Role of miR-148a in hepatitis B associated hepatocellular carcinoma

Hepatitis B virus encoded X antigen (HBx) is a trans-regulatory protein that alters the activity of selected transcription factors and cytoplasmic signal transduction pathways. HBx transcriptionally up-regulates the expression of a unique gene, URG11, which in turn transcriptionally up-regulates beta-catenin, thereby contributing importantly to hepatocarcinogenesis. HBx and URG11 also alter the expression of multiple microRNAs, and by miRNA array analysis, both were shown to promote the expression of miR-148a. Elevated miR-148a was also seen in HBx positive liver samples from infected patients. To study the function of miR-148a, anti-148a was introduced into HepG2 and Hep3B cells stably expressing HBx or stably over-expressing URG11. Anti-miR-148a suppressed cell proliferation, cell cycle progression, cell migration, anchorage independent growth in soft agar and subcutaneous tumor formation in SCID mice. Introduction of anti-miR-148a increased PTEN protein and mRNA expression, suggesting that PTEN was targeted by miR-148a. Anti-miR-148a failed to suppress PTEN expression when co-transfected with reporter gene mutants in the 3'UTR of PTEN mRNA. Introduction of anti-miR-148a also resulted in depressed Akt signaling by HBx and URG11, resulting in decreased expression of beta-catenin. Thus, miR-148a may play a central role in HBx/URG11 mediated HCC, and may be an early diagnostic marker and/or therapeutic target associated with this tumor type.published_or_final_versio

Elevated hemostasis markers after pneumonia increases one-year risk of all-cause and cardiovascular deaths

Background: Acceleration of chronic diseases, particularly cardiovascular disease, may increase long-term mortality after community-acquired pneumonia (CAP), but underlying mechanisms are unknown. Persistence of the prothrombotic state that occurs during an acute infection may increase risk of subsequent atherothrombosis in patients with pre-existing cardiovascular disease and increase subsequent risk of death. We hypothesized that circulating hemostasis markers activated during CAP persist at hospital discharge, when patients appear to have recovered clinically, and are associated with higher mortality, particularly due to cardiovascular causes. Methods: In a cohort of survivors of CAP hospitalization from 28 US sites, we measured D-Dimer, thrombin-antithrombin complexes [TAT], Factor IX, antithrombin, and plasminogen activator inhibitor-1 at hospital discharge, and determined 1-year all-cause and cardiovascular mortality. Results: Of 893 subjects, most did not have severe pneumonia (70.6% never developed severe sepsis) and only 13.4% required intensive care unit admission. At discharge, 88.4% of subjects had normal vital signs and appeared to have clinically recovered. D-dimer and TAT levels were elevated at discharge in 78.8% and 30.1% of all subjects, and in 51.3% and 25.3% of those without severe sepsis. Higher D-dimer and TAT levels were associated with higher risk of all-cause mortality (range of hazard ratios were 1.66-1.17, p = 0.0001 and 1.46-1.04, p = 0.001 after adjusting for demographics and comorbid illnesses) and cardiovascular mortality (p = 0.009 and 0.003 in competing risk analyses). Conclusions: Elevations of TAT and D-dimer levels are common at hospital discharge in patients who appeared to have recovered clinically from pneumonia and are associated with higher risk of subsequent deaths, particularly due to cardiovascular disease. © 2011 Yende et al

Statistical analysis of human boy movement and group interactions in response to music

Quantification of time series that relate to physiological data is challenging for empirical music research. Up to now, most studies have focused on time-dependent responses of individual subjects in controlled environments. However, little is known about time-dependent responses of between-subject interactions in an ecological context. This paper provides new findings on the statistical analysis of group synchronicity in response to musical stimuli. Different statistical techniques were applied to time-dependent data obtained from an experiment on embodied listening in individual and group settings. Analysis of inter group synchronicity are described. Dynamic Time Warping (DTW) and Cross Correlation Function (CCF) were found to be valid methods to estimate group coherence of the resulting movements. It was found that synchronicity of movements between individuals (human human interactions) increases significantly in the social context. Moreover, Analysis of Variance (ANOVA) revealed that the type of music is the predominant factor in both the individual and the social context

Key Physiological Parameters Dictate Triggering of Activity-Dependent Bulk Endocytosis in Hippocampal Synapses

To maintain neurotransmission in central neurons, several mechanisms are employed to retrieve synaptically exocytosed membrane. The two major modes of synaptic vesicle (SV) retrieval are clathrin-mediated endocytosis and activity-dependent bulk endocytosis (ADBE). ADBE is the dominant SV retrieval mode during intense stimulation, however the precise physiological conditions that trigger this mode are not resolved. To determine these parameters we manipulated rat hippocampal neurons using a wide spectrum of stimuli by varying both the pattern and duration of stimulation. Using live-cell fluorescence imaging and electron microscopy approaches, we established that stimulation frequency, rather than the stimulation load, was critical in the triggering of ADBE. Thus two hundred action potentials, when delivered at high frequency, were sufficient to induce near maximal bulk formation. Furthermore we observed a strong correlation between SV pool size and ability to perform ADBE. We also identified that inhibitory nerve terminals were more likely to utilize ADBE and had a larger SV recycling pool. Thus ADBE in hippocampal synaptic terminals is tightly coupled to stimulation frequency and is more likely to occur in terminals with large SV pools. These results implicate ADBE as a key modulator of both hippocampal neurotransmission and plasticity

Universality of interpersonal psychotherapy (IPT) problem areas in Thai depressed patients

<p>Abstract</p> <p>Background</p> <p>Many studies have shown the efficacy of interpersonal psychotherapy (IPT) on depression; however, there are limited studies concerning the universality of the IPT problem areas in different countries. This study identifies whether the interpersonal problem areas defined in the IPT manual are endorsed by Thai depressed patients.</p> <p>Methods</p> <p>The Thai Hamilton Rating Scale for Depression (Thai HRSD) and Thai Interpersonal Questionnaire were used to assess 90 depressed and 90 non-depressed subjects in King Chulalongkorn Memorial Hospital, during July 2007 - January 2008. The association between interpersonal problem areas/sociodemographic variables and depressive disorder were analyzed by chi-square test. A multivariable analysis was performed by using logistic regression to identify the remaining factors associated with depressive disorder.</p> <p>Results</p> <p>Most of the subjects were young to middle-aged females living in Bangkok and the Central Provinces. All four interpersonal problem areas (grief, interpersonal role disputes, role transitions, and interpersonal deficits) were increased in the depressed subjects as compared to the non-depressed subjects, as were the sociodemographic variables (low education, unemployment, low income, and having a physical illness). Logistic regression showed that all interpersonal problem areas still remained problems associated with depression (grief: adjusted OR = 6.01, 95%CI = 1.93 - 18.69, p < 0.01; interpersonal role disputes: adjusted OR = 6.01, 95%CI = 2.18 - 16.52, p < 0.01; role transitions: adjusted OR = 26.30, 95%CI = 7.84 - 88.25, p < 0.01; and interpersonal deficits: adjusted OR = 2.92, 95%CI = 1.12 - 7.60, p < 0.05).</p> <p>Conclusion</p> <p>All four interpersonal problem areas were applicable to Thai depressed patients.</p

A novel RFC1 repeat motif (ACAGG) in two Asia-Pacific CANVAS families

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a progressive late-onset, neurological disease. Recently, a pentanucleotide expansion in intron 2 of RFC1 was identified as the genetic cause of CANVAS. We screened an Asian-Pacific cohort for CANVAS and identified a novel RFC1 repeat expansion motif, (ACAGG)exp, in three affected individuals. This motif was associated with additional clinical features including fasciculations and elevated serum creatine kinase. These features have not previously been described in individuals with genetically-confirmed CANVAS. Haplotype analysis showed our patients shared the same core haplotype as previously published, supporting the possibility of a single origin of the RFC1 disease allele. We analysed data from >26 000 genetically diverse individuals in gnomAD to show enrichment of (ACAGG) in non-European populations

Análise integrada de sistemas de produção de tomateiro com base em indicadores edafobiológicos.

A análise integrada de indicadores edafobiológicos ligados ao manejo do solo constitui uma ferramenta importante para estimar níveis de sustentabilidade do agroecossistema, detectando-se pontos críticos para a devida correção de manejo. Essa ferramenta foi empregada na avaliação de sistemas de produção orgânica e convencional de tomate, em cultivo protegido e a campo aberto, no estado de São Paulo. Tomaram-se como referência solos de mata nativa e/ou pastagem natural, dependendo do local de estudo. Em Serra Negra, o solo sob sistema orgânico apresentou maior capacidade de campo e teor de argila dispersa mais baixo, indicativos da estabilidade dos agregados. No sistema convencional observou-se uma elevada condutividade elétrica, evidenciando a alta disponibilidade de sais solúveis. A análise de componentes principais (ACP) permitiu concluir que há maior grau de similaridade entre o solo sob sistema orgânico e aqueles das bases referenciais, com respeito aos indicadores químicos e biológicos. Constatou-se que C org, N total, polissacarídeos, FDA (hidrólise de diacetato de fluoresceína) e atividade enzimática de desidrogenase estão positivamente relacionados com o sistema orgânico, a mata nativa e a pastagem. Em contrapartida, a saturação por bases (V%), pH, teores de Mn, Mg e Ca, bem como a razão de dispersão estão inversamente relacionadas ao manejo orgânico. Já em Araraquara, os resultados da ACP distinguiram as áreas organicamente cultivadas das matas nativas, principalmente, com base nos indicadores biológicos