Chairman of the Hong Kong Trade Development Council (HKTDC) Dr Peter Lam welcomes the new 2020-21 Budget, including the additional HK$150 million funding to the HKTDC to help Hong Kong businesses find new opportunities and to help the...

John R. White
May 1, 2014; 27:82-86
From Research to Practice

β-1,3-d-Glucan is a ubiquitous glucose polymer produced by plants, bacteria, and most fungi. It has been used as a diagnostic tool in patients with invasive mycoses via a highly-sensitive reagent consisting of the blood coagulation system of horseshoe crab. However, no method is currently available for measuring β-1,6-glucan, another primary β-glucan structure of fungal polysaccharides. Herein, we describe the development of an economical and highly-sensitive and specific assay for β-1,6-glucan using a modified recombinant endo-β-1,6-glucanase having diminished glucan hydrolase activity. The purified β-1,6-glucanase derivative bound to the β-1,6-glucan pustulan with a KD of 16.4 nm. We validated the specificity of this β-1,6-glucan probe by demonstrating its ability to detect cell wall β-1,6-glucan from both yeast and hyphal forms of the opportunistic fungal pathogen Candida albicans, without any detectable binding to glucan lacking the long β-1,6-glucan branch. We developed a sandwich ELISA-like assay with a low limit of quantification for pustulan (1.5 pg/ml), and we successfully employed this assay in the quantification of extracellular β-1,6-glucan released by >250 patient-derived strains of different Candida species (including Candida auris) in culture supernatant in vitro. We also used this assay to measure β-1,6-glucan in vivo in the serum and in several organs in a mouse model of systemic candidiasis. Our work describes a reliable method for β-1,6-glucan detection, which may prove useful for the diagnosis of invasive fungal infections.

The developing nervous system is remarkably sensitive to environmental signals, including disruptive toxins, such as polybrominated diphenyl ethers (PBDEs). PBDEs are an environmentally pervasive class of brominated flame retardants whose neurodevelopmental toxicity mechanisms remain largely unclear. Using dissociated cortical neurons from embryonic Rattus norvegicus, we found here that chronic exposure to 6-OH–BDE-47, one of the most prevalent hydroxylated PBDE metabolites, suppresses both spontaneous and evoked neuronal electrical activity. On the basis of our previous work on mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) (MEK) biology and our observation that 6-OH–BDE-47 is structurally similar to kinase inhibitors, we hypothesized that certain hydroxylated PBDEs mediate neurotoxicity, at least in part, by impairing the MEK–ERK axis of MAPK signal transduction. We tested this hypothesis on three experimental platforms: 1) in silico, where modeling ligand–protein docking suggested that 6-OH–BDE-47 is a promiscuous ATP-competitive kinase inhibitor; 2) in vitro in dissociated neurons, where 6-OH–BDE-47 and another specific hydroxylated BDE metabolite similarly impaired phosphorylation of MEK/ERK1/2 and activity-induced transcription of a neuronal immediate early gene; and 3) in vivo in Drosophila melanogaster, where developmental exposures to 6-OH–BDE-47 and a MAPK inhibitor resulted in offspring displaying similarly increased frequency of mushroom-body β–lobe midline crossing, a metric of axonal guidance. Taken together, our results support that certain ortho-hydroxylated PBDE metabolites are promiscuous kinase inhibitors and can cause disruptions of critical neurodevelopmental processes, including neuronal electrical activity, pre-synaptic functions, MEK–ERK signaling, and axonal guidance.

(University of Massachusetts Lowell) UMass Medical School and UMass Lowell will perform a key role in a new National Institutes of Health initiative aimed at speeding innovation, development and commercialization of COVID-19 testing technologies via their Center for Advancing Point of Care Technologies collaboration.

The Hong Kong Special Administrative Region (HKSAR) Government welcomes the promulgation of the Meteorological Development Plan ...

(Paul Scherrer Institute) Researchers at the Paul Scherrer Institute PSI have collaborated with British economists to study how energy consumption by Swiss industry develops depending on energy pricing. To this end, they examined in particular the prices and consumption of both electricity and natural gas over the past decades. One result: For the most part, price increases have only long-term effects on energy consumption.

(Carnegie Mellon University) A new study developed a model of regulation in which the probability of a stricter standard being enacted increased with the proportion of firms in an industry that could meet the standard. The study found that regulations that consider the proportion of firms that can meet the new standard can motivate the development of a new green technology more effectively than regulations that do not consider this factor.

(University of Tsukuba) Researchers from the University of Tsukuba have revealed that pectin, a carbohydrate found in plant cell walls, plays a vital part in the development of female reproductive tissues of rice plants. It was found that the presence of a gene involved in pectin modification increased plant fertility relative to a modified plant with the gene removed. These findings could have major implications in crop variety development and genetic modification.

(Smithsonian Tropical Research Institute) Oil pollution is known to cause lethal and sublethal responses on coral communities in the short-term, but its long-term effects have not been widely studied. The Bahia Las Minas oil spill, which contaminated about 40 square kilometers (about 15 square miles) near the Smithsonian's Galeta Point Marine Laboratory in Colon and became the largest recorded near coastal habitats in Panama, served as an opportunity to understand how coral reefs in tropical ecosystems recover from acute contamination over time.

Barbara J. Anderson
Jan 1, 2004; 17:
Articles

The SBDC offers resources and guidance to Harlem’s small businesses amidst the COVID-19 crisis.

The developing nervous system is remarkably sensitive to environmental signals, including disruptive toxins, such as polybrominated diphenyl ethers (PBDEs). PBDEs are an environmentally pervasive class of brominated flame retardants whose neurodevelopmental toxicity mechanisms remain largely unclear. Using dissociated cortical neurons from embryonic Rattus norvegicus, we found here that chronic exposure to 6-OH–BDE-47, one of the most prevalent hydroxylated PBDE metabolites, suppresses both spontaneous and evoked neuronal electrical activity. On the basis of our previous work on mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) (MEK) biology and our observation that 6-OH–BDE-47 is structurally similar to kinase inhibitors, we hypothesized that certain hydroxylated PBDEs mediate neurotoxicity, at least in part, by impairing the MEK–ERK axis of MAPK signal transduction. We tested this hypothesis on three experimental platforms: 1) in silico, where modeling ligand–protein docking suggested that 6-OH–BDE-47 is a promiscuous ATP-competitive kinase inhibitor; 2) in vitro in dissociated neurons, where 6-OH–BDE-47 and another specific hydroxylated BDE metabolite similarly impaired phosphorylation of MEK/ERK1/2 and activity-induced transcription of a neuronal immediate early gene; and 3) in vivo in Drosophila melanogaster, where developmental exposures to 6-OH–BDE-47 and a MAPK inhibitor resulted in offspring displaying similarly increased frequency of mushroom-body β–lobe midline crossing, a metric of axonal guidance. Taken together, our results support that certain ortho-hydroxylated PBDE metabolites are promiscuous kinase inhibitors and can cause disruptions of critical neurodevelopmental processes, including neuronal electrical activity, pre-synaptic functions, MEK–ERK signaling, and axonal guidance.

Guan-Da Syu
Apr 17, 2020; 0:R120.001936v1-mcp.R120.001936
Review