Changepoint detection in base-resolution methylome data reveals a robust signature of methylated domain landscape

ABSTRACTLotta Dalenius Hahlin (2010) Mentorskap utifrån ett lösningsinriktat fokus. (Mentorship based on a solution-oriented focus. Skolutveckling och ledarskap, Lärarutbildningen halvfart/distans, Malmö HögskolaMånga elever hoppar av sin gymnasieutbildning pga. av olika orsaker. En av orsakerna kan vara att eleven inte har tillräckligt stöd i sin mentor på skolan. En mentor skall ju inte bara ta hand om elevens studiemässiga resultat utan får även ta hand om de många sociala frågor som ofta uppstår runt eleven. Kan det vara så att mentorn behöver en ram och metod att arbeta utifrån för att kunna stödja eleverna på bästa sätt?Syftet med arbetet är att beskriva den metodik som ligger bakom ett lösningsinriktat mentorskap,och att skapa ett kompendium av användbara verktyg utifrån lösningsinriktad pedagogik. Detta kompendium kan mentorn använda som mall/ram i sin arbetsuppgift som mentor.Forskningen tyder på att lyckade och bra samtal bygger på bra förberedelse, på öppna frågor och på ömsesidig respekt för varandra och att man använder sig av ett visst förhållningssätt gentemot varandra. Vidare pekar litteraturstudien på att mentorssamtalet bör ha tydliga mål och en gemensam uppfattning om vad man vill komma fram till för att eleven skall nå ökat ansvar, större självinsikt och önskat läge.Arbetet tar upp de olika verktyg som man främst använder inom lösningsinriktade metoder, och är utifrån litteraturen kommenterat för att ge en grundläggande kunskap och förförståelse för läsaren.Genom att som resultat skapa ett kompendium som mentorer kan använda i sitt arbete med det dagliga samtalet med eleverna, vill uppsatsen beskriva och ge grundläggande kunskap om de verktyg som finns i den lösningsinriktade verktygslådan. Syftet nås även med en enkätundersökning där mentorer som fått pröva på metoden plockat ut fördelar och nackdelar med metoden.Uppsatsen visar att regelbunden användning och övning krävs för att kunna tillgodogöra sig metoden, och även att mentorn genomgår en grundläggande utbildning. Den kommer också att visa att vinsterna och fördelarna med metoden överstiger de eventuella nackdelar som kan uppstå när man som mentor börjar arbeta med metoden

Characterization of Gastric Tissue-Resident T Cells in Autoimmune and Helicobacter pylori-Associated Gastritis

Data regarding the in-depth surface marker profiles of gastric tissue-resident lymphocytes in autoimmune and Helicobacter pylori-associated gastritis are lacking. In this study, we investigated potential differences in lymphocyte composition between these profiles. We enrolled patients with autoimmune (n = 14), active (current infection of H. pylori in the stomach; n = 10), and inactive gastritis (post-eradication of H. pylori; n = 20). Lymphocytes were isolated from the greater curvature of the stomach and lesser curvature of the body and analyzed using flow cytometry. The CD8(+)/CD3(+) and CD4(+)/CD3(+) ratios differed between the samples. Body CD4(+)/antrum CD4(+), which is calculated by dividing the CD4(+)/CD3(+) ratio in the body by that in the antrum, was significantly higher in autoimmune gastritis (3.54 +/- 3.13) than in active (1.47 +/- 0.41) and inactive gastritis (1.42 +/- 0.77). Antrum CD8(+)/CD4(+) in autoimmune gastritis (7.86 +/- 7.23) was also higher than that in active (1.49 +/- 0.58) and inactive gastritis (2.84 +/- 2.17). The area under the receiver operating characteristic curve of antrum CD8(+)/CD4(+) was 0.842, and the corresponding optimal cutoff point was 4.0, with a sensitivity of 71.4% and a specificity of 93.3%. We propose that an antrum CD8(+)/CD4(+) ratio > 4.0 is a potential diagnostic marker for autoimmune gastritis

Mapping of histone-binding sites in histone replacement-completed spermatozoa

The majority of histones are replaced by protamines during spermatogenesis, but small amounts are retained in mammalian spermatozoa. Since nucleosomes in spermatozoa influence epigenetic inheritance, it is important to know how histones are distributed in the sperm genome. Conflicting data, which may result from different conditions used for micrococcal nuclease (MNase) digestion, have been reported: retention of nucleosomes at either gene promoter regions or within distal gene-poor regions. Here, we find that the swim-up sperm used in many studies contain about 10% population of sperm which have not yet completed the histone-to-protamine replacement. We develop a method to purify histone replacement-completed sperm (HRCS) and to completely solubilize histones from cross-linked HRCS without MNase digestion. Our results indicate that histones are retained at specific promoter regions in HRCS. This method allows the study of epigenetic status in mature sperm

A case of hepatocellular carcinoma with skin injury of the upper abdominal wall after transcatheter arterial chemoembolization: a case report

Introduction Transcatheter arterial chemoembolization has been widely used to treat advanced hepatocellular carcinoma that cannot be treated by local ablation therapies or surgical resection. The effectiveness of transcatheter arterial chemoembolization in prolonging survival has been well established, and approximately one third of newly discovered hepatocellular carcinoma patients were repeatedly treated by transcatheter arterial chemoembolization in Japan. Various kinds of complications have been reported, and many of which are general complications such as hepatic coma, jaundice, fever-up, ascites, and bile duct injury. The hepatic falciform artery is found frequently during postmortem anatomic dissection and the incidence of hepatic falciform artery is reported to be over 60%. Hepatic falciform artery is known to be the responsible artery for supraumbilical skin rash development after arterial chemo infusion therapy; however, skin complications after transcatheter arterial chemoembolization are rare. Case presentation A 70-year-old female with chronic hepatitis C infection was diagnosed as having hepatocellular carcinoma (S4, 20 mm in diameter). Transcatheter arterial chemoembolization was performed via the left hepatic artery, which was a feeding artery of the hepatocellular carcinoma. Two days after that, supraumbilical skin rash with local tenderness and redness appeared. Retrospective analysis revealed that occlusion of the hepatic falciform artery branching from the left hepatic artery with micromaterials caused the skin lesion. Conclusion We should keep in mind that anticancer drugs or embolic materials can flow into the HFA and may cause abdominal wall injury after transcatheter arterial chemoembolization

Vasohibin-1 is identified as a master-regulator of endothelial cell apoptosis using gene network analysis.

BACKGROUND: Apoptosis is a critical process in endothelial cell (EC) biology and pathology, which has been extensively studied at protein level. Numerous gene expression studies of EC apoptosis have also been performed, however few attempts have been made to use gene expression data to identify the molecular relationships and master regulators that underlie EC apoptosis. Therefore, we sought to understand these relationships by generating a Bayesian gene regulatory network (GRN) model. RESULTS: ECs were induced to undergo apoptosis using serum withdrawal and followed over a time course in triplicate, using microarrays. When generating the GRN, this EC time course data was supplemented by a library of microarray data from EC treated with siRNAs targeting over 350 signalling molecules.The GRN model proposed Vasohibin-1 (VASH1) as one of the candidate master-regulators of EC apoptosis with numerous downstream mRNAs. To evaluate the role played by VASH1 in EC, we used siRNA to reduce the expression of VASH1. Of 10 mRNAs downstream of VASH1 in the GRN that were examined, 7 were significantly up- or down-regulated in the direction predicted by the GRN.Further supporting an important biological role of VASH1 in EC, targeted reduction of VASH1 mRNA abundance conferred resistance to serum withdrawal-induced EC death. CONCLUSION: We have utilised Bayesian GRN modelling to identify a novel candidate master regulator of EC apoptosis. This study demonstrates how GRN technology can complement traditional methods to hypothesise the regulatory relationships that underlie important biological processes

Gene network inference and visualization tools for biologists: application to new human transcriptome datasets.

Gene regulatory networks inferred from RNA abundance data have generated significant interest, but despite this, gene network approaches are used infrequently and often require input from bioinformaticians. We have assembled a suite of tools for analysing regulatory networks, and we illustrate their use with microarray datasets generated in human endothelial cells. We infer a range of regulatory networks, and based on this analysis discuss the strengths and limitations of network inference from RNA abundance data. We welcome contact from researchers interested in using our inference and visualization tools to answer biological questions

Quantum hydrodynamics

Quantum hydrodynamics in superfluid helium and atomic Bose-Einstein condensates (BECs) has been recently one of the most important topics in low temperature physics. In these systems, a macroscopic wave function appears because of Bose-Einstein condensation, which creates quantized vortices. Turbulence consisting of quantized vortices is called quantum turbulence (QT). The study of quantized vortices and QT has increased in intensity for two reasons. The first is that recent studies of QT are considerably advanced over older studies, which were chiefly limited to thermal counterflow in 4He, which has no analogue with classical traditional turbulence, whereas new studies on QT are focused on a comparison between QT and classical turbulence. The second reason is the realization of atomic BECs in 1995, for which modern optical techniques enable the direct control and visualization of the condensate and can even change the interaction; such direct control is impossible in other quantum condensates like superfluid helium and superconductors. Our group has made many important theoretical and numerical contributions to the field of quantum hydrodynamics of both superfluid helium and atomic BECs. In this article, we review some of the important topics in detail. The topics of quantum hydrodynamics are diverse, so we have not attempted to cover all these topics in this article. We also ensure that the scope of this article does not overlap with our recent review article (arXiv:1004.5458), "Quantized vortices in superfluid helium and atomic Bose--Einstein condensates", and other review articles.Comment: 102 pages, 29 figures, 1 tabl

Probiotic Bifidobacterium breve Induces IL-10-Producing Tr1 Cells in the Colon

Specific intestinal microbiota has been shown to induce Foxp3+ regulatory T cell development. However, it remains unclear how development of another regulatory T cell subset, Tr1 cells, is regulated in the intestine. Here, we analyzed the role of two probiotic strains of intestinal bacteria, Lactobacillus casei and Bifidobacterium breve in T cell development in the intestine. B. breve, but not L. casei, induced development of IL-10-producing Tr1 cells that express cMaf, IL-21, and Ahr in the large intestine. Intestinal CD103+ dendritic cells (DCs) mediated B. breve-induced development of IL-10-producing T cells. CD103+ DCs from Il10−/−, Tlr2−/−, and Myd88−/− mice showed defective B. breve-induced Tr1 cell development. B. breve-treated CD103+ DCs failed to induce IL-10 production from co-cultured Il27ra−/− T cells. B. breve treatment of Tlr2−/− mice did not increase IL-10-producing T cells in the colonic lamina propria. Thus, B. breve activates intestinal CD103+ DCs to produce IL-10 and IL-27 via the TLR2/MyD88 pathway thereby inducing IL-10-producing Tr1 cells in the large intestine. Oral B. breve administration ameliorated colitis in immunocompromised mice given naïve CD4+ T cells from wild-type mice, but not Il10−/− mice. These findings demonstrate that B. breve prevents intestinal inflammation through the induction of intestinal IL-10-producing Tr1 cells

Cell Cycle Gene Networks Are Associated with Melanoma Prognosis

BACKGROUND: Our understanding of the molecular pathways that underlie melanoma remains incomplete. Although several published microarray studies of clinical melanomas have provided valuable information, we found only limited concordance between these studies. Therefore, we took an in vitro functional genomics approach to understand melanoma molecular pathways. METHODOLOGY/PRINCIPAL FINDINGS: Affymetrix microarray data were generated from A375 melanoma cells treated in vitro with siRNAs against 45 transcription factors and signaling molecules. Analysis of this data using unsupervised hierarchical clustering and Bayesian gene networks identified proliferation-association RNA clusters, which were co-ordinately expressed across the A375 cells and also across melanomas from patients. The abundance in metastatic melanomas of these cellular proliferation clusters and their putative upstream regulators was significantly associated with patient prognosis. An 8-gene classifier derived from gene network hub genes correctly classified the prognosis of 23/26 metastatic melanoma patients in a cross-validation study. Unlike the RNA clusters associated with cellular proliferation described above, co-ordinately expressed RNA clusters associated with immune response were clearly identified across melanoma tumours from patients but not across the siRNA-treated A375 cells, in which immune responses are not active. Three uncharacterised genes, which the gene networks predicted to be upstream of apoptosis- or cellular proliferation-associated RNAs, were found to significantly alter apoptosis and cell number when over-expressed in vitro. CONCLUSIONS/SIGNIFICANCE: This analysis identified co-expression of RNAs that encode functionally-related proteins, in particular, proliferation-associated RNA clusters that are linked to melanoma patient prognosis. Our analysis suggests that A375 cells in vitro may be valid models in which to study the gene expression modules that underlie some melanoma biological processes (e.g., proliferation) but not others (e.g., immune response). The gene expression modules identified here, and the RNAs predicted by Bayesian network inference to be upstream of these modules, are potential prognostic biomarkers and drug targets

Grassroots Environmental Groups and Global Climate Change

ABSTRACT Despite the call by environmental advocates for grassroots movements addressing global climate change, there has been little strategic guidance for grassroots organizations in how to mobilize their constituents. This study explores how grassroots environmental groups can effectively address the global climate change issue so as to encourage active individual participation. This research found three types of strategic frames for grassroots organizations focusing on climate change: mainstream frames (MS) to reduce greenhouse gas emissions through mitigation policies, general climate justice frames (GCJ) to claim disproportionate impacts of climate change, and targeting polluter industry frames (TPI) to attribute climate change to hazardous facilities so as to support the anti-toxic environmental justice movement. The survey results indicate that these frames are not appealing enough to influence constituents’ concerns, attributions, and dissatisfactions regarding climate effects. Although the respondents are more likely to be willing to participate in activities offered by organizational prognostic frames, this study finds no single determinant inducing willingness to participate; clearly other determinants than prognoses, such as experience of climate effects, can play a role as well. The inability to specify these other determinants is partly due to a limitation of this study, which is based on a limited number of grassroots organizations involved in climate change. Climate change is an environmental issue which can be shared by mainstream and environmental justice organizations which have a history of confrontation. In order to develop and unite their efforts, this study offers three recommendations. First, climate justice organizations should ally with national mainstream organizations to address their lack of resources. Second, the movements should focus more on adaptation policies. Finally, grassroots organizations should educate people about climate change so that constituents can recognize the issue as a political problem.Master of ScienceSchool of Natural Resources and EnvironmentUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/49368/1/Hiromitsu Araki. Grassroots organizations addressing climat~1.pd