• T-Type Calcium Current and Calcium-Induced Calcium-Release in Developing Chick Myocardium

      Kitchens, Susan A.; Department of Cellular Biology and Anatomy (2002-02)
      HYPOTHESES 1. The contribution of T-type calcium currents to the calcium transient are greater at young developmental ages, but decline with chick heart development. The decrease in contribution of T-type calcium current to the calcium transient mirrors the normal developmental reduction in magnitude of T-type current in the chick heart. 2. T-type calcium current plays a role in calcium-induced calcium-release during chick heart development. T-type current plays a significant role in the calcium-induced calcium-release process in younger embryos due to the greater magnitude of the current at earlier developmental stages. 3. More than one isoform of the T-type calcium channel is present in developing chick myocardium. The multiple isoforms will function concomitantly to provide sufficient T-type calcium current for proper development. 4. The expression of the T-type calcium channel in ventricle decreases with development. There is a concomitant decrease in T-type Ca2* current stimulation of CICR. SPECIFIC AIMS 1. To determine the contribution of T-type calcium current to the calcium transient during development in chick ventricular myocytes. The approach is to use a fluorescent calcium indicator to measure the transients from myocytes at embryonic day (ED) 5, EDI 1 andED15. 2. To determine the contribution of T-type calcium current to calcium-induced calciumrelease during chick heart development. The approach is to use pharmacological agents to quantify the contribution to the Ca3* transient from T-type Ca3* current stimulated CICR. 3. To determine which isoforms of the T-type calcium channel are likely to be present in chick myocardium. The approach is to use PCR methods to identify any T-type channel isoform mRNA expressed in chick ventricle. 4. To determine the level of expression of T-type calcium channel isoforms during the development of chick ventricle. The approach is to use molecular quantitation methods to examine the expression pattern of T-type channel isoforms in chick ventricle during development.
    • A Tailored Intervention Program for Overweight and Obese Vetrans: Who Benefits and When

      Garvin, Jane; Department of Physiological & Technological Nursing (2012-06)
      This descriptive, exploratory study examined longitudinal clinical data for variables associated with weight reduction among veterans enrolled in a weight reduction intervention, the MOVE! Program. Variables of interest included background characteristics and exposure to components of the intervention. Background, intervention, and outcome variables were organized around the Interaction Model of Client Health Behavior. In addition to the outcomes related to weight, hemoglobin A1 Thirteen percent of participants (N = 53 of 404) achieved a 5% weight reduction. Overall, the sample was primarily non-Hispanic (96%), urban (83%), Black (58.4%), married (58.4%) and male (~80%). The mean age was 56 years. Common comorbidities associated with obesity were evident including diabetes (30.2%), hypertension (60.9%), and hyperlipidemia (54.0%). The average body mass index was ~35. All available data were collected from program entry to a designated stop date; therefore, participants had unequal and irregular data points. Participants were observed repeatedly over time with 51% having 10 or more observations. A little more than half of the participants were group attendees (~56%) rather than self-managed. The majority of the intervention exposures were group rather than individual or telephone visits with providers. C, blood pressure, and serum lipid levels were examined. Achieving a 5% weight reduction was significantly associated with age in years (OR 1.04), group attendance beyond the day of orientation (OR 6.61), attendance at the holiday eating class (OR 3.67), exposure over time (measured in weeks, OR 1.02), and the interaction between time and group (OR .97). Weight reduction in pounds was significantly associated with age, baseline body mass index, total number of group classes attended, and telephone contact with the registered nurse. Using repeated measures of weight, the trajectory of weight was significantly associated with gender, baseline body mass index, and exposure to the intervention over time. Examination of additional outcomes revealed that components of the intervention were associated with beneficial changes in hemoglobin A1C, blood pressure, and serum lipid levels. Further research is needed to more fully describe successful weight reducers and the identify best practices to convert unsuccessful weight reducers to successful ones.
    • Targeting cyclic GMP signaling for the treatment of gastrointestinal diseases

      Sharman, Sarah Kristen; Department of Biochemistry and Molecular Biology / Cancer Center (2017)
      Continual renewal of the luminal epithelium in the gut is essential for the maintenance of a healthy intestine as it sustains the barrier that protects underlying tissue from infiltration of material passing through the lumen. Dysregulation of homeostatic processes involved in maintenance of the barrier have been implicated in numerous gastrointestinal diseases. The cGMP signaling axis has emerged as an important regulator of homeostasis in the intestinal mucosa, and has been implicated in the suppression of visceral pain, colitis, and colon cancer. While there is considerable interest in exploiting this pathway, until recently the approaches used to increase cGMP have been limited. The present study sought to test the hypothesis that elevation of cGMP in the intestinal epithelium using PDE5 inhibitors will alter epithelial homeostasis and be therapeutic for constipation and preventative for colon cancer. Healthy mice treated with the PDE5 inhibitor sildenafil or the GC-C agonist linaclotide exhibited reduced proliferation and apoptosis, and increased numbers of differentiated secretory cells in the intestinal epithelium. In addition to these homeostatic effects, both drugs normalized intestinal transit and fecal water content in two mouse models of constipation. Furthermore, administration of sildenafil to mice treated with dextran sulfate sodium tightened the disrupted epithelial barrier. Treatment of ApcMin/+ mice with sildenafil or linaclotide significantly reduced the number of polyps per mouse (67% and 50%, respectively). The effect of these cGMP-elevating agents was not on the polyps themselves but was rather on the pre-neoplastic tissue, which was less proliferative and more apoptotic in the presence of the drugs. Taken together, the results of this study demonstrate that increasing cGMP with a pediatric dose of PDE5 inhibitors could be a potential alternative to GC-C agonists for the treatment of gastrointestinal diseases.
    • Teachers an students' beliefs about ELLs in mainstream mathematics classrooms

      Pettit, Stacie; Department of Teacher Education (The University of Mississippi, 2013-04)
      The purpose of this study was to explore the beliefs middle school mathematics teachers have about ELLs, to identify the strategies used to help ELLs, to explore the support teachers need to teach ELLs, and understand some of the experiences of ELLs in mainstream mathematics classrooms. In addition to student and teacher interviews, 106 middle school mathematics teachers from 11 school systems completed a questionnaire. The qualitative portion of the data is presented here.
    • Teachers' beliefs about English Language Learners in Mainstream Classrooms: A Review of the Literature

      Pettit, Stacie; Department of Teacher Education (2011)
      This literature review on teachers’ beliefs about English Language Learners (ELLs) in mainstream classrooms is organized into three sections: (1) inservice teachers’ existing beliefs, (2) predictors of inservice teachers’ beliefs, and (3) the connection between inservice teachers’ beliefs and practice. This body of literature points to a clear need for increased professional development for mainstream teachers because currently, teacher education possesses a “poverty of language learning.” According to the research included in this review, a relationship exists between beliefs and practice in relation to teaching ELLs in mainstream classrooms. Certain factors, such as training in teaching ELLs, years teaching experience, and exposure to language diversity, have been identified as predictors of mainstream teachers’ beliefs about English to Speakers of Other Languages (ESOL) students. It is important for teachers who hold deficit beliefs toward ELLs to adopt a new set of beliefs for successful inclusion of ELLs.
    • Teaching with Technology

      Armstrong, Jennifer; Instructional Resource Center (2016-09)
      Fasten your seatbelts and get ready to learn! In this fast paced session participants will explore a variety of innovative tools that are useful for productivity, assessment, and classroom creativity. Ms. Armstrong is the Manager of the Instructional Resource Center at Augusta University. Jennifer is also a Google for Education Certified Innovator and Certified Trainer. Previously, she has worked in professional learning in K-12 and as a middle school math teacher. Jennifer's passion is helping teachers learn about new instructional technology tools that will encourage innovation and creativity. Jennifer provides customized professional learning to meet the needs of the individual, school, or system.
    • Techniques Used to Establish the First Person Narrator and Perspective in Double Indemnity and Murder, My Sweet

      Walton, Breana; Department of English and Foreign Languages (Augusta University Libraries, 2017-05-11)
      Directed by Billy Wilder and Edward Dmytryk respectively, the films noir Double Indemnity (1944) and Murder, My Sweet (1944) each have a storyline that unfolds from a first person perspective as told by a narrator. The techniques used in the films establish this first person perspective through which the films are understood. Both films include voice over as a technique, which determines who the narrator is and the amount of information withheld or disclosed to the audience. Establishing the visual perspective of the narrator is portrayed through differently for each film. While, Double Indemnity utilizes camera angle, Murder, My Sweet uses camera filters and special effects. Lastly, to achieve the first person narration, the character narrating in each film must be present in every scene or give explanation of events that occur in his absence. The various techniques used in each film function cohesively to establish the narrator and achieve his perspective through which the plot is understood by the audience.
    • TEE to facilitate anesthetic management during thoracotamy in a patient with severe pulmonary hypertension and pulmonary venous obstruction

      Aryal, Anuj; Mehta, Anand; Arthur, Mary E.; Castresana, Manuel R.; Medical College of Georgia; Department of Anesthesiology and Perioperative Medicine (American Society of Anesthesiologists, 2009-10)
      The lateral decubitus position, use of one-lung ventilation, and the prevention and treatment of hypoxemia continue to present challenges to the anesthesiologist, particularly in the patient with pulmonary hypertension. We describe the utility of intraoperative transesophageal echocardiography in the management of a patient with severe pulmonary hypertension and pulmonary vein stenosis undergoing thoracotomy for tissue diagnosis.
    • Telehealth Interventions to Address Chronic Disease Self-Management Interventions within the Scope of Occupational Therapy: A Scoping Review

      Albritton, Liz; Fish, joJo; Henkel, Jeff; Lee, Shelby; Luttrel, Rachel; Rackleff, Layne; Department of Occupational Therapy (Augusta University, 2020-09-02)
      At the conclusion of this presentation, attendees will: 1) Distinguish between the types of telehealth interventions for chronic disease self-management within the scope of occupational therapy and 2) Describe the outcomes of using telehealth for chronic disease self-management based on the presented results of a scoping review of the literature.
    • TGF-β Inhibition Restores Terminal Osteoblast Differentiation to Suppress Myeloma Growth

      Takeuchi, Kyoko; Abe, Masahiro; Hiasa, Masahiro; Oda, Asuka; Amou, Hiroe; Kido, Shinsuke; Harada, Takeshi; Tanaka, Osamu; Miki, Hirokazu; Nakamura, Shingen; et al. (2010-03-25)
      Background: Multiple myeloma (MM) expands almost exclusively in the bone marrow and generates devastating bone lesions, in which bone formation is impaired and osteoclastic bone resorption is enhanced. TGF-β, a potent inhibitor of terminal osteoblast (OB) differentiation, is abundantly deposited in the bone matrix, and released and activated by the enhanced bone resorption in MM. The present study was therefore undertaken to clarify the role of TGF-β and its inhibition in bone formation and tumor growth in MM.
    • That's On You, Not Me

      Miles, Edgar; Department of Communication; O'Meara, Melanie; Augusta University (2019-02-13)
      �That�s On You, Not Me� is a performance piece that was created in response to an assignment prompt for Dr. Melanie O�Meara�s Voice and Movement class in Spring 2018. The assignment was to write a haiku and perform that haiku using at least 12 individual vocal variations. Gender expression and the ways alternative expressions are received in various social contexts are existing themes in my visual art practice, so I decided to continue that exploration in my performance work for Dr. O�Meara�s class. In doing so, my performance addresses the discomfort that people experience when faced with expression that violates their expectations and whose responsibility it is to mitigate that discomfort. I present to the audience twelve individual characters created through vocal and movement variation. My intention is to open conversations about gender norms, societal expectations, the experience of �othering,� and respect for individual expression. The performance itself lasts only about three minutes, but can be followed by a brief talk about the work and a question-and-answer session.
    • The Influence of Instructional Rounds on Teacher Metacognition in a Middle School Context: A Mixed Methods Study

      Hamilton, William B; Department of Advanced Studies and Innovation (Augusta University, 2020-05)
      This study investigated, quantified, and observed metacognitive transformation in middle school ELA and math teachers through the implementation of instructional rounds as a change agent in comparison to the traditional, one-stop workshop format of professional development. A mixed method design was utilized that addressed two research questions: How is teacher metacognition impacted through professional development, and what is the difference in teacher metacognition scores after receiving traditional professional development versus instructional rounds? The results of the study suggested that teacher metacognition is positively impacted by instructional rounds and there were positive attitudes towards instructional rounds as an alternative to traditional professional development. Additionally, the qualitative data indicated that instructional rounds did have a positive impact on instructional practices and supported a progressive maturation of teacher metacognition that could be ultimately transferred to the learner. First, the results elucidated that normal teaching practice is inherently metacognitive and embodies the metacognitive knowledge tenets: person, task, and strategy. Next, teacher collaboration supports the perpetuation of a metacognitive experience, which innately lends itself to reflection. Thirdly, teacher reflection fosters metacognitive goals, thereby resulting in regulation of actions or strategies. Finally, teacher action derived from goal setting is, by definition, metacognitive action. In summary, instructional rounds appeared to be an effective form of professional development that increased and matured teacher metacognition. Keywords: Instructional rounds, metacognition, professional development, teaching practice
    • The Influence of Instructional Rounds on Teacher Metacognition in a Middle School Context: A Mixed Methods Study

      Scoggins, Katherine; Department of Advanced Studies and Innovation (Augusta University, 2020-05)
      This study investigated, quantified, and observed metacognitive transformation in middle school ELA and math teachers through the implementation of instructional rounds as a change agent in comparison to the traditional, one-stop workshop format of professional development. A mixed method design was utilized that addressed two research questions: How is teacher metacognition impacted through professional development, and what is the difference in teacher metacognition scores after receiving traditional professional development versus instructional rounds? The results of the study suggested that teacher metacognition is positively impacted by instructional rounds and there were positive attitudes towards instructional rounds as an alternative to traditional professional development. Additionally, the qualitative data indicated that instructional rounds did have a positive impact on instructional practices and supported a progressive maturation of teacher metacognition that could be ultimately transferred to the learner. First, the results elucidated that normal teaching practice is inherently metacognitive and embodies the metacognitive knowledge tenets: person, task, and strategy. Next, teacher collaboration supports the perpetuation of a metacognitive experience, which innately lends itself to reflection. Thirdly, teacher reflection fosters metacognitive goals, thereby resulting in regulation of actions or strategies. Finally, teacher action derived from goal setting is, by definition, metacognitive action. In summary, instructional rounds appeared to be an effective form of professional development that increased and matured teacher metacognition.
    • The Influence of Instructional Rounds on Teacher Metacognition in a Middle School Context: A Mixed Methods Study

      Townsend, Holly; Department of Advanced Studies and Innovation (Augusta University, 2020-05)
      This study investigated, quantified, and observed metacognitive transformation in middle school ELA and math teachers through the implementation of instructional rounds as a change agent in comparison to the traditional, one-stop workshop format of professional development. A mixed method design was utilized that addressed two research questions: How is teacher metacognition impacted through professional development, and what is the difference in teacher metacognition scores after receiving traditional professional development versus instructional rounds? The results of the study suggested that teacher metacognition is positively impacted by instructional rounds and there were positive attitudes towards instructional rounds as an alternative to traditional professional development. Additionally, the qualitative data indicated that instructional rounds did have a positive impact on instructional practices and supported a progressive maturation of teacher metacognition that could be ultimately transferred to the learner. First, the results elucidated that normal teaching practice is inherently metacognitive and embodies the metacognitive knowledge tenets: person, task, and strategy. Next, teacher collaboration supports the perpetuation of a metacognitive experience, which innately lends itself to reflection. Thirdly, teacher reflection fosters metacognitive goals, thereby resulting in regulation of actions or strategies. Finally, teacher action derived from goal setting is, by definition, metacognitive action. In summary, instructional rounds appeared to be an effective form of professional development that increased and matured teacher metacognition.
    • THE ROLE OF GPR109A IN REGULATION OF RETINAL ANGIOGENESIS AND BLOOD-RETINAL BARRIER AS A POTENTIAL THERAPEUTIC TARGET IN DIABETIC RETINOPATHY

      Abdelrahman, Ammar; Department of Biochemistry and Molecular Biology (Augusta University, 2020-12)
      Currently, treatments of diabetic retinopathy (DR) have limited therapeutic benefits and limited accessibility to the growing diabetic population at risk because of the high expenses and complicated procedures. Inflammation, endothelial dysfunction, and microvascular damage are common features of diabetic complications including DR. GPR109A is the metabolite sensing receptor of beta-hydroxybutyrate (BHB) the principal ketone body in humans. Our previous studies have shown the role of GPR109A expression in promoting anti-inflammatory response in retinal pigmented epithelial (RPE) cells and the relevance of the receptor in DR. Expression of the GPR109A in microvascular endothelial cells (ECs) has been reported recently. However, the relevance of GPR109A expression and activation to retinal EC functions are yet to be studied. Our goal in this study was to identify the role of GPR109A expression and activation in barrier and angiogenic functions of retinal ECs in context of diabetic retinopathy. We used electrical cell impedance sensing (ECIS) technology to evaluate barrier functions in primary human retinal endothelial cells (HRECs) which constitute the inner BRB. Knocking down GPR109A in HRECs with siRNA decreased the transendothelial electrical resistance (TEER) compared to scrambled siRNA. Treating HRECs with BHB increased their TEER and counteracted VEGF-induced barrier disruption through activation of GPR109A and increasing zonula occludens-1 (ZO-1) expression. Treatment of STZ-diabetic mice with exogenous BHB for one month protected against the pathologic albumin leakage induced by diabetes and improved the visual acuity of this animal model of diabetes. Using the mouse model of oxygen induced retinopathy (OIR), we showed that Gpr109a-/- mice had slower vascular recovery from pathologic angiogenesis compared to age matched wild type mice. Moreover, physiologic revascularization of vaso-oblitrated retinas was impaired by loss of GPR109a and associated with dysregulated inflammatory and angiogenic signaling. Collectively, these data point to a role for GPR109A in the regulation of barrier and angiogenic mechanisms in retinal ECs and, promote the receptor as a potential druggable target for impacting these mechanisms in microvascular retinal diseases such as DR.
    • THE ROLE OF KYNURENINE, A TRYPTOPHAN METABOLITE THAT INCREASES WITH AGE, IN MUSCLE ATROPHY AND LIPID PEROXIDATION)

      Kaiser, Helen E.; Department of Cellular Biology and Anatomy (Augusta University, 2020-05)
      Loss of mobility and independence are risk factors for falls and mortality, and drastically reduce the quality of life among older adults. The cellular and molecular mechanisms underlying loss of muscle mass and strength with age (sarcopenia) are not well-understood; however, heterochronic parabiosis experiments show that circulating factors are likely to play a role. Kynurenine (KYN) is a circulating tryptophan metabolite that is known to increase with age and is implicated in several age-related pathologies. Here I tested the hypothesis that KYN contributes directly to muscle loss with aging. Results indicate that that KYN treatment of mouse and human myoblasts increased levels of reactive oxygen species (ROS) two-fold, and significantly increased lipid peroxidation enzymes. Small-molecule inhibition of the Aryl hydrocarbon receptor (Ahr), an endogenous KYN receptor, in vitro did not prevent KYN-induced increases in ROS, and homozygous Ahr knockout in vivo did not protect mice from KYN-induced stress, suggesting that KYN can directly increase ROS independent of Ahr activation. In vivo, wild-type mice treated with KYN had reduced skeletal muscle strength, size, and increased oxidative stress and lipid peroxidation. Old wild-type mice treated with 1MT, a small molecule that suppresses KYN production by IDO1, showed an increase in muscle fiber size, peak muscle strength, and oxidative stress. Protein analysis identified mitochondrial lipid peroxidation as a downstream mechanism that is increased upon KYN treatment. Lipid peroxidation enzymes increased with KYN have been shown to produce H2O2 outside of the electron transport chain. Our data suggest that IDO inhibition may represent a novel therapeutic approach for the attenuation of sarcopenia and possibly other age-associated conditions associated with KYN accumulation such as bone loss and neurodegeneration.
    • THE ROLE OF NEDDYLATION IN EARLY CARDIAC DEVELOPMENT

      Littlejohn, Rodney; Department of Cellular Biology and Anatomy (Augusta University, 2020-07)
      Background. Early cardiac development is a tightly regulated process, involving spatiotemporal coordination of multiple signaling pathways and heterogenous cell populations, both generated de novo and externally sourced. While the roles of transcription, environmental, and epigenetic factors have all been studied extensively in the context of heart development, the roles of post-translational protein modification in regulating this process remain to be elucidated. NEDD8 (neural precursor cell expressed developmentally downregulated 8) is a novel ubiquitin-like protein modifier. Conjugation of NEDD8 to protein targets, a process termed neddylation, has been shown to regulate cell proliferation, cell signaling, and protein homeostasis, and play important roles in multiple physiological and pathological events. We have previously shown that neddylation is developmentally downregulated in the developing heart and is essential for mid-to-late gestational ventricular chamber maturation. However, whether and how neddylation regulates early cardiogenic events remains unknown. Methods and results. Mice with constitutive, cardiac progenitor cell-specific, cardiomyocyte- and vascular smooth muscle cell-specific deletion of NAE1, a regulatory subunit of the NEDD8-specific E1 activating enzyme, were created. Constitutive deletion of NAE1 led to early embryonic lethality before E9.5. Nkx2.5Cre-mediated deletion of NAE1 decreased neddylated proteins in the heart, disrupted normal cardiogenesis and resulted in embryonic lethality by embryonic day (E) 12.5 due to heart failure. Similarly, SM22αCre-driven deletion of NAE1 also caused cardiac failure and embryonic lethality by E13.5. The striking cardiac phenotypes were associated with myocardial hypoplasia, ventricular hypo-trabeculation, and pronounced endocardial and/or epicardial defects in both models. Unbiased transcriptomic analysis revealed dysregulated expression of genes associated with cardiomyocyte differentiation, proliferation, and maturation in NAE1-deficient hearts. Indeed, inhibition of neddylation disturbed cardiomyocyte proliferation, and myofibril assembly in vitro and in vivo. Moreover, defects in cardiomyocyte differentiation and maturation were linked to downregulation of Nkx2.5 and Mef2c, two key transcription factors regulating early cardiogenesis. Conclusion. Collectively, our findings demonstrate that neddylation in cardiac progenitor cells and cardiomyocytes is essential in the regulation of cardiogenesis in transgenic mouse models. Our results uncover a previously unknown role of post-translational modification in the regulation of cardiac development via potential roles in mediating cardiomyocyte proliferation, differentiation, and maturation.
    • Therapeutic Targeting of P2X7 After Traumatic Brain Injury

      Kimbler, Donald E.; Department of Neurosurgery (2012-02)
      Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Cerebral edema, the abnormal accumulation of fluid within the brain parenchyma, contributes to elevated intracranial pressure (ICP) and is a common life-threatening neurological complication following TBI. Unfortunately, neurosurgical approaches to alleviate increased ICP remain controversial and medical therapies are lacking due in part, to the absence of viable drug targets. In the present study, genetic inhibition (P2X7-/- mice) of the purinergic P2X7 receptor attenuated the expression of the pro-inflammatory cytokine, interleukin-iP (IL-ip) and reduced cerebral edema following controlled cortical impact, as compared to wild-type mice. Similarly, the clinically useful P2X7 inhibitor, brilliant blue G (BBG), inhibited the expression of IL-ip, limited edemic development and prevented the development of post-traumatic depression and anxiety. The beneficial effects of BBG were observed following either prophylactic administration via the drinking water for one week prior to injury or via an intravenous bolus administration up to four hours after TBI, suggesting a clinically-implementable therapeutic window. Notably, P2X7 localized within astrocytic end feet and administration of BBG decreased the expression of glial fibrillary acidic protein (GFAP), a reactive astrocyte marker, and reduced the expression of aquaporin-4 (AQP4), an astrocytic water channel that promotes cellular edema. Together, these data implicate P2X7 as a novel therapeutic target to prevent secondary neurological injury after TBI, a finding that warrants further investigation.
    • Therapeutic targets and limits of minocycline neuroprotection in experimental ischemic stroke.

      Matsukawa, Noriyuki; Yasuhara, Takao; Hara, Koichi; Xu, Lin; Maki, Mina; Yu, Guolong; Kaneko, Yuji; Ojika, Kosei; Hess, David C.; Borlongan, Cesar V; et al. (2009-10-19)
      BACKGROUND: Minocycline, a second-generation tetracycline with anti-inflammatory and anti-apoptotic properties, has been shown to promote therapeutic benefits in experimental stroke. However, equally compelling evidence demonstrates that the drug exerts variable and even detrimental effects in many neurological disease models. Assessment of the mechanism underlying minocycline neuroprotection should clarify the drug's clinical value in acute stroke setting. RESULTS: Here, we demonstrate that minocycline attenuates both in vitro (oxygen glucose deprivation) and in vivo (middle cerebral artery occlusion) experimentally induced ischemic deficits by direct inhibition of apoptotic-like neuronal cell death involving the anti-apoptotic Bcl-2/cytochrome c pathway. Such anti-apoptotic effect of minocycline is seen in neurons, but not apparent in astrocytes. Our data further indicate that the neuroprotection is dose-dependent, in that only low dose minocycline inhibits neuronal cell death cascades at the acute stroke phase, whereas the high dose exacerbates the ischemic injury. CONCLUSION: The present study advises our community to proceed with caution to use the minimally invasive intravenous delivery of low dose minocycline in order to afford neuroprotection that is safe for stroke.
    • Thermodynamic Properties of Protein Folding Process

      Sivised, Vattika; De Silva, Theja; Department of Chemistry & Physics (2017-03)
      Proteins are one of the fundamental building blocks of life and they are present in almost all biological and cellular processes. Proteins consist of amino acids held together in a long chain by peptide bonds. When proteins function in biological processes, they fold in to three-dimensional structures by curling the chain. The folding of a peptide chain into a three dimensional structure is a thermodynamically driven process such that the chain naturally evolves to form domains of similar amino acids. The formation of this domain occurs by curling the one dimensional amino acid sequence by moving similar amino acids proximity to each other. We model this formation of domains or “ordering of amino acids” using q-state Potts model and study the thermodynamic Properties using a statistical mechanics approach. Converting the interacting amino acids into an effectively non-interacting model using a mean-field theory, we calculate the Helmholtz free energy (HFE). Then by investigating the HFE, we qualitatively study the properties of protein folding transition. We find that the protein folding phase transition is strongly first order and the specific heat shows the experimental signatures of this phase transition.