Effect of BRAF(V600E )mutation on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model

BACKGROUND: microRNAs (miRNAs) are a group of non-coding single stranded RNAs measuring approximately 22 nucleotides in length that have been found to control cell growth, differentiation and apoptosis. They negatively regulate target genes and have recently been implicated in tumourigenesis. Furthermore, miRNA expression profiling correlates with various cancers, with these genes thought to act as both tumour suppressors and oncogenes. Recently, a point mutation in the BRAF gene leading to a V600E substitution has been identified as the most common genetic change in papillary thyroid carcinoma (PTC) occurring in 29–69% of cases. This mutation leads to aberrant MAPK activation that is implicated in tumourigenesis. AIM: The aim of this study was to identify the effect that BRAF oncogene has on post-transcriptional regulation in PTC by using microRNA analysis. RESULTS: A unique miRNA expression signature differentiated between PTC cell lines with BRAF mutations and a normal thyroid cell line. 15 miRNAs were found to be upregulated and 23 miRNAs were downregulated. Several of these up/down regulated miRNAs may be involved in PTC pathogenesis. miRNA profiling will assist in the elucidation of disease pathogenesis and identification biomarkers and targets

Effect of ret/PTC 1 rearrangement on transcription and post-transcriptional regulation in a papillary thyroid carcinoma model

BACKGROUND: microRNAs (miRNAs) are a group of non-coding single stranded RNAs measuring approximately 22 nt in length that have been found to control cell growth, differentiation and apoptosis. miRNAs negatively regulate their target genes and recently have been implicated in tumourigenesis. Furthermore, miRNA expression profiling correlates with various cancers, with these genes thought to act as both tumour suppressors and oncogenes. ret/PTC 1 is an oncogene with constitutive kinase activity implicated in the development of papillary thyroid carcinoma (PTC). This rearrangement leads to aberrant MAPK activation that is implicated in PTC tumourigenesis. AIM: The aim of this study was to identify the effect that ret/PTC 1 has on transcription and post-transcriptional regulation in PTC by using DNA microarray and microRNA analysis. RESULTS: DNA microarray analysis revealed a group of genes differentially expressed between normal thyroid cell lines and those harbouring a ret/PTC 1 rearrangement. Furthermore, a unique miRNA expression signature differentiated between PTC cell lines with ret/PTC 1 and a normal thyroid cell line. 21 miRNAs showed significant overexpression and 14 miRNAs showed underexpression in these cell lines when compared to normal thyroid. Several of these up/down regulated miRNAs may be involved in PTC pathogenesis

Expression microarray analysis of papillary thyroid carcinoma and benign thyroid tissue: emphasis on the follicular variant and potential markers of malignancy

The most common sub-variant of papillary thyroid carcinoma (PTC) is the so-called follicular variant (FVPTC), which is a particularly problematic lesion and can be challenging from a diagnostic viewpoint even in resected lesions. Although fine needle aspiration cytology is very useful in the diagnosis of PTC, its accuracy and utility would be greatly facilitated by the development of specific markers for PTC and its common variants. We used the recently developed Applied Biosystems 1700 microarray system to interrogate a series of 11 benign thyroid lesions and conditions and 14 samples of PTC (six with classic morphology and eight with follicular variant morphology). TaqMan® reverse transcriptase-polymerase chain reaction was used to validate the expression portfolios of 50 selected transcripts. Our data corroborates potential biomarkers previously identified in the literature, such as LGALS3, S100A11, LYN, BAX, and cluster of differentiation 44 (CD44). However, we have also identified numerous transcripts never previously implicated in thyroid carcinogenesis, and many of which are not represented on other microarray platforms. Diminished expression of metallothioneins featured strongly among these and suggests a possible role for this family as tumour suppressors in PTC. Fifteen transcripts were significantly associated with FVPTC morphology. Surprisingly, these genes were associated with an extremely narrow repertoire of functions, including the major histocompatibility complex and cathepsin families

Ethnobotany in the Nepal Himalaya

<p>Abstract</p> <p>Background</p> <p>Indigenous knowledge has become recognized worldwide not only because of its intrinsic value but also because it has a potential instrumental value to science and conservation. In Nepal, the indigenous knowledge of useful and medicinal plants has roots in the remote past.</p> <p>Methods</p> <p>The present study reviews the indigenous knowledge and use of plant resources of the Nepal Himalayas along the altitudinal and longitudinal gradient. A total of 264 studies focusing on ethnobotany, ethnomedicine and diversity of medicinal and aromatic plants, carried out between 1979 and 2006 were consulted for the present analysis. In order to cross check and verify the data, seven districts of west Nepal were visited in four field campaigns.</p> <p>Results</p> <p>In contrast to an average of 21–28% ethnobotanically/ethnomedicinally important plants reported for Nepal, the present study found that up to about 55% of the flora of the study region had medicinal value. This indicates a vast amount of undocumented knowledge about important plant species that needs to be explored and documented. The richness of medicinal plants decreased with increasing altitude but the percentage of plants used as medicine steadily increased with increasing altitude. This was due to preferences given to herbal remedies in high altitude areas and a combination of having no alternative choices, poverty and trust in the effectiveness of folklore herbal remedies.</p> <p>Conclusion</p> <p>Indigenous knowledge systems are culturally valued and scientifically important. Strengthening the wise use and conservation of indigenous knowledge of useful plants may benefit and improve the living standard of poor people.</p

A pre-post evaluation of OpenMinds:A sustainable, peer-led mental health literacy programme in universities and secondary schools

Engaging young people in the design and delivery of mental health education could lead to more effective interventions; however, few of these interventions have been evaluated. This study aimed to gain preliminary evidence with regards to the efficacy and acceptability of OpenMinds: a peer-designed and facilitated mental health literacy programme for university and secondary school students. The programme involves a structured programme of education and training for university medical students, who then deliver workshops in secondary schools. Pre- and post-surveys were completed by 234 school students who received two workshops and 40 university medical students who completed the OpenMinds programme and delivered the workshops. The main outcomes in both groups were components of mental health literacy (non-stigmatising attitudes, knowledge, social distance and helping attitudes). Perceived teaching efficacy and interest in mental health careers (university medical students) and workshop acceptability (school students) were also examined. University and school student participation in OpenMinds was associated with significant improvements in three of four mental health literacy elements in both samples. Knowledge and attitudes improved in both samples, social distance improved only in the university sample and knowledge of helping behaviours increased in the school sample. University students' perceived teaching efficacy improved but there was no change in their reported interest in pursuing psychiatry in their career. Acceptability was high; over 70% of the school students agreed that they enjoyed the workshops and liked being taught by a university student. This study provides preliminary evidence for the acceptability and efficacy of OpenMinds as a sustainable peer-led model of mental health education for young people. The OpenMinds programme is ready for efficacy testing in a randomised trial

Comparative bone marrow responses during Trypanosoma congolense infection in N'Dama and Boran cattle

Anaemia is a major cause of morbidity and mortality in bovine trypanosomiasis and has served as the main parameter to monitor the severity of the disease. In fact, trypanosome-infected cattle experience intermittent episodes of pancytopaenia including anaemia, leucopaenia and trombocytopaenia. Considering the multiple blood cell lineages affected by the disease, it was hypothesized that a defect in the bone marrow, site of origin of those cells, might be a cause. Study of the bone marrow response was intitiated in the laboratory using a Trypanosoma congolense rechallenge infection in five Boran cattle. The cattle developed a non-responsive, normocytic, normocytic, normochromic anaemia during the first ten weeks of the infection, characterized by low levles of erythroid progenitors in the bone marrow. Subsequently, between week 10 and 14, a responsive macrocytic hypochromic anaemia followed, characterized by peaks of CFU-E, slight increase of BFU-E levels and appearance of BFU-E in the peripheral blood. During trypanosome infection the trypanotolerant N'Dama cattle usually develop a moderate anaemia associated with lower parasitaemia when compared to the susceptible Zebu cattle such as the Boran. The present study was undertaken to determine if the ability of the N'Dama cattle to better control anaemia resides in a superior bone marrow response

Double Jeopardy - 50 years on. Reviving a forgotten tool that still predicts brand loyalty

Scientific knowledge builds by continuously subjecting its known laws to differentiated replication. Empirical generalisations capturing the Law of Double Jeopardy have been extensively tested in this way for decades, and rightly so because they continue to provide a valuable managerial key to the multi-million dollar question of how brands grow. This research continues that work, first by extending knowledge of the operation of Double Jeopardy in the less familiar conditions of long-run continuous buying, emerging markets, capital purchasing and house of brand strategies, and second by validating the rather overlooked w(1- b) approximation as a simple tool with which to predict behavioural brand loyalty. Observations of competitive brand performance in 32 differentiated replications, some over thirty five years apart, find no boundary condition to the operation of the Double Jeopardy characteristic even in contexts that might initially suggest a challenge to its independence assumptions. We outline the implications for managers in these new findings in terms of insight, planning and brand audit

Trypanosoma congolense: Comparative effects of a primary infection on bone marrow progenitor cells from N'Dama and Boran cattle

Using in vitro clonogenic assays, the changes in haemopoietic progenitor cell levels were compared in the bone marrow of three adult trypanotolerant N'Dama cattle and three age-matched trypanosusceptible Boran cattle over 17 weeks (119 days) of a primary Trypanosoma congolense (clone IL 1180) infection. As the infection progressed, a clear tendency of the parasitaemia to decrease was seen in the N'Damas, while it remained high throughout the infection in the Borans. The decline in the colony-forming units-granulocyte macrophage (CFU-GM) between 7 and 42 days positinfection (dpi) corresponded withthe decreased numbers of neutrophils and monocytes in the blood observed in both breeds. Thereafter, a further significant drop in the CFU-GM levels was observed in the Borans which may partially explain the continued decrease in the numbers of neutrophils and monocytes in blood. In contrast, a significant peak of CFU-GM above preinfection levels was observed in the N'Damas on 49 dpi, which could partially explain the subsequent recovery of the numbers of neutrophils and monocytes in blood. When compared to the N'Damas, the Borans had a more dramatic drop in the packed cell volume (PCV) from 25 dpi onwards, resulting in significantly lower PCFrom 46-49 dpi on wards, the mean PCV stabilised at significantly lower levels in the Borans than in the N'Damas. The mean corpuscular volume (MCV) levels increased in both breeds, but at a much faster rate in the Borans. The clonogenic assays demonstrated an erythropoietic response, characterised by peaks above preinfecton levels of both the early and late erythroid progenitor cells (respectively, burstforming units-erythroid, BFU-E, and colony-forming units-erythroid, CFU-E), occurring between 35 and 70 dpi in both breeds of cattle. However, despite a more severe anaemia in the Borans, the magnitude of their erythroid response was similar to that of the N'Damas, suggesting that the response of the Borans was insufficient to compensate for the greater degree of anaemia. Moreover, the mean PCV did not improve in the Borans, indicating the ineffectiveness of their erythropoietic response. An increased rate of erythrocyte destruction and/or a defective differentiation and maturation of erythroid precursors have also been shown to be partially responsible for this persistent anaemia. From 98 dpi onwards, despite the persistent low PCV, the MCV decreased to preinfection levels and low CFU-E numbers were observed in the Borans. Over the same period, in the N'Damas the N'Damas the mean PCV progressively increased to reach 25 percent, which fell within the low normal range for cattle. This may partially explain the return of the BFU-E to preinfection levels and the slight decrease in the CFU-E in the N'Damas. During the acute phase of a T. congolense infection, both the granulomonocytic and erythroid progenitors were increased more effectively in the N'Dama cattle than in the Boran cattle, when compared to the degree of cytopaenia in blood; this might correlate with the superior ability of the N'Damas to maintain gigher numbers of granulocytes, monocytes, and erythrocytes in blood