A study of the regulatory role of retinoic acid receptor gamma in Zebrafish development

Retinoic acid (RA) is thought to signal through retinoic acid receptors (RARs), i.e. RARα, β, and γ to play important roles in embryonic development and tissue regeneration. In this thesis, the zebrafish (Danio rario) was used as a vertebrate model organism to examine the role of RARγ. Treatment of zebrafish embryos with a RARγ specific agonist reduced the axial length of developing embryos, associated with reduced somite number and loss of hoxb13a expression. There were no clear alterations in hoxc11a or myoD expression. Treatment with the RARγ agonist disrupted the formation of anterior structures of the head, the cranial bones and the anterior lateral line ganglia, associated with a loss of sox9 immunopositive cells in the same regions. Pectoral fin outgrowth was blocked by treatment with the RARγ agonist; however, this was not associated with loss of tbx5a immunopositive lateral plate cells and was reversed by wash out of the RARγ agonist or co-treatment with a RARγ antagonist. Regeneration of the transected caudal fin was also blocked by RARγ agonist treatment and restored by agonist washout or antagonist co-treatment; this phenotype was associated with a localised reduction in canonical Wnt signalling. Conversely, elevated canonical Wnt signalling after RARγ treatment was seen in other tissues, including ectopically in the notochord. Furthermore, some phenotypes seen in the RARγ treated embryos were present in mutant zebrafish embryos in which canonical Wnt signalling was constitutively increased. These data suggest that RARγ plays an essential role in maintaining neural crest and mesodermal stem/progenitor cells during normal embryonic development and tissue regeneration when the receptor is in its non-ligated state. In addition, this work has provided evidence that the activation status of RARγ may regulate hoxb13a gene expression and canonical Wnt signalling. Further research is required to confirm such novel regulatory roles

Control System for 3D Printable Robotic Hand

Humanoid robotics is a growing area of research due to its potential applications in orthosis and prosthesis for human beings. With the currently available technologies, the most advanced robotic hands used in prosthetics or robotics can cost from $11,000 to$90,000, making it inaccessible to the general population of amputees and robotics hobbyists. Most of the features provided by these expensive technologies are superfluous to many users, creating a great gap in cost and services between users and technology. Using the emerging 3D printing technology, my project is to construct a 3D printed robotic hand that can reproduce as many basic functionalities of the advanced expensive hands, while minimizing the cost. The project involves choosing a feasible 3D printed design plan, assembly of the mechanical and electrical components of the robotic hand, the design and implementation of the software interface for intuitive user control of the hand and ease of integrability to existing robotic systems. This new hand will allow mimicking, versatile gripping, human-recognizable gestures, feedback controlled force exertion, and a ROS integrated software interface. This project will further allow students at Union to extend their research in social robotics and human-computer interface by incorporating the inexpensive robotic han

Efforts towards the Asymmetric de novo Synthesis of Lanostanes and Euphanes

Tetracyclic triterpenoids are ubiquitous in nature and biology, with members displaying a wide range of medically relevant properties and occupying rather distinct regions of chemical space. Members of this large class include well-known steroid hormones and sterols as well as structurally interesting subclasses such as lanostanes and euphanes, among others. Comprised of the tetracyclic skeleton with three stereodefined quaternary centers at ring-junction positions, lanostanes and euphanes present synthetic challenges that are different from those encountered in efforts targeting the structurally less complex steroid hormones. Lanostanes, in particular, stand as a historically important class of compounds as significant attention has been directed at understanding the biosynthesis of lanosterol, the primary precursor to cholesterol, for the past 50 years. Though studies in this area have led to the development of new reaction methods and synthesis strategies, lanostanes and the structurally related euphanes continue to stand as challenges for asymmetric de novo synthesis. This thesis work describes progress towards the asymmetric total syntheses of lucidadone H, a hexanorlanostane natural product, and euphol, a euphane natural product. While the chemical technology that is central to both syntheses features metallacycle-mediated annulative cross-coupling, diastereoselective Friedel–Crafts cyclization and oxidative dearomatization/Wagner–Meerwein rearrangement to establish a functionalized tetracyclic intermediate, my efforts resulted in a concise synthesis of hexanorlanostanes, and an asymmetric approach to a C14-desmethyl euphane system, which was identified to be a novel modulator of the Liver X Receptor

Effect of Body Positions on Lungs Volume in Asthmatic Patients: A Cross-sectional Study

Aim: The purpose of our research was to investigate the effect of different body positions on lungs volume by conducting pulmonary function test (PFT) values of the asthmatic patients. The objectives were (1) to assess the correlation between pulmonary function and posture in adult patients with asthma, (2) to determine the best position with higher lungs volume that was preferable for the asthmatic patients to relieve the asthma attack and for rehabilitation approach. Study Design: Cross-sectional study. Place and Duration of Study: This study was conducted in the Reconstructive and Rehabilitative Center at University Malaysia Sarawak (UNIMAS) between December 2015 and June 2016. Methodology: The total of 30 participants was recruited in this study. Among them, 15 participants were asthmatic patients and 15 participants were non-asthmatic, control persons. All theparticipants were between 19-25 years of age and they were enrolled after they had signed a written consent. Participants were selected using the inclusion criteria and Spiro Excel PC based pulmonary function test (PFT Medicaid Systems) were administered. Spirometer measurements (FVC, FEV1) were taken in the standing, sitting and supine positions. Each measurement was taken two times and the average values were analyzed. The order of the body positions was randomized. Results: In the asthmatic group, the best position was supine with a mean±standard deviation (SD) of FEV1/FVC, 77.93±17.37. Whereas, in control group, the best position was standing with a mean±SD of FEV1/FVC, 90.12±5.97. The second best positions were sitting position in the asthmatic group (75.37±16.37) and supine position in control group (89.70±8.79). Finally, the standing position had the lowest lungs function in the asthmatic group (73.63±17.08) and sitting position in control group (88.53±11.17). Conclusion: Our study showed that supine was the best position for measuring FEV1 and FVC of asthmatic participants. Therefore, supportive positions such as supine or leaning to the wall are suggested to improve pulmonary function of the patients, especially during asthmatic attack

The Development and Growth of Tissues Derived From Cranial Neural Crest and Primitive Mesoderm Is Dependent on the Ligation Status of Retinoic Acid Receptor γ: Evidence That Retinoic Acid Receptor γ Functions to Maintain stem/progenitor Cells in the Absence of Retinoic Acid

An important study demonstrating how retinoic acid receptor gamma plays a key role in tissue formation and regenerationFinal publication is available from Mary Ann Liebert, Inc., publishers http://dx.doi.org/10.1089/scd.2014.0235Retinoic acid (RA) signaling is important to normal development. However, the function of the different RA receptors (RARs)--RARα, RARβ, and RARγ--is as yet unclear. We have used wild-type and transgenic zebrafish to examine the role of RARγ. Treatment of zebrafish embryos with an RARγ-specific agonist reduced somite formation and axial length, which was associated with a loss of hoxb13a expression and less-clear alterations in hoxc11a or myoD expression. Treatment with the RARγ agonist also disrupted formation of tissues arising from cranial neural crest, including cranial bones and anterior neural ganglia. There was a loss of Sox 9-immunopositive neural crest stem/progenitor cells in the same anterior regions. Pectoral fin outgrowth was blocked by RARγ agonist treatment. However, there was no loss of Tbx-5-immunopositive lateral plate mesodermal stem/progenitor cells and the block was reversed by agonist washout or by cotreatment with an RARγ antagonist. Regeneration of the caudal fin was also blocked by RARγ agonist treatment, which was associated with a loss of canonical Wnt signaling. This regenerative response was restored by agonist washout or cotreatment with the RARγ antagonist. These findings suggest that RARγ plays an essential role in maintaining stem/progenitor cells during embryonic development and tissue regeneration when the receptor is in its nonligated state

Randomized controlled trial of probiotics and vitamin B3 on gut microbiome and quality of life in people with Parkinson's disease

Doctor of PhilosophyDepartment of Food, Nutrition, Dietetics and HealthMajor Professor Not ListedEvidence suggests that administration of probiotics and vitamin B3 may improve multiple symptoms and outcomes of Parkinson’s Disease through alterations in gut microbiome. Therefore, the purpose of this dissertation is to determine whether a 12-week placebo-controlled randomized clinical trial is able to observe changes in constipation, drug efficacy, neuroendocrine levels, and indicators of quality of life in people with Parkinson’s disease. Methodology: A total of 54 people enrolled for this study, six were either excluded and/or did not meet inclusion criteria. Forty-eight participants were randomly assigned into three groups to receive: 1) probiotics + vitamin B3; 2) probiotics + vitamin B3 placebo; or, 3) the placebos for the probiotic and vitamin B3 for 12 weeks. Constipation, depression, anxiety, quality of life, mood, diet, and nutrition were assessed at the baseline, middle, and end of the supplementation period. Blood and stool samples were collected for blood chemistry and microbiome analyses, respectively. Next-generation sequencing of 16S rRNA genes (Illumina MiSeq) was used for gut microbiota analysis. Within-group and between-group differences were statistically analyzed, with significance set at p<0.05. Results: The results showed improvements in constipation problems, quality-of-life scores, Movement Disorder Society- the Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Parkinson’s Disease Questionnaire-39 (PDQ-39), decreased issues with communication via the PDQ-39 in probiotics and vitamin B3 groups compared to the placebo group. Blood chemistry were within normal reference ranges. Supplementation did not change assessments of anxiety, depression, or mood. Gut microbiome analyses indicated significant differences in alpha and beta diversity, salient gut microbiome composition relating to different interventions, disease status, anxiety, and depression. Conclusion: Probiotics and vitamin B3 supplementation was beneficial for constipation symptoms, gut microbiome, and quality of life in these patients. Vitamin B3 appeared to have a more stabilizing effect on the gut microbiome. Several differences were greater after 12 weeks compared with 6 weeks of the intervention. This appears to support that the duration of supplementation is greater than 6 weeks for most of the assessed outcome measures. For quality of life and mood measures, an increased duration of study and/or larger sample size may be necessary to detect differences

Is lifestyle modification effective for glycemic control among type II diabetic adults in Southeast Asia?

Master of Public HealthHuman NutritionRichard R. RosenkranzBackground: Type 2 diabetes mellitus (T2DM) is a costly and burdensome lifelong disease, and without proper glycemic control, severe life-threatening complications result. In Southeast Asia, the prevalence of T2DM is forecast to increase markedly from 2000 to 2030. Although literature reviews on lifestyle modification for glycemic control are available, these are mainly for the Western context, and there is a dearth of evidence for Southeast Asians who are at greater risk of T2DM and have differing patterns of diet, physical activity and body composition than Western populations. Objective: To systematically review literature on the effectiveness of lifestyle modification interventions for glycemic control in T2DM patients from Southeast Asia. Methods: Randomized controlled trials (RCT) with interventions ≥ 8 weeks that compared HbA1c or blood glucose for intervention (lifestyle modification) versus control groups were identified from searches in Cochrane Library, CINAHL, PubMed, ProQuest, Science Direct, SPORTDiscus, Scopus and Web of Science. Results: Seven RCTs (679 participants) meeting inclusion and exclusion criteria were identified. There was a significant reduction in HbA1c% (MD = -0.56%; 95% CI = -0.95,-0.16%; p = 0.006; n = 5 studies) and in blood glucose mg/dl (MD = -16.76 mg/dl; 95% CI = -31.36, -2.17 mg/dl; p = 0.02; n = 4 studies) over 3 months for lifestyle modification intervention groups. Lifestyle interventions included diet (n = 2), exercise (n = 2), and general lifestyle interventions (n = 3). Duration of interventions ranged from 12 weeks to 6 months. Studies included populations from Thailand (n = 5) and Malaysia (n = 2). Conclusion: Overall, lifestyle modification interventions are effective for the glycemic control of T2DM patients in countries of Southeast Asia

Gestational diabetes mellitus prevalence in Maela refugee camp on the Thai–Myanmar Border: a clinical report

Background: Individuals in conflict-affected areas rarely get appropriate care for chronic or non-infectious diseases. The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide, and new evidence shows conclusively that the negative effects of hyperglycemia occur even at mild glucose elevations and that these negative effects can be attenuated by treatment. Scientific literature on gestational diabetes in refugee camp settings is critically limited. Methods: A 75 g 2-hour glucose tolerance test was administered to 228 women attending the antenatal care (ANC) clinic in Maela refugee camp on the Thai–Myanmar border. Prevalence of GDM was determined using the HAPO trial cut-offs [≥92 mg/dL (fasting),≥180 (1 hour), and≥153 (2 hour)] and the WHO criteria [≥126 mg/dL (fasting), and 140 mg/dL (2 hour)]. Results: From July 2011 to March 2012, the prevalence of GDM was 10.1% [95% confidence interval (CI): 6.2–14.0] when the cut-off determined by the HAPO trial was applied. Applying the older WHO criteria yielded a prevalence of 6.6% (95% CI 3.3–9.8). Age, parity, and BMI emerged as characteristics that may be significantly associated with GDM in this population. Other risk factors that are commonly used in screening guidelines were not applicable in this diabetes-naïve population. Discussion: The prevalence of GDM is lower in this population compared with other populations, but still complicates 10% of pregnancies. New evidence regarding gestational diabetes raises new dilemmas for healthcare providers in resource-poor settings. Efforts to identify and treat patients at risk for adverse outcomes need to be balanced with awareness of the risks and burdens associated with over diagnosis and unnecessary interventions. Screening approaches based on risk factors or using higher cut-off values may help minimize this burden and identify those most likely to benefit from intervention

Blood RNA analysis can increase clinical diagnostic rate and resolve variants of uncertain significance

Purpose: Diagnosis of genetic disorders is hampered by large numbers of variants of uncertain significance (VUSs) identified through next-generation sequencing. Many such variants may disrupt normal RNA splicing. We examined effects on splicing of a large cohort of clinically identified variants and compared performance of bioinformatic splicing prediction tools commonly used in diagnostic laboratories. Methods: Two hundred fifty-seven variants (coding and noncoding) were referred for analysis across three laboratories. Blood RNA samples underwent targeted reverse transcription polymerase chain reaction (RT-PCR) analysis with Sanger sequencing of PCR products and agarose gel electrophoresis. Seventeen samples also underwent transcriptome-wide RNA sequencing with targeted splicing analysis based on Sashimi plot visualization. Bioinformatic splicing predictions were obtained using Alamut, HSF 3.1, and SpliceAI software. Results: Eighty-five variants (33%) were associated with abnormal splicing. The most frequent abnormality was upstream exon skipping (39/85 variants), which was most often associated with splice donor region variants. SpliceAI had greatest accuracy in predicting splicing abnormalities (0.91) and outperformed other tools in sensitivity and specificity. Conclusion: Splicing analysis of blood RNA identifies diagnostically important splicing abnormalities and clarifies functional effects of a significant proportion of VUSs. Bioinformatic predictions are improving but still make significant errors. RNA analysis should therefore be routinely considered in genetic disease diagnostics.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.This research was funded by National Institute for Health Research (NIHR) and the NewLife Foundation. The Baralle lab is supported by NIHR Research Professorship to D.B. (RP-2016-07-011).published version, accepted version (6 month embargo), submitted versio