Dermatan sulfate reduces monocyte chemoattractant protein 1 and TGF-β production, as well as macrophage recruitment and myofibroblast accumulation in mice with unilateral ureteral obstruction

Selectins play an essential role in most inflammatory reactions, mediating the initial leukocyte-rolling event on activated endothelium. Heparin and dermatan sulfate (DS) bind and block P- and L-selectin function in vitro. Recently, we reported that subcutaneous administration of DS inhibits colon inflammation in rats by reducing macrophage and T-cell recruitment and macrophage activation. In the present study, we examined the effect of porcine intestinal mucosa DS on renal inflammation and fibrosis in mice after unilateral ureteral obstruction (UUO). Twenty-four adult male Swiss mice weighing 20-25 g were divided into 4 groups: group C (N = 6) was not subjected to any surgical manipulation; group SH (N = 6) was subjected to surgical manipulation but without ureter ligation; group UUO (N = 6) was subjected to unilateral ureteral obstruction and received no treatment; group UUO plus DS (N = 6) was subjected to UUO and received DS (4 mg/kg) subcutaneously daily for 14 days. An immunoblot study was also performed for TGF-β. Collagen (stained area ~3700 µm²), MCP-1 (stained area ~1700 µm²), TGF-β (stained area ~13% of total area), macrophage (number of cells ~40), and myofibroblast (stained area ~1900 µm²) levels were significantly (P < 0.05) higher in the UUO group compared to control. DS treatment significantly (P < 0.05) reduced the content of collagen (stained area ~700 µm²), MCP-1 (stained area ~160 µm²) and TGF-β (stained area ~5% of total area), in addition to myofibroblast (stained area ~190 µm²) and macrophage (number of cells ~32) accumulation in the obstructed kidney. Overall, these results indicate that DS attenuates kidney inflammation by reducing macrophage recruitment, myofibroblast population and fibrosis in mice submitted to UUO.

Myocardial ischemic preconditioning upregulated protein 1(Mipu1):zinc finger protein 667 - a multifunctional KRAB/C2H2 zinc finger protein

Myocardial ischemic preconditioning upregulated protein 1 (Mipu1) is a newly discovered upregulated gene produced in rats during the myocardial ischemic preconditioning process. Mipu1 cDNA contains a 1824-base pair open reading frame and encodes a 608 amino acid protein with an N-terminal Krüppel-associated box (KRAB) domain and classical zinc finger C2H2 motifs in the C-terminus. Mipu1 protein is located in the cell nucleus. Recent studies found that Mipu1 has a protective effect on the ischemia-reperfusion injury of heart, brain, and other organs. As a nuclear factor, Mipu1 may perform its protective function through directly transcribing and repressing the expression of proapoptotic genes to repress cell apoptosis. In addition, Mipu1 also plays an important role in regulating the gene expression of downstream inflammatory mediators by inhibiting the activation of activator protein-1 and serum response element.

Sphingosine-1-phosphate-evoked invasion of follicular thyroid cancer cells : evidence for the involvement of HIF-Iα, MMP2 and MMP9

Sphingolipids are widely expressed molecules, which traditionally were considered to have majorly structural properties. Nowadays, however, they are implicated in a wide range of different biological processes. The bioactive lipid sphingosine 1-phosphate (S1P) has emerged during the past decade as one of the most studied molecules due to its proliferative and pro-migratory abilities both during normal physiology and in the pathology of a subset of different diseases. Migration and invasion of cancer cells require changes in cell behavior and modulation of the tissue microenvironment. Tumor aggressiveness is markedly enhanced by hypoxia, in which hypoxia inducible transcription factors 1-2α (HIF-1-2α) are activated to promote metabolism, proliferation and migration. Invasion requires degradation of the extracellular matrix (ECM) achieved by several degrading and remodeling enzymes. Matrix metalloproteinases (MMPs) are broadly expressed and well accepted as proteolytic enzymes with essential roles both in normal physiology and in pathology. Previously, S1P was shown to strongly evoke migration of follicular ML-1 thyroid cancer cells. The objective of this study was to further investigate and understand the mechanisms behind this regulation. In the first project it was demonstrated that S1P enhances the expression and activity of HIF-1α. S1P enhanced the expression of HIF-1α by increasing its synthesis and stability. The S1P-increased HIF-1α was mediated via S1P3, Gi/0, PI3K, PKCβI, ERK1/2, mTOR and translation factors p70S6K and eIF4E. Finally, it was shown that HIF-1α mediated S1P-induced migration. The ECM is constituted of a complex and coordinated assembly of many types of proteins. In order to be able to invade, cells need to break down the ECM, therefore several key players in this event were investigated in the second project. S1P increased the secretion and activity of MMP2 and MMP9 via S1P-receptor 1 and 3 and that these MMPs participated in the S1P-facilitated invasion of ML-1 cells. In this interplay, calpains and Rac1 were involved, both of which are crucial players in migration and invasion. The prognosis for some types of thyroid cancer is relatively good. However, there are forms of thyroid cancers, for which there are no treatments or the current available treatments are inefficient. Thus, new medical interventions are urgently needed. In the third project the significance of the S1P-receptor modulating drug FTY720, which is currently used for the treatment of multiple sclerosis (MS), was studied. The effect of FTY720 was tested on several thyroid cancer cell lines, and it inhibited the proliferation and invasion of all cancer cell lines tested. In ML-1 cells, FTY720 attenuated invasion by blocking signaling intermediates important for migration and invasion of the cells. Moreover, FTY720 inhibited the proliferation of ML-1 cells by increasing the expression of p21 and p27, hence, inducing cell arrest in G1 phase of the cell cycle. Thus, it can be suggested that FTY720 could be used in the treatment of thyroid cancer.

Language-specific aspects of reading acquisition: the case of Russian

We have investigated Russian children’s reading acquisition during an intermediate period in their development: after literacy onset, but before they have acquired well-developed decoding skills. The results of our study suggest that Russian first graders rely primarily on phonemes and syllables as reading grain-size units. Phonemic awareness seems to have reached the metalinguistic level more rapidly than syllabic awareness after the onset of reading instruction, the reversal which is typical for the initial stages of formal reading instruction creating external demand for phonemic awareness. Another reason might be the inherent instability of syllabic boundaries in Russian. We have shown that body-coda is a more natural representation of subsyllabic structure in Russian than onset-rime. We also found that Russian children displayed variability of syllable onset and offset decisions which can be attributed to the lack of congruence between syllabic and morphemic word division in Russian. We suggest that fuzziness of syllable boundary decisions is a sign of the transitional nature of this stage in the reading development and it indicates progress towards an awareness of morphologically determined closed syllables. Our study also showed that orthographic complexity exerts an influence on reading in Russian from the very start of reading acquisition. Besides, we found that Russian first graders experience fluency difficulties in reading orthographically simple words and nonwords of two and more syllables. The transition from monosyllabic to bisyllabic lexical items constitutes a certain threshold, for which the syllabic structure seemed to be of no difference. When we compared the outcomes of the Russian children with the ones produced by speakers of other languages, we discovered that in the tasks which could be performed with the help of alphabetic recoding Russian children’s accuracy was comparable to that of children learning to read in relatively shallow orthographies. In tasks where this approach works only partially, Russian children demonstrated accuracy results similar to those in deeper orthographies. This pattern of moderate results in accuracy and excellent performance in terms of reaction times is an indication that children apply phonological recoding as their dominant strategy to various reading tasks and are only beginning to develop suitable multiple strategies in dealing with orthographically complex material. The development of these strategies is not completed during Grade 1 and the shift towards diversification of strategies apparently continues in Grade 2.

Form(s)-of-life: agamben's reading of Wittgenstein and the potential uses of a notion

Giorgio Agamben and Ludwig Wittgenstein seem to have very little in common: the former is concerned with traditional ontological issues while the latter was interested in logics and ordinary language, avoiding metaphysical issues as something we cannot speak about. However, both share a crucial notion for their philosophical projects: form of life. In this paper, I try to show that, despite their different approaches and goals, form of life is for both a crucial notion for thinking ethics and life in-common. Addressing human existence in its constitutive relation to language, this notion deconstructs traditional dichotomies like bios and zoé, the cultural and the biological, enabling both authors to think of a life which cannot be separated from its forms, recognizing the commonality of logos as the specific trait of human existence. Through an analogical reading between both theoretical frameworks, I suggest that the notion of form-of-life, elaborated by Wittgenstein to address human production of meaning, becomes the key notion in Agamben's affirmative thinking since it enables us to consider the common ontologically in its relation to Human potentialities and to foresee a new, common use of the world and ourselves.

Exploring the use of prediction and summarization to increase students' listening and reading comprehension /

This study examined the effect of expHcitly instructing students to use a repertoire of reading comprehension strategies. Specifically, this study examined whether providing students with a "predictive story-frame" which combined the use of prediction and summarization strategies improved their reading comprehension relative to providing students with generic instruction on prediction and summarization. Results were examined in terms of instructional condition and reading ability. Students from 2 grade 4 classes participated in this study. The reading component of the Canadian Achievement Tests, Second Edition (CAT/2) was used to identify students as either "average or above average" or "below average" readers. Students received either strategic predication and summarization instruction (story-frame) or generic prediction and summarization instruction (notepad). Students were provided with new but comparable stories for each session. For both groups, the researcher modelled the strategic tools and provided guided practice, independent practice, and independent reading sessions. Comprehension was measured with an immediate and 1-week delayed comprehension test for each of the 4 stories, hi addition, students participated in a 1- week delayed interview, where they were asked to retell the story and to answer questions about the central elements (character, setting, problem, solution, beginning, middle, and ending events) of each story. There were significant differences, with medium to large effect sizes, in comprehension and recall scores as a fimction of both instructional condition and reading ability. Students in the story-frame condition outperformed students in the notepad condition, and average to above average readers performed better than below average readers. Students in the story-frame condition outperformed students in the notepad condition on the comprehension tests and on the oral retellings when teacher modelling and guidance were present. In the cued recall sessions, students in the story-frame instructional condition recalled more correct information and generated fewer errors than students in the notepad condition. Average to above average readers performed better than below average readers across comprehension and retelling measures. The majority of students in both instructional conditions reported that they would use their strategic tool again.

On affirmation and becoming : a Deleuzian reading of Nietzsche's critique of nihilism

The main thrust of this thesis is the re-exploration of Friedrich Nietzsche's "critique of nihilism" through the lenses of Gilles Deleuze. A Deleuzian reading of Nietzsche is motivated by a post-deconstrnctive style of interpretation, inasmuch as Deleuze goes beyond, or in between, henneneutics and deconstrnction. Deleuze's post-deconstrnctive reading of Nietzsche is, however, only secondary to the main aim of this thesis. The primary thrust of this study is the critique of a way of thinking characterized by Nietzsche as nihilistic. Therefore, it should be noted that this study is not about Deleuze's reading per se; rather, it is an appraisal of Nietzsche's "critique of nihilism" using Deleuze's experimental reading. We will accrue Nietzsche's critique and Deleuze's post-deconstrnctive reading in order to appraise Nietzsche's critique itself. Insofar as we have underscored Deleuze's purported experimentation of Nietzschean themes, this study is also an experiment in itself. Through this experimentation, we will find out whether it is possible to partly gloss Nietzsche's critique of nihilism through Deleuzian phraseology. Far from presenting a mere exposition of Nietzsche's text, we are, rather, re-reading, that is, re-evaluating Nietzsche's critique of nihilism through Deleuze's experimentation. This is our way of thinking with Nietzsche. Nihilism is the central problem upon which Nietzsche's philosophical musings are directed; he deems nihilism as a cultural experience and, as such, a phenomenon to be reckoned with. In our reconstruction of Nietzsche's critique of nihilism, we locate two related elements which constitute the structure of the prescription of a cure, Le., the ethics of affirmation and the ontology of becoming. Appraising Nietzsche's ethics and ontology amounts to clarifying what Deleuze thinks as the movement from the "dogmatic image of thought" to the "new image of thought." Through this new image of thought, Deleuze makes sense of a Nietzschean counterculture which is a perspective that resists traditional or representational metaphysics. Deleuze takes the reversal of Platonism or the transmutation of values to be the point of departure. We have to, according to Deleuze, abandon our old image of the world in order to free ourselves from the obscurantism of foundationalist or essentialist thinking. It is only through the transmutation of values that we can make sense of Nietzsche's ethics of affirmation and ontology of becoming. We have to think of Nietzsche's ethics as an "ethics" and not a moral philosophy, and we have to think of his ontology as 1/ ontology" and not as metaphysics. Through Deleuze, we are able to avoid reading Nietzsche as a moral philosopher and metaphysician. Rather, we are able to read Nietzsche as one espousing an ethical imperative through the thought of the eternal return and one advocating a theory of existence based on an immanent, as opposed to transcendent, image of the world.

Deviance of syntax in oral languages and oral reading behavior

The major hypothesis of this paper is that any deviance in syntax present in oral language will be evident in oral r eading behaviour. Using Lee and Canter's Developmental i 1 Sentence Scoring technique (1971) and Y. Goodman and Burke's Reading Miscue Inventory (1972) linguistic competence was established in t hree male children. ages 10 to 11. patterns of strengths and weaknesses in reading were determined. and the relationships t hat were established, were examined. Results of the study i ndicate that oral language behaviour is closely tied to oral r eading behaviour. This type of approach can be used as a basis for a diagnosis of a reading difficulty and then a prescription for language and reading skills.

The effect of motor-encoding activities on memory and performance in a grade one reading program

This study examined the effectiveness of motor-encoding activities on memory and performance of students in a Grade One reading program. There were two experiments in the study. Experiment 1 replicated a study by Eli Saltz and David Dixon (1982). The effect of motoric enactment (Le., pretend play) of sentences on memory for the sentences was investigated. Forty Grade One students performed a "memory-for-sentences" technique, devised by Saltz and Dixon. Only the experimental group used motoric enactment of the sentences. Although quantitative findings revealed no significant difference between the mean scores of the experimental group versus the control group, aspects of the experimental design could have affected the results. It was suggested that Saltz and Dixon's study could be replicated again, with more attention given to variables such as population size, nature of the test sentences, subjects' previous educational experience and conditions related to the testing environment. The second experiment was an application of Saltz and Dixon's theory that motoric imagery should facilitate memory for sentences. The intent was to apply this theory to Grade One students' ability to remember words from their reading program. An experimental gym program was developed using kinesthetic activities to reinforce the skills of the classroom reading program. The same subject group was used in Experiment 2. It was hypothesized that the subjects who experienced the experimental gym program would show greater signs of progress in reading ability, as evidenced by their scores on Form G of the Woodcock Reading Mastery Test--Revised. The data from the WRM--R were analyzed with a 3-way split-plot analysis of variance in which group (experimental vs. control) and sex were the between subjects variables and test-time (pre-test vs. post-test) was the within-subjects variable. Findings revealed the following: (a) both groups made substantial gains over time on the visual-auditory learning sub-test and the triple action of group x sex x time also was significant; (b) children in the experimental and control groups performed similarly on both the pre- and post-test of the letter identification test; (c) time was the only significant effect on subjects' performance on the word identification task; (d) work attack scores showed marked improvement in performance over time for both the experimenta+ and control groups; (e) passage comprehension scores indicated an improvement in performance for both groups over time. Similar to Experiment 1, it is suggested that several modifications in the experimental design could produce significant results. These factors are addressed with suggestions for further research in the area of active learning; more specifically, the effect of motor-encoding activities on memory and academic performance of children.

Pausing at the river's edge : a narrative inquiry into the practice of a reading teacher /

In this narrative self-study I retell and connect the stories ofmy personal journey with literacy from childhood to the present. I use narrative as both methodology and method as I story my life experiences and my personal encounters with literacy. The heart ofmy reflections comes from the pages of personal journals written and storied over many years of trying to make meaning of powerful literacy experiences in my life. Now, in going back through the stories and reconstructing meaning, I make connections between the memories along the journey and the place from which I now tell my story. The interpretations I construct give voice to beliefs 1 have lived by and illuminations to moments in time that I have come to see with new eyes as I have engaged in this inquiry. The journey and self-reflection within the pages of this inquiry provide understanding of the driving force behind my personal passion for literacy. I am better able to understand my motivations and share the stories that validate my personal and professional path through time.

The role of daytime napping in sleepiness and cognitive function in 24-70 year olds /

Daytime napping improves well-being and performance for young adults. The benefits of napping in older adults should be investigated because they have fragmented nocturnal sleep, cognitive declines, and more opportunity to nap. In addition, experience with napping might influence the benefits of napping. Study 1 examined the role of experience with napping in young adults. Habitual (n = 23) and non-habitual nappers (n = 16) were randomly assigned to a 20-minute nap or a 20- minute reading condition. Both groups slept the same according to macro architecture. However, microarchitecture showed greater theta, alpha, and beta power during Stage 1, and greater delta, alpha, and sigma power during Stage 2 for habitual nappers, for the most part indicating better sleep. Both groups felt less sleepy after the nap. P2 latency, reflecting information processing, decreased after the nap for habitual nappers, and after the control condition for non-habitual nappers. In sum, both groups who slept felt better, but only the habitual nappers who napped gained a benefit in terms of information processing. Based on this outcome, experience with napping was investigated in Study 2. Study 2 examined the extent to which daytime napping enhanced cognition in older adults, especially frontal lobe function. Cognitive deficits in older adults may be due to sleep loss and age-related decline in brain functioning. Longer naps were expected to provide greater improvement, particularly for older adults, by reducing sleep pressure. Thirty-two adults, aged 24-70 years, participated in a repeated measures dose-response manipulation of sleep pressure. Twenty- and sixty-minute naps were compared to a no-nap condition in three age groups. Mood, subjective sleepiness, reaction time, working memory, 11 novelty detection, and waking electro physiological measures were taken before and after each condition. EEG was also recorded during each nap or rest condition. Napping reduced subjective sleepiness, improved working memory (serial addition / subtraction task), and improved attention (reduced P2 amplitude). Physiological sleepiness (i.e., waking theta power) increased following the control condition, and decreased after the longer nap. Increased beta power after the short nap, and seen with older adults overall, may have reflected increased mental effort. Older adults had longer latencies and smaller amplitudes for several event-related potential components, and higher beta and gamma power. Following the longer nap, gamma power decreased for older adults, but increased for young adults. Beta and gamma power may represent enhanced alertness or mental effort. In addition, Nl amplitude showed that benefits depend on the preceding nap length as well as age. Since the middle group had smaller Nl amplitudes following the short nap and rest condition, it is possible that they needed a longer nap to maintain alertness. Older adults did not show improvements to Nl amplitude following any condition; they may have needed a nap longer than 60 minutes to gain benefits to attention or early information processing. Sleep characteristics were not related to benefits of napping. Experience with napping was also investigated. Subjective data confirmed habitual nappers were happier to nap, while non-habitual nappers were happier to stay awake, reflecting self-identified napping habits. Non-habitual nappers were sleepier after a nap, and had faster brain activity (i.e., heightened vigilance) at sleep onset. These reasons may explain why non-habitual nappers choose not to nap.

Orientation of Non-Native 2-Monosubstituted and 2,3-Disubstituted 1,4-Naphthoquinones in the A1 binding site of PSI and the effect on the rate of electron transfer : an electron paramagnetic resonance spectroscopy study

The proce-ss ofoxygenic photosynthesis is vital to life on Earth. the central event in photosynthesis is light induced electron transfer that converts light into energy for growth. Ofparticular significance is the membrane bound multisubunit protein known as Photosystem I (PSI). PSI is a reaction centre that is responsible for the transfer of electrons across the membrane to reduce NADP+ to NADPH. The recent publication ofa high resolution X-ray structure of PSI has shown new information about the structure, in particular the electron transfer cofactors, which allows us to study it in more detail. In PSI, the secondary acceptor is crucial for forward electron transfer. In this thesis, the effect of removing the native acceptor phylloquinone and replacing it with a series of structurally related quinones was investigated via transient electron paramagnetic resonance (EPR) experiments. The orientation of non native quinones in the binding site and their ability to function in the electron transfer process was determined. It was found that PSI will readily accept alkyl naphthoquinones and anthraquinone. Q band EPR experiments revealed that the non-native quinones are incorporated into the binding site with the same orientation of the headgroup as in the native system. X band EPR spectra and deuteration experiments indicate that monosubstituted naphthoquinones are bound to the Al site with their side group in the position occupied by the methyl group in native PSI (meta to the hydrogen bonded carbonyl oxygen). X band EPR experiments show that 2, 3- disubstituted methyl naphthoquinones are also incorporated into the Al site in the same orientation as phylloquinone, even with the presence of a halogen- or sulfur-containing side chain in the position normally occupied by the phytyl tail ofphylloquinone. The exception to this is 2-bromo-3-methyl --.- _. -. - -- - - 4 _._ _ _ - _ _ naphthoquinone which has a poorly resolved spectrum, making determination of the orientation difficuh. All of the non-native quinones studied act as efficient electron acceptors. However, forward electron transfer past the quinone could only be demonstrated for anthraquinone, which has a more negative midpoint potential than phylloquinone. In the case of anthraquinone, an increased rate of forward electron transfer compared to native PSI was found. From these results we can conclude that the rate ofelectron transfer from Al to Fx in native PSI lies in the normal region ofthe Marcus Curve.

The impact of a digital children's literature program on primary students' reading motivation

This qualitative study stemmed from a concern of the perceived decline in students' reading motivation after the early years of schooling, which has been attributed to the disconnect between the media students are accustomed to using outside the classroom and the media they predominantly use within the classroom. This research documented the effectiveness of a digital children's literature program and a postreading multimedia program on eight grade 1 students' reading motivation, word recognition, and comprehension abilities. Eight students were given ten 25-minute sessions with the software program over 15 weeks. Preprogram, interim-program, and postprogram qualitative data were collected from students, teachers, and parents through questionnaires, interviews, standardized reading assessment tools, classroom observations, field notes, and student behaviour observation checklists. Findings are summarized into 3 themes. The motivational aspects and constructivist styles of instruction in the digital reading programs may have contributed to 5 student participants' increased participation in online storybook reading at home. Qualitative data revealed that the digital children's literature program and multimedia postreading activities seemed to have a positive influence on the majority of grade 1 student participants' reading motivation, word recognition, and listening comprehension skills. These findings suggest the promise of multimedia and Internet-based reading software programs in supporting students with reading andlor behavioural difficulties. In keeping with current educational initiatives and efforts, increased use of media literacy practices in the grade 1 curriculum is suggested.

Major Sport Event Operational Planning Issues and Strategies: A Multi-Case Delphi Study

This study examined the operational planning, implementation and execution issues of major sport events, as well as the mitigation and management strategies used to address these issues, with the aim of determining best practices in sport event operational planning. The three Research Questions were: 1) What can previous major sport events provide to guide the operational management of future events? 2) What are the operational issues that arise in the planning and execution of a major sport event, how are they mitigated and what are the strategies used to deal with these issues? 3) What are the best practices for sport event operational planning and how can these practices aid future events? Data collection involved a modified Delphi technique that consisted of one round of in-depth interviews followed by two rounds of questionnaires. Both data collection and analysis were guided by an adaptation of the work of Parent, Rouillard & Leopkey (2011) with a focus on previously established issue and strategy categories. The results provided a list of Top 26 Prominent Issues and Top 17 Prominent Strategies with additional issue-strategy links that can be used to aid event managers producing future major sport events. The following issue categories emerged as having had the highest impact on previous major sport events that participants had managed: timing, funding and knowledge management. In addition, participants used strategies from the following categories most frequently: other, formalized agreements and communication.