Hear about all of Canada's UNESCO World Heritage Sites as the Amateur Traveler talks again to Gary Arndt of Everything-Everywhere.com about traveling to all 17 sites. Some sites like Old Québec are easy to reach and others like Wood Buffalo and Nahanni National Parks (the last two that Gary visited) are quite remote.

Hear about travel to the state of Guanajuato Mexico (including San Miguel de Allende) as the Amateur Traveler talks to Tim Leffel of perceptivetravel.com about his adopted home.

Hear about travel to New Orleans Louisiana as the Amateur Traveler talks to freelance journalist Jill Robinson. Jill agrees with Earl King "There ain't no city like New Orleans".

Hear about travel to Indianapolis, Indiana as the Amateur Traveler talked to Nancy Parode the Senior Travel Expert at about.com about travel to this mid-western capital.

Hear about travel to the Guna Yala region of Panama as the Amateur Traveler talks to Lynn Smith from lynnsmithdestinations.com about a small boat cruise in these remote islands.

Hear about travel to Botswana on safari as I, the Amateur Traveler, relates stories from his recent experience on mobile safari in Botswana's Okavango Delta and a Safari Camp experience in the Kalahari desert on a press trip with Botswana Trek.

Hear about travel to The Canal du Midi and Carcassonne in southern France as Chris from the Amateur Traveler talks about his recent luxury hotel barge cruise.

Hear about travel to Lafayette, Louisiana as the Amateur Traveler talks to Susan Moore from solotripsandtips.com about this center of Cajun culture.

Hear about traveling the Dempster Highway as the Amateur Traveler talks to Lisa from TheHotFlashPacker.com about this iconic drive into the Arctic Circle in Canada. 

Hear about travel to the Canary Islands as the Amateur Traveler talks to Alice Ford from alicesadventuresonearth.com about the best of the Canary Islands.

CTVNews.ca asked Canadians to share how they were using their CERB payments and got a flood of responses. Most said they were covering the basics -- housing, groceries, transportation and medicine.

If you’re already a software product manager (PM), you have a head start on becoming a PM for artificial intelligence (AI) or machine learning (ML). You already know the game and how it is played: you’re the coordinator who ties everything together, from the developers and designers to the executives. You’re responsible for the design, […]

Canada Post's main plant in Calgary has six confirmed cases of COVID-19. That news was confirmed Friday by Dr. Deena Hinshaw at her daily update.

Prime Minister Justin Trudeau says Canada will not pay the full price for medical masks that do not live up to medical standards.

The Vuelta a Espana organisers have confirmed that a race already rescheduled and shortened would also now cut its foray into neighbouring Portugal from the 2020 itinerary.

One day, a teacher entered her classroom and placed a glass jar on the table. She put two large rocks into the jar until no more could fit. She asked the class if the jar was full and they all said, “Yes.” She responded, “Really?” She pulled out a pile of small pebbles, added them […]

The post How to Become Great by Managing Procrastination appeared first on Dumb Little Man.

Manitoba’s unemployment rate nearly doubled between March and April, according to the monthly report from Statistics Canada released Friday morning.

Research Event

Event participants

Yezid Sayigh, Senior Fellow, Carnegie Middle East Center
David Butter, Associate Fellow, Middle East and North Africa Programme, Chatham House
Chair: Lina Khatib, Head, Middle East and North Africa Programme, Chatham House

Invitation Only Research Event

Event participants

Dr Lina Khatib, Head, Middle East and North Africa Programme, Chatham House
Dr Renad Mansour, Research Fellow, Middle East and North Africa Programme, Chatham House

12 March 2015 , Volume 91, Number 2

10 May 2016

As the United States’ international engagement changes, Canada and Europe should increase coordination with it to prevent power vacuums from emerging.

Myriam Ferro
May 1, 2003; 2:325-345
Research

Joe Carroll
Feb 1, 2003; 2:117-126
Research

Boris Macek
Feb 1, 2008; 7:299-307
Research

Tamar Geiger
Mar 1, 2012; 11:M111.014050-M111.014050
Special Issue: Prospects in Space and Time

Lawrence E. Ostrowski
Jun 1, 2002; 1:451-465
Research

Qiang Tian
Oct 1, 2004; 3:960-969
Research

Ludovic C. Gillet
Jun 1, 2012; 11:O111.016717-O111.016717
Research

Claudio P. Albuquerque
Jul 1, 2008; 7:1389-1396
Research

Linn Fagerberg
Feb 1, 2014; 13:397-406
Research

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.

Formate oxidation to carbon dioxide is a key reaction in one-carbon compound metabolism, and its reverse reaction represents the first step in carbon assimilation in the acetogenic and methanogenic branches of many anaerobic organisms. The molybdenum-containing dehydrogenase FdsABG is a soluble NAD+-dependent formate dehydrogenase and a member of the NADH dehydrogenase superfamily. Here, we present the first structure of the FdsBG subcomplex of the cytosolic FdsABG formate dehydrogenase from the hydrogen-oxidizing bacterium Cupriavidus necator H16 both with and without bound NADH. The structures revealed that the two iron-sulfur clusters, Fe4S4 in FdsB and Fe2S2 in FdsG, are closer to the FMN than they are in other NADH dehydrogenases. Rapid kinetic studies and EPR measurements of rapid freeze-quenched samples of the NADH reduction of FdsBG identified a neutral flavin semiquinone, FMNH•, not previously observed to participate in NADH-mediated reduction of the FdsABG holoenzyme. We found that this semiquinone forms through the transfer of one electron from the fully reduced FMNH−, initially formed via NADH-mediated reduction, to the Fe2S2 cluster. This Fe2S2 cluster is not part of the on-path chain of iron-sulfur clusters connecting the FMN of FdsB with the active-site molybdenum center of FdsA. According to the NADH-bound structure, the nicotinamide ring stacks onto the re-face of the FMN. However, NADH binding significantly reduced the electron density for the isoalloxazine ring of FMN and induced a conformational change in residues of the FMN-binding pocket that display peptide-bond flipping upon NAD+ binding in proper NADH dehydrogenases.

6 February 2014 , Volume 70, Number 1

Ghana’s leading undercover reporter uses disguises to expose trafficking rings and government corruption. His work has led to convictions and the recovery of millions of dollars in state funds. He talks to Libby Powell

7 May 2020 , Volume 96, Number 3

Systemic infection and proliferation of intracellular pathogens require the biogenesis of a growth-stimulating compartment. The gastrointestinal pathogen Salmonella enterica commonly forms highly dynamic and extensive tubular membrane compartments built from Salmonella-modified membranes (SMMs) in diverse host cells. Although the general mechanism involved in the formation of replication-permissive compartments of S. enterica is well researched, much less is known regarding specific adaptations to different host cell types. Using an affinity-based proteome approach, we explored the composition of SMMs in murine macrophages. The systematic characterization provides a broader landscape of host players to the maturation of Salmonella-containing compartments and reveals core host elements targeted by Salmonella in macrophages as well as epithelial cells. However, we also identified subtle host specific adaptations. Some of these observations, such as the differential involvement of the COPII system, Rab GTPases 2A, 8B, 11 and ER transport proteins Sec61 and Sec22B may explain cell line-dependent variations in the pathophysiology of Salmonella infections. In summary, our system-wide approach demonstrates a hitherto underappreciated impact of the host cell type in the formation of intracellular compartments by Salmonella.

Formate oxidation to carbon dioxide is a key reaction in one-carbon compound metabolism, and its reverse reaction represents the first step in carbon assimilation in the acetogenic and methanogenic branches of many anaerobic organisms. The molybdenum-containing dehydrogenase FdsABG is a soluble NAD+-dependent formate dehydrogenase and a member of the NADH dehydrogenase superfamily. Here, we present the first structure of the FdsBG subcomplex of the cytosolic FdsABG formate dehydrogenase from the hydrogen-oxidizing bacterium Cupriavidus necator H16 both with and without bound NADH. The structures revealed that the two iron-sulfur clusters, Fe4S4 in FdsB and Fe2S2 in FdsG, are closer to the FMN than they are in other NADH dehydrogenases. Rapid kinetic studies and EPR measurements of rapid freeze-quenched samples of the NADH reduction of FdsBG identified a neutral flavin semiquinone, FMNH•, not previously observed to participate in NADH-mediated reduction of the FdsABG holoenzyme. We found that this semiquinone forms through the transfer of one electron from the fully reduced FMNH−, initially formed via NADH-mediated reduction, to the Fe2S2 cluster. This Fe2S2 cluster is not part of the on-path chain of iron-sulfur clusters connecting the FMN of FdsB with the active-site molybdenum center of FdsA. According to the NADH-bound structure, the nicotinamide ring stacks onto the re-face of the FMN. However, NADH binding significantly reduced the electron density for the isoalloxazine ring of FMN and induced a conformational change in residues of the FMN-binding pocket that display peptide-bond flipping upon NAD+ binding in proper NADH dehydrogenases.

Research Event

Expert

V. V. Vlasov and N. A. Rautian
Trans. Moscow Math. Soc. 80 (2020), 169-188.
Abstract, references and article information

THERE'S nothing like the sweet taste of victory, especially when it's long in coming.

Sovereign nations typically measure economic success in terms of GDP (income) but this approach is risky as it fails to track and measure the impact of this on nature. Inclusive wealth, on the other hand captures financial and produced capital, but also the skills in our workforce (human capital), the cohesion in our society (social capital) and the value of our environment (natural capital).