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Search Results: 1 - 10 of 1998 matches for " Hannele Ruohola-Baker "
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Chronic Hypoxia Impairs Muscle Function in the Drosophila Model of Duchenne's Muscular Dystrophy (DMD)
Matias Mosqueira,Gabriel Willmann,Hannele Ruohola-Baker,Tejvir S. Khurana
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0013450
Abstract: Duchenne's muscular dystrophy (DMD) is a severe progressive myopathy caused by mutations in the DMD gene leading to a deficiency of the dystrophin protein. Due to ongoing muscle necrosis in respiratory muscles late-stage DMD is associated with respiratory insufficiency and chronic hypoxia (CH). To understand the effects of CH on dystrophin-deficient muscle in vivo, we exposed the Drosophila model for DMD (dmDys) to CH during a 16-day ascent to the summit of Mount Denali/McKinley (6194 meters above sea level). Additionally, dmDys and wild type (WT) flies were also exposed to CH in laboratory simulations of high altitude hypoxia. Expression profiling was performed using Affymetrix GeneChips? and validated using qPCR. Hypoxic dmDys differentially expressed 1281 genes, whereas the hypoxic WT flies differentially expressed 56 genes. Interestingly, a number of genes (e.g. heat shock proteins) were discordantly regulated in response to CH between dmDys and WT. We tested the possibility that the disparate molecular responses of dystrophin-deficient tissues to CH could adversely affect muscle by performing functional assays in vivo. Normoxic and CH WT and dmDys flies were challenged with acute hypoxia and time-to-recover determined as well as subjected to climbing tests. Impaired performance was noted for CH-dmDys compared to normoxic dmDys or WT flies (rank order: Normoxic-WT ≈ CH-WT> Normoxic-dmDys> CH-dmDys). These data suggest that dystrophin-deficiency is associated with a disparate, pathological hypoxic stress response(s) and is more sensitive to hypoxia induced muscle dysfunction in vivo. We hypothesize that targeting/correcting the disparate molecular response(s) to hypoxia may offer a novel therapeutic strategy in DMD.
Notch signaling through Tramtrack bypasses the mitosis promoting activity of the JNK pathway in the mitotic-to-endocycle transition of Drosophila follicle cells
Katherine C Jordan, Valerie Schaeffer, Karin A Fischer, Elizabeth E Gray, Hannele Ruohola-Baker
BMC Developmental Biology , 2006, DOI: 10.1186/1471-213x-6-16
Abstract: In this paper, we show that Notch signaling is modulated by Shaggy and temporally induced by the ligand Delta, at the mitotic-to-endocycle transition. In addition, a downstream target of Notch, tramtrack, acts at the mitotic-to-endocycle transition. We also demonstrate that the JNK pathway is required to promote mitosis prior to the transition, independent of the cell cycle components acted on by the Notch pathway.This work reveals new insights into the regulation of Notch-dependent mitotic-to-endocycle switch.The cell cycle in developing organisms is intricately orchestrated by extrinsic signals [1-3]. Different signaling pathways probably define the rate-limiting cell cycle steps in different cell types, thus providing and explanation for why different cancers target different tissues. Thus, understanding the control of cell cycle is critical for understanding both development and carcinogenesis.Studies on a natural variant of the mitotic cycle, the endocycle, have revealed how signaling pathways negatively regulate cell cycle [4,5]. The endocycle, as seen in megacaryocytes, trophoblasts, and Drosophila nurse and follicle cells, among other tissues, is a variation of the normal cell cycle in which rounds of DNA replication and growth occur without intervening mitoses [6]. The key question in endocycle regulation is how the transition from the mitotic phase to the endocycle is controlled. Two signaling pathways have been identified as regulators of the mitotic-to-endocycle transition: the thrombopoetin pathway, which acts during differentiation of megakaryocytes, and the Notch pathway, which acts during Drosophila oogenesis and during the differentiation of trophoblasts [7-11,6]. Human teratocarcinomas also arise from defects in the mitotic-to-endocycle transition in trophoblasts [12]. The cell cycle targets of these pathways have remained elusive until very recently [13,14].The Notch pathway is used for cell-cell communication throughout development. The basic com
Dystroglycan and Mitochondrial Ribosomal Protein L34 Regulate Differentiation in the Drosophila Eye
Yougen Zhan,Nadia Y. Melian,Mario Pantoja,Nicola Haines,Hannele Ruohola-Baker,Charles W. Bourque,Yong Rao,Salvatore Carbonetto
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0010488
Abstract: Mutations that diminish the function of the extracellular matrix receptor Dystroglycan (DG) result in muscular dystrophies, with associated neuronal migration defects in the brain and mental retardation e.g. Muscle Eye Brain Disease. To gain insight into the function of DG in the nervous system we initiated a study to examine its contribution to development of the eye of Drosophila melanogaster. Immuno-histochemistry showed that DG is concentrated on the apical surface of photoreceptors (R) cells during specification of cell-fate in the third instar larva and is maintained at this location through early pupal stages. In point mutations that are null for DG we see abortive R cell elongation during differentiation that first appears in the pupa and results in stunted R cells in the adult. Overexpression of DG in R cells results in a small but significant increase in their size. R cell differentiation defects appear at the same stage in a deficiency line Df(2R)Dg248 that affects Dg and the neighboring mitochondrial ribosomal gene, mRpL34. In the adult, these flies have severely disrupted R cells as well as defects in the lens and ommatidia. Expression of an mRpL34 transgene rescues much of this phenotype. We conclude that DG does not affect neuronal commitment but functions R cell autonomously to regulate neuronal elongation during differentiation in the pupa. We discuss these findings in view of recent work implicating DG as a regulator of cell metabolism and its genetic interaction with mRpL34, a member of a class of mitochondrial genes essential for normal metabolic function.
Assessment of Hypoxia Inducible Factor Levels in Cancer Cell Lines upon Hypoxic Induction Using a Novel Reporter Construct
Wenyu Zhou, Timothy L. Dosey, Travis Biechele, Randall T. Moon, Marshall S. Horwitz, Hannele Ruohola-Baker
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0027460
Abstract: Hypoxia Inducible Factor (HIF) signaling pathway is important for tumor cells with limited oxygen supplies, as it is shown to be involved in the process of proliferation and angiogenesis. Given its pivotal role in cancer biology, robust assays for tracking changes in HIF expression are necessary for understanding its regulation in cancer as well as developing therapies that target HIF signaling. Here we report a novel HIF reporter construct containing tandem repeats of minimum HIF binding sites upstream of eYFP coding sequence. We show that the reporter construct has an excellent signal to background ratio and the reporter activity is HIF dependent and directly correlates with HIF protein levels. By utilizing this new construct, we assayed HIF activity levels in different cancer cell lines cultured in various degrees of hypoxia. This analysis reveals a surprising cancer cell line specific variation of HIF activity in the same level of hypoxia. We further show that in two cervical cancer cell lines, ME180 and HeLa, the different HIF activity levels observed correlate with the levels of hsp90, a cofactor that protects HIF against VHL-independent degradation. This novel HIF reporter construct serves as a tool to rapidly define HIF activity levels and therefore the therapeutic capacity of potential HIF repressors in individual cancers.
Genetic Modifier Screens Reveal New Components that Interact with the Drosophila Dystroglycan-Dystrophin Complex
Mariya M. Kucherenko, Mario Pantoja, Andriy S. Yatsenko, Halyna R. Shcherbata, Karin A. Fischer, Dariya V. Maksymiv, Yaroslava I. Chernyk, Hannele Ruohola-Baker
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0002418
Abstract: The Dystroglycan-Dystrophin (Dg-Dys) complex has a capacity to transmit information from the extracellular matrix to the cytoskeleton inside the cell. It is proposed that this interaction is under tight regulation; however the signaling/regulatory components of Dg-Dys complex remain elusive. Understanding the regulation of the complex is critical since defects in this complex cause muscular dystrophy in humans. To reveal new regulators of the Dg-Dys complex, we used a model organism Drosophila melanogaster and performed genetic interaction screens to identify modifiers of Dg and Dys mutants in Drosophila wing veins. These mutant screens revealed that the Dg-Dys complex interacts with genes involved in muscle function and components of Notch, TGF-β and EGFR signaling pathways. In addition, components of pathways that are required for cellular and/or axonal migration through cytoskeletal regulation, such as Semaphorin-Plexin, Frazzled-Netrin and Slit-Robo pathways show interactions with Dys and/or Dg. These data suggest that the Dg-Dys complex and the other pathways regulating extracellular information transfer to the cytoskeletal dynamics are more intercalated than previously thought.
The conserved WW-domain binding sites in Dystroglycan C-terminus are essential but partially redundant for Dystroglycan function
AS Yatsenko, MM Kucherenko, M Pantoja, KA Fischer, J Madeoy, W-M Deng, M Schneider, S Baumgartner, J Akey, HR Shcherbata, H Ruohola-Baker
BMC Developmental Biology , 2009, DOI: 10.1186/1471-213x-9-18
Abstract: We now find that both WW binding sites are important for maintaining full Dg function in the establishment of oocyte polarity in Drosophila. If either WW binding site is mutated, the Dg protein can still be active. However, simultaneous mutations in both WW binding sites abolish the Dg activities in both overexpression and loss-of-function oocyte polarity assays in vivo. Additionally, sequence comparisons of WW binding sites in 12 species of Drosophila, as well as in humans, reveal a high level of conservation. This preservation throughout evolution supports the idea that both WW binding sites are functionally required.Based on the obtained results we propose that the presence of the two WW binding sites in Dystroglycan secures the essential interaction between Dg and Dys and might further provide additional regulation for the cytoskeletal interactions of this complex.The Dystroglycan-Dystrophin (Dg-Dys) complex has been shown to provide cells with structural integrity by forming a conduit between the extracellular matrix and the cytoskeletal network and there are lines of evidence that implicate an additional signaling role for the complex [1,2] Dystroglycan binds to extracellular matrix components, including Laminin at its N-terminus and the actin cytoskeleton via Dystrophin at its C-terminus [3,4] Defects in these interactions can result in muscular dystrophies (MD) and various epithelial cancers [5]The characterization of the Dystrophin Glycoprotein Complex (DGC) in Drosophila has revealed that it possesses similar roles in muscle integrity and neuronal migration in flies as it does in humans [6] These abnormalities include age dependent muscle degeneration, reduced mobility, defects in eye development as manifested by altered photoreceptor axon path finding and photoreceptor morphology. Additionally, mutations in Dys and Dg affect cell polarity in Drosophila [6-8] Interestingly, some of these phenotypes are affected by the nutrition or energy metabolism in the
Examining Boundaries In Health Care - Outline Of A Method For Studying Organizational Boundaries In Interaction
Hannele Kerosuo
Outlines : Critical Practice Studies , 2004,
Abstract: The care of patients with many illnesses often appears fragmented by many boundaries in the health care system when the care is provided in several locations of primary and secondary care. In the article, boundaries are examined in an interaction between patients and multiple providers in an effort to develop collaboration in inter-organizational provision in a Change Laboratory intervention. Firstly, it will be traced how the boundaries are expressed in the interaction. Secondly, it will be studied how the boundaries expressed in the interaction relate to health care organizations and patient care practices. Thirdly, the practical activity that was embedded in the interaction between patients and providers will be focused on at the laboratory. The expression of boundaries was examined in activity theoretical terms as discursive actions. In discursive actions the ‘lived past’ becomes involved in the situational actions that orient towards future activity. The findings suggest that expressing boundaries uses various linguistic means and it seems relevant to propose that boundaries cannot be studied in a formal way; the analysis needs to be related to the organizational context of the specific study. However, the linguistic means may serve as useful “landmarks” or “pointers” of boundaries that are often expressed implicitly in the interaction. The laboratory session provides an opportunity to study boundaries “on the spot”, or “in their own right”. The realization of the emergent inter-organizational care at the session created challenges for the provision while contradicting some elements of the prevailing provision. During these kinds of interaction, the boundaries between providers became obvious. Furthermore, challenging the boundaries in the normal flow of interaction may be a potential for boundary crossing and even further, a re-constitution of boundaries. Consequently, a boundary crossing represents an interesting unit of analysis for future studies of boundaries and boundary crossing in interaction and discourse. At the laboratory setting was displayed the ability to control others through an indirect use of power that may reflect a simultaneous value system supported by the prevailing hierarchies. In the studies to come, it will be important to pay attention to these implicit power linkages when monitoring the boundaries in horizontal collaborations.
‘Boundary Encounters’ as a Place for Learning and Development at Work
Hannele Kerosuo
Outlines : Critical Practice Studies , 2001,
Abstract: Care for patients with multiple illnesses is often provided by several professionals from different parts of the health care system. In these cases, there seem to arise new demands for the communication and the cooperation between different professionals in the primary and the specialized care. In this paper, I shall describe how these challenges are met in an encounter which is a part of interventions called “Implementation Laboratories”. In these encounters, a new tool (care agreement) and a new practice (care negotiation) are introduced and elaborated in internal-medicine patient care. I conceptualized the Implementation Laboratories as “border zones” where the learning processes between different communities are intensified. Learning in the Implementation Laboratories resembles learning at the Boundary Crossing Laboratory described by Engestr m, Engestr m &V h aho (1999a; 1999b). It is interwoven into the process of analyzing problems, planning and testing of solutions in order to improve the medical patient care. Learning appears as collisions between the different perspectives of the patient and professionals of different organizations, and may sometimes lead to reconstruction of boundaries.
Educating Student Teachers to Become High Quality Professionals – A Finnish Case
Hannele Niemi
CEPS Journal : Center for Educational Policy Studies Journal , 2011,
Abstract: For decades, the Finnish orientation toward teacher education has committed itself to the development of an inquiry oriented and research-based professional culture. The aims of teacher education are to train students to find and analyse problems they may expect to face in their future work. This study consists of a survey of student teachers (n=545) in two universities in Finland. Web-based surveys with quantitative and qualitative questions were sent to all student teachers in the beginning of May 2010. Students assessed how teacher education had provided them with the competences they need in a high standard profession, what kinds of active learning experiences they had in their TE studies, and how research studies of teacher educationhad contributed to their professional development. The participants of the study assessed that they had achieved good skills in planning teaching and curricula. They were capable of using different teaching methods. They were aware of their own teaching philosophy and their responsibilities as professionals and life-long learners. They consider the research component of TE valuable to their independent and critical thinking. They were very engaged in studies. Finnish pre-service teacher education seems to function very well and to be effective in providing the skills teachers need to work as ndependent professionals. The results of the study show, however, that students also need more supervision and guidance on how to collaborate with parents and other stakeholders outside school, such as representatives of working life as well as partners in business life and culture.
FINNISH-ENGLISH PHONETICS AND PHONOLOGY
Kari Sajavaara,Hannele Dufva
International Journal of English Studies (IJES) , 2001, DOI: 10.6018/ijes.1.1.47781
Abstract: This paper first gives a summary of the theoretical approaches to the role of phonetics and phonology in language learning and teaching as developed by the Finnish-English Cross-Language Project at the University of Jyvtkkyla. In the Finnish project, the analysis was extended over the the chains of connected speech to deal with all the phenomena that give them their rhythm in speech. The project did not find it sufficient to produce simple one-to-one equations between the best structural descriptions of the two languages because many of learners' difficulties in pronunciation cannot be assigned to phoneme paradigms. The paper also includes a survey of the findings of Finnish-English contrastive phonetics and phonology, and a description of potential sources of difficulties in Finns' pronunciation of English.
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