Gretchen Benson
Feb 1, 2011; 24:36-40
Nutrition FYI

Ruban Dhaliwal
Feb 1, 2014; 27:9-20
Research to Practice

Jeanette Ezzo
Oct 1, 2001; 14:
Articles

W. Guyton Hornsby
Apr 1, 2005; 18:102-107
Articles

Belinda S. O’Connell
Aug 1, 2001; 14:
Articles

Pasquale Passarella
Aug 1, 2018; 31:218-224
From Research to Practice

Amy P. Campbell
May 1, 2017; 30:76-81
From Research to Practice

Samuel Dagogo-Jack
Jan 1, 2002; 15:
Articles

Geralyn Spollett
Jan 1, 2003; 16:
Case Studies

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.

In cyanobacteria, metabolic pathways that use the nitrogen-rich amino acid arginine play a pivotal role in nitrogen storage and mobilization. The N-terminal domains of two recently identified bacterial enzymes: ArgZ from Synechocystis and AgrE from Anabaena, have been found to contain an arginine dihydrolase. This enzyme provides catabolic activity that converts arginine to ornithine, resulting in concomitant release of CO2 and ammonia. In Synechocystis, the ArgZ-mediated ornithine–ammonia cycle plays a central role in nitrogen storage and remobilization. The C-terminal domain of AgrE contains an ornithine cyclodeaminase responsible for the formation of proline from ornithine and ammonia production, indicating that AgrE is a bifunctional enzyme catalyzing two sequential reactions in arginine catabolism. Here, the crystal structures of AgrE in three different ligation states revealed that it has a tetrameric conformation, possesses a binding site for the arginine dihydrolase substrate l-arginine and product l-ornithine, and contains a binding site for the coenzyme NAD(H) required for ornithine cyclodeaminase activity. Structure–function analyses indicated that the structure and catalytic mechanism of arginine dihydrolase in AgrE are highly homologous with those of a known bacterial arginine hydrolase. We found that in addition to other active-site residues, Asn-71 is essential for AgrE's dihydrolase activity. Further analysis suggested the presence of a passage for substrate channeling between the two distinct AgrE active sites, which are situated ∼45 Å apart. These results provide structural and functional insights into the bifunctional arginine dihydrolase–ornithine cyclodeaminase enzyme AgrE required for arginine catabolism in Anabaena.

Numerous zinc ectoenzymes are metalated by zinc and activated in the compartments of the early secretory pathway before reaching their destination. Zn transporter (ZNT) proteins located in these compartments are essential for ectoenzyme activation. We have previously reported that ZNT proteins, specifically ZNT5–ZNT6 heterodimers and ZNT7 homodimers, play critical roles in the activation of zinc ectoenzymes, such as alkaline phosphatases (ALPs), by mobilizing cytosolic zinc into these compartments. However, this process remains incompletely understood. Here, using genetically-engineered chicken DT40 cells, we first determined that Zrt/Irt-like protein (ZIP) transporters that are localized to the compartments of the early secretory pathway play only a minor role in the ALP activation process. These transporters included ZIP7, ZIP9, and ZIP13, performing pivotal functions in maintaining cellular homeostasis by effluxing zinc out of the compartments. Next, using purified ALP proteins, we showed that zinc metalation on ALP produced in DT40 cells lacking ZNT5–ZNT6 heterodimers and ZNT7 homodimers is impaired. Finally, by genetically disrupting both ZNT5 and ZNT7 in human HAP1 cells, we directly demonstrated that the tissue-nonspecific ALP-activating functions of both ZNT complexes are conserved in human cells. Furthermore, using mutant HAP1 cells, we uncovered a previously-unrecognized and unique spatial regulation of ZNT5–ZNT6 heterodimer formation, wherein ZNT5 recruits ZNT6 to the Golgi apparatus to form the heterodimeric complex. These findings fill in major gaps in our understanding of the molecular mechanisms underlying zinc ectoenzyme activation in the compartments of the early secretory pathway.

Fabry disease is a heritable lipid disorder caused by the low activity of α-galactosidase A and characterized by the systemic accumulation of globotriaosylceramide (Gb3). Recent studies have reported a structural heterogeneity of Gb3 in Fabry disease, including Gb3 isoforms with different fatty acids and Gb3 analogs with modifications on the sphingosine moiety. However, Gb3 assays are often performed only on the selected Gb3 isoforms. To precisely determine the total Gb3 concentration, here we established two methods for determining both Gb3 isoforms and analogs. One was the deacylation method, involving Gb3 treatment with sphingolipid ceramide N-deacylase, followed by an assay of the deacylated products, globotriaosylsphingosine (lyso-Gb3) and its analogs, by ultra-performance LC coupled to tandem MS (UPLC-MS/MS). The other method was a direct assay established in the present study for 37 Gb3 isoforms and analogs/isoforms by UPLC-MS/MS. Gb3s from the organs of symptomatic animals of a Fabry disease mouse model were mainly Gb3 isoforms and two Gb3 analogs, such as Gb3(+18) containing the lyso-Gb3(+18) moiety and Gb3(−2) containing the lyso-Gb3(−2) moiety. The total concentrations and Gb3 analog distributions determined by the two methods were comparable. Gb3(+18) levels were high in the kidneys (24% of total Gb3) and the liver (13%), and we observed Gb3(−2) in the heart (10%) and the kidneys (5%). These results indicate organ-specific expression of Gb3 analogs, insights that may lead to a deeper understanding of the pathophysiology of Fabry disease.

VOLUME 295 (2020) PAGES 1898–1914Yichen Zhong's name was misspelled. The correct spelling is shown above.

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(Cleveland Clinic) A new Cleveland Clinic study demonstrates the importance of genetics evaluation and genetic testing for children, adolescents and young adults with solid tumor cancers. The study was published today in Nature Communications.

(University of Warwick) 21st century X-ray technology has allowed University of Warwick scientists to peer back through time at the production of the armour worn by the crew of Henry VIII's favoured warship, the Mary Rose.

(Harvard Medical School) An international research team has conducted the first in-depth, wide-scale study of the genomic history of ancient civilizations in the central Andes mountains and coast before European contact. The findings reveal early genetic distinctions between groups in nearby regions, population mixing within and beyond the Andes, surprising genetic continuity amid cultural upheaval, and ancestral cosmopolitanism among some of the region's most well-known ancient civilizations.

(University of California - Santa Cruz) Restoration ecologist Karen Holl has a simple message for anyone who thinks planting 1 trillion trees will reverse the damage of climate change: 'We can't plant our way out of climate change.'

Andrea López
Feb 1, 2012; 25:14-18
From Research to Practice

Linda J. Piccinino
May 1, 2017; 30:95-100
From Research to Practice

Gregory A. Maynard
Oct 1, 2008; 21:241-247
Articles

Jan Pearson
Apr 1, 2001; 14:
Articles

Carol Rees Parrish
Oct 1, 2007; 20:231-234
Nutrition FYI

Belinda S. O’Connell
Aug 1, 2001; 14:
Articles

Martha Mitchell Funnell
Oct 1, 2007; 20:221-226
Articles

Ruban Dhaliwal
Feb 1, 2014; 27:9-20
Research to Practice

Russell E. Glasgow
Jan 1, 2001; 14:
Articles

Emmy Suhl
Oct 1, 2006; 19:234-240
Articles

Russell E. Glasgow
Apr 1, 2001; 14:
Feature Articles

Daren R. Anderson
Apr 1, 2010; 23:97-105
Feature Articles

Tammie M. Johnson
Jan 1, 2010; 23:41-46
Feature Articles

Michele Heisler
Oct 1, 2007; 20:214-221
Articles

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

Sharlene Emerson
Apr 1, 2006; 19:79-83
Articles

T. Chas Skinner
Apr 1, 2003; 16:
Lifestyle and Behavior

Back in January when dancehall artiste Govana released the track HAMANTS Convo, the storyline captivated listeners across the globe. For weeks, the song, which highlights infidelity in relationships, trended at number one on the local YouTube...

Research Event

Event participants

Silkie Carlo, Director, Big Brother Watch
Professor David Kaye, UN Special Rapporteur on the Promotion and Protection of the Right to Freedom of Opinion and Expression, University of California, Irvine, School of Law  
Professor Lorna McGregor, Principal Investigator and Co-Director of the ESRC, Human Rights, Big Data and Technology Project
James Williams, Oxford Internet Institute
Chair: Harriet Moynihan, Associate Fellow, International Law Programme, Chatham House

Fabry disease is a heritable lipid disorder caused by the low activity of α-galactosidase A and characterized by the systemic accumulation of globotriaosylceramide (Gb3). Recent studies have reported a structural heterogeneity of Gb3 in Fabry disease, including Gb3 isoforms with different fatty acids and Gb3 analogs with modifications on the sphingosine moiety. However, Gb3 assays are often performed only on the selected Gb3 isoforms. To precisely determine the total Gb3 concentration, here we established two methods for determining both Gb3 isoforms and analogs. One was the deacylation method, involving Gb3 treatment with sphingolipid ceramide N-deacylase, followed by an assay of the deacylated products, globotriaosylsphingosine (lyso-Gb3) and its analogs, by ultra-performance LC coupled to tandem MS (UPLC-MS/MS). The other method was a direct assay established in the present study for 37 Gb3 isoforms and analogs/isoforms by UPLC-MS/MS. Gb3s from the organs of symptomatic animals of a Fabry disease mouse model were mainly Gb3 isoforms and two Gb3 analogs, such as Gb3(+18) containing the lyso-Gb3(+18) moiety and Gb3(−2) containing the lyso-Gb3(−2) moiety. The total concentrations and Gb3 analog distributions determined by the two methods were comparable. Gb3(+18) levels were high in the kidneys (24% of total Gb3) and the liver (13%), and we observed Gb3(−2) in the heart (10%) and the kidneys (5%). These results indicate organ-specific expression of Gb3 analogs, insights that may lead to a deeper understanding of the pathophysiology of Fabry disease.

Lucía Trilla-Fuertes
Apr 1, 2020; 19:690-700
Research

Xien Yu Chua
Apr 1, 2020; 19:730-743
Technological Innovation and Resources

Beatriz Rocha
Apr 1, 2020; 19:574-588
Research

Sonia Podvin
Apr 15, 2020; 0:RA120.002079v1-mcp.RA120.002079
Research

Yan Zhou Tran
Mar 31, 2020; 0:RA120.002036v1-mcp.RA120.002036
Research

Samuel W Entwisle
Apr 6, 2020; 0:RA120.001946v2-mcp.RA120.001946
Research

Yafeng Zhu
Mar 23, 2020; 0:TIR119.001646v1-mcp.TIR119.001646
Technological Innovation and Resources

Lindsay K Pino
Apr 20, 2020; 0:P119.001913v1-mcp.P119.001913
Perspective