School of BioSciences - Research Publications
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ItemConserved Glu-47 and Lys-50 residues are critical for UDP-N-acetylglucosamine/UMP antiport activity of the mouse Golgi-associated transporter Slc35a3(AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2019-06-28)Nucleotide sugar transporters (NSTs) regulate the flux of activated sugars from the cytosol into the lumen of the Golgi apparatus where glycosyltransferases use them for the modification of proteins, lipids, and proteoglycans. It has been well-established that NSTs are antiporters that exchange nucleotide sugars with the respective nucleoside monophosphate. Nevertheless, information about the molecular basis of ligand recognition and transport is scarce. Here, using topology predictors, cysteine-scanning mutagenesis, expression of GFP-tagged protein variants, and phenotypic complementation of the yeast strain Kl3, we identified residues involved in the activity of a mouse UDP-GlcNAc transporter, murine solute carrier family 35 member A3 (mSlc35a3). We specifically focused on the putative transmembrane helix 2 (TMH2) and observed that cells expressing E47C or K50C mSlc35a3 variants had lower levels of GlcNAc-containing glycoconjugates than WT cells, indicating impaired UDP-GlcNAc transport activity of these two variants. A conservative substitution analysis revealed that single or double substitutions of Glu-47 and Lys-50 do not restore GlcNAc glycoconjugates. Analysis of mSlc35a3 and its genetic variants reconstituted into proteoliposomes disclosed the following: (i) all variants act as UDP-GlcNAc/UMP antiporters; (ii) conservative substitutions (E47D, E47Q, K50R, or K50H) impair UDP-GlcNAc uptake; and (iii) substitutions of Glu-47 and Lys-50 dramatically alter kinetic parameters, consistent with a critical role of these two residues in mSlc35a3 function. A bioinformatics analysis revealed that an EXXK motif in TMH2 is highly conserved across SLC35 A subfamily members, and a 3D-homology model predicted that Glu-47 and Lys-50 are facing the central cavity of the protein.
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ItemWidespread cis-regulatory convergence between the extinct Tasmanian tiger and gray wolf(COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT, 2019-10)The extinct marsupial Tasmanian tiger, or thylacine, and the eutherian gray wolf are among the most widely recognized examples of convergent evolution in mammals. Despite being distantly related, these large predators independently evolved extremely similar craniofacial morphologies, and evidence suggests that they filled similar ecological niches. Previous analyses revealed little evidence of adaptive convergence between their protein-coding genes. Thus, the genetic basis of their convergence is still unclear. Here, we identified candidate craniofacial cis-regulatory elements across vertebrates and compared their evolutionary rates in the thylacine and wolf, revealing abundant signatures of convergent positive selection. Craniofacial thylacine-wolf accelerated regions were enriched near genes involved in TGF beta (TGFB) and BMP signaling, both of which are key morphological signaling pathways with critical roles in establishing the identities and boundaries between craniofacial tissues. Similarly, enhancers of genes involved in craniofacial nerve development showed convergent selection and involvement in these pathways. Taken together, these results suggest that adaptation in cis-regulators of TGF beta and BMP signaling may provide a mechanism to explain the coevolution of developmentally and functionally integrated craniofacial structures in these species. We also found that despite major structural differences in marsupial and eutherian brains, accelerated regions in both species were common near genes with roles in brain development. Our findings support the hypothesis that, relative to protein-coding genes, positive selection on cis-regulatory elements is likely to be an essential driver of adaptive convergent evolution and may underpin thylacine-wolf phenotypic similarities.
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ItemStevens-Johnson Syndrome complicated by obstructive uropathy, pneumothorax, and pneumomediastinum: a case report and literature review(BMC, 2019-06-11)BACKGROUND: Stevens-Johnson Syndrome (SJS) is an acute mucocutaneous eruption with blisters of the skin and haemorrhagic erosions of mucous membranes. This report describes air-leak syndrome and obstructive uropathy occurring simultaneously in a teenage patient affected by SJS. CASE PRESENTATION: A 17-year-old Malay female with SJS suffered from bilateral pneumothoraces, pneumomediastinum, and obstructive uropathy as early complications of her disease. She required intubation, chest tube insertion, and bilateral ureteric stenting as part of her intensive care management. These extra-cutaneous complications of renal and pulmonary systems were likely secondary to widespread epithelial detachment. CONCLUSION: Despite paucity of cases in adult literature, post-renal causes for acute kidney injury must be considered in SJS, especially in the setting of gross haematuria. Bedside point-of-care ultrasonography may be a useful tool for excluding obstructive uropathy. Pneumothorax is a rare but documented complication of SJS in paediatric cases and, to a lesser extent, adult patients. Extra care should be exercised when caring for mechanically ventilated patients suffering from SJS.
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ItemSubmillimeter diameter rotary-pullback fiber-optic endoscope for narrowband red-green-blue reflectance, optical coherence tomography, and autofluorescence in vivo imaging.(SPIE-Intl Soc Optical Eng, 2019-10)A fiber-based endoscopic imaging system combining narrowband red-green-blue (RGB) reflectance with optical coherence tomography (OCT) and autofluorescence imaging (AFI) has been developed. The system uses a submillimeter diameter rotary-pullback double-clad fiber imaging catheter for sample illumination and detection. The imaging capabilities of each modality are presented and demonstrated with images of a multicolored card, fingerprints, and tongue mucosa. Broadband imaging, which was done to compare with narrowband sources, revealed better contrast but worse color consistency compared with narrowband RGB reflectance. The measured resolution of the endoscopic system is 25 μm in both the rotary direction and the pullback direction. OCT can be performed simultaneously with either narrowband RGB reflectance imaging or AFI.
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ItemThe role of the environment in the evolution of nest shape in Australian passerines(NATURE PORTFOLIO, 2019-04-03)Avian nests present great variation in structure but, after excluding cavity nesters, probably the most obvious difference is that between open and domed nests. Some species lay their eggs in open structures, exposed to environmental variables, while other species build domed, enclosed nests with a roof, which are suggested to protect eggs and nestlings from weather conditions, high radiation levels, and predation. To date it is unclear which variables drove the evolution of different nest types. In this study, environmental and nest type information was extracted for continental Australian passerines, showing that species with open and closed nests are distributed in similar climates. However, species with open nests have larger ranges and are distributed in a wider variety of climatic conditions, suggesting open nests could be an evolutionary key innovation. This analysis was complemented with a detailed study of the evolution of particular nest traits in the largest Australasian avian radiation (Meliphagoidea), confirming that adult body size - but not environment - is an important factor in nest architecture, and larger species tend to build nests that are shallow and supported from underneath. Nest structure is a multidimensional trait that has probably evolved to match the phenotype of the nest owner, but that could also constrain or facilitate establishment in different environments.
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ItemPhysiological changes in post-hatchling green turtles (Chelonia mydas) following short-term fasting: implications for release protocols.(Oxford University Press (OUP), 2019)Relocation of sea turtle nests and the retention of post-hatchlings for head-starting programs are both commonly used to improve conservation outcomes and facilitate eco-tourism ventures. Currently, there is little literature surrounding the husbandry protocols required during these programs to optimize post-release outcomes. To assess the impact of varied feeding regimes on exercise performance, (which will hereafter be referred to as 'fitness'), 40 10-month-old captive post-hatchling green turtles (Chelonia mydas) were divided into four groups of 10 and fasted for either 3, 9, 10 or 15 h. The animals were then subjected to a fitness test via repetitive use of the 'righting reflex' on land. Health assessments were conducted prior to the fitness test, including; heart rate, haematocrit (Hct), heterophil to lymphocyte ratio and the measurement of 11 biochemical analytes, including pH, partial pressures of carbon dioxide (PvCO2) and oxygen (PvO2), lactate, bicarbonate (HCO3 -), sodium (Na+), potassium (K+), chloride (Cl-), ionized calcium (iCa2+), glucose and urea. Results were corrected for multiple comparisons and significant differences among groups were demonstrated for temperature, pH, HCO3 -, iCa2+, urea and lactate. To investigate physiological relationships between analytes, correlation coefficients were calculated between fitness and glucose, fitness and lactate, glucose and lactate, pH and iCa2+, pH and K+, pH and PvCO2, pH and HCO3 - and Hct and K+. Following correction for multiple comparisons, significant relationships were seen between pH and iCa2+ and pH and HCO3 -. Post-hatchling turtles appear to enter a catabolic state when exposed to short-term fasting. While this did not have a direct impact on fitness, the production of an intense energetic output from a catabolic state may induce a physiological debt. This study suggests that handling that induces a physical response should be minimized and animals should be fed within 10 h of release.
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ItemTherapeutic Potential of α- and β-Pinene: A Miracle Gift of Nature(MDPI, 2019-11)α- and β-pinene are well-known representatives of the monoterpenes group, and are found in many plants' essential oils. A wide range of pharmacological activities have been reported, including antibiotic resistance modulation, anticoagulant, antitumor, antimicrobial, antimalarial, antioxidant, anti-inflammatory, anti-Leishmania, and analgesic effects. This article aims to summarize the most prominent effects of α- and β-pinene, namely their cytogenetic, gastroprotective, anxiolytic, cytoprotective, anticonvulsant, and neuroprotective effects, as well as their effects against H2O2-stimulated oxidative stress, pancreatitis, stress-stimulated hyperthermia, and pulpal pain. Finally, we will also discuss the bioavailability, administration, as well as their biological activity and clinical applications.
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ItemDivergent evolutionary trajectories following speciation in two ectoparasitic honey bee mites(NATURE PORTFOLIO, 2019-10-01)Multispecies host-parasite evolution is common, but how parasites evolve after speciating remains poorly understood. Shared evolutionary history and physiology may propel species along similar evolutionary trajectories whereas pursuing different strategies can reduce competition. We test these scenarios in the economically important association between honey bees and ectoparasitic mites by sequencing the genomes of the sister mite species Varroa destructor and Varroa jacobsoni. These genomes were closely related, with 99.7% sequence identity. Among the 9,628 orthologous genes, 4.8% showed signs of positive selection in at least one species. Divergent selective trajectories were discovered in conserved chemosensory gene families (IGR, SNMP), and Halloween genes (CYP) involved in moulting and reproduction. However, there was little overlap in these gene sets and associated GO terms, indicating different selective regimes operating on each of the parasites. Based on our findings, we suggest that species-specific strategies may be needed to combat evolving parasite communities.
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ItemUnderstanding glycaemic control and current approaches for screening antidiabetic natural products from evidence-based medicinal plants(BMC, 2019-09-07)Type 2 Diabetes Mellitus has reached epidemic proportions as a result of over-nutrition and increasingly sedentary lifestyles. Current therapies, although effective, are not without limitations. These limitations, the alarming increase in the prevalence of diabetes, and the soaring cost of managing diabetes and its complications underscores an urgent need for safer, more efficient and affordable alternative treatments. Over 1200 plant species are reported in ethnomedicine for treating diabetes and these represents an important and promising source for the identification of novel antidiabetic compounds. Evaluating medicinal plants for desirable bioactivity goes hand-in-hand with methods in analytical biochemistry for separating and identifying lead compounds. This review aims to provide a comprehensive summary of current methods used in antidiabetic plant research to form a useful resource for researchers beginning in the field. The review summarises the current understanding of blood glucose regulation and the general mechanisms of action of current antidiabetic medications, and combines knowledge on common experimental approaches for screening plant extracts for antidiabetic activity and currently available analytical methods and technologies for the separation and identification of bioactive natural products. Common in vivo animal models, in vitro models, in silico methods and biochemical assays used for testing the antidiabetic effects of plants are discussed with a particular emphasis on in vitro methods such as cell-based bioassays for screening insulin secretagogues and insulinomimetics. Enzyme inhibition assays and molecular docking are also highlighted. The role of metabolomics, metabolite profiling, and dereplication of data for the high-throughput discovery of novel antidiabetic agents is reviewed. Finally, this review also summarises sample preparation techniques such as liquid-liquid extraction, solid phase extraction, and supercritical fluid extraction, and the critical function of nuclear magnetic resonance and high resolution liquid chromatography-mass spectrometry for the dereplication, putative identification and structure elucidation of natural compounds from evidence-based medicinal plants.
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ItemThe inhibitory effects of an eight-herb formula (RCM-107) on pancreatic lipase: enzymatic, HPTLC profiling and in silico approaches(ELSEVIER SCI LTD, 2019-09)AIMS: Obesity is a global, public health issue that causes or exacerbates serious medical disorders. Chinese herbal therapies have become one of the most popular alternatives due to intolerances of current anti-obesity treatments. The RCM-107 formula (granule) is modified from our previous studied RCM-104 formula, which has demonstrated significant effects on weight reduction in randomized clinical trials. Up to date, there is no published scientific evidence to evaluate the effect of this formula on the weight-loss target pancreatic lipase and therefore, the aim of this study is to investigate the inhibitory effect of RCM-107 and respective individual ingredient on the pancreatic lipase activities. MAIN METHODS: Fluorometric based enzymatic assays, high-performance thin-layer chromatography (HPTLC) profiling and in silico molecular docking techniques were used to investigate the lipase inhibitory effects of the RCM-107 herbal formula and its respective individual herbs. PRINCIPLE FINDINGS: The results demonstrated the potent lipase suppressing effect of the RCM-107 formula. The majority of the ingredients from this formula also showed pancreatic lipase inhibitory activities. The presence of the known weight-loss compounds such as (-)-epigallocatechin-3-gallate (EGCG), epicatechin-3-gallate (ECG), (-)-epicatechin (EC), rutin, crocin and caffeine were identified in the RCM-107 and related single herbs using HPTLC profiling approaches. In addition, EGCG, EC and the known lipase antagonist orlistat acted on the same site. These compounds form hydrogen bonds with corresponding residues HIS152, ASP80 and GLY77, which can be considered as markers of important areas in the ligand-binding site. This may explain the details of their roles in inhibiting pancreatic lipase activities. CONCLUSION: Our data has provided new knowledge to the mechanistic properties of the RCM-107 formula and its respective individual herbal ingredients for weight loss, in terms of reducing lipid absorption via the inhibition of pancreatic lipase.