• Identifying the Function of Nasal Embryonic LHRH factor (NELF) in Immortalized GnRH Neurons

      Ko, Eun Kyung; Department of Neuroscience and Regenerative Medicine (7/30/2018)
      Hypothalamic gonadotropin releasing hormone (GnRH) is crucial for the proper function of the hypothalamic-pituitary-gonadal (HPG) axis, puberty, and reproduction. When GnRH neuron migration or GnRH regulation is impaired, hypogonadotropic hypogonadism results. Mutations in the gene for nasal embryonic LHRH factor (NELF) have been identified in GnRH-deficient humans. NELF is a predominantly nuclear protein that may participate in gene transcription, but it is unlikely to be a transcription factor. Thus, our hypothesis is that NELF may indirectly regulate transcription via protein-protein interaction within a transcription complex. To address this question, RNA was extracted from NLT GnRH neuronal cells following either stable Nelf knockdown or scrambled control and subjected to cDNA arrays. Expression of transcription factors and cell migration gene expression was most commonly altered. Members of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, including Stat1, Stat2, Stat5a, Jak2, Irf7 and Irf9, were significantly down-regulated as assessed by RT-qPCR. Protein levels of STAT1, phospho-STAT1, and JAK2 were reduced, but the levels of phospho-JAK2 were not. These findings suggest a role for NELF in the regulation of the JAK/STAT signaling pathway, which has important functions in GnRH neurons. Jacob, the rat orthologue of NELF, is phosphorylated at the serine 180 residue by phosphorylated Erk1/2 which is activated by synaptic NMDA receptor activation and then translocates to the nucleus. Phosphorylated Jacob in the nucleus interacts with CREB and regulates the expression of BDNF, which is associated with synaptic plasticity in the brain. Proteins, such as caldendrin, importin-α and α-interxin, have been identified as binding proteins with Jacob. However, binding proteins, phosphorylation sites and/or kinases for NELF have not yet been reported. To demonstrate novel and putative functions of NELF in the nucleus, identification of binding proteins and phosphorylation sites is required. To address this question, co-immunoprecipitation (Co-IP), mass spectrometry and in vitro kinase assays were performed. We found six putative binding proteins that could interact with NELF, including 14-3-3ε. We also identified phosphorylation sites on NELF, including serine 288, which could be phosphorylated by AKT1 kinase. These new findings will be helpful to understand the function of NELF in the nucleus
    • Immediate healing responses to ceramic endosseous dental implants in dog gingiva

      Long, William Gregory; Department of Oral Biology (1990-05)
    • Immune regulation of tumor cell plasticity: A promising molecular target in breast cancer metastasis

      LEE, EUNMI; Department of Biochemistry and Molecular Biology / Cancer Center (2018-11-29)
      It is widely accepted that phenotypic plasticity of malignant cells is required during metastatic cascade. However, the specific mechanism of how the tumor microenvironment regulates tumor cell plasticity in metastasis is under intense investigation. We demonstrate here that monocytic and granulocytic subsets of myeloid-derived suppressor cells (MDSC), hereafter called mMDSCs and gMDSCs, infiltrate in the primary tumor and distant organs with different time kinetics and regulate spatiotemporal tumor plasticity. Using co-culture experiments and mouse transcriptome analyses in syngeneic mouse models, we provide evidence that tumor-infiltrating mMDSCs facilitate dissemination from the primary site by inducing the EMT/CSC phenotype. In contrast, pulmonary gMDSC infiltrates support metastatic growth by reverting the EMT/CSC phenotype and promoting tumor cell proliferation. We also observe that lung-derived gMDSCs isolated from tumor-bearing mice enhance metastatic growth of already disseminated tumor cells. Our ongoing studies reveal that calprotectin (S100A8 and S100A9 heterotetramer) is an important regulator of gMDSCs, which play a critical role in promoting breast cancer metastasis by inducing MET-like CSCs as well as suppressing anti-tumor immunity within the pre-metastatic niche. Furthermore, we develop a novel gMDSC-targeting compound that potentially binds to calprotectin and validate its therapeutic utility in a preclinical breast cancer model. Our goal for this study is to elucidate the molecular co-evolution of tumor and immune cells in cancer development and to identify molecular targets to provide alternative therapeutic options for women with metastatic disease.
    • Immune Response of Hamsters to Adenovirus

      Boudet, Robert; Department of Cell and Molecular Biology (1970-06)
    • Immunometabolic Regulation of Myeloid-Lymphoid Interactions Following Traumatic Brain Injury

      Braun, Molly; Biomedical Sciences (Augusta University, 2019-09)
      Traumatic brain injury (TBI) is a major public health issue, producing significant patient mortality and poor long-term outcomes. Increasing evidence suggests an important, yet poorly defined, role for the immune system in the development of progressive secondary injury. Herein, we tested the hypothesis that peripheral macrophage infiltration initiates long-lasting adaptive immune responses after TBI. Using a murine controlled cortical impact model, we found increased infiltration and pro-inflammatory (M1) polarization of macrophages for up to three weeks post-TBI. Monocytes purified from the injured brain stimulated the proliferation of naïve T lymphocytes, enhanced the polarization of T effector cells (Teff: TH1/TH17), and decreased the production of regulatory T cells (TREG) in a mixed lymphocyte reaction. Similarly, elevated Teff polarization within both blood and brain tissue was attenuated by myeloid cell depletion after TBI. Functionally, C3H/HeJ (TLR4 mutant) mice reversed both M1 macrophage and TH1/TH17 polarization after TBI, as compared to C3H/OuJ (wild-type) mice. Moreover, brain monocytes isolated from C3H/HeJ mice were less potent stimulators of T lymphocyte proliferation and TH1/TH17 polarization, as compared to C3H/OuJ monocytes. To further elucidate the mechanism underlying this myeloid TLR4-mediated Teff activation, we examined the metabolic regulator, 5’-adenosine monophosphate-activated protein kinase (AMPK), within infiltrating macrophages following TBI. We determined that reduced activation of myeloid AMPK induced the generation of pro-inflammatory, myelin reactive T-cells. Similarly, we detected myelin-laden macrophages within the cerebrospinal fluid of severe TBI patients. Administration of the AMPK activator, metformin, attenuated pro-inflammatory Teff cell generation and enhanced counter-inflammatory TREGs in wild-type mice; however, these effects were lost in myeloid-specific AMPKα1 knockout mice. Activation of AMPK restored myeloid expression and activity of Ten-eleven translocase 2 (TET2), a demethylase that regulated the expression of myeloid PD-L1 after TBI. Moreover, TET2-/- mice exhibited exaggerated T-cell activation in response to TBI. In line with these data, activation of myeloid AMPK reduced the loss of white matter and improved neurobehavioral outcomes after TBI. Our studies identify that immunometabolic dysfunction drives epigenetic regulation of the myeloid-lymphoid transition after TBI; suggesting targeted interventions during the early stage of injury may prevent progressive neurodegeneration.
    • Impact of Genetic Predisposition and Environmental Stress on Measures of Preclinical Essential Hypertension

      Poole, Joseph C.; Department of Cellular Biology and Anatomy (2006-06)
      The main objective of this project was to determine the impact of genetic risk and chronic environmental stress on measures of preclinical essential hypertension (EH) (e.g., exaggerated cardiovascular reactivity, increased resting hemodynamics and increased left ventricular mass [LVM]). A secondary objective was to evaluate the moderating and interactive effects of ethnicity, gender, body mass index [BMI] and anger expression on EH risk indices. Two genes with relevance for blood pressure (BP) control (e.g., beta-2 adrenergic receptor [ADRB2] gene and serotonin transporter [5-HTT] gene) were used to define genetic risk. Chronic environmental stress was assessed by socioeconomic status (SES) and subjective social status (SSS). The project consisted of three sequential studies on a large, multiethnic cohort of young adults (N>500). The first two studies were cross-sectional and based on the analysis of cardiovascular reactivity, resting hemodynamics and LVM data collected at a single visit. The third study was longitudinal and involved the tracking of BP and LVM over a 15-year span from childhood to early adulthood. In the first study, ADRB2 haplotype significantly interacted with anger suppression in African Americans such that high anger suppressing carriers had the highest resting SBP (p<.05) and TPR reactivity to a cold pressor task (p<.01). In European Americans, ADRB2 haplotype significantly interacted with BMI to predict resting hemodynamics, such that carriers who were high in BMI showed the highest SBP (p<.05). In the second study, a significant interaction between the 5-HTT promoter region polymorphism (5-HTTLPR) and social status was found for cardiovascular reactivity, such that S allele homozygotes who were low in SES and high in SSS exhibited the greatest BP and TPR reactivity to the video game stressor (p-values<.05). No significant interaction was found between 5- HTTLPR and social status in the longitudinal study, however a significant 5- HTTLPR by BMI interaction was determined for LVM, such that obese LL homozygotes had the greatest LVM over time (p<.001). Results from this project expand what is currently known with regard to EH etiology and carry implications for the prevention of EH through the early consideration of genetic, environmental and demographic risk factors.
    • Impaired Cognition in Spontaneously Hypertensive Rats: Role of Central Cholinergic Receptors

      Gattu, Mahanandeeshwar; Department of Pharmacology and Toxicology (1996-09)
      The cognitive impairment exhibited by the spontaneously hypertensive strain of rat is due to a reduction in the expression fo central cholinergic receptors. Therefore, the specific aims of this study are: 1. To determine whether the hypertensive state present in SHR contributes to impaired performance on spatial memory tasks. 2. To determine whether SHR exhibit altered expression of cholinergic receptor subtypes in brain regions important for memory function 3. To determine whether the decreased expression of central nicotinic-cholinergic receptors observed in SHR have functional significance.
    • Impaired Volume Regulation in Cardiovascular Disease in Two Distinct Populations

      Beavers, Melinda L. C.; Georgia Prevention Institute (2012-05)
      Volume dysregulation leads to congestive heart failure and death. The condition has been well-documented in both obesity-related cardiovascular disease and congenital heart disease. Our hypotheses are as follows: 1) Volume dysregulation, in the form of elevated systolic blood pressure and left ventricular mass index, is related to adiposity and aldosterone in adolescent boys but not girls. 2) Volume dysregulation, in the form of decreased nocturnal decline in blood pressure (non-dipping) is present in patients with tetralogy of Fallot, and is related to decreased left and right ventricular function. To test our first hypothesis, 100 healthy adolescents, recruited from area schools, were studied. Subjects were placed on a sodium-controlled diet for 4 days. Blood and urine samples were collected after one hour of rest. The protocol was repeated twice for each individual. Data were averaged between visits for greater statistical power. Adiposity and echocardiography measures were collected within 1 month of testing. Stepwise regression indicated that race and adiposity both contributed to the effects of aldosterone. For example, body mass index and race contributed to the model for aldosterone (Adjusted R2=0.303, p=0.002). In the aldosterone-hypertension risk relationship, stepwise regression indicated that only aldosterone contributed to the model for systolic blood pressure (Adjusted R2=0.098, p=0.023). To test our second hypothesis, 20 patients with repaired tetralogy of Fallot were recruited from clinic. Subjects completed a submaximal exercise test (modified Bruce) with echocardiography, and then wore an ambulatory blood pressure monitor for 24 hours. Of the 20 subjects with tetralogy of Fallot, 60% were 'non-dippers'. Race was significantly different between the dippers and non-dippers, with 1 of 8 African Americans being a dipper, and the remaining 7 African Americans being non-dippers (t=2.188, p=0.042). Right ventricular stroke volume (t=2.392, p=0.028) and ejection fraction (t=3.484, p=0.003) were significantly different between dippers and non-dippers. In a population of healthy adolescents with a well-distributed range of adiposity, increasing adiposity is associated with increasing aldosterone levels in boys but not girls. This is related to increasing systolic blood pressure and left ventricular mass in boys, but not in girls. These results may indicate an underlying volume dysregulation that contributes to hypertension and cardiovascular disease as a result of prolonged exposure to increased adiposity. In a population of 20 adolescents and young adults with repaired tetralogy of Fallot, nondipping is associated with decreased right ventricular stroke volume and ejection fraction, but is not associated with decreased left ventricular function. Patients with repaired tetralogy of Fallot and non-dipping may be at greater risk for failure due to the combination of pulmonary regurgitation with increased nocturnal pressures.
    • Impaired volume regulation in cardiovascular disease in two distinct populations

      Beavers, Melinda Lee Chambless; College of Gradate Studies (2012-05)
      Vohune dysregulation leads to congestive heart failure and death. The condition has been well-documented in both obesity-related cardiovascular disease and congenital heart disease. Our hypotheses are as follows: 1) Volume dysregulation, in the form of elevated systolic blood pressure and left ventricular mass index, is related to adiposity and aldosterone in adolescent boys but not girls. 2) Volume dysregulation, in the form of decreased nocturnal decline in blood pressure (non-dipping) is present in patients with tetralogy of Fallot, and is related to decreased left and right ventricular function. To test our first hypothesis, 100 healthy adolescents, recruited from area schools, were studied .. Subjects were placed on a sodium-controlled diet for 4 days. Blood and urine samples were collected after one hour of rest. The protocol was repeated twice for each individual. Data were averaged between visits for greater statistical power. Adiposity and echocardiography measures-were collected within 1 month of testing. Stepwise regression indicated that race and adiposity both contributed to the .effects of aldosterone. For example, body mass index and race contributed to the model for aldosterone (Adjusted R2=0.303, p=0.002). In the aldosterone-hypertension risk relationship, stepwise regression indicated that only aldosterone contributed to the model for systolic blood pressure (Adjusted R2=0.098, p=0.023). To test our second hypothesis, 20 patients with repaired tetralogy of Fallot were recruited from clinic. Subjects completed a submaximal exercise test (modified Bruce) with echocardiography, and then wore an ambulatory blood pressure monitor for 24 hours. Of the 20 subjects with tetralogy ofFallot, 60% were 'non-dippers'. Race was significantly different between the dippers and non-dippers, with 1 of 8 African Americans being a dipper, and the remaining 7 African Americans being non-dippers (t=2.188, p=0.042). Right ventricular stroke volume (t=2.392, p=0.028) and ejection fraction (t=3.484, p=0.003) were significantly different between dippers and non-dippers. In a population of healthy adolescents with a well-distributed range of adiposity, increasing adiposity is associated with increasing aldosterone levels in boys but not girls. This is related to increasing systolic blood pressure and left ventricular mass in boys, but not in girls. These results may indicate an underlying volume dysregulation that contributes to hypertension and cardiovascular disease as a result of prolonged exposure to increased adiposity. In a population of 20 adolescents and young adults with repaired tetralogy of Fallot, nondipping- is associated with decreased right ventricular stroke volume and ejection fraction, but is not associated with decreased left ventricular function. Patients with repaired tetralogy of Fallot and non-dipping may be at greater risk for failure due to the combination of pulmonary regurgitation with increased nocturnal pressures.
    • The Implementation of Controlled Physical Training and the Physiological Effects of Exercise in Women with Sickle Cell Disease

      Ramsey, Leigh-Taylor; Department of Physiology (1999-12)
      Sickle cell disease (SCD) comprises a group of genetic disorders of hemoglobin that affect more than 70,000 Americans and is associated with increased morbidity and health care cost (1). W ith improved medical management, individuals with SCD are now surviving well into adulthood. However, adults with SCD are often sedentary and because of medical conservatism are frequently discouraged from exercise fo r fear of precipitating acute vasoocclusive or painful episodes. A review of the literature revealed little baseline data on perceived health status and well-being, physical fitness (cardiovascular and muscular), and body composition in adults with SCD. It is currently unknown whether exercise or physical training (PT) will have beneficial, adverse, or no effect in SCD patients. As a result, exercise recommendations for adults with SCD are vague, and implementation and effectiveness of PT have not been reported. Moreover, there are no reports on the effects of controlled PT on perceived health status, physical fitness, and body composition parameters in patients with SCD. The effect of exercise on inflammatory mediators (i.e., tum or necrosis factor-alpha [TNF-a], interleukin - 6 [IL-6], and C-reactive protein [CRP]) and vasoactive mediators (i.e., nitric oxide metabolites [NOx] and endothelin-1 [ET-1]) has not been reported in patients with sickle cell anemia (SCA). Since changes in these parameters may influence the occurrence of vasoocclusive episodes by increasing adhesion of erythrocytes to the endothelium and by other mechanisms, such as vasoconstriction, it is important to clarify changes that may occur with exercise. Physical training holds the promise of allowing patients with SCD to preserve functional capacity and improve their quality of life, as has been reported for other chronic diseases. Yet, there are no repotted studies assessing the implementation and effectiveness of PT in adults with SCD. The study reported in this thesis provides new information concerning the impact of controlled PT on fitness and well-being in women with SCD. It also provides new information on the effects of three consecutive days of exercise, which might be used in a standard PT program. This project is a first step in the assessment of the role of regular exercise for SCD patients.
    • Implications based on these results support the need for critical care nurses to use caution to avoid overestimating parental stress. Parents should be included in care of the child whenever possible,· and recognized for their uniqu~ ability to parent their child, even when critically ill.

      Sanders, Cindy L.; School of Nursing (1993-03)
      Th~ admission of a child to the PICU is stressful t6 parents of that child. Critical care nurses caring f~r these critically ill children and their families are in a unique position to assess parental str~ss. The purpose of this st~dy was to compare nurses' (n=30) and parents• (n=30) perceptions of· parental strassors in the PICU, as,measured by scores 6n the Parental Str~ssor s6ale: Pediatric Intensive Care· (PSS: PICU) developed by Miles and Carter (1982). Differences between parents 1 and nurses' mean scores on the total PSS:PICU and each of seven dimertsibnai scores were analyzed using paired t-tests. Significantly higher scores were found for nurses in bo€h total PSS:PICU and four of seven sub,scales. Analysis of mean scores between mothers and fath~rs, nurses who ~ere afid were n6t parants, arid nurses wfth less than ·five and greater than fi'(e year-s PICU experience showed ·no significant differences. Parents who experienced unplanned PICU admissions scored signiticantly _higher than parents whose child's admission was planned on the dimension of child's appearance. Implications based on these results support the need for critical care nurses to use caution to avoid overestimating parental stress. Parents should be included in care of the child whenever possible,· and recognized for their uniqu~ ability to parent their child, even when critically ill.
    • Improving the efficacy of hormonal therapy in MCF-7 breast cancer cells grown in the presence of IGF-I by targeting the MAPK/MEK and JAK/STAT cell survival signaling pathways

      Welborn, April Eve; School of Graduate Studies (2007-04)
      Breast cancer is the leading cause of cancer and the second leading cause of cancer deaths in women in the United States. Approximately 30% of estrogen receptor positive breast cancers are inherently resistant to anti-estrogen therapy and the recurrence of breast cancer in women initially responsive ~o anti-estrogen treatment frequently occurs. Thus, new approaches to increase the efficacy of hormonal. therapy are needed. · Because epidemiological studies associate high IGF-I levels with a poor prognosis .for breast cancer patients, we inves.tigated the underlying mechanism(s) of IGF~l-mediated · protection. 4-Hydroxytamoxifen-and mifepristone-induced cell death is significantly attenuated by IGF-I. IGF-I induction of cell survival pathways was analyzed focusing on signaling pathways and it has been demonstrated that IGF-I-mediated protection ofMCF- 7 cells resulted_from activation of the MAPK/MEK and JAK/STAT signaling pathways. · Cell lifting and P ARP cleavage was · detected in tamoxifen-and m~fepristone-treated MCF-7 cells growing in the presence of IGF-I and PD98059, a MEK inhibitor and also in the presence of IGF-I and AG490, a JAK2 inhibitor. The amount of cleaved P ARP i:°MCF- 7 cells transfected with MEKl siRNA is higher in cells treated with estradiq\ 3/-~ne than with hormonal therapy. The MEKlsiRNA may cause growth arrest, interfering with the actions of the hormonal therapy. The degree of death caused by hormonal therapy in the absence and presence of IGF-I is similar indicating that MEKl has a role in the protection of MCF-7 cells from hormonal therapy-induced cell death Transfection of MCF-7 cells with dominant-negative JAK2 resulted in increased cell death. The JAK/STAT pathway appears to ·be an important pathway for the survival of breast cancer cells because even in the absence of hormonal therapy, as was evident by the death of the MCF-7 cells with the dominant-negative JAK2 constructs. Higher levels ?f PARP cleavage are present in MCF-7 cells transfected with JAK2siRNA. These pre-clinical in vitro studies provide a mechanistic rationale to why high circulating levels ·()~IGF~I may seriously impact the progression of breast cancer and its response to hormonal tlierap~1 • and why the efficacy of hormonal therapy of breast cancer can be significantly improved · by simultaneously targeting these signaling pathway.
    • In search of genetic mutations for familial keratoconus

      Khaled, Mariam Lotfy; Department of Cellular Biology and Anatomy (Augusta University, 2019-05)
      Keratoconus (KC) is the most common corneal degenerative disorder and a leading cause of corneal transplantation in developed countries. KC is a multi-factorial disease with involvement of genetic, environmental, and hormonal factors. Although KC has been widely studied, the main cause of the disease and the molecular mechanism remain unknown. We aimed to study the molecular genetics of KC via utilizing next-generation sequencing technology including RNA-Seq, whole exome sequencing, and whole genome sequencing. We used RNA-Seq to study the KC-affected corneal transcriptome. We identified 436 coding RNAs and 584 lncRNAs with differential expression in the KC-affected corneas with a |fold change| ≥ 2 and a false discovery rate ≤ 0.05. Pathway analysis, using WebGestalt, indicated the enrichment of the genes involved in the extracellular matrix, protein binding, glycosaminoglycan binding, and cell migration. Co-expression analysis revealed 296 pairs of genes with significant KC-specific correlations. The RNA-Seq data analysis highlighted the potential roles of several genes (CTGF, SFRP1, AQP5, lnc-WNT4-2:1, and lnc-ALDH3A2-2:1) and pathways (TGF-β, WNT signaling, and PI3K/AKT pathways) in KC pathogenesis. Next, we used whole genome and exome sequencing to figure out the causal mutation(s) in a four-generation KC family with a linkage locus on Chr5q14.3-q21.1. We found a missense mutation in the phosphatase domain of PPIP5K2 (c.1255T>G, p.Ser419Ala). We found another missense mutation in the same domain of PPIP5K2 (c.2528A>G, p.Asn843Ser) in a second KC family. PPIP5K2 is a bifunctional enzyme involved in the inositol phosphate metabolic pathway. In vitro functional assays indicated the impact of the identified mutations on the enzymatic activity of PPIP5K2. PPIP5K2 expresses at a higher level than its homolog PPIP5K1 in both human and mouse corneas. A transgenic mouse model with the loss of phosphatase activity and elevated kinase activity of Ppip5k2 exhibited corneal structural abnormalities emphasizing the important role of PPIP5K2 in the homeostasis of corneal integrity. This study advances our knowledge of KC genetic etiology and helps in identifying a potential therapeutic target for KC.
    • IN VITRO AND IN VIVO STUDIES DEMONSTRATE A ROLE FOR SH3PX1 IN LAMELLIPODIA FORMATION.

      Hicks, Lawrence Joseph; Department of Cellular Biology and Anatomy (5/22/2018)
      Actin remodeling and endocytosis are essential functions for most cells. Defects in these processes present in a variety of diseases. Sorting nexins are known to contribute to endocytic uptake, cytokinesis, the retromer complex, and autophagy. Sorting nexin 9 (Snx9) interacts with major endocytic factors and proteins involved in regulation of actin cytoskeleton dynamics. Nonetheless, Snx9’s exact in vivo roles in these basic cellular processes and disease mechanisms are not known. By examining the roles of Sh3px1, we can better understand the mechanism by which this protein contributes to endocytosis and actin remodeling in vivo. Two additional paralogs, Snx18 and Snx33, complicate studies in mammalian models due to potential redundant mechanisms. Utilizing the single ortholog in Drosophila, sh3px1, this report describes the function of Sh3px1 in membrane organization and actin dynamics. Drosophila S2 cells that are depleted of Sh3px1 fail to form lamellipodia, a process that is also dependent on the actin nucleation factor, Scar. In addition, over-expression of Sh3px1 in S2 cells results in the formation of tubules and also long membrane protrusions, atypical of a classical BAR domain protein. An intact PX-BAR domain is required for these overexpression phenotypes. sh3px1 null flies are viable; however, mutant females have significantly compromised fertility. Female sh3px1 null egg chambers show many morphological defects. The age-dependent degeneration of the null egg chamber is not likely due to compromised endocytosis. Additionally, collective border cell migration is attenuated in the absence of Sh3px1. These cells are known for their reliance on endocytosis and modulation of actin dynamics for migration. We have found that Sh3px1 is essential in efficient lamellipodia production at the start of border cell migration. Our findings also suggest that Scar directly interacts with Sh3px1 and is upregulated in sh3px1 nulls. Mutation of Scar enhances many reproductive defects in sh3px1 nulls. Thus, our work reveals a main in vivo function of Sh3px1 in actin regulation for the production of structures such as lamellipodia.
    • In Vitro mechanical Analysis of Full-Arch Mandibular Implant-Supported, Complete Fixed Prosthesis Retainer Screws After Cyclic Loading

      Sananez, Andreina J.; Department of Oral Biology (2012-04)
      The use of implant-retained and supported prostheses has become a very successful treatment for completely edentulous patients. One of the most common fixed solutions involving implants consists of 5 to 7 implants supporting a framework upon which either porcelain or prefabricated acrylic resin denture teeth are added. A screw is utilized to attach the framework/prosthesis to the implants. Screw loosening is the second most common clinical complication in the implant-prosthesis system. If clinicians fail to detect worn or loose retaining screws, prosthetic fracture could occur, leading to more complicated, time consuming, and expensive repairs. Unfortunately, there is no established parameter that indicates when to expect these complications, and there is no proven recall-maintenance protocol to prevent them. The aim of this study is to examine and compare differences among de-torque values and prosthetic retention screws, using a simulated 5 implant-supported, mandibular complete fixed prosthesis. Material and Methods: Nine groups, each with its respective control, using five Nobel Biocare implants and a milled titanium framework were fabricated, assembled and tested. Dynamic loading was p on the performed tested groups through a custom made loading device for anterior, posterior, and distal cantilevered segments of the prosthesis, calculated to simulate clinical usage time. Removal of screws after 2 years of simulated oral function was performed. Before and after testing, screws were evaluated with a Scanning Electronic Microscope (SEM), for presence of debris, thread striations and homogeneity. Control groups remained unloaded for the same time the loaded groups were tested. Results: Comparisons of the difference between initial tightening torque and de-torque screw values were performed between loaded/unloaded groups and with respect to implant position. The interaction between loaded and position was significant (p=0.002). The comparison between loaded/unloaded groups was not statistically significant (p=0.518). Loaded and unloaded groups were compared separately at each of the 5 implants position, which showed a significant difference (p=0.0002, α=0.001). The sequencing effect was only seen in the control groups and thus would only be relative to framework insertion. The sequence effect was found to be overcome by from loading and resulted in a totally different position related to screw tightness. Within the limitations of this in vitro study, it was concluded that sequence of torque application could play a role in the preload of screws even with a passive fit, regardless the load applied.
    • In vitro metabolism of cortisol and cortisone by guinea pig kidney tissue

      Ellegood, James o.; Department of Endocrinology (1963-06)