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M1
Kinds of M1 Terms modified by M1 Selected AbstractsMolecular characterization of regenerated cardiomyocytes derived from adult mesenchymal stem cellsCONGENITAL ANOMALIES, Issue 1 2002Keiichi Fukuda ABSTRACT, We recently isolated a cardiomyogenic (CMG) cell line from murine bone marrow stroma, and in this paper characterize regenerated cardiomyocytes derived from adult mesenchymal stem cells at the molecular level. Stromal cells were immortalized, exposed to 5-azacytidine, and repeatedly screened for spontaneously beating cells. CMG cells began to beat spontaneously after 2 weeks, and beat synchronously after 3 weeks. They exhibited sinus-node-like or ventricular-cell-like action potentials. Analysis of the isoforms of contractile protein genes, such as of myosin and ,-actin, indicated that their phenotype was similar to that of fetal ventricular cardiomyocytes. The cells expressed Nkx2.5, GATA4, TEF-1, and MEF2-C mRNA before 5-azacytidine exposure, and MEF2-A and MEF2-D after exposure. CMG cells expressed ,1A, ,1B, and ,1D -adrenergic receptor mRNA prior to differentiation, and ,1, ,2 -adrenergic and M1, M2 -muscarinic receptors after acquiring the cardiomyocyte phenotype. Phenylephrine induced phosphorylation of ERK1/ 2, and the phosphorylation was inhibited by prazosin. Isoproterenol increased the cAMP level 38-fold and beating rate, cell motion, % shortening, and contractile velocity by 48%, 38%, 27%, and 51%, respectively, and the increases were blocked by CGP20712A (,1 -selective blocker). Car-bachol increased IP3 32-fold, and the increase was inhibited by AFDX116 (M2 -selective blocker). These findings demonstrated that the regenerated cardiomyocytes were capable of responding to adrenergic and muscarinic stimulation. This new cell line provides a model for the study of cardiomyocyte transplantation. [source] The World Has Changed,Have Analytical Procedure Practices?CONTEMPORARY ACCOUNTING RESEARCH, Issue 2 2010GREG TROMPETER M1; M42 Analytical Procedures (APs) provide a means for auditors to evaluate the "reasonableness" of financial disclosures by comparing a client's reported performance to expectations gained through knowledge of the client based on past experience and developments within the company and its industry. Thus, APs are fundamentally different than other audit tests in taking a broader perspective of an entity's performance vis-à-vis its environment. As such, APs have been found to be a cost-effective means to detect misstatements, and many have argued that a number of prior financial frauds would have been detected had auditors employed effective APs. With several dramatic and far-reaching developments over the past decade, the current study examines whether and how APs have changed during this period. In particular, we focus on the impact of significant "enablers" and "drivers" of change such as technological advancements and the enactment of the Sarbanes-Oxley Act. We also compare our findings to an influential study of the practices of APs by Hirst and Koonce (1996) that was conducted over 10 years ago. We interview 36 auditors (11 seniors, 13 managers, and 12 partners) from all of the Big 4 firms using a structured questionnaire. The data reveal some similarities in findings when compared to prior research (e.g., auditors continue to use fairly simple analytical procedures). However, there are a number of significant differences reflecting changes in AP practices. For instance, as a result of technology auditors now rely more extensively on industry and analyst data than previously. Further, auditors report that they develop more precise quantitative expectations and use more non-financial information. They also appear to rely more on lower level audit staff to perform APs, conduct greater inquiry of non-accounting personnel, and are willing to reduce substantive testing to a greater extent as a result of APs conducted in the planning phase. Finally, the Sarbanes-Oxley Act has had an impact in greater consideration and knowledge of internal controls, which is seen as the most important factor driving the use and reliance on APs. [source] Le monde a changé,peut-on en dire autant des méthodes utilisées dans la mise en ,uvre des procédures analytiques?CONTEMPORARY ACCOUNTING RESEARCH, Issue 2 2010GREG TROMPETER M1; M42 Les procédures analytiques procurent aux auditeurs un mécanisme d'évaluation de la « vraisemblance » des informations financières, grâce à la comparaison de la performance présentée par l'entité cliente et des attentes découlant de leur connaissance de l'entité cliente, fondée sur l'expérience passée et l'évolution de l'organisation et de son secteur d'activité. Les procédures analytiques diffèrent donc foncièrement des autres procédures d'audit, du fait que la performance de l'entité est envisagée dans une perspective plus large, dans le contexte de son environnement. Cela explique que les procédures analytiques se soient révélées efficientes dans le dépistage des anomalies, et nombreux sont ceux qui affirment que plusieurs des fraudes financières passées auraient été décelées si les auditeurs avaient mis en ,uvre des procédures analytiques efficaces. Compte tenu de l'ampleur et de la portée des progrès réalisés au cours de la dernière décennie, les auteurs se demandent si les procédures analytiques ont changé au fil de ces années et, le cas échéant, comment ces changements se sont manifestés. Ils s'intéressent en particulier à l'incidence de « facilitateurs » et d'« inducteurs » de changement importants, comme les progrès technologiques et l'adoption de la loi Sarbanes-Oxley. Ils comparent également leurs observations aux résultats d'une étude marquante sur les méthodes utilisées dans la mise en ,uvre des procédures analytiques, réalisée par Hirst et Koonce (1996) il y a plus de 10 ans. Les auteurs interrogent en entrevue 36 auditeurs (11 chargés de missions, 13 chefs de groupe et 12 associés) provenant tous des Quatre Grands cabinets d'expertise comptable, à l'aide d'un questionnaire structuré. Les données recueillies révèlent certaines similitudes dans les observations lorsqu'elles sont comparées aux résultats des études antérieures (par exemple, les auditeurs continuent d'utiliser des procédures analytiques relativement simples). Toutefois, les auteurs relèvent bon nombre de différences sensibles attestant de l'évolution des méthodes utilisées dans la mise en ,uvre des procédures analytiques. Ainsi, par suite des progrès de la technologie, les auditeurs s'appuient maintenant plus largement qu'ils ne le faisaient auparavant sur les données sectorielles et les données des analystes. En outre, les auditeurs disent élaborer des prévisions quantitatives plus précises et utiliser davantage d'informations non financières. Ils semblent également confier plus fréquemment la mise en ,uvre des procédures analytiques au personnel d'audit d'échelon inférieur, prennent une quantité plus grande d'informations auprès du personnel non comptable et sont disposés à réduire davantage les tests de corroboration, compte tenu des procédures analytiques mises en ,uvre à la phase de planification. Enfin, la loi Sarbanes-Oxley a favorisé l'augmentation de la prise en compte et de la connaissance des contrôles internes, facteur que l'on estime avoir joué le rôle le plus important dans la recrudescence de l'utilisation des procédures analytiques et le renforcement de la confiance accordée à ce type de procédures. [source] Analysis of proliferating cell fraction determined by monoclonal antibody to M1-subunit ribonucleotide reductase and Ki-67 in relation to p53 protein expression in fine-needle aspirates from non-Hodgkin's lymphomasCYTOPATHOLOGY, Issue 5 2000V. Sviatoha Analysis of proliferating cell fraction determined by monoclonal antibody to M1-subunit ribonucleotide reductase and Ki-67 in relation to p53 protein expression in fine-needle aspirates from non Hodgkin's lymphomas The purpose of this study was to analyse the proliferative fraction with the monoclonal antibody M1-R-R to M1-subunit ribonucleotide reductase and with MIB-1 to Ki-67 antigen in relation to p53 protein expression in fine needle aspirates from B-cell non-Hodgkin's lymphomas. One hundred and thirty-seven cases, previously diagnosed and sub-typed according to the Kiel classification and characterized by immunophenotyping, were included in the study. The M-1 subunit ribonucleotide reductase (M1 -R-R), Ki-67 and p53 antigens were detected using monoclonal antibodies on stored cytospin preparations. There was a good correlation (r = 0.72) between Ki-67 and M1 -R-R positive cell fraction in both high and low grade lymphomas. High-grade lymphomas had a median percentage of M1 -R-R/MIB-1 positive cells of 53.0/73.0 for lymphoblastic, 61.0/52.0 for immunoblastic and 33.5/41.0 for centroblastic lymphomas, respectively. In low grade lymphomas figures of median percentage of M1 -R-R/MIB-1 were 9.0/15.0 for centroblastic/centrocytic, 11.0/9.5 for chronic lymphocytic leukaemia, 16.0/27.0 for centrocytic and 12.0/9.0 for immunocytomas, respectively. The median percentages of M1 -R-R/MIB-1 for high and low grade lymphomas were 37.0/50.5 and 11.0/12.0, respectively. In the p53 positive cases the proliferation rate as measured by staining for M1 -R-R and MIB-1 was higher than in p53 negative cases, but the difference was not statistically significant. The results show that cytospin material obtained by fine needle aspiration and stored at ,70 °C for years can be used reliably for both peroxidase-avidin-biotin and three-step alkaline phosphatase immunocytochemical staining. In addition, proliferation fraction determined by M1 -R-R monoclonal antibody staining correlates well with that measured by an established marker for cell proliferation, the Ki-67 antibody. However, the proliferation fraction as measured by the two antibodies differs in the various subtypes of non-Hodgkin's lymphoma which indicates that they may contribute different prognostic information. [source] Genetic polymorphisms in glutathione S-transferases T1, M1 and P1 and susceptibility to reflux esophagitisDISEASES OF THE ESOPHAGUS, Issue 6 2006B. Liu SUMMARY., Recent studies indicate that the prevalence of reflux esophagitis (RE) in China is increasing. RE is one of the most common esophageal complications associated with gastroesophageal reflux disease (GERD) and RE-Barrett's esophagus-esophageal adenocarcinoma (EAC) sequence has been considered as an histogenesis model for EAC in Western countries. RE is only present in a subset of patients with GERD, suggesting an altered susceptibility to RE may exist in these GERD individuals. However, the genetic changes related with high susceptibility to RE is largely unknown. The polymorphisms in glutathione S-transferases (GSTs) T1, M1 and P1 have been reported with high susceptibity to esophageal cancer in Chinese people. The present case-control study was thus undertaken to characterize the genetic polymorphisms of GSTs and their correlation with susceptibility to RE. One hundred and nine patients with RE, 97 patients with nonerosive reflux disease (NERD) and 97 normal controls were recruited in this study. All the subjects were from Beijing, China, and received endoscopic examination and questionnaires for RE. Genomic DNA was extracted from the lymphocytes of peripheral blood for each subject. Genotypes of the GSTM1 and GSTT1 genes were analyzed by a multiplex PCR method. A,G polymorphism of codon 104 of the GSTP1 gene was detected using PCR-based restriction fragment length polymorphisms (RFLP). The variant GSTP1 genotypes (*A/*B,*B/*B) was found with a high frequency in the case with RE (40%), and followed by NERD (25%) and normal control (22%). The differences were statistically significant (P < 0.05). The risk for RE increased 2.42-fold [odds ratio (OR); 95% confidence interval (95% CI), 2.42 (1.22,4.80)] in the subjects with variant GSTP1 genotype. The subjects with positive variant GSTP1 genotypes and negative H. pylori infection showed increasing tendency for risk of RE [OR (95% CI), 2.67 (1.06,6.70)]. However, the subjects with GSTT1 and GSTM1 polymorphisms did not show any correlation with high risk for RE or NERD. No significant interactions were identified between the variant GSTs and cigarette smoking, or alcohol drinking and subtype of RE. The present result suggests that GSTP1 genetic polymorphism may be one of the high susceptibility factors involved in the mechanisms of RE. H. pylori infection may play a protective role against RE. [source] The importance of independent risk-factors for long-term mortality prediction after cardiac surgeryEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2006I. K. Toumpoulis Abstract Background, The purpose of the present study was to determine independent predictors for long-term mortality after cardiac surgery. The European System for Cardiac Operative Risk Evaluation (EuroSCORE) was developed to score in-hospital mortality and recent studies have shown its ability to predict long-term mortality as well. We compared forecasts based on EuroSCORE with other models based on independent predictors. Methods, Medical records of patients with cardiac surgery who were discharged alive (n = 4852) were retrospectively reviewed. Their operative surgical risks were calculated according to EuroSCORE. Patients were randomly divided into two groups: training dataset (n = 3233) and validation dataset (n = 1619). Long-term survival data (mean follow-up 5·1 years) were obtained from the National Death Index. We compared four models: standard EuroSCORE (M1); logistic EuroSCORE (M2); M2 and other preoperative, intra-operative and post-operative selected variables (M3); and selected variables only (M4). M3 and M4 were determined with multivariable Cox regression analysis using the training dataset. Results, The estimated five-year survival rates of the quartiles in compared models in the validation dataset were: 94·5%, 87·8%, 77·1%, 64·9% for M1; 95·1%, 88·0%, 80·5%, 64·4% for M2; 93·4%, 89·4%, 80·8%, 64·1% for M3; and 95·8%, 90·9%, 81·0%, 59·9% for M4. In the four models, the odds of death in the highest-risk quartile was 8·4-, 8·5-, 9·4- and 15·6-fold higher, respectively, than the odds of death in the lowest-risk quartile (P < 0·0001 for all). Conclusions, EuroSCORE is a good predictor of long-term mortality after cardiac surgery. We developed and validated a model using selected preoperative, intra-operative and post-operative variables that has better discriminatory ability. [source] Pregnancy-induced sympathetic overactivity: a precursor of preeclampsia,EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2004T. Fischer Abstract Background, Preeclampsia has been shown to constitute a state of sympathetic overactivity. However, it remains unclear if the sympathetic activity precedes preeclampsia or represents only a secondary phenomenon. To further investigate this issue, we performed a prospective study in pregnant women considered to be at increased risk for preeclampsia owing to preeclampsia during a preceding pregnancy. Materials and methods, Twenty-two women with a history of preeclampsia were longitudinally studied on three occasions: twice during pregnancy (M1: 22 ± 4, M2: 33 ± 5 weeks) and once postpartum (M3: 26 ± 6 weeks postpartum). We measured muscle sympathetic nerve activity (MSNA), forearm blood flow, and blood pressure at rest and during reactive hyperaemia after forearm occlusion. Results, At M1 and M2, none of the subjects was hypertensive, however, muscle sympathetic nerve activity levels were significantly augmented, compared with their postpartum values (M1: 21 ± 9, M2: 29 ± 14, M3: 9 ± 5 bursts min,1; P < 0·05). Forearm vascular resistance did not significantly change from M1 through M3 (M1: 16 ± 9, M2: 15 ± 7, M3: 16 ± 7 U; P = NS). Gestational muscle sympathetic nerve activity values did not differ significantly among the subjects with subsequent preeclampsia compared with those who remained normotensive [with preeclampsia (n = 6): M1: 21 ± 5, M2: 27 ± 6, M3: 7 ± 4 bursts min,1; without preeclampsia (n = 16): M1: 21 ± 11, M2: 30 ± 16, M3: 9 ± 6 bursts min,1; P = NS]. Conclusion, Invariably, all women at risk for preeclampisa showed a pregnancy-induced increase in MSNA (pregnancy-induced sympathetic overactivity, PISO), which normalized after delivery. Most importantly, PISO is not necessarily associated with peripheral vasoconstriction and hypertension. Furthermore, only a subset of patients developed preeclampsia later on. Therefore, we hypothesize that PISO constitutes a precursor of preeclampsia which is physiologically compensated for by vasodilating mechanisms, leading to preeclampsia only when they fail. [source] Cytochrome P450 2D6 and glutathione S-transferase M1 genotypes and migraineEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2000Mattsson Background Migraine is thought to be a disease of the brain and trigeminovascular system. Migraine patients often claim that stress, food, and beverages trigger their attacks. Chemical substances in these foodstuffs with the property of triggering migraine attacks have not yet been characterised. Cytochrome P450 2D6 (CYP2D6) and glutathione S-transferase M1 (GSTM1) are thought to be present in the brain. They metabolise numerous environmental compounds. The genes exhibit genetic polymorphism that is associated with altered enzyme activity. The aim of this study was to determine if the genotypes of these two enzymes are associated with migraine. Materials and methods The study included 100 female patients and 245 female controls from the general population. Genomic DNA was isolated from whole blood. Allele specific PCR methods were used to identify the normal CYP2D6*1 allele and the mutated CYP2D6*3 and CYP2D6*4 alleles. Initially all samples were genotyped only for GSTM1 plus (+) and GSTM1 null (,) variants. All samples positive for GSTM1 were further analysed for the presence of allelic variants GSTM1*A and GSTM1*B. Results None of the CYP2D6 and GSTM1 genotypes was associated with migraine. We observed an odds ratio (OR) for the poor metaboliser genotype of CYP2D6 of 1.4 (95% CI = 0.5,3.6) and for the GSTM1 null genotype of 1.0 (95% CI = 0.6,1.5). Conclusion The results of this study indicate that deficient metabolism because of mutated CYP2D6 alleles or GSTM1 allele variants is not important in the aetiology of migraine. [source] A case of immune recovery vitritis induced by donor leukocyte infusion for the treatment of cytomegalovirus retinitisEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2005Manabu Kawakami Abstract:, Donor leukocyte infusion (DLI) has been successfully used for some life-threatening viral infections after stem cell transplantation (SCT). We describe here the first case of DLI treatment for cytomegalovirus (CMV) retinitis. A 49-year-old female patient with AML, M1 underwent SCT with a reduced-intensity conditioning regimen from HLA-haploidentical son. On day +140, the patient developed CMV retinitis of her left eye despite the continuing antiviral therapy. DLI at a dose of 1 × 105 CD3+ cells/kg was added to ganciclovir and foscarnet therapy. Eighteen days after the DLI, the funduscopic findings revealed improvement of the retinitis and the development of vitreous inflammation. Simultaneously, the number of CD4+ cells in the peripheral blood rapidly increased. Thus, we consider it likely that DLI induced a local immune response against CMV antigens, which resulted in the immune recovery vitritis. This case suggested the potentiality of DLI for the treatment of CMV retinitis. [source] Neurons in primary motor cortex engaged during action observationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2010Juliana Dushanova Abstract Neurons in higher cortical areas appear to become active during action observation, either by mirroring observed actions (termed mirror neurons) or by eliciting mental rehearsal of observed motor acts. We report the existence of neurons in the primary motor cortex (M1), an area that is generally considered to initiate and guide movement performance, responding to viewed actions. Multielectrode recordings in monkeys performing or observing a well-learned step-tracking task showed that approximately half of the M1 neurons that were active when monkeys performed the task were also active when they observed the action being performed by a human. These ,view' neurons were spatially intermingled with ,do' neurons, which are active only during movement performance. Simultaneously recorded ,view' neurons comprised two groups: approximately 38% retained the same preferred direction (PD) and timing during performance and viewing, and the remainder (62%) changed their PDs and time lag during viewing as compared with performance. Nevertheless, population activity during viewing was sufficient to predict the direction and trajectory of viewed movements as action unfolded, although less accurately than during performance. ,View' neurons became less active and contained poorer representations of action when only subcomponents of the task were being viewed. M1 ,view' neurons thus appear to reflect aspects of a learned movement when observed in others, and form part of a broadly engaged set of cortical areas routinely responding to learned behaviors. These findings suggest that viewing a learned action elicits replay of aspects of M1 activity needed to perform the observed action, and could additionally reflect processing related to understanding, learning or mentally rehearsing action. [source] Inter-hemispheric inhibition is impaired in mirror dystoniaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2009S. Beck Abstract Surround inhibition, a neural mechanism relevant for skilled motor behavior, has been shown to be deficient in the affected primary motor cortex (M1) in patients with focal hand dystonia (FHD). Even in unilateral FHD, however, electrophysiological and neuroimaging studies have provided evidence for bilateral M1 abnormalities. Clinically, the presence of mirror dystonia, dystonic posturing when the opposite hand is moved, also suggests abnormal interhemispheric interaction. To assess whether a loss of inter-hemispheric inhibition (IHI) may contribute to the reduced surround inhibition, IHI towards the affected or dominant M1 was examined in 13 patients with FHD (seven patients with and six patients without mirror dystonia, all affected on the right hand) and 12 right-handed, age-matched healthy controls (CON group). IHI was tested at rest and during three different phases of a right index finger movement in a synergistic, as well as in a neighboring, relaxed muscle. There was a trend for a selective loss of IHI between the homologous surrounding muscles in the phase 50 ms before electromyogram onset in patients with FHD. Post hoc analysis revealed that this effect was due to a loss of IHI in the patients with FHD with mirror dystonia, while patients without mirror dystonia did not show any difference in IHI modulation compared with healthy controls. We conclude that mirror dystonia may be due to impaired IHI towards neighboring muscles before movement onset. However, IHI does not seem to play a major role in the general pathophysiology of FHD. [source] Reorganization of cortical hand representation in congenital hemiplegiaEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2009Yves Vandermeeren Abstract When damaged perinatally, as in congenital hemiplegia (CH), the corticospinal tract usually undergoes an extensive reorganization, such as the stabilization of normally transient projections to the ipsilateral spinal cord. Whether the reorganization of the corticospinal projections occurring in CH patients is also accompanied by a topographical rearrangement of the hand representations in the primary motor cortex (M1) remains unclear. To address this issue, we mapped, for both hands, the representation of the first dorsal interosseous muscle (1DI) in 12 CH patients by using transcranial magnetic stimulation co-registered onto individual three-dimensional magnetic resonance imaging; these maps were compared with those gathered in age-matched controls (n = 11). In the damaged hemisphere of CH patients, the representation of the paretic 1DI was either found in the hand knob of M1 (n = 5), shifted caudally (n = 5), or missing (n = 2). In the intact hemisphere of six CH patients, an additional, ipsilateral, representation of the paretic 1DI was found in the hand knob, where it overlapped exactly the representation of the non-paretic 1DI. In the other six CH patients, the ipsilateral representation of the paretic 1DI was either shifted caudally (n = 2) or was lacking (n = 4). Surprisingly, in these two subgroups of patients, the representation of the contralateral non-paretic 1DI was found in a more medio-dorsal position than in controls. The present study demonstrates that, besides the well-known reorganization of the corticospinal projections, early brain injuries may also lead to a topographical rearrangement of the representations of both the paretic and non-paretic hands in M1. [source] 1-Hz repetitive TMS over ipsilateral motor cortex influences the performance of sequential finger movements of different complexityEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2008Laura Avanzino Abstract To elucidate the role of ipsilateral motor cortex (M1) in the control of unilateral finger movements (UFMs) in humans we used a conditioning protocol of 1-Hz repetitive transcranial magnetic stimulation (1-Hz rTMS) over M1 in 11 right-handed healthy subjects. We analysed the effects of conditioning rTMS on UFMs of different complexity (simple vs sequential finger movements), and performed with a different modality (internally vs externally paced movements). UFMs were monitored with a sensor-engineered glove, and a quantitative evaluation of the following parameters was performed: touch duration (TD); inter-tapping interval (ITI); timing error (TE); and number of errors (NE). 1-Hz rTMS over ipsilateral M1 was able to affect the performance of a sequence of finger opposition movements in a metronome-paced condition, significantly increasing TD and reducing ITI without TE changes. The effects on motor behaviour had a different magnitude as a function of the sequence complexity. Further, we found a different effect of the ipsilateral 1-Hz rTMS on externally paced movements with respect to an internally paced condition. All these findings indicate that ipsilateral M1 plays an important role in the execution of sequential UFMs. Interestingly, NE did not change in any experimental condition, suggesting that ipsilateral M1 influences only the temporal and not the spatial accuracy of UFMs. Finally, the duration (up to 30 min) of 1-Hz rTMS effects on ipsilateral M1 can indicate its direct action on the mechanisms of cortical plasticity, suggesting that rTMS can be used to modulate the communication between the two hemispheres in rehabilitative protocols. [source] Premotor transcranial direct current stimulation (tDCS) affects primary motor excitability in humansEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2008Klára Boros Abstract Recent studies have shown that repetitive transcranial magnetic stimulation (rTMS) over the premotor cortex (PM) modifies the excitability of the ipsilateral primary motor cortex (M1). Transcranial direct current stimulation (tDCS) is a new method to induce neuroplasticity in humans non-invasively. tDCS generates neuroplasticity directly in the cortical area under the electrode, but might also induce effects in distant brain areas, caused by activity modulation of interconnected areas. However, this has not yet been tested electrophysiologically. We aimed to study whether premotor tDCS can modify the excitability of the ipsilateral M1 via cortico-cortical connectivity. Sixteen subjects received cathodal and anodal tDCS of the PM and eight subjects of the dorsolateral prefrontal cortex. Premotor anodal, but not premotor cathodal or prefrontal tDCS, modified selectively short intracortical inhibition/intracortical facilitation (SICI/ICF), while motor thresholds, single test-pulse motor-evoked potential and input,output curves were stable throughout the experiments. Specifically, anodal tDCS decreased intracortical inhibition and increased paired-pulse excitability. The selective influence of premotor tDCS on intracortical excitability of the ipsilateral M1 suggests a connectivity-driven effect of tDCS on remote cortical areas. Moreover, this finding indirectly substantiates the efficacy of tDCS to modulate premotor excitability, which might be of interest for applications in diseases accompanied by pathological premotor activity. [source] Functional specificity of human premotor,motor cortical interactions during action selectionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2007Jacinta O'Shea Abstract Functional connections between dorsal premotor cortex (PMd) and primary motor cortex (M1) have been revealed by paired-pulse transcranial magnetic stimulation (TMS). We tested if such connections would be modulated during a cognitive process (response selection) known to rely on those circuits. PMd,M1 TMS applied 75 ms after a cue to select a manual response facilitated motor-evoked potentials (MEPs). MEPs were facilitated at 50 ms in a control task of response execution, suggesting that PMd,M1 interactions at 75 ms are functionally specific to the process of response selection. At 100 ms, PMd,M1 TMS delayed choice reaction time (RT). Importantly, the MEP (at 75 ms) and the RT (at 100 ms) effects were correlated in a way that was hand-specific. When the response was made with the M1-contralateral hand, MEPs correlated with slower RTs. When the response was made with the M1-ipsilateral hand, MEPs correlated with faster RTs. Paired-pulse TMS confined to M1 did not produce these effects, confirming the causal influence of PMd inputs. This study shows that a response selection signal evolves in PMd early during the reaction period (75,100 ms), impacts on M1 and affects behaviour. Such interactions are temporally, anatomically and functionally specific, and have a causal role in choosing which movement to make. [source] Disparate cholinergic currents in rat principal trigeminal sensory nucleus neurons mediated by M1 and M2 receptors: a possible mechanism for selective gating of afferent sensory neurotransmissionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2006Kristi A. Kohlmeier Abstract Neurons situated in the principal sensory trigeminal nucleus (PSTN) convey orofacial sensory inputs to thalamic relay regions and higher brain centres, and the excitability of these ascending tract cells is modulated across sleep/wakefulness states and during pain conditions. Moreover, acetylcholine release changes profoundly across sleep/wakefulness states and ascending sensory neurotransmission is altered by cholinergic agonists. An intriguing possibility is, therefore, that cholinergic mechanisms mediate such state-dependent modulation of PSTN tract neurons. We tested the hypotheses that cholinergic agonists can modulate PSTN cell excitability and that such effects are mediated by muscarinic receptor subtypes, using patch-clamp methods in rat and mouse. In all examined cells, carbachol elicited an electrophysiological response that was independent of action potential generation as it persisted in the presence of tetrodotoxin. Responses were of three types: depolarization, hyperpolarization or a biphasic response consisting of hyperpolarization followed by depolarization. In voltage-clamp mode, carbachol evoked corresponding inward, outward or biphasic currents. Moreover, immunostaining for the vesicle-associated choline transporter showed cholinergic innervation of the PSTN. Using muscarinic receptor antagonists, we found that carbachol-elicited PSTN neuron hyperpolarization was mediated by M2 receptors and depolarization, in large part, by M1 receptors. These data suggest that acetylcholine acting on M1 and M2 receptors may contribute to selective excitability enhancement or depression in individual, rostrally projecting sensory neurons. Such selective gating effects via cholinergic input may play a functional role in modulation of ascending sensory transmission, including across behavioral states typified by distinct cholinergic tone, e.g. sleep/wakefulness arousal levels or neuropathic pain conditions. [source] Presynaptic muscarinic acetylcholine receptors suppress GABAergic synaptic transmission in the intermediate grey layer of mouse superior colliculusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2004Fengxia Li Abstract The intermediate grey layer (the stratum griseum intermediale; SGI) of the superior colliculus (SC) receives cholinergic inputs from the parabrachial region of the brainstem. It has been shown that cholinergic inputs activate nicotinic acetylcholine (nACh) receptors on projection neurons in the SGI. Therefore, it has been suggested that they facilitate the initiation of orienting behaviours. In this study, we investigated the effect of muscarinic acetylcholine (mACh) receptor activation on GABAergic synaptic transmission to SGI neurons using the whole-cell patch-clamp recording technique in slice preparations from mice. The GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) evoked in SGI neurons by focal electrical stimulation were suppressed by bath application of 10 µm muscarine chloride. During muscarine application, both the paired-pulse facilitation index and the coefficient of variation of IPSCs increased; however, the current responses induced by a transient pressure application of 1 mm GABA were not affected by muscarine. Muscarine reduced frequencies of miniature IPSCs (mIPSCs) while the amplitudes of mIPSCs remained unchanged. These results suggestd that mAChR-mediated inhibition of IPSCs was of presynaptic origin. The suppressant effect of muscarine was antagonized by an M1 receptor antagonist, pirenzepine dihydrochloride (1 µm), and a relatively specific M3 receptor antagonist, 4-DAMP methiodide (50 nm). By contrast, an M2 receptor antagonist, methoctramine tetrahydrochloride (10 µm), was ineffective. These results suggest that the cholinergic inputs suppress GABAergic synaptic transmission to the SGI neurons at the presynaptic site via activation of M1 and, possibly, M3 receptors. This may be an additional mechanism by which cholinergic inputs can facilitate tectofugal command generation. [source] Postsynaptic M1 and M3 receptors are responsible for the muscarinic enhancement of retrograde endocannabinoid signalling in the hippocampusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2003Takako Ohno-Shosaku Abstract The cholinergic system is crucial for higher brain functions including learning and memory. These functions are mediated primarily by muscarinic acetylcholine receptors (mAChRs) that consist of five subtypes (M1,M5). A recent study suggested a novel role of acetylcholine as a potent enhancer of endocannabinoid signalling that acts retrogradely from postsynaptic to presynaptic neurons. In the present study, we further investigated the mechanisms of this cholinergic effect on endocannabinoid signalling. We made paired whole-cell recordings from cultured hippocampal neurons, and monitored inhibitory postsynaptic currents (IPSCs). The postsynaptic depolarization induced a transient suppression of IPSCs (DSI), a phenomenon known to involve retrograde signalling by endocannabinoids. The cholinergic agonist carbachol (CCh) markedly enhanced DSI at 0.01,0.3 µm without changing the presynaptic cannabinoid sensitivity. The facilitating effect of CCh on DSI was mimicked by the muscarinic agonist oxotremorine-M, whereas it was eliminated by the muscarinic antagonist atropine. It was also blocked by a non-hydrolizable analogue of GDP (GDP-,-S) that was applied intracellularly to postsynaptic neurons. The muscarinic enhancement of DSI persisted to a substantial degree in the neurons prepared from M1 -knockout and M3 -knockout mice, but was virtually eliminated in the neurons from M1/M3 -compound-knockout mice. CCh still enhanced DSI significantly under the blockade of postsynatpic K+ conductance, and did not significantly influence the depolarization-induced Ca2+ transients. These results indicate that the activation of postsynaptic M1 and M3 receptors facilitates the depolarization-induced release of endocannabinoids. [source] Modulation of ACh release by presynaptic muscarinic autoreceptors in the neuromuscular junction of the newborn and adult ratEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2003Manel M. Santafé Abstract We studied the presynaptic muscarinic autoreceptor subtypes controlling ACh release and their relationship with voltage-dependent calcium channels in the neuromuscular synapses of the Levator auris longus muscle from adult (30,40 days) and newborn (3,6 and 15 days postnatal) rats. Using intracellular recording, we studied how several muscarinic antagonists affected the evoked endplate potentials. In some experiments we previously incubated the muscle with calcium channel blockers (nitrendipine, ,-conotoxin-GVIA and ,-Agatoxin-IVA) before determining the muscarinic response. In the adult, the M1 receptor-selective antagonist pirenzepine (10 µm) reduced evoked neurotransmission (, 47%). The M2 receptor-selective antagonist methoctramine (1 µm) increased the evoked release (, 67%). Both M1- and M2-mediated mechanisms depend on calcium influx via P/Q-type synaptic channels. We found nothing to indicate the presence of M3 (4-DAMP-sensitive) or M4 (tropicamide-sensitive) receptors in the muscles of adult or newborn rats. In the 3,6-day newborn rats, pirenzepine reduced the evoked release (, 30%) by a mechanism independent of L-, N- and P/Q-type calcium channels, and the M2 antagonist methoctramine (1 µm) unexpectedly decreased the evoked release (, 40%). This methoctramine effect was a P/Q-type calcium-channel-dependent mechanism. However, upon maturation in the first two postnatal weeks, the M2 pathway shifted to perform the calcium-dependent release-inhibitory activity found in the adult. We show that the way in which M1 and M2 muscarinic receptors modulate neurotransmission can differ between the developing and adult rat neuromuscular synapse. [source] Modulation by adenosine of both muscarinic M1 -facilitation and M2 -inhibition of [3H]-acetylcholine release from the rat motor nerve terminalsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2002Laura Oliveira Abstract The crosstalk between adenosine and muscarinic autoreceptors regulating evoked [3H]-acetylcholine ([3H]-ACh) release was investigated on rat phrenic nerve-hemidiaphragm preparations. Motor nerve terminals possess facilitatory M1 and inhibitory M2 autoreceptors that can be activated by McN-A-343 (1,30 µm) and oxotremorine (0.3,100 µm), respectively. The muscarinic receptor antagonist, dicyclomine (3 nm,10 µm), caused a biphasic (inhibitory/facilitatory) effect, indicating that M1 -facilitation prevails during 5 Hz stimulation trains. Concomitant activation of AF,DX 116-sensitive M2 receptors was partially attenuated, as pretreatment with M1 antagonists, muscarinic toxin 7 (MT-7, 0.1 nm) and pirenzepine (1 nm), significantly enhanced inhibition by oxotremorine. Activation of A2A -adenosine receptors with CGS 21680C (2 nm) (i) potentiated oxotremorine inhibition, and (ii) shifted McN-A-343-induced facilitation into a small inhibitory effect. Conversely, the A1 -receptor agonist, R- N6 -phenylisopropyl adenosine (R-PIA, 100 nm), attenuated the inhibitory effect of oxotremorine, without changing facilitation by McN-A-343. Synergism between A2A and M2 receptors is regulated by a reciprocal interaction with facilitatory M1 receptors, which may be prevented by pirenzepine (1 nm). During 50 Hz-bursts, facilitation (M1) of [3H]-ACh release by McN-A-343 disappeared, while the inhibitory (M2) effect of oxotremorine became predominant. This muscarinic shift results from the interplay with A2A receptors, as it was precluded by the selective A2A receptor antagonist, ZM 241385 (10 nm). In conclusion, when the muscarinic M1 positive feedback loop is fully operative, negative regulation of ACh release is mediated by adenosine A1 receptors. During high frequency bursts, tonic activation of A2A receptors promotes M2 autoinhibition by braking the M1 receptor operated counteraction. [source] The role of the cutaneous cholinergic system in guttate psoriasisEXPERIMENTAL DERMATOLOGY, Issue 7 2008W. Dyck In previous studies, high levels of acetylcholine (ACh) have been reported in psoriasis lesions. In addition, patients with guttate psoriasis respond to oral treatment with atropine. We wanted to know how the cutaneous cholinergic system could be involved in this process. Since mast cells (MC) are characteristic components of the inflammatory infiltrate of guttate psoriasis, we compared ACh receptor (AChR) composition and ACh production in both epidermis and mast cells of 10 patients with guttate psoriasis in involved and uninvolved skin on protein level using immunofluorescence and in a MC line (HMC-1) using PCR. We could confirm the presence of numerous MC in guttate psoriasis lesion. Both in vivo and in vitro, MC lacked expression of cholinacetyltransferase (ChAT), vesicular acetylcholintransorter (VAChT) and cholintransporter-1 (ChT-1) but contained high levels of acetylcholinesterase (AChE). In mast cells of both involved and uninvolved skin we found both nicotinic (,3, ,5, ,7, ,9, ,10, ,2 and ,4 subunits) and muscarinic (M1, M3, M4, M5) AChR. In HMC-1 cells all AChR subunits found in skin where present on mRNA level, except ,7 and ,2. In lesional epidermis both ACh production and AChR expression was shifted from the basal to the suprabasal layers especially the nicotinic ,3, ,5, ,9, ,2 and ,4 and the muscarinic M3 and M5 AChR subunits. Our results exclude a role of the cholinergic system in the initiation of keratinocyte proliferation in the basal epidermal layer but point towards a role of epidermal AChR in suprabasal processes, most likely terminal differentiation and barrier formation as has been shown in other systems. Most importantly, mast cells are targets of paracrine and endocrine effects mediated by ACh and choline thus modulating inflammatory processes like guttate psoriasis and explaining the clinical efficacity of anticholinergic drugs like atropine. [source] The Helicobacter pylori plasticity region locus jhp0947,jhp0949 is associated with duodenal ulcer disease and interleukin-12 production in monocyte cellsFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2004Ramon De Jonge Abstract Colonization with Helicobacter pylori always results in chronic gastritis, which is controlled by infiltration of mononuclear cells and the subsequent release of cytokines like interleukin (IL)-12. To identify H. pylori factors involved in inducing cytokine production in mononuclear cells, a random H. pylori mutant library was screened for the inability to induce IL-12 production in monocyte THP-1 cells. Of the 231 random mutants screened, one mutant (M1) showed a consistent twofold decrease in the amount of IL-12 induction compared to the parental strain 1061 (P<0.01). Further characterization of mutant M1 revealed that the kanamycin resistance cassette had integrated in the jhp0945 gene, which is situated in an H. pylori strain-specific plasticity region. Three reference strains possessing this plasticity region induced significantly higher amounts of IL-12 when compared to the H. pylori 26695 reference strain, which does not possess this plasticity region. The role in disease outcome of jhp0945 as well as the neighbouring plasticity region genes jhp0947 and jhp049 was assessed in a Dutch population cohort. Firstly, the presence of jhp0947 was completely linked with that of jhp0949 and was roughly associated with jhp0945 (P=0.072), but not with the cag pathogenicity island (PAI) (P=0.464). The presence of the jhp0947 and jhp0949 genes, but not of jhp0945, was significantly associated with duodenal ulcer disease when compared to gastritis (P=0.027). Therefore, the jhp0947,jhp0949 locus may be a novel putative H. pylori marker for disease outcome independent of the cag PAI. [source] Isolation and identification of equol-producing bacterial strains from cultures of pig faecesFEMS MICROBIOLOGY LETTERS, Issue 1 2008Zhuo-Teng Yu Abstract Transformation of daidzein to equol was compared during fermentation of three growth media inoculated with faeces from Erhualian piglets, but equol was produced from only one medium, M1. Two equol-producing strains (D1 and D2) were subsequently isolated using medium M1. Both strains were identified as Eubacterium sp., on the basis of morphological and physiological characteristics, and 16S rRNA gene sequence analysis showed that strains D1 and D2 were most closely related to previously characterized daidzein-metabolizing bacteria isolated from human faecal and rumen samples, respectively. This suggests that the ability to metabolize daidzein can be found among bacteria present within the mammalian intestine. The results provided the first account of conversion of daidzein directly to equol by bacterial species from farm animals. These strains may be of importance to the improvement of animal performance, and the use of medium M1 could provide a simple way to isolate bacterial strains capable of transforming daidzein into equol. [source] New metabolic and pharmacokinetic characteristics of thiocolchicoside and its active metabolite in healthy humansFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2004M. Trellu Abstract Thiocolchicoside (TCC) has been prescribed for several years as a muscle relaxant drug, but its pharmacokinetic (PK) profile and metabolism still remain largely unknown. Therefore, we re-investigated its metabolism and PK, and we assessed the muscle relaxant properties of its metabolites. After oral administration of 8 mg (a therapeutic dose) of 14C-labelled TCC to healthy volunteers, we found no detectable TCC in plasma, urine or faeces. On the other hand, the aglycone derivative obtained after de-glycosylation of TCC (M2) was observed and, in addition, we identified, as the major circulating metabolic entity, 3-O-glucuronidated aglycone (M1) obtained after glucuro-conjugation of M2. One hour after oral administration, M1 plus M2 accounted for more than 75% of the circulating total radioactivity. The pharmacological activity of these metabolites was assessed using a rat model, the muscle relaxant activity of M1 was similar to that of TCC whereas M2 was devoid of any activity. Subsequently, to investigate the PK profile of TCC in human PK studies, we developed and validated a specific bioanalytical method that combines liquid chromatography and ultraviolet detection to assay both active entities. After oral administration, TCC was not quantifiable with an lower limit of quantification set at 1 ng/mL, whereas its active metabolite M1 was detected. M1 appeared rapidly in plasma (tmax = 1 h) and was eliminated with an apparent terminal half-life of 7.3 h. In contrast, after intramuscular administration both active entities (TCC and M1) were present; TCC was rapidly absorbed (tmax = 0.4 h) and eliminated with an apparent terminal half-life of 1.5 h. M1 concentration peaked at 5 h and this metabolite was eliminated with an apparent terminal half-life of 8.6 h. As TCC and M1 present an equipotent pharmacological activity, the relative oral pharmacological bioavailability of TCC vs. intramuscular administration was calculated and represented 25%. Therefore, to correctly investigate the PK and bioequivalence of TCC, the biological samples obtained must be assayed with a bioanalytical method able to specifically analyse TCC and its active metabolite M1. [source] Deficits in acetylcholine homeostasis, receptors and behaviors in choline transporter heterozygous miceGENES, BRAIN AND BEHAVIOR, Issue 5 2007M. H. Bazalakova Cholinergic neurons elaborate a hemicholinium-3 (HC-3) sensitive choline transporter (CHT) that mediates presynaptic, high-affinity choline uptake (HACU) in support of acetylcholine (ACh) synthesis and release. Homozygous deletion of CHT (,/,) is lethal shortly after birth (Ferguson et al. 2004), consistent with CHT as an essential component of cholinergic signaling, but precluding functional analyses of CHT contributions in adult animals. In contrast, CHT+/, mice are viable, fertile and display normal levels of synaptosomal HACU, yet demonstrate reduced CHT protein and increased sensitivity to HC-3, suggestive of underlying cholinergic hypofunction. We find that CHT+/, mice are equivalent to CHT+/+ siblings on measures of motor co-ordination (rotarod), general activity (open field), anxiety (elevated plus maze, light/dark paradigms) and spatial learning and memory (Morris water maze). However, CHT+/, mice display impaired performance as a result of physical challenge in the treadmill paradigm, as well as reduced sensitivity to challenge with the muscarinic receptor antagonist scopolamine in the open field paradigm. These behavioral alterations are accompanied by significantly reduced brain ACh levels, elevated choline levels and brain region-specific decreased expression of M1 and M2 muscarinic acetylcholine receptors. Our studies suggest that CHT hemizygosity results in adequate baseline ACh stores, sufficient to sustain many phenotypes, but normal sensitivities to physical and/or pharmacological challenge require full cholinergic signaling capacity. [source] Aliovalent Substitutions in Olivine Lithium Iron Phosphate and Impact on Structure and PropertiesADVANCED FUNCTIONAL MATERIALS, Issue 7 2009Nonglak Meethong Abstract Lithium transition metal phosphate olivines are enabling a new generation of high power, thermally stable, long-life rechargeable lithium batteries that may prove instrumental in the worldwide effort to develop cleaner and more sustainable energy. Nanoscale (<100,nm) derivatives of the olivine family LiMPO4 (M,=,Fe, Mn, Co, Ni) are being adopted in applications ranging in size scale from hybrid and plug-in hybrid electric vehicles to utilities-scale power regulation. Following the previous paradigm set with intercalation oxides, most studies have focused on the pure ordered compounds and isovalent substitutions. In contrast, even the possibility for, and role of, aliovalent doping has been widely debated. Here, critical tests of plausible defect compensation mechanisms using compositions designed to accommodate Mg2+, Al3+, Zr4+, Nb5+ ions on the M1,and/or M2 sites of LiFePO4 with appropriate charge-compensating defects are carried out, and conclusive crystallographic evidence for lattice doping, e.g., up to at least 12 atomic percent added Zr, is obtained. Structural and electrochemical analyses show that doping can reduce the lithium miscibility gap, increase phase transformation kinetics during cycling, and expand Li diffusion channels in the structure. Aliovalent modifications may be effective for introducing controlled atomic disorder into the ordered olivine structure to improve battery performance. [source] Monetary Policy and Forecasts for Real GDP Growth: An Empirical Investigation for the Federal Republic of GermanyGERMAN ECONOMIC REVIEW, Issue 4 2001Gebhardt Kirschgässner Using quarterly data for the Federal Republic of Germany, we generate four-quarter-ahead forecasts for real GDP growth. Throughout the 1970s and 1980s, other monetary indicators like real M1 or short-run interest rates clearly outperform forecasts which are based on interest rate spreads. This holds for within as well as for ex-post predictions. The same holds for the development after 1992. Moreover, it is shown that simple forecasts based on M1 or on short-run interest rates outperform the common biannual GNP forecasts of the group of German economic research institutes. [source] Protection of corticospinal tract neurons after dorsal spinal cord transection and engraftment of olfactory ensheathing cellsGLIA, Issue 4 2006Masanori Sasaki Abstract Transplantation of olfactory ensheathing cells (OECs) into the damaged rat spinal cord leads to directed elongative axonal regeneration and improved functional outcome. OECs are known to produce a number of neurotrophic molecules. To explore the possibility that OECs are neuroprotective for injured corticospinal tract (CST) neurons, we transplanted OECs into the dorsal transected spinal cord (T9) and examined primary motor cortex (M1) to assess apoptosis and neuronal loss at 1 and 4 weeks post-transplantation. The number of apoptotic cortical neurons was reduced at 1 week, and the extent of neuronal loss was reduced at 4 weeks. Biochemical analysis indicated an increase in BDNF levels in the spinal cord injury zone after OEC transplantation at 1 week. The transplanted OECs associated longitudinally with axons at 4 weeks. Thus, OEC transplantation into the injured spinal cord has distant neuroprotective effects on descending cortical projection neurons. © 2005 Wiley-Liss, Inc. [source] Isolation and Structure Elucidation of Enniatins L, M1, M2, and N: Novel Hydroxy AnalogsHELVETICA CHIMICA ACTA, Issue 8 2004Pornrapee Vongvilai Four new cyclohexadepsipeptides, enniatins L (1), M1 (2), M2 (3), and N (4), have been isolated from an unidentified fungus (BCC 2629), together with the known enniatins B (5), H (6), and I (7), MK1688 (8), and enniatin B4 (9). Compounds 1,4 are the first enniatin analogs with an OH group at the side chain of one of the 2-hydroxycarboxylic acid residues. The structures of 1,4 were elucidated by spectroscopic means and by X-ray crystallography. [source] MicroRNAs control hepatocyte proliferation during liver regeneration,HEPATOLOGY, Issue 5 2010Guisheng Song MicroRNAs (miRNAs) constitute a new class of regulators of gene expression. Among other actions, miRNAs have been shown to control cell proliferation in development and cancer. However, whether miRNAs regulate hepatocyte proliferation during liver regeneration is unknown. We addressed this question by performing 2/3 partial hepatectomy (2/3 PH) on mice with hepatocyte-specific inactivation of DiGeorge syndrome critical region gene 8 (DGCR8), an essential component of the miRNA processing pathway. Hepatocytes of these mice were miRNA-deficient and exhibited a delay in cell cycle progression involving the G1 to S phase transition. Examination of livers of wildtype mice after 2/3 PH revealed differential expression of a subset of miRNAs, notably an induction of miR-21 and repression of miR-378. We further discovered that miR-21 directly inhibits Btg2, a cell cycle inhibitor that prevents activation of forkhead box M1 (FoxM1), which is essential for DNA synthesis in hepatocytes after 2/3 PH. In addition, we found that miR-378 directly inhibits ornithine decarboxylase (Odc1), which is known to promote DNA synthesis in hepatocytes after 2/3 PH. Conclusion: Our results show that miRNAs are critical regulators of hepatocyte proliferation during liver regeneration. Because these miRNAs and target gene interactions are conserved, our findings may also be relevant to human liver regeneration. (HEPATOLOGY 2010) [source] | ||||||||||||||||||||||||||||||||||||||||||||||