

Tomuleasa, Ciprian; Fuji, Shigeo; Cucuianu, Andrei; Kapp, Markus; Pileczki, Valentina; Petrushev, Bobe; Selicean, Sonia; Tanase, Alina; Dima, Delia; Berindan-Neagoe, Ioana; Irimie, Alexandru; Einsele, Hermann

2015-07-01

Allogeneic hematopoietic stem cell transplantation (HCT) is a well-established treatment for many malignant and non-malignant hematological disorders. As frequent complication in up to 50 % of all patients, graft-versus-host disease (GVHD) is still the main cause for morbidity and non-relapse mortality. Diagnosis of GVHD is usually done clinically, even though confirmation by pathology is often used to support the clinical findings. Effective treatment requires intensified immunosuppression as early as possible. Although several promising biomarkers have been proposed for an early diagnosis, no internationally recognized consensus has yet been established. Here, microRNAs (miRs) represent an interesting tool since miRs have been recently reported to be an important regulator of various cells, including immune cells such as T cells. Therefore, we could assume that miRs play a key role in the pathogenesis of acute GVHD, and their detection might be an interesting possibility in the early diagnosis and monitoring of acute GVHD. Recent studies additionally demonstrated the implication of miRs in the pathogenesis of acute GVHD. In this review, we aim to summarize the previous reports of miRs, focusing on the pathogenesis of acute GVHD and possible implications in diagnostic approaches.

Optimization of operation conditions and configurations for solid-propellant ducted rocket combustors

NASA Astrophysics Data System (ADS)

Onn, Shing-Chung; Chiang, Hau-Jei; Hwang, Hang-Che; Wei, Jen-Ko; Cherng, Dao-Lien

1993-06-01

The dynamic behavior of a 2D turbulent mixing and combustion process has been studied numerically in the main combustion chamber of a solid-propellant ducted rocket (SDR). The mathematical model is based on the Favre-averaged conservation equations developed by Cherng (1990). Combustion efficiency, rather than specific impulse from earlier studies, is applied successfully to optimize the effects of two parameters by a multiple linear regression model. Specifically, the fuel-air equivalence ratio of the operating conditions and the air inlet location of configurations for the SDR combustor have been studied. For a equivalence ratio near the stoichiometric condition, the use of specific impulse or combustion efficiency will show similar trend in characterizing the reacting flow field in the combustor. For the overall fuel lean operating conditions, the change of combustion efficiency is much more sensitive to that of air inlet location than specific impulse does, suggesting combustion efficiency a better property than specific impulse in representing the condition toward flammability limits. In addition, the air inlet for maximum efficiency, in general, appears to be located at downstream of that for highest specific impulse. The optimal case for the effects of two parameters occurs at fuel lean condition, which shows a larger recirculation zone in front, deeper penetration of ram air into the combustor and much larger high temperature zone near the centerline of the combustor exit than those shown in the optimal case for overall equivalence ratio close to stoichiometric.

Study on the streamer inception characteristics under positive lightning impulse voltage

NASA Astrophysics Data System (ADS)

Wang, Zezhong; Geng, Yinan

2017-11-01

The streamer is the main process in an air gap discharge, and the inception characteristics of streamers have been widely applied in engineering. Streamer inception characteristics under DC voltage have been studied by many researchers, but the inception characteristics under impulse voltage, and particularly under lightning impulse voltage with a high voltage rise rate have rarely been studied. A measurement system based on integrated optoelectronic technology has been proposed in this paper, and the streamer inception characteristics in a 1-m-long rod-plane air gap that was energized by a positive lightning impulse voltage have been researched. We have also measured the streamer inception electric field using electrodes with different radii of curvature and different voltage rise rates. As a result, a modified empirical criterion for the streamer inception electric field that considers the voltage rise rate has been proposed, and the wide applicability of this criterion has been proved. Based on the streamer inception time-lag obtained, we determined that the field distribution obeys a Rayleigh distribution, which explains the change law of the streamer inception time-lag. The characteristic parameter of the Rayleigh distribution lies in the range from 0.6 to 2.5 when the radius of curvature of the electrode head is in the range from 0.5 cm to 2.5 cm and the voltage rise rate ranges from 80 kV/μs to 240kV/μs under positive lightning impulse voltage.

High trait aggression in men is associated with low 5-HT levels, as indexed by 5-HT4 receptor binding

PubMed Central

Mc Mahon, Brenda; MacDonald Fisher, Patrick; Jensen, Peter Steen; Svarer, Claus; Moos Knudsen, Gitte

2016-01-01

Impulsive aggression has commonly been associated with a dysfunction of the serotonin (5-HT) system: many, but not all, studies point to an inverse relationship between 5-HT and aggression. As cerebral 5-HT4 receptor (5-HT4R) binding has recently been recognized as a proxy for stable brain levels of 5-HT, we here test the hypothesis in healthy men and women that brain 5-HT levels, as indexed by cerebral 5-HT4R, are inversely correlated with trait aggression and impulsivity. Sixty-one individuals (47 men) underwent positron emission tomography scanning with the radioligand [11C]SB207145 for quantification of brain 5-HT4R binding. The Buss–Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale were used for assessment of trait aggression and trait impulsivity. Among male subjects, there was a positive correlation between global 5-HT4R and BPAQ total score (P = 0.037) as well as BPAQ physical aggression (P = 0.025). No main effect of global 5-HT4R on trait aggression or impulsivity was found in the mixed gender sample, but there was evidence for sex interaction effects in the relationship between global 5-HT4R and BPAQ physical aggression. In conclusion we found that low cerebral 5-HT levels, as indexed by 5-HT4R binding were associated with high trait aggression in males, but not in females. PMID:26772668

Weighted low-rank sparse model via nuclear norm minimization for bearing fault detection

NASA Astrophysics Data System (ADS)

Du, Zhaohui; Chen, Xuefeng; Zhang, Han; Yang, Boyuan; Zhai, Zhi; Yan, Ruqiang

2017-07-01

It is a fundamental task in the machine fault diagnosis community to detect impulsive signatures generated by the localized faults of bearings. The main goal of this paper is to exploit the low-rank physical structure of periodic impulsive features and further establish a weighted low-rank sparse model for bearing fault detection. The proposed model mainly consists of three basic components: an adaptive partition window, a nuclear norm regularization and a weighted sequence. Firstly, due to the periodic repetition mechanism of impulsive feature, an adaptive partition window could be designed to transform the impulsive feature into a data matrix. The highlight of partition window is to accumulate all local feature information and align them. Then, all columns of the data matrix share similar waveforms and a core physical phenomenon arises, i.e., these singular values of the data matrix demonstrates a sparse distribution pattern. Therefore, a nuclear norm regularization is enforced to capture that sparse prior. However, the nuclear norm regularization treats all singular values equally and thus ignores one basic fact that larger singular values have more information volume of impulsive features and should be preserved as much as possible. Therefore, a weighted sequence with adaptively tuning weights inversely proportional to singular amplitude is adopted to guarantee the distribution consistence of large singular values. On the other hand, the proposed model is difficult to solve due to its non-convexity and thus a new algorithm is developed to search one satisfying stationary solution through alternatively implementing one proximal operator operation and least-square fitting. Moreover, the sensitivity analysis and selection principles of algorithmic parameters are comprehensively investigated through a set of numerical experiments, which shows that the proposed method is robust and only has a few adjustable parameters. Lastly, the proposed model is applied to the wind turbine (WT) bearing fault detection and its effectiveness is sufficiently verified. Compared with the current popular bearing fault diagnosis techniques, wavelet analysis and spectral kurtosis, our model achieves a higher diagnostic accuracy.

MiR-100 regulates cell differentiation and survival by targeting RBSP3, a phosphatase-like tumor suppressor in acute myeloid leukemia

PubMed Central

Zheng, Y-S; Zhang, H; Zhang, X-J; Feng, D-D; Luo, X-Q; Zeng, C-W; Lin, K-Y; Zhou, H; Qu, L-H; Zhang, P; Chen, Y-Q

2012-01-01

Acute myeloblastic leukemia (AML) is characterized by the accumulation of abnormal myeloblasts (mainly granulocyte or monocyte precursors) in the bone marrow and blood. Though great progress has been made for improvement in clinical treatment during the past decades, only minority with AML achieve long-term survival. Therefore, further understanding mechanisms of leukemogenesis and exploring novel therapeutic strategies are still crucial for improving disease outcome. MicroRNA-100 (miR-100), a small non-coding RNA molecule, has been reported as a frequent event aberrantly expressed in patients with AML; however, the molecular basis for this phenotype and the statuses of its downstream targets have not yet been elucidated. In the present study, we found that the expression level of miR-100 in vivo was related to the stage of the maturation block underlying the subtypes of myeloid leukemia. In vitro experiments further demonstrated that miR-100 was required to promote the cell proliferation of promyelocytic blasts and arrest them differentiated to granulocyte/monocyte lineages. Significantly, we identified RBSP3, a phosphatase-like tumor suppressor, as a bona fide target of miR-100 and validated that RBSP3 was involved in cell differentiation and survival in AML. Moreover, we revealed a new pathway that miR-100 regulates G1/S transition and S-phase entry and blocks the terminal differentiation by targeting RBSP3, which partly in turn modulates the cell cycle effectors pRB/E2F1 in AML. These events promoted cell proliferation and blocked granulocyte/monocyte differentiation. Our data highlight an important role of miR-100 in the molecular etiology of AML, and implicate the potential application of miR-100 in cancer therapy. PMID:21643017

Menstrual Irregularity and Musculoskeletal Injury in Female High School Athletes

PubMed Central

Thein-Nissenbaum, Jill M.; Rauh, Mitchell J.; Carr, Kathleen E.; Loud, Keith J.; McGuine, Timothy A.

2012-01-01

Context: The female athlete triad describes the interrelatedness of energy availability, menstrual function, and bone density. Although associations between triad components and musculoskeletal injury (INJ) have been reported in collegiate athletes, limited information exists about menstrual irregularity (MI) and INJ in the high school population. Objective: To determine the prevalence of and relationship between MI and INJ in high school athletes. Design: Cross-sectional study. Setting: High schools. Patients or Other Participants: The sample consisted of 249 female athletes from 3 high schools who competed in 33 interscholastic, school-sponsored sport teams, dance teams, and cheerleading or pom-pon squad during the 2006–2007 school year. Each athlete remained on the roster throughout the season. Main Outcome Measure(s): Participants completed a survey regarding injury type, number of days of sport participation missed, and menstrual history in the past year. Results: The prevalences of MI and INJ were 19.7% and 63.1%, respectively. Athletes who reported MI sustained a higher percentage of severe injuries (missing ≥22 days of practice or competition) than did athletes who reported normal menses. Although the trend was not significant, athletes with MI were almost 3 times more likely to sustain an injury resulting in 7 or more days of time lost from sport (odds ratio = 2.7, 95% confidence interval = 0.8, 8.8) than those who sustained an injury resulting in 7 or fewer days of time lost. Conclusions: The incidences of MI and INJ in this high school population during the study period were high. Athletes who reported MI sustained a higher percentage of severe injuries than did athletes who reported normal menses. Education programs to increase knowledge and improve management of MI and its potential effects on injury in female high school athletes are warranted. PMID:22488233

An integrative transcriptomic approach to identify depot differences in genes and microRNAs in adipose tissues from high fat fed mice.

PubMed

Wijayatunga, Nadeeja N; Pahlavani, Mandana; Kalupahana, Nishan S; Kottapalli, Kameswara Rao; Gunaratne, Preethi H; Coarfa, Cristian; Ramalingam, Latha; Moustaid-Moussa, Naima

2018-02-06

Obesity contributes to metabolic disorders such as diabetes and cardiovascular disease. Characterization of differences between the main adipose tissue depots, white (WAT) [including subcutaneous (SAT) and visceral adipose tissue (VAT)] and brown adipose tissue (BAT) helps to identify their roles in obesity. Thus, we studied depot-specific differences in whole transcriptome and miRNA profiles of SAT, VAT and BAT from high fat diet (HFD/45% of calories from fat) fed mice using RNA sequencing and small RNA-Seq. Using quantitative real-time polymerase chain reaction, we validated depot-specific differences in endoplasmic reticulum (ER) stress related genes and miRNAs using mice fed a HFD vs. low fat diet (LFD/10% of calories from fat). According to the transcriptomic analysis, lipogenesis, adipogenesis, inflammation, endoplasmic reticulum (ER) stress and unfolded protein response (UPR) were higher in VAT compared to BAT, whereas energy expenditure, fatty acid oxidation and oxidative phosphorylation were higher in BAT than in VAT of the HFD fed mice. In contrast to BAT, ER stress marker genes were significantly upregulated in VAT of HFD fed mice than the LFD fed mice. For the first time, we report depot specific differences in ER stress related miRNAs including; downregulation of miR-125b-5p, upregulation miR-143-3p, and miR-222-3p in VAT following HFD and upregulation of miR-30c-2-3p only in BAT following a HFD in mice than the LFD mice. In conclusion, HFD differentially regulates miRNAs and genes in different adipose depots with significant induction of genes related to lipogenesis, adipogenesis, inflammation, ER stress, and UPR in WAT compared to BAT.

Genome wide predictions of miRNA regulation by transcription factors.

PubMed

Ruffalo, Matthew; Bar-Joseph, Ziv

2016-09-01

Reconstructing regulatory networks from expression and interaction data is a major goal of systems biology. While much work has focused on trying to experimentally and computationally determine the set of transcription-factors (TFs) and microRNAs (miRNAs) that regulate genes in these networks, relatively little work has focused on inferring the regulation of miRNAs by TFs. Such regulation can play an important role in several biological processes including development and disease. The main challenge for predicting such interactions is the very small positive training set currently available. Another challenge is the fact that a large fraction of miRNAs are encoded within genes making it hard to determine the specific way in which they are regulated. To enable genome wide predictions of TF-miRNA interactions, we extended semi-supervised machine-learning approaches to integrate a large set of different types of data including sequence, expression, ChIP-seq and epigenetic data. As we show, the methods we develop achieve good performance on both a labeled test set, and when analyzing general co-expression networks. We next analyze mRNA and miRNA cancer expression data, demonstrating the advantage of using the predicted set of interactions for identifying more coherent and relevant modules, genes, and miRNAs. The complete set of predictions is available on the supporting website and can be used by any method that combines miRNAs, genes, and TFs. Code and full set of predictions are available from the supporting website: http://cs.cmu.edu/~mruffalo/tf-mirna/ zivbj@cs.cmu.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Knowledge, attitudes, and practices concerning malaria in pregnancy: results from a qualitative study in Madang, Papua New Guinea.

PubMed

Andrew, Erin V W; Pell, Christopher; Angwin, Angeline; Auwun, Alma; Daniels, Job; Mueller, Ivo; Phuanukoonnon, Suparat; Pool, Robert

2015-01-01

Malaria is the leading cause of illness and death in Papua New Guinea (PNG). Infection during pregnancy with falciparum or vivax malaria, as occurs in PNG, has health implications for mother and child, causing complications such as maternal anemia, low birth weight and miscarriage. This article explores knowledge, attitudes and practices concerning malaria during pregnancy and it's prevention in Madang, PNG, a high prevalence area. As part of a qualitative study in Madang, exploring MiP, participatory techniques (free-listing and sorting) were conducted along with focus group discussions, in-depth interviews (with pregnant women, health staff and other community members) and observations in the local community and health facilities. The main themes explored were attitudes towards and knowledge of MiP, its risks, and prevention. Although there was a general awareness of the term "malaria", it was often conflated with general sickness or with pregnancy-related symptoms. Moreover, many preventive methods for MiP were related to practices of general healthy living. Indeed, varied messages from health staff about the risks of MiP were observed. In addition to ideas about the seriousness and risk of MiP, other factors influenced the uptake of interventions: availability and perceived comfort of sleeping under insecticide-treated mosquito nets were important determinants of usage, and women's heavy workload influenced Chloroquine adherence. The non-specific symptoms of MiP and its resultant conflation with symptoms of pregnancy that are perceived as normal have implications for MiP prevention and control. However, in Madang, PNG, this was compounded by the inadequacy of health staff's message about MiP.

Relationship between suicide and myocardial infarction with regard to changing physical environmental conditions

NASA Astrophysics Data System (ADS)

Stoupel, Eliahu; Abramson, Eugeny; Sulkes, Jaqueline; Martfel, Joseph; Stein, Nechama; Handelman, Meir; Shimshoni, Michael; Zadka, Pnina; Gabbay, Uri

1995-12-01

In recent years, the possible association of changes in mortality from cardiovascular disease and myocardial infarction (MI) and deaths related to violence and the suicide rate has been repeatedly discussed. This study examined the relationship between cosmic physical changes (solar, geomagnetic and other space activity parameters) and changes in the total number of in-hospital and MI-related deaths and deaths from suicide to determine if a relationship exists between the distribution of total and MI-related deaths with suicide over time; some differences in the serotonergic mechanisms involved in the pathogenesis of MI and suicide were also taken into account. All suicides ( n=2359) registered in the State of Israel from 1981 to 1989 (108 months) were analysed and compared with the total number of deaths ( n=15601) and deaths from MI ( n=1573) in a large university hospital over 180 months (1974 1989). The following were the main features of the Results. (1) Monthly suicide rate was correlated with space proton flux ( r=0.42, P=0.0001) and with geomagnetic activity ( r=-0.22, P=0.03). (2) Total hospital and MI-related deaths were correlated with solar activity parameters ( r=0.35, P<0.001) and radiowave propagation ( r=0.52-0.44, P<0.001), an with proton flux ( r=-0.3 to -0.26, P<0.01). (3) Monthly suicide distribution over 108 months was correlated with MI ( r=-0.33, P=0.0005) and total hospital mortality ( r=-0.22, P=0.024). (4) Gender differences were prominent. We conclude that the monthly distributions of suicides and deaths from MI are adversely related to many environmental physical parameters and negatively correlated with each other.

Myocardial Infarction and Exercise Training: Evidence from Basic Science.

PubMed

Moraes-Silva, Ivana C; Rodrigues, Bruno; Coelho-Junior, Hélio J; Feriani, Daniele Jardim; Irigoyen, Maria-Claudia

2017-01-01

In 2016, cardiovascular disease remains the first cause of mortality worldwide [1]. Coronary artery disease, which is the most important precursor of myocardial infarction (MI), is the main component of total cardiovascular mortality, being responsible for approximately seven million of deaths [1]. In approximately 20% of infarcted patients, MI is recurrent in the first year after the event [2]. Moreover, among cardiovascular disease, coronary artery disease accounts for the most increased index of life years lost due to morbidity and/or mortality [1]. Sedentarism highly contributes to cardiovascular disease burden, especially for coronary artery disease, and is also one of the MI risk factors [3]. For many years, it was recommended to avoid physical activity after a cardiovascular event; nowadays, it is a consensus that exercise training (ET) should be part of cardiac rehabilitation programs. There is increasing evidence confirming that, when adequately prescribed and supervised, ET after MI can prevent future complications and increase the quality of life and longevity of infarcted patients [4, 5]. ET after MI follows international specialized guidelines; however, there are different protocols adopted by several societies worldwide in cardiac rehabilitation [6], and there is still lack of information on which type and regimen of exercise may be the ideal after MI, as well as how these exercises act to promote beneficial effects to cardiovascular and other organic systems. Thus, experimental studies are important contributors to elicit mechanisms behind clinical results, and to test and compare different ET protocols. Therefore, exercise prescription can be optimized, individualized, and safely practiced by patients. In this chapter, we present a brief review of MI pathophysiology followed by an updated discussion of the most relevant discoveries regarding ET and MI in basic science.

MicroRNA Related Polymorphisms and Breast Cancer Risk

PubMed Central

Khan, Sofia; Greco, Dario; Michailidou, Kyriaki; Milne, Roger L.; Muranen, Taru A.; Heikkinen, Tuomas; Aaltonen, Kirsimari; Dennis, Joe; Bolla, Manjeet K.; Liu, Jianjun; Hall, Per; Irwanto, Astrid; Humphreys, Keith; Li, Jingmei; Czene, Kamila; Chang-Claude, Jenny; Hein, Rebecca; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Fletcher, Olivia; Peto, Julian; dos Santos Silva, Isabel; Johnson, Nichola; Gibson, Lorna; Aitken, Zoe; Hopper, John L.; Tsimiklis, Helen; Bui, Minh; Makalic, Enes; Schmidt, Daniel F.; Southey, Melissa C.; Apicella, Carmel; Stone, Jennifer; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel A.; van der Luijt, Rob B.; Meindl, Alfons; Schmutzler, Rita K.; Müller-Myhsok, Bertram; Lichtner, Peter; Turnbull, Clare; Rahman, Nazneen; Chanock, Stephen J.; Hunter, David J.; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Schmidt, Marjanka K.; Broeks, Annegien; Veer, Laura J. V. a. n't.; Hogervorst, Frans B.; Fasching, Peter A.; Schrauder, Michael G.; Ekici, Arif B.; Beckmann, Matthias W.; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Benitez, Javier; Zamora, Pilar M.; Perez, Jose I. A.; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Pharoah, Paul D. P.; Dunning, Alison M.; Shah, Mitul; Luben, Robert; Brown, Judith; Couch, Fergus J.; Wang, Xianshu; Vachon, Celine; Olson, Janet E.; Lambrechts, Diether; Moisse, Matthieu; Paridaens, Robert; Christiaens, Marie-Rose; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Mulot, Claire; Marme, Frederick; Burwinkel, Barbara; Schneeweiss, Andreas; Sohn, Christof; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Andrulis, Irene L.; Knight, Julia A.; Tchatchou, Sandrine; Mulligan, Anna Marie; Dörk, Thilo; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Anton-Culver, Hoda; Darabi, Hatef; Eriksson, Mikael; Garcia-Closas, Montserrat; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Devilee, Peter; Tollenaar, Robert A. E. M.; Seynaeve, Caroline; van Asperen, Christi J.; Kristensen, Vessela N.; Slager, Susan; Toland, Amanda E.; Ambrosone, Christine B.; Yannoukakos, Drakoulis; Lindblom, Annika; Margolin, Sara; Radice, Paolo; Peterlongo, Paolo; Barile, Monica; Mariani, Paolo; Hooning, Maartje J.; Martens, John W. M.; Collée, J. Margriet; Jager, Agnes; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Giles, Graham G.; McLean, Catriona; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Mannermaa, Arto; Hamann, Ute; Chenevix-Trench, Georgia; Blomqvist, Carl; Aittomäki, Kristiina; Easton, Douglas F.; Nevanlinna, Heli

2014-01-01

Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88–0.96), rs1052532 (OR 0.97; 95% CI: 0.95–0.99), rs10719 (OR 0.97; 95% CI: 0.94–0.99), rs4687554 (OR 0.97; 95% CI: 0.95–0.99, and rs3134615 (OR 1.03; 95% CI: 1.01–1.05) located in the 3′ UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects. PMID:25390939

MicroRNA related polymorphisms and breast cancer risk.

PubMed

Khan, Sofia; Greco, Dario; Michailidou, Kyriaki; Milne, Roger L; Muranen, Taru A; Heikkinen, Tuomas; Aaltonen, Kirsimari; Dennis, Joe; Bolla, Manjeet K; Liu, Jianjun; Hall, Per; Irwanto, Astrid; Humphreys, Keith; Li, Jingmei; Czene, Kamila; Chang-Claude, Jenny; Hein, Rebecca; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Fletcher, Olivia; Peto, Julian; dos Santos Silva, Isabel; Johnson, Nichola; Gibson, Lorna; Aitken, Zoe; Hopper, John L; Tsimiklis, Helen; Bui, Minh; Makalic, Enes; Schmidt, Daniel F; Southey, Melissa C; Apicella, Carmel; Stone, Jennifer; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel A; van der Luijt, Rob B; Meindl, Alfons; Schmutzler, Rita K; Müller-Myhsok, Bertram; Lichtner, Peter; Turnbull, Clare; Rahman, Nazneen; Chanock, Stephen J; Hunter, David J; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Schmidt, Marjanka K; Broeks, Annegien; Van't Veer, Laura J; Hogervorst, Frans B; Fasching, Peter A; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Benitez, Javier; Zamora, Pilar M; Perez, Jose I A; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Pharoah, Paul D P; Dunning, Alison M; Shah, Mitul; Luben, Robert; Brown, Judith; Couch, Fergus J; Wang, Xianshu; Vachon, Celine; Olson, Janet E; Lambrechts, Diether; Moisse, Matthieu; Paridaens, Robert; Christiaens, Marie-Rose; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Mulot, Claire; Marme, Frederick; Burwinkel, Barbara; Schneeweiss, Andreas; Sohn, Christof; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Andrulis, Irene L; Knight, Julia A; Tchatchou, Sandrine; Mulligan, Anna Marie; Dörk, Thilo; Bogdanova, Natalia V; Antonenkova, Natalia N; Anton-Culver, Hoda; Darabi, Hatef; Eriksson, Mikael; Garcia-Closas, Montserrat; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; van Asperen, Christi J; Kristensen, Vessela N; Slager, Susan; Toland, Amanda E; Ambrosone, Christine B; Yannoukakos, Drakoulis; Lindblom, Annika; Margolin, Sara; Radice, Paolo; Peterlongo, Paolo; Barile, Monica; Mariani, Paolo; Hooning, Maartje J; Martens, John W M; Collée, J Margriet; Jager, Agnes; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Giles, Graham G; McLean, Catriona; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Simard, Jacques; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Mannermaa, Arto; Hamann, Ute; Chenevix-Trench, Georgia; Blomqvist, Carl; Aittomäki, Kristiina; Easton, Douglas F; Nevanlinna, Heli

2014-01-01

Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.

MultiMiTar: a novel multi objective optimization based miRNA-target prediction method.

PubMed

Mitra, Ramkrishna; Bandyopadhyay, Sanghamitra

2011-01-01

Machine learning based miRNA-target prediction algorithms often fail to obtain a balanced prediction accuracy in terms of both sensitivity and specificity due to lack of the gold standard of negative examples, miRNA-targeting site context specific relevant features and efficient feature selection process. Moreover, all the sequence, structure and machine learning based algorithms are unable to distribute the true positive predictions preferentially at the top of the ranked list; hence the algorithms become unreliable to the biologists. In addition, these algorithms fail to obtain considerable combination of precision and recall for the target transcripts that are translationally repressed at protein level. In the proposed article, we introduce an efficient miRNA-target prediction system MultiMiTar, a Support Vector Machine (SVM) based classifier integrated with a multiobjective metaheuristic based feature selection technique. The robust performance of the proposed method is mainly the result of using high quality negative examples and selection of biologically relevant miRNA-targeting site context specific features. The features are selected by using a novel feature selection technique AMOSA-SVM, that integrates the multi objective optimization technique Archived Multi-Objective Simulated Annealing (AMOSA) and SVM. MultiMiTar is found to achieve much higher Matthew's correlation coefficient (MCC) of 0.583 and average class-wise accuracy (ACA) of 0.8 compared to the others target prediction methods for a completely independent test data set. The obtained MCC and ACA values of these algorithms range from -0.269 to 0.155 and 0.321 to 0.582, respectively. Moreover, it shows a more balanced result in terms of precision and sensitivity (recall) for the translationally repressed data set as compared to all the other existing methods. An important aspect is that the true positive predictions are distributed preferentially at the top of the ranked list that makes MultiMiTar reliable for the biologists. MultiMiTar is now available as an online tool at www.isical.ac.in/~bioinfo_miu/multimitar.htm. MultiMiTar software can be downloaded from www.isical.ac.in/~bioinfo_miu/multimitar-download.htm.

Dehydration mediated microRNA response in the African clawed frog Xenopus laevis.

PubMed

Wu, Cheng-Wei; Biggar, Kyle K; Storey, Kenneth B

2013-10-25

Exposure to various environmental stresses induces metabolic rate depression in many animal species, an adaptation that conserves energy until the environment is again conducive to normal life. The African clawed frog, Xenopus laevis, is periodically subjected to arid summers in South Africa, and utilizes entry into the hypometabolic state of estivation as a mechanism of long term survival. During estivation, frogs must typically deal with substantial dehydration as their ponds dry out and X. laevis can endure >30% loss of its body water. We hypothesize that microRNAs play a vital role in establishing a reversible hypometabolic state and responding to dehydration stress that is associated with amphibian estivation. The present study analyzes the effects of whole body dehydration on microRNA expression in three tissues of X. laevis. Compared to controls, levels of miR-1, miR-125b, and miR-16-1 decreased to 37±6, 64±8, and 80±4% of control levels during dehydration in liver. By contrast, miR-210, miR-34a and miR-21 were significantly elevated by 3.05±0.45, 2.11±0.08, and 1.36±0.05-fold, respectively, in the liver. In kidney tissue, miR-29b, miR-21, and miR-203 were elevated by 1.40±0.09, 1.31±0.05, and 2.17±0.31-fold, respectively, in response to dehydration whereas miR-203 and miR-34a were elevated in ventral skin by 1.35±0.05 and 1.74±0.12-fold, respectively. Bioinformatic analysis of the differentially expressed microRNAs suggests that these are mainly involved in two processes: (1) expression of solute carrier proteins, and (2) regulation of mitogen-activated protein kinase signaling. This study is the first report that shows a tissue specific mode of microRNA expression during amphibian dehydration, providing evidence for microRNAs as crucial regulators of metabolic depression. © 2013 Elsevier B.V. All rights reserved.

Disorder of G2-M Checkpoint Control in Aniline-Induced Cell Proliferation in Rat Spleen.

PubMed

Wang, Jianling; Wang, Gangduo; Khan, M Firoze

2015-01-01

Aniline, a toxic aromatic amine, is known to cause hemopoietic toxicity both in humans and animals. Aniline exposure also leads to toxic response in spleen which is characterized by splenomegaly, hyperplasia, fibrosis and the eventual formation of tumors on chronic in vivo exposure. Previously, we have shown that aniline exposure leads to iron overload, oxidative DNA damage, and increased cell proliferation, which could eventually contribute to a tumorigenic response in the spleen. Despite our demonstration that cell proliferation was associated with deregulation of G1 phase cyclins and increased expression of G1 phase cyclin-dependent kinases (CDKs), molecular mechanisms, especially the regulation of G2 phase and contribution of epigenetic mechanisms in aniline-induced splenic cellular proliferation remain largely unclear. This study therefore, mainly focused on the regulation of G2 phase in an animal model preceding a tumorigenic response. Male Sprague-Dawley rats were given aniline (0.5 mmol/kg/day) in drinking water or drinking water only (controls) for 30 days, and expression of G2 phase cyclins, CDK1, CDK inhibitors and miRNAs were measured in the spleen. Aniline treatment resulted in significant increases in cell cycle regulatory proteins, including cyclins A, B and CDK1, particularly phosphor-CDK1, and decreases in CDK inhibitors p21 and p27, which could promote the splenocytes to go through G2/M transition. Our data also showed upregulation of tumor markers Trx-1 and Ref-1 in rats treated with aniline. More importantly, we observed lower expression of miRNAs including Let-7a, miR-15b, miR24, miR-100 and miR-125, and greater expression of CDK inhibitor regulatory miRNAs such as miR-181a, miR-221 and miR-222 in the spleens of aniline-treated animals. Our findings suggest that significant increases in the expression of cyclins, CDK1 and aberrant regulation of miRNAs could lead to an accelerated G2/M transition of the splenocytes, and potentially to a tumorigenic response on chronic aniline exposure.

Disorder of G2-M Checkpoint Control in Aniline-Induced Cell Proliferation in Rat Spleen

PubMed Central

Wang, Jianling; Wang, Gangduo; Khan, M. Firoze

2015-01-01

Aniline, a toxic aromatic amine, is known to cause hemopoietic toxicity both in humans and animals. Aniline exposure also leads to toxic response in spleen which is characterized by splenomegaly, hyperplasia, fibrosis and the eventual formation of tumors on chronic in vivo exposure. Previously, we have shown that aniline exposure leads to iron overload, oxidative DNA damage, and increased cell proliferation, which could eventually contribute to a tumorigenic response in the spleen. Despite our demonstration that cell proliferation was associated with deregulation of G1 phase cyclins and increased expression of G1 phase cyclin-dependent kinases (CDKs), molecular mechanisms, especially the regulation of G2 phase and contribution of epigenetic mechanisms in aniline-induced splenic cellular proliferation remain largely unclear. This study therefore, mainly focused on the regulation of G2 phase in an animal model preceding a tumorigenic response. Male Sprague-Dawley rats were given aniline (0.5 mmol/kg/day) in drinking water or drinking water only (controls) for 30 days, and expression of G2 phase cyclins, CDK1, CDK inhibitors and miRNAs were measured in the spleen. Aniline treatment resulted in significant increases in cell cycle regulatory proteins, including cyclins A, B and CDK1, particularly phosphor-CDK1, and decreases in CDK inhibitors p21 and p27, which could promote the splenocytes to go through G2/M transition. Our data also showed upregulation of tumor markers Trx-1 and Ref-1 in rats treated with aniline. More importantly, we observed lower expression of miRNAs including Let-7a, miR-15b, miR24, miR-100 and miR-125, and greater expression of CDK inhibitor regulatory miRNAs such as miR-181a, miR-221 and miR-222 in the spleens of aniline-treated animals. Our findings suggest that significant increases in the expression of cyclins, CDK1 and aberrant regulation of miRNAs could lead to an accelerated G2/M transition of the splenocytes, and potentially to a tumorigenic response on chronic aniline exposure. PMID:26192324

Microarray expression profile of circular RNAs in chronic thromboembolic pulmonary hypertension

PubMed Central

Miao, Ran; Wang, Ying; Wan, Jun; Leng, Dong; Gong, Juanni; Li, Jifeng; Liang, Yan; Zhai, Zhenguo; Yang, Yuanhua

2017-01-01

Abstract Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but debilitating and life-threatening complication of acute pulmonary embolism. Circular RNAs (circRNAs), presenting as covalently closed continuous loops, are RNA molecules with covalently joined 3′- and 5′-ends formed by back-splicing events. circRNAs may be significant biological molecules to understand disease mechanisms and to identify biomarkers for disease diagnosis and therapy. The aim of this study was to investigate the potential roles of circRNAs in CTEPH. Methods: Ten human blood samples (5 each from CTEPH and control groups) were included in the Agilent circRNA chip. The differentially expressed circRNAs were evaluated using t test, with significance set at a P value of < .05. A functional enrichment analysis for differentially expressed circRNAs was performed using DAVID online tools, and a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis for target genes of miRNAs was performed using the R package clusterProfiler. Furthermore, miRNAs that interacted with differentially expressed circRNAs were predicted using the miRanda package. mRNAs that had clear biological functions and were regulated by miRNAs were predicted using miRWalk2.0 and then combined into a circRNA–miRNA–mRNA network. Results: In total, 351 differentially expressed circRNAs (122 upregulated and 229 downregulated) between CTEPH and control groups were obtained; among these circRNAs, hsa_circ_0002062 and hsa_circ_0022342 might be important because they can regulate 761 (e.g., hsa-miR-942–5p) and 453 (e.g., hsa-miR-940) miRNAs, respectively. Target genes (e.g., cyclin-dependent kinase 6) of hsa-miR-942–5p were mainly enriched in cancer-related pathways, whereas target genes (e.g., CRK-Like Proto-Oncogene, Adaptor Protein) of hsa-miR-940 were enriched in the ErbB signaling pathway. Therefore, these pathways are potentially important in CTEPH. Conclusions: Our findings suggested that hsa_circ_0002062 and hsa_circ_0022342 may be key circRNAs for CTEPH development and that their targeted regulation may be an effective approach for treating CTEPH. PMID:28682884

miREE: miRNA recognition elements ensemble

PubMed Central

2011-01-01

Background Computational methods for microRNA target prediction are a fundamental step to understand the miRNA role in gene regulation, a key process in molecular biology. In this paper we present miREE, a novel microRNA target prediction tool. miREE is an ensemble of two parts entailing complementary but integrated roles in the prediction. The Ab-Initio module leverages upon a genetic algorithmic approach to generate a set of candidate sites on the basis of their microRNA-mRNA duplex stability properties. Then, a Support Vector Machine (SVM) learning module evaluates the impact of microRNA recognition elements on the target gene. As a result the prediction takes into account information regarding both miRNA-target structural stability and accessibility. Results The proposed method significantly improves the state-of-the-art prediction tools in terms of accuracy with a better balance between specificity and sensitivity, as demonstrated by the experiments conducted on several large datasets across different species. miREE achieves this result by tackling two of the main challenges of current prediction tools: (1) The reduced number of false positives for the Ab-Initio part thanks to the integration of a machine learning module (2) the specificity of the machine learning part, obtained through an innovative technique for rich and representative negative records generation. The validation was conducted on experimental datasets where the miRNA:mRNA interactions had been obtained through (1) direct validation where even the binding site is provided, or through (2) indirect validation, based on gene expression variations obtained from high-throughput experiments where the specific interaction is not validated in detail and consequently the specific binding site is not provided. Conclusions The coupling of two parts: a sensitive Ab-Initio module and a selective machine learning part capable of recognizing the false positives, leads to an improved balance between sensitivity and specificity. miREE obtains a reasonable trade-off between filtering false positives and identifying targets. miREE tool is available online at http://didattica-online.polito.it/eda/miREE/ PMID:22115078

MicroRNAs regulate the main events in rice drought stress response by manipulating the water supply to shoots.

PubMed

Fard, Ehsan Mohseni; Bakhshi, Behnam; Farsi, Mohammad; Kakhki, Amin Mirshamsi; Nikpay, Nava; Ebrahimi, Mohammad Ali; Mardi, Mohsen; Salekdeh, Ghasem Hosseini

2017-10-24

MicroRNAs (miRNAs) are small endogenous regulatory RNAs that are involved in a variety of biological processes related to proliferation, development, and response to biotic and abiotic stresses. miRNA profiles of rice (Oryza sativa L. cv. IR64.) leaves in a partial root zone drying (PRD) system were analysed using a high-throughput sequencing approach to identify miRNAs associated with drought signalling. The treatments performed in this study were as follows: well-watered ("wet" roots, WW), wherein both halves of the pot were watered daily; drought ("dry" roots, DD), wherein water was withheld from both halves of the pot; and well-watered/drought ("wet" and "dry" roots, WD), wherein one half of each pot was watered daily, the same as in WW, and water was withheld from the other part, the same as in DD. High-throughput sequencing enabled us to detect novel miRNAs and study the differential expression of known miRNAs. A total of 209 novel miRNAs were detected in this study. Differential miRNA profiling of the DD, WD and WW conditions showed differential expression of 159 miRNAs, among which 83, 44 and 32 miRNAs showed differential expression under both DD and WD conditions. The detection of putative targets of the differentially expressed miRNAs and investigation of their functions showed that most of these genes encode transcription factors involved in growth and development, leaf morphology, regulation of hormonal homeostasis, and stress response. The most important differences between the DD and WD conditions involved regulation of the levels of hormones such as auxin, cytokinin, abscisic acid, and jasmonic acid and also regulation of phosphor homeostasis. Overall, differentially expressed miRNAs under WD conditions were found to differ from those under DD conditions, with such differences playing a role in adaptation and inducing the normal condition. The mechanisms involved in regulating hormonal homeostasis and involved in energy production and consumption were found to be the most important regulatory pathways distinguishing the DD and WD conditions.

Climate aberrations during the middle Miocene: evidence from the eastern North Atlantic Ocean

NASA Astrophysics Data System (ADS)

Quaijtaal, W.; Donders, T.; Schouten, S.; Louwye, S.

2013-12-01

During the Middle Miocene Climatic Optimum (MMCO; 17-14.5 Ma) the relatively warm climate of the Miocene reached peak temperatures. After the MMCO, the global climate started cooling through several short-lived cooling events, represented by positive oxygen isotope excursions: the Mi-events (Miocene isotope events). One of the more severe events, Mi-3, is associated with East Antarctic Ice Sheet growth and potential Northern Hemisphere ice expansion, as well as marine and terrestrial species turnover and aridification. The causes and consequences of the Mi-events are not well constrained yet. CO2 reconstructions combined with the abovementioned consequences suggest that a drawdown of CO2 and/or changes in ocean led to the changes surrounding Mi-3. A minimum node in both eccentricity and obliquity amplitude modulation, an orbital configuration creating favourable conditions for ice growth, has been suggested as a possible triggering mechanism as well. However, an exact cause cannot be pinpointed yet and more high-resolution records are needed in order to investigate the impact and order of events surrounding the Mi-events. Integrated Ocean Drilling Program (IODP) Leg 307 recovered such a high resolution record from the middle Miocene of the Porcupine Basin (offshore south-western Ireland). We have analyzed well-preserved palynomorphs (mainly organic-walled dinoflagellate cysts, acritarchs and pollen) and organic molecules for paleothermometry (e.g. TEX86 and UK'37) from site U1318. With these proxies, the development of the Mi-3 event and following Mi-4 have been reconstructed in high resolution (ca. 13 kyr), by assessing e.g. temperature, sea level, thermocline depth and productivity. A pronounced cooling can be observed at Mi-3, and to a lesser degree in Mi-4 as well, together with a sea-level fall and a turnover in the dinocyst record. Our findings also include indications of aridification and a change in wind patterns during Mi-3. This confirms the dramatic impact of the Mi-3 event, not only on the North Atlantic Ocean, but also on the continent.

Human microRNA target analysis and gene ontology clustering by GOmir, a novel stand-alone application

PubMed Central

Roubelakis, Maria G; Zotos, Pantelis; Papachristoudis, Georgios; Michalopoulos, Ioannis; Pappa, Kalliopi I; Anagnou, Nicholas P; Kossida, Sophia

2009-01-01

Background microRNAs (miRNAs) are single-stranded RNA molecules of about 20–23 nucleotides length found in a wide variety of organisms. miRNAs regulate gene expression, by interacting with target mRNAs at specific sites in order to induce cleavage of the message or inhibit translation. Predicting or verifying mRNA targets of specific miRNAs is a difficult process of great importance. Results GOmir is a novel stand-alone application consisting of two separate tools: JTarget and TAGGO. JTarget integrates miRNA target prediction and functional analysis by combining the predicted target genes from TargetScan, miRanda, RNAhybrid and PicTar computational tools as well as the experimentally supported targets from TarBase and also providing a full gene description and functional analysis for each target gene. On the other hand, TAGGO application is designed to automatically group gene ontology annotations, taking advantage of the Gene Ontology (GO), in order to extract the main attributes of sets of proteins. GOmir represents a new tool incorporating two separate Java applications integrated into one stand-alone Java application. Conclusion GOmir (by using up to five different databases) introduces miRNA predicted targets accompanied by (a) full gene description, (b) functional analysis and (c) detailed gene ontology clustering. Additionally, a reverse search initiated by a potential target can also be conducted. GOmir can freely be downloaded BRFAA. PMID:19534746

Functional Roles of microRNAs in Agronomically Important Plants—Potential as Targets for Crop Improvement and Protection

PubMed Central

Djami-Tchatchou, Arnaud T.; Sanan-Mishra, Neeti; Ntushelo, Khayalethu; Dubery, Ian A.

2017-01-01

MicroRNAs (miRNAs) are a class of small non-coding RNAs that have recently emerged as important regulators of gene expression, mainly through cleavage and/or translation inhibition of the target mRNAs during or after transcription. miRNAs play important roles by regulating a multitude of biological processes in plants which include maintenance of genome integrity, development, metabolism, and adaptive responses toward environmental stresses. The increasing population of the world and their food demands requires focused efforts for the improvement of crop plants to ensure sustainable food production. Manipulation of mRNA transcript abundance via miRNA control provides a unique strategy for modulating differential plant gene expression and miRNAs are thus emerging as the next generation targets for genetic engineering for improvement of the agronomic properties of crops. However, a deeper understanding of its potential and the mechanisms involved will facilitate the design of suitable strategies to obtain the desirable traits with minimum trade-offs in the modified crops. In this regard, this review highlights the diverse roles of conserved and newly identified miRNAs in various food and industrial crops and recent advances made in the uses of miRNAs to improve plants of agronomically importance so as to significantly enhance crop yields and increase tolerance to various environmental stress agents of biotic—or abiotic origin. PMID:28382044

The miRNA Transcriptome Directly Reflects the Physiological and Biochemical Differences between Red, White, and Intermediate Muscle Fiber Types

PubMed Central

Ma, Jideng; Wang, Hongmei; Liu, Rui; Jin, Long; Tang, Qianzi; Wang, Xun; Jiang, Anan; Hu, Yaodong; Li, Zongwen; Zhu, Li; Li, Ruiqiang; Li, Mingzhou; Li, Xuewei

2015-01-01

MicroRNAs (miRNAs) are small non-coding RNAs that can regulate their target genes at the post-transcriptional level. Skeletal muscle comprises different fiber types that can be broadly classified as red, intermediate, and white. Recently, a set of miRNAs was found expressed in a fiber type-specific manner in red and white fiber types. However, an in-depth analysis of the miRNA transcriptome differences between all three fiber types has not been undertaken. Herein, we collected 15 porcine skeletal muscles from different anatomical locations, which were then clearly divided into red, white, and intermediate fiber type based on the ratios of myosin heavy chain isoforms. We further illustrated that three muscles, which typically represented each muscle fiber type (i.e., red: peroneal longus (PL), intermediate: psoas major muscle (PMM), white: longissimus dorsi muscle (LDM)), have distinct metabolic patterns of mitochondrial and glycolytic enzyme levels. Furthermore, we constructed small RNA libraries for PL, PMM, and LDM using a deep sequencing approach. Results showed that the differentially expressed miRNAs were mainly enriched in PL and played a vital role in myogenesis and energy metabolism. Overall, this comprehensive analysis will contribute to a better understanding of the miRNA regulatory mechanism that achieves the phenotypic diversity of skeletal muscles. PMID:25938964

Covalent Strategies for Targeting Messenger and Non-Coding RNAs: An Updated Review on siRNA, miRNA and antimiR Conjugates

PubMed Central

Grijalvo, Santiago; Alagia, Adele

2018-01-01

Oligonucleotide-based therapy has become an alternative to classical approaches in the search of novel therapeutics involving gene-related diseases. Several mechanisms have been described in which demonstrate the pivotal role of oligonucleotide for modulating gene expression. Antisense oligonucleotides (ASOs) and more recently siRNAs and miRNAs have made important contributions either in reducing aberrant protein levels by sequence-specific targeting messenger RNAs (mRNAs) or restoring the anomalous levels of non-coding RNAs (ncRNAs) that are involved in a good number of diseases including cancer. In addition to formulation approaches which have contributed to accelerate the presence of ASOs, siRNAs and miRNAs in clinical trials; the covalent linkage between non-viral vectors and nucleic acids has also added value and opened new perspectives to the development of promising nucleic acid-based therapeutics. This review article is mainly focused on the strategies carried out for covalently modifying siRNA and miRNA molecules. Examples involving cell-penetrating peptides (CPPs), carbohydrates, polymers, lipids and aptamers are discussed for the synthesis of siRNA conjugates whereas in the case of miRNA-based drugs, this review article makes special emphasis in using antagomiRs, locked nucleic acids (LNAs), peptide nucleic acids (PNAs) as well as nanoparticles. The biomedical applications of siRNA and miRNA conjugates are also discussed. PMID:29415514

Human microRNA target analysis and gene ontology clustering by GOmir, a novel stand-alone application.

PubMed

Roubelakis, Maria G; Zotos, Pantelis; Papachristoudis, Georgios; Michalopoulos, Ioannis; Pappa, Kalliopi I; Anagnou, Nicholas P; Kossida, Sophia

2009-06-16

microRNAs (miRNAs) are single-stranded RNA molecules of about 20-23 nucleotides length found in a wide variety of organisms. miRNAs regulate gene expression, by interacting with target mRNAs at specific sites in order to induce cleavage of the message or inhibit translation. Predicting or verifying mRNA targets of specific miRNAs is a difficult process of great importance. GOmir is a novel stand-alone application consisting of two separate tools: JTarget and TAGGO. JTarget integrates miRNA target prediction and functional analysis by combining the predicted target genes from TargetScan, miRanda, RNAhybrid and PicTar computational tools as well as the experimentally supported targets from TarBase and also providing a full gene description and functional analysis for each target gene. On the other hand, TAGGO application is designed to automatically group gene ontology annotations, taking advantage of the Gene Ontology (GO), in order to extract the main attributes of sets of proteins. GOmir represents a new tool incorporating two separate Java applications integrated into one stand-alone Java application. GOmir (by using up to five different databases) introduces miRNA predicted targets accompanied by (a) full gene description, (b) functional analysis and (c) detailed gene ontology clustering. Additionally, a reverse search initiated by a potential target can also be conducted. GOmir can freely be downloaded BRFAA.

A Systematic Analysis on mRNA and MicroRNA Expression in Runting and Stunting Chickens

PubMed Central

Xu, Haiping; Xu, Zhenqiang; Ma, Jinge; Li, Bixiao; Lin, Shudai; Nie, Qinghua; Luo, Qingbin; Zhang, Xiquan

2015-01-01

Runting and stunting syndrome (RSS), which is characterized by lower body weight, widely occurs in broilers. Some RSS chickens simply exhibit slow growth without pathological changes. An increasing number of studies indicate that broiler strains differ in susceptibility to infectious diseases, most likely due to their genetic differences. The objective of this study was to detect the differentially expressed miRNAs and mRNAs in RSS and normal chickens. By integrating miRNA with mRNA expression profiling, potential molecular mechanisms involved in RSS could be further explored. Twenty-two known miRNAs and 1,159 genes were differentially expressed in RSS chickens compared with normal chickens (P < 0.05). qPCR validation results displayed similar patterns. The differentially expressed genes were primarily involved in energy metabolism pathways. The antisense transcripts were extensively expressed in chicken liver albeit with reduced abundance. Dual-luciferase reporter assay indicated that gga-miR-30b/c directly target CARS through binding to its 3′UTR. The miR-30b/c: CARS regulation mainly occurred in liver. In thigh muscle and the hypothalamus, miR-30b/c are expressed at higher levels in RSS chickens compared with normal chickens from 2 to 6 w of age, and notably significant differences are observed at 4 w of age. PMID:26010155

Neutrino flux predictions for the NuMI beam

NASA Astrophysics Data System (ADS)

Aliaga, L.; Kordosky, M.; Golan, T.; Altinok, O.; Bellantoni, L.; Bercellie, A.; Betancourt, M.; Bravar, A.; Budd, H.; Carneiro, M. F.; Dytman, S.; Díaz, G. A.; Endress, E.; Felix, J.; Fields, L.; Fine, R.; Gago, A. M.; Galindo, R.; Gallagher, H.; Gran, R.; Harris, D. A.; Higuera, A.; Hurtado, K.; Kiveni, M.; Kleykamp, J.; Le, T.; Maher, E.; Manly, S.; Mann, W. A.; Marshall, C. M.; Martinez Caicedo, D. A.; McFarland, K. S.; McGivern, C. L.; McGowan, A. M.; Messerly, B.; Miller, J.; Mislivec, A.; Morfín, J. G.; Mousseau, J.; Naples, D.; Nelson, J. K.; Norrick, A.; Nuruzzaman, Paolone, V.; Park, J.; Patrick, C. E.; Perdue, G. N.; Ransome, R. D.; Ray, H.; Ren, L.; Rimal, D.; Rodrigues, P. A.; Ruterbories, D.; Schellman, H.; Solano Salinas, C. J.; Sánchez Falero, S.; Tice, B. G.; Valencia, E.; Walton, T.; Wolcott, J.; Wospakrik, M.; Zhang, D.; MinerνA Collaboration

2016-11-01

Knowledge of the neutrino flux produced by the Neutrinos at the Main Injector (NuMI) beamline is essential to the neutrino oscillation and neutrino interaction measurements of the MINERvA, MINOS + , NOvA and MicroBooNE experiments at Fermi National Accelerator Laboratory. We have produced a flux prediction which uses all available and relevant hadron production data, incorporating measurements of particle production off of thin targets as well as measurements of particle yields from a spare NuMI target exposed to a 120 GeV proton beam. The result is the most precise flux prediction achieved for a neutrino beam in the one to tens of GeV energy region. We have also compared the prediction to in situ measurements of the neutrino flux and find good agreement.

Assessment of total nitrogen in the upper Connecticut River basin in New Hampshire, Vermont, and Massachusetts, December 2002-September 2005

USGS Publications Warehouse

Deacon, Jeffrey R.; Smith, Thor E.; Johnston, Craig M.; Moore, Richard B.; Blake, Laura J.; Weidman, Rebecca M.

2006-01-01

A study of total nitrogen concentrations and loads was conducted from December 2002 to September 2005 at 13 river sites in the upper Connecticut River Basin. Ten sites were selected to represent contributions of nitrogen from forested, agricultural, and urban land. Three sites were distributed spatially on the main stem of the Connecticut River to assess the cumulative total nitrogen loads. To further improve the understanding of the sources and concentrations and loads of total nitrogen in the upper Connecticut River Basin, ambient surface water-quality sampling was supplemented with sampling of effluent from 19 municipal and paper mill wastewater-treatment facilities. Mean concentrations of total nitrogen ranged from 0.19 to 2.8 milligrams per liter (mg/L) at river sampling sites. Instantaneous mean loads of total nitrogen ranged from 162 to 58,300 pounds per day (lb/d). Estimated mean annual loads of total nitrogen ranged from 49,100 to 21.6 million pounds per year (lb/yr) with about 30 to 55 percent of the loads being transported during the spring. The estimated mean annual yields of total nitrogen ranged from 1,190 to 7,300 pounds per square mile per year (lb/mi2)/yr. Mean concentrations of total nitrogen ranged from 4.4 to 30 mg/L at wastewater-treatment sampling sites. Instantaneous mean loads of total nitrogen from municipal wastewater-treatment facilities ranged from 36 to 1,780 lb/d. Instantaneous mean loads of total nitrogen from paper mill wastewater-treatment facilities ranged from 96 to 160 lb/d. The median concentration of total nitrogen was 0.24 mg/L at forested sites, 0.48 mg/L at agricultural sites, 0.54 mg/L at urban sites, 0.48 mg/L at main-stem sites, and 14 mg/L at wastewater-treatment sites. Concentrations of total nitrogen at forested sites were significantly less than at all other site types (p0.05) but were significantly greater (p<0.05) than at forested sites and significantly less than concentrations at wastewater-treatment sites (p<0.05). Total nitrogen concentrations at wastewater-treatment sites were significantly different from all other site types (p<0.05). Annual yields of total nitrogen ranged from 732 to 1,920 (lb/mi2)/yr at forested sites; 1,550 to 2,980 (lb/mi2)/yr at agricultural sites; 1,280 to 1,860 (lb/mi2)/yr at urban sites that were not directly affected by wastewater effluent; 7,090 to 7,770 (lb/mi2)/yr at an urban site directly affected by wastewater effluent; and 1,300 to 2,390 (lb/mi2)/yr at main-stem sites. In this study, the mean annual load and yield of total nitrogen at the Connecticut River at Wells River, VT, was estimated at 4.47 million lb/yr and 1,690 (lb/mi2)/yr, respectively. The mean annual load and yield of total nitrogen at the Connecticut River at North Walpole, NH, was estimated at 9.60 million lb/yr and 1,750 (lb/mi2)/yr, respectively. The mean annual load and yield of total nitrogen leaving the upper Connecticut River Basin, as estimated at the Connecticut River at Thompsonville, CT, was 21.6 million lb/yr and 2,230 (lb/mi2)/yr, respectively.

Helicopter model rotor-blade vortex interaction impulsive noise: Scalability and parametric variations

NASA Technical Reports Server (NTRS)

Splettstoesser, W. R.; Schultz, K. J.; Boxwell, D. A.; Schmitz, F. H.

1984-01-01

Acoustic data taken in the anechoic Deutsch-Niederlaendischer Windkanal (DNW) have documented the blade vortex interaction (BVI) impulsive noise radiated from a 1/7-scale model main rotor of the AH-1 series helicopter. Averaged model scale data were compared with averaged full scale, inflight acoustic data under similar nondimensional test conditions. At low advance ratios (mu = 0.164 to 0.194), the data scale remarkable well in level and waveform shape, and also duplicate the directivity pattern of BVI impulsive noise. At moderate advance ratios (mu = 0.224 to 0.270), the scaling deteriorates, suggesting that the model scale rotor is not adequately simulating the full scale BVI noise; presently, no proved explanation of this discrepancy exists. Carefully performed parametric variations over a complete matrix of testing conditions have shown that all of the four governing nondimensional parameters - tip Mach number at hover, advance ratio, local inflow ratio, and thrust coefficient - are highly sensitive to BVI noise radiation.

Microgravity liquid propellant management

NASA Technical Reports Server (NTRS)

Hung, R. J.

1990-01-01

The requirement to settle or to position liquid fluid over the outlet end of a spacecraft propellant tank prior to main engine restart, poses a microgravity fluid behavior problem. Resettlement or reorientation of liquid propellant can be accomplished by providing optimal acceleration to the spacecraft such that the propellant is reoriented over the tank outlet without any vapor entrainment, any excessive geysering, or any other undersirable fluid motion for the space fluid management under microgravity environment. The most efficient technique is studied for propellant resettling through the minimization of propellant usage and weight penalties. Both full scale and subscale liquid propellant tank of Space Transfer Vehicle were used to simulate flow profiles for liquid hydrogen reorientation over the tank outlet. In subscale simulation, both constant and impulsive resettling acceleration were used to simulate the liquid flow reorientation. Comparisons between the constant reverse gravity acceleration and impulsive reverse gravity acceleration to be used for activation of propellant resettlement shows that impulsive reverse gravity thrust is superior to constant reverse gravity thrust.

Main air pollutants and myocardial infarction: a systematic review and meta-analysis.

PubMed

Mustafic, Hazrije; Jabre, Patricia; Caussin, Christophe; Murad, Mohammad H; Escolano, Sylvie; Tafflet, Muriel; Périer, Marie-Cécile; Marijon, Eloi; Vernerey, Dewi; Empana, Jean-Philippe; Jouven, Xavier

2012-02-15

Short-term exposure to high levels of air pollution may trigger myocardial infarction (MI), but this association remains unclear. To assess and quantify the association between short-term exposure to major air pollutants (ozone, carbon monoxide, nitrogen dioxide, sulfur dioxide, and particulate matter ≤10 μm [PM(10)] and ≤2.5 μm [PM(2.5)] in diameter) on MI risk. EMBASE, Ovid MEDLINE in-process and other nonindexed citations, and Ovid MEDLINE (between 1948 and November 28, 2011), and EBM Reviews-Cochrane Central Register of Controlled Trials and EBM Reviews-Cochrane Database of Systematic Reviews (between 2005 and November 28, 2011) were searched for a combination of keywords related to the type of exposure (air pollution, ozone, carbon monoxide, nitrogen dioxide, sulfur dioxide, PM(10), and PM(2.5)) and to the type of outcome (MI, heart attack, acute coronary syndrome). Two independent reviewers selected studies of any study design and in any language, using original data and investigating the association between short-term exposure (for up to 7 days) to 1 or more air pollutants and subsequent MI risk. Selection was performed from abstracts and titles and pursued by reviewing the full text of potentially eligible studies. Descriptive and quantitative information was extracted from each selected study. Using a random effects model, relative risks (RRs) and 95% CIs were calculated for each increment of 10 μg/m(3) in pollutant concentration, with the exception of carbon monoxide, for which an increase of 1 mg/m(3) was considered. After a detailed screening of 117 studies, 34 studies were identified. All the main air pollutants, with the exception of ozone, were significantly associated with an increase in MI risk (carbon monoxide: 1.048; 95% CI, 1.026-1.070; nitrogen dioxide: 1.011; 95% CI, 1.006-1.016; sulfur dioxide: 1.010; 95% CI, 1.003-1.017; PM(10): 1.006; 95% CI, 1.002-1.009; and PM(2.5): 1.025; 95% CI, 1.015-1.036). For ozone, the RR was 1.003 (95% CI, 0.997-1.010; P = .36). Subgroup analyses provided results comparable with those of the overall analyses. Population attributable fractions ranged between 0.6% and 4.5%, depending on the air pollutant. All the main air pollutants, with the exception of ozone, were significantly associated with a near-term increase in MI risk.

Role of Conceptual Tempo in Concept Formation

ERIC Educational Resources Information Center

Cathcart, W. George; Liedtke, Werner W.

1973-01-01

The main purpose of this study was to select some 7 1/2 to 8 year old subjects and to determine if there was a difference between those classified as impulsive and those classified as reflective in their ability to conserve length. (Author)

Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expression.

PubMed

Zhang, Jing; Liu, Hui; Hou, Lidan; Wang, Ge; Zhang, Rui; Huang, Yanxia; Chen, Xiaoyu; Zhu, Jinshui

2017-09-11

Non-coding RNAs (ncRNAs) have been shown to regulate gene expression involved in tumor progression of multiple malignancies. Our previous studies indicated that large tumor suppressor kinase 1 (LATS1), a core part of Hippo signaling pathway, functions as a tumor suppressor in gastric cancer (GC). But, the underlying molecular mechanisms by which ncRNAs modulate LATS1 expression in GC remain undetermined. The correlation of LATS1 and has-miR-424-5p (miR-424) expression with clinicopathological characteristics and prognosis of GC patients was analyzed by TCGA RNA-sequencing data. A novel circular RNA_LARP4 (circLARP4) was identified to sponge miR-424 by circRNA expression profile and bioinformatic analysis. The binding site between miR-424 and LATS1 or circLARP4 was verified using dual luciferase assay and RNA immunoprecipitation (RIP) assay. The expression and localization of circLARP4 in GC tissues were investigated by fluorescence in situ hybridization (FISH). MTT, colony formation, Transwell and EdU assays were performed to assess the effects of miR-424 or circLARP4 on cell proliferation and invasion. Increased miR-424 expression or decreased LATS1 expression was associated with pathological stage and unfavorable prognosis of GC patients. Ectopic expression of miR-424 promoted proliferation and invasion of GC cells by targeting LATS1 gene. Furthermore, circLARP4 was mainly localized in the cytoplasm and inhibited biological behaviors of GC cells by sponging miR-424. The expression of circLARP4 was downregulated in GC tissues and represented an independent prognostic factor for overall survival of GC patients. circLARP4 may act as a novel tumor suppressive factor and a potential biomarker in GC.

Prostaglandin E2 Regulates Its Own Inactivating Enzyme, 15-PGDH, by EP2 Receptor-Mediated Cervical Cell-Specific Mechanisms

PubMed Central

Kishore, A. Hari; Owens, David

2014-01-01

Context: Prostaglandins play important roles in parturition and have been used to induce cervical ripening and labor. Prior to cervical ripening at term, 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is highly expressed in the cervix and metabolizes cyclooxygenase-2-mediated increases in active prostaglandin E2 (PGE2) to inactive 15-keto PGE2. At term, 15-PGDH gene expression decreases and PGE2 accumulates, leading to cervical ripening and labor. Previously, we found that the cervical isoform of microphthalmia-associated transcription factor (MiTF-CX) serves as a progestational transcription factor that represses IL-8 and hypoxia-mediated increases in cyclooxygenase-2. Objective: We tested the hypothesis that PGE2 regulates its own inactivation through MiTF-CX. Design: We used human cervical stromal cells to investigate the regulation of 15-PGDH. Setting: This was a laboratory-based study using cells from clinical tissue samples. Main Outcome Measures: We evaluated the mechanisms by which PGE2 regulates 15-PGDH in human cervical stromal cells. Results: PGE2 repressed MiTF-CX and 15-PGDH, whereas ectopic overexpression of MiTF-CX induced 15-PGDH expression levels. Stabilization of HIF-1α by deferoxamine resulted in concomitant down-regulation of MiTF-CX and 15-PGDH. Ectopic overexpression of MiTF-CX abrogated PGE2- and deferoxamine-mediated loss of MiTF-CX and 15-PGDH. PGE2-induced loss of MiTF-CX and 15-PGDH was mediated through prostaglandin E2 receptor (EP2) receptors (PTGER2), but not cAMP. Conclusions: The 15-PGDH gene is a MiTF-CX target gene in cervical stromal cells and is down-regulated by PGE2 through EP2 receptors. The findings suggest that EP2 receptor-specific antagonists may be used as an adjunct to present clinical management for the prevention of preterm cervical ripening and preterm labor. PMID:24471568

Selective inhibition of receptor activator of NF-κB ligand (RANKL) in hematopoietic cells improves outcome after experimental myocardial infarction.

PubMed

Slavic, Svetlana; Andrukhova, Olena; Ford, Kristopher; Handschuh, Stephan; Latic, Nejla; Reichart, Ursula; Sasgary, Soleman; Bergow, Claudia; Hofbauer, Lorenz C; Kostenuik, Paul J; Erben, Reinhold G

2018-05-08

The RANK (receptor activator of nuclear factor κB)/RANKL (RANK ligand)/OPG (osteoprotegerin) axis is activated after myocardial infarction (MI), but its pathophysiological role is not well understood. Here, we investigated how global and cell compartment-selective inhibition of RANKL affects cardiac function and remodeling after MI in mice. Global RANKL inhibition was achieved by treatment of human RANKL knock-in (huRANKL-KI) mice with the monoclonal antibody AMG161. huRANKL-KI mice express a chimeric RANKL protein wherein part of the RANKL molecule is humanized. AMG161 inhibits human and chimeric but not murine RANKL. To dissect the pathophysiological role of RANKL derived from hematopoietic and mesenchymal cells, we selectively exchanged the hematopoietic cell compartment by lethal irradiation and across-genotype bone marrow transplantation between wild-type and huRANKL-KI mice, exploiting the specificity of AMG161. After permanent coronary artery ligation, mice were injected with AMG161 or an isotype control antibody over 4 weeks post-MI. MI increased RANKL expression mainly in cardiomyocytes and scar-infiltrating cells 4 weeks after MI. Only inhibition of RANKL derived from hematopoietic cellular sources, but not global or mesenchymal RANKL inhibition, improved post-infarct survival and cardiac function. Mechanistically, hematopoietic RANKL inhibition reduced expression of the pro-inflammatory cytokine IL-1ß in the cardiac cellular infiltrate. In conclusion, inhibition of RANKL derived from hematopoietic cellular sources is beneficial to maintain post-ischemic cardiac function by reduction of pro-inflammatory cytokine production. Experimental myocardial infarction (MI) augments cardiac RANKL expression in mice. RANKL expression is increased in cardiomyocytes and scar-infiltrating cells after MI. Global or mesenchymal cell RANKL inhibition has no influence on cardiac function after MI. Inhibition of RANKL derived from hematopoietic cells improves heart function post-MI. Hematopoietic RANKL inhibition reduces pro-inflammatory cytokines in scar-infiltrating cells.

Women's Sexual Issues After Myocardial Infarction: A Literature Review.

PubMed

Emami Zeydi, Amir; Sharafkhani, Mohammad; Armat, Mohammad Reza; Gould, Kathleen Ahern; Soleimani, Aria; Hosseini, Seyed Javad

2016-01-01

Sexual activity after myocardial infarction (MI) is a concern for patients and often a challenge for health care professionals to address. It is widely recognized that most patients, of both sexes, report sexual problems or concerns after MI. However, there are reported differences between men and women. Women with sexual concerns may seek less help from health care providers and are more inclined to conceal them because of cultural barriers. The aim of the current study is to present a comprehensive review of the literature describing women's sexual issues after MI. A systematic search of the relevant literature was performed within international databases, including PubMed/Medline, Scopus, ScienceDirect, and ProQuest, as well as Google Scholar using relevant keywords. Also, Persian electronic databases such as Magiran, Scientific Information Databases, and Iran Medex were searched from the inception to October 2014. Articles focusing on the sexual issues after MI only in women, as well as articles on both sexes where women's results could be separated, were included in this review. A total of 8 articles were included in the final dataset. The main themes of women's sexual concerns after MI were "loss or decrease of sexual activity," "dissatisfaction of sexual relationship," "doubt about resumption time of sexual activity," "fear of reinfarction or sudden death during sexual activity after MI," "knowledge deficit regarding sexual activity after MI," and "poor performance of health care providers in sexual counseling." The results of this review demonstrate that women's post-MI sexual activity is affected by many concerns. The concerns may be a knowledge deficit related to not receiving necessary consultation on this topic. Nurses, as first-line care givers, can provide appropriate consultation and education for patients post-MI. As a result, breaking taboo imposed by cultural barriers, personal assumptions, or lack of confidence on giving sexual consultation may ultimately help patients to improve their quality of life.

Functional microRNAs in Alzheimer’s disease and cancer: differential regulation of common mechanisms and pathways

PubMed Central

Holohan, Kelly N.; Lahiri, Debomoy K.; Schneider, Bryan P.; Foroud, Tatiana; Saykin, Andrew J.

2013-01-01

Two of the main research priorities in the United States are cancer and neurodegenerative diseases, which are attributed to abnormal patterns of cellular behavior. MicroRNAs (miRNA) have been implicated as regulators of cellular metabolism, and thus are an active topic of investigation in both disease areas. There is presently a more extensive body of work on the role of miRNAs in cancer compared to neurodegenerative diseases, and therefore it may be useful to examine whether there is any concordance between the functional roles of miRNAs in these diseases. As a case study, the roles of miRNAs in Alzheimer’s disease (AD) and their functions in various cancers will be compared. A number of miRNA expression patterns are altered in individuals with AD compared with healthy older adults. Among these, some have also been shown to correlate with neuropathological changes including plaque and tangle accumulation, as well as expression levels of other molecules known to be involved in disease pathology. Importantly, these miRNAs have also been shown to have differential expression and or functional roles in various types of cancer. To examine possible intersections between miRNA functions in cancer and AD, we review the current literature on these miRNAs in cancer and AD, focusing on their roles in known biological pathways. We propose a pathway-driven model in which some molecular processes show an inverse relationship between cancer and neurodegenerative disease (e.g., proliferation and apoptosis) whereas others are more parallel in their activity (e.g., immune activation and inflammation). A critical review of these and other molecular mechanisms in cancer may shed light on the pathophysiology of AD, and highlight key areas for future research. Conclusions from this work may be extended to other neurodegenerative diseases for which some molecular pathways have been identified but which have not yet been extensively researched for miRNA involvement. PMID:23335942

Why standard brain-computer interface (BCI) training protocols should be changed: an experimental study.

PubMed

Jeunet, Camille; Jahanpour, Emilie; Lotte, Fabien

2016-06-01

While promising, electroencephaloraphy based brain-computer interfaces (BCIs) are barely used due to their lack of reliability: 15% to 30% of users are unable to control a BCI. Standard training protocols may be partly responsible as they do not satisfy recommendations from psychology. Our main objective was to determine in practice to what extent standard training protocols impact users' motor imagery based BCI (MI-BCI) control performance. We performed two experiments. The first consisted in evaluating the efficiency of a standard BCI training protocol for the acquisition of non-BCI related skills in a BCI-free context, which enabled us to rule out the possible impact of BCIs on the training outcome. Thus, participants (N = 54) were asked to perform simple motor tasks. The second experiment was aimed at measuring the correlations between motor tasks and MI-BCI performance. The ten best and ten worst performers of the first study were recruited for an MI-BCI experiment during which they had to learn to perform two MI tasks. We also assessed users' spatial ability and pre-training μ rhythm amplitude, as both have been related to MI-BCI performance in the literature. Around 17% of the participants were unable to learn to perform the motor tasks, which is close to the BCI illiteracy rate. This suggests that standard training protocols are suboptimal for skill teaching. No correlation was found between motor tasks and MI-BCI performance. However, spatial ability played an important role in MI-BCI performance. In addition, once the spatial ability covariable had been controlled for, using an ANCOVA, it appeared that participants who faced difficulty during the first experiment improved during the second while the others did not. These studies suggest that (1) standard MI-BCI training protocols are suboptimal for skill teaching, (2) spatial ability is confirmed as impacting on MI-BCI performance, and (3) when faced with difficult pre-training, subjects seemed to explore more strategies and therefore learn better.

The microRNA156-SQUAMOSA PROMOTER BINDING PROTEIN-LIKE3 Module Regulates Ambient Temperature-Responsive Flowering via FLOWERING LOCUS T in Arabidopsis1[C][W][OA

PubMed Central

Kim, Jae Joon; Lee, Jeong Hwan; Kim, Wanhui; Jung, Hye Seung; Huijser, Peter; Ahn, Ji Hoon

2012-01-01

The flowering time of plants is affected by modest changes in ambient temperature. However, little is known about the regulation of ambient temperature-responsive flowering by small RNAs. In this study, we show that the microRNA156 (miR156)-SQUAMOSA PROMOTER BINDING PROTEIN-LIKE3 (SPL3) module directly regulates FLOWERING LOCUS T (FT) expression in the leaf to control ambient temperature-responsive flowering. Overexpression of miR156 led to more delayed flowering at a lower ambient temperature (16°C), which was associated with down-regulation of FT and FRUITFULL expression. Among miR156 target genes, SPL3 mRNA levels were mainly reduced, probably because miR156-mediated cleavage of SPL3 mRNA was higher at 16°C. Overexpression of miR156-resistant SPL3 [SPL3(−)] caused early flowering, regardless of the ambient temperature, which was associated with up-regulation of FT and FRUITFULL expression. Reduction of miR156 activity by target mimicry led to a phenotype similar to that of SUC2::rSPL3 plants. FT up-regulation was observed after dexamethasone treatment in GVG-rSPL3 plants. Misexpression and artificial microRNA-mediated suppression of FT in the leaf dramatically altered the ambient temperature-responsive flowering of plants overexpressing miR156 and SPL3(−). Chromatin immunoprecipitation assay showed that the SPL3 protein directly binds to GTAC motifs within the FT promoter. Lesions in TERMINAL FLOWER1, SHORT VEGETATIVE PHASE, and EARLY FLOWERING3 did not alter the expression of miR156 and SPL3. Taken together, our data suggest that the interaction between the miR156-SPL3 module and FT is part of the regulatory mechanism controlling flowering time in response to ambient temperature. PMID:22427344

miR-342-3p suppresses hepatocellular carcinoma proliferation through inhibition of IGF-1R-mediated Warburg effect.

PubMed

Liu, Wenpeng; Kang, Lei; Han, Juqiang; Wang, Yadong; Shen, Chuan; Yan, Zhifeng; Tai, Yanhong; Zhao, Caiyan

2018-01-01

Insulin-like growth factor-1 receptor (IGF-1R) is a well-studied oncogenic factor that promotes cell proliferation and energy metabolism and is overexpressed in numerous cancers including hepatocellular carcinoma (HCC). Aerobic glycolysis is a hallmark of cancer, and drugs targeting its regulators, including IGF-1R, are being developed. However, the mechanisms of IGF-1R inhibition and the physiological significance of the IGF-1R inhibitors in cancer cells are unclear. Cell proliferation was evaluated by cell counting Kit-8 and colony formation assay. Western blot and real-time PCR were accordingly used to detect the relevant proteins, miRNA and gene expression. Luciferase reporter assays were used to illustrate the interaction between miR-342-3p and IGF-1R. The effect of miR-342-3p on glycolysis was determined by glucose uptake, ATP concentration, lactate generation, extracellular acidification rate and oxygen consumption rate assays. In vivo, subcutaneous tumor formation assay and PET were performed in nude mice. In this study, we demonstrate that by directly targeting the 3'-UTR (3'-untranslated regions) of IGF-1R, microRNA-342-3p (miR-342-3p) suppresses IGF-1R-mediated PI3K/AKT/GLUT1 signaling pathway both in vitro and in vivo. Through suppression of IGF-1R, miR-342-3p dampens glycolysis by decreasing glucose uptake, lactate generation, ATP production, and extracellular acidification rate (ECAR), and increasing oxygen consumption rate (OCR) in hepatoma cells. Importantly, glycolysis regulated by miR-342-3p is critical for its regulating HCC growth both in vitro and in vivo. Our findings provide clues regarding the role of miR-342-3p as a tumor suppressor in liver cancer mainly through the inhibition of IGF-1R. Targeting IGF-1R by miR-342-3p could be a potential therapeutic strategy in liver cancer.

Analysis of mirror neuron system activation during action observation alone and action observation with motor imagery tasks.

PubMed

Cengiz, Bülent; Vurallı, Doğa; Zinnuroğlu, Murat; Bayer, Gözde; Golmohammadzadeh, Hassan; Günendi, Zafer; Turgut, Ali Emre; İrfanoğlu, Bülent; Arıkan, Kutluk Bilge

2018-02-01

This study aimed to explore the relationship between action observation (AO)-related corticomotor excitability changes and phases of observed action and to explore the effects of pure AO and concurrent AO and motor imagery (MI) state on corticomotor excitability using TMS. It was also investigated whether the mirror neuron system activity is muscle-specific. Fourteen healthy volunteers were enrolled in the study. EMG recordings were taken from the right first dorsal interosseous and the abductor digiti minimi muscles. There was a significant main effect of TMS timing (after the beginning of the movement, at the beginning of motor output state, and during black screen) on the mean motor evoked potential (MEP) amplitude. Mean MEP amplitudes for AO combined with MI were significantly higher than pure AO session. There was a significant interaction between session and TMS timing. There was no significant main effect of muscle on MEP amplitude. The results indicate that corticomotor excitability is modulated by different phases of the observed motor movement and this modulation is not muscle-specific. Simultaneous MI and AO enhance corticomotor excitability significantly compared to pure AO.

Coronary microvascular dysfunction after myocardial infarction: increased coronary zero flow pressure both in the infarcted and in the remote myocardium is mainly related to left ventricular filling pressure.

PubMed

Van Herck, P L; Carlier, S G; Claeys, M J; Haine, S E; Gorissen, P; Miljoen, H; Bosmans, J M; Vrints, C J

2007-10-01

To investigate the underlying mechanisms of a decreased coronary flow reserve after myocardial infarction (MI) by analysing the characteristics of the diastolic hyperaemic coronary pressure-flow relationship. Prospective study. Tertiary care hospital. 68 patients with a recent MI and 27 patients with stable angina pectoris (AP; control group). The intercept with the pressure axis (the zero flow pressure or Pzf) and slope index of the pressure-flow relationship (SIPF) were calculated from the simultaneously recorded hyperaemic intracoronary blood flow velocity and aortic pressure after successful coronary stenting. A stepwise increase in Pzf from AP (14.6 (8.0) mm Hg), over non-Q-wave MI (22.5 (9.1) mm Hg), to Q-wave MI (37.1 (12.9) mm Hg; p<0.001) was observed. Similar changes in Pzf were found in a reference artery perfusing the non-infarcted myocardium. Multivariate analysis showed that in both regions the left ventricular end-diastolic pressure (LVEDP) was the most important determinant of the Pzf. The SIPF was not statistically different in the treated vessel between patients with MI and AP, but was increased in MI patients with a markedly increased LVEDP. After an MI, the coronary pressure-flow relationship is shifted to the right both in the infarcted and in the non-infarcted remote myocardium, as shown by the increased Pzf. The correlation with Pzf suggests that elevated left ventricular filling pressures contribute to the impediment of myocardial perfusion in patients with infarction.

MicroRNA-128 suppresses paclitaxel-resistant lung cancer by inhibiting MUC1-C and BMI-1 in cancer stem cells.

PubMed

Koh, Hyebin; Park, Hyeri; Chandimali, Nisansala; Huynh, Do Luong; Zhang, Jiao Jiao; Ghosh, Mrinmoy; Gera, Meeta; Kim, Nameun; Bak, Yesol; Yoon, Do-Young; Park, Yang Ho; Kwon, Taeho; Jeong, Dong Kee

2017-12-15

The existence of cancer stem cells (CSCs) is the main reason for failure of cancer treatment caused by drug resistance. Therefore, eradicating cancers by targeting CSCs remains a significant challenge. In the present study, because of the important role of BMI-1 proto-oncogene, polycomb ring finger (BMI-1) and C-terminal Mucin1 (MUC1-C) in tumor growth and maintenance of CSCs, we aimed to confirm that microRNA miR-128, as an inhibitor of BMI-1 and MUC1-C, could effectively suppress paclitaxel (PTX)-resistant lung cancer stem cells. We showed that CSCs have significantly higher expression levels of BMI-1, MUC1-C, stemness proteins, signaling factors, and higher malignancy compared with normal tumor cells. After transfection with miR-128, the BMI-1 and MUC1-C levels in CSCs were suppressed. When miR-128 was stably expressed in PTX-resistant lung cancer stem cells, the cells showed decreased proliferation, metastasis, self-renewal, migration, invasive ability, clonogenicity, and tumorigenicity in vitro and in vivo and increased apoptosis compared with miR-NC (negative control) CSCs. Furthermore, miR-128 effectively decreased the levels of β-catenin and intracellular signaling pathway-related factors in CSCs. MiR-128 also decreased the luciferase activity of MUC1 reporter constructs and reduced the levels of transmembrane MUC1-C and BMI-1. These results suggested miR-128 as an attractive therapeutic strategy for PTX-resistant lung cancer via inhibition of BMI-1 and MUC1-C.

Preservatives in cosmetics in the Israeli market conform well to the EU legislation.

PubMed

Horev, L; Isaksson, M; Engfeldt, M; Persson, L; Ingber, A; Bruze, M

2015-04-01

Preservatives are important and frequent skin sensitizers, found in a wide range of products for personal and occupational use. According to the European legislation, some cosmetic ingredients are restricted in terms of quantity and a detailed list of ingredients must be present on the product or packaging. To examine the use of preservatives in common cosmetics on the Israeli market. Sixty different Israeli brand cosmetics, including shampoos, liquid soaps, body creams and hand creams were randomly selected. Ingredient labels were examined. The products were investigated by the chromotropic acid method for release of formaldehyde and by high performance liquid chromatography for the presence of formaldehyde, DMDM hydantoin and methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and MI content. All products but one contained a detailed list of ingredients printed on the package. According to labelling, the most prevalent preservatives in Israeli shampoos and liquid soaps were DMDM hydantoin and MCI/MI. Hand creams and body creams contained mainly parabens but also iodopropynyl butylcarbamate, phenoxyethanol and DMDM hydantoin. Formaldehyde in doses from 4 to 429 ppm, and DMDM hydantoin were detected in 38 and 16 (63% and 27%) of the products, respectively. MCI/MI was detected in 11 (18%) of the products, with highest prevalence in rinse- off products (55%). Excluding one hand cream which measured 106 ppm MI, the amount of formaldehyde, DMDM hydantoin, MCI/MI and MI was within the allowed concentrations by the European directive in all cases. In Israel, adaptation of the European directive prevails, as shown by the measurements we performed on randomly selected products. © 2014 European Academy of Dermatology and Venereology.

The legume miR1514a modulates a NAC transcription factor transcript to trigger phasiRNA formation in response to drought

PubMed Central

Sosa-Valencia, Guadalupe; Palomar, Miguel; Covarrubias, Alejandra A.

2017-01-01

Abstract Recent studies have identified microRNAs as post-transcriptional regulators involved in stress responses. miR1514a is a legume microRNA that is induced in response to drought stress in Phaseolus vulgaris (common bean) and shows differential accumulation levels in roots during water deficit in two cultivars with different drought tolerance phenotypes. A recent degradome analysis revealed that miR1514a targets the transcripts of two NAC transcription factors (TFs), Phvul.010g121000 and Phvul.010g120700. Furthermore, expression studies and small RNA-seq data indicate that only Phvul.010g120700 generates phasiRNAs, which also accumulate under water deficit conditions. To confirm these results, we over-expressed miR1514a in transgenic hairy roots, and observed a reduced accumulation of Phvul.010g120700 and an increase in NAC-derived phasiRNAs; inhibition of miR1514a activity resulted in the opposite effect. Moreover, we determined that a NAC-derived phasiRNA associates with ARGONAUTE 1 (AGO1), suggesting that it is functional. In addition, a transcriptome analysis of transgenic hairy roots with reduced miR1514a levels revealed several differentially expressed transcripts, mainly involved in metabolism and stress responses, suggesting they are regulated by the NAC TF and/or by phasiRNAs. This work therefore demonstrates the participation of miR1514 in the regulation of a NAC transcription factor transcript through phasiRNA production during the plant response to water deficit. PMID:28338719

Take the Money and Run: Psychopathic Behavior in the Trust Game

PubMed Central

Ibáñez, Manuel I.; Sabater-Grande, Gerardo; Barreda-Tarrazona, Iván; Mezquita, Laura; López-Ovejero, Sandra; Villa, Helena; Perakakis, Pandelis; Ortet, Generós; García-Gallego, Aurora; Georgantzís, Nikolaos

2016-01-01

We study the association among different sources of individual differences such as personality, cognitive ability and risk attitudes with trust and reciprocate behavior in an incentivized experimental binary trust game in a sample of 220 (138 females) undergraduate students. The game involves two players, player 1 (P1) and player 2 (P2). In the first stage, P1 decides whether to trust and let P2 decide, or to secure an egalitarian payoff for both players. If P1 trusts P2, the latter can choose between a symmetric payoff that is double than the secure alternative discarded by P1, and an asymmetric payoff in which P2 earns more than in any other case but makes P1 worse off. Before the main experiment, we obtained participants’ scores for Abstract Reasoning (AR), risk attitudes, basic personality characteristics, and specific traits such as psychopathy and impulsivity. During the main experiment, we measured Heart Rate (HR) and ElectroDermal Activity (EDA) variation to account for emotional arousal caused by the decision and feedback processes. Our main findings indicate that, on one hand, P1 trust behavior associates to positive emotionality and, specifically, to the extraversion’s warmth facet. In addition, the impulsivity facet of positive urgency also favors trust behavior. No relation to trusting behavior was found for either other major personality aspects or risk attitudes. The physiological results show that participants scoring high in psychopathy exhibit increased EDA and reduced evoked HR deceleration at the moment in which they are asked to decide whether or not to trust. Regarding P2, we find that AR ability and mainly low disagreeable disinhibition favor reciprocal behavior. Specifically, lack of reciprocity significantly relates with a psychopathic, highly disinhibited and impulsive personality. Thus, the present study suggests that personality characteristics would play a significant role in different behaviors underlying cooperation, with extraversion/positive emotionality being more relevant for initiating cooperation, and low disagreeable disinhibition for maintaining it. PMID:27965606

A Neuropsychological Assessment of Frontal Cognitive Functions in Prader-Willi Syndrome

ERIC Educational Resources Information Center

Jauregi, J.; Arias, C.; Vegas, O.; Alen, F.; Martinez, S.; Copet, P.; Thuilleaux, D.

2007-01-01

Background: Prader-Willi syndrome (PWS) is associated with a characteristic behavioural phenotype whose main features are, alongside compulsive hyperphagia, deficits in social behaviour: social withdrawal, temper tantrums, perseverative speech and behaviour, mental rigidity, stereotyped behaviour, impulsiveness, etc. Similar symptoms may also be…

Motives underlying food consumption in the Western Balkans: consumers' profiles and public health strategies.

PubMed

Mardon, Julie; Thiel, Elise; Laniau, Martine; Sijtsema, Siet; Zimmermann, Karin; Barjolle, Dominique

2015-07-01

This study aims to identify subgroups of consumers based on the health motives underlying their food choice in Western Balkan Countries. The survey (n = 2943) was based on the Food Choice Questionnaire (FCQ) and elicited information on socio-demographic characteristics, consumption frequency of healthy food products, nutrition knowledge and impulsiveness. Analysis of the FCQ data focused on items of "health and natural content" and "weight control" factors to identify clusters. The biggest group of the sample was weight control and health-concerned individuals (34 %), mainly urban women older than 50. The second group of respondents (31 %) was moderately motivated about health and weight. A third group was health concerned but paid less attention to weight control (21 %), mainly comprising men and people living with children. The last group consisted of unconcerned young men (14 %) eating less fruit and showing higher impulsiveness. Western Balkan consumers differ in the importance they attach to health and natural content and weight control. This insight is needed to target interventions.

Calculation of impulse laser rangefinders' utmost operating range with sensitivity in different weather

NASA Astrophysics Data System (ADS)

Chen, Yu-dan; Zhou, Bing; Ying, Jia-ju; Mao, Shao-juan; Qian, Xian-mei

2015-10-01

As one of the main weapons, impulse laser rangefinders have become the main object of the electro-optical countermeasures. So its real maximum range (defined as utmost operating range in the paper) becomes the most concerned index to evaluate the performance of electro-optical countermeasure weapons. A method for calculating laser rangefinders' utmost operating range by its sensitivity in different weather is obtained. Then a method by experiment for getting the sensitivity is supplied. By analyzing the experiment data which the detectivity is 40%-60%, the laser rangefinders' sensitivity is in the range of 1.7×10-5 W to 9.8×10-5 W. For the reason that in order to get an exact utmost operating range, the experiment accuracy of sensitivity is very important, in the last part of paper, the factors which influence the experiment accuracy of sensitivity are analyzed, such as circuit of automatic gain control, the fluctuation of laser power, incident angle of laser.

Declarative Intonation in Korean: AN Acoustical Study of F(o) Declination.

NASA Astrophysics Data System (ADS)

Ko, Do-Heung

This dissertation investigates some acoustic features of declarative intonation in standard Korean based on the hypothesis that fundamental frequency (F_0 ) declination can be syntactically determined. In the course of this study, the following major issues are addressed: (i) What is the relation between sentence length and F_0 contours? (ii) Is there any difference in F_0 patterns between male and female speakers? (iii) Is F_0 declination exclusively a surface structure phenomenon? (iv) Are F_0 contours of parentheticals independent from those of the main clause? (v) What is the effect of word order on variations in F_0 ?. Ten subjects (seven male and three female speakers of the Seoul dialect) read sentences with various types of syntactic structure. In order to analyze F _0 declination phenomena, a software program, DoReMi, and an Impulse Audio Digitizer were used with a Macintosh computer. After obtaining the results from the computer, the Visi-Pitch was also used to confirm some F_0 traces. Major results from this research may be summarized as follows: (i) The rate of declination is not affected by the length of the syntactic unit. Particularly, initial and final values are nearly constant in both progressively longer simplex sentences and expanded embedded sentences. (ii) F_0 contours for male and female subjects are strikingly similar except for the different ranges. (iii) The deletion site plays a certain role in the process of F_0 contours, suggesting that declination may be determined at an underlying or abstract level. (iv) As in English, a parenthetical phrase or clause in Korean has a separate F_0 pattern in its own right, and the parenthetical does not perturb the F_0 pattern of the main clause. (v) Sentences with word orders which are used most frequently in discourse have shown the standard pattern of F_0 declination while orders which are used less frequently have unpredictable F _0 patterns in general.

A retrospective comparative study of minimally invasive extracorporeal circulation versus conventional extracorporeal circulation in emergency coronary artery bypass surgery patients: a single surgeon analysis.

PubMed

Rufa, Magdalena; Schubel, Jens; Ulrich, Christian; Schaarschmidt, Jan; Tiliscan, Catalin; Bauer, Adrian; Hausmann, Harald

2015-07-01

At the moment, the main application of minimally invasive extracorporeal circulation (MiECC) is reserved for elective cardiac operations such as coronary artery bypass grafting (CABG) and/or aortic valve replacement. The purpose of this study was to compare the outcome of emergency CABG operations using either MiECC or conventional extracorporeal circulation (CECC) in patients requiring emergency CABG with regard to the perioperative course and the occurrence of major adverse cardiac and cerebral events (MACCE). We analysed the emergency CABG operations performed by a single surgeon, between January 2007 and July 2013, in order to exclude the differences in surgical technique. During this period, 187 emergency CABG patients (113 MiECC vs 74 CECC) were investigated retrospectively with respect to the following parameters: in-hospital mortality, MACCE, postoperative hospital stay and perioperative transfusion rate. The mean logistic European System for Cardiac Operative Risk Evaluation was higher in the CECC group (MiECC 12.1 ± 16 vs CECC 15.0 ± 20.8, P = 0.15) and the number of bypass grafts per patient was similar in both groups (MiECC 2.94 vs CECC 2.93). There was no significant difference in the postoperative hospital stay or in major postoperative complications. The in-hospital mortality was higher in the CECC group 6.8% versus MiECC 4.4% (P = 0.48). The perioperative transfusion rate was lower with MiECC compared with CECC (MiECC 2.6 ± 3.2 vs CECC 3.8 ± 4.2, P = 0.025 units of blood per patient). In our opinion, the use of MiECC in urgent CABG procedures is safe, feasible and shows no disadvantages compared with the use of CECC. Emergency operations using the MiECC system showed a significantly lower blood transfusion rate and better results concerning the unadjusted in-hospital mortality. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Coronary artery disease severity and long-term cardiovascular risk in patients with myocardial infarction: a Danish nationwide register-based cohort study

PubMed Central

Özcan, Cengiz; Deleskog, Anna; Schjerning Olsen, Anne-Marie; Nordahl Christensen, Helene; Lock Hansen, Morten; Hilmar Gislason, Gunnar

2018-01-01

Abstract Aim Long-term prognostic impact of coronary artery disease (CAD) severity in stable post-myocardial infarction (MI) patients is not well known. We examined the impact of CAD severity and co-morbidity on the long-term (1 year and beyond) risk of cardiovascular events post-MI. Methods and results From nationwide administrative and clinical registers, we identified 55 747 MI patients, during 2004–2010, who had not experienced subsequent MI, stroke, or death within 7 days post-discharge. The risk for primary composite endpoint (MI, stroke, or cardiovascular death) was estimated for the first 365 days after MI (index MI) and from day 366 to study completion (stable post-MI population), corresponding to a mean follow-up of 3.6 (2.2) years. Risk was assessed using cumulative incidence, multivariable adjusted logistic regression and Cox proportional-hazards models. The 1-year cumulative incidence for primary endpoint was 20.0% [95% confidence interval (CI), (19.6–20.3)]. Correspondingly, the 4-year cumulative incidence for primary endpoint was 21.0% (95% CI, 20.6–21.4) in patients without events on the first year. In multivariable models with no significant stenosis as reference, CAD severity was the most important risk factor for cardiovascular events the first 365 days [left main stenosis (LMS): odds ratio and 95% CI, 4.37, 3.69–5.17; 3-vessel disease (VD), 4.18, 3.66–4.77; 2-VD, 3.23, 2.81–3.72; 1-VD, 2.12,–1.85–2.43] and remained from day 366 to study completion [LMS: hazard ratio and 95% CI, 1.91, 1.64–2.22; 3-VD, 1.85,1.65–2.07; 2-VD, 1.55, 1.38–1.74; 1-VD, 1.30, 1.16–1.45]. Conclusion Despite contemporary treatment at baseline, stable post-MI patients’ 4-year outcome was similar to 1-year outcome after MI, and CAD severity remained a critical risk factor the first year and thereafter. PMID:28444162

Modulation by Cocaine of Dopamine Receptors through miRNA-133b in Zebrafish Embryos

PubMed Central

Barreto-Valer, Katherine; López-Bellido, Roger; Macho Sánchez-Simón, Fátima; Rodríguez, Raquel E.

2012-01-01

The use of cocaine during pregnancy can affect the mother and indirectly might alter the development of the embryo/foetus. Accordingly, in the present work our aim was to study in vivo (in zebrafish embryos) the effects of cocaine on the expression of dopamine receptors and on miR-133b. These embryos were exposed to cocaine hydrochloride (HCl) at 5 hours post-fertilization (hpf) and were then collected at 8, 16, 24, 48 and 72 hpf to study the expression of dopamine receptors, drd1, drd2a, drd2b and drd3, by quantitative real time PCR (qPCR) and in situ hybridization (ISH, only at 24 hpf). Our results indicate that cocaine alters the expression of the genes studied, depending on the stage of the developing embryo and the type of dopamine receptor. We found that cocaine reduced the expression of miR-133b at 24 and 48 hpf in the central nervous system (CNS) and at the periphery by qPCR and also that the spatial distribution of miR-133b was mainly seen in somites, a finding that suggests the involvement of miR-133b in the development of the skeletal muscle. In contrast, at the level of the CNS miR-133b had a weak and moderate expression at 24 and 48 hpf. We also analysed the interaction of miR-133b with the Pitx3 and Pitx3 target genes drd2a and drd2b, tyrosine hydroxylase (th) and dopamine transporter (dat) by microinjection of the Pitx3-3'UTR sequence. Microinjection of Pitx3-3'UTR affected the expression of pitx3, drd2a, drd2b, th and dat. In conclusion, in the present work we describe a possible mechanism to account for cocaine activity by controlling miR-133b transcription in zebrafish. Via miR-133b cocaine would modulate the expression of pitx3 and subsequently of dopamine receptors, dat and th. These results indicate that miRNAs can play an important role during embryogenesis and in drug addiction. PMID:23285158

Association between Polymorphisms in MicroRNAs and Risk of Urological Cancer: A Meta-Analysis Based on 17,019 Subjects

PubMed Central

Wang, Yu-Hui; Hu, Han-Ning; Weng, Hong; Chen, Hao; Luo, Chang-Liang; Ji, Jia; Yin, Chang-Qing; Yuan, Chun-Hui; Wang, Fu-Bing

2017-01-01

Accumulating evidence has demonstrated that some single nucleotide polymorphisms (SNPs) existing in miRNAs correlate with the susceptibility to urological cancers. However, a clear consensus still not reached due to the limited statistical power in individual study. Thus, we concluded a meta-analysis to systematically evaluate the association between microRNA SNPs and urological cancer risk. Eligible studies were collected from PubMed, Embase, Web of Science, and CNKI databases. Pooled odds ratio (OR) and corresponding 95% confidence interval (95% CI) were calculated to assess the strength of the relationships between three SNPs (miR-196a2, C>T rs11614913; miR-146a, G>C rs2910164; and miR-499, A>G rs3746444) and the risk of urological cancers. In addition, the stability of our analysis was evaluated by publication bias, sensitivity and heterogeneity analysis. Overall, a total of 17,019 subjects from 14 studies were included in this meta-analysis. We found that CT (miR-196a2, C>T rs11614913) was a risk factor for renal cell carcinoma (CT vs. CC: OR = 1.72, 95%CI = 1.05–2.80, P = 0.03, I2 = 66%), especially in Asian population (CT vs. CC: OR = 1.17, 95%CI = 1.04–1.32, P < 0.01, I2 = 0%). miR-146a G>C rs2910164 was a protective factor of urological cancers (C vs. G: OR = 0.87, 95%CI = 0.81–0.93, P < 0.01, I2 = 0%), especially for bladder cancer. miR-499 A>G rs3746444 was correlated with an increased risk of urological cancers, specifically in Asian population. In conclusion, our meta-analysis suggests that polymorphisms in microRNAs, miR-196a2, C>T rs11614913, miR-146a G>C rs2910164 and miR-499 A>G rs3746444, may be associated with the development of urological cancers and the risks mainly exist in Asian populations. PMID:28579964

Asymmetric purine-pyrimidine distribution in cellular small RNA population of papaya

PubMed Central

2012-01-01

Background The small RNAs (sRNA) are a regulatory class of RNA mainly represented by the 21 and 24-nucleotide size classes. The cellular sRNAs are processed by RNase III family enzyme dicer (Dicer like in plant) from a self-complementary hairpin loop or other type of RNA duplexes. The papaya genome has been sequenced, but its microRNAs and other regulatory RNAs are yet to be analyzed. Results We analyzed the genomic features of the papaya sRNA population from three sRNA deep sequencing libraries made from leaves, flowers, and leaves infected with Papaya Ringspot Virus (PRSV). We also used the deep sequencing data to annotate the micro RNA (miRNA) in papaya. We identified 60 miRNAs, 24 of which were conserved in other species, and 36 of which were novel miRNAs specific to papaya. In contrast to the Chargaff’s purine-pyrimidine equilibrium, cellular sRNA was significantly biased towards a purine rich population. Of the two purine bases, higher frequency of adenine was present in 23nt or longer sRNAs, while 22nt or shorter sRNAs were over represented by guanine bases. However, this bias was not observed in the annotated miRNAs in plants. The 21nt species were expressed from fewer loci but expressed at higher levels relative to the 24nt species. The highly expressed 21nt species were clustered in a few isolated locations of the genome. The PRSV infected leaves showed higher accumulation of 21 and 22nt sRNA compared to uninfected leaves. We observed higher accumulation of miRNA* of seven annotated miRNAs in virus-infected tissue, indicating the potential function of miRNA* under stressed conditions. Conclusions We have identified 60 miRNAs in papaya. Our study revealed the asymmetric purine-pyrimidine distribution in cellular sRNA population. The 21nt species of sRNAs have higher expression levels than 24nt sRNA. The miRNA* of some miRNAs shows higher accumulation in PRSV infected tissues, suggesting that these strands are not totally functionally redundant. The findings open a new avenue for further investigation of the sRNA silencing pathway in plants. PMID:23216749

Asymmetric purine-pyrimidine distribution in cellular small RNA population of papaya.

PubMed

Aryal, Rishi; Yang, Xiaozeng; Yu, Qingyi; Sunkar, Ramanjulu; Li, Lei; Ming, Ray

2012-12-05

The small RNAs (sRNA) are a regulatory class of RNA mainly represented by the 21 and 24-nucleotide size classes. The cellular sRNAs are processed by RNase III family enzyme dicer (Dicer like in plant) from a self-complementary hairpin loop or other type of RNA duplexes. The papaya genome has been sequenced, but its microRNAs and other regulatory RNAs are yet to be analyzed. We analyzed the genomic features of the papaya sRNA population from three sRNA deep sequencing libraries made from leaves, flowers, and leaves infected with Papaya Ringspot Virus (PRSV). We also used the deep sequencing data to annotate the micro RNA (miRNA) in papaya. We identified 60 miRNAs, 24 of which were conserved in other species, and 36 of which were novel miRNAs specific to papaya. In contrast to the Chargaff's purine-pyrimidine equilibrium, cellular sRNA was significantly biased towards a purine rich population. Of the two purine bases, higher frequency of adenine was present in 23nt or longer sRNAs, while 22nt or shorter sRNAs were over represented by guanine bases. However, this bias was not observed in the annotated miRNAs in plants. The 21nt species were expressed from fewer loci but expressed at higher levels relative to the 24nt species. The highly expressed 21nt species were clustered in a few isolated locations of the genome. The PRSV infected leaves showed higher accumulation of 21 and 22nt sRNA compared to uninfected leaves. We observed higher accumulation of miRNA* of seven annotated miRNAs in virus-infected tissue, indicating the potential function of miRNA* under stressed conditions. We have identified 60 miRNAs in papaya. Our study revealed the asymmetric purine-pyrimidine distribution in cellular sRNA population. The 21nt species of sRNAs have higher expression levels than 24nt sRNA. The miRNA* of some miRNAs shows higher accumulation in PRSV infected tissues, suggesting that these strands are not totally functionally redundant. The findings open a new avenue for further investigation of the sRNA silencing pathway in plants.

Traffic-Related Air Pollution and the Onset of Myocardial Infarction: Disclosing Benzene as a Trigger? A Small-Area Case-Crossover Study

PubMed Central

Bard, Denis; Kihal, Wahida; Schillinger, Charles; Fermanian, Christophe; Ségala, Claire; Glorion, Sophie; Arveiler, Dominique; Weber, Christiane

2014-01-01

Background and Objectives Exposure to traffic is an established risk factor for the triggering of myocardial infarction (MI). Particulate matter, mainly emitted by diesel vehicles, appears to be the most important stressor. However, the possible influence of benzene from gasoline-fueled cars has not been explored so far. Methods and Results We conducted a case-crossover study from 2,134 MI cases recorded by the local Coronary Heart Disease Registry (2000–2007) in the Strasbourg Metropolitan Area (France). Available individual data were age, gender, previous history of ischemic heart disease and address of residence at the time of the event. Nitrogen dioxide, particles of median aerodynamic diameter <10 µm (PM10), ozone, carbon monoxide and benzene air concentrations were modeled on an hourly basis at the census block level over the study period using the deterministic ADMS-Urban air dispersion model. Model input data were emissions inventories, background pollution measurements, and meteorological data. We have found a positive, statistically significant association between concentrations of benzene and the onset of MI: per cent increase in risk for a 1 µg/m3 increase in benzene concentration in the previous 0, 0–1 and 1 day was 10.4 (95% confidence interval 3–18.2), 10.7 (2.7–19.2) and 7.2 (0.3–14.5), respectively. The associations between the other pollutants and outcome were much lower and in accordance with the literature. Conclusion We have observed that benzene in ambient air is strongly associated with the triggering of MI. This novel finding needs confirmation. If so, this would mean that not only diesel vehicles, the main particulate matter emitters, but also gasoline-fueled cars –main benzene emitters–, should be taken into account for public health action. PMID:24932584

High trait aggression in men is associated with low 5-HT levels, as indexed by 5-HT4 receptor binding.

PubMed

da Cunha-Bang, Sofi; Mc Mahon, Brenda; Fisher, Patrick MacDonald; Jensen, Peter Steen; Svarer, Claus; Knudsen, Gitte Moos

2016-04-01

Impulsive aggression has commonly been associated with a dysfunction of the serotonin (5-HT) system: many, but not all, studies point to an inverse relationship between 5-HT and aggression. As cerebral 5-HT4 receptor (5-HT4R) binding has recently been recognized as a proxy for stable brain levels of 5-HT, we here test the hypothesis in healthy men and women that brain 5-HT levels, as indexed by cerebral 5-HT4R, are inversely correlated with trait aggression and impulsivity. Sixty-one individuals (47 men) underwent positron emission tomography scanning with the radioligand [(11)C]SB207145 for quantification of brain 5-HT4R binding. The Buss-Perry Aggression Questionnaire (BPAQ) and the Barratt Impulsiveness Scale were used for assessment of trait aggression and trait impulsivity. Among male subjects, there was a positive correlation between global 5-HT4R and BPAQ total score (P = 0.037) as well as BPAQ physical aggression (P = 0.025). No main effect of global 5-HT4R on trait aggression or impulsivity was found in the mixed gender sample, but there was evidence for sex interaction effects in the relationship between global 5-HT4R and BPAQ physical aggression. In conclusion we found that low cerebral 5-HT levels, as indexed by 5-HT4R binding were associated with high trait aggression in males, but not in females. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Motivational Interviewing or Reminders for Glaucoma Medication Adherence? Results of a Multi-Site Randomized Controlled Trial

PubMed Central

Schmiege, Sarah J.; Mansberger, Steven L.; Sheppler, Christina; Kammer, Jeffrey; Fitzgerald, Timothy; Kahook, Malik Y.

2017-01-01

Objective Nonadherence reduces glaucoma treatment efficacy. Motivational interviewing (MI) is a well-studied adherence intervention, but has not been tested in glaucoma. Reminder interventions also may improve adherence. Design 201 patients with glaucoma or ocular hypertension were urn-randomized to receive MI delivered by an ophthalmic technician (OT), usual care, or a minimal behavioral intervention (reminder calls). Main Outcome Measures Outcomes included electronic monitoring with Medication Event Monitoring System (MEMS) bottles, two self-report adherence measures, patient satisfaction, and clinical outcomes. Multilevel modeling was used to test differences in MEMS results by group over time; ANCOVA was used to compare groups on other measures. Results Reminder calls increased adherence compared to usual care based on MEMS, p = .005, and self-report, p = .04. MI had a nonsignificant effect but produced higher satisfaction than reminder calls, p = .007. Treatment fidelity was high on most measures, with observable differences in behavior between groups. All groups had high baseline adherence that limited opportunities for change. Conclusion Reminder calls, but not MI, led to better adherence than usual care. Although a large literature supports MI, reminder calls might be a cost-effective intervention for patients with high baseline adherence. Replication is needed with less adherent participants. PMID:27701902

Single-trial effective brain connectivity patterns enhance discriminability of mental imagery tasks

NASA Astrophysics Data System (ADS)

Rathee, Dheeraj; Cecotti, Hubert; Prasad, Girijesh

2017-10-01

Objective. The majority of the current approaches of connectivity based brain-computer interface (BCI) systems focus on distinguishing between different motor imagery (MI) tasks. Brain regions associated with MI are anatomically close to each other, hence these BCI systems suffer from low performances. Our objective is to introduce single-trial connectivity feature based BCI system for cognition imagery (CI) based tasks wherein the associated brain regions are located relatively far away as compared to those for MI. Approach. We implemented time-domain partial Granger causality (PGC) for the estimation of the connectivity features in a BCI setting. The proposed hypothesis has been verified with two publically available datasets involving MI and CI tasks. Main results. The results support the conclusion that connectivity based features can provide a better performance than a classical signal processing framework based on bandpass features coupled with spatial filtering for CI tasks, including word generation, subtraction, and spatial navigation. These results show for the first time that connectivity features can provide a reliable performance for imagery-based BCI system. Significance. We show that single-trial connectivity features for mixed imagery tasks (i.e. combination of CI and MI) can outperform the features obtained by current state-of-the-art method and hence can be successfully applied for BCI applications.

Tumor-suppressive microRNA-497 targets IKKβ to regulate NF-κB signaling pathway in human prostate cancer cells.

PubMed

Kong, Xiang-Jie; Duan, Liu-Jian; Qian, Xiao-Qiang; Xu, Ding; Liu, Hai-Long; Zhu, Ying-Jian; Qi, Jun

2015-01-01

Prostate cancer (PCa) is one of the most prevalent malignant tumors, PCa-related death is mainly due to the high probability of metastasis. MicroRNAs (miRNAs) play an important role in cancer initiation, progression and metastasis by regulating their target genes. real-time PCR was used to detected the expression of microRNA-497. The molecular biological function was investigated by using cell proliferation assays, cell cycle assay, and migration and invasion assay. We used several Algorithms and confirmed that IKKβ is directly regulated by miR-497. Here, we found miR-497 is downregulated in human prostate cancer (PCa) and inhibites the proliferation activity, migration and invasion of PC3-AR cells. Subsequently, IKKβ is confi rmed as a target of miR-497. Furthermore, knockdown of IKKβ expression resulted in decreased proliferation activity, migration and invasion. Finally, similar results was found after treatment with a novel IKK-β inhibitor (IMD-0354) in PC3-AR cells. CDK8, MMP-9, and PSA were involved in all these process. Taken together, our results show evidence that miR-497 may function as a tumor suppressor genes by regulating IKK-β in PCa, and may provide a strategy for blocking PCa metastasis.

Neutrino flux predictions for the NuMI beam

DOE PAGES

Aliaga, L.; Kordosky, M.; Golan, T.; ...

2016-11-29

Knowledge of the neutrino flux produced by the Neutrinos at the Main Injector (NuMI) beamline is essential to the neutrino oscillation and neutrino interaction measurements of the MINERvA, MINOS+, NOvA and MicroBooNE experiments at Fermi National Accelerator Laboratory. We have produced a flux prediction which uses all available and relevant hadron production data, incorporating measurements of particle production off of thin targets as well as measurements of particle yields from a spare NuMI target exposed to a 120 GeV proton beam. The result is the most precise flux prediction achieved for a neutrino beam in the one to tens of GeVmore » energy region. Lastly, we have also compared the prediction to in situ measurements of the neutrino flux and find good agreement.« less

Increased miR-124-3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowth via their transfer into neurons.

PubMed

Huang, Shan; Ge, Xintong; Yu, Jinwen; Han, Zhaoli; Yin, Zhenyu; Li, Ying; Chen, Fanglian; Wang, Haichen; Zhang, Jianning; Lei, Ping

2018-01-01

Neuronal inflammation is the characteristic pathologic change of acute neurologic impairment and chronic traumatic encephalopathy after traumatic brain injury (TBI). Inhibiting the excessive inflammatory response is essential for improving the neurologic outcome. To clarify the regulatory mechanism of microglial exosomes on neuronal inflammation in TBI, we focused on studying the impact of microglial exosomal miRNAs on injured neurons in this research. We used a repetitive (r)TBI mouse model and harvested the injured brain extracts from the acute to the chronic phase of TBI to treat cultured BV2 microglia in vitro The microglial exosomes were collected for miRNA microarray analysis, which showed that the expression level of miR-124-3p increased most apparently in the miRNAs. We found that miR-124-3p promoted the anti-inflamed M2 polarization in microglia, and microglial exosomal miR-124-3p inhibited neuronal inflammation in scratch-injured neurons. Further, the mammalian target of rapamycin (mTOR) signaling was implicated as being involved in the regulation of miR-124-3p by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Using the mTOR activator MHY1485 we confirmed that the inhibitory effect of exosomal miR-124-3p on neuronal inflammation was exerted by suppressing the activity of mTOR signaling. PDE4B was predicted to be the target gene of miR-124-3p by pathway analysis. We proved that it was directly targeted by miR-124-3p with a luciferase reporter assay. Using a PDE4B overexpressed lentivirus transfection system, we suggested that miR-124-3p suppressed the activity of mTOR signaling mainly through inhibiting the expression of PDE4B. In addition, exosomal miR-124-3p promoted neurite outgrowth after scratch injury, characterized by an increase on the number of neurite branches and total neurite length, and a decreased expression on RhoA and neurodegenerative proteins [Aβ-peptide and p-Tau]. It also improved the neurologic outcome and inhibited neuroinflammation in mice with rTBI. Taken together, increased miR-124-3p in microglial exosomes after TBI can inhibit neuronal inflammation and contribute to neurite outgrowth via their transfer into neurons. miR-124-3p exerted these effects by targeting PDE4B, thus inhibiting the activity of mTOR signaling. Therefore, miR-124-3p could be a promising therapeutic target for interventions of neuronal inflammation after TBI. miRNAs manipulated microglial exosomes may provide a novel therapy for TBI and other neurologic diseases.-Huang, S., Ge, X., Yu, J., Han, Z., Yin, Z., Li, Y., Chen, F., Wang, H., Zhang, J., Lei, P. Increased miR-124-3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowth via their transfer into neurons. © FASEB.

Multiple imputation of missing data in nested case-control and case-cohort studies.

PubMed

Keogh, Ruth H; Seaman, Shaun R; Bartlett, Jonathan W; Wood, Angela M

2018-06-05

The nested case-control and case-cohort designs are two main approaches for carrying out a substudy within a prospective cohort. This article adapts multiple imputation (MI) methods for handling missing covariates in full-cohort studies for nested case-control and case-cohort studies. We consider data missing by design and data missing by chance. MI analyses that make use of full-cohort data and MI analyses based on substudy data only are described, alongside an intermediate approach in which the imputation uses full-cohort data but the analysis uses only the substudy. We describe adaptations to two imputation methods: the approximate method (MI-approx) of White and Royston () and the "substantive model compatible" (MI-SMC) method of Bartlett et al. (). We also apply the "MI matched set" approach of Seaman and Keogh () to nested case-control studies, which does not require any full-cohort information. The methods are investigated using simulation studies and all perform well when their assumptions hold. Substantial gains in efficiency can be made by imputing data missing by design using the full-cohort approach or by imputing data missing by chance in analyses using the substudy only. The intermediate approach brings greater gains in efficiency relative to the substudy approach and is more robust to imputation model misspecification than the full-cohort approach. The methods are illustrated using the ARIC Study cohort. Supplementary Materials provide R and Stata code. © 2018, The International Biometric Society.

Concerted functions of HDAC1 and microRNA-574-5p repress alternatively spliced ceramide synthase 1 expression in human cancer cells

PubMed Central

Meyers-Needham, Marisa; Ponnusamy, Suriyan; Gencer, Salih; Jiang, Wenhui; Thomas, Raquela J; Senkal, Can E; Ogretmen, Besim

2012-01-01

Histone deacetylases (HDACs) and microRNAs (miRs) have pro-survival roles, but the mechanism behind this is unclear. Repression of ceramide synthase 1 (CerS1), altering C18-ceramide generation, was linked to drug resistance and metastasis. Here we report that the CerS1 promoter was repressed by HDAC1-dependent inhibition of Sp1 recruitment to two specific GC-boxes spanning the −177 and −139 region. Moreover, an alternatively spliced variant CerS1 mRNA (CerS1-2) was detected mainly in cancer cells or primary tumour tissues compared to controls, which was targeted by miR-574-5p for degradation. A specific 3′UTR-targeting site, localized within the retained intron between exons 6 and 7, was identified, and its mutation, or miR-574-5p knockdown prevented the degradation of CerS1-2 mRNA. Interference with HDAC1 and miR-574-5p reconstituted CerS1-2 expression and C18-ceramide generation in multiple human cancer cell lines, which subsequently inhibited proliferation and anchorage-independent growth. Accordingly, knockdown of CerS1 partially protected cancer cells from MS-275/miR-574-5p siRNA-mediated growth inhibition. Thus, these data suggest that the HDAC1/miR-574-5p axis might provide a novel therapeutic target to reconstitute tumour suppressor CerS1/ceramide signalling. PMID:22180294

Motor Imagery and Tennis Serve Performance: The External Focus Efficacy

PubMed Central

Guillot, Aymeric; Desliens, Simon; Rouyer, Christelle; Rogowski, Isabelle

2013-01-01

There is now ample evidence that motor imagery (MI) contributes to enhance motor performance. Previous research also demonstrated that directing athletes’ attention to the effects of their movements on the environment is more effective than focusing on the action per se. The present study aimed therefore at evaluating whether adopting an external focus during MI contributes to enhance tennis serve performance. Twelve high-level young tennis players were included in a test-retest procedure. The effects of regular training were first evaluated. Then, players were subjected to a MI intervention during which they mentally focused on ball trajectory and specifically visualized the space above the net where the serve can be successfully hit. Serve performance was evaluated during both a validated serve test and a real match. The main results showed a significant increase in accuracy and velocity during the ecological serve test after MI practice, as well as a significant improvement in successful first serves and won points during the match. Present data therefore confirmed the efficacy of MI in combination of physical practice to improve tennis serve performance, and further provided evidence that it is feasible to adopt external attentional focus during MI. Practical applications are discussed. Key Points Motor imagery contributes to enhance tennis serve performance. Data provided evidence of the benefits of adopting an external focus of attention during imagery. Results showed significant improvement in successful first serves and won points during a real match. PMID:24149813

Evaluation and Verification of Decadal Predictions using the MiKlip Central Evaluation System - a Case Study using the MiKlip Prototype Model Data

NASA Astrophysics Data System (ADS)

Illing, Sebastian; Schuster, Mareike; Kadow, Christopher; Kröner, Igor; Richling, Andy; Grieger, Jens; Kruschke, Tim; Lang, Benjamin; Redl, Robert; Schartner, Thomas; Cubasch, Ulrich

2016-04-01

MiKlip is project for medium-term climate prediction funded by the Federal Ministry of Education and Research in Germany (BMBF) and aims to create a model system that is able provide reliable decadal climate forecasts. During the first project phase of MiKlip the sub-project INTEGRATION located at Freie Universität Berlin developed a framework for scientific infrastructures (FREVA). More information about FREVA can be found in EGU2016-13060. An instance of this framework is used as Central Evaluation System (CES) during the MiKlip project. Throughout the first project phase various sub-projects developed over 25 analysis tools - so called plugins - for the CES. The main focus of these plugins is on the evaluation and verification of decadal climate prediction data, but most plugins are not limited to this scope. They target a wide range of scientific questions. Starting from preprocessing tools like the "LeadtimeSelector", which creates lead-time dependent time-series from decadal hindcast sets, over tracking tools like the "Zykpak" plugin, which can objectively locate and track mid-latitude cyclones, to plugins like "MurCSS" or "SPECS", which calculate deterministic and probabilistic skill metrics. We also integrated some analyses from Model Evaluation Tools (MET), which was developed at NCAR. We will show the theoretical background, technical implementation strategies, and some interesting results of the evaluation of the MiKlip Prototype decadal prediction system for a selected set of these tools.

MicroRNA-Based Linkage between Aging and Cancer: from Epigenetics View Point.

PubMed

Saeidimehr, Saeid; Ebrahimi, Ammar; Saki, Najmaldin; Goodarzi, Parisa; Rahim, Fakher

2016-01-01

Ageing is a complex process and a broad spectrum of physical, psychological, and social changes over time. Accompanying diseases and disabilities, which can interfere with cancer treatment and recovery, occur in old ages. MicroRNAs (miRNAs) are a set of small non-coding RNAs, which have considerable roles in post-transcriptional regulation at gene expression level. In this review, we attempted to summarize the current knowledge of miRNAs functions in ageing, with mainly focuses on malignancies and all underlying genetic, molecular and epigenetics mechanisms. The evidences indicated the complex and dynamic nature of miRNA-based linkage of ageing and cancer at genomics and epigenomics levels which might be generally crucial for understanding the mechanisms of age-related cancer and ageing. Recently in the field of cancer and ageing, scientists claimed that uric acid can be used to regulate reactive oxygen species (ROS), leading to cancer and ageing prevention; these findings highlight the role of miRNA-based inhibition of the SLC2A9 antioxidant pathway in cancer, as a novel way to kill malignant cells, while a patient is fighting with cancer.

Complete characterization of wheat-alien metaphase I pairing in interspecific hybrids between durum wheat (Triticum turgidum L.) and jointed goatgrass (Aegilops cylindrica Host).

PubMed

Cifuentes, Marta; Benavente, Elena

2009-05-01

The pattern of homoeologous metaphase I (MI) pairing has been fully characterized in durum wheat x Aegilops cylindrica hybrids (2n = 4x = 28, ABC(c)D(c)) by an in situ hybridization procedure that has permitted individual discrimination of every wheat and wild constituent genome. One of the three hybrid genotypes examined carried the ph1c mutation. In all cases, MI associations between chromosomes of both species represented around two-third of total. Main results from the analysis are as follows (a) the A genome chromosomes are involved in wheat-wild MI pairing more frequently than the B genome partners, irrespective of the alien genome considered; (b) both durum wheat genomes pair preferentially with the D(c) genome of jointed goatgrass. These findings are discussed in relation to the potential of genetic transference between wheat crops and this weedy relative. It can also be highlighted that inactivation of Ph1 provoked a relatively higher promotion of MI associations involving B genome.

[Current anatomical and etiological aspects of chronic or subacute, surgical, pure mitral valve insufficiency in adults. Apropos of 75 medicosurgical cases].

PubMed

Penther, P; Boschat, J; Etienne, Y; Jobic, Y

1991-04-01

Seventy five medico-surgical cases (52 men, with a mean age at surgery of 59, and 23 women, with a mean age at surgery of 59) collected between 1983 and 1989, in an ethnically homogeneous and geographically stable population (West Brittany) confirmed that the current anatomical and etiological aspects of chronic (or subacute) pure mitral incompetence (MI) have changed radically. While rates for bacterial and ischemic etiologies remain stable, the share of rheumatic MI (14 cases) has fallen considerably, to the advantage of degenerative MI (51 cases) with a heavy male predominance (39 men) with in 33 cases rupture of the main chordae, and tending to affect the lesser mitral cusp more often. A precise diagnosis in terms of lesions and etiology is possible in almost all cases on the basis of clinical history and echocardiographic findings. In a perfectly homogeneous population, chronic surgical pure MI is currently essentially a male disease, of dystrophic origin, in patients in the 6th and 7th decades of life.

miRNome Expression Analysis Reveals New Players on Leprosy Immune Physiopathology

PubMed Central

Salgado, Claudio Guedes; Pinto, Pablo; Bouth, Raquel Carvalho; Gobbo, Angélica Rita; Messias, Ana Caroline Cunha; Sandoval, Tatiana Vinasco; dos Santos, André Mauricio Ribeiro; Moreira, Fabiano Cordeiro; Vidal, Amanda Ferreira; Goulart, Luiz Ricardo; Barreto, Josafá Gonçalves; da Silva, Moisés Batista; Frade, Marco Andrey Cipriani; Spencer, John Stewart; Santos, Sidney; Ribeiro-dos-Santos, Ândrea

2018-01-01

Leprosy remains as a public health problem and its physiopathology is still not fully understood. MicroRNAs (miRNA) are small RNA non-coding that can interfere with mRNA to regulate gene expression. A few studies using DNA chip microarrays have explored the expression of miRNA in leprosy patients using a predetermined set of genes as targets, providing interesting findings regarding the regulation of immune genes. However, using a predetermined set of genes restricted the possibility of finding new miRNAs that might be involved in different mechanisms of disease. Thus, we examined the miRNome of tuberculoid (TT) and lepromatous (LL) patients using both blood and lesional biopsies from classical leprosy patients (LP) who visited the Dr. Marcello Candia Reference Unit in Sanitary Dermatology in the State of Pará and compared them with healthy subjects. Using a set of tools to correlate significantly differentially expressed miRNAs with their gene targets, we identified possible interactions and networks of miRNAs that might be involved in leprosy immunophysiopathology. Using this approach, we showed that the leprosy miRNA profile in blood is distinct from that in lesional skin as well as that four main groups of genes are the targets of leprosy miRNA: (1) recognition and phagocytosis, with activation of immune effector cells, where the immunosuppressant profile of LL and immunoresponsive profile of TT are clearly affected by miRNA expression; (2) apoptosis, with supportive data for an antiapoptotic leprosy profile based on BCL2, MCL1, and CASP8 expression; (3) Schwann cells (SCs), demyelination and epithelial–mesenchymal transition (EMT), supporting a role for different developmental or differentiation gene families, such as Sox, Zeb, and Hox; and (4) loss of sensation and neuropathic pain, revealing that RHOA, ROCK1, SIGMAR1, and aquaporin-1 (AQP1) may be involved in the loss of sensation or leprosy pain, indicating possible new therapeutic targets. Additionally, AQP1 may also be involved in skin dryness and loss of elasticity, which are well known signs of leprosy but with unrecognized physiopathology. In sum, miRNA expression reveals new aspects of leprosy immunophysiopathology, especially on the regulation of the immune system, apoptosis, SC demyelination, EMT, and neuropathic pain. PMID:29593724

miRNome Expression Analysis Reveals New Players on Leprosy Immune Physiopathology.

PubMed

Salgado, Claudio Guedes; Pinto, Pablo; Bouth, Raquel Carvalho; Gobbo, Angélica Rita; Messias, Ana Caroline Cunha; Sandoval, Tatiana Vinasco; Dos Santos, André Mauricio Ribeiro; Moreira, Fabiano Cordeiro; Vidal, Amanda Ferreira; Goulart, Luiz Ricardo; Barreto, Josafá Gonçalves; da Silva, Moisés Batista; Frade, Marco Andrey Cipriani; Spencer, John Stewart; Santos, Sidney; Ribeiro-Dos-Santos, Ândrea

2018-01-01

Leprosy remains as a public health problem and its physiopathology is still not fully understood. MicroRNAs (miRNA) are small RNA non-coding that can interfere with mRNA to regulate gene expression. A few studies using DNA chip microarrays have explored the expression of miRNA in leprosy patients using a predetermined set of genes as targets, providing interesting findings regarding the regulation of immune genes. However, using a predetermined set of genes restricted the possibility of finding new miRNAs that might be involved in different mechanisms of disease. Thus, we examined the miRNome of tuberculoid (TT) and lepromatous (LL) patients using both blood and lesional biopsies from classical leprosy patients (LP) who visited the Dr. Marcello Candia Reference Unit in Sanitary Dermatology in the State of Pará and compared them with healthy subjects. Using a set of tools to correlate significantly differentially expressed miRNAs with their gene targets, we identified possible interactions and networks of miRNAs that might be involved in leprosy immunophysiopathology. Using this approach, we showed that the leprosy miRNA profile in blood is distinct from that in lesional skin as well as that four main groups of genes are the targets of leprosy miRNA: (1) recognition and phagocytosis, with activation of immune effector cells, where the immunosuppressant profile of LL and immunoresponsive profile of TT are clearly affected by miRNA expression; (2) apoptosis, with supportive data for an antiapoptotic leprosy profile based on BCL2, MCL1 , and CASP8 expression; (3) Schwann cells (SCs), demyelination and epithelial-mesenchymal transition (EMT), supporting a role for different developmental or differentiation gene families, such as Sox, Zeb, and Hox; and (4) loss of sensation and neuropathic pain, revealing that RHOA, ROCK1, SIGMAR1 , and aquaporin-1 ( AQP1 ) may be involved in the loss of sensation or leprosy pain, indicating possible new therapeutic targets. Additionally, AQP1 may also be involved in skin dryness and loss of elasticity, which are well known signs of leprosy but with unrecognized physiopathology. In sum, miRNA expression reveals new aspects of leprosy immunophysiopathology, especially on the regulation of the immune system, apoptosis, SC demyelination, EMT, and neuropathic pain.

Let-7b regulates the expression of the growth hormone receptor gene in deletion-type dwarf chickens.

PubMed

Lin, Shumao; Li, Hongmei; Mu, Heping; Luo, Wen; Li, Ying; Jia, Xinzheng; Wang, Sibing; Jia, Xiaolu; Nie, Qinghua; Li, Yugu; Zhang, Xiquan

2012-07-10

A deletion mutation in the growth hormone receptor (GHR) gene results in the inhibition of skeletal muscle growth and fat deposition in dwarf chickens. We used microarray techniques to determine microRNA (miRNA) and mRNA expression profiles of GHR in the skeletal muscles of 14-day-old embryos as well as 7-week-old deletion-type dwarf and normal-type chickens. Our aim was to elucidate the miRNA regulation of GHR expression with respect to growth inhibition and fat deposition. At the same developmental stages, different expression profiles in skeletal muscles of dwarf and normal chickens occurred for four miRNAs (miR-1623, miR-181b, let-7b, and miR-128). At different developmental stages, there was a significant difference in the expression profiles of a greater number of miRNAs. Eleven miRNAs were up-regulated and 18 down-regulated in the 7-week-old dwarf chickens when compared with profiles in 14-day-old embryos. In 7-week-old normal chickens, seven miRNAs were up-regulated and nine down-regulated compared with those in 14-day-old embryos. In skeletal muscles, 22 genes were up-regulated and 33 down-regulated in 14-day-old embryos compared with 7-week-old dwarf chickens. Sixty-five mRNAs were up-regulated and 108 down-regulated in 14-day-old embryos as compared with 7-week-old normal chickens. Thirty-four differentially expressed miRNAs were grouped into 18 categories based on overlapping seed and target sequences. Only let-7b was found to be complementary to its target in the 3' untranslated region of GHR, and was able to inhibit its expression. Kyoto Encyclopedia of Genes and Genomes pathway analysis and quantitative polymerase chain reactions indicated there were three main signaling pathways regulating skeletal muscle growth and fat deposition of chickens. These were influenced by let-7b-regulated GHR. Suppression of the cytokine signaling 3 (SOCS3) gene was found to be involved in the signaling pathway of adipocytokines. There is a critical miRNA, let-7b, involved in the regulation of GHR. SOCS3 plays a critical role in regulating skeletal muscle growth and fat deposition via let-7b-mediated GHR expression.

Let-7b regulates the expression of the growth hormone receptor gene in deletion-type dwarf chickens

PubMed Central

2012-01-01

Background A deletion mutation in the growth hormone receptor (GHR) gene results in the inhibition of skeletal muscle growth and fat deposition in dwarf chickens. We used microarray techniques to determine microRNA (miRNA) and mRNA expression profiles of GHR in the skeletal muscles of 14-day-old embryos as well as 7-week-old deletion-type dwarf and normal-type chickens. Our aim was to elucidate the miRNA regulation of GHR expression with respect to growth inhibition and fat deposition. Results At the same developmental stages, different expression profiles in skeletal muscles of dwarf and normal chickens occurred for four miRNAs (miR-1623, miR-181b, let-7b, and miR-128). At different developmental stages, there was a significant difference in the expression profiles of a greater number of miRNAs. Eleven miRNAs were up-regulated and 18 down-regulated in the 7-week-old dwarf chickens when compared with profiles in 14-day-old embryos. In 7-week-old normal chickens, seven miRNAs were up-regulated and nine down-regulated compared with those in 14-day-old embryos. In skeletal muscles, 22 genes were up-regulated and 33 down-regulated in 14-day-old embryos compared with 7-week-old dwarf chickens. Sixty-five mRNAs were up-regulated and 108 down-regulated in 14-day-old embryos as compared with 7-week-old normal chickens. Thirty-four differentially expressed miRNAs were grouped into 18 categories based on overlapping seed and target sequences. Only let-7b was found to be complementary to its target in the 3′ untranslated region of GHR, and was able to inhibit its expression. Kyoto Encyclopedia of Genes and Genomes pathway analysis and quantitative polymerase chain reactions indicated there were three main signaling pathways regulating skeletal muscle growth and fat deposition of chickens. These were influenced by let-7b-regulated GHR. Suppression of the cytokine signaling 3 (SOCS3) gene was found to be involved in the signaling pathway of adipocytokines. Conclusions There is a critical miRNA, let-7b, involved in the regulation of GHR. SOCS3 plays a critical role in regulating skeletal muscle growth and fat deposition via let-7b-mediated GHR expression. PMID:22781587

Purification of pre-miR-29 by a new O-phospho-l-tyrosine affinity chromatographic strategy optimized using design of experiments.

PubMed

Afonso, Adriana; Pereira, Patrícia; Queiroz, João A; Sousa, Ângela; Sousa, Fani

2014-05-23

MicroRNAs are the most studied small non-coding RNA molecules that are involved in post-transcriptional regulation of target genes. Their role in Alzheimer's disease is being studied and explored in order to develop a new therapeutic strategy based on specific gene silencing. This disease is characterized by protein deposits, mainly deposits of extracellular Aβ plaques, produced upon endoproteolytic cleavage of APP by ß-site APP-cleaving enzyme 1 (BACE1). Recent studies have shown that particularly miR-29 cluster can be involved in the decrease of Aβ plaques production, by acting on BACE1 expression silencing. In order to use this microRNA as potential therapeutic it is essential to guarantee its purity, stability and integrity. Hence, the main purpose of this study was the development of a new affinity chromatographic strategy by using an O-phospho-l-tyrosine matrix and applying Box-Behnken design (BBD) to obtain pre-miR-29 with high purity degree and yield, envisioning its application in gene therapy. Thus, after process optimization the best results were achieved with a decreasing ammonium sulfate gradient in 10mM Tris buffer, pH 8 (1.6M (NH4)2SO4, 1.11M (NH4)2SO4 and 0M (NH4)2SO4), at 16°C. These experimental conditions allowed the recovery of pre-miR-29 with 52% of purity and 71% of recovery yield. The O-phospho-l-tyrosine matrix was initially chosen to mimic the natural interactions that occur inside the cell, and in fact it was proved a satisfactory selectivity for pre-miR-29. Also the innovative application of BBD for this strategy was efficient (R(2)=0.98 for % relative recovery and R(2)=0.93 for % relative purity) and essential to achieve best purification results in short time, saving lab resources. Copyright © 2014 Elsevier B.V. All rights reserved.

MicroRNA-200a is up-regulated in aged rats with erectile dysfunction and could attenuate endothelial function via SIRT1 inhibition

PubMed Central

Pan, Feng; Qiu, Xue-Feng; Yu, Wen; Zhang, Qi-Peng; Chen, Qun; Zhang, Chen-Yu; Chen, Yun; Pan, Lian-Jun; Zhang, Ai-Xia; Dai, Yu-Tian

2016-01-01

MiR-200a was shown to be upregulated in the corpus cavernosum (CC) of rats with aging-related erectile dysfunction (A-ED) in our previous study. Among its target genes, SIRT1 was also reported as a protective factor in erectile function by our groups previously. Thus, miR-200a might attenuate the erectile function in A-ED via SIRT1 inhibition. In the present study, three animal groups were included: aged rats with ED (group AE, n = 8), aged rats with normal erectile function (group AN, n = 8), and young rats as normal controls (group YN, n = 8). CCs from each group were collected for histological and molecular measurements to validate the dysregulation of miR-200a and SIRT1. After that, the cavernous endothelial cells (CECs) from CC of aged rats with normal erectile function were transfected with miR-200a in vitro. Then the expression of SIRT1 and molecules within the eNOS/NO/PKG pathway were measured to investigate whether the transfection could imitate the attenuated process of erectile function in the aged. As a result, miR-200a was upregulated while the SIRT1, the levels of eNOS and cGMP were all downregulated in the CCs from AE group. After transfection in vitro, the miR-200a was upregulated while the SIRT1 and levels of eNOS and cGMP were obviously downregulated. Finally, based on the results of our previous study, we further verify that up-regulation of miR-200a could participate in the mechanisms of A-ED via SIRT1 inhibition, and mainly attenuate endothelial function via influencing the eNOS/NO/PKGpathway. PMID:25966629

MicroRNA expression, target genes, and signaling pathways in infants with a ventricular septal defect.

PubMed

Chai, Hui; Yan, Zhaoyuan; Huang, Ke; Jiang, Yuanqing; Zhang, Lin

2018-02-01

This study aimed to systematically investigate the relationship between miRNA expression and the occurrence of ventricular septal defect (VSD), and characterize the miRNA target genes and pathways that can lead to VSD. The miRNAs that were differentially expressed in blood samples from VSD and normal infants were screened and validated by implementing miRNA microarrays and qRT-PCR. The target genes regulated by differentially expressed miRNAs were predicted using three target gene databases. The functions and signaling pathways of the target genes were enriched using the GO database and KEGG database, respectively. The transcription and protein expression of specific target genes in critical pathways were compared in the VSD and normal control groups using qRT-PCR and western blotting, respectively. Compared with the normal control group, the VSD group had 22 differentially expressed miRNAs; 19 were downregulated and three were upregulated. The 10,677 predicted target genes participated in many biological functions related to cardiac development and morphogenesis. Four target genes (mGLUR, Gq, PLC, and PKC) were involved in the PKC pathway and four (ECM, FAK, PI3 K, and PDK1) were involved in the PI3 K-Akt pathway. The transcription and protein expression of these eight target genes were significantly upregulated in the VSD group. The 22 miRNAs that were dysregulated in the VSD group were mainly downregulated, which may result in the dysregulation of several key genes and biological functions related to cardiac development. These effects could also be exerted via the upregulation of eight specific target genes, the subsequent over-activation of the PKC and PI3 K-Akt pathways, and the eventual abnormal cardiac development and VSD.

MicroRNA-directed siRNA biogenesis in Caenorhabditis elegans.

PubMed

Corrêa, Régis L; Steiner, Florian A; Berezikov, Eugene; Ketting, René F

2010-04-08

RNA interference (RNAi) is a post-transcriptional silencing process, triggered by double-stranded RNA (dsRNA), leading to the destabilization of homologous mRNAs. A distinction has been made between endogenous RNAi-related pathways and the exogenous RNAi pathway, the latter being essential for the experimental use of RNAi. Previous studies have shown that, in Caenorhabditis elegans, a complex containing the enzymes Dicer and the Argonaute RDE-1 process dsRNA. Dicer is responsible for cleaving dsRNA into short interfering RNAs (siRNAs) while RDE-1 acts as the siRNA acceptor. RDE-1 then guides a multi-protein complex to homologous targets to trigger mRNA destabilization. However, endogenous role(s) for RDE-1, if any, have remained unexplored. We here show that RDE-1 functions as a scavenger protein, taking up small RNA molecules from many different sources, including the microRNA (miRNA) pathway. This is in striking contrast to Argonaute proteins functioning directly in the miRNA pathway, ALG-1 and ALG-2: these proteins exclusively bind miRNAs. While playing no significant role in the biogenesis of the main pool of miRNAs, RDE-1 binds endogenous miRNAs and triggers RdRP activity on at least one perfectly matching, endogenous miRNA target. The resulting secondary siRNAs are taken up by a set of Argonaute proteins known to act as siRNA acceptors in exogenous RNAi, resulting in strong mRNA destabilization. Our results show that RDE-1 in an endogenous setting is actively screening the transcriptome using many different small RNAs, including miRNAs, as a guide, with implications for the evolution of transcripts with a potential to be recognized by Dicer.

MicroRNA–Directed siRNA Biogenesis in Caenorhabditis elegans

PubMed Central

Corrêa, Régis L.; Steiner, Florian A.; Berezikov, Eugene; Ketting, René F.

2010-01-01

RNA interference (RNAi) is a post-transcriptional silencing process, triggered by double-stranded RNA (dsRNA), leading to the destabilization of homologous mRNAs. A distinction has been made between endogenous RNAi–related pathways and the exogenous RNAi pathway, the latter being essential for the experimental use of RNAi. Previous studies have shown that, in Caenorhabditis elegans, a complex containing the enzymes Dicer and the Argonaute RDE-1 process dsRNA. Dicer is responsible for cleaving dsRNA into short interfering RNAs (siRNAs) while RDE-1 acts as the siRNA acceptor. RDE-1 then guides a multi-protein complex to homologous targets to trigger mRNA destabilization. However, endogenous role(s) for RDE-1, if any, have remained unexplored. We here show that RDE-1 functions as a scavenger protein, taking up small RNA molecules from many different sources, including the microRNA (miRNA) pathway. This is in striking contrast to Argonaute proteins functioning directly in the miRNA pathway, ALG-1 and ALG-2: these proteins exclusively bind miRNAs. While playing no significant role in the biogenesis of the main pool of miRNAs, RDE-1 binds endogenous miRNAs and triggers RdRP activity on at least one perfectly matching, endogenous miRNA target. The resulting secondary siRNAs are taken up by a set of Argonaute proteins known to act as siRNA acceptors in exogenous RNAi, resulting in strong mRNA destabilization. Our results show that RDE-1 in an endogenous setting is actively screening the transcriptome using many different small RNAs, including miRNAs, as a guide, with implications for the evolution of transcripts with a potential to be recognized by Dicer. PMID:20386745

Nanocarrier mediated Delivery of siRNA/miRNA in Combination with Chemotherapeutic Agents for Cancer Therapy: Current Progress and Advances

PubMed Central

Gandhi, Nishant S.; Tekade, Rakesh K.; Chougule, Mahavir B.

2014-01-01

Chemotherapeutic agents have certain limitations when it comes to treating cancer, the most important being severe side effects along with multidrug resistance developed against them. Tumor cells exhibits drug resistance due to activation of various cellular level processes viz. activation of drug efflux pumps, anti-apoptotic defense mechanisms etc. Currently, RNA interference (RNAi) based therapeutic approaches are under vibrant scrutinization to seek cancer cure. Especially small interfering RNA (siRNA) and micro RNA (miRNA), are able to knock down the carcinogenic genes by targeting the mRNA expression, which underlies the uniqueness of this therapeutic approach. Recent research focus in the regime of cancer therapy involves the engagement of targeted delivery of siRNA/miRNA in combinations with other therapeutic agents (such as gene, DNA or chemotherapeutic drug) for targeting permeability glycoprotein (P-gp), Multidrug resistant protein 1(MRP-1), B-cell lymphoma (BCL-2) and other targets that are mainly responsible for resistance in cancer therapy. RNAi-chemotherapeutic drug combinations have also been found to be effective against different molecular targets as well and can increase the sensitization of cancer cells to therapy several folds. However, due to stability issues associated with siRNA/miRNA suitable protective carrier is needed and nanotechnology based approaches have been widely explored to overcome these drawbacks. Furthermore, it has been univocally advocated that the co-delivery of siRNA/miRNA with other chemodrugs significantly enhances their capability to overcome cancer resistance compared to naked counterparts. The objective of this article is to review recent nanocarrier based approaches adopted for the delivery of siRNA/miRNA combinations with other anticancer agents (siRNA/miRNA/pDNA/chemodrugs) to treat cancer. PMID:25204288

MicroRNA-181c targets Bcl-2 and regulates mitochondrial morphology in myocardial cells

PubMed Central

Wang, Hongjiang; Li, Jing; Chi, Hongjie; Zhang, Fan; Zhu, Xiaoming; Cai, Jun; Yang, Xinchun

2015-01-01

Apoptosis is an important mechanism for the development of heart failure. Mitochondria are central to the execution of apoptosis in the intrinsic pathway. The main regulator of mitochondrial pathway of apoptosis is Bcl-2 family which includes pro- and anti-apoptotic proteins. MicroRNAs are small noncoding RNA molecules that regulate gene expression by inhibiting mRNA translation and/or inducing mRNA degradation. It has been proposed that microRNAs play critical roles in the cardiovascular physiology and pathogenesis of cardiovascular diseases. Our previous study has found that microRNA-181c, a miRNA expressed in the myocardial cells, plays an important role in the development of heart failure. With bioinformatics analysis, we predicted that miR-181c could target the 3′ untranslated region of Bcl-2, one of the anti-apoptotic members of the Bcl-2 family. Thus, we have suggested that miR-181c was involved in regulation of Bcl-2. In this study, we investigated this hypothesis using the Dual-Luciferase Reporter Assay System. Cultured myocardial cells were transfected with the mimic or inhibitor of miR-181c. We found that the level of miR-181c was inversely correlated with the Bcl-2 protein level and that transfection of myocardial cells with the mimic or inhibitor of miR-181c resulted in significant changes in the levels of caspases, Bcl-2 and cytochrome C in these cells. The increased level of Bcl-2 caused by the decrease in miR-181c protected mitochondrial morphology from the tumour necrosis factor alpha-induced apoptosis. PMID:25898913

No Risk of Myocardial Infarction Associated With Initial Antiretroviral Treatment Containing Abacavir: Short and Long-Term Results from ACTG A5001/ALLRT

PubMed Central

Benson, Constance A.; Zheng, Yu; Koletar, Susan L.; Collier, Ann C.; Lok, Judith J.; Smurzynski, Marlene; Bosch, Ronald J.; Bastow, Barbara; Schouten, Jeffrey T.

2011-01-01

Background. Observational and retrospective clinical trial cohorts have reported conflicting results for the association of abacavir use with risk of myocardial infarction (MI), possibly related to issues that may bias estimation of treatment effects, such as time-varying confounders, informative dropout, and cohort loss due to competing events. Methods. We analyzed data from 5056 individuals initiating randomized antiretroviral treatment (ART) in AIDS Clinical Trials Group studies; 1704 started abacavir therapy. An intent-to-treat analysis adjusted for pretreatment covariates and weighting for informative censoring was used to estimate the hazard ratio (HR) of MIs after initiation of a regimen with or without abacavir. Results. Through 6 years after ART initiation, 36 MI events were observed in 17,404 person-years of follow-up. No evidence of an increased hazard of MI in subjects using abacavir versus no abacavir was seen (over a 1-year period: P = .50; HR, 0.7 [95% confidence interval {CI}, 0.2-2.4]); over a 6-year period: P = .24; HR, 0.6 [95% CI, 0.3-1.4]); these results were robust over as-treated and sensitivity analyses. Although the risk of MI decreased over time, there was no evidence to suggest a time-dependent abacavir effect. Classic cardiovascular disease (CVD) risk factors were the strongest predictors of MI. Conclusion. We find no evidence to suggest that initial ART containing abacavir increases MI risk over short-term and long-term periods in this population with relatively low MI risk. Traditional CVD risk factors should be the main focus in assessing CVD risk in individuals with human immunodeficiency virus infection. PMID:21427402

No risk of myocardial infarction associated with initial antiretroviral treatment containing abacavir: short and long-term results from ACTG A5001/ALLRT.

PubMed

Ribaudo, Heather J; Benson, Constance A; Zheng, Yu; Koletar, Susan L; Collier, Ann C; Lok, Judith J; Smurzynski, Marlene; Bosch, Ronald J; Bastow, Barbara; Schouten, Jeffrey T

2011-04-01

Observational and retrospective clinical trial cohorts have reported conflicting results for the association of abacavir use with risk of myocardial infarction (MI), possibly related to issues that may bias estimation of treatment effects, such as time-varying confounders, informative dropout, and cohort loss due to competing events. We analyzed data from 5056 individuals initiating randomized antiretroviral treatment (ART) in AIDS Clinical Trials Group studies; 1704 started abacavir therapy. An intent-to-treat analysis adjusted for pretreatment covariates and weighting for informative censoring was used to estimate the hazard ratio (HR) of MIs after initiation of a regimen with or without abacavir. Through 6 years after ART initiation, 36 MI events were observed in 17,404 person-years of follow-up. No evidence of an increased hazard of MI in subjects using abacavir versus no abacavir was seen (over a 1-year period: P=.50; HR, 0.7 [95% confidence interval {CI}, 0.2-2.4]); over a 6-year period: P=.24; HR, 0.6 [95% CI, 0.3-1.4]); these results were robust over as-treated and sensitivity analyses. Although the risk of MI decreased over time, there was no evidence to suggest a time-dependent abacavir effect. Classic cardiovascular disease (CVD) risk factors were the strongest predictors of MI. We find no evidence to suggest that initial ART containing abacavir increases MI risk over short-term and long-term periods in this population with relatively low MI risk. Traditional CVD risk factors should be the main focus in assessing CVD risk in individuals with human immunodeficiency virus infection. © The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

Post-infarct treatment with [Pyr1]apelin-13 exerts anti-remodelling and anti-apoptotic effects in rats' hearts.

PubMed

Azizi, Yaser; Imani, Alireza; Fanaei, Hamed; Khamse, Safoura; Parvizi, Mohammad Reza; Faghihi, Mahdieh

2017-01-01

Ischaemic heart disease is the main cause of mortality in the world. After myocardial infarction (MI) cardiomyocytes apoptosis and ventricular remodelling have occurred. Apelin is a peptide that has been shown to exert cardioprotective effects. The aim of this study was to investigate the anti-apoptotic and anti-remodelling effects of [Pyr¹]apelin-13 in the rat model of post-MI. Thirty-six male Wistar rats were randomly divided into three groups: (1) sham, (2) MI, and (3) MI treated with [Pyr¹] apelin-13 (MI+Apel). MI animals were subjected to 30-min ligation of the left anterior descending coronary artery (LAD) and 14 days of reperfusion. Twenty-four hours after LAD ligation, [Pyr¹]apelin-13 (10 nmol/kg/day, i.p.) was administered for five consecutive days. Hypertrophic parameters, left ventricular (LV) remodelling, and gene expression of Apel, apelin receptor (Apelr), Bax, caspase-3 (Casp-3), and Bcl-2 by real-time polymerase chain reaction and cardiomyocytes apoptosis by TUNEL immunostaining were assessed on day 14 post-MI. Post-infarct treatment with [Pyr¹]apelin-13 improved myocardial hypertrophic and LV remodelling parameters and led to a significant increase in the expression of Apel, Apelr, and Bcl-2, and a decrease in the expression of Bax and Casp-3. Furthermore, treatment with [Pyr¹]apelin-13 decreased cardiomyocyte apoptosis. [Pyr¹]apelin-13 has anti-hypertrophic, anti-remodelling, and anti-apoptotic effects via overexpression of Apel, Apelr, and Bcl-2 and reduces gene expression of Bax and Casp-3 in the infarcted myocardium, which can in turn lead to repair myocardium.