Comprehensive analysis of blood cells and plasma identifies tissue-specific miRNAs as potential novel circulating biomarkers in cattle

Abstract Background The potential of circulating miRNAs as biomarkers of tissue function, both in health and disease, has been extensively demonstrated in humans. In addition, circulating miRNA biomarkers offer significant potential towards improving the productivity of livestock species, however, such potential has been hampered by the absence of information on the nature and source of circulating miRNA populations in these species. In addition, many miRNAs originally proposed as robust biomarkers of a particular tissue or disease in humans have been later shown not to be tissue specific and thus to actually have limited biomarker utility. In this study, we comprehensively analysed miRNA profiles in plasma and cell fractions of blood from cattle with the aim to identify tissue-derived miRNAs which may be useful as biomarkers of tissue function in this important food animal species. Results Using small RNA sequencing, we identified 92 miRNAs with significantly higher expression in plasma compared to paired blood cell samples (n = 4 cows). Differences in miRNA levels between plasma and cell fractions were validated for eight out of 10 miRNAs using RT-qPCR (n = 10 cows). Among miRNAs found to be enriched in plasma, we confirmed miR-122 (liver), miR-133a (muscle) and miR-215 (intestine) to be tissue-enriched, as reported for other species. Profiling of additional miRNAs across different tissues identified the human homologue, miR-802, as highly enriched specifically in liver. Conclusions These results provide novel information on the source of bovine circulating miRNAs and could significantly facilitate the identification of production-relevant tissue biomarkers in livestock. In particular, miR-802, a circulating miRNA not previously identified in cattle, can reportedly regulate insulin sensitivity and lipid metabolism, and thus could potentially provide a specific biomarker of liver function, a key parameter in the context of post-partum negative energy balance in dairy cows

Multiplicity Distributions and Charged-neutral Fluctuations

Results from the multiplicity distributions of inclusive photons and charged particles, scaling of particle multiplicities, event-by-event multiplicity fluctuations, and charged-neutral fluctuations in 158$\cdot A$ GeV Pb+Pb collisions are presented and discussed. A scaling of charged particle multiplicity as $N_{part}^{1.07\pm 0.05}$ and photons as $N_{part}^{1.12\pm 0.03}$ have been observed, indicating violation of naive wounded nucleon model. The analysis of localized charged-neutral fluctuation indicates a model-independent demonstration of non-statistical fluctuations in both charged particles and photons in limited azimuthal regions. However, no correlated charged-neutral fluctuations are observed.Comment: Talk given at the International Symposium on Nuclear Physics (ISNP-2000), Mumbai, India, 18-22 Dec 2000, Proceedings to be published in Pramana, Journal of Physic

A randomized controlled multicenter trial of post-suicide attempt case management for the prevention of further attempts in Japan (ACTION-J)

<p>Abstract</p> <p>Background</p> <p>A previous suicide attempt is a potent risk factor for suicide later on. Crisis intervention, psychiatric and psychosocial evaluation at emergency medical facilities, and follow-up care for suicide attempters are considered important components for suicide prevention. The Japanese Multimodal Intervention Trials for Suicide Prevention (J-MISP) includes a randomized, controlled, multicenter trial of post-suicide attempt case management for the prevention of further attempts (ACTION-J) to address the continuing increase in suicides in Japan. The primary aim of ACTION-J is to examine the effectiveness of an extensive intervention for suicide attempters in prevention of recurrent suicidal behavior, as compared with standard intervention. This paper describes the rationale and protocol of the ACTION-J trial.</p> <p>Methods/Design</p> <p>In this clinical trial, case management intervention will be provided at 19 emergency medical facilities in Japan. After crisis intervention including psychiatric evaluation, psychosocial assessment, and psychological education, subjects will be randomly assigned to either a group receiving continuous case management or a control group receiving standard care. Suicidal ideation, depressive symptoms, and general health condition will be evaluated as secondary measures. The intervention was initiated in July 2006. By December, 2009, 842 subjects will be randomized. Subject follow-up will continue for 1.5 to 5 years.</p> <p>Discussion</p> <p>Suicide is a complex phenomenon that encompasses multiple factors. Case management by multi-sector collaboration is needed. ACTION-J may provide valuable information on suicide attempters and may develop effective case management to reduce future risk for suicide attempters.</p> <p>Trial registration</p> <p>UMIN Clinical Trials Registry number, UMIN000000444. ClinicalTrials.gov number, NCT00736918.</p

Cortactin expression predicts poor survival in laryngeal carcinoma

Amplification of the 11q13 region is one of the most frequent aberrations in squamous cell carcinomas of the head and neck region (HNSCC). Amplification of 11q13 has been shown to correlate with the presence of lymph node metastases and decreased survival. The 11q13.3 amplicon carries numerous genes including cyclin D1 and cortactin. Recently, we reported that FADD becomes overexpressed upon amplification and that FADD protein expression predicts for lymph node positivity and disease-specific mortality. However, the gene within the 11q13.3 amplicon responsible for this correlation is yet to be identified. In this paper, we compared, using immunohistochemical analysis for cyclin D1, FADD and cortactin in a series of 106 laryngeal carcinomas which gene correlates best with lymph node metastases and increased disease-specific mortality. Univariate Cox regression analysis revealed that high expression of cyclin D1 (P=0.016), FADD (P=0.003) and cortactin (P=0.0006) predict for increased risk to disease-specific mortality. Multivariate Cox analysis revealed that only high cortactin expression correlates with disease-specific mortality independent of cyclin D1 and/or FADD. Of genes located in the 11q13 amplicon, cortactin expression is the best predictor for shorter disease-specific survival in late stage laryngeal carcinomas