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Search Results: 1 - 10 of 228875 matches for " Jennifer R. Gatchel "
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Lithium Therapy Improves Neurological Function and Hippocampal Dendritic Arborization in a Spinocerebellar Ataxia Type 1 Mouse Model
Kei Watase,Jennifer R Gatchel,Yaling Sun,Effat Emamian,Richard Atkinson,Ronald Richman,Hidehiro Mizusawa,Harry T Orr,Chad Shaw,Huda Y Zoghbi
PLOS Medicine , 2007, DOI: 10.1371/journal.pmed.0040182
Abstract: Background Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disorder characterized by progressive motor and cognitive dysfunction. Caused by an expanded polyglutamine tract in ataxin 1 (ATXN1), SCA1 pathogenesis involves a multifactorial process that likely begins with misfolding of ATXN1, which has functional consequences on its interactions, leading to transcriptional dysregulation. Because lithium has been shown to exert neuroprotective effects in a variety of conditions, possibly by affecting gene expression, we tested the efficacy of lithium treatment in a knock-in mouse model of SCA1 (Sca1154Q/2Q mice) that replicates many features of the human disease. Methods and Findings Sca1154Q/2Q mice and their wild-type littermates were fed either regular chow or chow that contained 0.2% lithium carbonate. Dietary lithium carbonate supplementation resulted in improvement of motor coordination, learning, and memory in Sca1154Q/2Q mice. Importantly, motor improvement was seen when treatment was initiated both presymptomatically and after symptom onset. Neuropathologically, lithium treatment attenuated the reduction of dendritic branching in mutant hippocampal pyramidal neurons. We also report that lithium treatment restored the levels of isoprenylcysteine carboxyl methyltransferase (Icmt; alternatively, Pccmt), down-regulation of which is an early marker of mutant ATXN1 toxicity. Conclusions The effect of lithium on a marker altered early in the course of SCA1 pathogenesis, coupled with its positive effect on multiple behavioral measures and hippocampal neuropathology in an authentic disease model, make it an excellent candidate treatment for human SCA1 patients.
Pharmacometabolomic Signature of Ataxia SCA1 Mouse Model and Lithium Effects
Bertrand Perroud, Paymaan Jafar-Nejad, William R. Wikoff, Jennifer R. Gatchel, Lu Wang, Dinesh K. Barupal, Juan Crespo-Barreto, Oliver Fiehn, Huda Y. Zoghbi, Rima Kaddurah-Daouk
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0070610
Abstract: We have shown that lithium treatment improves motor coordination in a spinocerebellar ataxia type 1 (SCA1) disease mouse model (Sca1154Q/+). To learn more about disease pathogenesis and molecular contributions to the neuroprotective effects of lithium, we investigated metabolomic profiles of cerebellar tissue and plasma from SCA1-model treated and untreated mice. Metabolomic analyses of wild-type and Sca1154Q/+ mice, with and without lithium treatment, were performed using gas chromatography time-of-flight mass spectrometry and BinBase mass spectral annotations. We detected 416 metabolites, of which 130 were identified. We observed specific metabolic perturbations in Sca1154Q/+ mice and major effects of lithium on metabolism, centrally and peripherally. Compared to wild-type, Sca1154Q/+ cerebella metabolic profile revealed changes in glucose, lipids, and metabolites of the tricarboxylic acid cycle and purines. Fewer metabolic differences were noted in Sca1154Q/+ mouse plasma versus wild-type. In both genotypes, the major lithium responses in cerebellum involved energy metabolism, purines, unsaturated free fatty acids, and aromatic and sulphur-containing amino acids. The largest metabolic difference with lithium was a 10-fold increase in ascorbate levels in wild-type cerebella (p<0.002), with lower threonate levels, a major ascorbate catabolite. In contrast, Sca1154Q/+ mice that received lithium showed no elevated cerebellar ascorbate levels. Our data emphasize that lithium regulates a variety of metabolic pathways, including purine, oxidative stress and energy production pathways. The purine metabolite level, reduced in the Sca1154Q/+ mice and restored upon lithium treatment, might relate to lithium neuroprotective properties.
Neural correlates of focused attention in cognitively normal older adults  [PDF]
Jennifer R. Bowes, Patrick Stroman, Angeles Garcia
World Journal of Neuroscience (WJNS) , 2011, DOI: 10.4236/wjns.2011.12003
Abstract: Focused attention (FA) is among the cognitive functions that decline with aging. The Stroop task was used to investigate the neural correlates underlying FA in cognitively normal older adults. Twenty-one participants underwent a novel functional magnetic resonance imaging (fMRI) verbal Stroop task paradigm. Colour words were printed in an incongruent ink colour. Series 1 consisted of four blocks “Read the word” followed by four blocks “Say the colour of the ink”; Series 2 alternated between the two conditions. Functional data were analyzed using SPM5 to detect anatomical areas with significant signal intensity differences between the conditions. Within-group analyses of the “Say the colour of the ink” minus “Read the word” contrast yielded significant activation in the left supplementary motor area, bilateral inferior frontal gyrus, bilateral precentral gyrus, left insula and right superior frontal gyrus (p < 0.05, uncorrected). These results, using verbal responses, are consistent with previous manual modality Stroop-fMRI studies in older adults. Verbal responses may provide a more suitable modality for older adults and certain patient populations.
Neural correlates of focused attention in patients with mild Alzheimer’s disease  [PDF]
Jennifer R. Bowes, Patrick Stroman, Angeles Garcia
World Journal of Neuroscience (WJNS) , 2012, DOI: 10.4236/wjns.2012.24034
Abstract: Alzheimer’s Disease (AD) is characterized by an early and significant memory impairment, and progresses to affect other cognitive domains. Impairments in Focused Attention (FA) have been observed in patients diagnosed with mild AD. A functional magnetic resonance imaging (fMRI) Stroop paradigm with verbal responses was used to investigate the neural correlates of FA in AD patients. Twenty-one patients diagnosed with mild AD performed a verbal Stroop—fMRI paradigm. Colour words were printed in an incongruent ink colour. Series 1 consisted of four blocks “Read the word” followed by four blocks “Say the colour of the ink”; Series 2 alternated between the two conditions. Functional data were analyzed using SPM5 to detect anatomical areas with significant signal intensity differences between the conditions. Within-group analyses of the colour minus word contrast yielded significant activation in the following left hemisphere regions: precentral gyrus, inferior frontal gyrus, fusiform gyrus and supplementary motor area (p < 0.05, uncorrected). Relative to cognitively normal older adults who underwent the same experimental task, Stroop performance was significantly worse in AD patients. The fMRI task yielded similar activated brain regions between the two groups. The use of verbal responses in this novel fMRI Stroop task avoids the confusion and memorizing of button locations seen with the manual response modality, allowing the neural correlates of FA to be investigated in AD patients.
Fostering critical thinking skills: a strategy for enhancing evidence based wellness care
Jennifer R Jamison
Chiropractic & Manual Therapies , 2005, DOI: 10.1186/1746-1340-13-19
Abstract: This paper describes a unit which prepares chiropractic students for the role of "wellness coaches". Emphasis is placed on providing students with exercises in critical thinking in an effort to prepare them for the challenge of interfacing with an increasingly evidence based health care system.This case study describes how health may be promoted and disease prevented through development of personalized wellness programs. As critical thinking is essential to the provision of evidence based wellness care, diverse learning opportunities for developing and refining critical thinking skills have been created. Three of the learning opportunities are an intrinsic component of the subject and, taken together, contributed over 50% of the final grade of the unit. They include a literature review, developing a client wellness contract and peer evaluation. In addition to these 3 compulsory exercises, students were also given an opportunity to develop their critical appraisal skills by undertaking voluntary self- and unit evaluation. Several opportunities for informal self-appraisal were offered in a structured self-study guide, while unit appraisal was undertaken by means of a questionnaire and group discussion at which the Head of School was present.Formal assessment showed all students capable of preparing a wellness program consistent with current thinking in contemporary health care. The small group of students who appraised the unit seemed to value the diversity of learning experiences provided. Opportunities for voluntary unit and self-appraisal were used to varying degrees.Unit evaluation provided useful feedback that led to substantial changes in unit structure.Students have demonstrated themselves capable of applying critical thinking in construction of evidence based wellness programs. With respect to unit design, selective use of learning opportunities highlighted the desirability of using obligatory learning opportunities to ensure exposure to core constructs while
Rule Making and Rule Breaking: Game Development and the Governance of Emergent Behaviour
Jennifer R. Whitson
Fibreculture Journal , 2010,
Abstract: Discussions of ‘control’ in games often center on players and their myriad attempts to push back upon the systems that seek to constrain them. The fact that players resist the constraints imposed upon them is not surprising, nor is it surprising that counterplay and control are such rich topics for game studies academics. In this article, I argue that players are invited by games to bend the rules. It is in the very nature of play to find the movement between the rules, and for many players the ‘fun’ in play is the inherent challenge of attempting to master, defeat, or remake games’ formal structures. These rationalities of play preclude blind obedience to the rules and have distinct implications for how games are governed. While there have been numerous studies of players who bend or break the rules (Consalvo, 2007; Foo and Koivisto, 2004; Dibbell, 1998; Kolko and Reid, 1998; Williams, 2006; Mnookin, 1997) and players who alter and re-make the rules in their role of co-producers (Sotamaa, 2009; Kücklich, 2005; Humphreys, 2005; Taylor, 2006b), there is little research on game development companies and their attempts to harness these rationalities of play and uphold the rules beyond the reflexive writings of game designers themselves (Curtis, 1992; Morningstar and Farmer, 1991; Koster, 2002).
Jucys-Murphy Elements and a Combinatorial Proof of an Identity of S. Kerov
Jennifer R. Galovich
Mathematics , 2010,
Abstract: Consider the elements of the group algebra CS_{n} given by R_{j}=Sigma_{i=1}^{j-1}(ij), for 2<=j<=n. Jucys [3 - 5] and Murphy[7] showed that these elements act diagonally on elements of S_{n} and gave explicit formulas for the diagonal entries. As requested by the late S. Kerov, we give a combinatorial proof of this work in case j=n and present several similar results which arise from these combinatorial methods.
The Separate Development of Children’s Listener and Speaker Behavior and the Intercept as Behavioral Metamorphosis  [PDF]
R. Douglas Greer, Peter Pohl, Lin Du, Jennifer Lee Moschella
Journal of Behavioral and Brain Science (JBBS) , 2017, DOI: 10.4236/jbbs.2017.713045
Abstract: The study of verbal behavior focuses on communicative functions of the speakers/producers as they affect the behavior of listeners/observers. Effects on the listener reinforce the speaker and the listener/observer benefits (i.e., is reinforced) from the behavior of the speaker/producer. The interlocking of, and exchange of, the speaker and listener behavior between individuals and within one’s own skin constitute bidirectional operants. These bidirectional operants are instances of social interactions and measures of social behavior. Evidence suggests that the act of listening, among other observing responses, is initially developmentally independent from speaker behavior. How they become joined parallels the biological phenomenon of metamorphosis. The succession of changes has been empirically identified as a succession of verbal behavior development cusps, which are described in their sequence biologically as a manifestation of functional metamorphosis. The onset of a cusp constitutes first instances of behavior and accompanying stimulus control that allows infants and children to contact parts of the environment for the first time resulting in their learning things impossible to learn before or learning faster. Cusps for the intercept of the speaker and listener lead to bidirectional operants and provide explanations for how children incidentally learn the names of things, become increasingly social, and make subsequent complex behavior possible. Many of the cusps identified in our research resulted from the missing behavior and stimulus control of children with autism. Once cusps were established, these children learned things they could not learn before, learned faster, and learned by contacting parts of the social environment they could not contact before. These findings led to a theory of verbal behavior development that point to the selection of bidirectional operants as behavioral phenotypes during functional metamorphosis, which has enhanced the survival of Homo sapiens through emergent symbolic skills for more effective collaboration between two or more individuals.
Cryopreservation of Mammalian Oocyte for Conservation of Animal Genetics
Jennifer R. Prentice,Muhammad Anzar
Veterinary Medicine International , 2011, DOI: 10.4061/2011/146405
Abstract: The preservation of the female portion of livestock genetics has become an international priority; however, in situ conservation strategies are extremely expensive. Therefore, efforts are increasingly focusing on the development of a reliable cryopreservation method for oocytes, in order to establish ova banks. Slow freezing, a common method for cryopreservation of oocytes, causes osmotic shock (solution effect) and intracellular ice crystallization leading to cell damage. Vitrification is an alternative method for cryopreservation in which cells are exposed to a higher concentration of cryoprotectants and frozen with an ultra rapid freezing velocity, resulting in an ice crystal free, solid glass-like structure. Presently, vitrification is a popular method for cryopreservation of embryos. However, vitrification of oocytes is still challenging due to their complex structure and sensitivity to chilling. 1. Introduction Many domestic breeds of livestock are experiencing a gradual diminishment of genetic diversity; therefore, it is in the interest of the international community to conserve the livestock genetics. Ideally populations are saved as live animals; however, this approach is expensive, and unless the breed can be used for production, it is not likely to succeed. Therefore, ex situ in vitro conservation strategies are developed to cryopreserve animal genetic resources in genome/gene banks to regenerate a particular population in future [1, 2]. Although significant progress has been made in both semen and embryo cryopreservation of several domestic species, oocytes are extremely sensitive to chilling, and to date a standardized procedure has not been established. Long-term storage of oocytes would develop of ova banks, permitting female genetic material to be stored unfertilized until an appropriate male germplasm is selected. Successful cryopreservation of oocytes would also preserve the genetic material from unexpectedly dead animals and facilitate many assisted reproductive technologies [3–5]. 2. Loss of Farm Animal Genetic Diversity In the last few decades, farm animal genetic diversity has rapidly declined, mainly due to changing market demands and intensification of agriculture. Agriculture is moving away from small production systems to large commercial systems, and as a result, selection goals and production environments are now very similar throughout the world. Modern reproductive technologies have allowed a large number of progeny to be produced from a single individual,and contemporary transport has enabled the distribution of germplasm
Social participation and healthy ageing: a neglected, significant protective factor for chronic non communicable conditions
Wendy R Holmes, Jennifer Joseph
Globalization and Health , 2011, DOI: 10.1186/1744-8603-7-43
Abstract: Current international policy initiatives to address the increasing prevalence of non-communicable chronic diseases are focused on cardiovascular disease, diabetes, respiratory disease and cancers, responsible for much premature mortality. Interventions to modify their shared risk factors of high salt and fat diets, inactivity, smoking and alcohol use are advocated. But older people also suffer chronic conditions that primarily affect quality of life, and have a wider range of risk factors. There is strong epidemiological and physiological evidence that social isolation, in particular, is as important a risk factor for chronic diseases as the 'lifestyle' risk factors, yet it is currently neglected. There are useful experiences of inexpensive and sustainable strategies to improve social participation among older people in low and lower middle income countries. Our experience with forming Elders' Clubs with retired tea estate workers in Sri Lanka suggests many benefits, including social support and participation, inter-generational contact, a collective voice, and facilitated access to health promotion activities, and to health care and social welfare services.Policies to address the increase in chronic non-communicable diseases should include consideration of healthy ageing, conditions that affect quality of life, and strategies to increase social participation. There are useful examples showing that it is feasible to catalyse the formation of Elders' Clubs or older people's associations which become self-sustaining, promote social participation, and improve health and well-being of elders and their families.Governments and the World Health Organization have recognised the huge burden of preventable disease, disability, death and distress caused by the non communicable diseases (NCDs). Advocacy by the World Health Organization has recently pushed NCDs up the international health agenda. In September 2011 world leaders discussed the Prevention and Control of NCDs at th
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