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Cytochrome c oxidase (CcO) reduces O2 to water, coupled with a proton-pumping process. The structure of the O2-reduction site of CcO contains two reducing equivalents, Fea32+ and CuB1+, and suggests that a peroxide-bound state (Fea33+–O−–O−–CuB2+) rather than an O2-bound state (Fea32+–O2) is the initial catalytic intermediate. Unexpectedly, however, resonance Raman spectroscopy results have shown that the initial intermediate is Fea32+–O2, whereas Fea33+–O−–O−–CuB2+ is undetectable. Based on X-ray structures of static noncatalytic CcO forms and mutation analyses for bovine CcO, a proton-pumping mechanism has been proposed. It involves a proton-conducting pathway (the H-pathway) comprising a tandem hydrogen-bond network and a water channel located between the N- and P-side surfaces. However, a system for unidirectional proton-transport has not been experimentally identified. Here, an essentially identical X-ray structure for the two catalytic intermediates (P and F) of bovine CcO was determined at 1.8 Å resolution. A 1.70 Å Fe–O distance of the ferryl center could best be described as Fea34+ = O2−, not as Fea34+–OH−. The distance suggests an ∼800-cm−1 Raman stretching band. We found an interstitial water molecule that could trigger a rapid proton-coupled electron transfer from tyrosine-OH to the slowly forming Fea33+–O−–O−–CuB2+ state, preventing its detection, consistent with the unexpected Raman results. The H-pathway structures of both intermediates indicated that during proton-pumping from the hydrogen-bond network to the P-side, a transmembrane helix closes the water channel connecting the N-side with the hydrogen-bond network, facilitating unidirectional proton-pumping during the P-to-F transition.

Optic atrophy 1 (OPA1) is a dynamin protein that mediates mitochondrial fusion at the inner membrane. OPA1 is also necessary for maintaining the cristae and thus essential for supporting cellular energetics. OPA1 exists as membrane-anchored long form (L-OPA1) and short form (S-OPA1) that lacks the transmembrane region and is generated by cleavage of L-OPA1. Mitochondrial dysfunction and cellular stresses activate the inner membrane–associated zinc metallopeptidase OMA1 that cleaves L-OPA1, causing S-OPA1 accumulation. The prevailing notion has been that L-OPA1 is the functional form, whereas S-OPA1 is an inactive cleavage product in mammals, and that stress-induced OPA1 cleavage causes mitochondrial fragmentation and sensitizes cells to death. However, S-OPA1 contains all functional domains of dynamin proteins, suggesting that it has a physiological role. Indeed, we recently demonstrated that S-OPA1 can maintain cristae and energetics through its GTPase activity, despite lacking fusion activity. Here, applying oxidant insult that induces OPA1 cleavage, we show that cells unable to generate S-OPA1 are more sensitive to this stress under obligatory respiratory conditions, leading to necrotic death. These findings indicate that L-OPA1 and S-OPA1 differ in maintaining mitochondrial function. Mechanistically, we found that cells that exclusively express L-OPA1 generate more superoxide and are more sensitive to Ca2+-induced mitochondrial permeability transition, suggesting that S-OPA1, and not L-OPA1, protects against cellular stress. Importantly, silencing of OMA1 expression increased oxidant-induced cell death, indicating that stress-induced OPA1 cleavage supports cell survival. Our findings suggest that S-OPA1 generation by OPA1 cleavage is a survival mechanism in stressed cells.

Aos primeiros sinais de visão embaçada, as hipóteses mais frequentes sempre são miopia, astigmatismo, hipermetropia. Mas esses sintomas podem indicar outra doença ocular chamada ceratocone - uma deformidade progressiva da córnea, que assume o formato...

The post Visão embaçada e distorcida nem sempre é miopia: fique atento aos sinais do ceratocone appeared first on Saúde Próspera.

Tem tomado seus cuidados com a pele? Neste artigo vamos ensinar a fazer limpeza de pele caseira. Conhecer  os benefícios para limpeza de pele. Conheça o passo a passo a…

The post Cuidados com a pele – Aprenda a fazer limpeza de pele caseira appeared first on Saúde Próspera.

Publication Date: Apr 10 2020 Yes. According to the SEC, once an ETF becomes eligible to operate under Rule 6c-11 and elects to list on Nasdaq under Nasdaq Rule 5704, the existing order related to that fund (and all other funds under that exemptive order) will be rescinded. Once a fund is listed under Nasdaq Rule 5704, it will not be able to relist under Nasdaq Rule 5705(b) (Index Fund Shares) or Nasdaq Rule 5735 (Managed Fund Shares) unless a new exemptive relief order is obtained from the SEC....

Publication Date: Apr 10 2020 Funds listed under Nasdaq Rule 5704 are required to submit an annual certification regarding the funds compliance with Rule 6c-11 during the most recent fiscal year. The certification is required within 30 calendar days of a fund’s fiscal year end. The certification can be found here....

Publication Date: Apr 10 2020 On or before December 22, 2020, all ETFs that meet the definition of "Exchange Traded Fund" in Nasdaq Rule 5704(a)(1)(A) will need to be compliant with Rule 6c-11. If it is determined that an ETF no longer complies with Rule 6c-11 and therefore no longer complies Nasdaq Rule 5704, Nasdaq will generally issue a letter of deficiency. The ETF will generally be given 45 days to submit a plan to regain compliance. If the plan is accepted, Nasdaq Staff can grant an...

Publication Date: May 4 2020 On May 1, 2020, Nasdaq adopted Rule 5636T, operative through, and including, June 30, 2020, to provide listed companies with a temporary exception from certain shareholder approval requirements. A Company must submit an application to Nasdaq’s Listing Qualifications Department demonstrating that the transaction satisfies the requirements in Rule 5636T and must provide the Notification Form: Listing of Additional Shares (“LAS Form”) required by...

7 November 2019

The current dispute between the US and China goes far beyond trade tariffs and tit-for-tat reprisals: the underlying driver is a race for global technological supremacy. This paper examines the risks of greater strategic competition as well as potential solutions for mitigating the impacts of the US–China economic confrontation.

8 January 2020 , Volume 96, Number 1

8 January 2020 , Volume 96, Number 1

8 January 2020 , Volume 96, Number 1

6 November 2019 , Volume 96, Number 1

The first issue of International Affairs in 2020 explores the geopolitics of the 'Indo-Pacific' region.

Research Event

Event participants

Jennifer Lind, Associate Fellow, US and the Americas Programme and Asia-Pacific Programme, Chatham House
Chair: Tania Branigan, Leader Writer, The Guardian  

Research Event

Event participants

Vasuki Shastry, Associate Fellow, Asia-Pacific Programme
Ravi Velloor, Associate Editor, The Straits Times
Chair: Yu Jie, Senior Research Fellow on China, Asia-Pacific Programme, Chatham House

Research Event

Event participants

Yu Jie, Senior Research Fellow on China, Asia-Pacific Programme, Chatham House
Kerry Brown, Associate Fellow, Asia-Pacific Programme, Chatham House; Professor of Chinese Studies and Director of Lau China Institute, King’s College London

Stents are expandable tubes that are inserted into blocked or damaged blood vessels. They offer a practical way to treat coronary artery disease, repairing vessels and keeping them open so that blood can flow freely. When stents work, they are a great alternative to radical surgery, but they can deteriorate or become dislodged. Mathematical models of blood vessels and stents are helping to determine better shapes and materials for the tubes. These models are so accurate that the FDA is considering requiring mathematical modeling in the design of stents before any further testing is done, to reduce the need for expensive experimentation. Precise modeling of the entire human vascular system is far beyond the reach of current computational power, so researchers focus their detailed models on small subsections, which are coupled with simpler models of the rest of the system. The Navier-Stokes equations are used to represent the flow of blood and its interaction with vessel walls. A mathematical proof was the central part of recent research that led to the abandonment of one type of stent and the design of better ones. The goal now is to create better computational fluid-vessel models and stent models to improve the treatment and prediction of coronary artery disease the major cause of heart attacks. For More Information: Design of Optimal Endoprostheses Using Mathematical Modeling, Canic, Krajcer, and Lapin, Endovascular Today, May 2006.

Stents are expandable tubes that are inserted into blocked or damaged blood vessels. They offer a practical way to treat coronary artery disease, repairing vessels and keeping them open so that blood can flow freely. When stents work, they are a great alternative to radical surgery, but they can deteriorate or become dislodged. Mathematical models of blood vessels and stents are helping to determine better shapes and materials for the tubes. These models are so accurate that the FDA is considering requiring mathematical modeling in the design of stents before any further testing is done, to reduce the need for expensive experimentation. Precise modeling of the entire human vascular system is far beyond the reach of current computational power, so researchers focus their detailed models on small subsections, which are coupled with simpler models of the rest of the system. The Navier-Stokes equations are used to represent the flow of blood and its interaction with vessel walls. A mathematical proof was the central part of recent research that led to the abandonment of one type of stent and the design of better ones. The goal now is to create better computational fluid-vessel models and stent models to improve the treatment and prediction of coronary artery disease the major cause of heart attacks. For More Information: Design of Optimal Endoprostheses Using Mathematical Modeling, Canic, Krajcer, and Lapin, Endovascular Today, May 2006.

Consolidated sales of EUR 146.7 million EBITDA (before IFRS 16) increased strongly by EUR 3.8 million to EUR 2.1 million Forecast for 2019 as a whole confirmed Working capital ratio declines by 2 percentage points to 10.6% euromicron AG, a medium-sized technology group and specialist for the digital networking of business and production processes, published its preliminary figures for the first half of 2019 today.

euromicron AG, a medium-sized technology group and specialist for the digital support of business processes through secure infrastructures, is pooling its digital expertise at KORAMIS GmbH, the group subsidiary that specializes in cyber security and automation. With focus on digital platforms and services KORAMIS’ portfolio will also cover the areas Smart IoT, Smart Building as well as Data Management in the future. For this step the management of KORAMIS GmbH was extended by Andreas Schmidt.

euromicron AG, a medium-sized technology group and expert on the digital networking of business and production processes, has now fully placed the capital increase it resolved on July 10, 2019.

ssm euromicron GmbH, a system house subsidiary of euromicron AG, is involved in a project to provide the technical equipment for the new building for the Institute of Geosciences at Kiel’s Christian Albrechts University. The seven-story new building is part of a campus-wide modernization initiative that is one of the largest public high-rise projects in the federal state of Schleswig-Holstein.

Hydel, despite trailing their rivals for two straight days, easily retained their title

In-form American sprinter, Michael Rodgers, ran a world-leading 9.94 seconds and there were no Caribbean

Tropical rainforests are the world's richest land habitats for biodiversity, harbouring stunning numbers of plant and animal species. The Amazon and the Congo basins, together with Asian rainforests, represent only 6 per cent of earth's land surface, and yet more than 50 per cent of global biodiversity can be found under their shade.

The surprise player in affecting workplace safety overseas? Multinational buyers.

The world's two largest economies are both partners and rivals, deeply intertwined but also with divergent interests. How will these contradictions resolve themselves following COVID-19?