ORCID Profile
0000-0002-1708-9430
Current Organisation
RMIT University
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In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Molecular Evolution | Characterisation of Biological Macromolecules | Biochemistry And Cell Biology Not Elsewhere Classified | Soft Condensed Matter | Biochemistry and Cell Biology | Analytical Biochemistry | Condensed Matter Physics | Chemical Thermodynamics and Energetics
Expanding Knowledge in the Chemical Sciences | Expanding Knowledge in the Physical Sciences | Health related to ageing |
Publisher: Public Library of Science (PLoS)
Date: 16-11-2011
Publisher: Springer Science and Business Media LLC
Date: 22-01-2008
DOI: 10.1007/S00360-007-0250-8
Abstract: The marsupial genus Antechinus is a group of small carnivorous marsupials from the order Dasyuromorphia (Family Dasyuridae) and is found in eastern Australia. The life history of all species in the genus is characterized by a complex, but highly synchronized life cycle in both sexes, culminating in a short mating period followed by total male mortality (semelparity). The breeding season is defined by a specific rate of increase in photoperiod, which is different for each species. In Antechinus spp., male mortality is due to the effects of high free testosterone and cortisol levels on many organ systems. Unusually, spermatogenesis is complete before testosterone levels begin to rise at the winter solstice. In males, low sperm counts have been compensated for by high proportions of sperm reaching the isthmus of the female reproductive tract and long-term storage in the crypts. The females survive to rear their young and may mate again in their second year. Gestation lasts from 26 to 34 days, depending on the species. However, developmental arrest can occur at several stages during embryogenesis, elongating the apparent gestation duration by several days. Several species have strong female sex biases in their litters. The high degree of life history synchrony and the cascade of endocrine-driven physiological events that result in male death are unusual physiological characteristics for mammals. Suggestions why semelparity may have evolved in Antechinus are discussed.
Publisher: Wiley
Date: 22-05-2023
DOI: 10.1002/VMS3.1091
Abstract: Thrombocytopenia is a common laboratory abnormality in dogs, and numerous diseases have been associated with its development. Estimates for the sensitivity and specificity of the degree of reduction of platelet concentration for the diagnosis of primary immune‐mediated thrombocytopenia (pITP) have not been reported. To report the prevalence of different causes of thrombocytopenia in dogs in the United Kingdom and to investigate the utility of platelet concentration to differentiate causes of thrombocytopenia. Medical records of 762 dogs with thrombocytopenia presented to seven referral hospitals from January 2017 to December 2018 were retrospectively reviewed. Cases were assigned into the following categories: pITP, infectious diseases, neoplasia, inflammatory/other immune‐mediated disorders and miscellaneous causes. The prevalence of the different categories was estimated, and platelet concentrations were compared. Receiver‐operating characteristic (ROC) curves were used to investigate the utility of platelet concentration to differentiate between causes of thrombocytopenia. The most common disease category associated with thrombocytopenia was neoplasia (27.3%), followed by miscellaneous causes (26.9%), pITP (18.8%), inflammatory/immune‐mediated disorders (14.4%) and infectious diseases (12.6%). Dogs with pITP had significantly lower platelet concentrations (median 8 × 10 9 /L, range: 0–70 × 10 9 /L) than dogs in the other four categories. Platelet concentration was useful for distinguishing pITP from other causes of thrombocytopenia (area under ROC curve = 0.89, 95% confidence interval 0.87, 0.92), with a platelet concentration ≤12 × 10 9 /L being 60% sensitive and 90% specific. Severe thrombocytopenia was highly specific for a diagnosis of pITP, which was more prevalent in this UK population of thrombocytopenic dogs compared with previous epidemiological studies. Conversely, the proportion of dogs with infectious diseases was lower than in previous reports from other locations.
Publisher: Elsevier BV
Date: 11-2001
Publisher: Wiley
Date: 31-07-2006
DOI: 10.1111/J.1742-4658.2006.05404.X
Abstract: The relationship between the structure of the N-terminal sequence of transthyretin (TTR) and the binding of thyroid hormone was studied. A recombinant human TTR and two derivatives of Crocodylus porosus TTRs, one with the N-terminal sequence replaced by that of human TTR (human/crocTTR), the other with the N-terminal segment removed (truncated crocTTR), were synthesized in Pichia pastoris. Subunit mass, native molecular weight, tetramer formation, cross-reactivity to TTR antibodies and binding to retinol-binding protein of these recombinant TTRs were similar to TTRs found in nature. Analysis of the binding affinity to thyroid hormones of recombinant human TTR showed a dissociation constant (Kd) for triiodothyronine (T3) of 53.26+/-3.97 nM and for thyroxine (T4) of 19.73+/-0.13 nM. These values are similar to those found for TTR purified from human serum, and gave a Kd T3/T4 ratio of 2.70. The affinity for T4 of human/crocTTR (Kd=22.75+/-1.89 nM) was higher than those of both human TTR and C. porosus TTR, but the affinity for T3 (Kd=5.40+/-0.25 nM) was similar to C. porosus TTR, giving a Kd T3/T4 ratio of 0.24. A similar affinity for both T3 (Kd=57.78+/-5.65 nM) and T4 (Kd=59.72+/-3.38 nM), with a Kd T3/T4 ratio of 0.97, was observed for truncated crocTTR. The obtained results strongly confirm the hypothesis that the unstructured N-terminal region of TTR critically influences the specificity and affinity of thyroid hormone binding to TTR.
Publisher: Springer Science and Business Media LLC
Date: 23-12-2019
DOI: 10.1038/S41598-019-56156-W
Abstract: Choroid plexus epithelial cells produce and secrete transthyretin (TTR). TTR binds and distributes thyroid hormone (TH) to brain cells via the cerebrospinal fluid. The adult murine subventricular zone (SVZ) is in close proximity to the choroid plexus. In the SVZ, TH determines neural stem cell (NSC) fate towards a neuronal or a glial cell. We investigated whether the loss of TTR also disrupted NSC fate choice. Our results show a decreased neurogenic versus oligodendrogenic balance in the lateroventral SVZ of Ttr knockout mice. This balance was also decreased in the dorsal SVZ, but only in Ttr knockout male mice, concomitant with an increased oligodendrocyte precursor density in the corpus callosum. Quantitative RTqPCR analysis following FACS-dissected SVZs, or marked-coupled microbeads sorting of in vitro neurospheres, showed elevated Ttr mRNA levels in neuronal cells, as compared to uncommitted precursor and glial cells. However, TTR protein was undetectable in vivo using immunostaining, and this despite the presence of Ttr mRNA-expressing SVZ cells. Altogether, our data demonstrate that TTR is an important factor in SVZ neuro- and oligodendrogenesis. They also reveal important gender-specific differences and spatial heterogeneity, providing new avenues for stimulating endogenous repair in neurodegenerative diseases.
Publisher: Wiley
Date: 1998
DOI: 10.1002/(SICI)1097-0134(1998)33:2+<3::AID-PROT2>3.0.CO;2-H
Publisher: Elsevier BV
Date: 1991
DOI: 10.1016/0305-0491(91)90035-C
Abstract: 1. The major protein synthesized and secreted by the choroid plexus from mammals, birds, reptiles and probably hibians is similar in subunit structure to transthyretin. 2. In mammals and birds the proportion of transthyretin mRNA is much higher in choroid plexus RNA than in liver RNA. No transthyretin mRNA is found in brain outside the choroid plexus. 3. Transthyretin-like protein, such as that secreted by the choroid plexus, was not detected in hibian serum and was present in very low levels in reptile serum. 4. It is proposed that transthyretin synthesis and secretion arose earlier in evolution in the choroid plexus than in the liver.
Publisher: Springer Berlin Heidelberg
Date: 2009
Publisher: Mary Ann Liebert Inc
Date: 08-2015
Abstract: Canine tumors are valuable comparative oncology models. This research was designed to create a sustainable biobank of canine mammary tumors for breast cancer research. The aim was to provide a well-characterized s le cohort for specimen sharing, data mining, and long-term research aims. Canine mammary tumors are most frequently managed at a local veterinary clinic or hospital. We adopted a biobank framework based on a large number of participating veterinary hospitals and clinics acting as collection centers that were serviced by a centralized storage facility. Recruitment was targeted at rural veterinary clinics. A tailored, stable collection kit (DogMATIC) was designed that was used by veterinarians in remote or rural locations to collect both fresh and fixed tissue for submission to the biobank. To validate this methodology the kit design, collection rate, and s le quality were analyzed. The Australian Veterinary Cancer Biobank was established as a network of 47 veterinary clinics and three veterinary pathology laboratories spanning over 200,000 km(2). In the first 12 months, 30 canine mammary tumor cases were submitted via the DogMATIC kit. Pure intact RNA was isolated in over 80% of s les with an average yield of 14.49 μg. A large network biobank, utilizing off-site collection with the DogMATIC kit, was successfully coordinated. The creation of the Australian Veterinary Cancer Biobank has established a long-term, sustainable, comparative oncology research resource in Australia. There are broader implications for biobanking with this very different form of collection and banking.
Publisher: Elsevier BV
Date: 06-2006
DOI: 10.1016/J.JMB.2006.04.057
Abstract: The mechanism of binding of thyroid hormones by the transport protein transthyretin (TTR) in vertebrates is structurally well characterised. However, a homologous family of transthyretin-like proteins (TLPs) present in bacteria as well as eukaryotes do not bind thyroid hormones, instead they are postulated to perform a role in the purine degradation pathway and function as 5-hydroxyisourate hydrolases. Here we describe the 2.5 Angstroms X-ray crystal structure of the TLP from the Gram-negative bacterium Salmonella dublin, and compare and contrast its structure with vertebrate TTRs. The overall architecture of the homotetramer is conserved and, despite low sequence homology with vertebrate TTRs, structural differences within the monomer are restricted to flexible loop regions. However, sequence variation at the dimer-dimer interface has profound consequences for the ligand binding site and provides a structural rationalisation for the absence of thyroid hormone binding affinity in bacterial TLPs: the deep, negatively charged thyroxine-binding pocket that characterises vertebrate TTR contrasts with a shallow and elongated, positively charged cleft in S. dublin TLP. We have demonstrated that Sdu_TLP is a 5-hydroxyisourate hydrolase. Furthermore, using site-directed mutagenesis, we have identified three conserved residues located in this cleft that are critical to the enzyme activity. Together our data reveal that the active site of Sdu_TLP corresponds to the thyroxine binding site in TTRs.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Elsevier BV
Date: 10-2024
Publisher: Elsevier BV
Date: 02-2002
Publisher: Informa UK Limited
Date: 15-03-2018
Publisher: Springer Berlin Heidelberg
Date: 2009
Publisher: MDPI AG
Date: 25-10-2022
DOI: 10.3390/MOLECULES27217206
Abstract: Human transthyretin (hTTR) can form amyloid deposits that accumulate in nerves and organs, disrupting cellular function. Molecules such as tafamidis that bind to and stabilize the TTR tetramer can reduce such amyloid formation. Here, we studied the interaction of VCP-6 (2-((3,5-dichlorophenyl)amino)benzoic acid) with hTTR. VCP-6 binds to hTTR with 5 times the affinity of the cognate ligand, thyroxine (T4). The structure of the hTTR:VCP-6 complex was determined by X-ray crystallography at 1.52 Å resolution. VCP-6 binds deeper in the binding channel than T4 with the 3′,5′-dichlorophenyl ring binding in the ‘forward’ mode towards the channel centre. The dichlorophenyl ring lies along the 2-fold axis coincident with the channel centre, while the 2-carboxylatephenylamine ring of VCP-6 is symmetrically displaced from the 2-fold axis, allowing the 2-carboxylate group to form a tight intermolecular hydrogen bond with Nζ of Lys15 and an intramolecular hydrogen bond with the amine of VCP-6, stabilizing its conformation and explaining the greater affinity of VCP-6 compared to T4. This arrangement maintains optimal halogen bonding interactions in the binding sites, via chlorine atoms rather than iodine of the thyroid hormone, thereby explaining why the dichloro substitution pattern is a stronger binder than either the diiodo or dibromo analogues.
Publisher: Elsevier BV
Date: 2011
DOI: 10.1016/J.YGCEN.2010.10.023
Abstract: Bone is considered to be a feature of higher vertebrates and one of the features that was required for the movement from water onto land. But there are a number of evolutionarily important species that have cartilaginous skeletons, including sharks. Both bony and cartilaginous fish are believed to have a common ancestor who had a bony skeleton. A number of factors and pathways have been shown to be involved in the development and maintenance of bony skeleton including the Wnt pathway and the parathyroid hormone gene family. The study of these pathways and factors in cartilaginous animals may shed light on the evolution of the vertebrate skeleton.
Publisher: Frontiers Media SA
Date: 12-02-2015
Publisher: American Meteorological Society
Date: 06-2023
Abstract: This study describes flash drought (FD) inferred from the evaporative stress index (ESI) over Australia and its relationship to vegetation. During 1975–2020, FD occurrence ranges from less than 1 per decade in the central arid regions to 10 per decade toward the coasts. Although FD can occur in any season, its occurrence is more frequent in summer in the north, winter in the southern interior and southwest, and across a range of months in the far southeast and Tasmania. With a view toward real-time monitoring, FD “declaration” is defined as the date when the ESI declines to at least −1, i.e., drought conditions, after at least 2 weeks of rapid decline. Composite analysis shows that evaporative demand begins to increase about 5–6 weeks before declaration with an increase in solar radiation, while evapotranspiration initially increases with evaporative demand but then decreases in response to the soil moisture depletion. Solar radiation increases simultaneously with precipitation deficit, both reaching their peak around declaration. FD intensity peaks with soil moisture depletion, 2–3 weeks after declaration. The composite wind speed only shows a modest increase around declaration. The composite FD ends 4 weeks after rapid decreases in solar radiation and increases in precipitation. Satellite-derived vegetation health composites show pronounced decline in the nonforested regions, peaking about 4–8 weeks after FD declaration, followed by a recovery period lasting about 12 weeks after flash drought ends. The forest-dominated regions, however, are little impacted. Modeled pasture growth data show reduced values for up to 3 months after the declaration month covering the main agricultural areas of Australia. Flash drought describes a fast intensification or rapid development of drought conditions with potential severe impacts on agriculture and ecosystems. This study describes the climatology and typical evolution of flash drought over Australia for the period 1975–2020. An objective definition of flash drought, using high-resolution observational-based datasets, is proposed and its spatiotemporal variability is provided, as well as its relationship with vegetation health and pasture growth. This constitutes a guideline for understanding flash drought in Australia and its impacts on vegetation.
Publisher: Springer Berlin Heidelberg
Date: 2009
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.JCPA.2017.07.005
Abstract: Osteosarcoma (OS) originates from bone-forming mesenchymal cells and represents one of the primary bone tumours. It is the most common primary bone tumour in dogs and man. The characterization of an appropriate natural disease animal model to study human OS is essential to elucidate the pathogenesis of the disease. This study aimed to validate canine OS as a model for the human disease by evaluating immunohistochemically the expression of markers known to be important in human OS. The immunohistochemical panel included vimentin, alkaline phosphatase (ALP), desmin, S100, neuron-specific enolase (NSE), runt-related transcription factor 2 (Runx2) and bone morphogenetic protein 4 (BMP4). Immunohistochemistry was conducted on formalin-fixed, paraffin wax-embedded tissue sections from 59 dogs with confirmed primary OS. Vimentin, ALP, Runx2 and BMP4 were highly expressed by all tumours, while desmin, S100 and NSE were expressed variably. The findings were similar to those described previously for human OS and suggest that canine OS may represent a useful model for the study of the human disease.
Publisher: Elsevier BV
Date: 02-1997
DOI: 10.1016/S0305-0491(96)00212-X
Abstract: Thyroxine, the most abundant thyroid hormone in blood, partitions into lipid membranes. In a network-like system, thyroxine-binding plasma proteins counteract this partitioning and establish intravascular, protein-bound thyroxine pools. These are far larger than the free thyroxine pools. In larger eutherians, proteins specifically binding thyroxine are albumin, transthyretin, and thyroxine-binding globulin. Some binding of thyroxine can also occur to lipoproteins. During evolution, transthyretin synthesis first appeared in the choroid plexus of the stem reptiles, about 300 million years ago. Transthretin synthesis in the liver evolved much later, independently, in birds, eutherians and some marsupial species. Analysis of 57 human transthyretin variants suggests that most mutations in transthyretin are not compatible with its normal metabolism and lead to its deposition as amyloid. Analysis of transthyretin or its gene in 20 different species shows that evolutionary changes of transthyretin predominantly occurred near the N-termini. A change in RNA splicing between exon 1 and exon 2 led to a decrease in hydrophobicity and length of the N-termini. It is proposed that the selection pressure producing these changes was the need for a more effective prevention of thyroxine partitioning into lipids. Lipid pools increased during evolution with the increases in relative sizes of brains and internal organs and changes in lipid composition of membranes in ectothermic and endothermic species.
Publisher: Frontiers Media SA
Date: 03-03-2015
Publisher: American Thoracic Society
Date: 05-2004
Publisher: Elsevier BV
Date: 2002
Publisher: Frontiers Media SA
Date: 11-02-2015
Publisher: Research Square Platform LLC
Date: 13-03-2023
DOI: 10.21203/RS.3.RS-2654880/V1
Abstract: This paper aims to propose a hybrid deep learning (DL) model that combines a convolutional neural network (CNN) with a bi-directional long-short term memory (BiLSTM) for week-ahead prediction of daily flood index ( I F ) for Bangladesh. The neighbourhood component analysis (NCA) is assigned for significant feature selection with synoptic-scale climatic indicators. The results successfully reveal that the hybrid CNN-BiLSTM model outperforms the respective benchmark models based on forecasting capability, as supported by a minimal mean absolute error and high-efficiency metrics. With respect to I F prediction, the hybrid CNN-BiLSTM model shows over 98% of the prediction errors were less than 0.015, resulting in a low relative error and superiority performance against the benchmark models in this study. The adaptability and potential utility of the suggested model may be helpful in subsequent flood monitoring and may also be beneficial to policymakers at the federal and state levels.
Publisher: Wiley
Date: 23-11-2010
DOI: 10.1002/JBMR.178
Abstract: The development of bone was a major step in the evolution of vertebrates. A bony skeleton provided structural support and a calcium reservoir essential for the movement from an aquatic to a terrestrial environment. Cartilaginous fishes are the oldest living group of jawed vertebrates. In this study we have identified three members of the parathyroid hormone (Pth) gene family in a cartilaginous fish, the elephant shark (Callorhinchus milii). The three genes include two Pth genes, designated as Pth1 and Pth2, and a Pthrp gene. Phylogenetic analysis suggested that elephant shark Pth2 is an ancient gene whose orthologue is lost in bony vertebrates. The Pth1 and Pth2 genes have the same structure as the Pth gene in bony vertebrates, whereas the structure of the Pthrp gene is more complex in tetrapods compared with elephant shark. The three elephant shark genes showed distinct patterns of expression, with Pth2 being expressed only in the brain and spleen. This contrasts with localization of the corresponding proteins, which showed considerable overlap in their distribution. There were conserved sites of localization for Pthrp between elephant shark and mammals, including tissues such as kidney, skin, skeletal and cardiac muscle, pancreas, and cartilage. The elephant shark Pth1(1-34) and Pthrp(1-34) peptides were able to stimulate cAMP accumulation in mammalian UMR106.01 cells. However, Pth2(1-34) peptide did not show such PTH-like biologic activity. The presence of Pth and Pthrp genes in the elephant shark indicates that these genes played fundamental roles before their recruitment to bone development in bony jawed vertebrates.
Publisher: Elsevier BV
Date: 06-1993
DOI: 10.1016/0305-0491(93)90235-W
Abstract: 1. Transthyretin was found to be synthesized and secreted by choroid plexus from rats, echidnas, and lizards, but not toads. 2. Transthyretin was observed in blood from placental mammals, birds, and marsupials, but not reptiles and monotremes. 3. The obtained data suggest that transthyretin synthesis by the liver evolved independently in the lineage leading to the placental mammals and marsupials and in that leading to the birds. 4. It is proposed that transthyretin gene expression in mammalian liver appeared about 200 million years later than its first occurrence in the choroid plexus of the stem reptiles.
Publisher: Elsevier BV
Date: 09-2000
Publisher: Elsevier BV
Date: 1998
DOI: 10.1016/S0305-0491(97)00304-0
Abstract: In eutherians, patterns of plasma protein levels in blood change during the acute phase response to trauma and inflammation. Until now, such an acute phase response has not been characterised in a noneutherian species. Here we describe the acute phase response in a marsupial species, the South American polyprotodont marsupial Monodelphis domestica, after brain surgery or injection of lipopolysaccharide. Several days after brain surgery, transthyretin was not detected in plasma. For 48 hr following injection of lipopolysaccharide, the concentration of haptoglobin in plasma increased, that of transthyretin decreased, and the concentration of albumin in plasma did not change significantly. The American polyprotodont marsupials are probably more closely related to the common ancestor marsupial than the Australian marsupials are. It is most likely that the transthyretin gene was not expressed in the liver of this common ancestor. As the transthyretin gene is expressed in the liver of M. domestica, it seems that as soon as transthyretin is synthesised by the liver, it is under negative acute phase control.
Publisher: American Chemical Society (ACS)
Date: 08-2005
DOI: 10.1021/BI050700M
Abstract: Transthyretin (TTR) can deposit as amyloid in the peripheral nervous system and induce a peripheral neuropathy. We examined the mechanism of TTR amyloid neurotoxicity on SH-SY5Y neuroblastoma cells. Wild-type (WT) TTR and two amyloidogenic mutants (V30M and L55P) were expressed in Escherichia coli. Incubation (aging) of WT TTR at 37 degrees C for 1 week caused no significant aggregation. However, there was a significant increase in the extent of amyloid fibril formation after the amyloidogenic mutants had been aged. L55P TTR aggregated more readily than V30M TTR. Both amyloidogenic mutants were neurotoxic after aging. The order of neurotoxicity was as follows: L55P > V30M > WT. As binding of amyloid proteins to the plasma membrane may cause cytotoxicity, we studied the binding of TTR to a plasma membrane-enriched preparation from SH-SY5Y cells by surface plasmon resonance. All three forms bound to the plasma membrane through electrostatic interactions. The binding of the amyloidogenic mutants was increased by aging. The amount of binding correlated closely with the amount of aggregation and with the cytotoxicity of each form. As membrane fluidity can influence cell viability, we also examined the effect of TTR on membrane fluidity using a fluorescence anisotropy method. Binding of the amyloidogenic TTR mutants increased membrane fluidity, and once again, the order of potency was as follows: L55P > V30M > WT. These results demonstrate that TTR can bind to the plasma membrane and cause a change in membrane fluidity. Altered membrane fluidity may be the cause of the neurotoxicity.
Publisher: Wiley
Date: 2000
DOI: 10.1002/1097-0029(20010101)52:1<21::AID-JEMT4>3.0.CO;2-Z
Publisher: Elsevier BV
Date: 11-2023
Publisher: Proceedings of the National Academy of Sciences
Date: 07-09-2010
Abstract: With the notable exception of humans, uric acid is degraded to (S)-allantoin in a biochemical pathway catalyzed by urate oxidase, 5-hydroxyisourate (HIU) hydrolase, and 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase in most vertebrate species. A point mutation in the gene encoding mouse HIU hydrolase, Urah , that perturbed uric acid metabolism within the liver was discovered during a mutagenesis screen in mice. The predicted substitution of cysteine for tyrosine in a conserved helical region of the mutant-encoded HIU hydrolase resulted in undetectable protein expression. Mice homozygous for this mutation developed elevated platelet counts secondary to excess thrombopoietin production and hepatomegaly. The majority of homozygous mutant mice also developed hepatocellular carcinoma, and tumor development was accelerated by exposure to radiation. The development of hepatomegaly and liver tumors in mice lacking Urah suggests that uric acid metabolites may be toxic and that urate oxidase activity without HIU hydrolase function may affect liver growth and transformation. The absence of HIU hydrolase in humans predicts slowed metabolism of HIU after clinical administration of exogenous urate oxidase in conditions of uric acid-related pathology. The data suggest that prolonged urate oxidase therapy should be combined with careful assessment of toxicity associated with extrahepatic production of uric acid metabolites.
Publisher: Elsevier BV
Date: 04-1996
Publisher: Elsevier BV
Date: 05-1993
Abstract: Thyroid hormone-binding proteins in blood plasma were identified in 28 different marsupial species by their capacity to bind radioactive thyroxine. All species contained albumin. Transthyretin was not found in the blood from any of 12 polyprotodont marsupial species, but was abundant in the blood from all of 16 diprotodont marsupial species investigated. Transthyretin mRNA was absent from the liver of the stripe-faced dunnart, a polyprotodont marsupial, but abundant in the liver of the diprotodont grey kangaroo. Diprotodont marsupials probably evolved in Australia from polyprotodont marsupials after their transantarctic migration from South America, about 40 million years ago. It is suggested that hepatic transthyretin expression evolved in marsupials during the radiation of herbivorous, diprotodont species in Australia. The earlier appearance of transthyretin gene expression in the choroid plexus of the stem reptiles, about 300 million years ago, contrasts with hepatic transthyretin synthesis, a relatively late evolutionary event, occurring independently in at least three lineages.
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.NEULET.2021.136287
Abstract: Thyroid hormones (THs) impact nearly every tissue in the body, including the adult and developing central nervous system. The distribution of THs around the body is facilitated by specific TH distributor proteins including transthyretin (TTR). In addition to being produced in the liver, TTR is synthesized in the choroid plexus of the brain. The synthesis of TTR by choroid plexus epithelial cells allows transport of THs from the blood into the brain. Adequate supply of THs to the brain is required for developmental myelination of axons and the maintenance of mature myelin throughout adult life, essential for the proper conduction of nerve impulses. Insufficient THs in developing mice results in hypo-myelination (thinner myelin around axons). However, confounding evidence demonstrated that in developing brain of TTR null mice, hyper-myelination of axons was observed in the corpus callosum. This raised the question whether increased myelination occurs during re-myelination in the adult brain following targeted demyelination. To investigate the effect of TTR during re-myelination, cuprizone induced depletion of myelin in the corpus callosum of adult mice was initiated, followed by a period of myelin repair. Myelin thickness was measured to assess re-myelination rates for 6 weeks. TTR null mice displayed expedited rates of early re-myelination, preferentially re-myelinating smaller axons compared to those of wild type mice. Furthermore, TTR null mice produced thicker myelin than wild type mice during re-myelination. These results may have broader implications in understanding mechanisms governing re-myelination, particularly in potential therapeutic contexts for acquired demyelinating diseases such as multiple sclerosis.
Publisher: Public Library of Science (PLoS)
Date: 21-12-2012
Publisher: Elsevier BV
Date: 10-2008
Publisher: AIP Publishing
Date: 28-06-2010
DOI: 10.1063/1.3460288
Abstract: Significant photocurrent enhancement has been achieved for evaporated solid-phase-crystallized polycrystalline silicon thin-film solar cells on glass, due to light trapping provided by Ag nanoparticles located on the rear silicon surface of the cells. This configuration takes advantage of the high scattering cross-section and coupling efficiency of rear-located particles formed directly on the optically dense silicon layer. We report short-circuit current enhancement of 29% due to Ag nanoparticles, increasing to 38% when combined with a detached back surface reflector. Compared to conventional light trapping schemes for these cells, this method achieves 1/3 higher short-circuit current.
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.MCE.2017.02.038
Abstract: Thyroid hormones (THs) are evolutionarily old hormones, having effects on metabolism in bacteria, invertebrates and vertebrates. THs bind specific distributor proteins (THDPs) to ensure their efficient distribution through the blood and cerebrospinal fluid in vertebrates. Albumin is a THDP in the blood of all studied species of vertebrates, so may be the original vertebrate THDP. However, albumin has weak affinity for THs. Transthyretin (TTR) has been identified in the blood across different lineages in adults vs juveniles. TTR has intermediate affinity for THs. Thyroxine-binding globulin has only been identified in mammals and has high affinity for THs. Of these THDPs, TTR is the only one known to be synthesised in the brain and is involved in moving THs from the blood into the cerebrospinal fluid. We analysed the rates of evolution of these three THDPs: TTR has been most highly conserved and albumin has had the highest rate of ergence.
Publisher: Elsevier BV
Date: 04-2002
Publisher: American Physiological Society
Date: 2013
DOI: 10.1152/AJPENDO.00216.2012
Abstract: Thyroid hormones (THs) are vital for normal postnatal development. Extracellular TH distributor proteins create an intravascular reservoir of THs. Transthyretin (TTR) is a TH distributor protein in the circulatory system and is the only TH distributor protein synthesized in the central nervous system. We investigated the phenotype of TTR null mice during development. Total and free 3′,5′,3,5-tetraiodo-l-thyronine (T 4 ) and free 3′,3,5-triiodo-l-thyronine (T 3 ) in plasma were significantly reduced in 14-day-old (P14) TTR null mice. TTR null mice also displayed a delayed suckling-to-weaning transition, decreased muscle mass, delayed growth, and retarded longitudinal bone growth. In addition, ileums from postnatal day 0 (P0) TTR null mice displayed disordered architecture and contained fewer goblet cells than wild type. Protein concentrations in cerebrospinal fluid from P0 and P14 TTR null mice were higher than in age-matched wild-type mice. In contrast to the current literature based on analyses of adult TTR null mice, our results demonstrate that TTR has an important and nonredundant role in influencing the development of several organs.
Publisher: Wiley
Date: 16-06-2006
DOI: 10.1002/PROT.21033
Abstract: Transthyretin (TTR) is a tetrameric protein involved in the distribution of thyroid hormones in vertebrates. The amino acid sequence of TTR is highly conserved across vertebrates. Hypothetical TTR-like proteins (TLPs) were inferred from the identification of genes in nonvertebrate species. Here, we identified five motifs defining TLPs and three motifs defining both TTRs and TLPs. These motifs were mapped onto structurally conserved and functionally important regions of TTRs. These motifs were used to build hidden Markov models for accurate identification of TLPs in other organisms. TLPs were ided into three main groups based on their N-terminal regions. Most TLPs are cytosolic, but in plants and slime mold, we predict they are peroxisomal. We verified that the TLPs from enterobacteria were periplasmic. We demonstrated that TLP genes are expressed in a bacterium (E. coli), an invertebrate animal (C. elegans), and a plant (A. thaliana). These TLPs have similar subunit molecular weights to TTRs, are tetramers, and are predicted to have similar three-dimensional (3D) structures to TTRs, but do not bind thyroid hormones or similar ligands. We suggest that like TTRs, the N-terminal and C-terminal regions of TLPs are integral in defining the function of TLPs in nonvertebrate species and that the TLP gene duplicated in primitive vertebrates to produce the TTR gene. TLP/TTR has retained its overall structure, but changed function and localization during evolution in bacteria, invertebrates, plants, and vertebrates.
Publisher: Springer Science and Business Media LLC
Date: 26-07-2023
DOI: 10.1007/S11069-023-06089-5
Abstract: Assessing areas prone to flash floods is crucial for effective disaster management and mitigation. This study proposes a framework for mapping flood-prone areas by integrating geographic information system (GIS), remote sensing data, and multi-criteria decision-making (MCDM) techniques. The hybrid MCDM model combines the decision-making trial and evaluation laboratory (DEMATEL) with GIS-based analytic network process (ANP) to evaluate flood vulnerability in Golestan province, Iran. Fourteen criteria related to flood potential, including elevation, slope, aspect, vegetation density, soil moisture, flow direction, river distance, rainfall and runoff, flow time, geomorphology, drainage density, soil type, lithology, and land use, were considered. In areas where official data was lacking, a questionnaire was administered to gather information from 15 specialists, experts, and 20 local managers. The relationships between criteria were analyzed using the DEMATEL method, and their weights were determined using the ANP method. Topography was found to have the greatest impact on flood risk, followed by the type of surface and vegetation cover. Hydrographic, soil and geology, climatic also influence flooding in the region. The study identified the northern and central parts of the study area being at higher risk of flooding compared to the southern part. Based on the flood intensity map, 68 villages (50% of all villages in the Qarasu watershed) with a population of approximately 83,595 were identified as at risk of flooding. The proposed GIS-DANP model provides a valuable tool for flood management and decision-making, aiding in risk reduction and minimizing casualties.
Publisher: Elsevier BV
Date: 04-2020
Publisher: Elsevier BV
Date: 09-2023
Publisher: Elsevier BV
Date: 09-2000
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.YGCEN.2015.02.021
Abstract: Thyroid hormones (THs) are key regulators in the development of the vertebrate brain. Therefore, TH access to the developing brain needs to be strictly regulated. The brain barriers separate the central nervous system from the rest of the body and impose specific transport mechanisms on the exchange of molecules between the general circulation and the nervous system. As such they form ideal structures for regulating TH exchange between the blood and the brain. To investigate the mechanism by which the developing brain regulates TH availability, we investigated the ontogenetic expression profiles of TH transporters, deiodinases and the TH distributor protein transthyretin (TTR) at the brain barriers during embryonic and early postnatal development using the chicken as a model. In situ hybridisation revealed expression of the TH transporters monocarboxylate transporter 8 (MCT8) and 10 (MCT10), organic anion transporting polypeptide 1C1 (OATP1C1) and L-type amino acid transporter 1 (LAT1) and the inactivating type 3 deiodinase (D3) in the choroid plexus which forms the blood-cerebrospinal fluid barrier. This was confirmed by quantitative PCR which additionally indicated strongly increasing expression of TTR as well as detectable expression of the activating type 2 deiodinase (D2) and the (in)activating type 1 deiodinase (D1). In the brain capillaries forming the blood-brain barrier in situ hybridisation showed exclusive expression of LAT1 and D2. The combined presence of LAT1 and D2 in brain capillaries suggests that the blood-brain barrier forms the main route for receptor-active T3 uptake into the embryonic chicken brain. Expression of multiple transporters, deiodinases and TTR in the choroid plexus indicates that the blood-cerebrospinal fluid barrier is also important in regulating early TH availability. The impact of these barrier systems can be deduced from the clear difference in T3 and T4 levels as well as the T3/T4 ratio between the developing brain and the general circulation. We conclude that the tight regulation of TH exchange at the brain barriers from early embryonic stages is one of the factors needed to allow the brain to develop within a relative microenvironment.
Publisher: Wiley
Date: 06-1995
DOI: 10.1111/J.1432-1033.1995.TB20645.X
Abstract: Thyroxine binding to proteins in pig plasma during electrophoresis was observed in the albumin, but not in the prealbumin and post-albumin regions. Transthyretin could be identified in medium from in vitro pig choroid plexus incubations by size and number of subunits and a very high rate of synthesis and secretion. Its electrophoretic mobility was intermediate between that of thyroxine-binding globulin and albumin. It bound thyroxine, retinol-binding protein, anti-(rat transthyretin) antibodies and behaved similarly to transthyretins from other vertebrate species when plasma was extracted with phenol. Inhibition experiments with the synthetic flavonoid F 21388, analysing the binding of thyroxine, suggested that transthyretin is not a major thyroxine carrier in the bloodstream of pigs. Cloning and sequencing of transthyretin cDNA from both choroid plexus and liver showed that the same transthyretin mRNA is expressed in pig choroid plexus and liver. The amino acid sequence derived from the nucleotide sequence revealed that pig transthyretin differs from the transthyretins of all other studied vertebrate species by an unusual C-terminal extension consisting of the amino acids glycine, alanine and leucine. This extension results from the mutation of a stop codon into a codon for glycine. The unusual C-terminal extensions do not seem to interfere with the access of thyroxine to its binding site in the central channel of transthyretin.
Publisher: Wiley
Date: 04-2005
Abstract: Transthyretin (TTR) is an extracellular thyroid hormone distributor protein in vertebrates, whose structure has been highly conserved between fish and humans. However, the ligand preferentially bound by TTR has changed during evolution from 3',3,5-L-triiodothyronine (T3) to 3',5',3,5-l-tetraiodothyronine (T4). We identified genes in the genomes of >50 species of nonvertebrates, which could code for TTR-like proteins. Molecular modeling suggested most would have similar 3D structures and electrostatic surface potentials to vertebrate TTRs. We lified TTR-like genes from a C. elegans cDNA library, demonstrating that it is transcribed. We synthesized recombinant TTR-like proteins from S. dublin and C. elegans. These proteins form tetramers similarly to vertebrate TTRs, but their ligands remain elusive.
Publisher: Frontiers Media SA
Date: 08-08-2019
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.YGCEN.2013.06.021
Abstract: Jawed vertebrates (Gnasthostomes) are broadly separated into cartilaginous fishes (Chondricthyes) and bony vertebrates (Osteichthyes). Cartilaginous fishes are ided into chimaeras (e.g. ratfish, rabbit fish and elephant shark) and elasmobranchs (e.g. sharks, rays and skates). Both cartilaginous fish and bony vertebrates are believed to have a common armoured bony ancestor (Class Placodermi), however cartilaginous fish are believed to have lost bone. This study has identified and investigated genes involved in skeletal development in vertebrates, in the cartilaginous fish, elephant shark (Callorhinchus milii). Ctnnb1 (β-catenin), Sfrp (secreted frizzled protein) and a single Sost or Sostdc1 gene (sclerostin or sclerostin domain-containing protein 1) were identified in the elephant shark genome and found to be expressed in a number of tissues, including cartilage. β-catenin was also localized in several elephant shark tissues. The expression of these genes, which belong to the Wnt/β-catenin pathway, is required for normal bone formation in mammals. These findings in the cartilaginous skeleton of elephant shark support the hypothesis that the common ancestor of cartilaginous fishes and bony vertebrates had the potential for making bone.
Publisher: MDPI AG
Date: 18-11-2021
Abstract: Red pitaya (Hylocereus polyrhizus, red pulp with pink peel), also known as dragon fruit, is a well-known species of pitaya fruit. Pitaya seeds and peels have been reported to exhibit higher concentrations of total polyphenols, beta-cyanins and amino acid than pulp, while anthocyanins (i.e., cyanidin 3-glucoside, delphinidin 3-glucoside and pelargonidin 3-glucoside) were only detected in the pulp extracts. Beta-cyanins, phenolics and flavonoids were found to increase gradually during fruit maturation and pigmentation appeared earlier in the pulp than peel. The phytochemicals were extracted and purified by various techniques and broadly used as natural, low-cost, and beneficial healthy compounds in foods, including bakery, wine, dairy, meat and confectionery products. These bioactive components also exhibit regulative influences on the human gut microbiota, glycaemic response, lipid accumulation, inflammation, growth of microbials and mutagenicity, but the mechanisms are yet to be understood. The objective of this study was to systematically summarise the effect of red pitaya’s maturation process on the nutritional profile and techno-functionality in a variety of food products. The findings of this review provide valuable suggestions for the red pitaya fruit processing industry, leading to novel formulations supported by molecular research.
Publisher: Springer Berlin Heidelberg
Date: 2009
Publisher: Wiley
Date: 1999
DOI: 10.1046/J.1432-1327.1999.00076.X
Abstract: Transthyretin, a protein synthesized and secreted by the choroid plexus and liver, binds thyroid hormones in extracellular compartments. This binding prevents accumulation of thyroid hormones in the lipids of membranes, establishing extracellular thyroid hormone pools for the distribution of the hormones throughout the body and brain. The N‐termini of the transthyretin subunits are longer and more hydrophobic in chicken than in eutherian transthyretins. Here, we show that this is a general structural feature of avian transthyretins. Systematic changes of protein structure during evolution result from selection pressure leading to changes in function. The evolution of transthyretin function, namely, the binding of thyroid hormones, was studied in nine vertebrate species. The affinity of thyroxine binding to transthyretin is lowest in avians (mean K d of about 30 n m ), intermediate in metatherians (mean K d of about 17 n m ) and highest in eutherians (mean K d of about 11 n m ). The affinity for 3,5,3′‐triiodothyronine shows an opposite trend, being four times higher for avian transthyretins than for mammalian transthyretins.
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.JCPA.2017.03.005
Abstract: Canine mixed mammary tumours (CMMTs) and human metaplastic breast carcinomas (HMBCs) share several histopathological features and risk factors. In both species, these tumours display epithelial and stromal components. HMBCs are rare malignant tumours, but CMMTs are one of the most common mammary tumours in dogs and are more often benign than malignant. In this study, benign (n = 88) and malignant (n = 13) CMMTs were characterized using specific antibodies against oestrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, cytokeratin 5/6, cytokeratin AE1/AE3, vimentin, Ki67, E-cadherin and p63. Cartilage and bone matrices associated with benign and malignant CMMTs were characterized using specific antibodies against BMP4, Runx2, Sox9 and osteopontin. The current study suggested that CMMTs are of epithelial origin, but display a myoepithelial-like differentiation. The findings suggest key roles for Sox9, Runx2 and BMP4 in chondrogenesis and bone formation in CMMTs. The high expression of osteopontin in CMMTs appears to be unrelated to tumour malignancy.
Publisher: Elsevier BV
Date: 2000
DOI: 10.1016/S0305-0491(99)00150-9
Abstract: The uptake of transferrin by the rat visceral yolk sac membranes, and the fate of this protein, were measured in a two-chambered system which allowed access to both surfaces of these membranes, i.e. that facing the maternal compartment and that facing the fetal compartment. 125I-labeled transferrin was internalized by the maternal surface of the visceral yolk sac but not by the fetal surface. Following internalization, this transferrin was degraded and the amino acids were secreted exclusively towards the fetal compartment. Transcytosis of intact transferrin was not detected in either direction. These results suggest that transport across the rat visceral yolk sac bound to maternally derived transferrin is not a major mechanism of iron transport in vivo. These results support a role for the visceral yolk sac in fetal metabolism, or supplying the fetus with amino acids derived from degradation of specific maternal plasma proteins, in this case, transferrin.
Publisher: Informa UK Limited
Date: 03-2007
Abstract: Initial studies on neural stem cell biology were performed mainly with embryonic stem cells, but exciting discoveries and advances in knowledge about tissue-specific stem cells have emerged in the last few years. This review focuses on stem and/or progenitor cells in the brain that drive adult neurogenesis in mammals. Neuronal precursor cells are found in two regions of the adult brain: the subventricular zone and the hippoc us. Adult neurogenesis in the subventricular zone has implications for behavior and olfactory function and, in the hippoc us, is involved in mood, learning and memory. Several neurodegenerative diseases (e.g., Alzheimer's disease, Huntington's disease and Parkinson's disease) are increasing in frequency as the population is aging. Understanding the hormonal aspects of how adult neurogenesis is regulated could lead to advances in understanding, managing and eventually, treating neurodegenerative disorders. In this review, we summarize what is currently known about the influence of hormones on adult neurogenesis. Many hormones that act through nuclear receptors are implicated in regulating neural progenitor cell biology. Given that nuclear receptors are well defined, drugable targets, further research on their mechanisms of action in adult neurogenesis are likely to engender new replacement, repair and therapeutic approaches.
Publisher: American Physiological Society
Date: 05-2005
DOI: 10.1152/AJPREGU.00793.2004
Abstract: Thyroid hormones are essential for vertebrate development. There is a characteristic rise in thyroid hormone levels in blood during critical periods of thyroid hormone-regulated development. Thyroid hormones are lipophilic compounds, which readily partition from an aqueous environment into a lipid environment. Thyroid hormone distributor proteins are required to ensure adequate distribution of thyroid hormones, throughout the aqueous environment of the blood, and to counteract the avid partitioning of thyroid hormones into the lipid environment of cell membranes. In human blood, these proteins are albumin, transthyretin and thyroxine-binding globulin. We analyzed the developmental profile of thyroid hormone distributor proteins in serum from a representative of each order of marsupials ( M. eugenii S.crassicaudata), a reptile ( C. porosus), in two species of salmonoid fishes ( S. salar O. tshawytsch), and throughout a calendar year for sea bream ( S. aurata). We demonstrated that during development, these animals have a thyroid hormone distributor protein present in their blood which is not present in the adult blood. At least in mammals, this additional protein has higher affinity for thyroid hormones than the thyroid hormone distributor proteins in the blood of the adult. In fish, reptile and polyprotodont marsupial, this protein was transthyretin. In a diprotodont marsupial, it was thyroxine-binding globulin. We propose an hypothesis that an augmented thyroid hormone distributor protein network contributes to the rise in total thyroid hormone levels in the blood during development.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Elsevier
Date: 2007
Publisher: Wiley
Date: 14-09-2009
DOI: 10.1111/J.1742-4658.2009.07244.X
Abstract: Thyroid hormones are involved in growth and development, particularly of the brain. Thus, it is imperative that these hormones get from their site of synthesis to their sites of action throughout the body and the brain. This role is fulfilled by thyroid hormone distributor proteins. Of particular interest is transthyretin, which in mammals is synthesized in the liver, choroid plexus, meninges, retinal and ciliary pigment epithelia, visceral yolk sac, placenta, pancreas and intestines, whereas the other thyroid hormone distributor proteins are synthesized only in the liver. Transthyretin is synthesized by all classes of vertebrates however, the tissue specificity of transthyretin gene expression varies widely between classes. This review summarizes what is currently known about the evolution of transthyretin synthesis in vertebrates and presents hypotheses regarding tissue-specific synthesis of transthyretin in each vertebrate class.
Publisher: Elsevier BV
Date: 10-2023
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.YGCEN.2017.09.012
Abstract: Normal development of the brain is dependent on the required amounts of thyroid hormones (THs) reaching specific regions of the brain during each stage of ontogeny. Many proteins are involved with regulation of TH bioavailability in the brain: the TH distributor protein transthyretin (TTR), TH transmembrane transporters (e.g. MCT8, MCT10, LAT1, OATP1C1) and deiodinases (D1, D2 and D3) which either activate or inactivate THs. Previous studies revealed that in mammals, T
Publisher: Elsevier BV
Date: 06-2007
Publisher: No publisher found
Date: 1996
Publisher: Elsevier BV
Date: 05-2023
Publisher: Wiley
Date: 16-04-2015
DOI: 10.1111/JNE.12271
Abstract: Transthyretin (TTR) is a protein that binds and distributes thyroid hormones (THs). TTR synthesised in the liver is secreted into the bloodstream and distributes THs around the body, whereas TTR synthesised in the choroid plexus is involved in movement of thyroxine from the blood into the cerebrospinal fluid and the distribution of THs in the brain. This is important because an adequate amount of TH is required for normal development of the brain. Nevertheless, there has been heated debate on the role of TTR synthesised by the choroid plexus during the past 20 years. We present both sides of the debate and how they can be reconciled by the discovery of TH transporters. New roles for TTR have been suggested, including the promotion of neuroregeneration, protection against neurodegeneration, and involvement in schizophrenia, behaviour, memory and learning. Recently, TTR synthesis was revealed in neurones and peripheral Schwann cells. Thus, the synthesis of TTR in the central nervous system (CNS) is more extensive than previously considered and bolsters the hypothesis that TTR may play wide roles in neurobiological function. Given the high conservation of TTR structure, function and tissue specificity and timing of gene expression, this implies that TTR has a fundamental role, during development and in the adult, across vertebrates. An alarming number of 'unnatural' chemicals can bind to TTR, thus potentially interfering with its functions in the brain. One role of TTR is delivery of THs throughout the CNS. Reduced TH availability during brain development results in a reduced IQ. The combination of the newly discovered sites of TTR synthesis in the CNS, the increasing number of neurological diseases being associated with TTR, the newly discovered functions of TTR and the awareness of the chemicals that can interfere with TTR biology render this a timely review on TTR in neurobiology.
Publisher: Springer Science and Business Media LLC
Date: 28-11-2018
DOI: 10.1007/S10911-018-9422-2
Abstract: Mixed tumors are characterized by the histological identification of two or more cell types. Commonly, a mixture of epithelial and myoepithelial cells is included in abundant stroma, which can consist of myxoid, chondroid or bony matrices. Spontaneously arising mixed tumors are rare lesions in the human breast but are common in human salivary glands and canine mammary glands. Subtle histopathological characteristics and overlapping attributes of malignant lesions with other benign lesions can lead to a diagnostic challenge. Mixed tumors can present as benign or malignant. While malignant mixed tumors are quite rare in the human breast they have a poor prognosis. Benign mixed mammary tumors occur more frequently in female dogs than in humans and are usually associated with a good prognosis. This review will provide a comprehensive overview of mixed mammary tumors, across various mammalian species.
Publisher: Elsevier BV
Date: 07-1997
DOI: 10.1016/S0305-0491(97)00139-9
Abstract: The binding of thyroxine to proteins in the blood plasma of the turtle, Trachemys scripta, was analyzed by incubation with radioactive thyroxine, electrophoresis and autoradiography. Albumin and an alpha-globulin were found to bind thyroxine no thyroxine-binding transthyretin was detected in the prealbumin region. In contrast to blood plasma, a thyroxine-binding prealbumin was observed in medium from T. scripta choroid plexus incubated in vitro. RNA was extracted from brain tissue containing choroid plexus and from liver of T. scripta and Chelydra serpentina and analyzed by hybridization with transthyretin cDNA from the lizard Tiliqua rugosa. The brain RNAs contained substantial amounts of transthyretin mRNA, whereas only trace amounts of transthyretin mRNA were detected in RNA from liver. No transthyretin mRNA was observed in RNA from kidney. The results support the hypothesis that the expression of the transthyretin gene first evolved in the choroid plexus of the brain at the stage of the stem reptiles, whereas abundant transthyretin synthesis in liver evolved much later, and independently, in mammals and birds.
Publisher: Elsevier BV
Date: 10-2008
DOI: 10.1016/J.MCE.2008.04.002
Abstract: Marsupials are a group of mammals that are under-exploited, in particular in developmental and evolutionary studies of biological systems. In this review, the roles that marsupials have played in elucidating the evolution of thyroid hormone distribution systems are summarised. Marsupials are born at very early developmental stages, and most development occurs during lactation rather than in utero. Studying thyroid hormone distribution systems during marsupial development, in addition to comparing the two Orders of marsupials, gave clues as to the selection pressures acting on the hepatic gene expression of transthyretin (TTR), one of the major thyroid hormone distributor proteins in blood. The structure of TTR in marsupials is intermediate between that of avian/reptilian TTRs and eutherian ("placental mammalian") TTRs. Consequently, the function of marsupial TTR is intermediate between those of avian/reptilian TTRs and eutherian TTRs. Thus, in some respects marsupials can be considered as "missing links" in vertebrate evolution.
Publisher: Oxford University Press
Date: 07-2011
DOI: 10.1093/MED/9780199235292.001.1
Abstract: Provides an up-to-date, stimulating, and comprehensive account of endocrinology and diabetes. Containing first rate, pragmatic advice on diagnosis and clear guidelines for recommended management, it also covers the scientific principles that underlie medical practice.
Publisher: Elsevier BV
Date: 10-2023
Publisher: Walter de Gruyter GmbH
Date: 10-01-2002
Publisher: Springer Science and Business Media LLC
Date: 06-03-2020
DOI: 10.1038/S41598-020-60699-8
Abstract: Transthyretin (TTR) is a protein that binds and distributes thyroid hormones (THs) in blood and cerebrospinal fluid. Previously, two reports identified TTR null mice as hypothyroid in the central nervous system (CNS). This prompted our investigations into developmentally regulated TH-dependent processes in brains of wildtype and TTR null mice. Despite logical expectations of a hypomyelinating phenotype in the CNS of TTR null mice, we observed a hypermyelination phenotype, synchronous with an increase in the density of oligodendrocytes in the corpus callosum and anterior commissure of TTR null mice during postnatal development. Furthermore, absence of TTR enhanced proliferation and migration of OPCs with decreased apoptosis. Neural stem cells (NSCs) isolated from the subventricular zone of TTR null mice at P21 revealed that the absence of TTR promoted NSC differentiation toward a glial lineage. Importantly, we identified TTR synthesis in OPCs, suggestive of an alternate biological function in these cells that may extend beyond an extracellular TH-distributor protein. The hypermyelination mechanism may involve increased pAKT (involved in oligodendrocyte maturation) in TTR null mice. Elucidating the regulatory role of TTR in NSC and OPC biology could lead to potential therapeutic strategies for the treatment of acquired demyelinating diseases.
Publisher: Elsevier BV
Date: 07-2001
Publisher: Springer Science and Business Media LLC
Date: 31-01-1206
DOI: 10.1038/S41598-020-58524-3
Abstract: Osteosarcoma (OS) is the most common malignant primary bone tumour in humans and dogs. Several studies have established the vital role of parathyroid hormone-related protein (PTHrP) and its receptor (PTHR1) in bone formation and remodeling. In addition, these molecules play a role in the progression and metastasis of many human tumour types. This study investigated the expression of PTHR1 and PTHrP in canine OS tissues and assessed their prognostic value. Formalin-fixed, paraffin-embedded tissue s les from 50 dogs diagnosed with primary OS were immunolabeled with antibodies specific for PTHR1 and PTHrP. The immunostaining intensity of tumours from patients with OS was correlated with survival time. Both PTHR1 and PTHrP were detected in all OS s les (n = 50). Dogs with OS tumours showing high immunostaining intensity for PTHR1 (n = 36) had significantly shorter survival times (p = 0.028, Log Rank p = 0.04, Cox regression) when compared with OS that had low immunostaining intensity for PTHR1 (n = 14).PTHrP immunostaining intensity did not correlate with survival time (p 0.05). The results of this study indicate that increased expression of PTHR1 antigen in canine OS is associated with poor prognosis. This suggests that PTHR1 may be useful as a prognostic indicator in canine OS.
Publisher: The Endocrine Society
Date: 10-2012
DOI: 10.1210/EN.2012-1463
Abstract: Thyroid hormone (TH) is essential for vertebrate brain development. Most research on TH and neuronal development focuses on late development, mainly the perinatal period in mammals. However, in human infants neuromotor development correlates best with maternal TH levels in the first trimester of pregnancy, suggesting that TH signaling could affect early brain development. Studying TH signaling in early embryogenesis in mammals is experimentally challenging. In contrast, free-living embryos, such as Xenopus laevis, permit physiological experimentation independent of maternal factors. We detailed key elements of TH signaling: ligands, receptors (TR), and deiodinases during early X. laevis development, before embryonic thyroid gland formation. Dynamic profiles for all components were found. Between developmental stages 37 and 41 (~48 h after hatching, coincident with a phase of continuing neurogenesis) significant increases in T(3) levels as well as in mRNA encoding deiodinases and TR occurred. Exposure of embryos at this developmental stage for 24 h to either a TH antagonist, NH-3, or to tetrabromobisphenol A, a flame retardant and known TH disruptor, differentially modulated the expression of a number of TH target genes implicated in neural stem cell function or neural differentiation. Moreover, 24-h exposure to either NH-3 or tetrabromobisphenol A diminished cell proliferation in the brain. Thus, these data show first, that TH signaling exerts regulatory roles in early X. laevis neurogenesis and second, that this period represents a potential window for endocrine disruption.
Publisher: Elsevier BV
Date: 06-2007
DOI: 10.1016/J.NEULET.2007.05.040
Abstract: Thyroid hormones (THs) are fundamental in regulation of growth and development, particularly of the brain. THs are required for full proliferative activity of neural stem cells in the subventricular zone (SVZ) of adult mouse brains, and also affect the normal fate of progenitor cells: apoptosis. Transthyretin (TTR) is a TH distributor protein in the blood and cerebrospinal fluid. TTR secretion by the choroid plexus is involved in transport of THs from blood into cerebrospinal fluid. We investigated the regulation of neural stem cell cycle in the SVZ of adult TTR null mice. Markers for neural stem cell mitosis that are reduced during hypothyroidism, did not differ between genotypes. However, in TTR null mice the level of apoptosis, the fate of most progenitor cells, was as low as that in brains of hypothyroid wildtype mice. Thus, lack of TTR results in reduced availability of TH to progenitor cells in the SVZ. We show that proliferation and apoptosis in the SVZ neural stem cell niche are differentially affected by the lack of TTR synthesis.
Publisher: Wiley
Date: 1995
DOI: 10.1111/J.1432-1033.1995.TB20402.X
Abstract: The evolution of the expression and the structure of the gene for transthyretin, a thyroxine‐binding plasma protein formerly called prealbumin, was studied in three marsupial species: the South American polyprotodont Monodelphis domestica , the Australian polyprotodont Sminthopsis macroura and the Australian diprotodont Petaurus breviceps. The transthyretin gene was found to be expressed in the choroid plexus of all three species. In liver it was expressed in P. breviceps and in M. domestica , but not in S. macroura. This, together with previous studies [Richardson, S. J., Bradley, A. J., Duan, W., Wettenhall, R. E. H., Harms, P. J., Babon, J. J., Southwell, B. R., Nicol, S., Donnellan, S. C. & Schreiber, G. (1994) Am. J. Physiol. 266 , R1359–R1370], suggests the independent evolution of transthyretin synthesis in the liver of the American Polyprotodonta and the Australian Diprotodonta. The results obtained from cloning and sequencing of the cDNA for transthyretin from the three species suggested that, in the evolution of the structure of transthyretin in vertebrates, marsupial transthyretin structures are intermediate between bird/reptile and eutherian transthyretin structures. In marsupials, as in birds and reptiles, a hydrophobic tripeptide beginning with valine and ending with histidine was found in transthyretin at a position which has been identified in eutherians as the border between exon 1 and intron 1. In humans, rats and mice, the nine nucleotides, coding for this tripeptide in marsupials/reptiles/birds, are found at the 5′ end of intron 1. They are no longer present in mature transthyretin mRNA. This results in a change in character of the N‐termini of the subunits of transthyretin from hydrophobic to hydrophilic. This change might affect the accessibility of the thyroxine‐binding site in the central channel of transthyretin, since, at least in humans, the N‐termini of the subunits of transthyretin are located in the vicinity of the channel entrance [Hamilton, J. A., Steinrauf, L. K., Braden, B. C., Liepnieks, J., Benson, M. D., Holmgren, G., Sandgren, O. & Steen, L. (1993) J. Biol. Chem. 268 , 2416–24241.
Start Date: 01-2012
End Date: 12-2013
Amount: $370,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 2010
End Date: 12-2015
Amount: $225,000.00
Funder: Australian Research Council
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